From 301c417801564f9219ddacdc0a0982a01848219b Mon Sep 17 00:00:00 2001 From: Susheel Varma Date: Wed, 12 Jun 2024 00:49:41 +0000 Subject: [PATCH] Commit new papers --- data/covid/ack-preprints.csv | 42 +- data/covid/papers.csv | 58 +- data/papers.csv | 532 +-- data/papers.json | 8380 +++++++++++++++++----------------- 4 files changed, 4506 insertions(+), 4506 deletions(-) diff --git a/data/covid/ack-preprints.csv b/data/covid/ack-preprints.csv index 7e2912d9..145c732b 100644 --- a/data/covid/ack-preprints.csv +++ b/data/covid/ack-preprints.csv @@ -34,8 +34,8 @@ PPR302793,https://doi.org/10.2139/ssrn.3803364,"A Common PPR215604,https://doi.org/10.1101/2020.09.17.20196469,Renin-angiotensin system inhibitors and susceptibility to COVID-19 in patients with hypertension: a propensity score-matched cohort study in primary care,"Haroon S, Subramanian A, Cooper J, Anand A, Gokhale K, Byne N, Dhalla S, Acosta-Mena D, Taverner T, Okoth K, Wang J, Chandan JS, Sainsbury C, Zemedikun DT, Thomas GN, Parekh D, Marshall T, Sapey E, Adderley NJ, Nirantharakumar K.",,No Journal Info,2020,2020-09-18,Y,,,,"

Introduction

A significant proportion of patients with Coronavirus Disease-19 (COVID-19) have hypertension and are treated with renin-angiotensin system (RAS) inhibitors, namely angiotensin-converting enzyme I inhibitors (ACE inhibitors) or angiotensin II type-1 receptor blockers (ARBs). These medications have been postulated to influence susceptibility to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The objective of this study was to assess a possible association between prescription of RAS inhibitors and the incidence of COVID-19 and all-cause mortality.

Methods

We conducted a propensity-score matched cohort study to assess the incidence of COVID-19 among patients with hypertension who were prescribed ACE inhibitors or ARBs compared to patients treated with calcium channel blockers (CCBs) in a large UK-based primary care database (The Health Improvement Network). We estimated crude incidence rates for confirmed/suspected COVID-19 among those prescribed ACE inhibitors, ARBs and CCBs. We used a Cox proportional hazards model to produce adjusted hazard ratios for COVID-19 comparing patients prescribed ACE inhibitors or ARBs to those prescribed CCBs. We further assessed all-cause mortality as a secondary outcome and a composite of accidents, trauma or fractures as a negative control outcome to assess for residual confounding.

Results

In the propensity score matched analysis, 83 of 18,895 users (0.44%) of ACE inhibitors developed COVID-19 over 8,923 person-years, an incidence rate of 9.3 per 1000 person-years. 85 of 18,895 (0.45%) users of CCBs developed COVID-19 over 8,932 person-years, an incidence rate of 9.5 per 1000 person-years. The adjusted hazard ratio for suspected/confirmed COVID-19 for users of ACE inhibitors compared to CCBs was 0.92 (95% CI 0.68 to 1.26). 79 out of 10,623 users (0.74%) of ARBs developed COVID-19 over 5010 person-years, an incidence rate of 15.8 per 1000 person-years, compared to 11.6 per 1000 person-years among users of CCBs. The adjusted hazard ratio for suspected/confirmed COVID-19 for users of ARBs compared to CCBs was 1.38 (95% CI 0.98 to 1.95). There were no significant associations between use of ACE inhibitors or ARBs and all-cause mortality, compared to use of CCBs. We found no evidence of significant residual confounding with the negative control analysis.

Conclusion

Current use of ACE inhibitors was not associated with the risk of suspected or confirmed COVID-19 whereas use of ARBs was associated with a statistically non-significant 38% relative increase in risk compared to use of CCBs. However, no significant associations were observed between prescription of either ACE inhibitors or ARBs and all-cause mortality during the peak of the pandemic.",,pdf:http://pure-oai.bham.ac.uk/ws/files/118117066/s12879_021_05951_w.pdf; doi:https://doi.org/10.1101/2020.09.17.20196469; html:https://europepmc.org/article/PPR/PPR215604; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR215604&type=FILE&fileName=EMS96164-pdf.pdf&mimeType=application/pdf PPR293775,https://doi.org/10.1101/2021.03.04.21252931,A common TMPRSS2 variant protects against severe COVID-19,"David A, Parkinson N, Peacock TP, Pairo-Castineira E, Khanna T, Cobat A, Tenesa A, Sancho-Shimizu V, Casanova J, Abel L, Barclay WS, Baillie JK, Sternberg MJ, GenOMICC Investigators, ISARIC4C Investigators.",,No Journal Info,2021,2021-03-08,Y,,,,"

Summary

Infection with SARS-CoV-2 has a wide range of clinical presentations, from asymptomatic to life-threatening. Old age is the strongest factor associated with increased COVID19-related mortality, followed by sex and pre-existing conditions. The importance of genetic and immunological factors on COVID19 outcome is also starting to emerge, as demonstrated by population studies and the discovery of damaging variants in genes controlling type I IFN immunity and of autoantibodies that neutralize type I IFNs. The human protein transmembrane protease serine type 2 (TMPRSS2) plays a key role in SARS-CoV-2 infection, as it is required to activate the virus’ spike protein, facilitating entry into target cells. We focused on the only common TMPRSS2 non-synonymous variant predicted to be damaging (rs12329760), which has a minor allele frequency of ∼25% in the population. In a large population of SARS-CoV-2 positive patients, we show that this variant is associated with a reduced likelihood of developing severe COVID19 (OR 0.87, 95%CI:0.79-0.97, p=0.01). This association was stronger in homozygous individuals when compared to the general population (OR 0.65, 95%CI:0.50-0.84, p=1.3×10 −3 ). We demonstrate in vitro that this variant, which causes the amino acid substitution valine to methionine, impacts the catalytic activity of TMPRSS2 and is less able to support SARS-CoV-2 spike-mediated entry into cells. TMPRSS2 rs12329760 is a common variant associated with a significantly decreased risk of severe COVID19. Further studies are needed to assess the expression of the TMPRSS2 across different age groups. Moreover, our results identify TMPRSS2 as a promising drug target, with a potential role for camostat mesilate, a drug approved for the treatment of chronic pancreatitis and postoperative reflux esophagitis, in the treatment of COVID19. Clinical trials are needed to confirm this.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/03/08/2021.03.04.21252931.full.pdf; doi:https://doi.org/10.1101/2021.03.04.21252931; html:https://europepmc.org/article/PPR/PPR293775; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR293775&type=FILE&fileName=EMS118903-pdf.pdf&mimeType=application/pdf PPR506156,https://doi.org/10.1101/2022.06.09.22276196,Accelerated waning of the humoral response to SARS-CoV-2 vaccines in obesity,"van der Klaauw AA, Horner EC, Pereyra-Gerber P, Agrawal U, Foster WS, Spencer S, Vergese B, Smith M, Henning E, Ramsay ID, Smith JA, Guillaume SM, Sharpe HJ, Hay IM, Thompson S, Innocentin S, Booth LH, Robertson C, McCowan C, Mulroney TE, O’Reilly MJ, Gurugama TP, Gurugama LP, Rust MA, Ferreira A, Ebrahimi S, Ceron-Gutierrez L, Scotucci J, Kronsteiner B, Dunachie SJ, Klenerman P, Park AJ, Rubino F, Stark H, Kingston N, Doffinger R, Linterman MA, Matheson NJ, Sheikh A, Farooqi IS, Thaventhiran JED, PITCH Consortium.",,No Journal Info,2022,2022-06-14,N,,,,"

ABSTRACT

Obesity is associated with an increased risk of severe Covid-19. However, the effectiveness of SARS-CoV-2 vaccines in people with obesity is unknown. Here we studied the relationship between body mass index (BMI), hospitalization and mortality due to Covid-19 amongst 3.5 million people in Scotland. Vaccinated people with severe obesity (BMI>40 kg/m 2 ) were significantly more likely to experience hospitalization or death from Covid-19. Excess risk increased with time since vaccination. To investigate the underlying mechanisms, we conducted a prospective longitudinal study of the immune response in a clinical cohort of vaccinated people with severe obesity. Compared with normal weight people, six months after their second vaccine dose, significantly more people with severe obesity had unquantifiable titres of neutralizing antibody against authentic SARS-CoV-2 virus, reduced frequencies of antigen-experienced SARS-CoV-2 Spike-binding B cells, and a dissociation between anti-Spike antibody levels and neutralizing capacity. Neutralizing capacity was restored by a third dose of vaccine, but again declined more rapidly in people with severe obesity. We demonstrate that waning of SARS-CoV-2 vaccine-induced humoral immunity is accelerated in people with severe obesity and associated with increased hospitalization and mortality from breakthrough infections. Given the prevalence of obesity, our findings have significant implications for global public health.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/06/14/2022.06.09.22276196.full.pdf; doi:https://doi.org/10.1101/2022.06.09.22276196; html:https://europepmc.org/article/PPR/PPR506156; doi:https://doi.org/10.1101/2022.06.09.22276196 -PPR802874,https://doi.org/10.1101/2024.02.08.24302486,Bidirectional relationship between sleep problems and long COVID: a longitudinal analysis of data from the COVIDENCE UK study,"Vivaldi G, Talaei M, Blaikley J, Jackson C, Pfeffer PE, Shaheen SO, Martineau AR.",,No Journal Info,2024,2024-02-08,Y,,,,"

Summary

Background

Studies into the bidirectional relationship between sleep and long COVID have been limited by retrospective pre-infection sleep data and infrequent post-infection follow-up. We therefore used prospectively collected monthly data to evaluate how pre-infection sleep characteristics affect risk of long COVID, and to track changes in sleep duration during the year after SARS-CoV-2 infection.

Methods

COVIDENCE UK is a prospective, population-based UK study of COVID-19 in adults. We included non-hospitalised participants with evidence of SARS-CoV-2 infection, and estimated odds ratios (ORs) for the association between pre-infection sleep characteristics and long COVID using logistic regression, adjusting for potential confounders. We assessed changes in sleep duration after infection using multilevel mixed models. We defined long COVID as unresolved symptoms at least 12 weeks after infection. We defined sleep quality according to age-dependent combinations of sleep duration and efficiency. COVIDENCE UK is registered with ClinicalTrials.gov, NCT04330599 .

Findings

We included 3994 participants in our long COVID risk analysis, of whom 327 (8.2%) reported long COVID. We found an inverse relationship between pre-infection sleep quality and risk of long COVID (medium vs good quality: OR 1.37 [95% CI 1.04–1.81]; medium–low vs good: 1.55 [1.12–2.16]; low vs good: 1.94 [1.11–3.38]). Greater variability in pre-infection sleep efficiency was also associated with long COVID (OR per percentage-point increase 1.06 [1.01–1.11]). We assessed post-infection sleep duration in 6860 participants, observing a 0.11 h (95% CI 0.08–0.13) increase in the first month after infection compared with pre-infection, with larger increases for more severe infections. After 1 month, sleep duration largely returned to pre-infection levels, although fluctuations in duration lasted up to 6 months after infection among people reporting long COVID.

Interpretation

Our findings highlight the bidirectional relationship between sleep and long COVID. While poor-quality sleep before SARS-CoV-2 infection associates with increased risk of long COVID thereafter, changes in sleep duration after infection in these non-hospitalised cases were modest and generally quick to resolve.

Funding

Barts Charity.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2024/02/08/2024.02.08.24302486.full.pdf; doi:https://doi.org/10.1101/2024.02.08.24302486; html:https://europepmc.org/article/PPR/PPR802874; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR802874&type=FILE&fileName=EMS193995-pdf.pdf&mimeType=application/pdf PPR550732,https://doi.org/10.1101/2022.09.27.22280397,Vaccine effectiveness for preventing COVID-19 hospital admission during pregnancy: a population-based cohort study in England during the Alpha and Delta waves of the SARS-CoV-2 pandemic,"Bosworth ML, Schofield R, Ayoubkhani D, Charlton L, Nafilyan V, Khunti K, Zaccardi F, Gillies C, Akbari A, Knight M, Wood R, Hardelid P, Zuccolo L, Harrison C.",,No Journal Info,2022,2022-09-27,Y,,,,"

Objective

To estimate vaccine effectiveness (VE) for preventing COVID-19 hospital admission in women first infected with SARS-CoV-2 during pregnancy, and assess how this compares to VE among women of reproductive age who were not pregnant when first infected.

Design

Population-based cohort study using national, linked Census and administrative data.

Setting

England, United Kingdom, from 8 th December 2020 to 31 st August 2021.

Participants

815,4777 women aged 18 to 45 years (mean age, 30.4 years) who had documented evidence of a first SARS-CoV-2 infection in NHS Test and Trace data or Hospital Episode Statistics.

Main outcome measures

A hospital inpatient episode where COVID-19 was recorded as the primary diagnosis. Cox proportional hazards models, adjusted for calendar time of infection and sociodemographic factors related to vaccine uptake and risk of severe COVID-19, were used to estimate VE as the complement of the hazard ratio for COVID-19 hospital admission.

Results

Compared with unvaccinated pregnant women, the adjusted rate of COVID-19 hospital admission was 76% (95% confidence interval 69% to 82%) lower for single-vaccinated pregnant women and 83% (75% to 88%) lower for double-vaccinated pregnant women. These estimates were similar to those found for non-pregnant women: 79% (76% to 81%) for single-vaccinated and 82% (80% to 83%) for double-vaccinated. Among those vaccinated more than 90 days before infection, being double-vaccinated was associated with a greater reduction in risk than being single-vaccinated.

Conclusions

COVID-19 vaccination is associated with reduced rates of severe illness in pregnant women infected with SARS-CoV-2, and the reduction in risk is similar to that for non-pregnant women. Waning of vaccine effectiveness occurs more quickly after one dose of a vaccine than two doses.

What is already known on this topic

Being pregnant is a risk factor for severe illness and mortality following infection with SARS-CoV-2. Existing evidence suggests that COVID-19 vaccines are effective for preventing severe outcomes in pregnant women. However, research directly comparing vaccine effectiveness between pregnant and non-pregnant women of reproductive age at the population level are lacking.

What this study adds

Our study provides real-world evidence that COVID-19 vaccination reduces the risk of hospital admission by a similar amount for both women infected with SARS-CoV-2 during pregnancy and women who were not pregnant when infected, during the Alpha and Delta dominant periods in England.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/09/27/2022.09.27.22280397.full.pdf; doi:https://doi.org/10.1101/2022.09.27.22280397; html:https://europepmc.org/article/PPR/PPR550732; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR550732&type=FILE&fileName=EMS155049-pdf.pdf&mimeType=application/pdf +PPR802874,https://doi.org/10.1101/2024.02.08.24302486,Bidirectional relationship between sleep problems and long COVID: a longitudinal analysis of data from the COVIDENCE UK study,"Vivaldi G, Talaei M, Blaikley J, Jackson C, Pfeffer PE, Shaheen SO, Martineau AR.",,No Journal Info,2024,2024-02-08,Y,,,,"

Summary

Background

Studies into the bidirectional relationship between sleep and long COVID have been limited by retrospective pre-infection sleep data and infrequent post-infection follow-up. We therefore used prospectively collected monthly data to evaluate how pre-infection sleep characteristics affect risk of long COVID, and to track changes in sleep duration during the year after SARS-CoV-2 infection.

Methods

COVIDENCE UK is a prospective, population-based UK study of COVID-19 in adults. We included non-hospitalised participants with evidence of SARS-CoV-2 infection, and estimated odds ratios (ORs) for the association between pre-infection sleep characteristics and long COVID using logistic regression, adjusting for potential confounders. We assessed changes in sleep duration after infection using multilevel mixed models. We defined long COVID as unresolved symptoms at least 12 weeks after infection. We defined sleep quality according to age-dependent combinations of sleep duration and efficiency. COVIDENCE UK is registered with ClinicalTrials.gov, NCT04330599 .

Findings

We included 3994 participants in our long COVID risk analysis, of whom 327 (8.2%) reported long COVID. We found an inverse relationship between pre-infection sleep quality and risk of long COVID (medium vs good quality: OR 1.37 [95% CI 1.04–1.81]; medium–low vs good: 1.55 [1.12–2.16]; low vs good: 1.94 [1.11–3.38]). Greater variability in pre-infection sleep efficiency was also associated with long COVID (OR per percentage-point increase 1.06 [1.01–1.11]). We assessed post-infection sleep duration in 6860 participants, observing a 0.11 h (95% CI 0.08–0.13) increase in the first month after infection compared with pre-infection, with larger increases for more severe infections. After 1 month, sleep duration largely returned to pre-infection levels, although fluctuations in duration lasted up to 6 months after infection among people reporting long COVID.

Interpretation

Our findings highlight the bidirectional relationship between sleep and long COVID. While poor-quality sleep before SARS-CoV-2 infection associates with increased risk of long COVID thereafter, changes in sleep duration after infection in these non-hospitalised cases were modest and generally quick to resolve.

Funding

Barts Charity.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2024/02/08/2024.02.08.24302486.full.pdf; doi:https://doi.org/10.1101/2024.02.08.24302486; html:https://europepmc.org/article/PPR/PPR802874; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR802874&type=FILE&fileName=EMS193995-pdf.pdf&mimeType=application/pdf PPR717811,https://doi.org/10.1101/2023.08.30.23294821,Symptom experience before vs. after confirmed SARS-CoV-2 infection: a population and case control study using prospectively recorded symptom data,"Sudre CH, Antonelli M, Cheetham NJ, Molteni E, Canas LS, Bowyer V, Murray B, Rjoob K, Modat M, Pujol JC, Hu C, Wolf J, Spector TD, Hammers A, Steves CJ, Ourselin S, Duncan EL.",,No Journal Info,2023,2023-09-01,Y,,,,"

Background

Some individuals experience prolonged illness after acute COVID-19. We assessed whether pre-infection symptoms affected post-COVID illness duration.

Methods

Survival analysis was performed in adults (n=23,452) with community-managed SARC-CoV-2 infection prospectively self-logging data through the ZOE COVID Symptom Study app, at least weekly, from 8 weeks before to 12 weeks after COVID-19 onset, conditioned on presence vs. absence of baseline symptoms (4-8 weeks before COVID-19). A case-control study was performed in 1350 individuals with long illness (≥8 weeks, 906 [67.1%] with illness ≥12 weeks), matched 1:1 (for age, sex, body mass index, testing week, prior infection, vaccination, smoking, index of multiple deprivation) with 1350 individuals with short illness (<4 weeks). Baseline symptoms were compared between the two groups; and against post-COVID symptoms.

Findings

Individuals reporting baseline symptoms had longer post-COVID symptom duration (from 10 to 15 days) with baseline fatigue nearly doubling duration. Two-thirds (910 of 1350 [67.4%]) of individuals with long illness were asymptomatic beforehand. However, 440 (32.6%) had baseline symptoms, vs. 255 (18.9%) of 1350 individuals with short illness (p<0.0001). Baseline symptoms increased the odds ratio for long illness (2.14 [CI: 1.78; 2.57]). Prior comorbidities were more common in individuals with long vs. short illness. In individuals with long illness, baseline symptomatic (vs. asymptomatic) individuals were more likely to be female, younger, and have prior comorbidities; and baseline and post-acute symptoms and symptom burden correlated strongly.

Interpretation

Individuals experiencing symptoms before COVID-19 have longer illness duration and increased odds of long illness. However, many individuals with long illness are well before SARS-CoV-2 infection.",,doi:https://doi.org/10.1101/2023.08.30.23294821; html:https://europepmc.org/article/PPR/PPR717811; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR717811&type=FILE&fileName=EMS187353-pdf.pdf&mimeType=application/pdf PPR805294,https://doi.org/10.1101/2024.02.12.24302698,Cohort study of cardiovascular safety of different COVID-19 vaccination doses among 46 million English adults,"Ip S, North T, Torabi F, Li Y, Abbasizanjani H, Akbari A, Horne E, Denholm R, Keene S, Denaxas S, Banerjee A, Khunti K, Sudlow C, Whiteley WN, Sterne JAC, Wood AM, Walker V.",,No Journal Info,2024,2024-02-13,Y,,,,"

ABSTRACT

Using longitudinal health records from 45.7 million adults in England followed for a year, our study compared the incidence of thrombotic and cardiovascular complications after first, second and booster doses of brands and combinations of COVID-19 vaccines used during the first two years of the UK vaccination program with the incidence before or without the corresponding vaccination. The incidence of common arterial thrombotic events (mainly acute myocardial infarction and ischaemic stroke) was generally lower after each vaccine dose, brand and combination. Similarly, the incidence of common venous thrombotic events, (mainly pulmonary embolism and lower limb deep venous thrombosis) was lower after vaccination. There was a higher incidence of previously reported rare harms after vaccination: vaccine-induced thrombotic thrombocytopenia after first ChAdOx1 vaccination, and myocarditis and pericarditis after first, second and transiently after booster mRNA vaccination (BNT-162b2 and mRNA-1273). These findings support the wide uptake of future COVID-19 vaccination programs.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2024/02/13/2024.02.12.24302698.full.pdf; doi:https://doi.org/10.1101/2024.02.12.24302698; html:https://europepmc.org/article/PPR/PPR805294; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR805294&type=FILE&fileName=EMS194133-pdf.pdf&mimeType=application/pdf PPR625922,https://doi.org/10.1101/2023.03.01.23286627,Effectiveness of successive booster vaccine doses against SARS-CoV-2 related mortality in residents of Long-Term Care Facilities in the VIVALDI study,"Stirrup O, Shrotri M, Adams NL, Krutikov M, Azmi B, Monakhov I, Tut G, Moss P, Hayward A, Copas A, Shallcross L.",,No Journal Info,2023,2023-03-03,Y,,,,"We evaluated the effectiveness of 1-3 booster vaccinations against SARS-CoV-2 related mortality among a cohort of 13407 older residents of long-term care facilities (LTCFs) participating in the VIVALDI study in England in 2022. Cox regression was used to estimate relative hazards of SARS-CoV-2 related death following booster vaccination relative to 2 doses (after 84+ days), stratified by previous SARS-CoV-2 infection and adjusting for age, sex and LTCF capacity. Each booster provided additional short-term protection relative to primary vaccination, with consistent pattern of waning to 45-75% reduction in risk beyond 112 days.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/03/03/2023.03.01.23286627.full.pdf; doi:https://doi.org/10.1101/2023.03.01.23286627; html:https://europepmc.org/article/PPR/PPR625922; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR625922&type=FILE&fileName=EMS171894-pdf.pdf&mimeType=application/pdf @@ -113,11 +113,11 @@ PPR436211,https://doi.org/10.1101/2021.12.23.21268276,Risk of myocarditis follow PPR417646,https://doi.org/10.21203/rs.3.rs-1051010/v1,COVID-19 vaccination rates and SARS-CoV-2 infection in pregnant women in Scotland,"Stock S, Carruthers J, Calvert C, Denny C, Donaghy J, Goulding A, Hopcroft L, Hopkins L, McLaughlin T, Pan J, Shi T, Taylor J, Agrawal U, Auyeung B, Katikireddi S, McCowan C, Murray J, Simpson C, Robertson C, Vasileiou E, Sheikh A, Wood R.",,No Journal Info,2021,2021-11-09,Y,,,,"We describe SARS-CoV-2 infection and COVID-19 vaccine uptake in Scotland in a prospective cohort of all pregnant women in Scotland drawn from national databases. As of mid-October 2021, the Covid-19 in pregnancy in Scotland (COPS) cohort included linked data on a total of 139,136 pregnancies in 126,749 women. Up to September 30, 2021, a total of 22,779 COVID-19 vaccinations had been administered to 16,229 pregnant women. Vaccine coverage was substantially lower in pregnant women than in the general female population of reproductive age (23.7% of women giving birth in September 2021 were fully vaccinated compared to 74.9 % in women 18-44 years). Of the 4,274 cases of COVID-19 in pregnancy (confirmed by SARS-CoV-2 viral reverse transcriptase polymerase chain reaction) between December 2020 (the month the COVID-19 vaccination programme started in Scotland) and September 2021 inclusive, 629 women (14.7%) were admitted to hospital and 89 (2.1%) were admitted to critical care. Of the COVID-19 cases occurring in pregnant women, 81.7% (3,491/4,274; 95% CI 80.5-82.8) were in unvaccinated women. Of the COVID-19 associated hospital admissions, 93.0% (585/629; 95% CI 90.7-94.8) were in women who were unvaccinated at the time of COVID-19 diagnosis. Of the COVID-19 associated critical care admissions 98.9% (88/89; 95% CI 93.9-100) were in women who were unvaccinated at the time of COVID-19 diagnosis. The extended perinatal mortality rate for women who gave birth within 28 days of COVID-19 diagnosis was 15.9 per 1000 births (95% CI 7.8 to 31.0; background rate in 2020 6.3 per 1,000 total births [95% CI 5.7-7.1]; background rate 2019 5.7 per 1,000 total births [95% CI 5.0-6.4]). All baby deaths occurred after pregnancies in women who were unvaccinated at the time of COVID-19 diagnosis. Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies.",,pdf:https://www.nature.com/articles/s41591-021-01666-2.pdf; doi:https://doi.org/10.21203/rs.3.rs-1051010/v1; html:https://europepmc.org/article/PPR/PPR417646; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR417646&type=FILE&fileName=EMS138218-pdf.pdf&mimeType=application/pdf PPR587506,https://doi.org/10.1101/2022.12.15.22283507,Antidepressant drug prescription and incidence of COVID-19: a retrospective cohort study,"Glebov OO, Mueller C, Stewart R, Aarsland D, Perera G.",,No Journal Info,2022,2022-12-20,Y,,,,"While antidepressant drugs (ADs) have shown some efficacy in treatment of COVID-19, their preventative potential remains unexplored. To investigate association between AD and COVID-19 incidence in the community, we analysed data from community-living, non-hospitalized adults admitted to inpatient care of the South London&’Maudsley (SLaM) NHS Foundation Trust during the 1st wave of COVID-19 pandemic in the UK. Prescription of ADs within the period of 1 to 3 months before admission was associated with an approximately 40% decrease in positive COVID-19 test results when adjusted for socioeconomic parameters and physical health. This association was specifically observed for ADs of the Selective Serotonin Reuptake Inhibitor (SSRI) class. These results suggest that ADs, specifically SSRIs, may help prevent COVID-19 infection in the community. Definitive determination of AD preventative potential warrants prospective studies in the wider general population.

Key points

Question

Is there an association between prescription of antidepressants and incidence of COVID-19 in the general population?

Findings

In this retrospective cohort study of mental health outpatients with a recent (1-3 months) antidepressant prescription, there was a statistically significant 40% decrease in positive COVID-19 tests. This association was specifically observed for the most commonly prescribed antidepressant class, Selective Serotonin Reuptake Inhibitors, and remained when adjusted for socioeconomic parameters and physical health.

Meaning

Antidepressant prescription was associated with lower incidence of COVID-19 in the community, warranting further investigation as prophylactics in prospective clinical studies.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/12/20/2022.12.15.22283507.full.pdf; doi:https://doi.org/10.1101/2022.12.15.22283507; html:https://europepmc.org/article/PPR/PPR587506; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR587506&type=FILE&fileName=EMS158832-pdf.pdf&mimeType=application/pdf PPR532697,https://doi.org/10.1101/2022.08.13.22278733,QCovid 4 - Predicting risk of death or hospitalisation from COVID-19 in adults testing positive for SARS-CoV-2 infection during the Omicron wave in England,"Hippisley-Cox J, Khunti K, Sheikh A, Nguyen-Van-Tam JS, Coupland CA.",,No Journal Info,2022,2022-08-16,Y,,,,"

ABSTRACT

Objectives

To (a) derive and validate risk prediction algorithms (QCovid4) to estimate risk of COVID-19 mortality and hospitalisation in UK adults with a SARS-CoV-2 positive test during the ‘Omicron’ pandemic wave in England and (b) evaluate performance with earlier versions of algorithms developed in previous pandemic waves and the high-risk cohort identified by NHS Digital in England.

Design

Population-based cohort study using the QResearch database linked to national data on COVID-19 vaccination, high risk patients prioritised for COVID-19 therapeutics, SARS-CoV-2 results, hospitalisation, cancer registry, systemic anticancer treatment, radiotherapy and the national death registry.

Settings and study period

1.3 million adults in the derivation cohort and 0.15 million adults in the validation cohort aged 18-100 years with a SARS-CoV-2 positive test between 11 th December 2021 and 31 st March 2022 with follow up to 30 th June 2022.

Main outcome measures

Our primary outcome was COVID-19 death. The secondary outcome of interest was COVID-19 hospital admission. Models fitted in the derivation cohort to derive risk equations using a range of predictor variables. Performance evaluated in a separate validation cohort.

Results

Of 1,297,984 people with a SARS-CoV-2 positive test in the derivation cohort, 18,756 (1.45%) had a COVID-19 related hospital admission and 3,878 (0.3%) had a COVID-19 death during follow-up. Of the 145,404 people in the validation cohort, there were 2,124 (1.46%) COVID-19 admissions and 461 (0.3%) COVID-19 deaths. The COVID-19 mortality rate in men increased with age and deprivation. In the QCovid4 model in men hazard ratios were highest for those with the following conditions (for 95% CI see Figure 1): kidney transplant (6.1-fold increase); Down’s syndrome (4.9-fold); radiotherapy (3.1-fold); type 1 diabetes (3.4-fold); chemotherapy grade A (3.8-fold), grade B (5.8-fold); grade C (10.9-fold); solid organ transplant ever (2.4-fold); dementia (1.62-fold); Parkinson’s disease (2.2-fold); liver cirrhosis (2.5-fold). Other conditions associated with increased COVID-19 mortality included learning disability, chronic kidney disease (stages 4 and 5), blood cancer, respiratory cancer, immunosuppressants, oral steroids, COPD, coronary heart disease, stroke, atrial fibrillation, heart failure, thromboembolism, rheumatoid/SLE, schizophrenia/bipolar disease sickle cell/HIV/SCID; type 2 diabetes. Results were similar in the model in women. COVID-19 mortality risk was lower among those who had received COVID-19 vaccination compared with unvaccinated individuals with evidence of a dose response relationship. The reduced mortality rates associated with prior SARS-CoV-2 infection were similar in men (adjusted hazard ratio (HR) 0.51 (95% CI 0.40, 0.64)) and women (adjusted HR 0.55 (95%CI 0.45, 0.67)). The QCOVID4 algorithm explained 76.6% (95%CI 74.4 to 78.8) of the variation in time to COVID-19 death (R 2 ) in women. The D statistic was 3.70 (95%CI 3.48 to 3.93) and the Harrell’s C statistic was 0.965 (95%CI 0.951 to 0.978). The corresponding results for COVID-19 death in men were similar with R 2 76.0% (95% 73.9 to 78.2); D statistic 3.65 (95%CI 3.43 to 3.86) and C statistic of 0.970 (95%CI 0.962 to 0.979). QCOVID4 discrimination for mortality was slightly higher than that for QCOVID1 and QCOVID2, but calibration was much improved.

Conclusion

The QCovid4 risk algorithm modelled from data during the UK’s Omicron wave now includes vaccination dose and prior SARS-CoV-2 infection and predicts COVID-19 mortality among people with a positive test. It has excellent performance and could be used for targeting COVID-19 vaccination and therapeutics. Although large disparities in risks of severe COVID-19 outcomes among ethnic minority groups were observed during the early waves of the pandemic, these are much reduced now with no increased risk of mortality by ethnic group.

What is known

The QCOVID risk assessment algorithm for predicting risk of COVID-19 death or hospital admission based on individual characteristics has been used in England to identify people at high risk of severe COVID-19 outcomes, adding an additional 1.5 million people to the national shielded patient list in England and in the UK for prioritising people for COVID-19 vaccination. There are ethnic disparities in severe COVID-19 outcomes which were most marked in the first pandemic wave in 2020. COVID-19 vaccinations and therapeutics (monoclonal antibodies and antivirals) are available but need to be targeted to those at highest risk of severe outcomes.

What this study adds

The QCOVID4 risk algorithm using data from the Omicron wave now includes number of vaccination doses and prior SARS-CoV-2 infection. It has excellent performance both for ranking individuals (discrimination) and predicting levels of absolute risk (calibration) and can be used for targeting COVID-19 vaccination and therapeutics as well as individualised risk assessment. QCOVID4 more accurately identifies individuals at highest levels of absolute risk for targeted interventions than the ‘conditions-based’ approach adopted by NHS Digital based on relative risk of a list of medical conditions. Although large disparities in risks of severe COVID-19 outcomes among ethnic minority groups were observed during the early waves of the pandemic, these are much reduced now with no increased risk of mortality by ethnic group.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/08/16/2022.08.13.22278733.full.pdf; doi:https://doi.org/10.1101/2022.08.13.22278733; html:https://europepmc.org/article/PPR/PPR532697; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR532697&type=FILE&fileName=EMS152911-pdf.pdf&mimeType=application/pdf -PPR584146,https://doi.org/10.1101/2022.12.12.22283200,"COVID-19 Vaccination in Pregnancy: The Impact of Multimorbidity and Smoking Status on Vaccine Hesitancy, a Cohort Study of 25,111 Women in Wales, UK","Mhereeg M, Jones H, Kennedy J, Seaborne M, Parker M, Kennedy N, Akbari A, Zuccolo L, Azcoaga-Lorenzo A, Davies A, Nirantharakumar K, Brophy S.",,No Journal Info,2022,2022-12-14,Y,,,,"

Background

Multimorbidity and pregnancy are two risk factors for more severe outcomes after a SARS-CoV-2 infection, thus vaccination uptake is important for pregnant women living with multimorbidity. This study aimed to examine the impact of multimorbidity, smoking status, and demographics (age, ethnic group, area of deprivation) on vaccine hesitancy among pregnant women in Wales using electronic health records (EHR) linkage.

Methods

This cohort study utilised routinely collected, individual-level, anonymised population-scale linked data within the Secure Anonymised Information Linkage (SAIL) Databank. Pregnant women were identified from 13 th April 2021 to 31 st December 2021. Survival analysis was utilised to examine and compare the length of time to vaccination uptake in pregnancy by multimorbidity and smoking status, as well as depression, diabetes, asthma, and cardiovascular conditions independently. Variation in uptake by; multimorbidity, smoking status, and demographics was examined jointly and separately for the independent conditions using hazard ratios (HR) from the Cox regression model. A bootstrapping internal validation was conducted to assess the performance of the models.

Results

Within the population cohort, 8,203 (32.7%) received at least one dose of the COVID-19 vaccine during pregnancy, with 8,572 (34.1%) remaining unvaccinated throughout the follow-up period, and 8,336 (33.2%) receiving the vaccine postpartum. Women aged 30 years or older were more likely to have the vaccine in pregnancy. Those who had depression were slightly but significantly more likely to have the vaccine compared to those without depression (HR = 1.08, 95% CI 1.03 to 1.14, p = 0.02). Women living with multimorbidity (> 1 health condition) were 1.12 times more likely to have the vaccine compared to those living without multimorbidity (HR = 1.12, 95% CI 1.04 to 1.19, p = 0.001). Vaccine uptakes were significantly lower among both current smokers and former smokers compared to never smokers (HR = 0.87, 95% CI 0.81 to 0.94, p < 0.001 and HR = 0.92, 95% CI 0.85 to 0.98, p = 0.015 respectively). Uptake was also lower among those living in the most deprived areas compared to those living in the most affluent areas (HR = 0.89, 95% CI 0.83 to 0.96, p = 0.002). The validated model had similar performance and revealed that multimorbidity, smoking status, age, and deprivation level together have a significant impact on vaccine hesitancy (p < 0.05 for all).

Conclusion

Younger women, living without multimorbidity (zero or only one health condition), current and former smokers, and those living in the more deprived areas are less likely to have the vaccine, thus, a targeted approach to vaccinations may be required for these groups. Women living with multimorbidity are slightly but significantly less likely to be hesitant about COVID-19 vaccination when pregnant.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa62207/Download/62207__28856__f089034a71e842eeaba218ce327754fe.pdf; doi:https://doi.org/10.1101/2022.12.12.22283200; html:https://europepmc.org/article/PPR/PPR584146; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR584146&type=FILE&fileName=EMS158540-pdf.pdf&mimeType=application/pdf PPR371282,https://doi.org/10.1101/2021.07.14.21260497,"Vaccine uptake and SARS-CoV-2 antibody prevalence among 207,337 adults during May 2021 in England: REACT-2 study","Ward H, Whitaker M, Tang SN, Atchison C, Darzi A, Donnelly CA, Diggle PJ, Ashby D, Riley S, Barclay WS, Elliott P, Cooke G.",,No Journal Info,2021,2021-07-18,Y,,,,"

Background

The programme to vaccinate adults in England has been rapidly implemented since it began in December 2020. The community prevalence of SARS-CoV-2 anti-spike protein antibodies provides an estimate of total cumulative response to natural infection and vaccination. We describe the distribution of SARS-CoV-2 IgG antibodies in adults in England in May 2021 at a time when approximately 7 in 10 adults had received at least one dose of vaccine.

Methods

Sixth round of REACT-2 (REal-time Assessment of Community Transmission-2), a cross-sectional random community survey of adults in England, from 12 to 25 May 2021; 207,337 participants completed questionnaires and self-administered a lateral flow immunoassay test producing a positive or negative result.

Results

Vaccine coverage with one or more doses, weighted to the adult population in England, was 72.9% (95% confidence interval 72.7-73.0), varying by age from 25.1% (24.5-25.6) of those aged 18 to 24 years, to 99.2% (99.1-99.3) of those 75 years and older. In adjusted models, odds of vaccination were lower in men (odds ratio [OR] 0.89 [0.85-0.94]) than women, and in people of Black (0.41 [0.34-0.49]) compared to white ethnicity. There was higher vaccine coverage in the least deprived and highest income households. People who reported a history of COVID-19 were less likely to be vaccinated (OR 0.61 [0.55-0.67]). There was high coverage among health workers (OR 9.84 [8.79-11.02] and care workers (OR 4.17 [3.20-5.43]) compared to non-key workers, but lower in hospitality and retail workers (OR 0.73 [0.64-0.82] and 0.77 [0.70-0.85] respectively) after adjusting for age and key covariates. The prevalence of antibodies (weighted to the adult population of England and adjusted for test characteristics) was 61.1% (95% CI 60.9-61.4), up from 6.6% (5.4-5.7) in round 4 (27 October to 10 November 2020) and 13.9% (13.7-14.1) in round 5 (26 January to 8 February 2021). Prevalence (adjusted and weighted) increased with age, from 35.8% (35.1-36.5) in those aged 18 to 24 years, to 95.3% (94.6-95.9) in people 75 and over. Antibodies were 30% less likely to be detected in men than women (adjusted OR 0.69, 0.68-0.70), and were higher in people of Asian (OR 1.67 [1.58-1.77]), Black (1.55 [1.41-1.69]), mixed 1.17 [1.06-1.29] and other (1.37 [1.23-1.51]) ethnicities compared with white ethnicity. Workers in hospitality (OR 0.69 [0.63-0.74]) and retail (0.71 [0.67-0.75]) were less likely to have antibodies. Following two doses of Pfizer-BioNTech vaccine, antibody positivity (adjusted for test performance) was 100% (100-100) at all ages except 80 years and older when it was 97.8% (95.9-99.6). For AstraZeneca positivity was over 90% up to age 69, and then 89.2% (88.5-89.9) in 70-79 year olds and 83.6% (78.5-88.3) in those aged 80 and over. Following a single dose of Pfizer-BioNTech positivity ranged from 100.0% (91.1-100.0) in those aged 18-29 to 32.2% (18.2-51.1) in those aged 70-79 years. For AstraZeneca this was 72.2% (68.5-75.9) in the youngest and 46.2% (40.0-52.7) in the oldest age group.

Discussion

The successful roll out of the vaccination programme in England has led to a high proportion of individuals having detectable antibodies, particularly in older age groups and those who have had two doses of vaccine. This is likely to be associated with high levels of protection from severe disease, and possibly from infection. Nonetheless, there remain some key groups with a lower prevalence of antibody, notably unvaccinated younger people, certain minority ethnic groups, those living in deprived areas and workers in some public facing employment. Obtaining improved rates of vaccination in these groups is essential to achieving high levels of protection against the virus through population immunity.

Funding

Department of Health and Social Care in England.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/07/18/2021.07.14.21260497.full.pdf; doi:https://doi.org/10.1101/2021.07.14.21260497; html:https://europepmc.org/article/PPR/PPR371282; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR371282&type=FILE&fileName=EMS130807-pdf.pdf&mimeType=application/pdf +PPR584146,https://doi.org/10.1101/2022.12.12.22283200,"COVID-19 Vaccination in Pregnancy: The Impact of Multimorbidity and Smoking Status on Vaccine Hesitancy, a Cohort Study of 25,111 Women in Wales, UK","Mhereeg M, Jones H, Kennedy J, Seaborne M, Parker M, Kennedy N, Akbari A, Zuccolo L, Azcoaga-Lorenzo A, Davies A, Nirantharakumar K, Brophy S.",,No Journal Info,2022,2022-12-14,Y,,,,"

Background

Multimorbidity and pregnancy are two risk factors for more severe outcomes after a SARS-CoV-2 infection, thus vaccination uptake is important for pregnant women living with multimorbidity. This study aimed to examine the impact of multimorbidity, smoking status, and demographics (age, ethnic group, area of deprivation) on vaccine hesitancy among pregnant women in Wales using electronic health records (EHR) linkage.

Methods

This cohort study utilised routinely collected, individual-level, anonymised population-scale linked data within the Secure Anonymised Information Linkage (SAIL) Databank. Pregnant women were identified from 13 th April 2021 to 31 st December 2021. Survival analysis was utilised to examine and compare the length of time to vaccination uptake in pregnancy by multimorbidity and smoking status, as well as depression, diabetes, asthma, and cardiovascular conditions independently. Variation in uptake by; multimorbidity, smoking status, and demographics was examined jointly and separately for the independent conditions using hazard ratios (HR) from the Cox regression model. A bootstrapping internal validation was conducted to assess the performance of the models.

Results

Within the population cohort, 8,203 (32.7%) received at least one dose of the COVID-19 vaccine during pregnancy, with 8,572 (34.1%) remaining unvaccinated throughout the follow-up period, and 8,336 (33.2%) receiving the vaccine postpartum. Women aged 30 years or older were more likely to have the vaccine in pregnancy. Those who had depression were slightly but significantly more likely to have the vaccine compared to those without depression (HR = 1.08, 95% CI 1.03 to 1.14, p = 0.02). Women living with multimorbidity (> 1 health condition) were 1.12 times more likely to have the vaccine compared to those living without multimorbidity (HR = 1.12, 95% CI 1.04 to 1.19, p = 0.001). Vaccine uptakes were significantly lower among both current smokers and former smokers compared to never smokers (HR = 0.87, 95% CI 0.81 to 0.94, p < 0.001 and HR = 0.92, 95% CI 0.85 to 0.98, p = 0.015 respectively). Uptake was also lower among those living in the most deprived areas compared to those living in the most affluent areas (HR = 0.89, 95% CI 0.83 to 0.96, p = 0.002). The validated model had similar performance and revealed that multimorbidity, smoking status, age, and deprivation level together have a significant impact on vaccine hesitancy (p < 0.05 for all).

Conclusion

Younger women, living without multimorbidity (zero or only one health condition), current and former smokers, and those living in the more deprived areas are less likely to have the vaccine, thus, a targeted approach to vaccinations may be required for these groups. Women living with multimorbidity are slightly but significantly less likely to be hesitant about COVID-19 vaccination when pregnant.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa62207/Download/62207__28856__f089034a71e842eeaba218ce327754fe.pdf; doi:https://doi.org/10.1101/2022.12.12.22283200; html:https://europepmc.org/article/PPR/PPR584146; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR584146&type=FILE&fileName=EMS158540-pdf.pdf&mimeType=application/pdf PPR488094,https://doi.org/10.1101/2022.04.29.22274267,Multi-omics identify LRRC15 as a COVID-19 severity predictor and persistent pro-thrombotic signals in convalescence,"Gisby JS, Buang NB, Papadaki A, Clarke CL, Malik TH, Medjeral-Thomas N, Pinheiro D, Mortimer PM, Lewis S, Sandhu E, McAdoo SP, Prendecki MF, Willicombe M, Pickering MC, Botto M, Thomas DC, Peters JE.",,No Journal Info,2022,2022-05-01,Y,,,,"Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. Here, we performed longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identified transcriptomic and proteomic signatures of COVID-19 severity, and found distinct temporal molecular profiles in patients with severe disease. Supervised learning revealed that the plasma proteome was a superior indicator of clinical severity than the PBMC transcriptome. We showed that both the levels and trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, are the strongest predictors of clinical outcome. Strikingly, we observed that two months after the acute infection, patients still display dysregulated gene expression related to vascular, platelet and coagulation pathways, including PF4 (platelet factor 4), which may explain the prolonged thrombotic risk following COVID-19.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/05/01/2022.04.29.22274267.full.pdf; doi:https://doi.org/10.1101/2022.04.29.22274267; html:https://europepmc.org/article/PPR/PPR488094; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR488094&type=FILE&fileName=EMS149480-pdf.pdf&mimeType=application/pdf -PPR850159,https://doi.org/10.1101/2024.05.08.24306990,The impact of the COVID-19 pandemic on Antidepressant Prescribing with a focus on people with learning disability and autism: An interrupted time-series analysis in England using OpenSAFELY-TPP,"Cunningham C, Macdonald O, Schaffer AL, Brown A, Wiedemann M, Higgins R, Bates C, Parry J, Fisher L, Curtis HJ, Mehrkar A, Hart LC, Bacon S, Hulme W, Speed V, Ward T, Croker R, Wood C, Walker A, Andrews C, Butler-Cole B, Evans D, Inglesby P, Dillingham I, Davy S, Bridges L, O’Dwyer T, Maude S, Smith R, Goldacre B, MacKenna B.",,No Journal Info,2024,2024-05-08,Y,,,,"

Background

COVID-19 lockdowns led to increased reports of depressive symptoms in the general population and impacted the health and social care services of people with learning disability and autism. We explored whether the COVID-19 pandemic had an impact on antidepressant prescribing trends within these and the general population.

Methods

With the approval of NHS England, we used >24 million patients’ primary care data from the OpenSAFELY-TPP platform. We identified patients with learning disability or autism and used an interrupted time series analysis to quantify trends in those prescribed and newly prescribed an antidepressant across key demographic and clinical subgroups, comparing pre-COVID-19 (January 2018-February 2020), COVID-19 lockdown (March 2020-February 2021) and the recovery period (March 2021-December 2022).

Results

Prior to COVID-19 lockdown, antidepressant prescribing was increasing at 0.3% (95% CI 0.2% to 0.3%) patients per month, in the general population and in those with learning disability, and 0.3% (95% CI 0.2% to 0.4%) in those with autism. We did not find evidence that the pandemic was associated with a change in trend of antidepressant prescribing in the general population (RR 1.00 (95% CI 0.97 to 1.02)), in those with autism (RR 0.99 (95% CI 0.97 to 1.01)), or in those with learning disability (RR 0.98 (95% CI 0.96 to 1.00)). New prescribing post lockdown was 13% and 12% below expected if COVID-19 had not happened in both the general population and those with autism (RR 0.87 (95% CI 0.83 to 0.93), RR 0.88 (95% CI 0.83 to 0.92))), but not learning disability (RR 0.96 (95% CI 0.87 to 1.05)).

Conclusions and Implications

Pre-COVID-19, antidepressant prescribing was increasing at 0.3% per month. While we did not see an impact of COVID-19 on overall prescribing in the general population, prescriptions to those aged 0-19, 20-29, and new prescriptions were lower than pre-COVID-19 trends would have predicted, but tricyclics and new prescriptions in care homes were higher than expected.

What is already known on this topic

⇒ The prescribing of antidepressants in the UK has been increasing for more than a decade. ⇒ Studies globally have found differing impacts of COVID-19 on mental health outcomes in the general population, by age, sex, socio-economic status, and care home status.

What this study adds

⇒ This study describes the impact of COVID-19 on antidepressant prescribing in England with additional follow-up through December 2022, with a focus on people with a learning disability or autism.

How this study might affect research, practice, or policy

⇒ This study demonstrates how the pandemic did not lead to an increase in antidepressant prescriptions in the general population, but more is needed to ensure that antidepressants are used appropriately within vulnerable populations. ⇒ Improvements are needed in the documentation of diagnosis when prescribing medicines.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2024/05/08/2024.05.08.24306990.full.pdf; doi:https://doi.org/10.1101/2024.05.08.24306990; html:https://europepmc.org/article/PPR/PPR850159 PPR725114,https://doi.org/10.21203/rs.3.rs-3316645/v1,"Uptake, effectiveness and safety of COVID-19 vaccines in the immunocompromised population: A population-based cohort study in England","Chen D, Copland E, Hirst J, Mi E, Dixon S, Coupland C, Hippisley-Cox J.",,No Journal Info,2023,2023-09-14,Y,,,,"Immunocompromised individuals face increased risks of severe COVID-19 outcomes, underscoring the importance of receiving COVID-19 vaccination. However, there's a lack of comprehensive real-world data on their COVID-19 vaccine uptake, effectiveness, and safety profile. We analysed data in the QResearch UK database from 01/12/2020 to 11/04/2022. We included 12,274,948 people aged ≥ 12 years in our analysis, of whom 583,541 (4.8%) were immunocompromised, defined as on immune-modifying drugs, chemotherapy, organ transplants, or dialysis. Overall, 93.7% of immunocompromised patients received at least one COVID-19 vaccine dose. Uptake reduced with increasing deprivation (Hazard Ratio [HR] 0.78 [95% CI 0.77–0.79] in the most deprived quintile compared to the least for the first dose). Using a nested case-control design, estimated vaccine effectiveness against COVID-19 hospitalisation 2–6 weeks after the second and third doses compared to the unvaccinated was 78% (95%CI 72–83) and 91% (95%CI 88–93) for the immunocompromised, versus 85% (95%CI 83–86) and 86% (95%CI 85–89) respectively for the general population. COVID-19 vaccines were protective against intensive care unit admission and death in both groups. There were no differing risks of adverse events during the first 28 days after each dose between the two populations. These findings underscore the importance of ongoing vaccination prioritisation for immunocompromised individuals to maximise protection against severe COVID-19-related outcomes.",,pdf:https://www.researchsquare.com/article/rs-3316645/latest.pdf; doi:https://doi.org/10.21203/rs.3.rs-3316645/v1; html:https://europepmc.org/article/PPR/PPR725114; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR725114&type=FILE&fileName=EMS188044-pdf.pdf&mimeType=application/pdf +PPR850159,https://doi.org/10.1101/2024.05.08.24306990,The impact of the COVID-19 pandemic on Antidepressant Prescribing with a focus on people with learning disability and autism: An interrupted time-series analysis in England using OpenSAFELY-TPP,"Cunningham C, Macdonald O, Schaffer AL, Brown A, Wiedemann M, Higgins R, Bates C, Parry J, Fisher L, Curtis HJ, Mehrkar A, Hart LC, Bacon S, Hulme W, Speed V, Ward T, Croker R, Wood C, Walker A, Andrews C, Butler-Cole B, Evans D, Inglesby P, Dillingham I, Davy S, Bridges L, O’Dwyer T, Maude S, Smith R, Goldacre B, MacKenna B.",,No Journal Info,2024,2024-05-08,Y,,,,"

Background

COVID-19 lockdowns led to increased reports of depressive symptoms in the general population and impacted the health and social care services of people with learning disability and autism. We explored whether the COVID-19 pandemic had an impact on antidepressant prescribing trends within these and the general population.

Methods

With the approval of NHS England, we used >24 million patients’ primary care data from the OpenSAFELY-TPP platform. We identified patients with learning disability or autism and used an interrupted time series analysis to quantify trends in those prescribed and newly prescribed an antidepressant across key demographic and clinical subgroups, comparing pre-COVID-19 (January 2018-February 2020), COVID-19 lockdown (March 2020-February 2021) and the recovery period (March 2021-December 2022).

Results

Prior to COVID-19 lockdown, antidepressant prescribing was increasing at 0.3% (95% CI 0.2% to 0.3%) patients per month, in the general population and in those with learning disability, and 0.3% (95% CI 0.2% to 0.4%) in those with autism. We did not find evidence that the pandemic was associated with a change in trend of antidepressant prescribing in the general population (RR 1.00 (95% CI 0.97 to 1.02)), in those with autism (RR 0.99 (95% CI 0.97 to 1.01)), or in those with learning disability (RR 0.98 (95% CI 0.96 to 1.00)). New prescribing post lockdown was 13% and 12% below expected if COVID-19 had not happened in both the general population and those with autism (RR 0.87 (95% CI 0.83 to 0.93), RR 0.88 (95% CI 0.83 to 0.92))), but not learning disability (RR 0.96 (95% CI 0.87 to 1.05)).

Conclusions and Implications

Pre-COVID-19, antidepressant prescribing was increasing at 0.3% per month. While we did not see an impact of COVID-19 on overall prescribing in the general population, prescriptions to those aged 0-19, 20-29, and new prescriptions were lower than pre-COVID-19 trends would have predicted, but tricyclics and new prescriptions in care homes were higher than expected.

What is already known on this topic

⇒ The prescribing of antidepressants in the UK has been increasing for more than a decade. ⇒ Studies globally have found differing impacts of COVID-19 on mental health outcomes in the general population, by age, sex, socio-economic status, and care home status.

What this study adds

⇒ This study describes the impact of COVID-19 on antidepressant prescribing in England with additional follow-up through December 2022, with a focus on people with a learning disability or autism.

How this study might affect research, practice, or policy

⇒ This study demonstrates how the pandemic did not lead to an increase in antidepressant prescriptions in the general population, but more is needed to ensure that antidepressants are used appropriately within vulnerable populations. ⇒ Improvements are needed in the documentation of diagnosis when prescribing medicines.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2024/05/08/2024.05.08.24306990.full.pdf; doi:https://doi.org/10.1101/2024.05.08.24306990; html:https://europepmc.org/article/PPR/PPR850159 PPR373622,https://doi.org/10.1101/2021.07.19.21260770,Uptake of infant and pre-school immunisations in Scotland and England during the COVID-19 pandemic: an observational study of routinely collected data,"McQuaid F, Mulholland R, Rai YS, Agrawal U, Bedford H, Claire Cameron J, Gibbons C, Roy P, Sheikh A, Shi T, Simpson CR, Tait J, Tessier E, Turner S, Ortega JV, White J, Wood R.",,No Journal Info,2021,2021-07-22,N,,,,"

Background

In 2020, the COVID-19 pandemic and control measures such as national lockdowns threatened to disrupt routine childhood immunisation programmes. Initial reports from the early weeks of lockdown in the UK and worldwide suggested that uptake could fall putting children at risk from multiple other infectious diseases. In Scotland and England, enhanced surveillance of national data for childhood immunisations was established to inform and rapidly assess the impact of the pandemic on infant and preschool immunisation uptake rates.

Methods and findings

We undertook an observational study using routinely collected data for the year prior to the pandemic (2019), and immediately before, during and after the first period of the UK ‘lockdown’ in 2020. Data were obtained for Scotland from the Public Health Scotland “COVID19 wider impacts on the health care system” dashboard ( https://scotland.shinyapps.io/phs-covid-wider-impact/ ) and for England from ImmForm. Five vaccinations delivered at different ages were evaluated; three doses of the ‘6-in-1’ DTaP/IPV/Hib/HepB vaccine and two doses of MMR. Uptake in the periods in 2020 compared to that in the baseline year of 2019 using binary logistic regression analysis. For Scotland, we analysed timely uptake of immunisations, defined as uptake within four weeks of the child becoming eligible by age for each immunisation and data were also analysed by geographical region and indices of deprivation. For both Scotland and England, we assessed whether immunisations were up to date at approximately 6 months (all doses 6-in-1) and 16-18 months (first MMR) of age. We found that uptake rates within four weeks of eligibility in Scotland for all the five vaccine visits were higher during the 2020 lockdown period than in 2019. The difference ranged from 1.3% for the first dose of the 6-in-1 vaccine (95.3 vs 94%, OR 1.28, CI 1.18-1.39) to 14.3% for the second MMR dose (66.1 vs 51.8 %, OR 1.8, CI 1.74-1.87). Significant increases in uptake were seen across all deprivation levels, though, for MMR, there was evidence of greater improvement for children living in the least deprived areas. In England, fewer children who had been due to receive their immunisations during the lockdown period were up to date at 6 months (6-in-1) or 18 months (first dose MMR). The fall in percentage uptake ranged from 0.5% for first 6-in1 (95.8 vs 96.3%, OR 0.89, CI 0.86-0.91) to 2.1% for third 6-in-1 (86.6 vs 88.7%, OR 0.82, CI 0.81-0.83).

Conclusions

This study suggests that the national lockdown in Scotland was associated with a positive effect on timely childhood immunisation uptake, however in England a lower percentage of children were up to date at 6 and 18 months. Reason for the improve uptake in Scotland may include active measures taken to promote immunisation at local and national level during this period. Promoting immunisation uptake and addressing potential vaccine hesitancy is particularly important given the ongoing pandemic and COVID-19 vaccination campaigns.",,pdf:https://discovery.ucl.ac.uk/10144866/3/Bedford_Uptake%20of%20infant%20and%20preschool%20immunisations%20in%20Scotland%20and%20England%20during%20the%20COVID-19%20pandemic_VoR.pdf; doi:https://doi.org/10.1101/2021.07.19.21260770; html:https://europepmc.org/article/PPR/PPR373622; doi:https://doi.org/10.1101/2021.07.19.21260770 PPR453191,https://doi.org/10.1101/2022.02.10.22270799,Evaluating the effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control teams: the COG-UK hospital-onset COVID-19 infection study,"Stirrup O, Blackstone J, Mapp F, MacNeil A, Panca M, Holmes A, Machin N, Shin GY, Mahungu T, Saeed K, Saluja T, Taha Y, Mahida N, Pope C, Chawla A, Cutino-Moguel M, Tamuri A, Williams R, Darby A, Robertson D, Flaviani F, Nastouli E, Robson S, Smith D, Loose M, Laing K, Monahan I, Kele B, Haldenby S, George R, Bashton M, Witney A, Byott M, Coll F, Chapman M, Peacock S, Hughes J, Nebbia G, Partridge DG, Parker M, Price J, Peters C, Roy S, Snell LB, de Silva TI, Thomson E, Flowers P, Copas A, Breuer J, COG-UK HOCI Investigators, The COVID-19 Genomics UK (COG-UK) consortium.",,No Journal Info,2022,2022-02-13,Y,,,,"

Introduction

Viral sequencing of SARS-CoV-2 has been used for outbreak investigation, but there is limited evidence supporting routine use for infection prevention and control (IPC) within hospital settings.

Methods

We conducted a prospective non-randomised trial of sequencing at 14 acute UK hospital trusts. Sites each had a 4-week baseline data-collection period, followed by intervention periods comprising 8 weeks of ‘rapid’ (<48h) and 4 weeks of ‘longer-turnaround’ (5-10 day) sequencing using a sequence reporting tool (SRT). Data were collected on all hospital onset COVID-19 infections (HOCIs; detected ≥48h from admission). The impact of the sequencing intervention on IPC knowledge and actions, and on incidence of probable/definite hospital-acquired infections (HAIs) was evaluated.

Results

A total of 2170 HOCI cases were recorded from October 2020-April 2021, with sequence reports returned for 650/1320 (49.2%) during intervention phases. We did not detect a statistically significant change in weekly incidence of HAIs in longer-turnaround (IRR 1.60, 95%CI 0.85-3.01; P= 0.14) or rapid (0.85, 0.48-1.50; P= 0.54) intervention phases compared to baseline phase. However, IPC practice was changed in 7.8% and 7.4% of all HOCI cases in rapid and longer-turnaround phases, respectively, and 17.2% and 11.6% of cases where the report was returned. In a per-protocol sensitivity analysis there was an impact on IPC actions in 20.7% of HOCI cases when the SRT report was returned within 5 days.

Conclusion

While we did not demonstrate a direct impact of sequencing on the incidence of nosocomial transmission, our results suggest that sequencing can inform IPC response to HOCIs, particularly when returned within 5 days.",,doi:https://doi.org/10.7554/elife.78427; doi:https://doi.org/10.1101/2022.02.10.22270799; html:https://europepmc.org/article/PPR/PPR453191; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR453191&type=FILE&fileName=EMS143624-pdf.pdf&mimeType=application/pdf PPR501055,https://doi.org/10.21203/rs.3.rs-1656915/v1,"Long-COVID in Scotland Study: a nationwide, population cohort study","Pell J, Hastie C, Lowe D, McAuley A, Winter A, Mills N, Black C, Scott J, O'Donnell C, Blane D, Browne S, Ibbotson T.",,No Journal Info,2022,2022-05-24,Y,,,,"BACKGROUNDWith increasing numbers of people infected with SARS-CoV-2, a better understanding of long-COVID is required to inform health and social care support.METHODSA nationwide, ambidirectional, population cohort was constructed of adults in Scotland with a positive SARS-CoV-2 PCR test from April 2020 to May 2021 and a matched, never infected comparison group. Recovery status, symptoms, quality of life, impaired daily activities, hospitalization and death were ascertained via repeated self-completed questionnaires, at 6, 12 and 18-months follow-up, and linkage to hospitalization and death records.RESULTSThe cohort comprised 31,486 symptomatic and 1,795 asymptomatic infected individuals, and 62,957 never infected individuals. Of the former, 1,856 (6%) had not recovered and 13,350 (42%) only partially. Lack of recovery was associated with severe (hospitalized) infection, older age, female sex, deprivation, respiratory disease, depression and multimorbidity. Twenty-four persistent symptoms were independently associated with previous infection including breathlessness (OR 3.44, 95% CI 3.29–3.59), palpitations (OR 2.51, OR 2.37–2.67), chest pain (OR 2.10, 95% CI 1.97–2.24), and confusion (OR 2.93, 95% CI 2.78–3.08). Pre-infection vaccination was associated with reduced risk of seven symptoms. Previous symptomatic infection was also associated with poorer quality of life (EQ-5D median 75 vs 80, p < 0.001) and impairment across all daily activities. Asymptomatic infection was not associated with adverse outcomes.CONCLUSIONSThe sequelae of SARS-CoV-2 infection are wide-ranging and not explained by confounding. The risk of long-COVID is greater following severe infections requiring hospitalization and absent following asymptomatic infection, whilst pre-infection vaccination may be protective.",,pdf:https://www.researchsquare.com/article/rs-1656915/latest.pdf; doi:https://doi.org/10.21203/rs.3.rs-1656915/v1; html:https://europepmc.org/article/PPR/PPR501055; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR501055&type=FILE&fileName=EMS145691-pdf.pdf&mimeType=application/pdf @@ -134,8 +134,8 @@ PPR698319,https://doi.org/10.1101/2023.07.25.23293143,The Cost of Keeping Patien PPR271404,https://doi.org/10.1101/2021.01.20.21250158,REACT-1 round 8 interim report: SARS-CoV-2 prevalence during the initial stages of the third national lockdown in England,"Riley S, Wang H, Eales O, Walters CE, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P.",,No Journal Info,2021,2021-01-22,Y,,,,"

Background

High prevalence of SARS-CoV-2 virus in many northern hemisphere populations is causing extreme pressure on healthcare services and leading to high numbers of fatalities. Even though safe and effective vaccines are being deployed in many populations, the majority of those most at-risk of severe COVID-19 will not be protected until late spring, even in countries already at a more advanced stage of vaccine deployment.

Methods

The REal-time Assessment of Community Transmission study-1 (REACT-1) obtains throat and nose swabs from between 120,000 and 180,000 people in the community in England at approximately monthly intervals. Round 8a of REACT-1 mainly covers a period from 6th January 2021 to 15th January 2021. Swabs are tested for SARS-CoV-2 virus and patterns of swab-positivity are described over time, space and with respect to individual characteristics. We compare swab-positivity prevalence from REACT-1 with mobility data based on the GPS locations of individuals using the Facebook mobile phone app. We also compare results from round 8a with those from round 7 in which swabs were collected from 13th November to 24th November (round 7a) and 25th November to 3rd December 2020 (round 7b).

Results

In round 8a, we found 1,962 positives from 142,909 swabs giving a weighted prevalence of 1.58% (95% CI, 1.49%, 1.68%). Using a constant growth model, we found no strong evidence for either growth or decay averaged across the period; rather, based on data from a limited number of days, prevalence may have started to rise at the end of round 8a. Facebook mobility data showed a marked decrease in activity at the end of December 2020, followed by a rise at the start of the working year in January 2021. Between round 7b and round 8a, prevalence increased in all adult age groups, more than doubling to 0.94% (0.83%, 1.07%) in those aged 65 and over. Large household size, living in a deprived neighbourhood, and Black and Asian ethnicity were all associated with increased prevalence. Both healthcare and care home workers, and other key workers, had increased odds of swab-positivity compared to other workers.

Conclusion

During the initial 10 days of the third COVID-19 lockdown in England in January 2021, prevalence of SARS-CoV-2 was very high with no evidence of decline. Until prevalence in the community is reduced substantially, health services will remain under extreme pressure and the cumulative number of lives lost during this pandemic will continue to increase rapidly.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/01/22/2021.01.20.21250158.full.pdf; doi:https://doi.org/10.1101/2021.01.20.21250158; html:https://europepmc.org/article/PPR/PPR271404; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR271404&type=FILE&fileName=EMS113524-pdf.pdf&mimeType=application/pdf PPR423873,https://doi.org/10.1101/2021.11.22.21266584,"Behaviour, booster vaccines and waning immunity: modelling the medium-term dynamics of SARS-CoV-2 transmission in England in the Omicron era","Barnard RC, Davies NG, Jit M, Edmunds WJ, Centre for Mathematical Modelling of Infectious Diseases COVID-19 working group.",,No Journal Info,2021,2021-11-24,Y,,,,"England has experienced a heavy burden of COVID-19, with multiple waves of SARS-CoV-2 transmission since early 2020 and high infection levels following the emergence and spread of Omicron variants since late 2021. In response to rising Omicron cases, booster vaccinations were accelerated and offered to all adults in England. Using a model fitted to more than 2 years of epidemiological data, we project potential dynamics of SARS-CoV-2 infections, hospital admissions and deaths in England to December 2022. We consider key uncertainties including future behavioural change and waning immunity, and assess the effectiveness of booster vaccinations in mitigating SARS-CoV-2 disease burden between October 2021 and December 2022. If no new variants emerge, SARS-CoV-2 transmission is expected to decline, with low levels remaining in the coming months. The extent to which projected SARS-CoV-2 transmission resurges later in 2022 depends largely on assumptions around waning immunity and to some extent, behaviour and seasonality.",,doi:https://doi.org/10.1101/2021.11.22.21266584; html:https://europepmc.org/article/PPR/PPR423873; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR423873&type=FILE&fileName=EMS140157-pdf.pdf&mimeType=application/pdf PPR463822,https://doi.org/10.21203/rs.3.rs-1140332/v1,The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020,"Knight G, Pham TM, Stimson J, Funk S, Jafari Y, Pople D, Evans S, Yin M, Brown CS, Bhattacharya A, Hope R, Semple MG, Read JM, Cooper BS, Robotham JV.",,No Journal Info,2022,2022-03-03,Y,,,,"

Background:

SARS-CoV-2 is known to transmit in hospital settings, but the contribution of infections acquired in hospitals to the epidemic at a national scale is unknown.

Methods:

We used comprehensive national English datasets to determine the number of COVID-19 patients with identified hospital-acquired infections (with symptom onset >7 days after admission and before discharge) in acute English hospitals up to August 2020. As patients may leave the hospital prior to detection of infection or have rapid symptom onset, we combined measures of the length of stay and the incubation period distribution to estimate how many hospital-acquired infections may have been missed. We used simulations to estimate the total number (identified and unidentified) of symptomatic hospital-acquired infections, as well as infections due to onward community transmission from missed hospital-acquired infections, to 31 st July 2020.

Results:

In our dataset of hospitalised COVID-19 patients in acute English hospitals with a recorded symptom onset date (n = 65,028), 7% were classified as hospital-acquired. We estimated that only 30% (range across weeks and 200 simulations: 20-41%) of symptomatic hospital-acquired infections would be identified, with up to 15% (mean, 95% range over 200 simulations: 14.1%-15.8%) of cases currently classified as community-acquired COVID-19 potentially linked to hospital transmission. We estimated that 26,600 (25,900 to 27,700) individuals acquired a symptomatic SARS-CoV-2 infection in an acute Trust in England before 31st July 2020, resulting in 15,900 (15,200-16,400) or 20.1% (19.2%-20.7%) of all identified hospitalised COVID-19 cases.

Conclusions:

Transmission of SARS-CoV-2 to hospitalised patients likely caused approximately a fifth of identified cases of hospitalised COVID-19 in the “first wave” in England, but less than 1% of all infections in England. Using time to symptom onset from admission for inpatients as a detection method likely misses a substantial proportion (>60%) of hospital-acquired infections.",,doi:https://doi.org/10.21203/rs.3.rs-1140332/v1; html:https://europepmc.org/article/PPR/PPR463822; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR463822&type=FILE&fileName=EMS147320-pdf.pdf&mimeType=application/pdf -PPR412915,https://doi.org/10.1101/2021.10.28.21265615,Transmission dynamics of SARS-CoV-2 in a strictly-Orthodox Jewish community in the UK,"Waites W, Pearson CA, Gaskell KM, House T, Pellis L, Johnson M, Gould V, Hunt A, Stone NR, Kasstan B, Chantler T, Lal S, Roberts Ch, Goldblatt D, Marks M, Eggo RM, CMMID COVID-19 Working Group.",,No Journal Info,2021,2021-10-29,Y,,,,"Some social settings such as households and workplaces, have been identified as high risk for SARS-CoV-2 transmission. Identifying and quantifying the importance of these settings is critical for designing interventions. A tightly-knit religious community in the UK experienced a very large COVID-19 epidemic in 2020, reaching 64.3% seroprevalence within 10 months, and we surveyed this community both for serological status and individual-level attendance at particular settings. Using these data, and a network model of people and places represented as a stochastic graph rewriting system, we estimated the relative contribution of transmission in households, schools and religious institutions to the epidemic, and the relative risk of infection in each of these settings. All congregate settings were important for transmission, with some such as primary schools and places of worship having a higher share of transmission than others. We found that the model needed a higher general-community transmission rate for women (3.3-fold), and lower susceptibility to infection in children to recreate the observed serological data. The precise share of transmission in each place was related to assumptions about the internal structure of those places. Identification of key settings of transmission can allow public health interventions to be targeted at these locations.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/107815/2/Transmission%20dynamics%20of%20SARS-CoV-2%20in%20a%20strictly-Orthodox%20Jewish%20community%20in%20the%20UK.pdf; doi:https://doi.org/10.1101/2021.10.28.21265615; html:https://europepmc.org/article/PPR/PPR412915; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR412915&type=FILE&fileName=EMS137713-pdf.pdf&mimeType=application/pdf PPR312488,https://doi.org/10.1101/2021.04.13.21255342,Protocol for the COG-UK hospital onset COVID-19 infection (HOCI) multicentre interventional clinical study: evaluating the efficacy of rapid genome sequencing of SARS-CoV-2 in limiting the spread of COVID-19 in United Kingdom NHS hospitals,"Blackstone J, Stirrup O, Mapp F, Panca M, Copas A, Flowers P, Hockey L, Price J, Partridge D, Peters C, de Silva T, Nebbia G, Snell LB, McComish R, Breuer J, the COVID-19 Genomics UK (COG-UK) Consortium.",,No Journal Info,2021,2021-04-15,N,,,,"

Introduction

Nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a significant cause of mortality in National Health Service (NHS) hospitals during the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study is to evaluate the impact of rapid whole genome sequencing of SARS-CoV-2, supported by a novel probabilistic reporting methodology, to inform infection prevention and control (IPC) practice within NHS hospital settings.

Methods and analysis

COG-UK HOCI (COG-UK Consortium Hospital-Onset COVID-19 Infections study) is a multicentre, prospective, interventional, superiority study. Eligible patients must be admitted to hospital with first confirmed SARS-CoV-2 PCR positive test result >48h from time of admission, where COVID-19 diagnosis was not suspected upon admission. The projected sample size for 14 participating sites covering all study phases over winter-spring 2020/2021 in the United Kingdom is 2,380 patients. The intervention is the return of a sequence report, within 48 hours in one phase (rapid local lab) and within 5-10 days in a second phase (mimicking central lab use), comparing the viral genome from an eligible study participant with others within and outside the hospital site. The primary outcomes are the incidence of Public Health England (PHE)/IPC-defined SARS-CoV-2 hospital-acquired infection during the baseline and two interventional phases, and proportion of hospital-onset cases with genomic evidence of transmission linkage following implementation of the intervention where such linkage was not suspected by initial IPC investigation. Secondary outcomes include incidence of hospital outbreaks, with and without sequencing data; actual and desirable changes to IPC actions; periods of healthcare worker (HCW) absence. A process evaluation using qualitative interviews with HCWs will be conducted alongside the study and analysis, underpinned by iterative programme theory of the sequence report. Health economic analysis will be conducted to determine cost-benefit of the intervention, and whether this leads to economic advantages within the NHS setting.

Ethics and dissemination

The protocol has been approved by the National Research Ethics Service Committee (Cambridge South 20/EE/0118). This manuscript is based on version 5.0 of the protocol. The study findings will be disseminated through peer-reviewed publications.

Study Registration number

ISRCTN50212645

Strengths and limitations of this study

The COG-UK HOCI study harnesses the infrastructure of the UK’s existing national COVID-19 genome sequencing platform to evaluate the specific benefit of sequencing to hospital infection control. The evaluation is thought to be the first interventional study globally to assess effectiveness of genomic sequencing for infection control in an unbiased patient selection in secondary care settings. A range of institutional settings will participate, from specialist NHS-embedded or academic centres experienced in using pathogen genomics to district general hospitals. The findings are likely to have wider applicability in future decisions to utilise genome sequencing for infection control of other pathogens (such as influenza, respiratory syncytial virus, norovirus, clostridium difficile and antimicrobial resistant pathogens) in secondary care settings. The study has been awarded UK NIHR Urgent Public Health status, ensuring prioritised access to NIHR Clinical Research Network (CRN) research staff to recruit patients. The study does not have a randomised controlled design due to the logistics of managing this against diverse standard practice.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e052514.full.pdf; doi:https://doi.org/10.1101/2021.04.13.21255342; html:https://europepmc.org/article/PPR/PPR312488; doi:https://doi.org/10.1101/2021.04.13.21255342 +PPR412915,https://doi.org/10.1101/2021.10.28.21265615,Transmission dynamics of SARS-CoV-2 in a strictly-Orthodox Jewish community in the UK,"Waites W, Pearson CA, Gaskell KM, House T, Pellis L, Johnson M, Gould V, Hunt A, Stone NR, Kasstan B, Chantler T, Lal S, Roberts Ch, Goldblatt D, Marks M, Eggo RM, CMMID COVID-19 Working Group.",,No Journal Info,2021,2021-10-29,Y,,,,"Some social settings such as households and workplaces, have been identified as high risk for SARS-CoV-2 transmission. Identifying and quantifying the importance of these settings is critical for designing interventions. A tightly-knit religious community in the UK experienced a very large COVID-19 epidemic in 2020, reaching 64.3% seroprevalence within 10 months, and we surveyed this community both for serological status and individual-level attendance at particular settings. Using these data, and a network model of people and places represented as a stochastic graph rewriting system, we estimated the relative contribution of transmission in households, schools and religious institutions to the epidemic, and the relative risk of infection in each of these settings. All congregate settings were important for transmission, with some such as primary schools and places of worship having a higher share of transmission than others. We found that the model needed a higher general-community transmission rate for women (3.3-fold), and lower susceptibility to infection in children to recreate the observed serological data. The precise share of transmission in each place was related to assumptions about the internal structure of those places. Identification of key settings of transmission can allow public health interventions to be targeted at these locations.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/107815/2/Transmission%20dynamics%20of%20SARS-CoV-2%20in%20a%20strictly-Orthodox%20Jewish%20community%20in%20the%20UK.pdf; doi:https://doi.org/10.1101/2021.10.28.21265615; html:https://europepmc.org/article/PPR/PPR412915; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR412915&type=FILE&fileName=EMS137713-pdf.pdf&mimeType=application/pdf PPR276226,https://doi.org/10.1101/2021.01.28.21250606,REACT-1 round 8 final report: high average prevalence with regional heterogeneity of trends in SARS-CoV-2 infection in the community in England during January 2021,"Riley S, Eales O, Walters CE, Wang H, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P.",,No Journal Info,2021,2021-01-31,Y,,,,"In early January 2021, England entered its third national lockdown of the COVID-19 pandemic to reduce numbers of deaths and pressure on healthcare services, while rapidly rolling out vaccination to healthcare workers and those most at risk of severe disease and death. REACT-1 is a survey of SARS-CoV-2 prevalence in the community in England, based on repeated cross-sectional samples of the population. Between 6th and 22nd January 2021, out of 167,642 results, 2,282 were positive giving a weighted national prevalence of infection of 1.57% (95% CI, 1.49%, 1.66%). The R number nationally over this period was estimated at 0.98 (0.92, 1.04). Prevalence remained high throughout, but with suggestion of a decline at the end of the study period. The average national trend masked regional heterogeneity, with robustly decreasing prevalence in one region (South West) and increasing prevalence in another (East Midlands). Overall prevalence at regional level was highest in London at 2.83% (2.53%, 3.16%). Although prevalence nationally was highest in the low-risk 18 to 24 year old group at 2.44% (1.96%, 3.03%), it was also high in those over 65 years who are most at risk, at 0.93% (0.82%, 1.05%). Large household size, living in a deprived neighbourhood, and Black and Asian ethnicity were all associated with higher levels of infections compared to smaller households, less deprived neighbourhoods and other ethnicities. Healthcare and care home workers, and other key workers, were more likely to test positive compared to other workers. If sustained lower prevalence is not achieved rapidly in England, pressure on healthcare services and numbers of COVID-19 deaths will remain unacceptably high.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/01/31/2021.01.28.21250606.full.pdf; doi:https://doi.org/10.1101/2021.01.28.21250606; html:https://europepmc.org/article/PPR/PPR276226; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR276226&type=FILE&fileName=EMS115605-pdf.pdf&mimeType=application/pdf PPR526793,https://doi.org/10.1101/2022.07.30.22278161,Changes in COVID-19-related mortality across key demographic and clinical subgroups: an observational cohort study using the OpenSAFELY platform on 18 million adults in England,"The OpenSAFELY Collaborative, Nab L, Parker EP, Andrews CD, Hulme WJ, Fisher L, Morley J, Mehrkar A, MacKenna B, Inglesby P, Morton CE, Bacon SC, Hickman G, Evans D, Ward T, Smith RM, Davey S, Dillingham I, Maude S, Butler-Cole BF, O’Dwyer T, Stables CL, Bridges L, Bates C, Cockburn J, Parry J, Hester F, Harper S, Zheng B, Williamson EJ, Eggo RM, Evans S, Goldacre B, Tomlinson LA, Walker AJ.",,No Journal Info,2022,2022-08-02,Y,,,,"

Objectives

To quantify in absolute and relative terms how population-level COVID-19 death rates have changed in demographic and clinical subgroups.

Design

Retrospective cohort study on behalf of NHS England.

Setting

Linked primary care and death registry data from the OpenSAFELY-TPP platform, covering the first three pandemic waves in England (wave 1: March 23 to May 30, 2020; wave 2: September 7, 2020 to April 24, 2021; and wave 3, delta: May 28 to December 14, 2021).

Participants

In total, 18.7, 18.8, and 18.7 million adults were included for waves 1, 2, and 3 respectively.

Main outcome measures

COVID-19-related mortality based on linked death registry records.

Results

The crude absolute COVID-19-related death rate per 1,000 person-years decreased from 4.48 in wave 1 (95%CI 4.41;4.55), to 2.70 in wave 2 (95%CI 2.67;2.73), to 0.64 in wave 3 (95%CI 0.63;0.66). The absolute death rate decreased by 90% between waves 1 and 3 in patients aged 80+, but by only 20% in patients aged 18-39. This higher proportional reduction in age- and sex-standardised death rates was also seen for other groups, such as neurological disease, learning disability and severe mental illness. Conversely, standardised death rates in transplant recipients stayed constant across successive waves at 10 per 1,000 person-years. There was also only a small decrease in death rates between waves in people with kidney disease, haematological malignancies or conditions associated with immunosuppression. Consequently, the relative hazard of COVID-19-related death decreased over time for some variables (e.g. age), remained similar for some (e.g. sex, ethnicity), and increased for others (e.g. transplant).

Conclusions

COVID-19 death rates decreased over the first three pandemic waves. An especially large decrease was seen in older age groups and people with neurological disease, learning disability or severe mental illness. Some demographic inequalities in death rates persisted over time. Groups more likely to experience impaired vaccine effectiveness did not see the same benefit in COVID-19 mortality reduction.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/08/02/2022.07.30.22278161.full.pdf; doi:https://doi.org/10.1101/2022.07.30.22278161; html:https://europepmc.org/article/PPR/PPR526793; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR526793&type=FILE&fileName=EMS152162-pdf.pdf&mimeType=application/pdf PPR357531,https://doi.org/10.1101/2021.06.15.21258542,"Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial","RECOVERY Collaborative Group, Horby PW, Mafham M, Peto L, Campbell M, Pessoa-Amorim G, Spata E, Staplin N, Emberson JR, Prudon B, Hine P, Brown T, Green CA, Sarkar R, Desai P, Yates B, Bewick T, Tiberi S, Felton T, Baillie JK, Buch MH, Chappell LC, Day JN, Faust SN, Jaki T, Jeffery K, Juszczak E, Lim WS, Montgomery A, Mumford A, Rowan K, Thwaites G, Weinreich DM, Haynes R, Landray MJ.",,No Journal Info,2021,2021-06-16,Y,,,,"

SUMMARY

Background

REGEN-COV is a combination of 2 monoclonal antibodies (casirivimab and imdevimab) that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike protein. We aimed to evaluate the efficacy and safety of REGEN-COV in patients admitted to hospital with COVID-19.

Methods

In this randomised, controlled, open-label platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Eligible and consenting patients were randomly allocated (1:1) to either usual standard of care alone (usual care group) or usual care plus a single dose of REGEN-COV 8g (casirivimab 4g and imdevimab 4g) by intravenous infusion (REGEN-COV group). The primary outcome was 28-day mortality assessed first among patients without detectable antibodies to SARS-CoV-2 at randomisation (seronegative) and then in the overall population. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov ( NCT04381936 ).

Findings

Between 18 September 2020 and 22 May 2021, 9785 patients were randomly allocated to receive usual care plus REGEN-COV or usual care alone, including 3153 (32%) seronegative patients, 5272 (54%) seropositive patients and 1360 (14%) patients with unknown baseline antibody status. In the primary efficacy population of seronegative patients, 396 (24%) of 1633 patients allocated to REGEN-COV and 451 (30%) of 1520 patients allocated to usual care died within 28 days (rate ratio 0·80; 95% CI 0·70-0·91; p=0·0010). In an analysis involving all randomised patients (regardless of baseline antibody status), 944 (20%) of 4839 patients allocated to REGEN-COV and 1026 (21%) of 4946 patients allocated to usual care died within 28 days (rate ratio 0·94; 95% CI 0·86-1·03; p=0·17). The proportional effect of REGEN-COV on mortality differed significantly between seropositive and seronegative patients (p value for heterogeneity = 0·001).

Interpretation

In patients hospitalised with COVID-19, the monoclonal antibody combination of casirivimab and imdevimab (REGEN-COV) reduced 28-day mortality among patients who were seronegative at baseline.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).",,pdf:https://nottingham-repository.worktribe.com/preview/7415985/1-s2.0-S0140673622001635-main.pdf; doi:https://doi.org/10.1101/2021.06.15.21258542; html:https://europepmc.org/article/PPR/PPR357531; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR357531&type=FILE&fileName=EMS127953-pdf.pdf&mimeType=application/pdf @@ -163,8 +163,8 @@ PPR605135,https://doi.org/10.2139/ssrn.4066712,Using National Electronic Health PPR731647,https://doi.org/10.2139/ssrn.4580461,A Comprehensive Benchmark for COVID-19 Predictive Modeling Using Electronic Health Records in Intensive Care,"Gao J, Zhu Y, Wang W, Dong G, Tang W, Wang H, Wang Y, Harrison EM, Ma L.",,No Journal Info,2023,2023-09-27,N,,,,"The COVID-19 pandemic highlighted the need for predictive deep learning models in healthcare. However, practical prediction task design, fair comparison and model selection for clinical applications remain a challenge. To address this, we introduced and evaluated two new prediction tasks - Outcome-specific length-of-stay and Early mortality prediction for COVID-19 patients in intensive care - which better reflect clinical realities. We developed evaluation metrics, model adaptation designs, and open-source data preprocessing pipelines for these tasks, while also evaluating 18 predictive models, including clinical scoring methods, traditional machine learning, basic deep learning, and advanced deep learning models tailored for EHR data. Benchmarking results from two real-world COVID-19 EHR datasets are provided, and all results and trained models are released on an online platform for use by clinicians and researchers. Our efforts contribute to the advancement of deep learning and machine learning research in pandemic predictive modeling.",,doi:https://doi.org/10.2139/ssrn.4580461; html:https://europepmc.org/article/PPR/PPR731647; doi:https://doi.org/10.2139/ssrn.4580461 PPR573047,https://doi.org/10.1101/2022.11.16.22282396,Comparative effectiveness of two- and three-dose schedules involving AZD1222 and BNT162b2 in people with kidney disease: a linked OpenSAFELY and UK Renal Registry cohort study,"The OpenSAFELY Collaborative, Parker EP, Horne EM, Hulme WJ, Tazare J, Zheng B, Carr EJ, Loud F, Lyon S, Mahalingasivam V, MacKenna B, Mehrkar A, Scanlon M, Santhakumaran S, Steenkamp R, Goldacre B, Sterne JA, Nitsch D, Tomlinson LA, The LH&W NCS (or CONVALESCENCE) Collaborative.",,No Journal Info,2022,2022-11-18,Y,,,,"

Background

Kidney disease is a key risk factor for COVID-19-related mortality and suboptimal vaccine response. Optimising vaccination strategies is essential to reduce the disease burden in this vulnerable population.

Methods

With the approval of NHS England, we performed a retrospective cohort study to estimate the comparative effectiveness of schedules involving AZD1222 (AZ; ChAdOx1-S) and BNT162b2 (BNT) among people with kidney disease. Using linked primary care and UK Renal Registry records in the OpenSAFELY-TPP platform, we identified adults with stage 3– 5 chronic kidney disease, dialysis recipients, and kidney transplant recipients. We used Cox proportional hazards models to compare COVID-19-related outcomes and non-COVID-19 death after two-dose (AZ–AZ vs BNT–BNT) and three-dose (AZ–AZ–BNT vs BNT–BNT– BNT) schedules.

Findings

After two doses, incidence during the Delta wave was higher in AZ–AZ (n=257,580) than BNT–BNT recipients (n=169,205; adjusted hazard ratios [95% CIs] 1·43 [1·37–1·50], 1·59 [1·43–1·77], 1·44 [1·12–1·85], and 1·09 [1·02–1·17] for SARS-CoV-2 infection, COVID-19-related hospitalisation, COVID-19-related death, and non-COVID-19 death, respectively). Findings were consistent across disease subgroups, including dialysis and transplant recipients. After three doses, there was little evidence of differences between AZ– AZ–BNT (n=220,330) and BNT–BNT–BNT recipients (n=157,065) for any outcome during a period of Omicron dominance.

Interpretation

Among individuals with moderate-to-severe kidney disease, two doses of BNT conferred stronger protection than AZ against SARS-CoV-2 infection and severe disease. A subsequent BNT dose levelled the playing field, emphasising the value of heterologous RNA doses in vulnerable populations.

Funding

National Core Studies, Wellcome Trust, MRC, and Health Data Research UK.

Research in context

Evidence before this study

We searched Medline for studies published between 1 st December 2020 and 7 th September 2022 using the following term: “(coronavir* or covid* or sars*) and (vaccin* or immunis* or immuniz*) and (kidney or dialysis or h?emodialysis or transplant or renal) and (efficacy or effectiveness)” . We identified studies reporting on the effectiveness of various COVID-19 vaccines in individuals with chronic kidney disease (CKD) or end-stage renal disease. Several studies have reported no clear differences in effectiveness against outcomes of varying severity after two doses of BNT162b2 or AZD1222 compared to unvaccinated controls, which is contrary to the significantly higher antibody levels observed after BNT162b2 in immunogenicity studies. One study also showed that a third dose of RNA vaccine restored some protection against the Omicron variant among BNT162b2- and AZD1222-primed individuals, with no clear differences between these groups. This finding is consistent with immunogenicity data suggesting that a third dose of BNT162b2 may reduce the gap in antibody levels observed after two of AZD1222 versus BNT162b2. Notably, we found few studies directly comparing effectiveness in BNT162b2 versus AZD1222 recipients, which reduces biases associated with comparison to a small and potentially unrepresentative group of unvaccinated controls. We also found no studies exploring COVID-19 vaccine effectiveness in kidney disease groups of varying severity (CKD, dialysis, and kidney transplant).

Added value of this study

This is the largest study to compare the effectiveness of two- and three-dose regimens involving AZD1222 and BNT162b2 among people with moderate-to-severe kidney disease. We compared effectiveness after two and three doses in 426,780 and 377,395 individuals, respectively, and harnessed unique data linkages between primary care records and UK Renal Registry data to identify people with CKD and end-stage renal disease (including dialysis and kidney transplant recipients) with high accuracy. During the Delta wave of infection, we observed a higher risk of COVID-19-related outcomes of varying severity after two doses of AZD1222 versus BNT162b2, with consistent findings in CKD, dialysis, and transplant subgroups. After a third dose of BNT162b2, AZD1222- and BNT162b2-primed individuals had similar rates of COVID-19-related outcomes during a period of Omicron dominance. Implications of all the available evidence A growing body of immunogenicity and effectiveness data – including the present study – suggest that two doses of BNT162b2 confers stronger protection than AZD1222 among people with moderate-to-severe kidney disease. However, a third dose of BNT162b2 appears to compensate for this immunity deficit, providing equivalent protection in BNT162b2- and AZD1222-primed individuals. Achieving high coverage with additional RNA vaccine doses (whether homologous or heterologous) has the capacity to reduce the burden of disease in this vulnerable population.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/11/18/2022.11.16.22282396.full.pdf; doi:https://doi.org/10.1101/2022.11.16.22282396; html:https://europepmc.org/article/PPR/PPR573047; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR573047&type=FILE&fileName=EMS157362-pdf.pdf&mimeType=application/pdf PPR278785,https://doi.org/10.1101/2021.02.03.21251004,Ethnic differences in COVID-19 mortality during the first two waves of the Coronavirus Pandemic: a nationwide cohort study of 29 million adults in England,"Nafilyan V, Islam N, Mathur R, Ayoubkhani D, Banerjee A, Glickman M, Humberstone B, Diamond I, Khunti K.",,No Journal Info,2021,2021-02-05,Y,,,,"

Background

Ethnic minorities have experienced disproportionate COVID-19 mortality rates in the UK and many other countries. We compared the differences in the risk of COVID-19 related death between ethnic groups in the first and second waves the of COVID-19 pandemic in England. We also investigated whether the factors explaining differences in COVID-19 death between ethnic groups changed between the two waves.

Methods

Using data from the Office for National Statistics Public Health Data Asset on individuals aged 30-100 years living in private households, we conducted an observational cohort study to examine differences in the risk of death involving COVID-19 between ethnic groups in the first wave (from 24 th January 2020 until 31 st August 2020) and second wave (from 1 st September to 28 th December 2020). We estimated age-standardised mortality rates (ASMR) in the two waves stratified by ethnic groups and sex. We also estimated hazard ratios (HRs) for ethnic-minority groups compared with the White British population, adjusted for geographical factors, socio-demographic characteristics, and pre-pandemic health conditions.

Results

The study population included over 28.9 million individuals aged 30-100 years living in private households. In the first wave, all ethnic minority groups had a higher risk of COVID-19 related death compared to the White British population. In the second wave, the risk of COVID-19 death remained elevated for people from Pakistani (ASMR: 339.9 [95% CI: 303.7 – 376.2] and 166.8 [141.7 – 191.9] deaths per 100,000 population in men and women) and Bangladeshi (318.7 [247.4 – 390.1] and 127.1 [91.1 – 171.3] in men and women)background but not for people from Black ethnic groups. Adjustment for geographical factors explained a large proportion of the differences in COVID-19 mortality in the first wave but not in the second wave. Despite an attenuation of the elevated risk of COVID-19 mortality after adjusting for sociodemographic characteristics and health status, the risk was substantially higher in people from Bangladeshi and Pakistani background in both the first and the second waves.

Conclusion

Between the first and second waves of the pandemic, the reduction in the difference in COVID-19 mortality between people from Black ethnic background and people from the White British group shows that ethnic inequalities in COVID-19 mortality can be addressed. The continued higher rate of mortality in people from Bangladeshi and Pakistani background is alarming and requires focused public health campaign and policy changes. *VN and NI contributed equally to this paper

Research in context

Evidence before this study

A recent systematic review by Pan and colleagues demonstrated that people of ethnic minority background in the UK and the USA have been disproportionately affected by the Coronavirus (COVID-19) pandemic, compared to White populations. While several studies have investigated whether adjusting for socio-demographic and economic factors and medical history reduces the estimated difference in risk of mortality and hospitalisation, the reasons for the differences in the risk of experiencing harms from COVID-19 are still being explored during the course of the pandemic. Studies so far have analysed the ethnic differences in COVID-19 mortality in the first wave of the pandemic. The evidence on the temporal trend of ethnic inequalities in COVID-19 mortality, especially those from the second wave of the pandemic, is scarce.

Added value of this study

Using data from the Office for National Statistics (ONS) Public Health Data Asset on 29 million adults aged 30-100 years living in private households in England, we conducted an observational cohort study to examine the differences in the risk of death involving COVID-19 between ethnic groups in the first wave (from 24 th January 2020 until 31 st August 2020) and second wave (from 1 st September to 28 th December 2020). We find that in the first wave all ethnic minority groups were at elevated risk of COVID-19 related death compared to the White British population. In the second wave, the differences in the risk of COVID-19 related death attenuated for Black African and Black Caribbean groups, remained substantially higher in people from Bangladeshi background, and worsened in people from Pakistani background. We also find that some of the factors explaining these differences in mortality have changed in the two waves.

Implications of all the available evidence

The risk of COVID-19 mortality during the first wave of the pandemic was elevated in people from ethnic minority background. An appreciable reduction in the difference in COVID-19 mortality in the second wave of the pandemic between people from Black ethnic background and people from the White British group is reassuring, but the continued higher rate of mortality in people from Bangladeshi and Pakistani background is alarming and requires focused public health campaign and policy response. Focusing on treating underlying conditions, although important, may not be enough in reducing the inequalities in COVID-19 mortality. Focused public health policy as well as community mobilisation and participatory public health campaign involving community leaders may help reduce the existing and widening inequalities in COVID-19 mortality.",,pdf:https://link.springer.com/content/pdf/10.1007/s10654-021-00765-1.pdf; doi:https://doi.org/10.1101/2021.02.03.21251004; html:https://europepmc.org/article/PPR/PPR278785; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR278785&type=FILE&fileName=EMS116038-pdf.pdf&mimeType=application/pdf -PPR265251,https://doi.org/10.1101/2021.01.15.21249724,Development and evaluation of rapid data-enabled access to routine clinical information to enhance early recruitment to the national clinical platform trial of COVID-19 community treatments,"Cake C, Ogburn E, Pinches H, Coleman G, Seymour D, Woodard F, Manohar S, Monsur M, Landray M, Dalton G, Morris AD, Chinnery PF, Hobbs FR, Butler C, UK COVID-19 National Core Studies Consortium.",,No Journal Info,2021,2021-01-15,Y,,,,"

ABSTRACT

Background

The COVID-19 pandemic has presented unique challenges for rapidly designing, initiating, and delivering therapeutic clinical trials. PRINCIPLE is the UK national platform investigating repurposed therapies for COVID-19 treatment of older people in the community at high risk of complications. Standard methods of patient recruitment were failing to meet the required pace and scale of enrolment. This paper describes the development and appraisal of a near real-time, data-driven, ethical approach for enhancing recruitment in community care by contacting people with a recent COVID-19 positive test result from the central NHS Test and Trace service within 24-48 hours of their test result.

Methods

A multi-disciplinary team was formed to solve the technical, ethical, public perception, logistical and information governance issues required to provide a near-real time (within 24-48 hours of receiving a positive test) feed of potential trial participants from test result data to the research team. PRINCIPLE was also given unique access to the Summary Care Record (SCR) to ensure safe prescribing, and to enable the trial team to quickly and safely bring consented patients into the trial. A survey of the public was used to understand public perceptions of the use of test data for this proposed methodology.

Results

Prior to establishing the data service, PRINCIPLE registered on average 87 participants per week. This increased by up to 87 additional people registered per week from the test data, contributing to an increase from 1,013 recruits to PRINCIPLE at the start of October 2020 to 2,802 recruits by 20 th December 2020. While procedural caveats were identified by the public consultation, out of 2,639 people contacted by PRINCIPLE following a positive test result, no one raised a concern about being approached.

Conclusions

This paper describes a novel approach to using near-real time NHS operational data to recruit community-based patients within a few days of presentation with acute illness. This approach increased recruitment, and reduced time between positive test and randomisation, allowing more rapid evaluation of treatments and increased safety for participants. End-to-end public and patient involvement in the design of the approach provided evidence to inform information governance decisions.

Trial registration

PRINCIPLE is funded by UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research. EudraCT number: 2020-001209-22 ISRCTN registry: ISRCTN86534580 REC number: 20/SC/058 IRAS number: 281958",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-021-05965-4; doi:https://doi.org/10.1101/2021.01.15.21249724; html:https://europepmc.org/article/PPR/PPR265251; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR265251&type=FILE&fileName=EMS110588-pdf.pdf&mimeType=application/pdf PPR230575,https://doi.org/10.1101/2020.10.26.20219725,"Declining prevalence of antibody positivity to SARS-CoV-2: a community study of 365,000 adults","Ward H, Cooke G, Atchison C, Whitaker M, Elliott J, Moshe M, Brown JC, Flower B, Daunt A, Ainslie K, Ashby D, Donnelly C, Riley S, Darzi A, Barclay W, Elliott P, for the REACT study team.",,No Journal Info,2020,2020-10-27,Y,,,,"

Background

The prevalence and persistence of antibodies following a peak SARS-CoV-2 infection provides insights into its spread in the community, the likelihood of reinfection and potential for some level of population immunity.

Methods

Prevalence of antibody positivity in England, UK (REACT2) with three cross-sectional surveys between late June and September 2020. 365104 adults used a self-administered lateral flow immunoassay (LFIA) test for IgG. A laboratory comparison of LFIA results to neutralization activity in panel of sera was performed.

Results

There were 17,576 positive tests over the three rounds. Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% [5.8, 6.1], to 4.8% [4.7, 5.0] and 4.4% [4.3, 4.5], a fall of 26.5% [-29.0, −23.8] over the three months of the study. There was a decline between rounds 1 and 3 in all age groups, with the highest prevalence of a positive result and smallest overall decline in positivity in the youngest age group (18-24 years: −14.9% [-21.6, −8.1]), and lowest prevalence and largest decline in the oldest group (75+ years: −39.0% [-50.8, −27.2]); there was no change in antibody positivity between rounds 1 and 3 in healthcare workers (+3.45% [-5.7, +12.7]). The decline from rounds 1 to 3 was largest in those who did not report a history of COVID-19, (−64.0% [-75.6, −52.3]), compared to −22.3% ([-27.0, −17.7]) in those with SARS-CoV-2 infection confirmed on PCR.

Discussion

These findings provide evidence of variable waning in antibody positivity over time such that, at the start of the second wave of infection in England, only 4.4% of adults had detectable IgG antibodies using an LFIA. Antibody positivity was greater in those who reported a positive PCR and lower in older people and those with asymptomatic infection. These data suggest the possibility of decreasing population immunity and increasing risk of reinfection as detectable antibodies decline in the population.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/10/27/2020.10.26.20219725.full.pdf; doi:https://doi.org/10.1101/2020.10.26.20219725; html:https://europepmc.org/article/PPR/PPR230575; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR230575&type=FILE&fileName=EMS101563-pdf.pdf&mimeType=application/pdf +PPR265251,https://doi.org/10.1101/2021.01.15.21249724,Development and evaluation of rapid data-enabled access to routine clinical information to enhance early recruitment to the national clinical platform trial of COVID-19 community treatments,"Cake C, Ogburn E, Pinches H, Coleman G, Seymour D, Woodard F, Manohar S, Monsur M, Landray M, Dalton G, Morris AD, Chinnery PF, Hobbs FR, Butler C, UK COVID-19 National Core Studies Consortium.",,No Journal Info,2021,2021-01-15,Y,,,,"

ABSTRACT

Background

The COVID-19 pandemic has presented unique challenges for rapidly designing, initiating, and delivering therapeutic clinical trials. PRINCIPLE is the UK national platform investigating repurposed therapies for COVID-19 treatment of older people in the community at high risk of complications. Standard methods of patient recruitment were failing to meet the required pace and scale of enrolment. This paper describes the development and appraisal of a near real-time, data-driven, ethical approach for enhancing recruitment in community care by contacting people with a recent COVID-19 positive test result from the central NHS Test and Trace service within 24-48 hours of their test result.

Methods

A multi-disciplinary team was formed to solve the technical, ethical, public perception, logistical and information governance issues required to provide a near-real time (within 24-48 hours of receiving a positive test) feed of potential trial participants from test result data to the research team. PRINCIPLE was also given unique access to the Summary Care Record (SCR) to ensure safe prescribing, and to enable the trial team to quickly and safely bring consented patients into the trial. A survey of the public was used to understand public perceptions of the use of test data for this proposed methodology.

Results

Prior to establishing the data service, PRINCIPLE registered on average 87 participants per week. This increased by up to 87 additional people registered per week from the test data, contributing to an increase from 1,013 recruits to PRINCIPLE at the start of October 2020 to 2,802 recruits by 20 th December 2020. While procedural caveats were identified by the public consultation, out of 2,639 people contacted by PRINCIPLE following a positive test result, no one raised a concern about being approached.

Conclusions

This paper describes a novel approach to using near-real time NHS operational data to recruit community-based patients within a few days of presentation with acute illness. This approach increased recruitment, and reduced time between positive test and randomisation, allowing more rapid evaluation of treatments and increased safety for participants. End-to-end public and patient involvement in the design of the approach provided evidence to inform information governance decisions.

Trial registration

PRINCIPLE is funded by UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research. EudraCT number: 2020-001209-22 ISRCTN registry: ISRCTN86534580 REC number: 20/SC/058 IRAS number: 281958",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-021-05965-4; doi:https://doi.org/10.1101/2021.01.15.21249724; html:https://europepmc.org/article/PPR/PPR265251; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR265251&type=FILE&fileName=EMS110588-pdf.pdf&mimeType=application/pdf PPR233362,https://doi.org/10.1101/2020.10.30.20223123,High prevalence of SARS-CoV-2 swab positivity and increasing R number in England during October 2020: REACT-1 round 6 interim report,"Riley S, Ainslie KEC, Eales O, Walters CE, Wang H, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P.",,No Journal Info,2020,2020-11-03,Y,,,,"

Background

REACT-1 measures prevalence of SARS-CoV-2 infection in representative samples of the population in England using PCR testing from self-administered nose and throat swabs. Here we report interim results for round 6 of observations for swabs collected from the 16th to 25th October 2020 inclusive.

Methods

REACT-1 round 6 aims to collect data and swab results from 160,000 people aged 5 and above. Here we report results from the first 86,000 individuals. We estimate prevalence of PCR-confirmed SARS-CoV-2 infection, reproduction numbers (R) and temporal trends using exponential growth or decay models. Prevalence estimates are presented both unweighted and weighted to be representative of the population of England, accounting for response rate, region, deprivation and ethnicity. We compare these interim results with data from round 5, based on swabs collected from 18th September to 5th October 2020 inclusive.

Results

Overall prevalence of infection in the community in England was 1.28% or 128 people per 10,000, up from 60 per 10,000 in the previous round. Infections were doubling every 9.0 (6.1, 18) days with a national reproduction number (R) estimated at 1.56 (1.27, 1.88) compared to 1.16 (1.05, 1.27) in the previous round. Prevalence of infection was highest in Yorkshire and The Humber at 2.72% (2.12%, 3.50%), up from 0.84% (0.60%, 1.17%), and the North West at 2.27% (1.90%, 2.72%), up from 1.21% (1.01%, 1.46%), and lowest in South East at 0.55% (0.45%, 0.68%), up from 0.29% (0.23%, 0.37%). Clustering of cases was more prevalent in Lancashire, Manchester, Liverpool and West Yorkshire, West Midlands and East Midlands. Interim estimates of R were above 2 in the South East, East of England, London and South West, but with wide confidence intervals. Nationally, prevalence increased across all age groups with the greatest increase in those aged 55-64 at 1.20% (0.99%, 1.46%), up 3-fold from 0.37% (0.30%, 0.46%). In those aged over 65, prevalence was 0.81% (0.58%, 0.96%) up 2-fold from 0.35% (0.28%, 0.43%). Prevalence remained highest in 18 to 24-year olds at 2.25% (1.47%, 3.42%).

Conclusion

The co-occurrence of high prevalence and rapid growth means that the second wave of the epidemic in England has now reached a critical stage. Whether via regional or national measures, it is now time-critical to control the virus and turn R below one if further hospital admissions and deaths from COVID-19 are to be avoided.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/11/03/2020.10.30.20223123.full.pdf; doi:https://doi.org/10.1101/2020.10.30.20223123; html:https://europepmc.org/article/PPR/PPR233362; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR233362&type=FILE&fileName=EMS103475-pdf.pdf&mimeType=application/pdf PPR339757,https://doi.org/10.1101/2021.05.08.21256867,SARS-CoV-2 lineage dynamics in England from January to March 2021 inferred from representative community samples,"Eales O, Page AJ, Tang SN, Walters CE, Wang H, Haw D, Trotter AJ, Viet TL, Foster-Nyarko E, Prosolek S, Atchison C, Ashby D, Cooke G, Barclay W, Donnelly CA, O’Grady J, Volz E, Darzi A, Ward H, Elliott P, Riley S, The COVID-19 Genomics UK (COG-UK) Consortium.",,No Journal Info,2021,2021-05-14,Y,,,,"Genomic surveillance for SARS-CoV-2 lineages informs our understanding of possible future changes in transmissibility and vaccine efficacy. However, small changes in the frequency of one lineage over another are often difficult to interpret because surveillance samples are obtained from a variety of sources. Here, we describe lineage dynamics and phylogenetic relationships using sequences obtained from a random community sample who provided a throat and nose swab for rt-PCR during the first three months of 2021 as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Overall, diversity decreased during the first quarter of 2021, with the B.1.1.7 lineage (first identified in Kent) predominant, driven by a 0.3 unit higher reproduction number over the prior wild type. During January, positive samples were more likely B.1.1.7 in younger and middle-aged adults (aged 18 to 54) than in other age groups. Although individuals infected with the B.1.1.7 lineage were no more likely to report one or more classic COVID-19 symptoms compared to those infected with wild type, they were more likely to be antibody positive 6 weeks after infection. Viral load was higher in B.1.1.7 infection as measured by cycle threshold (Ct) values, but did not account for the increased rate of testing positive for antibodies. The presence of infections with non-imported B.1.351 lineage (first identified in South Africa) during January, but not during February or March, suggests initial establishment in the community followed by fade-out. However, this occurred during a period of stringent social distancing and targeted public health interventions and does not immediately imply similar lineages could not become established in the future. Sequence data from representative community surveys such as REACT-1 can augment routine genomic surveillance.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/05/14/2021.05.08.21256867.full.pdf; doi:https://doi.org/10.1101/2021.05.08.21256867; html:https://europepmc.org/article/PPR/PPR339757; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR339757&type=FILE&fileName=EMS127680-pdf.pdf&mimeType=application/pdf PPR354056,https://doi.org/10.1101/2021.06.08.21258535,Altered neutrophil phenotype and function in non-ICU hospitalised COVID-19 patients correlated with disease severity,"Belchamber K, Thein O, Hazeldine J, Grudzinska F, Hughes M, Jasper A, Yip K, Sapey E, Parekh D, Thickett D, Scott A.",,No Journal Info,2021,2021-06-08,Y,,,,"

Rational

Infection with the SARS-CoV2 virus is associated with elevated neutrophil counts. Evidence of neutrophil dysfunction in COVID-19 is based predominantly on transcriptomics or single functional assays. Cell functions are interwoven pathways, and so understanding the effect of COVID-19 across the spectrum of neutrophil function may identify tractable therapeutic targets.

Objectives

Examine neutrophil phenotype and functional capacity in COVID-19 patients versus age-matched controls (AMC)

Methods

Isolated neutrophils from 41 hospitalised, non-ICU COVID-19 patients and 23 AMC underwent ex vivo analyses for migration, bacterial phagocytosis, ROS generation, NET formation (NETosis) and cell surface receptor expression. DNAse 1 activity was measured, alongside circulating levels of cfDNA, MPO, VEGF, IL-6 and sTNFRI. All measurements were correlated to clinical outcome. Serial sampling on day 3-5 post hospitalisation were also measured.

Results

Compared to AMC, COVID-19 neutrophils demonstrated elevated transmigration (p=0.0397) and NETosis (p=0.0366), but impaired phagocytosis (p=0.0236) associated with impaired ROS generation (p<0.0001). Surface expression of CD54 (p<0.0001) and CD11c (p=0.0008) was significantly increased and CD11b significantly decreased (p=0.0229) on COVID-19 patient neutrophils. COVID-19 patients showed increased systemic markers of NETosis including increased cfDNA (p=0.0153) and impaired DNAse activity (p<0.0.001). MPO (p<0.0001), VEGF (p<0.0001), TNFRI (p<0.0001) and IL-6 (p=0.009) were elevated in COVID-19, which positively correlated with disease severity by 4C score.

Conclusion

COVID-19 is associated with neutrophil dysfunction across all main effector functions, with altered phenotype, elevated migration, impaired antimicrobial responses and elevated NETosis. These changes represent a clear mechanism for tissue damage and highlight that targeting neutrophil function may help modulate COVID-19 severity.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/06/08/2021.06.08.21258535.full.pdf; doi:https://doi.org/10.1101/2021.06.08.21258535; html:https://europepmc.org/article/PPR/PPR354056; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR354056&type=FILE&fileName=EMS127476-pdf.pdf&mimeType=application/pdf @@ -186,13 +186,13 @@ PPR167068,https://doi.org/10.1101/2020.05.19.20106278,Benefit-risk analysis of h PPR468085,https://doi.org/10.1101/2022.03.11.22272276,Risk factors for SARS-CoV-2 infection after primary vaccination with ChAdOx1 nCoV-19 or BNT1262b2 and after booster vaccination with BNT1262b2 or mRNA-1273: a population-based cohort study (COVIDENCE UK),"Vivaldi G, Jolliffe DA, Holt H, Tydeman F, Talaei M, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Shaheen SO, Martineau AR.",,No Journal Info,2022,2022-03-13,Y,,,,"

Background

Little is known about the relative influence of demographic, behavioural, and vaccine-related factors on risk of post-vaccination SARS-CoV-2 infection. We aimed to identify risk factors for SARS-CoV-2 infection after primary and booster vaccinations.

Methods

We undertook a prospective population-based study in UK adults (≥16 years) vaccinated against SARS-CoV-2, including data from Jan 12, 2021, to Feb 21, 2022. We modelled risk of post-vaccination SARS-CoV-2 infection separately for participants who had completed a primary course of vaccination (two-dose or, in the immunosuppressed, three-dose course of either ChAdOx1 nCoV-19 [ChAdOx1] or BNT1262b2) and for those who had additionally received a booster dose (BNT1262b2 or mRNA-1273). Cox regression models were used to explore associations between sociodemographic, behavioural, clinical, pharmacological, and nutritional factors and breakthrough infection, defined as a self-reported positive result on a lateral flow or reverse transcription PCR (RT-PCR) test for SARS-CoV-2. Models were further adjusted for weekly SARS-CoV-2 incidence at the local (lower tier local authority) level.

Findings

14,713 participants were included in the post-primary analysis and 10,665 in the post-booster analysis, with a median follow-up of 203 days (IQR 195–216) in the post-primary cohort and 85 days (66–103) in the post-booster cohort. 1051 (7.1%) participants in the post-primary cohort and 1009 (9.4%) participants in the post-booster cohort reported a breakthrough SARS-CoV-2 infection. A primary course of ChAdOx1 ( vs BNT182b2) was associated with higher risk of infection, both in the post-primary cohort (adjusted hazard ratio 1.63, 95% CI 1.41–1.88) and in the post-booster cohort after boosting with mRNA-1273 (1.29 [1.03–1.61] vs BNT162b2 primary plus BNT162b2 booster). A lower risk of breakthrough infection was associated with older age (post-primary: 0.96 [0.96–0.97] per year; post-booster: 0.97 [0.96–0.98]), whereas a higher risk of breakthrough infection was associated with lower levels of education (post-primary: 1.66 [1.35–2.06] for primary or secondary vs postgraduate; post-booster: 1.36 [1.08–1.71]) and at least three weekly visits to indoor public places (post-primary: 1.38 [1.15–1.66] vs none; post-booster: 1.33 [1.10–1.60]).

Conclusions

Vaccine type, socioeconomic status, age, and behaviours affect risk of breakthrough SARS-CoV-2 infection following a primary schedule and a booster dose.

Research in context

Evidence before this study

We searched PubMed, medRxiv, and Google Scholar for papers published up to Feb 18, 2022, using the search terms (breakthrough OR post-vaccin*) AND (SARS-CoV-2 OR COVID) AND (disease OR infection) AND (determinant OR “risk factor” OR associat*), with no language restrictions. Existing studies on risk factors for breakthrough SARS-CoV-2 infection among vaccinated individuals have found associations with age, comorbidities, vaccine type, and previous infection; however, findings have been inconsistent across studies. Most studies have been limited to specific subgroups or have focused on severe outcomes, and very few have considered breakthrough infections after a booster dose or have adjusted for behaviours affecting exposure to other people.

Added value of this study

This study is among the first to provide a detailed analysis of a wide range of risk factors for breakthrough SARS-CoV-2 infection, both after the primary course of vaccination and after a booster dose. Our large study size and detailed data have allowed us to investigate associations with various sociodemographic, clinical, pharmacological, and nutritional factors. Monthly follow-up data have additionally given us the opportunity to consider the effects of behaviours that may have changed across the pandemic, while adjusting for local SARS-CoV-2 incidence.

Implications of all the available evidence

Our findings add to growing evidence that risk factors for SARS-CoV-2 infection after primary or booster vaccinations can differ to those in unvaccinated populations, with effects attenuated for previously observed risk factors such as body-mass index and Asian ethnicity. The clear difference we observed between the efficacies of ChAdOx1 and BNT162b2 as the primary course of vaccination appears to have been reduced by the use of BNT162b2 boosters, but not by mNRA-1273 boosters. As more countries introduce booster vaccinations, future population-based studies with longer follow-up will be needed to investigate our findings further.",,pdf:https://pure.qub.ac.uk/files/383171042/1_s2.0_S2666776222001971_main.pdf; doi:https://doi.org/10.1101/2022.03.11.22272276; html:https://europepmc.org/article/PPR/PPR468085; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR468085&type=FILE&fileName=EMS148998-pdf.pdf&mimeType=application/pdf PPR371208,https://doi.org/10.1101/2021.07.14.21260488,SARS-CoV-2 Antibody Lateral Flow Assay for antibody prevalence studies following vaccine roll out: a Diagnostic Accuracy Study,"Cann A, Clarke C, Brown J, Thomson T, Prendecki M, Moshe M, Badhan A, Elliott P, Darzi A, Riley S, Ashby D, Willicombe M, Kelleher P, Randell P, Ward H, Barclay WS, Cooke G.",,No Journal Info,2021,2021-07-16,Y,,,,"

Background

Lateral flow immunoassays (LFIAs) have the potential to deliver affordable, large scale antibody testing and provide rapid results without the support of central laboratories. As part of the development of the REACT programme extensive evaluation of LFIA performance was undertaken with individuals following natural infection. Here we assess the performance of the selected LFIA to detect antibody responses in individuals who have received at least one dose of SARS-CoV-2 vaccine.

Methods

This is a prospective diagnostic accuracy study.

Setting

Sampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Laboratory analyses were performed across Imperial College London sites and university facilities.

Participants

Two cohorts of patients were recruited; the first was a cohort of 108 renal transplant patients attending clinic following SARS-CoV-2 vaccine booster, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination, and 21 day follow up. A total of 186 paired samples were collected.

Interventions

During the participants visit, capillary blood samples were analysed on LFIA device, while paired venous sampling was sent for serological assessment of antibodies to the spike protein (anti-S) antibodies. Anti-S IgG were detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA.

Main outcome measures

The accuracy of Fortress LFIA in detecting IgG antibodies to SARS-CoV-2 compared to anti-spike protein detection on Abbott Assay.

Results

Using the threshold value for positivity on serological testing of ≥7.10 BAU/ml, the overall performance of the test produces an estimate of sensitivity of 91.94% (95% CI 85.67% to 96.06%) and specificity of 93.55% (95% CI 84.30% to 98.21%) using the Abbott assay as reference standard.

Conclusions

Fortress LFIA performs well in the detection of antibody responses for intended purpose of population level surveys, but does not meet criteria for individual testing.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/07/16/2021.07.14.21260488.full.pdf; doi:https://doi.org/10.1101/2021.07.14.21260488; html:https://europepmc.org/article/PPR/PPR371208; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR371208&type=FILE&fileName=EMS130798-pdf.pdf&mimeType=application/pdf PPR850975,https://doi.org/10.1101/2024.05.09.24307105,Impacts of the COVID-19 pandemic on deprivation-level differences in cardiovascular hospitalisations: A comparison of England and Denmark using the OpenSAFELY platform and National Registry Data,"Costello RE, Henderson AD, Tazare J, Pedersen L, Sorensen HT, Vandenbroucke JP, Mansfield KE, Mahalingasivam V, Zheng B, Carreira H, Bidulka P, Piehlmaier D, Wong AY, Warren-Gash C, Hayes JF, Quint JK, Katikireddi SV, MacKenna B, Mehrkar A, Bacon S, Goldacre B, Tomlinson L, Langan SM, Mathur R, The LH&W NCS (or CONVALESCENCE) Collaborative and the OpenSAFELYcollaborative.",,No Journal Info,2024,2024-05-09,Y,,,,"

Objectives

To examine the impact of the pandemic on deprivation-related inequalities in hospitalisations for CVD conditions in Denmark and England between March 2018 and December 2021.

Design

A series of monthly cross-sectional studies separately in England and Denmark.

Setting:

With the approval of NHS England, we used English primary care electronic health records, linked to secondary care and death registry data through the OpenSAFELY platform, and nationwide Danish health registry data.

Participants

Adults aged 18 and over, without missing age, sex or deprivation information were included. On 1st March 2020, 16,234,700 people in England, and 4,491,336 people in Denmark met the inclusion criteria.

Primary and secondary outcome measures

Hospital admissions with the primary reason myocardial infarction (MI), ischaemic or haemorrhagic stroke, heart failure, and venous thromboembolism (VTE).

Results

We saw deprivation gradients in monthly CVD hospitalisations in both countries, with differences more pronounced in Denmark. Based on pre-pandemic trends, in England, there were an estimated 2608 fewer admissions than expected for heart failure in the most deprived quintile during the pandemic, compared to an estimated 979 fewer admissions in the least deprived quintile. In Denmark, there were an estimated 1013 fewer admissions than expected over the pandemic for MI in the most deprived quintile compared to 619 in the least deprived quintile. Similar trends were seen for stroke and VTE, though absolute numbers were smaller.

Conclusions

Overall, we did not find that the pandemic substantially worsened pre-existing deprivation-related differences in CVD hospitalisations, though there were exceptions in both countries.

Strengths and limitations

This was one of the largest studies of the impact of the pandemic on deprivation inequalities, covering 20 million people in two countries (England and Denmark). Followed-up was until the end of 2021, which is longer than most previous studies. We compared the impact in two countries that have free at the point of use healthcare, but different responses to the pandemic. The measures of deprivation were different in the two countries, with the measure in England (Index of Multiple Deprivation 2019) capturing more aspects of deprivation compared to the Danish measure (income) which may have resulted in misclassification. Our results are descriptive so do not provide insight into the causes of observed differences.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2024/05/09/2024.05.09.24307105.full.pdf; doi:https://doi.org/10.1101/2024.05.09.24307105; html:https://europepmc.org/article/PPR/PPR850975 -PPR585732,https://doi.org/10.1101/2022.12.16.22283578,"Higher dose corticosteroids in hospitalised COVID-19 patients with hypoxia but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial","RECOVERY Collaborative Group, Horby PW, Emberson JR, Basnyat B, Basnyat B, Campbell M, Peto L, Pessoa-Amorim G, Staplin N, Hamers RL, Amuasi J, Nel J, Kestelyn E, Rawal M, Jha RK, Phong NT, Samardi U, Paudel D, Thach PN, Nasronudin N, Stratton E, Mew L, Sarkar R, Baillie JK, Buch MH, Day J, Faust SN, Jaki T, Jeffery K, Juszczak E, Knight M, Lim WS, Mafham M, Montgomery A, Mumford A, Rowan K, Thwaites G, Haynes R, Landray MJ.",,No Journal Info,2022,2022-12-17,Y,,,,"

SUMMARY

Background

Low-dose corticosteroids have been shown to reduce mortality for hypoxic COVID-19 patients requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation or extra-corporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group.

Methods

This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (i.e. receiving oxygen or with oxygen saturation <92% on room air) were randomly allocated (1:1) to either usual care with higher dose corticosteroids (dexamethasone 20 mg once daily for 5 days followed by 10 mg once daily for 5 days or until discharge if sooner) or usual standard of care alone (which includes dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality. On 11 May 2022, the independent Data Monitoring Committee recommended stopping recruitment of patients receiving no oxygen or simple oxygen only to this comparison due to safety concerns. We report the results for these participants only. Recruitment of patients receiving ventilatory support continues. The RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov ( NCT04381936 ).

Findings

Between 25 May 2021 and 12 May 2022, 1272 COVID-19 patients with hypoxia and receiving no oxygen (1%) or simple oxygen only (99%) were randomly allocated to receive usual care plus higher dose corticosteroids versus usual care alone (of whom 87% received low dose corticosteroids during the follow-up period). Of those randomised, 745 (59%) were in Asia, 512 (40%) in the UK and 15 (1%) in Africa. 248 (19%) had diabetes mellitus. Overall, 121 (18%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio [RR] 1·56; 95% CI 1·18-2·06; p=0·0020). There was also an excess of pneumonia reported to be due to non-COVID infection (10% vs. 6%; absolute difference 3.7%; 95% CI 0.7-6.6) and an increase in hyperglycaemia requiring increased insulin dose (22% vs. 14%; absolute difference 7.4%; 95% CI 3.2-11.5).

Interpretation

In patients hospitalised for COVID-19 with clinical hypoxia but requiring either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared to usual care, which included low dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation or extra-corporeal membrane oxygenation.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health and Care Research (Grant ref: MC_PC_19056), and Wellcome Trust (Grant Ref: 222406/Z/20/Z).",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/12/17/2022.12.16.22283578.full.pdf; doi:https://doi.org/10.1101/2022.12.16.22283578; html:https://europepmc.org/article/PPR/PPR585732; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR585732&type=FILE&fileName=EMS158665-pdf.pdf&mimeType=application/pdf PPR417361,https://doi.org/10.1101/2021.11.08.21265312,"Understanding COVID-19 trajectories from a nationwide linked electronic health record cohort of 56 million people: phenotypes, severity, waves & vaccination","Thygesen JH, Tomlinson C, Hollings S, Mizani M, Handy A, Akbari A, Banerjee A, Cooper J, Lai A, Li K, Mateen B, Sattar N, Sofat R, Torralbo A, Wu H, Wood A, Sterne JAC, Pagel C, Whiteley W, Sudlow C, Hemingway H, Denaxas S.",,No Journal Info,2021,2021-11-09,Y,,,,"

Background

Updatable understanding of the onset and progression of individuals COVID-19 trajectories underpins pandemic mitigation efforts. In order to identify and characterize individual trajectories, we defined and validated ten COVID-19 phenotypes from linked electronic health records (EHR) on a nationwide scale using an extensible framework.

Methods

Cohort study of 56.6 million people in England alive on 23/01/2020, followed until 31/05/2021, using eight linked national datasets spanning COVID-19 testing, vaccination, primary & secondary care and death registrations data. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity using a combination of international clinical terminologies (e.g. SNOMED-CT, ICD-10) and bespoke data fields; positive test, primary care diagnosis, hospitalisation, critical care (four phenotypes), and death (three phenotypes). Using these phenotypes, we constructed patient trajectories illustrating the transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status.

Findings

We identified 3,469,528 infected individuals (6.1%) with 8,825,738 recorded COVID-19 phenotypes. Of these, 364,260 (11%) were hospitalised and 140,908 (4%) died. Of those hospitalised, 38,072 (10%) were admitted to intensive care (ICU), 54,026 (15%) received non-invasive ventilation and 21,404 (6%) invasive ventilation. Amongst hospitalised patients, first wave mortality (30%) was higher than the second (23%) in non-ICU settings, but remained unchanged for ICU patients. The highest mortality was for patients receiving critical care outside of ICU in wave 1 (51%). 13,083 (9%) COVID-19 related deaths occurred without diagnoses on the death certificate, but within 30 days of a positive test while 10,403 (7%) of cases were identified from mortality data alone with no prior phenotypes recorded. We observed longer patient trajectories in the second pandemic wave compared to the first.

Interpretation

Our analyses illustrate the wide spectrum of severity that COVID-19 displays and significant differences in incidence, survival and pathways across pandemic waves. We provide an adaptable framework to answer questions of clinical and policy relevance; new variant impact, booster dose efficacy and a way of maximising existing data to understand individuals progression through disease states.

Research in Context

Evidence before the study

We searched PubMed on October 14, 2021, for publications with the terms “COVID-19” or “SARS-CoV-2”, “severity”, and “electronic health records” or “EHR” without date or language restrictions. Multiple studies explore factors associated with severity of COVID-19 infection, and model predictions of outcome for hospitalised patients. However, most work to date focused on isolated facets of the healthcare system, such as primary or secondary care only, was conducted in subpopulations (e.g. hospitalised patients) of limited sample size, and often utilized dichotomised outcomes (e.g. mortality or hospitalisation) ignoring the full spectrum of disease. We identified no studies which comprehensively detailed severity of infections while describing disease severity across pandemic waves, vaccination status, and patient trajectories.

Added value of this study

To our knowledge, this is the first study providing a comprehensive view of COVID-19 across pandemic waves using national data and focusing on severity, vaccination, and patient trajectories. Drawing on linked electronic health record (EHR) data on a national scale (56.6 million people alive and registered with GP in England), we describe key demographic factors, frequency of comorbidities, impact of the two main waves in England, and effect of full vaccination on COVID-19 severities. Additionally, we identify and describe patient trajectory networks which illustrate the main transition pathways of COVID-19 patients in the healthcare system. Finally, we provide reproducible COVID-19 phenotyping algorithms reflecting clinically relevant stages of disease severity i.e. positive tests, primary care diagnoses, hospitalisation, critical care treatments (e.g. ventilatory support) and mortality.

Implications of all the available evidence

The COVID-19 phenotypes and trajectory analysis framework outlined produce a reproducible, extensible and repurposable means to generate national-scale data to support critical policy decision making. By modelling patient trajectories as a series of interactions with healthcare systems, and linking these to demographic and outcome data, we provide a means to identify and prioritise care pathways associated with adverse outcomes and highlight healthcare system ‘touch points’ which may act as tangible targets for intervention.",,pdf:http://www.thelancet.com/article/S2589750022000917/pdf; doi:https://doi.org/10.1101/2021.11.08.21265312; html:https://europepmc.org/article/PPR/PPR417361; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR417361&type=FILE&fileName=EMS138265-pdf.pdf&mimeType=application/pdf +PPR585732,https://doi.org/10.1101/2022.12.16.22283578,"Higher dose corticosteroids in hospitalised COVID-19 patients with hypoxia but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial","RECOVERY Collaborative Group, Horby PW, Emberson JR, Basnyat B, Basnyat B, Campbell M, Peto L, Pessoa-Amorim G, Staplin N, Hamers RL, Amuasi J, Nel J, Kestelyn E, Rawal M, Jha RK, Phong NT, Samardi U, Paudel D, Thach PN, Nasronudin N, Stratton E, Mew L, Sarkar R, Baillie JK, Buch MH, Day J, Faust SN, Jaki T, Jeffery K, Juszczak E, Knight M, Lim WS, Mafham M, Montgomery A, Mumford A, Rowan K, Thwaites G, Haynes R, Landray MJ.",,No Journal Info,2022,2022-12-17,Y,,,,"

SUMMARY

Background

Low-dose corticosteroids have been shown to reduce mortality for hypoxic COVID-19 patients requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation or extra-corporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group.

Methods

This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (i.e. receiving oxygen or with oxygen saturation <92% on room air) were randomly allocated (1:1) to either usual care with higher dose corticosteroids (dexamethasone 20 mg once daily for 5 days followed by 10 mg once daily for 5 days or until discharge if sooner) or usual standard of care alone (which includes dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality. On 11 May 2022, the independent Data Monitoring Committee recommended stopping recruitment of patients receiving no oxygen or simple oxygen only to this comparison due to safety concerns. We report the results for these participants only. Recruitment of patients receiving ventilatory support continues. The RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov ( NCT04381936 ).

Findings

Between 25 May 2021 and 12 May 2022, 1272 COVID-19 patients with hypoxia and receiving no oxygen (1%) or simple oxygen only (99%) were randomly allocated to receive usual care plus higher dose corticosteroids versus usual care alone (of whom 87% received low dose corticosteroids during the follow-up period). Of those randomised, 745 (59%) were in Asia, 512 (40%) in the UK and 15 (1%) in Africa. 248 (19%) had diabetes mellitus. Overall, 121 (18%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio [RR] 1·56; 95% CI 1·18-2·06; p=0·0020). There was also an excess of pneumonia reported to be due to non-COVID infection (10% vs. 6%; absolute difference 3.7%; 95% CI 0.7-6.6) and an increase in hyperglycaemia requiring increased insulin dose (22% vs. 14%; absolute difference 7.4%; 95% CI 3.2-11.5).

Interpretation

In patients hospitalised for COVID-19 with clinical hypoxia but requiring either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared to usual care, which included low dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation or extra-corporeal membrane oxygenation.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health and Care Research (Grant ref: MC_PC_19056), and Wellcome Trust (Grant Ref: 222406/Z/20/Z).",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/12/17/2022.12.16.22283578.full.pdf; doi:https://doi.org/10.1101/2022.12.16.22283578; html:https://europepmc.org/article/PPR/PPR585732; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR585732&type=FILE&fileName=EMS158665-pdf.pdf&mimeType=application/pdf PPR447312,https://doi.org/10.1101/2022.01.26.22269885,SARS-CoV-2 anti-spike antibody levels following second dose of ChAdOx1 nCov-19 or BNT162b2 in residents of long-term care facilities in England (VIVALDI),"Stirrup O, Krutikov M, Tut G, Palmer T, Bone D, Bruton R, Fuller C, Azmi B, Lancaster T, Sylla P, Kaur N, Spalkova E, Bentley C, Amin U, Jadir A, Hulme S, Giddings R, Nacer-Laidi H, Baynton V, Irwin-Singer A, Hayward A, Moss P, Copas A, Shallcross L.",,No Journal Info,2022,2022-01-27,Y,,,,"

Background

General population studies have shown strong humoral response following SARS-CoV-2 vaccination with subsequent waning of anti-spike antibody levels. Vaccine-induced immune responses are often attenuated in frail and older populations such as Long-Term Care Facility (LTCF) residents but published data are scarce.

Methods

VIVALDI is a prospective cohort study in England which links serial blood sampling in LTCF staff and residents to routine healthcare records. We measured quantitative titres of SARS-CoV-2 anti-spike antibodies in residents and staff following second vaccination dose with ChAdOx1 nCov-19 (Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech). We investigated differences in peak antibody levels and rates of decline using linear mixed effects models.

Results

We report on 1317 samples from 402 residents (median age 86 years, IQR 78-91) and 632 staff (50 years, 37-58), ≤280 days from second vaccination dose. Peak antibody titres were 7.9-fold higher after Pfizer-BioNTech vaccine compared to Oxford-AstraZeneca (95%CI 3.6-17.0; P <0.01) but rate of decline was increased, and titres were similar at 6 months. Prior infection was associated with higher peak antibody levels in both Pfizer-BioNTech (2.8-fold, 1.9-4.1; P <0.01) and Oxford-AstraZeneca (4.8-fold, 3.2-7.1; P <0.01) recipients and slower rates of antibody decline. Increasing age was associated with a modest reduction in peak antibody levels for Oxford-AstraZeneca recipients.

Conclusions

Double-dose vaccination elicits robust and stable antibody responses in older LTCF residents, suggesting comparable levels of vaccine-induced immunity to that in the general population. Antibody levels are higher after Pfizer-BioNTech vaccination but fall more rapidly compared to Oxford-AstraZeneca recipients and are enhanced by prior infection in both groups.",,pdf:https://discovery.ucl.ac.uk/10147322/1/spike-waning-JID.pdf; doi:https://doi.org/10.1101/2022.01.26.22269885; html:https://europepmc.org/article/PPR/PPR447312; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR447312&type=FILE&fileName=EMS142768-pdf.pdf&mimeType=application/pdf PPR558653,https://doi.org/10.1101/2022.10.13.22281031,Indirect effects of the first two years of the COVID-19 pandemic on secondary care for cardiovascular disease in the UK: an electronic health record analysis across three countries,"Wright FL, Cheema K, Goldacre R, Hall N, Herz N, Islam N, Karim Z, Moreno-Martos D, Morales DR, O’Connell D, Spata E, Akbari A, Ashworth M, Barber M, Briffa N, Canoy D, Denaxas S, Khunti K, Kurdi A, Mamas M, Priedon R, Sudlow C, Morris EJ, Lacey B, Banerjee A.",,No Journal Info,2022,2022-10-17,Y,,,,"

Background

Although morbidity and mortality from COVID-19 have been widely reported, the indirect effects of the pandemic beyond 2020 on other major diseases and health service activity have not been well described.

Methods

Analyses used national administrative electronic hospital records in England, Scotland and Wales for 2016-2021. Admissions and procedures during the pandemic (2020-2021) related to six major cardiovascular conditions (acute coronary syndrome, heart failure, stroke/transient ischaemic attack, peripheral arterial disease, aortic aneurysm, and venous thromboembolism) were compared to the annual average in the pre-pandemic period (2016-2019). Differences were assessed by time period and urgency of care.

Results

In 2020, there were 31,064 (−6%) fewer hospital admissions (14,506 [-4%] fewer emergencies, 16,560 [-23%] fewer elective admissions) compared to 2016-2019 for the six major cardiovascular diseases combined. The proportional reduction in admissions was similar in all three countries. Overall, hospital admissions returned to pre-pandemic levels in 2021. Elective admissions remained substantially below expected levels for almost all conditions in all three countries (−10,996 [-15%] fewer admissions). However, these reductions were offset by higher than expected total emergency admissions (+25,878 [+6%] higher admissions), notably for heart failure and stroke in England, and for venous thromboembolism in all three countries. Analyses for procedures showed similar temporal variations to admissions.

Conclusion

This study highlights increasing emergency cardiovascular admissions as a result of the pandemic, in the context of a substantial and sustained reduction in elective admissions and procedures. This is likely to increase further the demands on cardiovascular services over the coming years.

Key Question

What is the impact in 2020 and 2021 of the COVID-19 pandemic on hospital admissions and procedures for six major cardiovascular diseases in England, Scotland and Wales?

Key Finding

In 2020, there were 6% fewer hospital admissions (emergency: -4%, elective: -23%) compared to 2016-2019 for six major cardiovascular diseases, across three UK countries. Overall, admissions returned to pre-pandemic levels in 2021, but elective admissions remained below expected levels.

Take-home Message

There was increasing emergency cardiovascular admissions as a result of the pandemic, with substantial and sustained reduction in elective admissions and procedures. This is likely to increase further the demands on cardiovascular services over the coming years.",,pdf:https://eprints.keele.ac.uk/id/eprint/12374/1/2022.10.13.22281031v1.full.pdf; doi:https://doi.org/10.1101/2022.10.13.22281031; html:https://europepmc.org/article/PPR/PPR558653; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR558653&type=FILE&fileName=EMS155821-pdf.pdf&mimeType=application/pdf PPR166764,https://doi.org/10.1101/2020.05.20.20107904,Coronavirus (COVID-19) infection in children at a specialist centre: outcome and implications of underlying ‘high-risk’ comorbidities in a paediatric population,"Issitt R, Booth J, Bryant W, Spiridou A, Taylor A, du Pré P, Ramnarayan P, Hartley J, Cortina-Borja M, Moshal K, Dunn H, Hemingway H, Sebire N.",,No Journal Info,2020,2020-05-25,Y,,,,"

Background

There is evolving evidence of significant differences in severity and outcomes of coronavirus disease 2019 (COVID-19) in children compared to adults. Underlying medical conditions associated with increased risk of severe disease are based on adult data, but have been applied across all ages resulting in large numbers of families undertaking social ‘shielding’ (vulnerable group). We conducted a retrospective analysis of children with suspected COVID-19 at a Specialist Children’s Hospital to determine outcomes based on COVID-19 testing status and underlying health vulnerabilities.

Methods

Routine clinical data were extracted retrospectively from the Institution’s Electronic Health Record system and Digital Research Environment for patients with suspected and confirmed COVID-19 diagnoses. Data were compared between Sars-CoV-2 positive and negative patients (CoVPos / CoVNeg respectively), and in relation to presence of underlying health vulnerabilities based on Public Health England guidance.

Findings

Between 1 st March and 15 th May 2020, 166 children (<18 years of age) presented to a specialist children’s hospital with clinical features of possible COVID-19 infection. 65 patients (39.2%) tested positive for SARS-CoV-2 virus. CoVPos patients were older (median 9 [0.9 - 14] years vs median 1 [0.1 - 5.7.5] years respectively, p <0.001). There was a significantly reduced proportion of vulnerable cases (47.7% vs 72.3%, p =0.002), but no difference in proportion of vulnerable patients requiring ventilation (61% vs 64.3%, p = 0.84) between CoVPos and CoVNeg groups. However, a significantly lower proportion of CoVPos patients required mechanical ventilation support compared to CoVNeg patients (27.7 vs 57.4%, p <0.001). Mortality was not significantly different between CoVPos and CoVNeg groups (1.5 vs 4% respectively, p =0.67) although there were no direct COVID-19 related deaths in this highly preselected paediatric population.

Interpretation

COVID-19 infection may be associated with severe disease in childhood presenting to a specialist hospital, but does not appear significantly different in severity to other causes of similar clinical presentations. In children presenting with pre-existing ‘COVID-19 vulnerable’ medical conditions at a specialist centre, there does not appear to be significantly increased risk of either contracting COVID-19 or severe complications, apart from those undergoing chemotherapy, who are over-represented.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/05/25/2020.05.20.20107904.full.pdf; doi:https://doi.org/10.1101/2020.05.20.20107904; html:https://europepmc.org/article/PPR/PPR166764; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR166764&type=FILE&fileName=EMS91012-pdf.pdf&mimeType=application/pdf -PPR520994,https://doi.org/10.21203/rs.3.rs-1831644/v1,"COVID-19 vaccination in pregnancy: views and vaccination uptake rates in pregnancy, a mixed methods analysis from the Born In Wales study","Mhereeg M, Jones H, Kennedy J, Seaborne M, Parker M, Kennedy N, Beeson S, Akbari A, Zuccolo L, Davies A, Brophy S.",,No Journal Info,2022,2022-07-20,Y,,,,"

Background:

Vaccine hesitancy amongst pregnant women has been found to be a concern during past epidemics. This study aimed to 1) estimate COVID-19 vaccination rates among pregnant women in Wales and their association with age, ethnicity, and area of deprivation, using electronic health records (EHR) linkage, and 2) explore pregnant women’s views on receiving the COVID-19 vaccine during pregnancy using data from a survey recruiting via social media (Facebook, Twitter), through midwives, and posters in hospitals (Born in Wales Cohort). Methods This was a mixed-methods study utilising routinely collected linked data from the Secure Anonymised Information Linkage (SAIL) (Objective 1) and the Born-In-Wales Birth Cohort participants (Objective 2). Survival analysis was utilised to examine and compare the length of time to vaccination uptake in pregnancy, and variation in uptake by; age, ethnicity, and deprivation area was examined using hazard ratios (HR) from Cox regression. Codebook thematic analysis was used to generate themes from an open-ended question on the survey. Results Population-level data linkage (objective 1) Within the population cohort, 32.7% (n = 8,203) were vaccinated (at least one dose of the vaccine) during pregnancy, 34.1% (n = 8,572) remained unvaccinated throughout follow-up period, and 33.2% (n = 8,336) received the vaccine postpartum. Younger women (< 30 years) were less likely to have the vaccine and those living in areas of high deprivation were also less likely to have the vaccine (HR = 0.88, 95% CI 0.82 to 0.95). Asian and other ethnic groups were 1.12 and 1.18 times more likely to have the vaccine in pregnancy compared to women of White ethnicity (HR = 1.12, 95% CI 1.00 to 1.25) and (HR = 1.18, 95% CI 1.03 to 1.37) respectively. Survey responses (objective 2) 69% of participants stated that they would be happy to have the vaccine during pregnancy (n = 207). The remainder, 31%, indicated that they would not have the vaccine during pregnancy (n = 94). Reasons for having the vaccine included protecting self and baby, perceived risk level, and receipt of sufficient evidence and advice. Reasons for vaccine refusal included lack of research about long-term outcomes for the baby, anxiety about vaccines, inconsistent advice/information, and preference to wait until after the pregnancy. Conclusion Potentially only 1 in 3 pregnant women would have the COVID-19 vaccine during pregnancy, even though 2 in 3 reported they would have the vaccination, thus it is critical to develop tailored strategies to increase its acceptance rate and to decrease vaccine hesitancy. A targeted approach to vaccinations may be required for groups such as younger people and those living in higher deprivation level areas.",,pdf:https://www.researchsquare.com/article/rs-1831644/latest.pdf; doi:https://doi.org/10.21203/rs.3.rs-1831644/v1; html:https://europepmc.org/article/PPR/PPR520994; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR520994&type=FILE&fileName=EMS151343-pdf.pdf&mimeType=application/pdf PPR496296,https://doi.org/10.1101/2022.05.09.22274769,"COVID-19 vaccination in pregnancy: views and vaccination uptake rates in pregnancy, a mixed methods analysis from the Born In Wales study","Mhereeg M, Jones H, Kennedy J, Seaborne M, Parker M, Kennedy N, Beeson S, Zuccolo L, Davies A, Brophy S.",,No Journal Info,2022,2022-05-11,N,,,,"

Background

Vaccine hesitancy amongst pregnant women has been found to be a concern during past epidemics.

Objectives

The aims of this study were to 1) estimate COVID-19 vaccination rates among pregnant women in Wales and their association with age, ethnicity, and area of deprivation, using electronic health records (EHR) linkage, and 2) explore pregnant women’s views on receiving the COVID-19 vaccine during pregnancy using data from a survey recruiting via social media (Facebook, Twitter), through midwives, and posters in hospitals (Born in Wales Cohort).

Design

A mixed methods study utilising routinely collected linked data from the Secure Anonymised Information Linkage (SAIL) (Objective 1) and the Born In Wales Birth Cohort participants (Objective 2). SAIL combines data from general practice, hospital admissions, the national community child health dataset, maternal indicators dataset, and COVID-19 vaccination databases.

Setting and participants

Objective:

1) All women documented as being pregnant on or after 13 th April 2021, aged 18 years or older, and eligible for COVID-19 vaccination were identified in routine health care. They were linked to the vaccination data up to and including 31 st December 2021. Objective 2) Separately, a cross-section of pregnant women in Wales were invited to complete an online survey via social media advertising. The survey asked what their views were on having the COVID-19 vaccination during pregnancy, and if they had already received, or intended to receive, the COVID-19 vaccination during their pregnancies. They were also asked to give reasons for their decisions.

Outcomes

1 (a). Rate of vaccination uptake per month during pregnancy among women eligible for vaccination. 1 (b). Survival analysis was utilised to examine and compare the length of time to vaccination uptake in pregnancy, and variation in uptake by; age, ethnicity, and deprivation area was examined using hazard ratios (HR) from Cox regression. 2.Expectant mothers’ views of the COVID-19 vaccination during pregnancy.

Results

Population-level data linkage (objective 1)

Within the population cohort, 32.7% (n = 8,203) were vaccinated (at least one dose of the vaccine) during pregnancy, 34.1% (n = 8,572) remained unvaccinated throughout follow-up period, and 33.2% (n = 8,336) received the vaccine postpartum. Younger women (<30 years) were less likely to have the vaccine and those living in areas of high deprivation were also less likely to have the vaccine (HR=0.88, 95% CI 0.82 to 0.95). Asian and other ethnic groups were 1.12 and 1.18 times more likely to have the vaccine in pregnancy compared to women of White ethnicity (HR=1.12, 95% CI 1.00 to 1.25) and (HR=1.18, 95% CI 1.03 to 1.37) respectively.

Survey responses (objective 2)

69% of participants stated that they would be happy to have the vaccine during pregnancy (n = 207). The remainder, 31%, indicated that they would not have the vaccine during pregnancy (n = 94). Reasons for having the vaccine related to protecting self and baby, perceived risk level, and receipt of sufficient evidence and advice. Reasons for vaccine refusal included lack of research about long-term outcomes for the baby, anxiety about vaccines, inconsistent advice/information, and preference to wait until after the pregnancy.

Conclusion

Potentially only 1 in 3 pregnant women would have the COVID-19 vaccine during pregnancy, even though 2 in 3 reported they would have the vaccination, thus it is critical to develop tailored strategies to increase its acceptance rate and to decrease vaccine hesitancy. A targeted approach to vaccinations may be required for groups such as younger people and those living in higher deprivation level areas.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/05/11/2022.05.09.22274769.full.pdf; doi:https://doi.org/10.1101/2022.05.09.22274769; html:https://europepmc.org/article/PPR/PPR496296; doi:https://doi.org/10.1101/2022.05.09.22274769 +PPR520994,https://doi.org/10.21203/rs.3.rs-1831644/v1,"COVID-19 vaccination in pregnancy: views and vaccination uptake rates in pregnancy, a mixed methods analysis from the Born In Wales study","Mhereeg M, Jones H, Kennedy J, Seaborne M, Parker M, Kennedy N, Beeson S, Akbari A, Zuccolo L, Davies A, Brophy S.",,No Journal Info,2022,2022-07-20,Y,,,,"

Background:

Vaccine hesitancy amongst pregnant women has been found to be a concern during past epidemics. This study aimed to 1) estimate COVID-19 vaccination rates among pregnant women in Wales and their association with age, ethnicity, and area of deprivation, using electronic health records (EHR) linkage, and 2) explore pregnant women’s views on receiving the COVID-19 vaccine during pregnancy using data from a survey recruiting via social media (Facebook, Twitter), through midwives, and posters in hospitals (Born in Wales Cohort). Methods This was a mixed-methods study utilising routinely collected linked data from the Secure Anonymised Information Linkage (SAIL) (Objective 1) and the Born-In-Wales Birth Cohort participants (Objective 2). Survival analysis was utilised to examine and compare the length of time to vaccination uptake in pregnancy, and variation in uptake by; age, ethnicity, and deprivation area was examined using hazard ratios (HR) from Cox regression. Codebook thematic analysis was used to generate themes from an open-ended question on the survey. Results Population-level data linkage (objective 1) Within the population cohort, 32.7% (n = 8,203) were vaccinated (at least one dose of the vaccine) during pregnancy, 34.1% (n = 8,572) remained unvaccinated throughout follow-up period, and 33.2% (n = 8,336) received the vaccine postpartum. Younger women (< 30 years) were less likely to have the vaccine and those living in areas of high deprivation were also less likely to have the vaccine (HR = 0.88, 95% CI 0.82 to 0.95). Asian and other ethnic groups were 1.12 and 1.18 times more likely to have the vaccine in pregnancy compared to women of White ethnicity (HR = 1.12, 95% CI 1.00 to 1.25) and (HR = 1.18, 95% CI 1.03 to 1.37) respectively. Survey responses (objective 2) 69% of participants stated that they would be happy to have the vaccine during pregnancy (n = 207). The remainder, 31%, indicated that they would not have the vaccine during pregnancy (n = 94). Reasons for having the vaccine included protecting self and baby, perceived risk level, and receipt of sufficient evidence and advice. Reasons for vaccine refusal included lack of research about long-term outcomes for the baby, anxiety about vaccines, inconsistent advice/information, and preference to wait until after the pregnancy. Conclusion Potentially only 1 in 3 pregnant women would have the COVID-19 vaccine during pregnancy, even though 2 in 3 reported they would have the vaccination, thus it is critical to develop tailored strategies to increase its acceptance rate and to decrease vaccine hesitancy. A targeted approach to vaccinations may be required for groups such as younger people and those living in higher deprivation level areas.",,pdf:https://www.researchsquare.com/article/rs-1831644/latest.pdf; doi:https://doi.org/10.21203/rs.3.rs-1831644/v1; html:https://europepmc.org/article/PPR/PPR520994; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR520994&type=FILE&fileName=EMS151343-pdf.pdf&mimeType=application/pdf PPR340395,https://doi.org/10.1101/2021.05.13.21257144,REACT-1 round 11 report: low prevalence of SARS-CoV-2 infection in the community prior to the third step of the English roadmap out of lockdown,"Riley S, Haw D, Walters CE, Wang H, Eales O, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Page AJ, Trotter AJ, Le Viet T, Alikhan N, O’Grady J, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P, The COVID-19 Genomics UK (COG-UK) Consortium.",,No Journal Info,2021,2021-05-17,Y,,,,"

Background

National epidemic dynamics of SARS-CoV-2 infections are being driven by: the degree of recent indoor mixing (both social and workplace), vaccine coverage, intrinsic properties of the circulating lineages, and prior history of infection (via natural immunity). In England, infections, hospitalisations and deaths fell during the first two steps of the “roadmap” for exiting the third national lockdown. The third step of the roadmap in England takes place on 17 May 2021.

Methods

We report the most recent findings on community infections from the REal-time Assessment of Community Transmission-1 (REACT-1) study in which a swab is obtained from a representative cross-sectional sample of the population in England and tested using PCR. Round 11 of REACT-1 commenced self-administered swab-collection on 15 April 2021 and completed collections on 3 May 2021. We compare the results of REACT-1 round 11 to round 10, in which swabs were collected from 11 to 30 March 2021.

Results

Between rounds 10 and 11, prevalence of swab-positivity dropped by 50% in England from 0.20% (0.17%, 0.23%) to 0.10% (0.08%, 0.13%), with a corresponding R estimate of 0.90 (0.87, 0.94). Rates of swab-positivity fell in the 55 to 64 year old group from 0.17% (0.12%, 0.25%) in round 10 to 0.06% (0.04%, 0.11%) in round 11. Prevalence in round 11 was higher in the 25 to 34 year old group at 0.21% (0.12%, 0.38%) than in the 55 to 64 year olds and also higher in participants of Asian ethnicity at 0.31% (0.16%, 0.60%) compared with white participants at 0.09% (0.07%, 0.11%). Based on sequence data for positive samples for which a lineage could be identified, we estimate that 92.3% (75.9%, 97.9%, n=24) of infections were from the B.1.1.7 lineage compared to 7.7% (2.1%, 24.1%, n=2) from the B.1.617.2 lineage. Both samples from the B.1.617.2 lineage were detected in London from participants not reporting travel in the previous two weeks. Also, allowing for suitable lag periods, the prior close alignment between prevalence of infections and hospitalisations and deaths nationally has diverged.

Discussion

We observed marked reductions in prevalence from March to April and early May 2021 in England reflecting the success of the vaccination programme and despite easing of restrictions during lockdown. However, there is potential upwards pressure on prevalence from the further easing of lockdown regulations and presence of the B.1.617.2 lineage. If prevalence rises in the coming weeks, policy-makers will need to assess the possible impact on hospitalisations and deaths. In addition, consideration should be given to other health and economic impacts if increased levels of community transmission occur.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/05/17/2021.05.13.21257144.full.pdf; doi:https://doi.org/10.1101/2021.05.13.21257144; html:https://europepmc.org/article/PPR/PPR340395; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR340395&type=FILE&fileName=EMS124703-pdf.pdf&mimeType=application/pdf PPR247290,https://doi.org/10.1101/2020.11.30.20239806,REACT-1 round 7 interim report: fall in prevalence of swab-positivity in England during national lockdown,"Riley S, Eales O, Walters CE, Wang H, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P.",,No Journal Info,2020,2020-12-02,Y,,,,"

Background

The second wave of the 2020 COVID-19 pandemic in England has been characterized by high growth and prevalence in the North with lower prevalence in the South. High prevalence was first observed at younger adult ages before spreading out to school-aged children and older adults. Local tiered interventions were in place up to 5th November 2020 at which time a second national lockdown was implemented.

Methods

REACT-1 is a repeated cross-sectional survey of SARS-CoV-2 swab-positivity in random samples of the population of England. The current period of data collection (round 7) commenced on 13th November 2020 and we report interim results here for swabs collected up to and including 24th November 2020. Because there were two distinct periods of growth during the previous round 6, here we compare results from round 7 (mainly) with the second half of round 6, which obtained swabs between 26th October and 2nd November 2020. We report prevalence both unweighted and reweighted to be representative of the population of England. We describe trends in unweighted prevalence with daily growth rates, doubling times, reproduction numbers (R) and splines. We estimated odds ratios for swab-positivity using mutually-adjusted multivariable logistic regression models.

Results

We found 821 positives from 105,123 swabs giving an unweighted prevalence of 0.78% (95% CI, 0.73%, 0.84%) and a weighted prevalence of 0.96% (0.87%, 1.05%). The weighted prevalence estimate was ∼30% lower than that of 1.32% (1.20%, 1.45%) obtained in the second half of round 6. This decrease corresponds to a halving time of 37 (30, 47) days and an R number of 0.88 (0.86, 0.91). Using only data from the most recent period, we estimate an R number of 0.71 (0.54, 0.90). A spline fit to prevalence showed a rise shortly after the previous period of data collection followed by a fall coinciding with the start of lockdown. The national trends were driven mainly by reductions in higher-prevalence northern regions, with prevalence approximately unchanged in the Midlands and London, and smaller reductions in southern lower-prevalence regions. Sub-regional analyses showed variable changes in prevalence at the local level including marked declines in the North, but also local areas of growth in East and West Midlands. Mutually adjusted models in the most recent period indicated: people of Asian ethnicity, those living in the most deprived neighbourhoods, and those living in the largest households, had higher odds of swab-positivity.

Conclusion

Three weeks into the second national lockdown in England there has been a ∼30% proportionate reduction in prevalence overall, with greater reductions in the North. As a result, inter-regional heterogeneity has reduced, although average absolute prevalence remains high at ∼1%. Continued monitoring of the epidemic in the community remains essential until prevalence is reliably suppressed to much lower levels, for example, through widespread vaccination.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/12/02/2020.11.30.20239806.full.pdf; doi:https://doi.org/10.1101/2020.11.30.20239806; html:https://europepmc.org/article/PPR/PPR247290; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR247290&type=FILE&fileName=EMS107598-pdf.pdf&mimeType=application/pdf PPR187496,https://doi.org/10.1101/2020.07.15.20151852,"Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial","Horby P, Mafham M, Linsell L, Bell JL, Staplin N, Emberson JR, Wiselka M, Ustianowski A, Elmahi E, Prudon B, Whitehouse A, Felton T, Williams J, Faccenda J, Underwood J, Baillie JK, Chappell L, Faust SN, Jaki T, Jeffery K, Lim WS, Montgomery A, Rowan K, Tarning J, Watson JA, White NJ, Juszczak E, Haynes R, Landray MJ.",,No Journal Info,2020,2020-07-15,Y,,,,"

ABSTRACT

Background

Hydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (COVID-19) on the basis of in vitro activity, uncontrolled data, and small randomized studies.

Methods

The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of hydroxychloroquine vs. usual care alone. The primary outcome was 28-day mortality.

Results

1561 patients randomly allocated to receive hydroxychloroquine were compared with 3155 patients concurrently allocated to usual care. Overall, 418 (26.8%) patients allocated hydroxychloroquine and 788 (25.0%) patients allocated usual care died within 28 days (rate ratio 1.09; 95% confidence interval [CI] 0.96 to 1.23; P=0.18). Consistent results were seen in all pre-specified subgroups of patients. Patients allocated to hydroxychloroquine were less likely to be discharged from hospital alive within 28 days (60.3% vs. 62.8%; rate ratio 0.92; 95% CI 0.85-0.99) and those not on invasive mechanical ventilation at baseline were more likely to reach the composite endpoint of invasive mechanical ventilation or death (29.8% vs. 26.5%; risk ratio 1.12; 95% CI 1.01-1.25). There was no excess of new major cardiac arrhythmia.

Conclusions

In patients hospitalized with COVID-19, hydroxychloroquine was not associated with reductions in 28-day mortality but was associated with an increased length of hospital stay and increased risk of progressing to invasive mechanical ventilation or death.

Funding

Medical Research Council and NIHR (Grant ref: MC_PC_19056).

Trial registrations

The trial is registered with ISRCTN (50189673) and clinicaltrials.gov ( NCT04381936 ).",,pdf:https://www.nejm.org/doi/pdf/10.1056/NEJMoa2022926?articleTools=true; doi:https://doi.org/10.1101/2020.07.15.20151852; html:https://europepmc.org/article/PPR/PPR187496; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR187496&type=FILE&fileName=EMS87168-pdf.pdf&mimeType=application/pdf @@ -200,12 +200,12 @@ PPR241483,https://doi.org/10.1101/2020.11.19.20234849,Community factors and exce PPR287082,https://doi.org/10.1101/2021.02.18.21251973,REACT-1 round 9 interim report: downward trend of SARS-CoV-2 in England in February 2021 but still at high prevalence,"Riley S, Walters CE, Wang H, Eales O, Haw D, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P.",,No Journal Info,2021,2021-02-23,Y,,,,"

Background and Methods

England entered its third national lockdown of the COVID-19 pandemic on 6th January 2021 with the aim of reducing the daily number of deaths and pressure on healthcare services. The real-time assessment of community transmission study (REACT-1) obtains throat and nose swabs from randomly selected people in England in order to describe patterns of SARS-CoV-2 prevalence. Here, we report data from round 9a of REACT-1 for swabs collected between 4th and 13th February 2021.

Results

Out of 85,473 tested-swabs, 378 were positive. Overall weighted prevalence of infection in the community in England was 0.51%, a fall of more than two thirds since our last report (round 8) in January 2021 when 1.57% of people tested positive. We estimate a halving time of 14.6 days and a reproduction number R of 0.72, based on the difference in prevalence between the end of round 8 and the beginning of round 9. Although prevalence fell in all nine regions of England over the same period, there was greater uncertainty in the trend for North West, North East, and Yorkshire and The Humber. Prevalence fell substantially across all age groups with highest prevalence among 18- to 24-year olds at 0.89% (0.47%, 1.67%) and those aged 5 to12 years at 0.86% (0.60%, 1.24%). Large household size, living in a deprived neighbourhood, and Asian ethnicity were all associated with increased prevalence. Healthcare and care home workers were more likely to test positive compared to other workers.

Conclusions

There is a strong decline in prevalence of SARS-CoV-2 in England among the general population five to six weeks into lockdown, but prevalence remains high: at levels similar to those observed in late September 2020. Also, the number of COVID-19 cases in hospitals is higher than at the peak of the first wave in April 2020. The effects of easing of social distancing when we transition out of lockdown need to be closely monitored to avoid a resurgence in infections and renewed pressure on health services.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/02/23/2021.02.18.21251973.full.pdf; doi:https://doi.org/10.1101/2021.02.18.21251973; html:https://europepmc.org/article/PPR/PPR287082; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR287082&type=FILE&fileName=EMS117383-pdf.pdf&mimeType=application/pdf PPR367549,https://doi.org/10.1101/2021.07.08.21260185,REACT-1 round 13 interim report: acceleration of SARS-CoV-2 Delta epidemic in the community in England during late June and early July 2021,"Riley S, Eales O, Haw D, Wang H, Walters CE, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly CA, Barclay W, Cooke G, Ward H, Darzi A, Elliott P.",,No Journal Info,2021,2021-07-08,Y,,,,"

Background

Despite high levels of vaccination in the adult population, cases of COVID-19 have risen exponentially in England since the start of May 2021 driven by the Delta variant. However, with far fewer hospitalisations and deaths per case during the recent growth in cases compared with 2020, it is intended that all remaining social distancing legislation in England will be removed from 19 July 2021.

Methods

We report interim results from round 13 of the REal-time Assessment of Community Transmission-1 (REACT-1) study in which a cross-sectional sample of the population of England was asked to provide a throat and nose swab for RT-PCR and to answer a questionnaire. Data collection for this report (round 13 interim) was from 24 June to 5 July 2021.

Results

In round 13 interim, we found 237 positives from 47,729 swabs giving a weighted prevalence of 0.59% (0.51%, 0.68%) which was approximately four-fold higher compared with round 12 at 0.15% (0.12%, 0.18%). This resulted from continued exponential growth in prevalence with an average doubling time of 15 (13, 17) days between round 12 and round 13. However, during the recent period of round 13 interim only, we observed a shorter doubling time of 6.1 (4.0, 12) days with a corresponding R number of 1.87 (1.40, 2.45). There were substantial increases in all age groups under the age of 75 years, and especially at younger ages, with the highest prevalence in 13 to 17 year olds at 1.33% (0.97%, 1.82%) and in 18 to 24 years olds at 1.40% (0.89%, 2.18%). Infections have increased in all regions with the largest increase in London where prevalence increased more than eight-fold from 0.13% (0.08%, 0.20%) in round 12 to 1.08% (0.79%, 1.47%) in round 13 interim. Overall, prevalence was over 3 times higher in the unvaccinated compared with those reporting two doses of vaccine in both round 12 and round 13 interim, although there was a similar proportional increase in prevalence in vaccinated and unvaccinated individuals between the two rounds.

Discussion

We are entering a critical period with a number of important competing processes: continued vaccination rollout to the whole adult population in England, increased natural immunity through infection, reduced social mixing of children during school holidays, increased proportion of mixing occurring outdoors during summer, the intended full opening of hospitality and entertainment and cessation of mandated social distancing and mask wearing. Surveillance programmes are essential during this next phase of the epidemic to provide clear evidence to the government and the public on the levels and trends in prevalence of infections and their relationship to vaccine coverage, hospitalisations, deaths and Long COVID.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/07/08/2021.07.08.21260185.full.pdf; doi:https://doi.org/10.1101/2021.07.08.21260185; html:https://europepmc.org/article/PPR/PPR367549; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR367549&type=FILE&fileName=EMS130294-pdf.pdf&mimeType=application/pdf PPR397279,https://doi.org/10.1101/2021.09.16.21263629,Access to personal protective equipment in healthcare workers during the COVID-19 pandemic in the United Kingdom: results from a nationwide cohort study (UK-REACH),"Martin CA, Pan D, Nazareth J, Aujayeb A, Bryant L, Carr S, Gray LJ, Gregary B, Gupta A, Guyatt AL, Gopal A, Hine T, John C, McManus IC, Melbourne C, Nellums LB, Reza R, Simpson S, Tobin MD, Woolf K, Zingwe S, Khunti K, Pareek M.",,No Journal Info,2021,2021-09-21,Y,,,,"

Objectives

To determine the prevalence and predictors of self-reported access to appropriate personal protective equipment (aPPE) for healthcare workers (HCWs) in the United Kingdom (UK) during the first UK national COVID-19 lockdown (March 2020) and at the time of questionnaire response (December 2020 – February 2021).

Design

Two cross sectional analyses using data from a questionnaire-based cohort study.

Setting

Nationwide questionnaire from 4 th December 2020 to 28 th February 2021.

Participants

A representative sample of HCWs or ancillary workers in a UK healthcare setting aged 16 or over, registered with one of seven main UK healthcare regulatory bodies.

Main outcome measure

Binary measure of self-reported aPPE (access all of the time vs access most of the time or less frequently) at two timepoints: the first national lockdown in the UK (primary analysis) and at the time of questionnaire response (secondary analysis).

Results

10,508 HCWs were included in the primary analysis, and 12,252 in the secondary analysis. 3702 (35.2%) of HCWs reported aPPE at all times in the primary analysis; 6806 (83.9%) reported aPPE at all times in the secondary analysis. After adjustment (for age, sex, ethnicity, migration status, occupation, aerosol generating procedure exposure, work sector, work region, working hours, night shift frequency and trust in employing organisation), older HCWs (per decade increase in age: aOR 1.2, 95% CI 1.16-1.26, p<0.001) and those working in Intensive Care Units (1.61, 1.38 – 1.89, p<0.001) were more likely to report aPPE at all times. Those from Asian ethnic groups compared to White (0.77, 0.67-0.89, p<0.001), those in allied health professional (AHPs) and dental roles (vs those in medical roles; AHPs: 0.77, 0.68 – 0.87, p<0.001; dental: 0.63, 0.49-0.81, p<0.001), and those who saw a higher number of COVID-19 patients compared to those who saw none (≥21 patients 0.74, 0.61-0.90, p=0.003) were less likely to report aPPE at all times in the primary analysis. aPPE at all times was also not uniform across UK regions (reported access being better in South West and North East England than London). Those who trusted their employing organisation to deal with concerns about unsafe clinical practice, compared to those who did not, were twice as likely to report aPPE at all times (2.18, 1.97-2.40, p<0.001). With the exception of occupation, these factors were also significantly associated with aPPE at all times in the secondary analysis.

Conclusions

We found that only a third of HCWs in the UK reported aPPE at all times during the period of the first lockdown and that aPPE had improved later in the pandemic. We also identified key sociodemographic and occupational determinants of aPPE during the first UK lockdown, the majority of which have persisted since lockdown was eased. These findings have important public health implications for HCWs, particularly as cases of infection and long-COVID continue to rise in the UK.

Trial registration

ISRCTN 11811602

What is already known on this topic

Access to personal protective equipment (PPE) is crucial to protect healthcare workers (HCWs) from infection. Limited data exist concerning the prevalence of, and factors relating to, PPE access for HCWs in the United Kingdom (UK) during the COVID-19 pandemic.

What this study adds

Only a third of HCWs reported having access to appropriate PPE all of the time during the first UK national lockdown. Older HCWs, those working in Intensive Care Units and those who trusted their employing organisation to deal with concerns about unsafe clinical practice, were more likely to report access to adequate PPE. Those from Asian ethnic groups (compared to White ethnic groups) and those who saw a high number of COVID-19 were less likely to report access to adequate PPE. Our findings have important implications for the mental and physical health of HCWs working during the pandemic in the UK.",,pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-022-08202-z; doi:https://doi.org/10.1101/2021.09.16.21263629; html:https://europepmc.org/article/PPR/PPR397279; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR397279&type=FILE&fileName=EMS135495-pdf.pdf&mimeType=application/pdf -PPR725396,https://doi.org/10.1101/2023.09.14.23295499,Mechanisms for Integrating Real Data into Search Game Simulations: An Application to Winter Health Service Pressures and Preventative Policies,"Chapman M, G-Medhin A, Daneshi K, Bramwell T, Durbaba S, Curcin V, Parmar D, Boulding H, Becares L, Morgan C, Molokhia M, McBurney P, Harding S, Wolfe I, Ashworth M, Poston L.",,No Journal Info,2023,2023-09-15,Y,,,,"While modelling and simulation are powerful techniques for exploring complex phenomena, if they are not coupled with suitable real-world data any results obtained are likely to require extensive validation. We consider this problem in the context of search game modelling, and suggest that both demographic and behaviour data are used to configure certain model parameters. We show this integration in practice by using a combined dataset of over 150,000 individuals to configure a specific search game model that captures the environment, population, interventions and individual behaviours relating to winter health service pressures. The presence of this data enables us to more accurately explore the potential impact of service pressure interventions, which we do across 33,000 simulations using a computational version of the model. We find government advice to be the best-performing intervention in simulation, in respect of improved health, reduced health inequalities, and thus reduced pressure on health service utilisation.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/09/15/2023.09.14.23295499.full.pdf; doi:https://doi.org/10.1101/2023.09.14.23295499; html:https://europepmc.org/article/PPR/PPR725396; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR725396&type=FILE&fileName=EMS188071-pdf.pdf&mimeType=application/pdf PPR179126,https://doi.org/10.1101/2020.06.22.20137216,"Proteomic blood profiling in mild, severe and critical COVID-19 patients","Patel H, Ashton NJ, Dobson RJ, Andersson L, Yilmaz A, Blennow K, Gisslen M, Zetterberg H.",,No Journal Info,2020,2020-06-23,N,,,,"The recent SARS-CoV-2 pandemic manifests itself as a mild respiratory tract infection in the majority of individuals leading to COVID-19 disease. However, in some infected individuals, this can progress to severe pneumonia and acute respiratory distress syndrome (ARDS), leading to multi-organ failure and death. The purpose of this study is to explore the proteomic differences between mild, severe and critical COVID-19 positive patients. Blood protein profiling was performed on 59 COVID-19 mild (n=26), severe (n=9) or critical (n=24) cases and 28 controls using the OLINK inflammation, autoimmune, cardiovascular and neurology panels. Differential expression analysis was performed within and between disease groups to generate nine different analyses. From the 368 proteins measured per individual, more than 75% were observed to be significantly perturbed in COVID-19 cases. Six proteins (IL6, CKAP4, Gal-9, IL-1ra, LILRB4 and PD-L1) were identified to be associated with disease severity. The results have been made readily available through an interactive web-based application for instant data exploration and visualization, and can be accessed at https://phidatalab-shiny.rosalind.kcl.ac.uk/COVID19/ . Our results demonstrate that dynamic changes in blood proteins that associate with disease severity can potentially be used as early biomarkers to monitor disease severity in COVID-19 and serve as potential therapeutic targets.",,pdf:https://www.nature.com/articles/s41598-021-85877-0.pdf; doi:https://doi.org/10.1101/2020.06.22.20137216; html:https://europepmc.org/article/PPR/PPR179126; doi:https://doi.org/10.1101/2020.06.22.20137216 +PPR725396,https://doi.org/10.1101/2023.09.14.23295499,Mechanisms for Integrating Real Data into Search Game Simulations: An Application to Winter Health Service Pressures and Preventative Policies,"Chapman M, G-Medhin A, Daneshi K, Bramwell T, Durbaba S, Curcin V, Parmar D, Boulding H, Becares L, Morgan C, Molokhia M, McBurney P, Harding S, Wolfe I, Ashworth M, Poston L.",,No Journal Info,2023,2023-09-15,Y,,,,"While modelling and simulation are powerful techniques for exploring complex phenomena, if they are not coupled with suitable real-world data any results obtained are likely to require extensive validation. We consider this problem in the context of search game modelling, and suggest that both demographic and behaviour data are used to configure certain model parameters. We show this integration in practice by using a combined dataset of over 150,000 individuals to configure a specific search game model that captures the environment, population, interventions and individual behaviours relating to winter health service pressures. The presence of this data enables us to more accurately explore the potential impact of service pressure interventions, which we do across 33,000 simulations using a computational version of the model. We find government advice to be the best-performing intervention in simulation, in respect of improved health, reduced health inequalities, and thus reduced pressure on health service utilisation.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/09/15/2023.09.14.23295499.full.pdf; doi:https://doi.org/10.1101/2023.09.14.23295499; html:https://europepmc.org/article/PPR/PPR725396; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR725396&type=FILE&fileName=EMS188071-pdf.pdf&mimeType=application/pdf PPR301060,https://doi.org/10.1101/2021.03.20.21254010,Older biological age is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank,"Wang Q, Codd V, Raisi-Estabragh Z, Musicha C, Bountziouka V, Kaptoge S, Allara E, Angelantonio ED, Butterworth AS, Wood AM, Thompson JR, Petersen SE, Harvey NC, Danesh JN, Samani NJ, Nelson CP.",,No Journal Info,2021,2021-03-22,Y,,,,"

Background

Older chronological age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain, however, whether older biological age, as assessed by leucocyte telomere length (LTL), is also associated with COVID-19 outcomes.

Methods

We associated LTL values obtained from participants recruited into UK Biobank (UKB) during 2006-2010 with adverse COVID-19 outcomes recorded by 30 November 2020, defined as a composite of any of the following: hospital admission, need for critical care, respiratory support, or mortality. Using information on 131 LTL-associated genetic variants, we conducted exploratory Mendelian randomisation (MR) analyses in UKB to evaluate whether observational associations might reflect cause-and-effect relationships.

Findings

Of 6,775 participants in UKB who had tested positive for infection with SARS-CoV-2 in the community, there were 914 (13.5%) with adverse COVID-19 outcomes. The odds ratio (OR) for adverse COVID-19 outcomes was 1·17 (95% CI 1·05-1·31; P=0·004) per 1-SD shorter usual LTL, after adjustment for chronological age, sex and ethnicity. Similar ORs were observed in analyses that: adjusted for additional risk factors; disaggregated the composite outcome and reduced the scope for selection or collider bias. In MR analyses, the OR for adverse COVID-19 outcomes was directionally concordant but non-significant.

Interpretation

Shorter LTL, indicative of older biological age, is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including chronological age. Further data are needed to determine whether this association reflects causality.

Funding

UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/03/22/2021.03.20.21254010.full.pdf; doi:https://doi.org/10.1101/2021.03.20.21254010; html:https://europepmc.org/article/PPR/PPR301060; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR301060&type=FILE&fileName=EMS120573-pdf.pdf&mimeType=application/pdf PPR401642,https://doi.org/10.1101/2021.09.27.21264166,Prevalence and duration of detectable SARS-CoV-2 nucleocapsid antibody in staff and residents of long-term care facilities over the first year of the pandemic (VIVALDI study): prospective cohort study,"Krutikov M, Palmer T, Tut G, Fuller C, Azmi B, Giddings R, Shrotri M, Kaur N, Sylla P, Lancaster T, Irwin-Singer A, Hayward A, Moss P, Copas A, Shallcross L.",,No Journal Info,2021,2021-09-29,Y,,,,"

Background

Long Term Care Facilities (LTCF) have reported high SARS-CoV-2 infection rates and related mortality, but the proportion infected amongst survivors and duration of the antibody response to natural infection is unknown. We determined the prevalence and stability of nucleocapsid antibodies – the standard assay for detection of prior infection - in staff and residents from 201 LTCFs.

Methods

Prospective cohort study of residents aged >65 years and staff of LTCFs in England (11 June 2020-7 May 2021). Serial blood samples were tested for IgG antibodies against SARS-CoV-2 nucleocapsid protein. Prevalence and cumulative incidence of antibody-positivity were weighted to the LTCF population. Cumulative incidence of sero-reversion was estimated from Kaplan-Meier curves.

Results

9488 samples were included, 8636 (91%) of which could be individually-linked to 1434 residents or 3288 staff members. The cumulative incidence of nucleocapsid seropositivity was 35% (95% CI: 30-40%) in residents and 26% (95% CI: 23-30%) in staff over 11 months. The incidence rate of loss of antibodies (sero-reversion) was 2·1 per 1000 person-days at risk, and median time to reversion was around 8 months.

Interpretation

At least one-quarter of staff and one-third of surviving residents were infected during the first two pandemic waves. Nucleocapsid-specific antibodies often become undetectable within the first year following infection which is likely to lead to marked underestimation of the true proportion of those with prior infection. Since natural infection may act to boost vaccine responses, better assays to identify natural infection should be developed.

Funding

UK Government Department of Health and Social Care.

Research in context

Evidence before this study

A search was conducted of Ovid MEDLINE and MedRxiv on 21 July 2021 to identify studies conducted in long term care facilities (LTCF) that described seroprevalence using the terms “COVID-19” or “SARS-CoV-2” and “nursing home” or “care home” or “residential” or “long term care facility” and “antibody” or “serology” without date or language restrictions. One meta-analysis was identified, published before the introduction of vaccination, that included 2 studies with a sample size of 291 which estimated seroprevalence as 59% in LTCF residents. There were 28 seroprevalence surveys of naturally-acquired SARS-CoV-2 antibodies in LTCFs; 16 were conducted in response to outbreaks and 12 conducted in care homes without known outbreaks. 16 studies included more than 1 LTCF and all were conducted in Autumn 2020 after the first wave of infection but prior to subsequent peaks. Seroprevalence studies conducted following a LTCF outbreak were biased towards positivity as the included population was known to have been previously infected. In the 12 studies that were conducted outside of known outbreaks, seroprevalence varied significantly according to local prevalence of infection. The largest of these was a cross-sectional study conducted in 9,000 residents and 10,000 staff from 362 LTCFs in Madrid, which estimated seroprevalence in staff as 31·5% and 55·4% in residents. However, as this study was performed in one city, it may not be generalisable to the whole of Spain and sequential sampling was not performed. Of the 28 studies, 9 undertook longitudinal sampling for a maximum of four months although three of these reported from the same cohort of LTCFs in London. None of the studies reported on antibody waning amongst the whole resident population.

Added value of this study

We estimated the proportion of care home staff and residents with evidence of SARS-CoV-2 natural infection using data from over 3,000 staff and 1,500 residents in 201 geographically dispersed LTCFs in England. Population selection was independent of outbreak history and the sample is therefore more reflective of the population who reside and work in LTCFs. Our estimates of the proportion of residents with prior natural infection are substantially higher than estimates based on population-wide PCR testing, due to limited testing coverage at the start of the pandemic. 1361 individuals had at least one positive antibody test and participants were followed for up to 11 months, which allowed modelling of the time to loss of antibody in over 600 individuals in whom the date of primary infection could be reliably estimated. This is the longest reported serological follow up in a population of LTCF residents, a group who are known to be most at risk of severe outcomes following infection with SARS-CoV-2 and provides important evidence on the duration that nucleocapsid antibodies remained detectable over the first and second waves of the pandemic.

Implications of all available research

A substantial proportion of the LTCF population will have some level of natural immunity to infection as a result of past infection. Immunological studies have highlighted greater antibody responses to vaccination in seropositive individuals, so vaccine efficacy in this population may be affected by this large pool of individuals who have survived past infection. In addition, although the presence of nucleocapsid-specific antibodies is generally considered as the standard marker for prior infection, we find that antibody waning is such that up to 50% of people will lose detectable antibody responses within eight months. Individual prior natural infection history is critical to assess the impact of factors such as vaccine response or protection against re-infection. These findings may have implications for duration of immunity following natural infection and indicate that alternative assays for prior infection should be developed.",,pdf:http://www.thelancet.com/article/S2666756821002828/pdf; doi:https://doi.org/10.1101/2021.09.27.21264166; html:https://europepmc.org/article/PPR/PPR401642; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR401642&type=FILE&fileName=EMS136680-pdf.pdf&mimeType=application/pdf -PPR443102,https://doi.org/10.1101/2022.01.13.22269211,"Assessing the clinical severity of the Omicron variant in the Western Cape Province, South Africa, using the diagnostic PCR proxy marker of RdRp target delay to distinguish between Omicron and Delta infections – a survival analysis","Hussey H, Davies M, Heekes A, Williamson C, Valley-Omar Z, Hardie D, Korsman S, Doolabh D, Preiser W, Maponga T, Iranzadeh A, Wasserman S, Boloko L, Symons G, Raubenheimer P, Viljoen A, Parker A, Schrueder N, Solomon W, Rousseau P, Wolter N, Jassat W, Cohen C, Lessells R, Wilkinson RJ, Boulle A, Hsiao N.",,No Journal Info,2022,2022-01-14,Y,,,,"

Background

Emerging data suggest that SARS-CoV-2 Omicron variant of concern (VOC)is associated with reduced risk of severe disease. The extent to which this reflects a difference in the inherent virulence of Omicron, or just higher levels of population immunity, is currently not clear.

Methods

RdRp target delay (RTD: a difference in cycle threshold value of RdRp - E > 3.5) in the Seegene Allplex™ 2019-nCoV PCR assay is a proxy marker for the Delta VOC. The absence of this proxy marker in the period of transition to Omicron was used to identify suspected Omicron VOC infections. Cox regression was performed for the outcome of hospital admission in those who tested positive for SARS-CoV-2 on the Seegene Allplex™ assay from 1 November to 14 December 2021 in the Western Cape Province, South Africa, public sector. Vaccination status at time of diagnosis, as well as prior diagnosed infection and comorbidities, were adjusted for.

Results

150 cases with RTD (proxy for Delta) and 1486 cases without RTD (proxy for Omicron) were included. Cases without RTD had a lower hazard of admission (adjusted Hazard Ratio [aHR] of 0.56, 95% confidence interval [CI] 0.34-0.91). Complete vaccination was protective of admission with an aHR of 0.45 (95%CI 0.26-0.77).

Conclusion

Omicron has resulted in a lower risk of hospital admission, compared to contemporaneous Delta infection in the Western Cape Province, when using the proxy marker of RTD. Under-ascertainment of reinfections with an immune escape variant like Omicron remains a challenge to accurately assessing variant virulence.",,pdf:https://figshare.com/articles/journal_contribution/Assessing_the_clinical_severity_of_the_Omicron_variant_in_the_Western_Cape_Province_South_Africa_using_the_diagnostic_PCR_proxy_marker_of_RdRp_target_delay_to_distinguish_between_Omicron_and_Delta_infections_-_a_survival_analysis_/19481834/1/files/34622237.pdf; doi:https://doi.org/10.1101/2022.01.13.22269211; html:https://europepmc.org/article/PPR/PPR443102; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR443102&type=FILE&fileName=EMS142448-pdf.pdf&mimeType=application/pdf PPR277515,https://doi.org/10.1101/2021.02.01.21250839,Extremely high SARS-CoV-2 seroprevalence in a strictly-Orthodox Jewish community in the UK,"Gaskell KM, Johnson M, Gould V, Hunt A, Stone NR, Waites W, Kasstan B, Chantler T, Lal S, Roberts Ch, Goldblatt D, Eggo RM, Marks M.",,No Journal Info,2021,2021-02-03,Y,,,,"

Background

Ethnic and religious minorities have been disproportionately affected by SARS-CoV-2 worldwide. The UK strictly-Orthodox Jewish community has been severely affected by the pandemic. This group shares characteristics with other ethnic minorities including larger family sizes, higher rates of household crowding and relative socioeconomic deprivation. We studied a UK strictly-Orthodox Jewish population to understand how COVID-19 had spread within this community.

Methods

We performed a household-focused cross-sectional SARS-CoV-2 serosurvey specific to three antigen targets. Randomly-selected households completed a standardised questionnaire and underwent serological testing with a multiplex assay for SARS-CoV-2 IgG antibodies. We report clinical illness and testing before the serosurvey, seroprevalence stratified by age and gender. We used random-effects models to identify factors associated with infection and antibody titres.

Findings

A total of 343 households, consisting of 1,759 individuals, were recruited. Serum was available for 1,242 participants. The overall seroprevalence for SARS-CoV-2 was 64.3% (95% CI 61.6-67.0%). The lowest seroprevalence was 27.6% in children under 5 years and rose to 73.8% in secondary school children and 74% in adults. Antibody titres were higher in symptomatic individuals and declined over time since reported COVID-19 symptoms, with the decline more marked for nucleocapsid titres.

Interpretation

In this tight-knit religious minority population in the UK, we report one of the highest SARS-CoV-2 seroprevalence levels in the world to date. In the context of this high force of infection, all age groups experienced a high burden of infection. Actions to reduce the burden of disease in this and other minority populations are urgently required.

Funding

This work was jointly funded by UKRI and NIHR [COV0335; MR/V027956/1], a donation from the LSHTM Alumni COVID-19 response fund, HDR UK, the MRC and the Wellcome Trust. The funders had no role in the design, conduct or analysis of the study or the decision to publish. The authors have no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Research In Context

Evidence before the study

In January 2020, we searched PubMed for articles on rates of SARS-CoV-2 infection amongst ethnic minority groups and amongst the Jewish population. Search teams included “COVID-19”, “SARS-CoV-2”, seroprevalence, “ethnic minority”, and “Jewish” with no language restrictions. We also searched UK government documents on SARS-CoV-2 infection amongst minority groups. By January 2020, a large number of authors had reported that ethnic minority groups experienced higher numbers of cases and increased hospitalisations due to COVID-19. A small number of articles provided evidence that strictly-Orthodox Jewish populations had experienced a high rate of SARS-CoV-2 infection but extremely limited data was available on overall population level rates of infection amongst specific ethnic minority population groups. There was also extremely limited data on rates of infection amongst young children from ethnic minority groups.

Added value of the study

We report findings from a population representative, household survey of SARS-CoV-2 infection amongst a UK strictly Orthodox Jewish population. We demonstrate an extremely high seroprevalence rate of SARS-CoV-2 in this population which is more than five times the estimated seroprevalence nationally and five times the estimated seroprevalence in London. In addition the large number of children in our survey, reflective of the underlying population structure, allows us to demonstrate that in this setting there is a significant burden of disease in all age groups with secondary school aged children having an equivalent seroprevalence to adults.

Implications of the available evidence

Our data provide clear evidence of the markedly disproportionate impact of SARS-CoV-2 in minority populations. In this setting infection occurs at high rates across all age groups including pre-school, primary school and secondary school-age children. Contextually appropriate measures to specifically reduce the impact of SARS-CoV-2 amongst minority populations are urgently required.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/02/03/2021.02.01.21250839.full.pdf; doi:https://doi.org/10.1101/2021.02.01.21250839; html:https://europepmc.org/article/PPR/PPR277515; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR277515&type=FILE&fileName=EMS115861-pdf.pdf&mimeType=application/pdf +PPR443102,https://doi.org/10.1101/2022.01.13.22269211,"Assessing the clinical severity of the Omicron variant in the Western Cape Province, South Africa, using the diagnostic PCR proxy marker of RdRp target delay to distinguish between Omicron and Delta infections – a survival analysis","Hussey H, Davies M, Heekes A, Williamson C, Valley-Omar Z, Hardie D, Korsman S, Doolabh D, Preiser W, Maponga T, Iranzadeh A, Wasserman S, Boloko L, Symons G, Raubenheimer P, Viljoen A, Parker A, Schrueder N, Solomon W, Rousseau P, Wolter N, Jassat W, Cohen C, Lessells R, Wilkinson RJ, Boulle A, Hsiao N.",,No Journal Info,2022,2022-01-14,Y,,,,"

Background

Emerging data suggest that SARS-CoV-2 Omicron variant of concern (VOC)is associated with reduced risk of severe disease. The extent to which this reflects a difference in the inherent virulence of Omicron, or just higher levels of population immunity, is currently not clear.

Methods

RdRp target delay (RTD: a difference in cycle threshold value of RdRp - E > 3.5) in the Seegene Allplex™ 2019-nCoV PCR assay is a proxy marker for the Delta VOC. The absence of this proxy marker in the period of transition to Omicron was used to identify suspected Omicron VOC infections. Cox regression was performed for the outcome of hospital admission in those who tested positive for SARS-CoV-2 on the Seegene Allplex™ assay from 1 November to 14 December 2021 in the Western Cape Province, South Africa, public sector. Vaccination status at time of diagnosis, as well as prior diagnosed infection and comorbidities, were adjusted for.

Results

150 cases with RTD (proxy for Delta) and 1486 cases without RTD (proxy for Omicron) were included. Cases without RTD had a lower hazard of admission (adjusted Hazard Ratio [aHR] of 0.56, 95% confidence interval [CI] 0.34-0.91). Complete vaccination was protective of admission with an aHR of 0.45 (95%CI 0.26-0.77).

Conclusion

Omicron has resulted in a lower risk of hospital admission, compared to contemporaneous Delta infection in the Western Cape Province, when using the proxy marker of RTD. Under-ascertainment of reinfections with an immune escape variant like Omicron remains a challenge to accurately assessing variant virulence.",,pdf:https://figshare.com/articles/journal_contribution/Assessing_the_clinical_severity_of_the_Omicron_variant_in_the_Western_Cape_Province_South_Africa_using_the_diagnostic_PCR_proxy_marker_of_RdRp_target_delay_to_distinguish_between_Omicron_and_Delta_infections_-_a_survival_analysis_/19481834/1/files/34622237.pdf; doi:https://doi.org/10.1101/2022.01.13.22269211; html:https://europepmc.org/article/PPR/PPR443102; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR443102&type=FILE&fileName=EMS142448-pdf.pdf&mimeType=application/pdf PPR814122,https://doi.org/10.1101/2024.03.03.24303615,Redeployment Experiences of Healthcare Workers in the UK during COVID-19: data from the nationwide UK-REACH study,"Lal ZZ, Martin CA, Gogoi M, Qureshi I, Bryant L, Papineni P, Lagrata S, Nellums LB, Al-Oraibi A, Chaloner J, Woolf K, Pareek M.",,No Journal Info,2024,2024-03-04,Y,,,,"

Background

Increasing demands of COVID-19 on the healthcare system necessitated redeployment of HCWs outside their routine specialties. Previous studies, highlighting ethnic and occupational inequalities in redeployment, are limited by small cohorts with limited ethnic diversity.

Aims

To assess how ethnicity, migration status, and occupation are associated with HCWs’ redeployment experiences during COVID-19 in a nationwide ethnically diverse sample.

Methods

We conducted a cross-sectional analysis using data from the nationwide United Kingdom Research Study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH) cohort study. We used logistic regression to examine associations of ethnicity, migration status, and occupation with redeployment experiences of HCWs, including provision of training and supervision, patient contact during redeployment and interaction with COVID-19 patients.

Results

Of the 10,889 HCWs included, 20.4% reported being redeployed during the first UK national lockdown in March 2020. Those in nursing roles (Odds Ratio (OR) 1.22, 95% Confidence Interval (CI) 1.04 – 1.42, p=0.009) (compared to medical roles) had higher likelihood of being redeployed as did migrants compared to those born in the UK (OR 1.26, 95% CI 1.06 - 1.49, p=0.01) (in a subcohort of HCWs on the agenda for change (AfC) pay scales). Asian HCWs were less likely to report receiving training (OR 0.66, 95% CI 0.50 – 0.88, p=0.005) and Black HCWs (OR 2.02, 95% CI 1.14 – 3.57, p=0.02) were more likely to report receiving supervision, compared to White colleagues. Finally, redeployed Black (OR 1.33, 95% CI 1.07 – 1.66, p=0.009) and Asian HCWs (OR 1.30, 95% CI 1.14 – 1.48, p<0.001) were more likely to report face-to-face interaction with COVID-19 patients than White HCWs.

Conclusions

Our findings highlight disparities in HCWs’ redeployment experiences by ethnicity, migration, and job role which are potentially related to structural inequities in healthcare. For future emergencies, redeployment should be contingent upon risk assessments, accompanied by training and supervision tailored to individual HCWs’ experience and skillset. What is already known on this topic: Ethnic minority healthcare workers (HCWs) were at an elevated risk of infection during COVID-19 due to occupational and socio-demographic factors. The strain on healthcare systems during the pandemic resulted in acute staffing shortages, prompting redeployment of HCWs to areas outside their professional training. However, recent research suggests inconsistent implementation of redeployment across ethnic groups, revealing structural disparities within the healthcare system. What this study adds: Our study, the largest of its kind, found no ethnic differences in the process of redeployment itself, but disparities emerged in the experiences of redeployment. Asian HCWs reported less likelihood of receiving training, while Black HCWs reported more likelihood of receiving supervision compared to their White counterparts. Ethnic minority HCWs were also more likely to report interaction with COVID-19 patients than their White colleagues. While there were no ethnic differences in the process of redeployment, occupational and migration differences reveal that those in nursing and midwifery roles (in comparison to medical roles), as well as migrant HCWs on the AfC payscale (in comparison to those born in the UK), were more likely to report being redeployed. How this study might affect research, practice or policy: This UK-wide study highlights inconsistencies in the redeployment process, training, supervision, and patient interactions based on occupation, ethnicity and migration status. Further investigation, incorporating qualitative and human resources data, is crucial to understand the complexities and address potential structural discrimination within the NHS. For future practice, redeployment should align with risk assessments and include training and supervision tailored to HCWs’ experience and skillset.

Teaser text

This study explores how ethnicity, migration status, and occupation were associated with healthcare workers’ (HCWs) redeployment experiences during COVID-19. After adjustment of covariates, we found that nursing roles and migration to the UK increase redeployment likelihood. Asian HCWs reported lesser training and Black HCWs reported more supervision, compared to White colleagues. Redeployed Black and Asian HCWs were more likely to report interaction with COVID-19 patients. Findings highlight disparities in HCWs’ redeployment experiences in an ethnically diverse sample.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2024/03/04/2024.03.03.24303615.full.pdf; doi:https://doi.org/10.1101/2024.03.03.24303615; html:https://europepmc.org/article/PPR/PPR814122; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR814122&type=FILE&fileName=EMS194583-pdf.pdf&mimeType=application/pdf PPR293368,https://doi.org/10.1101/2021.03.03.21252856,REACT-1 round 9 final report: Continued but slowing decline of prevalence of SARS-CoV-2 during national lockdown in England in February 2021,"Riley S, Wang H, Eales O, Haw D, Walters CE, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P.",,No Journal Info,2021,2021-03-06,Y,,,,"

Background

England will start to exit its third national lockdown in response to the COVID-19 pandemic on 8th March 2021, with safe effective vaccines being rolled out rapidly against a background of emerging transmissible and immunologically novel variants of SARS-CoV-2. A subsequent increase in community prevalence of infection could delay further relaxation of lockdown if vaccine uptake and efficacy are not sufficiently high to prevent increased pressure on healthcare services.

Methods

The PCR self-swab arm of the REal-time Assessment of Community Transmission Study (REACT-1) estimates community prevalence of SARS-CoV-2 infection in England based on random cross-sections of the population ages five and over. Here, we present results from the complete round 9 of REACT-1 comprising round 9a in which swabs were collected from 4th to 12th February 2021 and round 9b from 13th to 23rd February 2021. We also compare the results of REACT-1 round 9 to round 8, in which swabs were collected mainly from 6th January to 22nd January 2021.

Results

Out of 165,456 results for round 9 overall, 689 were positive. Overall weighted prevalence of infection in the community in England was 0.49% (0.44%, 0.55%), representing a fall of over two thirds from round 8. However the rate of decline of the epidemic has slowed from 15 (13, 17) days, estimated for the period from the end of round 8 to the start of round 9, to 31 days estimated using data from round 9 alone (lower confidence limit 17 days). When comparing round 9a to 9b there were apparent falls in four regions, no apparent change in one region and apparent rises in four regions, including London where there was a suggestion of sub-regional heterogeneity in growth and decline. Smoothed prevalence maps suggest large contiguous areas of growth and decline that do not align with administrative regions. Prevalence fell by 50% or more across all age groups in round 9 compared to round 8, with prevalence (round 9) ranging from 0.21% in those aged 65 and over to 0.71% in those aged 13 to 17 years. Round 9 prevalence was highest among Pakistani participants at 2.1% compared to white participants at 0.45% and Black participants at 0.83%. There were higher adjusted odds of infection for healthcare and care home workers, for those working in public transport and those working in education, school, nursery or childcare and lower adjusted odds for those not required to work outside the home.

Conclusions

Community prevalence of swab-positivity has declined markedly between January and February 2021 during lockdown in England, but remains high; the rate of decline has slowed in the most recent period, with a suggestion of pockets of growth. Continued adherence to social distancing and public health measures is required so that infection rates fall to much lower levels. This will help to ensure that the benefits of the vaccination roll-out programme in England are fully realised.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/03/06/2021.03.03.21252856.full.pdf; doi:https://doi.org/10.1101/2021.03.03.21252856; html:https://europepmc.org/article/PPR/PPR293368; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR293368&type=FILE&fileName=EMS118777-pdf.pdf&mimeType=application/pdf PPR186543,https://doi.org/10.1101/2020.07.10.20150656,Diagnostic value of skin manifestation of SARS-CoV-2 infection,"Bataille V, Visconti A, Rossi N, Murray B, Bournot A, Wolf J, Wolf J, Ourselin S, Steves C, Spector T, Falchi M.",,No Journal Info,2020,2020-07-11,Y,,,,"SARS-CoV-2 causes multiple immune-related reactions at various stages of the disease. The wide variety of skin presentations has delayed linking these to the virus. Previous studies had attempted to look at the prevalence and timing of SARS-COV-2 rashes but were based on mostly hospitalized severe cases and had little follow up. Using data collected on a subset of 336,847 eligible UK users of the COVID Symptom Study app, we observed that 8.8% of the swab positive cases (total: 2,021 subjects) reported either a body rash or an acral rash, compared to 5.4% of those with a negative swab test (total: 25,136). Together, these two skin presentations showed an odds ratio (OR) of 1.67 (95% confidence interval [CI]: 1.41-1.96) for being swab positive. Skin rashes were also predictive in the larger untested group of symptomatic app users (N=54,652), as 8.2% of those who had reported at least one classical COVID-19 symptom, i . e ., fever, persistent cough, and/or anosmia, also reported a rash. Data from an independent online survey of 11,546 respondents with a rash showed that in 17% of swab positive cases, the rash was the initial presentation. Furthermore, in 21%, the rash was the only clinical sign. Skin rashes cluster with other COVID-19 symptoms, are predictive of a positive swab test and occur in a significant number of cases, either alone or before other classical symptoms. Recognising rashes is important in identifying new and earlier COVID-19 cases.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/10/26/2020.07.10.20150656.full.pdf; doi:https://doi.org/10.1101/2020.07.10.20150656; html:https://europepmc.org/article/PPR/PPR186543; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR186543&type=FILE&fileName=EMS87210-pdf.pdf&mimeType=application/pdf @@ -259,17 +259,17 @@ PPR370874,https://doi.org/10.1101/2021.07.12.21260360,The impact of hypoxia on B PPR182791,https://doi.org/10.1101/2020.07.01.182709,Genetic architecture of host proteins interacting with SARS-CoV-2,"Pietzner M, Wheeler E, Carrasco-Zanini J, Raffler J, Kerrison ND, Oerton E, Auyeung VP, Luan J, Finan C, Casas JP, Ostroff R, Williams SA, Kastenmüller G, Ralser M, Gamazon ER, Wareham NJ, Hingorani AD, Langenberg C.",,No Journal Info,2020,2020-07-01,Y,,,,"

ABSTRACT

Strategies to develop therapeutics for SARS-CoV-2 infection may be informed by experimental identification of viral-host protein interactions in cellular assays and measurement of host response proteins in COVID-19 patients. Identification of genetic variants that influence the level or activity of these proteins in the host could enable rapid ‘in silico’ assessment in human genetic studies of their causal relevance as molecular targets for new or repurposed drugs to treat COVID-19. We integrated large-scale genomic and aptamer-based plasma proteomic data from 10,708 individuals to characterize the genetic architecture of 179 host proteins reported to interact with SARS-CoV-2 proteins or to participate in the host response to COVID-19. We identified 220 host DNA sequence variants acting in cis (MAF 0.01-49.9%) and explaining 0.3-70.9% of the variance of 97 of these proteins, including 45 with no previously known protein quantitative trait loci (pQTL) and 38 encoding current drug targets. Systematic characterization of pQTLs across the phenome identified protein-drug-disease links, evidence that putative viral interaction partners such as MARK3 affect immune response, and establish the first link between a recently reported variant for respiratory failure of COVID-19 patients at the ABO locus and hypercoagulation, i.e. maladaptive host response. Our results accelerate the evaluation and prioritization of new drug development programmes and repurposing of trials to prevent, treat or reduce adverse outcomes. Rapid sharing and dynamic and detailed interrogation of results is facilitated through an interactive webserver ( https://omicscience.org/apps/covidpgwas/ ).",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337378; doi:https://doi.org/10.1101/2020.07.01.182709; html:https://europepmc.org/article/PPR/PPR182791; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR182791&type=FILE&fileName=EMS93113-pdf.pdf&mimeType=application/pdf PPR683852,https://doi.org/10.21203/rs.3.rs-3054644/v1,Implementing Germ Defence digital behaviour change intervention via all primary care practices in England to reduce respiratory infections during the COVID-19 pandemic: an efficient cluster randomised controlled trial using the OpenSAFELY platform.,"Ainsworth B, Horwood J, Walter SR, Miller S, Chalder M, De Vocht F, Denison-Day J, Elwenspoek M, Curtis H, Bates C, Mehrkar A, Bacon S, Goldacre B, Collaborative TO, Craggs P, Amlot R, Francis N, Little P, MacLeod J, Moore M, Morton K, Rice C, Sterne J, Stuart B, Towler L, Willcox M, Yardley L.",,No Journal Info,2023,2023-06-29,Y,,,,"

Background:

Germ Defence (www.germdefence.org) is an evidence-based interactive website that promotes behaviour change for infection control within households. To maximise the potential of Germ Defence to effectively reduce the spread of COVID-19 the intervention needed to be implemented at scale rapidly.

Methods:

: With the approval of NHS England, we implemented an efficient two-arm (1:1 ratio) cluster randomised controlled trial (RCT) to examine the effectiveness of randomising implementation of Germ Defence via GP practices across England, UK, compared with usual care. GP practices randomised to the intervention arm (n=3292) were emailed and asked to disseminate the Germ Defence intervention to all adult patients via mobile phone text, email or social media. GP practices randomised to the usual care arm (n=3287) maintained standard management for the 4-month trial period after and then asked to share Germ Defence with their adult patients. The primary outcome was the rate of GP presentations for respiratory tract infections (RTI) per patient. Secondary outcomes comprised rates of acute RTIs, confirmed COVID-19 diagnoses, suspected COVID-19 diagnoses, COVID-19 symptoms, gastrointestinal infection diagnoses, antibiotic usage, hospital admissions. The impact of the intervention on outcome rates was assessed using negative binomial regression modelling within the OpenSAFELY platform. The uptake of intervention by GP practice, and by patients were measured via website analytics.

Results:

: Germ Defence was used 310,731 times. The average satisfaction score after using the website was 7.52 (0-10 not at all to very satisfied, N = 9933). There was no evidence of a difference in the rate of RTIs between intervention and control practices (rate ratio (RR) 1.01, 95%CI 0.96, 1.06, p=0.70). This was similar to all other eight health outcomes. Patient engagement within intervention arm practices ranged from 0- 48% of a practice list. Practices with high levels of intervention uptake (>11%) had a lower proportion of minority ethnic groups.

Conclusions:

: We demonstrated that rapid large-scale implementation of a digital behavioural intervention can be evaluated with a novel efficient prospective RCT methodology analysing routinely collected patient data entirely within a trusted research environment. Trial registration: This trial was registered in the ISRCTN registry (14602359) on 12 August 2020.",,pdf:https://www.researchsquare.com/article/rs-3054644/latest.pdf; doi:https://doi.org/10.21203/rs.3.rs-3054644/v1; html:https://europepmc.org/article/PPR/PPR683852; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR683852&type=FILE&fileName=EMS178343-pdf.pdf&mimeType=application/pdf PPR373497,https://doi.org/10.1101/2021.07.22.21260416,"Obesity, Ethnicity, and Covid-19 Mortality: A population-based cohort study of 12.6 Million Adults in England","Yates T, Summerfield A, Razieh C, Banerjee A, Chudasama Y, Davies MJ, Gillies C, Islam N, Lawson C, Mirkes E, Zaccardi F, Khunti K, Nafilyan V.",,No Journal Info,2021,2021-07-23,Y,,,,"

Importance

Obesity and ethnicity are well characterised risk factors for severe COVID-19 outcomes, but the differential effects of obesity on COVID-19 outcomes by race/ethnicity has not been examined robustly in the general population.

Objective

To investigate the association between body mass index (BMI) and COVID-19 mortality across different ethnic groups.

Design, Setting, and Participants

This is a retrospective cohort study using linked national Census, electronic health records and mortality data for English adults aged 40 years or older who were alive at the start of pandemic (24 th January 2020).

Exposures

BMI obtained from electronic health records. Self-reported ethnicity (white, black, South Asian, other) was the effect-modifying variable.

Main Outcomes and Measures

COVID-19 related death identified by ICD-10 codes U07.1 or U07.2 mentioned on the death certificate from 24 th January 2020 until December 28 th 2020.

Results

The analysis included white (n = 11,074,708; mean age 61.9 [±13.4] years; 54% women), black (n = 416,542; 56.4 [±11.7] years; 57% women), South Asian (621,691; 55.7 [±12.4] years; 51% women) and other (n = 478,196; 55.3 [±11.6] years; 55% women) ethnicities with linked BMI data. The association between BMI and COVID-19 mortality was stronger in ethnic minority groups. Compared to a BMI of 22.5 kg/m 2 in white ethnicities, the adjusted HR for COVID-19 mortality at a BMI of 30 kg/m 2 in white, black, South Asian and other ethnicities was 0.95 (95% CI: 0.87-1.03), 1.72 (1.52-1.94), 2.00 (1.78-2.25) and 1.39 (1.21-1.61), respectively. The estimated risk of COVID-19 mortality at a BMI of 40 kg/m 2 in white ethnicities (HR = 1.73) was equivalent to the risk observed at a BMI of 30.1 kg/m 2 , 27.0 kg/m 2 , and 32.2 kg/m 2 in black, South Asian and other ethnic groups, respectively.

Conclusions

This population-based study using linked Census and electronic health care records demonstrates that the risk of COVID-19 mortality associated with obesity is greater in ethnic minority groups compared to white populations.

Question

Does the association between BMI and COVID-19 mortality vary by ethnicity?

Findings

In this study of 12.6 million adults, BMI was associated with COVID-19 in all ethnicities, but with stronger associations in ethnic minority populations such that the risk of COVID-19 mortality for a BMI of 40 kg/m 2 in white ethnicities was observed at a BMI of 30.1 kg/m 2 , 27.0 kg/m 2 , and 32.2 kg/m 2 in black, South Asian and other ethnicities, respectively.

Meaning

BMI is a stronger risk factor for COVID-19 mortality in ethnic minorities. Obesity management is therefore a priority in these populations.",,pdf:https://www.nature.com/articles/s41467-022-28248-1.pdf; doi:https://doi.org/10.1101/2021.07.22.21260416; html:https://europepmc.org/article/PPR/PPR373497; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR373497&type=FILE&fileName=EMS132179-pdf.pdf&mimeType=application/pdf -PPR700382,https://doi.org/10.1101/2023.07.31.23293419,The impact of COVID-19 on medication reviews in English primary care. An OpenSAFELY-TPP analysis of 20 million adult electronic health records,"The OpenSAFELY Collaborative, Wood C, Speed V, Fisher L, Curtis HJ, Schaffer AL, Walker AJ, Croker R, Brown AD, Cunningham C, Hulme WJ, Andrews CD, Butler-Cole BFC, Evans D, Inglesby P, Dillingham I, Bacon SC, Davy S, Ward T, Hickman G, Bridges L, O’Dwyer T, Maude S, Smith RM, Mehrkar A, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, MacKenna B.",,No Journal Info,2023,2023-07-31,Y,,,,"

Background

The COVID-19 pandemic caused significant disruption to routine activity in primary care. Medication reviews are an important primary care activity to ensure safety and appropriateness of ongoing prescribing and a disruption could have significant negative implications for patient care.

Aim

Using routinely collected data, our aim was to i) describe the SNOMED CT codes used to report medication review activity ii) report the impact of COVID-19 on the volume and variation of medication reviews.

Design and setting

With the approval of NHS England, we conducted a cohort study of 20 million adult patient records in general practice, in-situ using the OpenSAFELY platform.

Method

For each month between April 2019 - March 2022, we report the percentage of patients with a medication review coded monthly and in the previous 12 months. These measures were broken down by regional, clinical and demographic subgroups and amongst those prescribed high risk medications.

Results

In April 2019, 32.3% of patients had a medication review coded in the previous 12 months. During the first COVID-19 lockdown, monthly activity substantially decreased (-21.1% April 2020), but the rate of patients with a medication review coded in the previous 12 months was not substantially impacted according to our classification (-10.5% March 2021). There was regional and ethnic variation (March 2022 - London 21.9% vs North West 33.6%; Chinese 16.8% vs British 33.0%). Following the introduction of “structured medication reviews”, the rate of structured medication review in the last 12 months reached 2.9% by March 2022, with higher percentages in high risk groups (March 2022 - care home residents 34.1%, 90+ years 13.1%, high risk medications 10.2%). The most used SNOMED CT medication review code across the study period was Medication review done - 314530002 (59.5%).

Conclusion

We have reported a substantial reduction in the monthly rate of medication reviews during the pandemic but rates recovered by the end of the study period.

What is already known about this subject

The COVID-19 pandemic brought substantial disruption to the delivery of routine tasks in primary care. For the first time on this scale, our study reports the impact of COVID-19 on medication review activity, including the launch of the structured medication review service in England broken down by key demographic, social, and clinical factors.

What this study adds

There was a substantial reduction in the monthly rate of medication reviews during the pandemic but rates recovered quickly. The percentage of patients with a medication review varies according to region and ethnicity. Structured medication reviews were adopted rapidly and prioritised for patients at greatest risk of harm from their medicines.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/08/07/2023.07.31.23293419.full.pdf; doi:https://doi.org/10.1101/2023.07.31.23293419; html:https://europepmc.org/article/PPR/PPR700382; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR700382&type=FILE&fileName=EMS183904-pdf.pdf&mimeType=application/pdf PPR289244,https://doi.org/10.2139/ssrn.3789264,Effectiveness of First Dose of COVID-19 Vaccines Against Hospital Admissions in Scotland: National Prospective Cohort Study of 5.4 Million People,"Vasileiou E, Simpson CR, Robertson C, Shi T, Kerr S, Agrawal U, Akbari A, Bedston S, Beggs J, Bradley D, Chuter A, Lusignan Sd, Docherty A, Ford D, Hobbs R, Joy M, Katikireddi SV, Marple J, McCowan C, McGagh D, McMenamin J, Moore E, Murray J, Pan J, Ritchie LD, Shah SA, Stock S, Torabi F, Tsang RSM, Wood R, Woolhouse M, Sheikh A.",,No Journal Info,2021,2021-02-19,N,,,,"Background: The BNT162b2 mRNA (Pfizer-BioNTech) and ChAdOx1 (Oxford-AstraZeneca) COVID-19 vaccines have demonstrated high efficacy against infection in phase 3 clinical trials and are now being used in national vaccination programmes in the UK and several other countries. There is an urgent need to study the ‘real-world’ effects of these vaccines. The aim of our study was to estimate the effectiveness of the first dose of these COVID-19 vaccines in preventing hospital admissions.

Methods: We conducted a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) database comprising of linked vaccination, primary care, Real-Time Polymerase Chain Reaction (RT-PCR) testing, hospitalisation and mortality records for 5.4 million people in Scotland (covering ~99% of population). A time-dependent Cox model and Poisson regression models were fitted to estimate effectiveness against COVID-19 related hospitalisation (defined as 1- Adjusted Hazard Ratio) following the first dose of vaccine.

Findings: The first dose of the BNT162b2 vaccine was associated with a vaccine effect of 85% (95% confidence interval [CI] 76 to 91) for COVID-19 related hospitalisation at 28-34 days post-vaccination. Vaccine effect at the same time interval for the ChAdOx1 vaccine was 94% (95% CI 73 to 99). Results of combined vaccine effect for prevention of COVID-19 related hospitalisation were comparable when restricting the analysis to those aged ≥80 years (81%; 95% CI 65 to 90 at 28-34 days post-vaccination).

Interpretation: A single dose of the BNT162b2 mRNA and ChAdOx1 vaccines resulted in substantial reductions in the risk of COVID-19 related hospitalisation in Scotland.

Funding: UK Research and Innovation (Medical Research Council); Research and Innovation Industrial Strategy Challenge Fund; Health Data Research UK.

Conflict of Interest: AS is a member of the Scottish Government Chief Medical Officer’s COVID-19Advisory Group and the New and Emerging Respiratory Virus Threats (NERVTAG) Risk Stratification Subgroup. CRS declares funding from the MRC, NIHR, CSO and New Zealand Ministry for Business, Innovation and Employment and Health Research Council during the conduct of this study. SVK is co-chair of the Scottish Government’s Expert Reference Group on COVID-19 and ethnicity, is a member of the Scientific Advisory Group on Emergencies (SAGE) subgroup on ethnicity and acknowledges funding from a NRS Senior Clinical Fellowship, MRC and CSO. All other authors report no conflicts of interest.

Ethical Approval: Approvals were obtained from the National Research Ethics Service Committee, Southeast Scotland 02 (reference number: 12/SS/0201) and Public Benefit and Privacy Panel for Health and Social Care (reference number: 1920-0279).",,pdf:https://www.pure.ed.ac.uk/ws/files/197030199/SSRN_id3789264.pdf; doi:https://doi.org/10.2139/ssrn.3789264; html:https://europepmc.org/article/PPR/PPR289244; doi:https://doi.org/10.2139/ssrn.3789264 PPR393010,https://doi.org/10.1101/2021.09.03.21263023,Evaluation of antithrombotic use and COVID-19 outcomes in a nationwide atrial fibrillation cohort,"Handy A, Banerjee A, Wood A, Dale CE, Sudlow C, Tomlinson C, Bean D, Thygesen JH, Mizani MA, Katsoulis M, Sofat R, Dobson R, Takhar R, Hollings S, Denaxas S, Walker V.",,No Journal Info,2021,2021-09-10,N,,,,"

ABSTRACT

Objective

Evaluate antithrombotic (AT) use in individuals with atrial fibrillation (AF) and high stroke risk (CHA 2 DS 2 -VASc score>=2) and investigate whether pre-existing AT use may improve COVID-19 outcomes.

Methods

Individuals with AF and a CHA 2 DS 2 -VASc score>=2 on January 1 st 2020 were identified using pseudonymised, linked electronic health records for 56 million people in England and followed-up until May 1 st 2021. Factors associated with pre-existing AT use were analysed using logistic regression. Differences in COVID-19 related hospitalisation and death were analysed using logistic and Cox regression for individuals exposed to pre-existing AT use vs no AT use, anticoagulants (AC) vs antiplatelets (AP) and direct oral anticoagulants (DOACs) vs warfarin.

Results

From 972,971 individuals with AF and a CHA 2 DS 2 -VASc score>=2, 88.0% (n=856,336) had pre-existing AT use, 3.8% (n=37,418) had a COVID-19 related hospitalisation and 2.2% (n=21,116) died. Factors associated with no AT use included comorbidities that may contraindicate AT use (liver disease and history of falls) and demographics (socioeconomic status and ethnicity). Pre-existing AT use was associated with lower odds of death (OR=0.92 [0 . 87-0 . 96 at 95% CI] ), but higher odds of hospitalisation OR=1.20 [1 . 15-1 . 26 at 95% CI] ). The same pattern was observed for AC vs AP (death (OR=0.93 [0.87-0.98]), hospitalisation (OR=1.17 [1.11-1.24])) but not for DOACs vs warfarin (death (OR=1.00 [0.95-1.05]), hospitalisation (OR=0.86 [0.82-0.89]).

Conclusions

Pre-existing AT use may offer marginal protection against COVID-19 death, with AC offering more protection than AP. Although this association may not be causal, it provides further incentive to improve AT coverage for eligible individuals with AF.

KEY QUESTIONS

What is already known about this subject?

Anticoagulants (AC), a sub-class of antithrombotics (AT), reduce the risk of stroke and are recommended for individuals with atrial fibrillation (AF) and at high risk of stroke (CHA 2 DS 2 -VASc score>=2, National Institute for Health and Care Excellence threshold). However, previous evaluations suggest that up to one third of these individuals may not be taking AC. Over estimation of bleeding and fall risk in elderly patients have been identified as potential factors in this under medicating. In response to the COVID-19 pandemic, several observational studies have observed correlations between pre-existing AT use, particularly anticoagulants (AC), and lower risk of severe COVID-19 outcomes such as hospitalisation and death. However, these correlations are inconsistent across studies and have not compared all major sub-types of AT in one study.

What does this study add?

This study uses datasets covering primary care, secondary care, pharmacy dispensing, death registrations, multiple COVID-19 diagnoses routes and vaccination records for 56 million people in England and is the largest scale evaluation of AT use to date. This provides the statistical power to robustly analyse targeted sub-types of AT and control for a wide range of potential confounders. All code developed for the study is opensource and an updated nationwide evaluation can be rapidly created for future time points. In 972,971 individuals with AF and a CHA 2 DS 2 -VASc score>=2, we observed 88.0% (n=856,336) with pre-existing AT use which was associated with marginal protection against COVID-19 death (OR=0.92 [0 . 87-0 . 96 at 95% CI] ).

How might this impact on clinical practice?

These findings can help shape global AT medication policy and provide population-scale, observational analysis results alongside gold-standard randomised control trials to help assess whether a potential beneficial effect of pre-existing AT use on COVID-19 death alters risk to benefit assessments in AT prescribing decisions.",,pdf:https://heart.bmj.com/content/heartjnl/108/12/923.full.pdf; doi:https://doi.org/10.1101/2021.09.03.21263023; html:https://europepmc.org/article/PPR/PPR393010; doi:https://doi.org/10.1101/2021.09.03.21263023 +PPR700382,https://doi.org/10.1101/2023.07.31.23293419,The impact of COVID-19 on medication reviews in English primary care. An OpenSAFELY-TPP analysis of 20 million adult electronic health records,"The OpenSAFELY Collaborative, Wood C, Speed V, Fisher L, Curtis HJ, Schaffer AL, Walker AJ, Croker R, Brown AD, Cunningham C, Hulme WJ, Andrews CD, Butler-Cole BFC, Evans D, Inglesby P, Dillingham I, Bacon SC, Davy S, Ward T, Hickman G, Bridges L, O’Dwyer T, Maude S, Smith RM, Mehrkar A, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, MacKenna B.",,No Journal Info,2023,2023-07-31,Y,,,,"

Background

The COVID-19 pandemic caused significant disruption to routine activity in primary care. Medication reviews are an important primary care activity to ensure safety and appropriateness of ongoing prescribing and a disruption could have significant negative implications for patient care.

Aim

Using routinely collected data, our aim was to i) describe the SNOMED CT codes used to report medication review activity ii) report the impact of COVID-19 on the volume and variation of medication reviews.

Design and setting

With the approval of NHS England, we conducted a cohort study of 20 million adult patient records in general practice, in-situ using the OpenSAFELY platform.

Method

For each month between April 2019 - March 2022, we report the percentage of patients with a medication review coded monthly and in the previous 12 months. These measures were broken down by regional, clinical and demographic subgroups and amongst those prescribed high risk medications.

Results

In April 2019, 32.3% of patients had a medication review coded in the previous 12 months. During the first COVID-19 lockdown, monthly activity substantially decreased (-21.1% April 2020), but the rate of patients with a medication review coded in the previous 12 months was not substantially impacted according to our classification (-10.5% March 2021). There was regional and ethnic variation (March 2022 - London 21.9% vs North West 33.6%; Chinese 16.8% vs British 33.0%). Following the introduction of “structured medication reviews”, the rate of structured medication review in the last 12 months reached 2.9% by March 2022, with higher percentages in high risk groups (March 2022 - care home residents 34.1%, 90+ years 13.1%, high risk medications 10.2%). The most used SNOMED CT medication review code across the study period was Medication review done - 314530002 (59.5%).

Conclusion

We have reported a substantial reduction in the monthly rate of medication reviews during the pandemic but rates recovered by the end of the study period.

What is already known about this subject

The COVID-19 pandemic brought substantial disruption to the delivery of routine tasks in primary care. For the first time on this scale, our study reports the impact of COVID-19 on medication review activity, including the launch of the structured medication review service in England broken down by key demographic, social, and clinical factors.

What this study adds

There was a substantial reduction in the monthly rate of medication reviews during the pandemic but rates recovered quickly. The percentage of patients with a medication review varies according to region and ethnicity. Structured medication reviews were adopted rapidly and prioritised for patients at greatest risk of harm from their medicines.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/08/07/2023.07.31.23293419.full.pdf; doi:https://doi.org/10.1101/2023.07.31.23293419; html:https://europepmc.org/article/PPR/PPR700382; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR700382&type=FILE&fileName=EMS183904-pdf.pdf&mimeType=application/pdf PPR184537,https://doi.org/10.1101/2020.07.03.20145912,Ultraviolet A Radiation and COVID-19 Deaths in the USA with replication studies in England and Italy,"Cherrie M, Clemens T, Colandrea C, Feng Z, Webb DJ, Dibben C, Weller RB.",,No Journal Info,2020,2020-07-06,Y,,,,"

Objectives

To determine whether UVA exposure might be associated with COVID-19 deaths

Design

Ecological regression, with replication in two other countries and pooled estimation

Setting

2,474 counties of the contiguous USA, 6,755 municipalities in Italy, 6,274 small areas in England. Only small areas in their ‘Vitamin D winter’ (monthly mean UV vitd of under 165 KJ/m 2 ) from Jan to April 2020. Participants The ‘at-risk’ population is the total small area population, with measures to incorporate spatial infection into the model. The model is adjusted for potential confounders including long-term winter temperature and humidity.

Main outcome measures

We derive UVA measures for each area from remote sensed data and estimate their relationship with COVID-19 mortality with a random effect for States, in a multilevel zero-inflated negative binomial model. In the USA and England death certificates had to record COVID-19. In Italy excess deaths in 2020 over expected from 2015-19.

Data sources

Satellite derived mean daily UVA dataset from Japan Aerospace Exploration Agency. Data on deaths compiled by Center for Disease Control (USA), Office for National Statistics (England) and Italian Institute of Statistics.

Results

Daily mean UVA (January-April 2020) varied between 450 to 1,000 KJ/m 2 across the three countries. Our fully adjusted model showed an inverse correlation between UVA and COVID-19 mortality with a Mortality Risk Ratio (MRR) of 0.71 (0.60 to 0.85) per 100KJ/m 2 increase UVA in the USA, 0.81 (0.71 to 0.93) in Italy and 0.49 (0.38 to 0.64) in England. Pooled MRR was 0.68 (0.52 to 0.88).

Conclusions

Our analysis, replicated in 3 independent national datasets, suggests ambient UVA exposure is associated with lower COVID-19 specific mortality. This effect is independent of vitamin D, as it occurred at irradiances below that likely to induce significant cutaneous vitamin D3 synthesis. Causal interpretations must be made cautiously in observational studies. Nonetheless this study suggests strategies for reduction of COVID-19 mortality.",,pdf:https://academic.oup.com/bjd/article-pdf/185/2/363/47150299/bjd0363.pdf; doi:https://doi.org/10.1101/2020.07.03.20145912; html:https://europepmc.org/article/PPR/PPR184537; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR184537&type=FILE&fileName=EMS87521-pdf.pdf&mimeType=application/pdf PPR341282,https://doi.org/10.1101/2021.05.17.21257315,Impact of non-pharmaceutical interventions on SARS-CoV-2 outbreaks in English care homes: a modelling study,"Roselló A, Barnard RC, Smith DRM, Evans S, Grimm F, Davies NG, Deeny SR, Knight GM, Edmunds WJ, Centre for Mathematical Modelling of Infectious Diseases COVID-19 modelling working group.",,No Journal Info,2021,2021-05-18,N,,,,"

Background

COVID-19 outbreaks are still occurring in English care homes despite the non-pharmaceutical interventions (NPIs) in place.

Methods

We developed a stochastic compartmental model to simulate the spread of SARS-CoV-2 within an English care home. We quantified the outbreak risk under the NPIs already in place, the role of community prevalence in driving outbreaks, and the relative contribution of all importation routes into the care home. We also considered the potential impact of additional control measures, namely: increasing staff and resident testing frequency, using lateral flow antigen testing (LFD) tests instead of PCR, enhancing infection prevention and control (IPC), increasing the proportion of residents isolated, shortening the delay to isolation, improving the effectiveness of isolation, restricting visitors and limiting staff to working in one care home.

Findings

The model suggests that importation of SARS-CoV-2 by staff, from the community, is the main driver of outbreaks, that importation by visitors or from hospitals is rare, and that the past testing strategy (monthly testing of residents and daily testing of staff by PCR) likely provides negligible benefit in preventing outbreaks. Daily staff testing by LFD was 39% (95% 18-55%) effective in preventing outbreaks at 30 days compared to no testing.

Interpretation

Increasing the frequency of testing in staff and enhancing IPC are important to preventing importations to the care home. Further work is needed to understand the impact of vaccination in this population, which is likely to be very effective in preventing outbreaks.

Funding

The National Institute for Health Research, European Union Horizon 2020, Canadian Institutes of Health Research, French National Research Agency, UK Medical Research Council. The World Health Organisation funded the development of the COS-LTCF Shiny application.

Research in Context

Evidence before this study

Care homes have been identified as being at increased risk of COVID-19 outbreaks, and a number of modelling studies have considered the transmission dynamics of SARS-CoV-2 in this setting. We searched the PubMed database and bioRxiv and medRxiv’s COVID-19 SARS-CoV-2 preprints for English-language articles on the 11th May 2021, with the search terms (“COVID-19” OR “SARS-CoV-2” OR “coronavirus”) AND (“care home” OR “LTCF” OR “long term care facility” OR “nursing home”) AND (“model”). In addition to these searches, we identified articles relevant to this work through informal networks. These searches returned 87 studies, of which 12 explicitly modelled SARS-CoV-2 transmission within care homes and explored the effectiveness of non-pharmaceutical interventions in these settings. These studies employed a number of modelling approaches (agent-based and compartmental models) and considered various strategies for mitigating epidemic spread within care homes. Only one of these studies modelled care homes in England, but didn’t consider individual care homes as separate entities (transmission between residents in separate facilities was equally likely as within one facility) and only modelled one intervention within the care home: the effect of restricting visitors. Another study modelled a different type of long-term care facility, a rehabilitation facility in France. Other studies modelled care homes in Canada, Scotland, and the US. These modelled care homes were larger than the average English care home. Only one study included importation of SARS-CoV-2 to care homes from hospitals through resident hospitalisation.

Added value of this study

We developed a stochastic compartmental model describing the transmission dynamics of SARS-CoV-2 within English care homes. This study is the first to assess the relative importance of all SARS-CoV-2 importation routes to care homes (including resident hospitalisation) and to quantify the impact of a range of non-pharmaceutical interventions against SARS-CoV-2 particularly for English care homes. We found that community prevalence, through staff importations, was the main driver of outbreaks in care homes at 30 days, not importation from hospital visits nor by visitors. In line with this, we found daily testing of staff to be the most effective testing strategy in preventing outbreaks. We show the previous testing strategy (PCR testing residents once every 28 days and staff once a week) to be ineffective in preventing outbreaks and suggest that more frequent testing of staff is required. Restricting visitors bore little effect on the probability of an outbreak occurring by day 30. Interventions focusing on decreasing the transmission of SARS-CoV-2 in the care home were the most effective in reducing the frequency of outbreaks. We provide a Shiny application for users to explore alternative care home characteristics, outbreak characteristics and interventions.

Implications of all the available evidence

Preventing the importation of SARS-CoV-2 to care homes from the community through staff is key to preventing outbreaks. Infection prevention and control (IPC) measures targeting transmission within the care home and frequent testing of staff, ideally daily, are the most effective strategies considered. Many care homes in England are currently unable to meet the additional workload daily testing would entail, therefore additional support should be considered to enable these measures. Allowing visitors should be considered given their general positive contribution to residents’ physical and mental health and likely negligible contribution to outbreaks.",,pdf:https://bmcinfectdis.biomedcentral.com/track/pdf/10.1186/s12879-022-07268-8; doi:https://doi.org/10.1101/2021.05.17.21257315; html:https://europepmc.org/article/PPR/PPR341282; doi:https://doi.org/10.1101/2021.05.17.21257315 PPR626309,https://doi.org/10.21203/rs.3.rs-2573712/v1,How much did the Covid-19 shielding policy cost in Wales? A Retrospective Cost analysis within the EVITE Immunity study,"Sewell B, Farr A, Akbari A, Carson-Stevens A, Edwards A, Evans BA, John A, Torabi F, Dale J, Jolles S, Kingston MR, Lyons J, Lyons RA, Porter A, Watkins A, Williams V, Snooks H.",,No Journal Info,2023,2023-03-06,Y,,,,"

Background:

The EVITE Immunity study investigates the effects of shielding Clinically Extremely Vulnerable (CEV) people during the COVID-19 pandemic on health outcomes and healthcare costs in Wales, UK, to help prepare for future pandemics. Shielding was intended to protect those at highest risk of serious harm from COVID-19. We report the cost of implementing shielding in Wales.

Methods:

The number of people shielding was extracted from the Secure Anonymised Information Linkage Databank. Resources supporting shielding between March and June 2020 were mapped using published reports, web pages, freedom of information requests to Welsh Government and personal communications (e.g. the office of the Chief Medical Officer for Wales).

Results:

At the beginning of shielding, 117,415 people were on the shielding list. The total additional cost to support those advised to stay home during the initial 14 weeks of the pandemic was £13,307,654 (£113 per person shielded). This included the new resources required to compile the shielding list, inform CEV people of the shielding intervention and provide medicine and food deliveries. The list was adjusted weekly over the 3-month period (130,000 people identified by June 2020) therefore the cost per person shielded lies between £102 and £113.

Conclusion:

This is the first evaluation of the cost of the measures put in place to support those identified to shield in Wales. However, no data on opportunity cost was available. The true cost of shielding including its budget impact and opportunity costs need to be investigated to decide whether shielding is a worthwhile policy for future health emergencies.",,pdf:https://www.researchsquare.com/article/rs-2573712/latest.pdf; doi:https://doi.org/10.21203/rs.3.rs-2573712/v1; html:https://europepmc.org/article/PPR/PPR626309; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR626309&type=FILE&fileName=EMS171864-pdf.pdf&mimeType=application/pdf PPR247907,https://doi.org/10.2139/ssrn.3724855,A Prospective Study of Risk Factors Associated with Seroprevalence of SARS-CoV-2 Antibodies in Healthcare Workers at a Large UK Teaching Hospital,"Cooper DJ, Lear S, Watson L, Shaw A, Ferris M, Doffinger R, Bousfield R, Sharrocks K, Weekes MP, Warne B, Sparkes D, Jones NK, Rivett L, Routledge M, Chaudhry A, Dempsey K, Matson M, Lakha A, Gathercole G, O’Connor O, Wilson E, Shahzad O, Toms K, Thompson R, Halsall I, Halsall D, Houghton S, Papadia S, Kingston N, Stirrups KE, Graves B, Walker N, Stark H, Group CBCC, DeAngelis D, Seaman S, Dougan G, Bradley JR, Török ME, Goodfellow I, Baker S.",,No Journal Info,2020,2020-12-01,N,,,,"Background: The COVID-19 pandemic continues to grow at an unprecedented rate. Healthcare workers (HCWs) are at higher risk of SARS-CoV-2 infection than the general population but risk factors for HCW infection are not well described.

Methods: We conducted a prospective sero-epidemiological study of HCWs at a UK teaching hospital using a SARS-CoV-2 immunoassay. Risk factors for seropositivity were analysed using multivariate logistic regression.

Findings: 410/5,698 (7·2%) staff tested positive for SARS-CoV-2 antibodies. Seroprevalence was higher in those working in designated COVID-19 areas compared with other areas (9·47% versus 6·16%) Healthcare assistants (aOR 2·06 [95%CI 1·14-3·71]; p =0·016) and domestic and portering staff (aOR 3·45 [95% CI 1·07-11·42]; p =0·039) had significantly higher seroprevalence than other staff groups after adjusting for age, sex, ethnicity and COVID-19 working location. Staff working in acute medicine and medical sub-specialities were also at higher risk (aOR 2·07 [95% CI 1·31-3·25]; p <0·002). Staff from Black, Asian and minority ethnic (BAME) backgrounds had an aOR of 1·65 (95% CI 1·32 – 2·07; p <0·001) compared to white staff; this increased risk was independent of COVID-19 area working. The only symptoms significantly associated with seropositivity in a multivariable model were loss of sense of taste or smell, fever and myalgia; 31% of staff testing positive reported no prior symptoms.

Interpretation: Risk of SARS-CoV-2 infection amongst HCWs is heterogeneous and influenced by COVID-19 working location, role, age and ethnicity. Increased risk amongst BAME staff cannot be accounted for solely by occupational factors.

Funding: Wellcome Trust, Addenbrookes Charitable Trust, National Institute for Health Research, Academy of Medical Sciences, the Health Foundation and the NIHR Cambridge Biomedical Research Centre.

Declaration of Interests: None to declare.

Ethics Approval Statement: Ethical approval for this study was granted by the East of England – Cambridge Central Research Ethics Committee (IRAS ID: 220277).",,pdf:https://www.repository.cam.ac.uk/bitstreams/3ef04015-fa68-40ca-84d6-076095101624/download; doi:https://doi.org/10.2139/ssrn.3724855; html:https://europepmc.org/article/PPR/PPR247907; doi:https://doi.org/10.2139/ssrn.3724855 -PPR807617,https://doi.org/10.1101/2024.02.16.24302936,Similar and different: systematic investigation of proteogenomic variation between sexes and its relevance for human diseases,"Koprulu M, Wheeler E, Kerrison ND, Denaxas S, Carrasco-Zanini J, Orkin CM, Hemingway H, Wareham NJ, Pietzner M, Langenberg C.",,No Journal Info,2024,2024-02-18,Y,,,,"To better understand sex differences in human health and disease, we conducted a systematic, large-scale investigation of sex differences in the genetic regulation of the plasma proteome (>5,000 targets), including their disease relevance. Plasma levels of two-thirds of protein targets differed significantly by sex. In contrast, genetic effects on protein targets were remarkably similar, with very few protein quantitative loci (pQTLs, n=74) showing significant sex-differential effects (for 3.9% and 0.3% of protein targets from antibody- and aptamer-based platforms, respectively). Most of these 74 pQTLs represented directionally concordant effects significant in both sexes, with only 21 pQTLs showing evidence of sexual dimorphism, i.e. effects restricted to one sex (n=20) or with opposite directions between sexes (n=1 for CDH15). None of the sex-differential pQTLs translated into sex-differential disease risk. Our results demonstrate strong similarity in the genetic regulation of the plasma proteome between sexes with important implications for genetically guided drug target discovery and validation.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2024/02/18/2024.02.16.24302936.full.pdf; doi:https://doi.org/10.1101/2024.02.16.24302936; html:https://europepmc.org/article/PPR/PPR807617; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR807617&type=FILE&fileName=EMS194226-pdf.pdf&mimeType=application/pdf PPR463503,https://doi.org/10.1101/2022.03.02.22271623,"Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis","RECOVERY Collaborative Group, Horby PW, Emberson JR, Mafham M, Campbell M, Peto L, Pessoa-Amorim G, Spata E, Staplin N, Lowe C, Chadwick DR, Brightling C, Stewart R, Collini P, Ashish A, Green CA, Prudon B, Felton T, Kerry A, Baillie JK, Buch MH, Day JN, Faust SN, Jaki T, Jeffery K, Juszczak E, Knight M, Lim WS, Montgomery A, Mumford A, Rowan K, Thwaites G, Haynes R, Landray MJ.",,No Journal Info,2022,2022-03-03,Y,,,,"

SUMMARY

Background

We evaluated the use of baricitinib, a Janus kinase (JAK) 1/2 inhibitor, for the treatment of patients admitted to hospital because of COVID-19.

Methods

This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting patients were randomly allocated (1:1) to either usual standard of care alone (usual care group) or usual care plus baricitinib 4 mg once daily by mouth for 10 days or until discharge if sooner (baricitinib group). The primary outcome was 28-day mortality assessed in the intention-to-treat population. A meta-analysis was conducted that included the results from the RECOVERY trial and all previous randomised controlled trials of baricitinib or other JAK inhibitor in patients hospitalised with COVID-19. The RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov ( NCT04381936 ).

Findings

Between 2 February 2021 and 29 December 2021, 8156 patients were randomly allocated to receive usual care plus baricitinib versus usual care alone. At randomisation, 95% of patients were receiving corticosteroids and 23% receiving tocilizumab (with planned use within the next 24 hours recorded for a further 9%). Overall, 513 (12%) of 4148 patients allocated to baricitinib versus 546 (14%) of 4008 patients allocated to usual care died within 28 days (age-adjusted rate ratio 0·87; 95% CI 0·77-0·98; p=0·026). This 13% proportional reduction in mortality was somewhat smaller than that seen in a meta-analysis of 8 previous trials of a JAK inhibitor (involving 3732 patients and 425 deaths) in which allocation to a JAK inhibitor was associated with a 43% proportional reduction in mortality (rate ratio 0.57; 95% CI 0.45-0.72). Including the results from RECOVERY into an updated meta-analysis of all 9 completed trials (involving 11,888 randomised patients and 1484 deaths) allocation to baricitinib or other JAK inhibitor was associated with a 20% proportional reduction in mortality (rate ratio 0.80; 95% CI 0.71-0.89; p<0.001). In RECOVERY, there was no significant excess in death or infection due to non-COVID-19 causes and no excess of thrombosis, or other safety outcomes.

Interpretation

In patients hospitalised for COVID-19, baricitinib significantly reduced the risk of death but the size of benefit was somewhat smaller than that suggested by previous trials. The total randomised evidence to date suggests that JAK inhibitors (chiefly baricitinib) reduce mortality in patients hospitalised for COVID-19 by about one-fifth.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).",,pdf:https://nottingham-repository.worktribe.com/preview/9409854/PIIS0140673622011096.pdf; doi:https://doi.org/10.1101/2022.03.02.22271623; html:https://europepmc.org/article/PPR/PPR463503; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR463503&type=FILE&fileName=EMS148878-pdf.pdf&mimeType=application/pdf PPR233548,https://doi.org/10.1101/2020.11.01.20222315,Association between living with children and outcomes from COVID-19: an OpenSAFELY cohort study of 12 million adults in England,"Forbes H, Morton CE, Bacon S, McDonald HI, Minassian C, Brown JP, Rentsch CT, Mathur R, Schultze A, DeVito NJ, MacKenna B, Hulme WJ, Croker R, Walker AJ, Williamson EJ, Bates C, Mehrkar A, Curtis HJ, Evans D, Wing K, Inglesby P, Drysdale H, Wong AY, Cockburn J, McManus R, Parry J, Hester F, Harper S, Douglas IJ, Smeeth L, Evans SJ, Bhaskaran K, Eggo RM, Goldacre B, Tomlinson LA.",,No Journal Info,2020,2020-11-02,Y,,,,"

Background

Close contact with children may provide cross-reactive immunity to SARs-CoV-2 due to more frequent prior coryzal infections from seasonal coronaviruses. Alternatively, close contact with children may increase risk of SARs-CoV-2 infection. We investigated whether risk of infection with SARs-CoV-2 and severe outcomes differed between adults living with and without children.

Methods

Working on behalf of NHS England, we conducted a population-based cohort study using primary care data and pseudonymously-linked hospital and intensive care admissions, and death records, from patients registered in general practices representing 40% of England. Using multivariable Cox regression, we calculated fully-adjusted hazard ratios (HR) of outcomes from 1st February-3rd August 2020 comparing adults living with and without children in the household.

Findings

Among 9,157,814 adults ≤65 years, living with children 0-11 years was not associated with increased risks of recorded SARS-CoV-2 infection, COVID-19 related hospital or ICU admission but was associated with reduced risk of COVID-19 death (HR 0.75, 95%CI 0.62-0.92). Living with children aged 12-18 years was associated with a small increased risk of recorded SARS-CoV-2 infection (HR 1.08, 95%CI 1.03-1.13), but not associated with other COVID-19 outcomes. Living with children of any age was also associated with lower risk of dying from non-COVID-19 causes. Among 2,567,671 adults >65 years there was no association between living with children and outcomes related to SARS-CoV-2. We observed no consistent changes in risk following school closure.

Interpretation

For adults living with children there is no evidence of an increased risk of severe COVID-19 outcomes. These findings have implications for determining the benefit-harm balance of children attending school in the COVID-19 pandemic.

Funding

This work was supported by the Medical Research Council MR/V015737/1.

Research in context

Evidence before this study

We searched MEDLINE on 19th October 2020 for population-based epidemiological studies comparing the risk of SARS-CoV-2 infection and COVID-19 disease in people living with and without children. We searched for articles published in 2020, with abstracts available, and terms “(children or parents or dependants) AND (COVID or SARS-CoV-2 or coronavirus) AND (rate or hazard or odds or risk), in the title, abstract or keywords. 244 papers were identified for screening but none were relevant. One additional study in preprint was identified on medRxiv and found a reduced risk of hospitalisation for COVID-19 and a positive SARS-CoV-2 infection among adult healthcare workers living with children.

Added value of this study

This is the first population-based study to investigate whether the risk of recorded SARS-CoV-2 infection and severe outcomes from COVID-19 differ between adults living in households with and without school-aged children during the UK pandemic. Our findings show that for adults living with children there is no evidence of an increased risk of severe COVID-19 outcomes although there may be a slightly increased risk of recorded SARS-CoV-2 infection for working-age adults living with children aged 12 to 18 years. Working-age adults living with children 0 to 11 years have a lower risk of death from COVID-19 compared to adults living without children, with the effect size being comparable to their lower risk of death from any cause. We observed no consistent changes in risk of recorded SARS-CoV-2 infection and severe outcomes from COVID-19 comparing periods before and after school closure.

Implications of all the available evidence

Our results demonstrate no evidence of serious harms from COVID-19 to adults in close contact with children, compared to those living in households without children. This has implications for determining the benefit-harm balance of children attending school in the COVID-19 pandemic.",,pdf:https://www.bmj.com/content/bmj/372/bmj.n628.full.pdf; doi:https://doi.org/10.1101/2020.11.01.20222315; html:https://europepmc.org/article/PPR/PPR233548; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR233548&type=FILE&fileName=EMS103455-pdf.pdf&mimeType=application/pdf PPR371921,https://doi.org/,Explainable Automated Coding of Clinical Notes using Hierarchical Label-wise Attention Networks and Label Embedding Initialisation,"Dong H, Suárez-Paniagua V, Whiteley W, Wu H.",,No Journal Info,2021,2021-07-16,Y,,,,"Diagnostic or procedural coding of clinical notes aims to derive a coded summary of disease-related information about patients. Such coding is usually done manually in hospitals but could potentially be automated to improve the efficiency and accuracy of medical coding. Recent studies on deep learning for automated medical coding achieved promising performances. However, the explainability of these models is usually poor, preventing them to be used confidently in supporting clinical practice. Another limitation is that these models mostly assume independence among labels, ignoring the complex correlation among medical codes which can potentially be exploited to improve the performance. We propose a Hierarchical Label-wise Attention Network (HLAN), which aimed to interpret the model by quantifying importance (as attention weights) of words and sentences related to each of the labels. Secondly, we propose to enhance the major deep learning models with a label embedding (LE) initialisation approach, which learns a dense, continuous vector representation and then injects the representation into the final layers and the label-wise attention layers in the models. We evaluated the methods using three settings on the MIMIC-III discharge summaries: full codes, top-50 codes, and the UK NHS COVID-19 shielding codes. Experiments were conducted to compare HLAN and LE initialisation to the state-of-the-art neural network based methods. HLAN achieved the best Micro-level AUC and $F_1$ on the top-50 code prediction and comparable results on the NHS COVID-19 shielding code prediction to other models. By highlighting the most salient words and sentences for each label, HLAN showed more meaningful and comprehensive model interpretation compared to its downgraded baselines and the CNN-based models. LE initialisation consistently boosted most deep learning models for automated medical coding.",,arxiv:https://arxiv.org/abs/2010.15728v4; html:https://europepmc.org/article/PPR/PPR371921; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR371921&type=FILE&fileName=EMS130963-pdf.pdf&mimeType=application/pdf +PPR807617,https://doi.org/10.1101/2024.02.16.24302936,Similar and different: systematic investigation of proteogenomic variation between sexes and its relevance for human diseases,"Koprulu M, Wheeler E, Kerrison ND, Denaxas S, Carrasco-Zanini J, Orkin CM, Hemingway H, Wareham NJ, Pietzner M, Langenberg C.",,No Journal Info,2024,2024-02-18,Y,,,,"To better understand sex differences in human health and disease, we conducted a systematic, large-scale investigation of sex differences in the genetic regulation of the plasma proteome (>5,000 targets), including their disease relevance. Plasma levels of two-thirds of protein targets differed significantly by sex. In contrast, genetic effects on protein targets were remarkably similar, with very few protein quantitative loci (pQTLs, n=74) showing significant sex-differential effects (for 3.9% and 0.3% of protein targets from antibody- and aptamer-based platforms, respectively). Most of these 74 pQTLs represented directionally concordant effects significant in both sexes, with only 21 pQTLs showing evidence of sexual dimorphism, i.e. effects restricted to one sex (n=20) or with opposite directions between sexes (n=1 for CDH15). None of the sex-differential pQTLs translated into sex-differential disease risk. Our results demonstrate strong similarity in the genetic regulation of the plasma proteome between sexes with important implications for genetically guided drug target discovery and validation.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2024/02/18/2024.02.16.24302936.full.pdf; doi:https://doi.org/10.1101/2024.02.16.24302936; html:https://europepmc.org/article/PPR/PPR807617; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR807617&type=FILE&fileName=EMS194226-pdf.pdf&mimeType=application/pdf PPR233926,https://doi.org/10.1101/2020.11.03.20220699,A prospective study of risk factors associated with seroprevalence of SARS-CoV-2 antibodies in healthcare workers at a large UK teaching hospital,"Cooper DJ, Lear S, Watson L, Shaw A, Ferris M, Doffinger R, Bousfield R, Sharrocks K, Weekes MP, Warne B, Sparkes D, Jones NK, Rivett L, Routledge M, Chaudhry A, Dempsey K, Matson M, Lakha A, Gathercole G, O’Connor O, Wilson E, Shahzad O, Toms K, Thompson R, Halsall I, Halsall D, Houghton S, Papadia S, Kingston N, Stirrups KE, Graves B, Walker N, Stark H, De Angelis D, Seaman S, Bradley JR, Török ME, Goodfellow I, Baker S, the CITIID-NIHR BioResource COVID-19 Collaboration.",,No Journal Info,2020,2020-11-04,Y,,,,"

Background

The COVID-19 pandemic continues to grow at an unprecedented rate. Healthcare workers (HCWs) are at higher risk of SARS-CoV-2 infection than the general population but risk factors for HCW infection are not well described.

Methods

We conducted a prospective sero-epidemiological study of HCWs at a UK teaching hospital using a SARS-CoV-2 immunoassay. Risk factors for seropositivity were analysed using multivariate logistic regression.

Findings

410/5,698 (7·2%) staff tested positive for SARS-CoV-2 antibodies. Seroprevalence was higher in those working in designated COVID-19 areas compared with other areas (9·47% versus 6·16%) Healthcare assistants (aOR 2·06 [95%CI 1·14-3·71]; p =0·016) and domestic and portering staff (aOR 3·45 [95% CI 1·07-11·42]; p =0·039) had significantly higher seroprevalence than other staff groups after adjusting for age, sex, ethnicity and COVID-19 working location. Staff working in acute medicine and medical sub-specialities were also at higher risk (aOR 2·07 [95% CI 1·31-3·25]; p <0·002). Staff from Black, Asian and minority ethnic (BAME) backgrounds had an aOR of 1·65 (95% CI 1·32 – 2·07; p <0·001) compared to white staff; this increased risk was independent of COVID-19 area working. The only symptoms significantly associated with seropositivity in a multivariable model were loss of sense of taste or smell, fever and myalgia; 31% of staff testing positive reported no prior symptoms.

Interpretation

Risk of SARS-CoV-2 infection amongst HCWs is heterogeneous and influenced by COVID-19 working location, role, age and ethnicity. Increased risk amongst BAME staff cannot be accounted for solely by occupational factors.

Funding

Wellcome Trust, Addenbrookes Charitable Trust, National Institute for Health Research, Academy of Medical Sciences, the Health Foundation and the NIHR Cambridge Biomedical Research Centre.

Research in context

Evidence before this study

Specific risk factors for SARS-CoV-2 infection in healthcare workers (HCWs) are not well defined. Additionally, it is not clear how population level risk factors influence occupational risk in defined demographic groups. Only by identifying these factors can we mitigate and reduce the risk of occupational SARS-CoV-2 infection. We performed a review of the evidence for HCW-specific risk factors for SARS-CoV-2 infection. We searched PubMed with the terms “SARS-CoV-2” OR “COVID-19” AND “Healthcare worker” OR “Healthcare Personnel” AND “Risk factor” to identify any studies published in any language between December 2019 and September 2020. The search identified 266 studies and included a meta-analysis and two observational studies assessing HCW cohort seroprevalence data. Seroprevalence and risk factors for HCW infections varied between studies, with contradictory findings. In the two serological studies, one identified a significant increased risk of seroprevalence in those working with COVID-19 patients (Eyre et al 2020), as well as associations with job role and department. The other study (Dimcheff et al 2020) found no significant association between seropositivity and any identified demographic or occupational factor. A meta-analysis of HCW (Gomez-Ochoa et al 2020) assessed >230,000 participants as a pooled analysis, including diagnoses by both RT-PCR and seropositivity for SARS-CoV-2 antibodies and found great heterogeneity in study design and reported contradictory findings. Of note, they report a seropositivity rate of 7% across all studies reporting SARS-CoV-2 antibodies in HCWs. Nurses were the most frequently affected healthcare personnel and staff working in non-emergency inpatient settings were the most frequently affected group. Our search found no prospective studies systematically evaluating HCW specific risk factors based entirely on seroprevalence data.

Added value of this study

Our prospective cohort study of almost 6,000 HCWs at a large UK teaching hospital strengthens previous findings from UK-based cohorts in identifying an increased risk of SARS-CoV-2 exposure amongst HCWs. Specifically, factors associated with SARS-CoV-2 exposure include caring for confirmed COVID-19 cases and identifying as being within specific ethnic groups (BAME staff). We further delineated the risk amongst BAME staff and demonstrate that occupational factors alone do not account for all of the increased risk amongst this group. We demonstrate for the first time that healthcare assistants represent a key at-risk occupational group, and challenge previous findings of significantly higher risk amongst nursing staff. Seroprevalence in staff not working in areas with confirmed COVID-19 patients was only marginally higher than that of the general population within the same geographical region. This observation could suggest the increased risk amongst HCWs arises through occupational exposure to confirmed cases and could account for the overall higher seroprevalence in HCWs, rather than purely the presence of staff in healthcare facilities. Over 30% of seropositive staff had not reported symptoms consistent with COVID-19, and in those who did report symptoms, differentiating COVID-19 from other causes based on symptom data alone was unreliable.

Implications of all the available evidence

International efforts to reduce the risk of SARS-CoV-2 infection amongst HCWs need to be prioritised. The risk of SARS-CoV-2 infection amongst HCWs is heterogenous but also follows demonstrable patterns. Potential mechanisms to reduce the risk for staff working in areas with confirmed COVID-19 patients include improved training in hand hygiene and personal protective equipment (PPE), better access to high quality PPE, and frequent asymptomatic testing. Wider asymptomatic testing in healthcare facilities has the potential to reduce spread of SARS-CoV-2 within hospitals, thereby reducing patient and staff risk and limiting spread between hospitals and into the wider community. The increased risk of COVID-19 amongst BAME staff cannot be explained by purely occupational factors; however, the increased risk amongst minority ethnic groups identified here was stark and necessitates further evaluation.",,pdf:https://www.repository.cam.ac.uk/bitstreams/3ef04015-fa68-40ca-84d6-076095101624/download; doi:https://doi.org/10.1101/2020.11.03.20220699; html:https://europepmc.org/article/PPR/PPR233926; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR233926&type=FILE&fileName=EMS103610-pdf.pdf&mimeType=application/pdf PPR285619,https://doi.org/10.1101/2021.02.17.21251812,Changes in the rate of cardiometabolic and pulmonary events during the COVID-19 pandemic,"Walker AJ, Tazare J, Hickman G, Rentsch CT, Williamson EJ, Bhaskaran K, Evans D, Wing K, Mathur R, Wong AY, Schultze A, Bacon SC, Bates C, Morton CE, Curtis HJ, Nightingale E, McDonald HI, Mehrkar A, Inglesby P, MacKenna B, Cockburn J, Hulme WJ, Forbes H, Minassian C, Croker R, Parry J, Hester F, Harper S, Eggo RM, Evans SJ, Smeeth L, Douglas IJ, Tomlinson L, Goldacre B.",,No Journal Info,2021,2021-02-19,Y,,,,"

Background

There has been extensive speculation about the relationship between COVID-19 and various cardiometabolic and pulmonary conditions. This a complex question: COVID-19 may cause a cardiometabolic or respiratory event; admission for a clinical event may result in hospital-acquired SARS-CoV-2 infection; both may contribute to a patient surpassing the threshold for presenting to services; and the presence of a pandemic may change whether patients present to services at all. To inform analysis of these questions, we set out to describe the overall rate of various key clinical events over time, and their relationship with COVID-19.

Methods

Working on behalf of NHS England, we used data from the OpenSAFELY platform containing data from approximately 40% of the population of England. We selected the whole adult population of 17m patients and within this identified two further mutually exclusive groups: patients who tested positive for SARS-CoV-2 in the community; and patients hospitalised with COVID-19. We report counts of death, DVT, PE, ischaemic stroke, MI, heart failure, AKI and diabetic ketoacidosis in each month between February 2019 and October 2020 within each of: the general population, community SARS-CoV-2 cases, and hospitalised patients with COVID-19. Outcome events were defined using hospitalisations, GP records and cause of death data.

Results

For all outcomes except death there was a lower count of events in April 2020 compared to April 2019. For most outcomes the minimum count of events was in April 2020, where the decrease compared to April 2019 in events ranged from 5.9% (PE) to 40.0% (heart failure). Despite hospitalised COVID-19 patients making up just 0.14% of the population in April 2020, these patients accounted for an extremely high proportion of cardiometabolic and respiratory events in that month (range of proportions 10.3% (DVT) to 33.5% (AKI)).

Interpretation

We observed a substantial drop in the incidence of cardiometabolic and pulmonary events in the non-COVID-19 general population, but high occurrence of COVID-19 among patients with these events. Shortcomings in routine NHS secondary care data, especially around the timing and order of events, make causal interpretations challenging. We caution that the intermediate findings reported here should be used to inform the design and interpretation of any studies using a general population comparator to evaluate the relationship between COVID-19 and other clinical events.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/02/19/2021.02.17.21251812.full.pdf; doi:https://doi.org/10.1101/2021.02.17.21251812; html:https://europepmc.org/article/PPR/PPR285619; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR285619&type=FILE&fileName=EMS117195-pdf.pdf&mimeType=application/pdf PPR409852,https://doi.org/10.2139/ssrn.3944582,Determinants of Pre-Vaccination Antibody Responses to SARS-CoV-2: A Population-Based Longitudinal Study (COVIDENCE UK),"Talaei M, Faustini S, Holt H, Jolliffe D, Vivaldi G, Greenig M, Perdek N, Maltby S, Symons J, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Richter AG, Shaheen SO, Martineau AR.",,No Journal Info,2021,2021-10-18,Y,,,,"Background: Prospective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking.

Methods: We did a prospective population-based study in SARS-CoV-2 vaccine-naive UK adults between May 1 and Nov 2, 2020. Information on 88 potential risk factors was obtained through online questionnaires, and combined IgG/IgA/IgM responses to SARS-CoV-2 spike glycoprotein were determined in dried blood spots. We used logistic and linear regression to estimate adjusted odds ratios (aORs) and adjusted geometric mean ratios (aGMRs) for potential determinants of SARS-CoV-2 seropositivity (all participants) and antibody titres (seropositive participants only), respectively.

Findings: 1696 (15.2%) of 11,130 participants were seropositive. Factors independently associated with increased risk included frontline health/care occupation (aOR 1.86, 95% CI 1.49–2.33), international travel (1.22, 1.08–1.37), BMI >30 vs <25 kg/m² (1.22, 1.05–1.42), Asian/Asian British vs White ethnicity (1.65, 1.10–2.47), and alcohol consumption ≥15 vs 0 units/week (1.26, 1.06–1.49). Light physical exercise associated with decreased risk (0.80, 0.69–0.93, for ≥10 vs 0–4 h/week). Higher titres associated with frontline health/care occupation (aGMR 1.26, 95% CI 1.13–1.41), international travel (1.10, 1.04–1.16), BMI >30 vs <25 kg/m² (1.09, 1.01–1.17), and Asian/Asian British vs White ethnicity (1.23, 1.03–1.46); these associations were not substantially attenuated by adjustment for disease severity.

Interpretation: Higher alcohol consumption and reduced physical exercise represent new modifiable risk factors for SARS-CoV-2 infection. Recognised associations between Asian/Asian British ethnic origin and obesity and increased risk of SARS-CoV-2 seropositivity were independent of other sociodemographic, clinical, or behavioural factors investigated.

Funding: Barts Charity, Health Data Research UK.

Declaration of Interest: JS declares receipt of payments from Reach plc for news stories written about recruitment to, and findings of, the COVIDENCE UK study. AS is a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group and its Standing Committee on Pandemics. He is also a member of the UK Government’s NERVTAG’s Risk Stratification Subgroup. ARM declares receipt of funding in the last 36 months to support vitamin D research from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd, DSM Nutritional Products Ltd, Thornton & Ross Ltd, Cytoplan Ltd and Hyphens Pharma Ltd. ARM also declares support for attending meetings from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd and Abiogen Pharma Ltd. ARM also declares participation on the Data and Safety Monitoring Board for the Chair, DSMB, VITALITY trial (Vitamin D for Adolescents with HIV to reduce musculoskeletal morbidity and immunopathology). ARM also declares unpaid work as a Programme Committee member for the Vitamin D Workshop. ARM also declares receipt of vitamin D capsules for clinical trial use from Pharma Nord Ltd, Synergy Biologics Ltd and Cytoplan Ltd.

Ethical Approval: COVIDENCE UK was sponsored by Queen Mary University of London and approved by Leicester South Research Ethics Committee (ref 20/EM/0117). It is registered with
ClinicalTrials.gov (NCT04330599).",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02286-4; doi:https://doi.org/10.2139/ssrn.3944582; html:https://europepmc.org/article/PPR/PPR409852; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR409852&type=FILE&fileName=EMS137289-pdf.pdf&mimeType=application/pdf @@ -282,8 +282,8 @@ PPR403434,https://doi.org/10.1101/2021.09.30.21264338,"COVID-19 risk factors amo PPR672054,https://doi.org/10.1101/2023.06.06.23290826,"OpenSAFELY: The impact of COVID-19 on azathioprine, leflunomide, and methotrexate monitoring, and factors associated with change in monitoring rate","The OpenSAFELY Collaborative, Brown AD, Fisher L, Curtis HJ, Wiedemann M, Hulme WJ, Hopcroft LE, Cunningham C, Speed V, Costello RE, Galloway JB, Russell MD, Bechman K, Kurt Z, Croker R, Wood C, Walker AJ, Schaffer AL, Bacon SC, Mehrkar A, Hickman G, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, MacKenna B.",,No Journal Info,2023,2023-06-07,Y,,,,"

Background

The COVID-19 pandemic created unprecedented pressure on healthcare services. This study aimed to investigate if disease-modifying anti-rheumatic drug (DMARD) safety monitoring was affected during the COVID-19 pandemic.

Methods

A population-based cohort study was conducted with the approval of NHS England, using the OpenSAFELY platform to access electronic health record data from 24·2 million patients registered at general practices using TPP’s SystmOne software. Patients were included for further analysis if prescribed azathioprine, leflunomide, or methotrexate between November 2019 and July 2022. Outcomes were assessed as monthly trends and variation between various sociodemographic and clinical groups for adherence with standard safety monitoring recommendations.

Findings

An acute increase in the rate of missed monitoring occurred across the study population (+12·4 percentage points) when lockdown measures were implemented in March 2020. This increase was more pronounced for some patient groups (70-79 year-olds: +13·7 percentage points; females: +12·8 percentage points), regions (North West: +17·0 percentage points), medications (Leflunomide: +20·7 percentage points), and monitoring tests (Blood Pressure: +24·5 percentage points). Missed monitoring rates decreased substantially for all groups by July 2022. Substantial and consistent differences were observed in overall missed monitoring rates between several groups throughout the study.

Interpretation

DMARD monitoring rates temporarily deteriorated during the COVID-19 pandemic. Deterioration coincided with the onset of lockdown measures, with monitoring rates recovering rapidly as lockdown measures were eased. Differences observed in monitoring rates between medications, tests, regions, and patient groups, highlight opportunities to tackle potential inequalities in the provision or uptake of monitoring services. Further research should aim to evaluate the causes of the differences identified between groups.

Funding

None.

Research in context

Evidence before this study

Disease-modifying anti-rheumatic drugs (DMARDs) are immunosuppressive and/or immunomodulatory drugs, which carry risks of serious adverse effects such as; gastrointestinal, renal, hepatic, and pulmonary toxicity; myelosuppression; and increased susceptibility to infection. To mitigate these safety risks, national safety guidance recommends that patients taking these drugs receive regular monitoring. We searched PubMed, Web of Science and Scopus for studies published between database inception and July 28th, 2022, using the terms ([covid-19] AND [monitoring OR shared care OR dmard OR outcome factors] AND [primary care]), with no language restrictions. Studies that investigated the effect of the COVID-19 pandemic on healthcare services were identified. One key study in England showed disruption to various monitoring services in primary care had occurred during the pandemic. Another English study highlighted a disproportionate impact of the COVID-19 pandemic on health outcomes in certain groups.

Added value of this study

Prior to this study knowledge of how high-risk drugs, such as DMARDs, were affected by the COVID-19 pandemic was limited. This study reports the impact of COVID-19 on the safety monitoring of DMARDs. Moreover, it reports variation in DMARD monitoring rates between demographic, clinical and regional subgroups, which has not yet been described. This is enabled through use of the OpenSAFELY platform, which provides secure access to pseudonymised primary care patient records in England for the purposes of analysing the COVID-19 pandemic impact.

Implications of all the available evidence

DMARD monitoring rates transiently deteriorated during the COVID-19 pandemic, consistent with previous research on other monitoring tests. Deterioration coincided with the onset of lockdown measures, with performance recovering rapidly as lockdown measures were eased. Differences observed in monitoring rates between demographic, clinical and regional subgroups highlight opportunities to identify and tackle potential inequalities in the provision or uptake of monitoring services. Further research should aim to evaluate the causes of the differences identified between groups, and establish the clinical relevance of missed monitoring. Several studies have demonstrated the capability of the OpenSAFELY platform as a secure and efficient approach for analysing NHS primary care data at scale, generating meaningful insights on service delivery.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/06/07/2023.06.06.23290826.full.pdf; doi:https://doi.org/10.1101/2023.06.06.23290826; html:https://europepmc.org/article/PPR/PPR672054; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR672054&type=FILE&fileName=EMS177037-pdf.pdf&mimeType=application/pdf PPR415629,https://doi.org/10.1101/2021.11.02.21265767,Determinants of pre-vaccination antibody responses to SARS-CoV-2: a population-based longitudinal study (COVIDENCE UK),"Talaei M, Faustini S, Holt H, Jolliffe DA, Vivaldi G, Greenig M, Perdek N, Maltby S, Bigogno CM, Symons J, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Richter AG, Shaheen SO, Martineau AR.",,No Journal Info,2021,2021-11-03,Y,,,,"

Background

Prospective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking.

Methods

We did a prospective population-based study in SARS-CoV-2 vaccine-naive UK adults recruited between May 1 and November 2, 2020, without a positive swab test result for SARS-CoV-2 prior to enrolment. Information on 88 potential sociodemographic, behavioural, nutritional, clinical and pharmacological risk factors was obtained through online questionnaires, and combined IgG/IgA/IgM responses to SARS-CoV-2 spike glycoprotein were determined in dried blood spots obtained between November 6, 2020 and April 18, 2021. We used logistic and linear regression to estimate adjusted odds ratios (aORs) and adjusted geometric mean ratios (aGMRs) for potential determinants of SARS-CoV-2 seropositivity (all participants) and antibody titres (seropositive participants only), respectively.

Results

1696 (15.2%) of 11,130 participants were seropositive. Factors independently associated with increased risk of SARS-CoV-2 seropositivity included frontline health/care occupation (aOR 1.86, 95% CI 1.48–2.33), international travel (1.20, 1.07–1.35), number of visits to shops and other indoor public places (≥5 vs. 0/week: 1.29, 1.06-1.57, P-trend=0.01), body mass index (BMI) ≥25 vs <25 kg/m 2 (1.24, 1.11–1.39), Asian/Asian British vs White ethnicity (1.65, 1.10–2.49), and alcohol consumption ≥15 vs 0 units/week (1.23, 1.04–1.46). Light physical exercise associated with decreased risk (0.80, 0.70–0.93, for ≥10 vs 0–4 h/week). Among seropositive participants, higher titres of anti-Spike antibodies associated with factors including BMI ≥30 vs <25 kg/m 2 (aGMR 1.10, 1.02–1.19), Asian/Asian British vs White ethnicity (1.22, 1.04–1.44), frontline health/care occupation (1.24, 95% CI 1.11–1.39), international travel (1.11, 1.05–1.16), and number of visits to shops and other indoor public places (≥5 vs. 0/week: 1.12, 1.02-1.23, P-trend=0.01); these associations were not substantially attenuated by adjustment for COVID-19 disease severity.

Conclusions

Higher alcohol consumption and reduced light physical exercise represent new modifiable risk factors for SARS-CoV-2 infection. Recognised associations between Asian/Asian British ethnic origin and obesity and increased risk of SARS-CoV-2 seropositivity were independent of other sociodemographic, behavioural, nutritional, clinical and pharmacological factors investigated. Among seropositive participants, higher titres of anti-Spike antibodies in people of Asian ancestry and in obese people were not explained by greater COVID-19 disease severity in these groups.

Funding

Barts Charity, Health Data Research UK.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-022-02286-4; doi:https://doi.org/10.1101/2021.11.02.21265767; html:https://europepmc.org/article/PPR/PPR415629; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR415629&type=FILE&fileName=EMS138031-pdf.pdf&mimeType=application/pdf PPR204608,https://doi.org/10.1101/2020.08.19.20178137,Testing for coronavirus (SARS-CoV-2) infection in populations with low infection prevalence: the largely ignored problem of false positives and the value of repeat testing,"Sudlow C, Diggle P, Warlow O, Seymour D, Gordon B, Walker R, Warlow C.",,No Journal Info,2020,2020-08-22,Y,,,,"

ABSTRACT

Background

Calls are increasing for widespread SARS-CoV-2 infection testing of people from populations with a very low prevalence of infection. We quantified the impact of less than perfect diagnostic test accuracy on populations, and on individuals, in low prevalence settings, focusing on false positives and the role of confirmatory testing.

Methods

We developed a simple, interactive tool to assess the impact of different combinations of test sensitivity, specificity and infection prevalence in a notional population of 100,000. We derived numbers of true positives, true negatives, false positives and false negatives, positive predictive value (PPV – the percentage of test positives that are true positives) and overall test accuracy for three testing strategies: (1) single test for all; (2) add repeat testing in test positives; (3) add further repeat testing in those with discrepant results. We also assessed the impact on test results for individuals having one, two or three tests under these three strategies.

Results

With sensitivity of 80%, infection prevalence of 1 in 2,000, and specificity 99.9% on all tests, PPV in the tested population of 100,000 will be only 29% with one test, increasing to > 99.5% (100% when rounded to the nearest %) with repeat testing in strategies 2 or 3. More realistically, if specificity is 95% for the first and 99.9% for subsequent tests, single test PPV will be only 1%, increasing to 86% with repeat testing in strategy 2, or 79% with strategy 3 (albeit with 6 fewer false negatives than strategy 2). In the whole population, or in particular individuals, PPV increases as infection becomes more common in the population but falls to unacceptably low levels with lower test specificity.

Conclusion

To avoid multiple unnecessary restrictions on whole populations, and in particular individuals, from widespread population testing for SARS-CoV-2, the crucial roles of extremely high test specificity and of confirmatory testing must be fully appreciated and incorporated into policy decisions.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/08/22/2020.08.19.20178137.full.pdf; doi:https://doi.org/10.1101/2020.08.19.20178137; html:https://europepmc.org/article/PPR/PPR204608; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR204608&type=FILE&fileName=EMS95538-pdf.pdf&mimeType=application/pdf -PPR703602,https://doi.org/10.1101/2023.08.02.23293505,COVID pandemic impact on hypertension management in North-East London: an observational cohort study using electronic health records,"Rison SC, Redfern O, Mathur R, Dostal I, Carvalho C, Raisi-Estabragh Z, Robson JP.",,No Journal Info,2023,2023-08-06,Y,,,,"

ABSTRACT

Background

The COVID19 pandemic had a major impact on primary care management of long-term conditions such as hypertension. This observational cohort study of adults with hypertension registered in 193 primary care practices in North-East London between January 2019 and October 2022 investigated the impact of the COVID19 pandemic on the treatment and control of blood pressure including demographic and social inequities.

Method and findings

In 224,329 adults with hypertension, the proportion with a blood pressure (BP) recorded within the preceding 1 year fell from a 91% pre-pandemic peak to 62% at the end of the pandemic lock-down phase and improved to 77% by the end of the study. The proportion with controlled hypertension (<80 years old, BP ≤140/90mmHg; 80 or more years old: ≤150/90mmHg) for the same time points was 81%, 50% and 60% respectively. Using ‘blood pressure control’ (which considered only patients with a valid blood pressure recording) as the indicator attenuated the reduction to 83%, 80% and 78% respectively. The study used multivariable logistic analysis at four representative time points (Pre-pandemic: April 2019; Pre lockdown: April 2020; Lockdown: April 2021; Post-lockdown: April 2022) to identify temporal, clinical and demographic influences on blood pressure monitoring and control. Pre-pandemic inequities in the management of hypertension were not significantly altered by the pandemic. Throughout the pandemic phases, in comparison to the White ethnic group, the Black ethnic group was less likely to achieve blood pressure control (ORs 0.81 [95% CI = 0.78 to 0.85, p-value<0.001] to 0.87 [95% CI = 0.84 to 0.91, p-value<0.001]). Conversely, the Asian ethnic group was more likely to have controlled blood pressure (ORs 1.09 [95% CI = 1.05 to 1.14, p-value<0.001] to 1.28 [95% CI = 1.23 to 1.32, p-value<0.001]). Younger, male, more affluent individuals, individuals with unknown or unrecorded ethnicity or those untreated were less likely to have blood pressure controlled to target throughout the study.

Conclusion

The COVID pandemic had a greater impact on blood pressure recording than on blood pressure control. Although recording and control have improved, these had not returned to pre-pandemic levels by the end of the study period. Ethnic inequalities in blood pressure control persisted during the pandemic and remain outstanding.",,doi:https://doi.org/10.1101/2023.08.02.23293505; html:https://europepmc.org/article/PPR/PPR703602; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR703602&type=FILE&fileName=EMS184893-pdf.pdf&mimeType=application/pdf PPR354446,https://doi.org/10.1101/2021.06.08.21258132,"Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial","RECOVERY Collaborative Group, Horby PW, Pessoa-Amorim G, Staplin N, Emberson JR, Campbell M, Spata E, Peto L, Brunskill NJ, Tiberi S, Chew V, Brown T, Tahir H, Ebert B, Chadwick D, Whitehouse T, Sarkar R, Graham C, Baillie JK, Basnyat B, Buch MH, Chappell LC, Day J, Faust SN, Hamers RL, Jaki T, Juszczak E, Jeffery K, Lim WS, Montgomery A, Mumford A, Rowan K, Thwaites G, Mafham M, Haynes R, Landray MJ.",,No Journal Info,2021,2021-06-08,Y,,,,"

SUMMARY

Background

Aspirin has been proposed as a treatment for COVID-19 on the basis of its antithrombotic properties.

Methods

In this randomised, controlled, open-label platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care plus 150mg aspirin once daily until discharge or usual standard of care alone using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov ( NCT04381936 ).

Findings

Between 01 November 2020 and 21 March 2021, 7351 patients were randomly allocated to receive aspirin and 7541 patients to receive usual care alone. Overall, 1222 (17%) patients allocated to aspirin and 1299 (17%) patients allocated to usual care died within 28 days (rate ratio 0·96; 95% confidence interval [CI] 0·89-1·04; p=0·35). Consistent results were seen in all pre-specified subgroups of patients. Patients allocated to aspirin had a slightly shorter duration of hospitalisation (median 8 vs. 9 days) and a higher proportion were discharged from hospital alive within 28 days (75% vs. 74%; rate ratio 1·06; 95% CI 1·02-1·10; p=0·0062). Among those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs. 22%; risk ratio 0·96; 95% CI 0·90-1·03; p=0·23). Aspirin use was associated with an absolute reduction in thrombotic events of 0.6% (SE 0.4%) and an absolute increase in major bleeding events of 0.6% (SE 0.2%).

Interpretation

In patients hospitalised with COVID-19, aspirin was not associated with reductions in 28-day mortality or in the risk of progressing to invasive mechanical ventilation or death but was associated with a small increase in the rate of being discharged alive within 28 days.

Funding

UK Research and Innovation (Medical Research Council), National Institute of Health Research (Grant ref: MC_PC_19056), and the Wellcome Trust (Grant Ref: 222406/Z/20/Z) through the COVID-19 Therapeutics Accelerator.",,pdf:https://nottingham-repository.worktribe.com/preview/6737802/PIIS0140673621018250.pdf; doi:https://doi.org/10.1101/2021.06.08.21258132; html:https://europepmc.org/article/PPR/PPR354446; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR354446&type=FILE&fileName=EMS127500-pdf.pdf&mimeType=application/pdf +PPR703602,https://doi.org/10.1101/2023.08.02.23293505,COVID pandemic impact on hypertension management in North-East London: an observational cohort study using electronic health records,"Rison SC, Redfern O, Mathur R, Dostal I, Carvalho C, Raisi-Estabragh Z, Robson JP.",,No Journal Info,2023,2023-08-06,Y,,,,"

ABSTRACT

Background

The COVID19 pandemic had a major impact on primary care management of long-term conditions such as hypertension. This observational cohort study of adults with hypertension registered in 193 primary care practices in North-East London between January 2019 and October 2022 investigated the impact of the COVID19 pandemic on the treatment and control of blood pressure including demographic and social inequities.

Method and findings

In 224,329 adults with hypertension, the proportion with a blood pressure (BP) recorded within the preceding 1 year fell from a 91% pre-pandemic peak to 62% at the end of the pandemic lock-down phase and improved to 77% by the end of the study. The proportion with controlled hypertension (<80 years old, BP ≤140/90mmHg; 80 or more years old: ≤150/90mmHg) for the same time points was 81%, 50% and 60% respectively. Using ‘blood pressure control’ (which considered only patients with a valid blood pressure recording) as the indicator attenuated the reduction to 83%, 80% and 78% respectively. The study used multivariable logistic analysis at four representative time points (Pre-pandemic: April 2019; Pre lockdown: April 2020; Lockdown: April 2021; Post-lockdown: April 2022) to identify temporal, clinical and demographic influences on blood pressure monitoring and control. Pre-pandemic inequities in the management of hypertension were not significantly altered by the pandemic. Throughout the pandemic phases, in comparison to the White ethnic group, the Black ethnic group was less likely to achieve blood pressure control (ORs 0.81 [95% CI = 0.78 to 0.85, p-value<0.001] to 0.87 [95% CI = 0.84 to 0.91, p-value<0.001]). Conversely, the Asian ethnic group was more likely to have controlled blood pressure (ORs 1.09 [95% CI = 1.05 to 1.14, p-value<0.001] to 1.28 [95% CI = 1.23 to 1.32, p-value<0.001]). Younger, male, more affluent individuals, individuals with unknown or unrecorded ethnicity or those untreated were less likely to have blood pressure controlled to target throughout the study.

Conclusion

The COVID pandemic had a greater impact on blood pressure recording than on blood pressure control. Although recording and control have improved, these had not returned to pre-pandemic levels by the end of the study period. Ethnic inequalities in blood pressure control persisted during the pandemic and remain outstanding.",,doi:https://doi.org/10.1101/2023.08.02.23293505; html:https://europepmc.org/article/PPR/PPR703602; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR703602&type=FILE&fileName=EMS184893-pdf.pdf&mimeType=application/pdf PPR162356,https://doi.org/10.1101/2020.05.11.20097709,"Systemic corticosteroids show no benefit in severe and critical COVID-19 patients in Wuhan, China: A retrospective cohort study","Wu J, Huang J, Zhu G, Liu Y, Xiao H, Zhou Q, Si X, Yi H, Wang C, Yang D, Chen S, Liu X, Liu Z, Wang Q, Lv Q, Huang Y, Yu Y, Guan X, Li Y, Nirantharakumar K, Cheng K, Peng S, Xiao H.",,No Journal Info,2020,2020-05-14,Y,,,,"

Background:

Systemic corticosteroids are recommended by some treatment guidelines and used in severe and critical COVID-19 patients, though evidence supporting such use is limited.

Methods:

From December 26, 2019 to March 15, 2020, 1514 severe and 249 critical hospitalized COVID-19 patients were collected from two medical centers in Wuhan, China. We performed multivariable Cox models, Cox model with time-varying exposure and propensity score analysis (both inverse-probability-of-treatment-weighting (IPTW) and propensity score matching (PSM)) to estimate the association of corticosteroid use with the risk of in-hospital mortality among severe and critical cases.

Results:

Corticosteroids were administered in 531 (35.1%) severe and 159 (63.9%) critical patients. Compared to no corticosteroid use group, systemic corticosteroid use showed no benefit in reducing in-hospital mortality in both severe cases (HR=1.77, 95% CI: 1.08-2.89, p=0.023), and critical cases (HR=2.07, 95% CI: 1.08-3.98, p=0.028). In the time-varying Cox analysis that with time varying exposure, systemic corticosteroid use still showed no benefit in either population (for severe patients, HR=2.83, 95% CI: 1.72-4.64, p< 0.001; for critical patients, HR=3.02, 95% CI: 1.59-5.73, p=0.001). Baseline characteristics were matched after IPTW and PSM analysis. For severe COVID-19 patients at admission, corticosteroid use was not associated with improved outcome in either the IPTW analysis. For critical COVID-19 patients at admission, results were consistent with former analysis that corticosteroid use did not reduce in-hospital mortality.

Conclusions:

Corticosteroid use showed no benefit in reducing in-hospital mortality for severe or critical cases. The routine use of systemic corticosteroids among severe and critical COVID-19 patients was not recommended.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/05/14/2020.05.11.20097709.full.pdf; doi:https://doi.org/10.1101/2020.05.11.20097709; html:https://europepmc.org/article/PPR/PPR162356; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR162356&type=FILE&fileName=EMS91863-pdf.pdf&mimeType=application/pdf PPR601851,https://doi.org/10.2139/ssrn.3970709,Impact of First UK COVID-19 Lockdown on Hospital Admissions: Interrupted Time Series Study of 32 Million People,"Shah SA, Brophy S, Kennedy J, Fisher L, Walker A, Mackenna B, Curtis H, Inglesby P, Davy S, Bacon S, Goldacre B, Group OC, Agrawal U, Moore E, Simpson C, Macleod J, Cooksey R, Sheikh A, Katikireddi SV.",,No Journal Info,2021,2021-11-24,N,,,,"Background: Uncontrolled infection and lockdown measures introduced in response have resulted in an unprecedented challenge for health systems internationally. Whether such disruption was due to lockdown itself and recedes when such measures are lifted is unclear. We assessed the short- and medium-term impacts of the first lockdown measures on hospital care for exemplar non-COVID-19 conditions in England, Scotland and Wales across diseases, sexes, and socioeconomic and ethnic groups.

Methods: We used OpenSAFELY (for England), EAVEII (Scotland), and SAIL Databank (Wales) to extract weekly hospital admission rates for cancer, cardiovascular and respiratory conditions (excluding COVID-19) from the pre-pandemic period until 25/10/2020 and conducted a controlled interrupted time series analysis. We undertook stratified analyses and assessed admission rates over seven months during which lockdown restrictions were gradually lifted.

Findings: Our combined dataset included 32 million people who contributed over 74 million person-years. Admission rates for all three conditions fell by 34.2% in England, 20.9% in Scotland, and 24.7% in Wales, with falls across every stratum considered. In all three nations, cancer-related admissions fell the most while respiratory-related admissions fell the least (e.g., rates fell by 40.5%, 21.9%, and 19.0% in England for cancer, cardiovascular-related, and respiratory-related admissions respectively). Unscheduled admissions rates fell more in the most than the least deprived quintile across all three nations. Some ethnic minority groups experienced greater falls in admissions (e.g., in England, unscheduled admissions fell by 9.5% for Whites, but 44.3%, 34.6%, and 25.6% for Mixed, Other and Black ethnic groups respectively). Despite easing of restrictions, the overall admission rates remained lower in England, Scotland, and Wales by 20.8%, 21.6%, and 22.0% respectively when compared to the same period (August-September) during the pre-pandemic years.

Interpretation: Hospital care for non-COVID diseases fell substantially across England, Scotland, and Wales during the first lockdown, with disruptions persisting for at least six months. The most deprived and minority ethnic groups were impacted more severely.

Funding Information: Medical Research Council; Health Data Research UK; Industrial Strategy Challenge Fund; Scottish Government; National Institute for Health Research; Asthma UK-BLF; Wellcome Trust

Declaration of Interests: SVK is co-chair of the Scottish Government’s Expert Reference Group on ethnicity and COVID-19 and is a member of the Scientific Advisory Group on Emergencies subgroup on ethnicity. AS is a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group and its Standing Committee on Pandemics, and NERVTAG’s Risk Stratification Subgroup. All other authors declare no conflict of interest related to this work.

Ethics Approval Statement: There were database-specific ethics approvals that allowed the use of the anonymised datasets for the current research study. These approvals were by the Health Research Authority (20/LO/0651) and LSHTM Ethics Board (21863) for OpenSAFELY, South East Scotland Research Ethics Committee 02 (12/SS/0201) and Public Benefit and Privacy Panel Committee of Public Health Scotland (1920-0279) for EAVE-II, and SAIL’s independent Information Governance Review Panel (IGRP) for the SAIL Databank.",,pdf:https://research-repository.st-andrews.ac.uk/bitstream/10023/25440/1/Shah_2022_eCM_Impact_first_UK_COVID_19_lockdown_CC.pdf; doi:https://doi.org/10.2139/ssrn.3970709; html:https://europepmc.org/article/PPR/PPR601851; doi:https://doi.org/10.2139/ssrn.3970709 PPR435234,https://doi.org/10.1101/2021.12.20.21268113,A nationwide deep learning pipeline to predict stroke and COVID-19 death in atrial fibrillation,"Handy A, Wood A, Sudlow C, Tomlinson C, Kee F, Thygesen JH, Mamouei M, Sofat R, Dobson R, Ip S, Denaxas S.",,No Journal Info,2021,2021-12-21,N,,,,"

ABSTRACT

Deep learning (DL) and machine learning (ML) models trained on long-term patient trajectories held as medical codes in electronic health records (EHR) have the potential to improve disease prediction. Anticoagulant prescribing decisions in atrial fibrillation (AF) offer a use case where the benchmark stroke risk prediction tool (CHA 2 DS 2 -VASc) could be meaningfully improved by including more information from a patient’s medical history. In this study, we design and build the first DL and ML pipeline that uses the routinely updated, linked EHR data for 56 million people in England accessed via NHS Digital to predict first ischaemic stroke in people with AF, and as a secondary outcome, COVID-19 death. Our pipeline improves first stroke prediction in AF by 17% compared to CHA 2 DS 2 -VASc (0.61 (0.57-0.65) vs 0.52 (0.52-0.52) area under the receiver operating characteristics curves, 95% confidence interval) and provides a generalisable, opensource framework that other researchers and developers can build on.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/12/21/2021.12.20.21268113.full.pdf; doi:https://doi.org/10.1101/2021.12.20.21268113; html:https://europepmc.org/article/PPR/PPR435234; doi:https://doi.org/10.1101/2021.12.20.21268113 @@ -296,8 +296,8 @@ PPR180964,https://doi.org/10.1101/2020.06.26.20140921,Short Communication: Vitam PPR252028,https://doi.org/10.1101/2020.12.08.20246231,Artificial intelligence-enabled analysis of UK and US public attitudes on Facebook and Twitter towards COVID-19 vaccinations,"Hussain A, Tahir A, Hussain Z, Sheikh Z, Gogate M, Dashtipour K, Ali A, Sheikh A.",,No Journal Info,2020,2020-12-11,Y,,,,"

Background

Global efforts towards the development and deployment of a vaccine for SARS-CoV-2 are rapidly advancing. We developed and applied an artificial-intelligence (AI)-based approach to analyse social-media public sentiment in the UK and the US towards COVID-19 vaccinations, to understand public attitude and identify topics of concern.

Methods

Over 300,000 social-media posts related to COVID-19 vaccinations were extracted, including 23,571 Facebook-posts from the UK and 144,864 from the US, along with 40,268 tweets from the UK and 98,385 from the US respectively, from 1 st March - 22 nd November 2020. We used natural language processing and deep learning based techniques to predict average sentiments, sentiment trends and topics of discussion. These were analysed longitudinally and geo-spatially, and a manual reading of randomly selected posts around points of interest helped identify underlying themes and validated insights from the analysis.

Results

We found overall averaged positive, negative and neutral sentiment in the UK to be 58%, 22% and 17%, compared to 56%, 24% and 18% in the US, respectively. Public optimism over vaccine development, effectiveness and trials as well as concerns over safety, economic viability and corporation control were identified. We compared our findings to national surveys in both countries and found them to correlate broadly.

Conclusions

AI-enabled social-media analysis should be considered for adoption by institutions and governments, alongside surveys and other conventional methods of assessing public attitude. This could enable real-time assessment, at scale, of public confidence and trust in COVID-19 vaccinations, help address concerns of vaccine-sceptics and develop more effective policies and communication strategies to maximise uptake.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/12/11/2020.12.08.20246231.full.pdf; doi:https://doi.org/10.1101/2020.12.08.20246231; html:https://europepmc.org/article/PPR/PPR252028; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR252028&type=FILE&fileName=EMS108377-pdf.pdf&mimeType=application/pdf PPR672704,https://doi.org/,A Comprehensive Benchmark for COVID-19 Predictive Modeling Using Electronic Health Records in Intensive Care,"Gao J, Zhu Y, Wang W, Wang Y, Tang W, Harrison EM, Ma L.",,No Journal Info,2023,2023-06-07,Y,,,,"The COVID-19 pandemic has posed a heavy burden to the healthcare system worldwide and caused huge social disruption and economic loss. Many deep learning models have been proposed to conduct clinical predictive tasks such as mortality prediction for COVID-19 patients in intensive care units using Electronic Health Record (EHR) data. Despite their initial success in certain clinical applications, there is currently a lack of benchmarking results to achieve a fair comparison so that we can select the optimal model for clinical use. Furthermore, there is a discrepancy between the formulation of traditional prediction tasks and real-world clinical practice in intensive care. To fill these gaps, we propose two clinical prediction tasks, Outcome-specific length-of-stay prediction and Early mortality prediction for COVID-19 patients in intensive care units. The two tasks are adapted from the naive length-of-stay and mortality prediction tasks to accommodate the clinical practice for COVID-19 patients. We propose fair, detailed, open-source data-preprocessing pipelines and evaluate 17 state-of-the-art predictive models on two tasks, including 5 machine learning models, 6 basic deep learning models and 6 deep learning predictive models specifically designed for EHR data. We provide benchmarking results using data from two real-world COVID-19 EHR datasets. One dataset is publicly available without needing any inquiry and another dataset can be accessed on request. We provide fair, reproducible benchmarking results for two tasks. We deploy all experiment results and models on an online platform. We also allow clinicians and researchers to upload their data to the platform and get quick prediction results using our trained models. We hope our efforts can further facilitate deep learning and machine learning research for COVID-19 predictive modeling.",,arxiv:https://arxiv.org/abs/2209.07805v3; html:https://europepmc.org/article/PPR/PPR672704; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR672704&type=FILE&fileName=EMS177023-pdf.pdf&mimeType=application/pdf PPR191969,https://doi.org/10.1101/2020.07.22.20159772,Projecting contact matrices in 177 geographical regions: an update and comparison with empirical data for the COVID-19 era,"Prem K, van Zandvoort K, Klepac P, Eggo RM, Davies NG, Cook AR, Jit M, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group.",,No Journal Info,2020,2020-07-25,Y,,,,"Mathematical models have played a key role in understanding the spread of directly-transmissible infectious diseases such as Coronavirus Disease 2019 (COVID-19), as well as the effectiveness of public health responses. As the risk of contracting directly-transmitted infections depends on who interacts with whom, mathematical models often use contact matrices to characterise the spread of infectious pathogens. These contact matrices are usually generated from diary-based contact surveys. However, the majority of places in the world do not have representative empirical contact studies, so synthetic contact matrices have been constructed using more widely available setting-specific survey data on household, school, classroom, and workplace composition combined with empirical data on contact patterns in Europe. In 2017, the largest set of synthetic contact matrices to date were published for 152 geographical locations. In this study, we update these matrices with the most recent data and extend our analysis to 177 geographical locations. Due to the observed geographic differences within countries, we also quantify contact patterns in rural and urban settings where data is available. Further, we compare both the 2017 and 2020 synthetic matrices to out-of-sample empirically-constructed contact matrices, and explore the effects of using both the empirical and synthetic contact matrices when modelling physical distancing interventions for the COVID-19 pandemic. We found that the synthetic contact matrices reproduce the main traits of the contact patterns in the empirically-constructed contact matrices. Models parameterised with the empirical and synthetic matrices generated similar findings with few differences observed in age groups where the empirical matrices have missing or aggregated age groups. This finding means that synthetic contact matrices may be used in modelling outbreaks in settings for which empirical studies have yet to be conducted.

Author summary

The risk of contracting a directly transmitted infectious disease such as the Coronavirus Disease 2019 (COVID-19) depends on who interacts with whom. Such person-to-person interactions vary by age and locations—e.g., at home, at work, at school, or in the community—due to the different social structures. These social structures, and thus contact patterns, vary across and within countries. Although social contact patterns can be measured using contact surveys, the majority of countries around the world, particularly low- and middle-income countries, lack nationally representative contact surveys. A simple way to present contact data is to use matrices where the elements represent the rate of contact between subgroups such as age groups represented by the columns and rows. In 2017, we generated age- and location-specific synthetic contact matrices for 152 geographical regions by adapting contact pattern data from eight European countries using country-specific data on household size, school and workplace composition. We have now updated these matrices with the most recent data (Demographic Household Surveys, World Bank, UN Population Division) extending the coverage to 177 geographical locations, covering 97.2% of the world’s population. We also quantified contact patterns in rural and urban settings. When compared to out-of-sample empirically-measured contact patterns, we found that the synthetic matrices reproduce the main features of these contact patterns.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/07/28/2020.07.22.20159772.full.pdf; doi:https://doi.org/10.1101/2020.07.22.20159772; html:https://europepmc.org/article/PPR/PPR191969; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR191969&type=FILE&fileName=EMS87995-pdf.pdf&mimeType=application/pdf -PPR630589,https://doi.org/10.1101/2023.03.15.23287292,Living alone and mental health: parallel analyses in longitudinal population surveys and electronic health records prior to and during the COVID-19 pandemic,"McElroy E, Herrett E, Patel K, Piehlmaier DM, Di Gessa G, Huggins C, Green MJ, Kwong A, Thompson EJ, Zhu J, Mansfield KE, Silverwood RJ, Mansfield R, Maddock J, Mathur R, Costello RE, Matthews A, Tazare J, Henderson A, Wing K, Bridges L, Bacon S, Mehrkar A, Shaw RJ, Wels J, Katikireddi SV, Chaturvedi N, Tomlinson L, Patalay P, OpenSafely Collaborative.",,No Journal Info,2023,2023-03-15,Y,,,,"

ABSTRACT

Objectives

To describe the mental health gap between those who live alone and those who live with others, and to examine whether the COVID-19 pandemic had an impact on this gap.

Design

Ten population based prospective cohort studies, and a retrospective descriptive cohort study based on electronic health records (EHRs).

Setting

UK Longitudinal population-based surveys (LPS), and primary and secondary care records within the OpenSAFELY-TPP database.

Participants

Participants from the LPS were included if they had information on living status in early 2020, valid data on mental ill-health at the closest pre-pandemic assessment and at least once during the pandemic, and valid data on a key minimum set of covariates. The EHR dataset included 16 million adults registered with primary care practices in England using TPP SystmOne software on 1st February 2020, with at least three months of registration, valid address data, and living in households of <16 people.

Main outcome measures

In the LPS, self-reported survey measures of psychological distress and life satisfaction were assessed in the nearest pre-pandemic sweep and three periods during the pandemic: April-June 2020, July-October 2020, and November 2020-March 2021. In the EHR analyses, outcomes were morbidity codes recorded in primary or secondary care between March 2018 and January 2022 reflecting the diagnoses of depression, self-harm, anxiety, obsessive compulsive disorder, eating disorders, and severe mental illnesses.

Results

The LPS consisted of 37,544 participants (15.2% living alone) and we found greater psychological distress (SMD: 0.09 (95% CI: 0.04, 0.14) and lower life satisfaction (SMD: -0.22 (95% CI: -0.30, -0.15) in those living alone pre-pandemic, and the gap between the two groups stayed similar after the onset of the pandemic. In the EHR analysis of almost 16 million records (21.4% living alone), codes indicating mental health conditions were more common in those who lived alone compared to those who lived with others (e.g., depression 26 and severe mental illness 58 cases more per 100,000). Recording of mental health conditions fell during the pandemic for common mental health disorders and the gap between the two groups narrowed.

Conclusions

Multiple sources of data indicate that those who live alone experience greater levels of common and severe mental illnesses, and lower life satisfaction. During the pandemic this gap in need remained, however, there was a narrowing of the gap in service use, suggesting greater barriers to healthcare access for those who live alone.

Summary Box

What is already known on the topic?

Households with one individual are an increasing demographic, comprising over a quarter of all households in the UK in 2021. However, the mental health gap between those who live alone compared to those who live with others is not well described and even less is known about the relative gaps in need and healthcare-seeking and access. The pandemic and associated restrictive measures further increased the likelihood of isolation for this group, which may have impacted mental health.

What this study adds?

We present comprehensive evidence from both population-based surveys and electronic health records regarding the greater levels of mental health symptoms and in recorded diagnoses for common (anxiety, depression) and less common (OCD, eating disorders, SMIs) mental health conditions for people living alone compared to those living with others. Our analyses indicate that mental health conditions are more common among those who live alone compared to those who live with others. Although levels of reported distress increased for both groups during the pandemic, healthcare-seeking dropped in both groups, and the rates of healthcare-seeking among those who live alone converged with those who live with others for common mental health conditions. This suggests greater barriers for treatment access among those that live alone. The findings have implications for mental health service planning and efforts to reduce barriers to treatment access, especially for individuals who live on their own.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/03/15/2023.03.15.23287292.full.pdf; doi:https://doi.org/10.1101/2023.03.15.23287292; html:https://europepmc.org/article/PPR/PPR630589; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR630589&type=FILE&fileName=EMS172468-pdf.pdf&mimeType=application/pdf PPR178487,https://doi.org/10.1101/2020.06.19.20135491,"Inhaled corticosteroid use and risk COVID-19 related death among 966,461 patients with COPD or asthma: an OpenSAFELY analysis","The OpenSAFELY Collaborative, Schultze A, Walker AJ, MacKenna B, Morton CE, Bhaskaran K, Brown JP, Rentsch CT, Williamson E, Drysdale H, Croker R, Bacon S, Hulme W, Bates C, Curtis HJ, Mehrkar A, Evans D, Inglesby P, Cockburn J, McDonald HI, Tomlinson L, Mathur R, Wing K, Wong AY, Forbes H, Parry J, Hester F, Harper S, Evans SJ, Quint J, Smeeth L, Douglas IJ, Goldacre B.",,No Journal Info,2020,2020-06-20,Y,,,,"

Background

Early descriptions of the coronavirus outbreak showed a lower prevalence of asthma and COPD than was expected for people diagnosed with COVID-19, leading to speculation that inhaled corticosteroids (ICS) may protect against infection with SARS-CoV-2, and development of serious sequelae. We evaluated the association between ICS and COVID-19 related death using linked electronic health records in the UK.

Methods

We conducted cohort studies on two groups of people (COPD and asthma) using the OpenSAFELY platform to analyse data from primary care practices linked to national death registrations. People receiving an ICS were compared to those receiving alternative respiratory medications. Our primary outcome was COVID-19 related death.

Findings

We identified 148,588 people with COPD and 817,973 people with asthma receiving relevant respiratory medications in the four months prior to 01 March 2020. People with COPD receiving ICS were at a greater risk of COVID-19 related death compared to those receiving a long-acting beta agonist (LABA) and a long-acting muscarinic antagonist (LAMA) (adjusted HR = 1.38, 95% CI = 1.08 – 1.75). People with asthma receiving high dose ICS were at an increased risk of death compared to those receiving a short-acting beta agonist (SABA) only (adjusted HR = 1.52, 95%CI = 1.08 – 2.14); the adjusted HR for those receiving low-medium dose ICS was 1.10 (95% CI = 0.82 – 1.49). Quantitative bias analyses indicated that an unmeasured confounder of only moderate strength of association with exposure and outcome could explain the observed associations in both populations.

Interpretation

These results do not support a major role of ICS in protecting against COVID-19 related deaths. Observed increased risks of COVID-19 related death among people with COPD and asthma receiving ICS can be plausibly explained by unmeasured confounding due to disease severity.

Funding

This work was supported by the Medical Research Council MR/V015737/1.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/06/20/2020.06.19.20135491.full.pdf; doi:https://doi.org/10.1101/2020.06.19.20135491; html:https://europepmc.org/article/PPR/PPR178487; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR178487&type=FILE&fileName=EMS88284-pdf.pdf&mimeType=application/pdf +PPR630589,https://doi.org/10.1101/2023.03.15.23287292,Living alone and mental health: parallel analyses in longitudinal population surveys and electronic health records prior to and during the COVID-19 pandemic,"McElroy E, Herrett E, Patel K, Piehlmaier DM, Di Gessa G, Huggins C, Green MJ, Kwong A, Thompson EJ, Zhu J, Mansfield KE, Silverwood RJ, Mansfield R, Maddock J, Mathur R, Costello RE, Matthews A, Tazare J, Henderson A, Wing K, Bridges L, Bacon S, Mehrkar A, Shaw RJ, Wels J, Katikireddi SV, Chaturvedi N, Tomlinson L, Patalay P, OpenSafely Collaborative.",,No Journal Info,2023,2023-03-15,Y,,,,"

ABSTRACT

Objectives

To describe the mental health gap between those who live alone and those who live with others, and to examine whether the COVID-19 pandemic had an impact on this gap.

Design

Ten population based prospective cohort studies, and a retrospective descriptive cohort study based on electronic health records (EHRs).

Setting

UK Longitudinal population-based surveys (LPS), and primary and secondary care records within the OpenSAFELY-TPP database.

Participants

Participants from the LPS were included if they had information on living status in early 2020, valid data on mental ill-health at the closest pre-pandemic assessment and at least once during the pandemic, and valid data on a key minimum set of covariates. The EHR dataset included 16 million adults registered with primary care practices in England using TPP SystmOne software on 1st February 2020, with at least three months of registration, valid address data, and living in households of <16 people.

Main outcome measures

In the LPS, self-reported survey measures of psychological distress and life satisfaction were assessed in the nearest pre-pandemic sweep and three periods during the pandemic: April-June 2020, July-October 2020, and November 2020-March 2021. In the EHR analyses, outcomes were morbidity codes recorded in primary or secondary care between March 2018 and January 2022 reflecting the diagnoses of depression, self-harm, anxiety, obsessive compulsive disorder, eating disorders, and severe mental illnesses.

Results

The LPS consisted of 37,544 participants (15.2% living alone) and we found greater psychological distress (SMD: 0.09 (95% CI: 0.04, 0.14) and lower life satisfaction (SMD: -0.22 (95% CI: -0.30, -0.15) in those living alone pre-pandemic, and the gap between the two groups stayed similar after the onset of the pandemic. In the EHR analysis of almost 16 million records (21.4% living alone), codes indicating mental health conditions were more common in those who lived alone compared to those who lived with others (e.g., depression 26 and severe mental illness 58 cases more per 100,000). Recording of mental health conditions fell during the pandemic for common mental health disorders and the gap between the two groups narrowed.

Conclusions

Multiple sources of data indicate that those who live alone experience greater levels of common and severe mental illnesses, and lower life satisfaction. During the pandemic this gap in need remained, however, there was a narrowing of the gap in service use, suggesting greater barriers to healthcare access for those who live alone.

Summary Box

What is already known on the topic?

Households with one individual are an increasing demographic, comprising over a quarter of all households in the UK in 2021. However, the mental health gap between those who live alone compared to those who live with others is not well described and even less is known about the relative gaps in need and healthcare-seeking and access. The pandemic and associated restrictive measures further increased the likelihood of isolation for this group, which may have impacted mental health.

What this study adds?

We present comprehensive evidence from both population-based surveys and electronic health records regarding the greater levels of mental health symptoms and in recorded diagnoses for common (anxiety, depression) and less common (OCD, eating disorders, SMIs) mental health conditions for people living alone compared to those living with others. Our analyses indicate that mental health conditions are more common among those who live alone compared to those who live with others. Although levels of reported distress increased for both groups during the pandemic, healthcare-seeking dropped in both groups, and the rates of healthcare-seeking among those who live alone converged with those who live with others for common mental health conditions. This suggests greater barriers for treatment access among those that live alone. The findings have implications for mental health service planning and efforts to reduce barriers to treatment access, especially for individuals who live on their own.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/03/15/2023.03.15.23287292.full.pdf; doi:https://doi.org/10.1101/2023.03.15.23287292; html:https://europepmc.org/article/PPR/PPR630589; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR630589&type=FILE&fileName=EMS172468-pdf.pdf&mimeType=application/pdf PPR179288,https://doi.org/10.1101/2020.06.22.20137273,Effect of Dexamethasone in Hospitalized Patients with COVID-19 – Preliminary Report,"Horby P, Lim WS, Emberson J, Mafham M, Bell J, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ, RECOVERY Collaborative Group.",,No Journal Info,2020,2020-06-22,Y,,,,"

ABSTRACT

Background

Coronavirus disease 2019 (COVID-19) is associated with diffuse lung damage. Corticosteroids may modulate immune-mediated lung injury and reducing progression to respiratory failure and death.

Methods

The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, adaptive, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of dexamethasone 6 mg given once daily for up to ten days vs. usual care alone. The primary outcome was 28-day mortality.

Results

2104 patients randomly allocated to receive dexamethasone were compared with 4321 patients concurrently allocated to usual care. Overall, 454 (21.6%) patients allocated dexamethasone and 1065 (24.6%) patients allocated usual care died within 28 days (age-adjusted rate ratio [RR] 0.83; 95% confidence interval [CI] 0.74 to 0.92; P<0.001). The proportional and absolute mortality rate reductions varied significantly depending on level of respiratory support at randomization (test for trend p<0.001): Dexamethasone reduced deaths by one-third in patients receiving invasive mechanical ventilation (29.0% vs. 40.7%, RR 0.65 [95% CI 0.51 to 0.82]; p<0.001), by one-fifth in patients receiving oxygen without invasive mechanical ventilation (21.5% vs. 25.0%, RR 0.80 [95% CI 0.70 to 0.92]; p=0.002), but did not reduce mortality in patients not receiving respiratory support at randomization (17.0% vs. 13.2%, RR 1.22 [95% CI 0.93 to 1.61]; p=0.14).

Conclusions

In patients hospitalized with COVID-19, dexamethasone reduced 28-day mortality among those receiving invasive mechanical ventilation or oxygen at randomization, but not among patients not receiving respiratory support.

Trial registrations

The RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov ( NCT04381936 ).

Funding

Medical Research Council and National Institute for Health Research (Grant ref: MC_PC_19056).",,pdf:https://www.nejm.org/doi/pdf/10.1056/NEJMoa2021436?articleTools=true; doi:https://doi.org/10.1101/2020.06.22.20137273; html:https://europepmc.org/article/PPR/PPR179288; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR179288&type=FILE&fileName=EMS88343-pdf.pdf&mimeType=application/pdf PPR602096,https://doi.org/10.2139/ssrn.4260125,The Impact of the First Year of COVID-19 Vaccination Strategy in Brazil: An Ecological Study,"Aguilar S, Bastos LdSL, Maçaira P, Baiao FA, Simões P, Cerbino-Neto J, Ranzani O, Hamacher S, Bozza FA.",,No Journal Info,2022,2022-10-27,Y,,,,"Background: Countries have used different strategies to prioritize who be vaccinated first during the COVID-19 vaccination roll-out. No consensus exists about the best strategy to be adopted by low-and-middle-income countries with limited access to vaccines. Brazil adopted an age-based calendar strategy to reduce mortality and the burden over the healthcare system. The impact of this strategy on preventing deaths and years of life lost was not estimated.

Methods: This ecological study analyses the dynamic of vaccination coverage and COVID-19 deaths in adults (≥20 years) during the first year of the COVID-19 vaccination roll-out (January-December, 2021) using nationwide data (DATASUS). We stratified the adult population into 20-49, 50-59, 60-69, and 70+ years. The dynamic effect of the vaccination campaign on mortality rates was estimated using Differences-in-Differences. The prevented and preventable deaths (observed deaths higher than expected), and Potential Years of Life Lost (PYLL), for each age group were obtained in a counterfactual analysis.

Findings: During the first year of COVID-19 vaccination 266,153,517 doses were administered, achieving 91% first-dose coverage. 380,594 deaths were reported, being 154,091 (40%) in 70+, and 136,804 (36%) from 50-59 or 20-49 years. The mortality rates of 70+ decreased 52% (RRR [95% CI]: 0.48 [0.43-0.53]) in 6 months, whereas rates for 20-49 were still increasing due to the low coverage (52%). The vaccination roll-out strategy prevented 59,618 deaths, 53,088 (89%) from those aged 70+ years. However, the strategy did not prevent 54,797 deaths, 85% from those under 60 years, being 26,344 (45%) only in 20-49, corresponding to 1,589,271 PYLL, being 1,080,104 PYLL (68%) from those aged 20-49 years.

Interpretation: The adopted aged-based calendar vaccination strategy initially reduced the mortality in the oldest, but did not significantly prevent the deaths of the youngest. Countries with high burden, limited vaccine supply and young population should consider other factors besides age to prioritise who to vaccine first.

Funding Information: This work is part of the Grand Challenges ICODA pilot initiative, delivered by Health Data Research UK and funded by the Bill & Melinda Gates Foundation and the Minderoo Foundation. This study was supported by the National Council for Scientific and Technological Development (CNPq), the Coordination for the Improvement of Higher Education Personnel (CAPES) - Finance Code 001, Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ) and the Pontifical Catholic University of Rio de Janeiro. OTR is funded by a Sara Borrell grant from the Instituto de Salud Carlos III (CD19/00110). OTR acknowledges support from the Spanish Ministry of Science and Innovation and State Research Agency through the ""Centro de Excelencia Severo Ochoa 2019-2023"" Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program.

Declaration of Interests: The authors declare no potential conflicts of interest.

Ethics Approval Statement: Data was publicly available, anonymized, and de-identified. Following ethically agreed principles on open data, this analysis did not require ethical approval in Brazil.",,doi:https://doi.org/10.2139/ssrn.4260125; html:https://europepmc.org/article/PPR/PPR602096; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR602096&type=FILE&fileName=EMS164205-pdf.pdf&mimeType=application/pdf PPR291347,https://doi.org/10.21203/rs.3.rs-279400/v1,Unraveling COVID-19: a large-scale characterization of 4.5 million COVID-19 cases using CHARYBDIS,"Prieto-Alhambra D, Kostka K, Duarte-Salles T, Prats-Uribe A, Sena A, Pistillo A, Khalid S, Lai L, Golozar A, Alshammari TM, Dawoud D, Nyberg F, Wilcox A, Andryc A, Williams A, Ostropolets A, Areia C, Jung CY, Harle C, Reich C, Blacketer C, Morales D, Dorr DA, Burn E, Roel E, Tan EH, Minty E, DeFalco F, de Maeztu G, Lipori G, Alghoul H, Zhu H, Thomas J, Bian J, Park J, Roldán JM, Posada J, Banda JM, Horcajada JP, Kohler J, Shah K, Natarajan K, Lynch K, Liu L, Schilling L, Recalde M, Spotnitz M, Gong M, Matheny M, Valveny N, Weiskopf N, Shah N, Alser O, Casajust P, Park RW, Schuff R, Seager S, DuVall S, You SC, Song S, Fernández-Bertolín S, Fortin S, Magoc T, Falconer T, Subbian V, Huser V, Ahmed W, Carter W, Guan Y, Galvan Y, He X, Rijnbeek P, Hripcsak G, Ryan P, Suchard M.",,No Journal Info,2021,2021-03-01,Y,,,,"

Background:

Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response [1,2]. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) [3] Characterizing Health Associated Risks, and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD.

Methods:

: We conducted a descriptive cohort study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11 th June 2020 and are iteratively updated via GitHub [4].

Findings:

We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19 , and 113,627 hospitalized with COVID-19 requiring intensive services . All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts, and are available in an interactive website: https://data.ohdsi.org/Covid19CharacterizationCharybdis/. Interpretation: CHARYBDIS findings provide benchmarks that contribute to our understanding of COVID-19 progression, management and evolution over time. This can enable timely assessment of real-world outcomes of preventative and therapeutic options as they are introduced in clinical practice.",,pdf:http://repositori.upf.edu/bitstream/10230/53956/1/Kostka_ce_unra.pdf; doi:https://doi.org/10.21203/rs.3.rs-279400/v1; html:https://europepmc.org/article/PPR/PPR291347; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR291347&type=FILE&fileName=EMS118164-pdf.pdf&mimeType=application/pdf @@ -307,8 +307,8 @@ PPR150220,https://doi.org/10.1101/2020.04.07.20056788,ACE-inhibitors and Angiote PPR319210,https://doi.org/10.1101/2021.04.30.21256119,Association between oral anticoagulants and COVID-19 related outcomes: two cohort studies,"The OpenSAFELY Collaborative, Wong AY, Tomlinson L, Brown JP, Elson W, Walker AJ, Schultze A, Morton CE, Evans D, Inglesby P, MacKenna B, Bhaskaran K, Rentsch CT, Powell E, Williamson E, Croker R, Bacon S, Hulme W, Bates C, Curtis HJ, Mehrkar A, Cockburn J, McDonald HI, Mathur R, Wing K, Forbes H, Eggo RM, Evans SJ, Smeeth L, Goldacre B, Douglas IJ.",,No Journal Info,2021,2021-04-30,Y,,,,"

Objectives

We investigated the role of routinely prescribed oral anticoagulants (OACs) in COVID-19 outcomes, comparing current OAC use versus non-use in Study 1; and warfarin versus direct oral anticoagulants (DOACs) in Study 2.

Design

Two cohort studies, on behalf of NHS England.

Setting

Primary care data and pseudonymously-linked SARS-CoV-2 antigen testing data, hospital admissions, and death records from England.

Participants

Study 1: 70,464 people with atrial fibrillation (AF) and CHA□DS□-VASc score of 2. Study 2: 372,746 people with non-valvular AF.

Main outcome measures

Time to test for SARS-CoV-2, testing positive for SARS-CoV-2, COVID-19 related hospital admission, COVID-19 deaths or non-COVID-19 deaths in Cox regression.

Results

In Study 1, we included 52,416 current OAC users and 18,048 non-users. We observed no difference in risk of being tested for SARS-CoV-2 associated with current use (adjusted HR, 1.01, 95%CI, 0.96 to 1.05) versus non-use. We observed a lower risk of testing positive for SARS-CoV-2 (adjusted HR, 0.73, 95%CI, 0.60 to 0.90), and COVID-19 deaths (adjusted HR, 0.69, 95%CI, 0.49 to 0.97) associated with current use versus non-use. In Study 2, we included 92,339 warfarin users and 280,407 DOAC users. We observed a lower risk of COVID-19 deaths (adjusted HR, 0.79, 95%CI, 0.76 to 0.83) associated with warfarin versus DOACs. Similar associations were found for all other outcomes.

Conclusions

Among people with AF and a CHA□DS□-VASc score of 2, those receiving OACs had a lower risk of receiving a positive COVID-19 test and severe COVID-19 outcomes than non-users; this might be explained by a causal effect of OACs in preventing severe COVID-19 outcomes or more cautious behaviours leading to reduced infection risk. There was no evidence of a higher risk of severe COVID-19 outcomes associated with warfarin versus DOACs in people with non-valvular AF regardless of CHA□DS□-VASc score.

Key points

What is already known on this topic

Current studies suggest that prophylactic or therapeutic anticoagulant use, particularly low molecular weight heparin, lower the risk of pulmonary embolism and mortality during hospitalisation among patients with COVID-19. Reduced vitamin K status has been reported to be correlated with severity of COVID-19. This could mean that warfarin, as a vitamin K antagonist, is associated with more severe COVID-19 disease than non-vitamin K anticoagulants.

What this study adds

In 70,464 people with atrial fibrillation, at the threshold of being treated with an OAC based on risk of stroke, we observed a lower risk of testing positive for SARS-CoV-2 and COVID-19 related deaths associated with routinely prescribed OACs, relative to non-use. This might be explained by OACs preventing severe COVID-19 outcomes, or more cautious behaviours and environmental factors reducing the risk of SARS-CoV-2 infection in those taking OACs. In 372,746 people with non-valvular atrial fibrillation, there was no evidence of a higher risk of severe COVID-19 outcomes associated with warfarin compared with DOACs.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/04/30/2021.04.30.21256119.full.pdf; doi:https://doi.org/10.1101/2021.04.30.21256119; html:https://europepmc.org/article/PPR/PPR319210; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR319210&type=FILE&fileName=EMS123890-pdf.pdf&mimeType=application/pdf PPR404742,https://doi.org/10.1101/2021.10.07.21264681,Monitoring sociodemographic inequality in COVID-19 vaccination coverage in England: a national linked data study,"Dolby T, Finning K, Baker A, Dowd L, Khunti K, Razieh C, Yates T, Nafilyan V.",,No Journal Info,2021,2021-10-07,Y,,,,"

Background

The UK began an ambitious COVID-19 vaccination programme on 8 th December 2020. This study describes variation in vaccination coverage by sociodemographic characteristics between December 2020 and August 2021.

Methods

Using population-level administrative records linked to the 2011 Census, we estimated monthly first dose vaccination rates by age group and sociodemographic characteristics amongst adults aged 18 years or over in England. We also present a tool to display the results interactively.

Findings

Our study population included 35,223,466 adults. A lower percentage of males than females were vaccinated in the young and middle age groups (18-59 years) but not in the older age groups. Vaccination rates were highest among individuals of White British and Indian ethnic backgrounds and lowest among Black Africans (aged ≥80 years) and Black Caribbeans (18-79 years). Differences by ethnic group emerged as soon as vaccination roll-out commenced and widened over time. Vaccination rates were also lower among individuals who identified as Muslim, lived in more deprived areas, reported having a disability, did not speak English as their main language, lived in rented housing, belonged to a lower socio-economic group, and had fewer qualifications.

Interpretation

We found inequalities in COVID-19 vaccination rates by sex, ethnicity, religion, area deprivation, disability status, English language proficiency, socio-economic position, and educational attainment, but some of these differences varied by age group. Research is urgently needed to understand why these inequalities exist and how they can be addressed.

Research in context

Evidence before this study

We searched PubMed for publications on sociodemographic inequalities in COVID-19 vaccination coverage. Several studies have reported differences in coverage by characteristics such as ethnicity and religion, however these have focused on older adults and the clinically vulnerable who were initially prioritized for vaccination. There is little evidence on sociodemographic inequalities in vaccination coverage among younger adults and evidence is also lacking on coverage by a wider range of characteristics such as sex, disability status, English language proficiency, socio-economic position, and educational attainment.

Added value of this study

This study provides the first evidence for sociodemographic inequalities in COVID-19 vaccination coverage among the entire adult population in England, using population-level administrative records linked to the 2011 Census. By disaggregating the data by age group, we were able to show that disparities in coverage by some sociodemographic characteristics differed by age group. For example, a lower proportion of males than females were vaccinated in the young and middle age groups (18-59 years) but not in the older age groups, and vaccination rates were lowest among Black Africans in those aged ≥80 years but lowest among Black Caribbeans for all other age groups. Vaccination rates were also lower among individuals who identified as Muslim, lived in more deprived areas, reported having a disability, did not speak English as their main language, lived in rented housing, belonged to a lower socio-economic group, and had fewer qualifications.

Implications of all the available evidence

Many of the groups with the lowest rates of COVID-19 vaccination are also the groups that have been disproportionately affected by the pandemic, including severe illness and mortality. Research is urgently needed to understand why these disparities exist and how they can be addressed, for example through public health or community engagement programmes. Since the relationships between sociodemographic characteristics and vaccination coverage may differ by age group, it is important for future research to disaggregate by age group when examining these inequalities.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/10/07/2021.10.07.21264681.full.pdf; doi:https://doi.org/10.1101/2021.10.07.21264681; html:https://europepmc.org/article/PPR/PPR404742; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR404742&type=FILE&fileName=EMS136793-pdf.pdf&mimeType=application/pdf PPR465564,https://doi.org/10.1101/2022.03.07.22271833,GWAS and meta-analysis identifies multiple new genetic mechanisms underlying severe Covid-19,"Pairo-Castineira E, Rawlik K, Klaric L, Kousathanas A, Richmond A, Millar J, Russell CD, Malinauskas T, Thwaites R, Stuckey A, Odhams CA, Walker S, Griffiths F, Oosthuyzen W, Morrice K, Keating S, Nichol A, Semple MG, Knight J, Shankar-Hari M, Summers C, Hinds C, Horby P, Ling L, McAuley D, Montgomery H, Openshaw PJ, Walsh T, Tenesa A, Scott RH, Caulfield MJ, Moutsianas L, Ponting CP, Wilson JF, Vitart V, Pereira AC, Luchessi A, Parra E, Cruz-Guerrero R, Carracedo A, Fawkes A, Murphy L, Rowan K, Law A, Hendry SC, Baillie JK, GenOMICC Investigators, SCOURGE Consortium, ISARIC4C Investigators, 23andMe.",,No Journal Info,2022,2022-03-07,Y,,,,"Pulmonary inflammation drives critical illness in Covid-19, 1;2 creating a clinically homogeneous extreme phenotype, which we have previously shown to be highly efficient for discovery of genetic associations. 3;4 Despite the advanced stage of illness, we have found that immunomodulatory therapies have strong beneficial effects in this group. 1;5 Further genetic discoveries may identify additional therapeutic targets to modulate severe disease. 6 In this new data release from the GenOMICC (Genetics Of Mortality in Critical Care) study we include new microarray genotyping data from additional critically-ill cases in the UK and Brazil, together with cohorts of severe Covid-19 from the ISARIC4C 7 and SCOURGE 8 studies, and meta-analysis with previously-reported data. We find an additional 14 new genetic associations. Many are in potentially druggable targets, in inflammatory signalling (JAK1, PDE4A), monocyte-macrophage differentiation (CSF2), immunometabolism (SLC2A5, AK5), and host factors required for viral entry and replication (TMPRSS2, RAB2A). As with our previous work, these results provide tractable therapeutic targets for modulation of harmful host-mediated inflammation in Covid-19.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/03/07/2022.03.07.22271833.full.pdf; doi:https://doi.org/10.1101/2022.03.07.22271833; html:https://europepmc.org/article/PPR/PPR465564; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR465564&type=FILE&fileName=EMS161994-pdf.pdf&mimeType=application/pdf -PPR507260,https://doi.org/10.1101/2022.06.14.22276391,Factors associated with COVID-19 vaccine uptake in people with kidney disease: an OpenSAFELY cohort study,"The OpenSAFELY Collaborative, Parker EP, Tazare J, Hulme WJ, Bates C, Beale R, Carr EJ, Cockburn J, Curtis HJ, Fisher L, Green AC, Harper S, Hester F, Horne EM, Loud F, Lyon S, Mahalingasivam V, Mehrkar A, Nab L, Parry J, Santhakumaran S, Steenkamp R, Sterne JA, Walker AJ, Williamson EJ, Willicombe M, Zheng B, Goldacre B, Nitsch D, Tomlinson LA.",,No Journal Info,2022,2022-06-16,Y,,,,"

Background

Kidney disease is a significant risk factor for COVID-19-related mortality. Achieving high COVID-19 vaccine coverage among people with kidney disease is therefore a public health priority.

Methods

With the approval of NHS England, we performed a retrospective cohort study using the OpenSAFELY-TPP platform. Individual-level routine clinical data from 24 million people in England were included. A cohort of individuals with stage 3–5 chronic kidney disease (CKD) or receiving renal replacement therapy (RRT) at the start of the COVID-19 vaccine roll-out was identified based on evidence of reduced estimated glomerular filtration rate or inclusion in the UK Renal Registry. Individual-level factors associated with vaccine uptake were explored via Cox proportional hazards models.

Results

948,845 people with stage 3–5 CKD or receiving RRT were included. Cumulative vaccine coverage as of 11 th May 2022 was 97.5%, 97.0%, and 93.5% for doses 1, 2, and 3, respectively, and 61.1% among individuals with one or more indications for receipt of a fourth dose. Delayed 3-dose vaccine uptake was associated with non-White ethnicity, social deprivation, and severe mental illness – associations that were consistent across CKD stages and in RRT recipients. Similar associations were observed for 4-dose uptake, which was also delayed among care home residents.

Conclusion

Although high primary and booster dose coverage has been achieved among people with kidney disease in England, key disparities in vaccine uptake remain across demographic groups. Identifying how to address these disparities remains a priority to reduce the risk of severe disease in this vulnerable patient group.",,pdf:https://figshare.com/articles/journal_contribution/Factors_associated_with_COVID-19_vaccine_uptake_in_people_with_kidney_disease_an_OpenSAFELY_cohort_study/22035716/1/files/39108458.pdf; doi:https://doi.org/10.1101/2022.06.14.22276391; html:https://europepmc.org/article/PPR/PPR507260; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR507260&type=FILE&fileName=EMS146125-pdf.pdf&mimeType=application/pdf PPR157865,https://doi.org/10.1101/2020.04.27.20081810,Clinical classifiers of COVID-19 infection from novel ultra-high-throughput proteomics,"Messner CB, Demichev V, Wendisch D, Michalick L, White M, Freiwald A, Textoris-Taube K, Vernardis SI, Egger A, Kreidl M, Ludwig D, Kilian C, Agostini F, Zelezniak A, Thibeault C, Pfeiffer M, Hippenstiel S, Hocke A, von Kalle C, Campbell A, Hayward C, Porteous DJ, Marioni RE, Langenberg C, Lilley KS, Kuebler WM, Mülleder M, Drosten C, Witzenrath M, Kurth F, Sander LE, Ralser M.",,No Journal Info,2020,2020-05-03,Y,,,,"

Summary

The COVID-19 pandemic is an unprecedented global challenge. Highly variable in its presentation, spread and clinical outcome, novel point-of-care diagnostic classifiers are urgently required. Here, we describe a set of COVID-19 clinical classifiers discovered using a newly designed low-cost high-throughput mass spectrometry-based platform. Introducing a new sample preparation pipeline coupled with short-gradient high-flow liquid chromatography and mass spectrometry, our methodology facilitates clinical implementation and increases sample throughput and quantification precision. Providing a rapid assessment of serum or plasma samples at scale, we report 27 biomarkers that distinguish mild and severe forms of COVID-19, of which some may have potential as therapeutic targets. These proteins highlight the role of complement factors, the coagulation system, inflammation modulators as well as pro-inflammatory signalling upstream and downstream of Interleukin 6. Application of novel methodologies hence transforms proteomics from a research tool into a rapid-response, clinically actionable technology adaptable to infectious outbreaks.

Highlights

- A completely redesigned clinical proteomics platform increases throughput and precision while reducing costs. - 27 biomarkers are differentially expressed between WHO severity grades for COVID-19. - The study highlights potential therapeutic targets that include complement factors, the coagulation system, inflammation modulators as well as pro-inflammatory signalling both upstream and downstream of interleukin 6.",This study successfully uses mass spectrometry to distinguish mild and severe forms of COVID ,pdf:http://www.cell.com/article/S2405471220301976/pdf; doi:https://doi.org/10.1101/2020.04.27.20081810; html:https://europepmc.org/article/PPR/PPR157865; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR157865&type=FILE&fileName=EMS91998-pdf.pdf&mimeType=application/pdf +PPR507260,https://doi.org/10.1101/2022.06.14.22276391,Factors associated with COVID-19 vaccine uptake in people with kidney disease: an OpenSAFELY cohort study,"The OpenSAFELY Collaborative, Parker EP, Tazare J, Hulme WJ, Bates C, Beale R, Carr EJ, Cockburn J, Curtis HJ, Fisher L, Green AC, Harper S, Hester F, Horne EM, Loud F, Lyon S, Mahalingasivam V, Mehrkar A, Nab L, Parry J, Santhakumaran S, Steenkamp R, Sterne JA, Walker AJ, Williamson EJ, Willicombe M, Zheng B, Goldacre B, Nitsch D, Tomlinson LA.",,No Journal Info,2022,2022-06-16,Y,,,,"

Background

Kidney disease is a significant risk factor for COVID-19-related mortality. Achieving high COVID-19 vaccine coverage among people with kidney disease is therefore a public health priority.

Methods

With the approval of NHS England, we performed a retrospective cohort study using the OpenSAFELY-TPP platform. Individual-level routine clinical data from 24 million people in England were included. A cohort of individuals with stage 3–5 chronic kidney disease (CKD) or receiving renal replacement therapy (RRT) at the start of the COVID-19 vaccine roll-out was identified based on evidence of reduced estimated glomerular filtration rate or inclusion in the UK Renal Registry. Individual-level factors associated with vaccine uptake were explored via Cox proportional hazards models.

Results

948,845 people with stage 3–5 CKD or receiving RRT were included. Cumulative vaccine coverage as of 11 th May 2022 was 97.5%, 97.0%, and 93.5% for doses 1, 2, and 3, respectively, and 61.1% among individuals with one or more indications for receipt of a fourth dose. Delayed 3-dose vaccine uptake was associated with non-White ethnicity, social deprivation, and severe mental illness – associations that were consistent across CKD stages and in RRT recipients. Similar associations were observed for 4-dose uptake, which was also delayed among care home residents.

Conclusion

Although high primary and booster dose coverage has been achieved among people with kidney disease in England, key disparities in vaccine uptake remain across demographic groups. Identifying how to address these disparities remains a priority to reduce the risk of severe disease in this vulnerable patient group.",,pdf:https://figshare.com/articles/journal_contribution/Factors_associated_with_COVID-19_vaccine_uptake_in_people_with_kidney_disease_an_OpenSAFELY_cohort_study/22035716/1/files/39108458.pdf; doi:https://doi.org/10.1101/2022.06.14.22276391; html:https://europepmc.org/article/PPR/PPR507260; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR507260&type=FILE&fileName=EMS146125-pdf.pdf&mimeType=application/pdf PPR287050,https://doi.org/10.1101/2021.02.22.21252185,Linked electronic health records for research on a nationwide cohort including over 54 million people in England,"CVD-COVID-UK consortium, Wood A, Denholm R, Hollings S, Cooper J, Ip S, Walker V, Denaxas S, Akbari A, Sterne J, Sudlow C, Wood (chair) A, Denholm R, Hollings S, Cooper J, Ip S, Walker V, Denaxas S, Banerjee A, Whiteley W, Lai A, Priedon R, Sudlow C, Morrice L, Ringham D, Power S, Laidlaw L, Molete M, Walsh J, Coleman G, Day C, Gaffney E, Gentry T, Gray L, Hollings S, Irvine R, Roberts B, Spence E, Waterhouse J, Manuscript drafting and revising, Data wrangling, QA and analysis (including generating phenotype definitions), Figures/graphics, Consortium coordination (BHF Data Science Centre core team), Public and patient advisory panel, NHS Digital (coordination, data management/provision, data access request and information governance support Trusted Research Environment support.",,No Journal Info,2021,2021-02-23,Y,,,,"

ABSTRACT

Objectives

Describe a new England-wide electronic health record (EHR) resource enabling whole population research on Covid-19 and cardiovascular disease whilst ensuring data security and privacy and maintaining public trust.

Design

Cohort comprising linked person-level records from national healthcare settings for the English population accessible within NHS Digital’s new Trusted Research Environment.

Setting

EHRs from primary care, hospital episodes, death registry, Covid-19 laboratory test results and community dispensing data, with further enrichment planned from specialist intensive care, cardiovascular and Covid-19 vaccination data.

Participants

54.4 million people alive on 1 st January 2020 and registered with an NHS general practitioner in England.

Main measures of interest

Confirmed and suspected Covid-19 diagnoses, exemplar cardiovascular conditions (incident stroke or transient ischaemic attack (TIA) and incident myocardial infarction (MI)) and all-cause mortality between 1 st January and 31 st October 2020.

Results

The linked cohort includes over 96% of the English population. By combining person-level data across national healthcare settings, data on age, sex and ethnicity are complete for over 95% of the population. Among 53.2M people with no prior diagnosis of stroke/TIA, 98,721 had an incident stroke/TIA, of which 30% were recorded only in primary care and 4% only in death registry records. Among 53.1M people with no prior history of MI, 62,966 had an incident MI, of which 8% were recorded only in primary care and 12% only in death records. A total of 959,067 people had a confirmed or suspected Covid-19 diagnosis (714,162 in primary care data, 126,349 in hospital admission records, 776,503 in Covid-19 laboratory test data and 48,433 participants in death registry records). While 58% of these were recorded in both primary care and Covid-19 laboratory test data, 15% and 18% respectively were recorded in only one.

Conclusions

This population-wide resource demonstrates the importance of linking person-level data across health settings to maximize completeness of key characteristics and to ascertain cardiovascular events and Covid-19 diagnoses. Although established initially to support research on Covid-19 and cardiovascular disease to benefit clinical care and public health and to inform health care policy, it can broaden further to enable a very wide range of research.",,doi:https://doi.org/10.1101/2021.02.22.21252185; doi:https://doi.org/10.1101/2021.02.22.21252185; html:https://europepmc.org/article/PPR/PPR287050; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR287050&type=FILE&fileName=EMS117369-pdf.pdf&mimeType=application/pdf PPR217801,https://doi.org/10.1101/2020.09.22.20198754,"Ethnic differences in COVID-19 infection, hospitalisation, and mortality: an OpenSAFELY analysis of 17 million adults in England","The OpenSAFELY Collaborative, Mathur R, Mathur R, Rentsch CT, Morton CE, Hulme WJ, Hulme WJ, Schultze A, MacKenna B, Eggo R, Bhaskaran K, Wong AY, Williamson EJ, Forbes H, Wing K, McDonald HI, Bates C, Bacon S, Walker AJ, Evans D, Inglesby P, Mehrkar A, Curtis HJ, DeVito NJ, Croker R, Drysdale H, Cockburn J, Parry J, Hester F, Harper S, Douglas IJ, Tomlinson L, Evans SJ, Grieve R, Harrison D, Rowan K, Khunti K, Chaturvedi N, Smeeth L, Goldacre B.",,No Journal Info,2020,2020-09-23,Y,,,,"

Background

COVID-19 has had a disproportionate impact on ethnic minority populations, both in the UK and internationally. To date, much of the evidence has been derived from studies within single healthcare settings, mainly those hospitalised with COVID-19. Working on behalf of NHS England, the aim of this study was to identify ethnic differences in the risk of COVID-19 infection, hospitalisation and mortality using a large general population cohort in England.

Methods

We conducted an observational cohort study using linked primary care records of 17.5 million adults between 1 February 2020 and 3 August 2020. Exposure was self-reported ethnicity collapsed into the 5 and 16 ethnicity categories of the English Census. Multivariable Cox proportional hazards regression was used to identify ethnic differences in the risk of being tested and testing positive for SARS-CoV-2 infection, COVID-19 related intensive care unit (ICU) admission, and COVID-19 mortality, adjusted for socio-demographic factors, clinical co-morbidities, geographic region, care home residency, and household size.

Results

A total of 17,510,002 adults were included in the study; 63% white (n=11,030,673), 6% south Asian (n=1,034,337), 2% black (n=344,889), 2% other (n=324,730), 1% mixed (n=172,551), and 26% unknown (n=4,602,822). After adjusting for measured explanatory factors, south Asian, black, and mixed groups were marginally more likely to be tested (south Asian HR 1.08, 95%CI 1.07-1.09; black HR 1.08; 95%CI 1.06-1.09, mixed HR 1.03, 95%CI 1.01-1.05), and substantially more likely to test positive for SARS-CoV-2 compared with white adults (south Asian HR 2.02. 95% CI 1.97-2.07; black HR 1.68, 95%CI 1.61-1.76; mixed HR 1.46, 95%CI 1.36-1.56). The risk of being admitted to ICU for COVID-19 was substantially increased in all ethnic minority groups compared with white adults (south Asian HR 2.22, 95%CI 1.96-2.52; black HR 3.07, 95%CI 2.61-3.61; mixed HR 2.86, 95%CI 2.19-3.75, other HR 2.86, 95%CI 2.31-3.63). Risk of COVID-19 mortality was increased by 25-56% in ethnic minority groups compared with white adults (south Asian HR 1.27, 95%CI 1.17-1.38; black HR 1.55, 95%CI 1.38-1.75; mixed HR 1.40, 95%CI 1.12-1.76; other HR 1.25, 95%CI 1.05-1.49). We observed heterogeneity of associations after disaggregation into detailed ethnic groupings; Indian and African groups were at higher risk of all outcomes; Pakistani, Bangladeshi and Caribbean groups were less or equally likely to be tested for SARS-CoV-2, but at higher risk of all other outcomes, Chinese groups were less likely to be tested for and test positive for SARS-CoV-2, more likely to be admitted to ICU, and equally likely to die from COVID-19.

Conclusions

We found evidence of substantial ethnic inequalities in the risk of testing positive for SARS-CoV-2, ICU admission, and mortality, which persisted after accounting for explanatory factors, including household size. It is likely that some of this excess risk is related to factors not captured in clinical records such as occupation, experiences of structural discrimination, or inequitable access to health and social services. Prioritizing linkage between health, social care, and employment data and engaging with ethnic minority communities to better understand their lived experiences is essential for generating evidence to prevent further widening of inequalities in a timely and actionable manner.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/09/23/2020.09.22.20198754.full.pdf; doi:https://doi.org/10.1101/2020.09.22.20198754; html:https://europepmc.org/article/PPR/PPR217801; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR217801&type=FILE&fileName=EMS96320-pdf.pdf&mimeType=application/pdf PPR611882,https://doi.org/10.1101/2023.02.01.23285333,Associations between reported healthcare disruption due to COVID-19 and avoidable hospitalisation: Evidence from seven linked longitudinal studies for England,"Green MA, McKee M, Hamilton O, Shaw RJ, Macleod J, Boyd A, The LH&W NCS Collaborative, and Srinivasa Vittal Katikireddi.",,No Journal Info,2023,2023-02-02,Y,,,,"

Background

Health services across the UK struggled to cope during the COVID-19 pandemic. Many treatments were postponed or cancelled, although the impact was mitigated by new models of delivery. While the scale of disruption has been studied, much less is known about if this disruption impacted health outcomes. The aim of our paper is to examine whether there is an association between individuals experiencing disrupted access to healthcare during the pandemic and risk of an avoidable hospitalisation.

Methods

We used individual-level data for England from seven longitudinal cohort studies linked to electronic health records from NHS Digital (n = 29 276) within the UK Longitudinal Linkage Collaboration trusted research environment. Avoidable hospitalisations were defined as emergency hospital admissions for ambulatory care sensitive and emergency urgent care sensitive conditions (1 st March 2020 to 25 th August 2022). Self-reported measures of whether people had experienced disruption during the pandemic to appointments (e.g., visiting their GP or an outpatient department), procedures (e.g., surgery, cancer treatment) or medications were used as our exposures. Logistic regression models examined associations.

Results

35% of people experienced some form of disrupted access to healthcare. Those whose access was disrupted were at increased risk of any (Odds Ratio (OR) = 1.80, 95% Confidence Intervals (CIs) = 1.34-2.41), acute (OR = 1.68, CIs = 1.13-2.53) and chronic (OR = 1.93, CIs = 1.40-2.64) ambulatory care sensitive hospital admissions. There were positive associations between disrupted access to appointments and procedures to measures of avoidable hospitalisations as well.

Conclusions

Our study presents novel evidence from linked individual-level data showing that people whose access to healthcare was disrupted were more likely to have an avoidable or potentially preventable hospitalisation. Our findings highlight the need to increase healthcare investment to tackle the short- and long-term implications of the pandemic beyond directly dealing with SARS-CoV-2 infections.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/02/02/2023.02.01.23285333.full.pdf; doi:https://doi.org/10.1101/2023.02.01.23285333; html:https://europepmc.org/article/PPR/PPR611882; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR611882&type=FILE&fileName=EMS164989-pdf.pdf&mimeType=application/pdf @@ -321,8 +321,8 @@ PPR408531,https://doi.org/10.1101/2021.10.18.21265046,Comparative assessment of PPR496265,https://doi.org/10.1101/2022.05.10.22274890,Biopsychosocial response to the COVID-19 lockdown in people with major depressive disorder and multiple sclerosis,"Siddi S, Giné-Vázquez I, Bailon R, Matcham F, Lamers F, Kontaxis S, Laporta E, Garcia E, Arranz B, Dalla Costa G, Guerrero Pérez A, Zabalza A, Buron M, Comi G, Leocani L, Annas P, Hotopf M, Penninx B, Magyari M, Sørensen PS, Montalban X, Lavelle G, Ivan A, Oetzmann C, White MK, Difrancesco S, Locatelli P, Mohr D, Aguiló J, Narayan V, Folarin A, Dobson R, Dineley J, Leightley D, Cummins N, Vairavan S, Ranjan Y, Rashid Z, Rintala A, De Girolamo G, Preti A, Simblett S, Wykes T, Myin-Germeys I, Haro J, PAB members.",,No Journal Info,2022,2022-05-10,N,,,,"

ABSTRACT

Background

Changes in lifestyle, finances and work status during COVID-19 lockdowns may have led to biopsychosocial changes in people with pre-existing vulnerabilities such as Major Depressive Disorders (MDD) and Multiple Sclerosis (MS).

Methods

Data were collected as a part of the RADAR-CNS (Remote Assessment of Disease and Relapse – Central Nervous System) programme. We analyzed the following data from long-term participants in a decentralized multinational study: symptoms of depression, heart rate (HR) during the day and night; social activity; sedentary state, steps and physical activity of varying intensity. Linear mixed-effects regression analyses with repeated measures were fitted to assess the changes among three time periods (pre, during and post-lockdown) across the groups, adjusting for depression severity before the pandemic and gender.

Results

Participants with MDD (N=255) and MS (N=214) were included in the analyses. Overall, depressive symptoms remained stable across the three periods in both groups. Lower mean HR and HR variation were observed between pre and during lockdown during the day for MDD and during the night for MS. HR variation during rest periods also decreased between pre-and post-lockdown in both clinical conditions. We observed a reduction of physical activity for MDD and MS upon the introduction of lockdowns. The group with MDD exhibited a net increase in social interaction via social network apps over the three periods.

Conclusions

Behavioral response to the lockdown measured by social activity, physical activity and HR may reflect changes in stress in people with MDD and MS.",,pdf:https://ddd.uab.cat/pub/artpub/2022/271957/271957.pdf; doi:https://doi.org/10.1101/2022.05.10.22274890; html:https://europepmc.org/article/PPR/PPR496265; doi:https://doi.org/10.1101/2022.05.10.22274890 PPR341253,https://doi.org/10.1101/2021.05.18.21257267,"Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial","RECOVERY Collaborative Group, Horby PW, Campbell M, Spata E, Emberson JR, Emberson JR, Staplin N, Pessoa-Amorim G, Peto L, Wiselka M, Wiffen L, Tiberi S, Caplin B, Wroe C, Green C, Hine P, Prudon B, George T, Wight A, Baillie JK, Basnyat B, Buch MH, Chappell LC, Day JN, Faust SN, Hamers RL, Jaki T, Juszczak E, Jeffery K, Lim WS, Montgomery A, Mumford A, Rowan K, Thwaites G, Mafham M, Haynes R, Landray MJ.",,No Journal Info,2021,2021-05-18,Y,,,,"

SUMMARY

Background

Colchicine has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory actions.

Methods

In this randomised, controlled, open-label trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus colchicine twice daily for 10 days or until discharge (or one of the other treatment arms) using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov ( NCT04381936 ).

Findings

Between 27 November 2020 and 4 March 2021, 5610 patients were randomly allocated to receive colchicine and 5730 patients to receive usual care alone. Overall, 1173 (21%) patients allocated to colchicine and 1190 (21%) patients allocated to usual care died within 28 days (rate ratio 1.01; 95% confidence interval [CI] 0.93-1.10; p=0.77). Consistent results were seen in all pre-specified subgroups of patients. There was no significant difference in duration of hospitalisation (median 10 days vs. 10 days) or the proportion of patients discharged from hospital alive within 28 days (70% vs. 70%; rate ratio 0.98; 95% CI 0.94-1.03; p=0.44). Among those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (25% vs. 25%; risk ratio 1.02; 95% CI 0.96-1.09; p=0.47).

Interpretation

In adults hospitalised with COVID-19, colchicine was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056). Wellcome Trust (Grant Ref: 222406/Z/20/Z) through the COVID-19 Therapeutics Accelerator.",,pdf:https://discovery.ucl.ac.uk/10138014/1/1-s2.0-S2213260021004355-main.pdf; doi:https://doi.org/10.1101/2021.05.18.21257267; html:https://europepmc.org/article/PPR/PPR341253; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR341253&type=FILE&fileName=EMS129811-pdf.pdf&mimeType=application/pdf PPR203834,https://doi.org/10.1101/2020.08.17.20175117,Real-time spatial health surveillance: mapping the UK COVID-19 epidemic,"Fry R, Hollinghurst J, R Stagg H, A Thompson D, Fronterre C, Orton C, A Lyons R, V Ford D, Sheikh A, J Diggle P.",,No Journal Info,2020,2020-08-21,Y,,,,"The COVID-19 pandemic has highlighted the need for robust data linkage systems and methods for identifying outbreaks of disease in near real-time. Using self-reported app data and the Secure Anonymised Information Linkage (SAIL) Databank, we demonstrate the use of sophisticated spatial modelling for near-real-time prediction of COVID-19 prevalence at small-area resolution to inform strategic government policy areas. A pre-requisite to an effective control strategy is that predictions need to be accompanied by estimates of their precision, to guard against over-reaction to potentially spurious features of ‘best guess’ predictions. In the UK, important emerging risk-factors such as social deprivation or ethnicity vary over small distances, hence risk needs to be modelled at fine spatial resolution to avoid aggregation bias. We demonstrate that existing geospatial statistical methods originally developed for global health applications are well-suited to this task and can be used in an anonymised databank environment, thus preserving the privacy of the individuals who contribute their data.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa55271/Download/55271__19477__8ee05d6fecff47d6a9e21d2b84e5de22.pdf; doi:https://doi.org/10.1101/2020.08.17.20175117; html:https://europepmc.org/article/PPR/PPR203834; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR203834&type=FILE&fileName=EMS95676-pdf.pdf&mimeType=application/pdf -PPR721144,https://doi.org/10.1101/2023.09.04.23295015,Combinations of multiple long-term conditions and risk of hospitalisation and death during the winter season: population-based study of 48 million people in England,"Islam N, Shabnam S, Khan N, Gillies C, Zaccardi F, Banerjee A, Nafilyan V, Khunti K, Dambha-Miller H.",,No Journal Info,2023,2023-09-06,Y,,,,"

Background

The annual winter season poses substantial challenges to the National Health Service (NHS) in England. Hospitalisation and mortality increase during winter, especially in people with multiple long-term conditions (MLTC or multimorbidity). We aimed to describe which combinations of long-term conditions (LTC) are associated with a higher risk of hospitalisation and death during winter amongst adults in England.

Methods

In this population-based study, we used linked primary and secondary care data from the General Practice Extraction Service Data for Pandemic Planning (GDPPR) database, Hospital Episode Statistics, and Office for National Statistics death registry. We included individuals aged ≥18 years and alive on 1 st December 2021 and used overdispersed Poisson models to estimate the incidence rate ratios of all-cause hospitalisations and deaths associated with the combinations of MLTCs – compared to those with no LTC – during the winter season (1 December 2021 to 31 March 2022).

Findings

Complete data were available for 48,253,125 adults, of which 15 million (31.2%) had MLTC. Hospitalisation per 1000 person-years was higher in individuals with MLTCs, and varied by combination, e.g.: 96, 1643, and 1552 in individuals with no LTC, cancer+chronic kidney disease (CKD)+cardiovascular disease (CVD)+type 2 diabetes mellitus, and cancer+CKD+CVD+osteoarthritis, respectively. Incidence of death (per 1000 person-years) was 345 in individuals with cancer+CKD+CVD+dementia and 1 with no LTC. CVD+dementia appeared in all the top five MLTC combinations by death and was associated with a substantially higher rate of death than many 3-, 4- and 5-disease combinations.

Interpretation

Risks of hospitalisation and death vary by combinations of MLTCs and are substantially higher in those with vs. without any LTCs. We have highlighted high-risk combinations for prioritisation and preventive action by policymakers to help manage the challenges imposed by winter pressures on the NHS.

Funding

National Institute for Health and Care Research (NIHR) through Health Data Research UK rapid funding call for the research activity “Data Science to inform NHS compound winter pressure policy response” (grant number: HDRUK2022.0313)

Research in context

Evidence before this study

We searched PubMed, from inception to April 2023, for published population-based studies examining MLTC combinations in cohorts of adults aged 18 years and over. The search terms were “multimorbidity” or ‘’multiple-long-term conditions’’ alongside “groups” or “combinations”. We found no previous studies examining MLTC in relation to death or hospitalisation during the winter season.

Added value of this study

We have identified distinct combinations of LTCs and estimated the associated risk of hospitalisation and deaths during the winter season using the whole-population primary and secondary care data in England.

Implications of all the available evidence

Understanding which combinations of MLTCs are associated with the highest risk of hospitalisation and death allows clinicians and policymakers to prioritise resources for preventative measures, such as vaccination to those that will benefit most during winter seasons.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/09/06/2023.09.04.23295015.full.pdf; doi:https://doi.org/10.1101/2023.09.04.23295015; html:https://europepmc.org/article/PPR/PPR721144; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR721144&type=FILE&fileName=EMS187607-pdf.pdf&mimeType=application/pdf PPR362014,https://doi.org/10.2139/ssrn.3864079,Indirect Effects of the COVID-19 Pandemic on Childhood Infection in England: A Population Based Observational Study,"Kadambari S, Goldacre R, Morris E, Goldacre M, Pollard A.",,No Journal Info,2021,2021-06-21,N,,,,"Background: Children are largely unaffected following Sars-CoV-2 infection with low rates of significant disease and the inflammatory syndrome MIS-C. However, the lives of children have been substantially disrupted by the pandemic through physical distancing measures and the impact on health systems and economies. In this study, the impact of the COVID-19 pandemic on hospital admissions for childhood respiratory infections, severe invasive infections, and vaccine preventable disease in England was assessed along with associated mortality outcomes.

Methods: In this population-based observational study, we examined hospital admission data from every National Health Service hospital from Mar 1 2017 to Feb 28 2021. We report monthly and annual numbers of individuals hospitalised with 19 common childhood respiratory, severe invasive, and vaccine preventable infections. We compare the frequency of admissions for these conditions before and after the onset of the pandemic in England and calculate percentage changes since Mar 1 2020 for each infection overall and by demographic characteristics including age, region, deprivation, and comorbidity, and quantify mortality outcomes.

Findings: In the 12 months from Mar 1 2020, there were significant reductions compared with the preceding 36 months in the numbers of children admitted for every infection studied except pyelonephritis. These reductions were seen in all geographic regions, Index of Multiple Deprivation categories, ethnic groups and in those with underlying comorbidities. Among the respiratory infections, the greatest percentage reductions were for influenza where the number of individuals admitted decreased by 94% (95% CI 88, 97) from 5,061 (annual mean from Mar 1 2017 - Feb 29 2020) to 290 in the 12 months after Mar 1 2020, and for bronchiolitis where the number of individuals admitted decreased by over 80% (95% CI 78, 83) from 41,777 (annual mean 2017–2020) to 7,883 in 2020-21. Among the severe invasive infections, percentage decreases ranged from 20% (95% CI 13, 26) for osteomyelitis to 54% (95% CI 51, 56) for meningitis. Among the vaccine preventable infections, the greatest reduction was for measles, where the number of individuals admitted in the 12 months after Mar 1 2020 (n=12) was 92% lower (95% CI 84, 96) than the average number admitted in the previous three years (n=143). Admissions for Neisseria meningitidis decreased by 70% (95% CI 55, 80), and admissions for Streptococcus pneumoniae, Haemophilus influenzae and mumps more than halved. Alongside the decreases in admissions, there were also decreases in the absolute numbers of 60-day fatalities after admission for sepsis, meningitis, bronchiolitis, pneumonia, viral wheeze and upper respiratory tract infection (RTI). For pneumonia, although the absolute number of 60-day fatalities decreased (from a 3-year average of 159 to 115 after Mar 1 2020), the proportion of individuals admitted who died within 60 days increased (age-sex adjusted odds ratio 1.73, 95% CI 1.42, 2.11).

Interpretation: During the COVID-19 pandemic, a range of behavioural changes (adoption of non-pharmacological interventions (NPIs)) and societal strategies (school closures, lockdowns and restricted travel) were used to reduce transmission of SARS CoV2 which have also significantly reduced transmission of common and severe childhood infections. NPIs could be used in the future to better protect healthcare systems and the most vulnerable children in society.

Funding Information: Public Health England, Health Data Research UK, and the National Institute for Health Research Oxford Biomedical Research Centre.

Declaration of Interests: None to declare.

Ethics Approval Statement: Ethical approval to study the record-linked datasets was obtained from the Central and South Bristol Multi-Centre Research Ethics Committee (04/Q2006/176). All patient records were pseudonymized by the data providers through encryption of personal identifiers.",,pdf:https://discovery.ucl.ac.uk/10158356/1/Indirect%20effects%20of%20the%20covid-19%20pandemic%20on%20childhood%20infection%20in%20England%20population%20based%20observational%20study.pdf; doi:https://doi.org/10.2139/ssrn.3864079; html:https://europepmc.org/article/PPR/PPR362014; doi:https://doi.org/10.2139/ssrn.3864079 +PPR721144,https://doi.org/10.1101/2023.09.04.23295015,Combinations of multiple long-term conditions and risk of hospitalisation and death during the winter season: population-based study of 48 million people in England,"Islam N, Shabnam S, Khan N, Gillies C, Zaccardi F, Banerjee A, Nafilyan V, Khunti K, Dambha-Miller H.",,No Journal Info,2023,2023-09-06,Y,,,,"

Background

The annual winter season poses substantial challenges to the National Health Service (NHS) in England. Hospitalisation and mortality increase during winter, especially in people with multiple long-term conditions (MLTC or multimorbidity). We aimed to describe which combinations of long-term conditions (LTC) are associated with a higher risk of hospitalisation and death during winter amongst adults in England.

Methods

In this population-based study, we used linked primary and secondary care data from the General Practice Extraction Service Data for Pandemic Planning (GDPPR) database, Hospital Episode Statistics, and Office for National Statistics death registry. We included individuals aged ≥18 years and alive on 1 st December 2021 and used overdispersed Poisson models to estimate the incidence rate ratios of all-cause hospitalisations and deaths associated with the combinations of MLTCs – compared to those with no LTC – during the winter season (1 December 2021 to 31 March 2022).

Findings

Complete data were available for 48,253,125 adults, of which 15 million (31.2%) had MLTC. Hospitalisation per 1000 person-years was higher in individuals with MLTCs, and varied by combination, e.g.: 96, 1643, and 1552 in individuals with no LTC, cancer+chronic kidney disease (CKD)+cardiovascular disease (CVD)+type 2 diabetes mellitus, and cancer+CKD+CVD+osteoarthritis, respectively. Incidence of death (per 1000 person-years) was 345 in individuals with cancer+CKD+CVD+dementia and 1 with no LTC. CVD+dementia appeared in all the top five MLTC combinations by death and was associated with a substantially higher rate of death than many 3-, 4- and 5-disease combinations.

Interpretation

Risks of hospitalisation and death vary by combinations of MLTCs and are substantially higher in those with vs. without any LTCs. We have highlighted high-risk combinations for prioritisation and preventive action by policymakers to help manage the challenges imposed by winter pressures on the NHS.

Funding

National Institute for Health and Care Research (NIHR) through Health Data Research UK rapid funding call for the research activity “Data Science to inform NHS compound winter pressure policy response” (grant number: HDRUK2022.0313)

Research in context

Evidence before this study

We searched PubMed, from inception to April 2023, for published population-based studies examining MLTC combinations in cohorts of adults aged 18 years and over. The search terms were “multimorbidity” or ‘’multiple-long-term conditions’’ alongside “groups” or “combinations”. We found no previous studies examining MLTC in relation to death or hospitalisation during the winter season.

Added value of this study

We have identified distinct combinations of LTCs and estimated the associated risk of hospitalisation and deaths during the winter season using the whole-population primary and secondary care data in England.

Implications of all the available evidence

Understanding which combinations of MLTCs are associated with the highest risk of hospitalisation and death allows clinicians and policymakers to prioritise resources for preventative measures, such as vaccination to those that will benefit most during winter seasons.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/09/06/2023.09.04.23295015.full.pdf; doi:https://doi.org/10.1101/2023.09.04.23295015; html:https://europepmc.org/article/PPR/PPR721144; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR721144&type=FILE&fileName=EMS187607-pdf.pdf&mimeType=application/pdf PPR670288,https://doi.org/10.1101/2023.05.31.23290774,POST-COVID ORTHOPAEDIC ELECTIVE RESOURCE PLANNING USING SIMULATION MODELLING,"Harper A, Monks T, Wilson R, Redaniel MT, Eyles E, Jones T, Penfold C, Elliott A, Keen T, Pitt M, Blom A, Whitehouse M, Judge A.",,No Journal Info,2023,2023-06-05,Y,,,,"

ABSTRACT

Objectives

To develop a simulation model to support orthopaedic elective capacity planning.

Methods

An open-source, generalisable discrete-event simulation was developed, including a web-based application. The model used anonymised patient records between 2016-2019 of elective orthopaedic procedures from an NHS Trust in England. In this paper, it is used to investigate scenarios including resourcing (beds and theatres) and productivity (lengths-of-stay, delayed discharges, theatre activity) to support planning for meeting new NHS targets aimed at reducing elective orthopaedic surgical backlogs in a proposed ring fenced orthopaedic surgical facility. The simulation is interactive and intended for use by health service planners and clinicians.

Results

A higher number of beds (65-70) than the proposed number (40 beds) will be required if lengths-of-stay and delayed discharge rates remain unchanged. Reducing lengths-of-stay in line with national benchmarks reduces bed utilisation to an estimated 60%, allowing for additional theatre activity such as weekend working. Further, reducing the proportion of patients with a delayed discharge by 75% reduces bed utilisation to below 40%, even with weekend working. A range of other scenarios can also be investigated directly by NHS planners using the interactive web app.

Conclusions

The simulation model is intended to support capacity planning of orthopaedic elective services by identifying a balance of capacity across theatres and beds and predicting the impact of productivity measures on capacity requirements. It is applicable beyond the study site and can be adapted for other specialties.

Strengths and Limitations of this study

The simulation model provides rapid quantitative estimates to support post-COVID elective services recovery toward medium-term elective targets. Parameter combinations include changes to both resourcing and productivity. The interactive web app enables intuitive parameter changes by users while underlying source code can be adapted or re-used for similar applications. Patient attributes such as complexity are not included in the model but are reflected in variables such as length-of-stay and delayed discharge rates. Theatre schedules are simplified, incorporating the five key orthopaedic elective surgical procedures.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/06/05/2023.05.31.23290774.full.pdf; doi:https://doi.org/10.1101/2023.05.31.23290774; html:https://europepmc.org/article/PPR/PPR670288; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR670288&type=FILE&fileName=EMS176961-pdf.pdf&mimeType=application/pdf PPR676615,https://doi.org/10.1101/2023.06.14.23291389,"Cohort Profile: Born in Wales - a birth cohort with maternity, parental, and child data linkage for life course research in Wales, UK","Jones H, Seaborne M, Kennedy N, James M, Dredge S, Bandyopadhyay A, Battaglia A, Davies S, Brophy S.",,No Journal Info,2023,2023-06-15,Y,,,,"

Purpose

Parental and neonatal child health and education records have been linked to provide an entire country birth cohort, to examine what will improve the health and wellbeing of families growing up in Wales. Established in 2020, Born in Wales utilised data linkage techniques to connect information from the 2011 census with health, social care, and education routine data in the Secure Anonymised Information Linkage (SAIL) Databank. We present the descriptive data available in the linked database, emphasise the robust data security and governance frameworks, and present the future expansion plans for the database beyond its initial development stage.

Participants

Descriptive information from 2011 to 2023 has been gathered from SAIL. This comprehensive dataset comprises over 400,000 child electronic records. To augment this data, the Born in Wales and primary school surveys have contributed quantitative and qualitative responses.

Findings to date

The cohort comprises all children born in Wales since 2011, with follow-up conducted until they finish primary school at age 11. 2,500 parents and 30,000 primary school children have been recruited for enhanced data collection and linkage to the data spine. The child cohort is 51%: 49% female: male, and 6% are from ethnic minority backgrounds. When considering age distribution, 26.8% of children are under the age of 5, while 63.2% fall within the age range of 5-11.

Future plans

Born in Wales will expand by 30,000 new births annually in Wales, while including follow-up data of children and parents already in the database. Supplementary datasets complement the existing linkage, including primary care, hospital data, educational attainment and social care. Future research includes exploring the long-term implications of COVID-19 on child health and development, the influence of environmental factors including climate change on health and examining the impact of parental work environment on child health and development.

Strengths and limitations of this study

Born in Wales has established a comprehensive, Wales-wide population-based database which consolidates clinical data from maternity, neonatal, child health, and education records. This national-scale database is supplemented by quantitative and qualitative results from surveys conducted by Born in Wales, providing rich insights into details that cannot be obtained through routinely collected data. The existence of this database enables further data linkage, facilitating life course research on the health and wellbeing of the Wales population. Missing data or errors in routine and administrative data may be constraint. A potential restriction of Born in Wales is the loss of data pertaining to individuals who relocate outside of Wales during pregnancy or after the child’s birth.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/06/15/2023.06.14.23291389.full.pdf; doi:https://doi.org/10.1101/2023.06.14.23291389; html:https://europepmc.org/article/PPR/PPR676615; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR676615&type=FILE&fileName=EMS177701-pdf.pdf&mimeType=application/pdf PPR302424,https://doi.org/10.1101/2021.03.19.21253940,"COVID-19 Infection Risk amongst 14,104 Vaccinated Care Home Residents: A national observational longitudinal cohort study in Wales, United Kingdom, December 2020 to March 2021","Hollinghurst J, North L, Perry M, Akbari A, Gravenor MB, Lyons RA, Fry R.",,No Journal Info,2021,2021-03-24,Y,,,,"

ABSTRACT

Background

Vaccinations for COVID-19 have been prioritised for older people living in care homes. However, vaccination trials included limited numbers of older people.

Aim

We aimed to study infection rates of SARS-CoV-2 for older care home residents following vaccination and identify factors associated with increased risk of infection.

Study Design and Setting

We conducted an observational data-linkage study including 14,104 vaccinated older care home residents in Wales (UK) using anonymised electronic health records and administrative data.

Methods

We used Cox proportional hazards models to estimate hazard ratios (HRs) for the risk of testing positive for SARS-CoV-2 infection following vaccination, after landmark times of either 7 or 21-days post-vaccination. We adjusted hazard ratios for age, sex, frailty, prior SARS-CoV-2 infections and vaccination type.

Results

We observed a small proportion of care home residents with positive PCR tests following vaccination 1.05% (N=148), with 90% of infections occurring within 28-days. For the 7-day landmark analysis we found a reduced risk of SARS-CoV-2 infection for vaccinated individuals who had a previous infection; HR (95% confidence interval) 0.54 (0.30,0.95), and an increased HR for those receiving the Pfizer-BioNTECH vaccine compared to the Oxford-AstraZeneca; 3.83 (2.45,5.98). For the 21-day landmark analysis we observed high HRs for individuals with low and intermediate frailty compared to those without; 4.59 (1.23,17.12) and 4.85 (1.68,14.04) respectively.

Conclusions

Increased risk of infection after 21-days was associated with frailty. We found most infections occurred within 28-days of vaccination, suggesting extra precautions to reduce transmission risk should be taken in this time frame.",,pdf:https://academic.oup.com/ageing/article-pdf/51/1/afab223/42083726/afab223.pdf; doi:https://doi.org/10.1101/2021.03.19.21253940; html:https://europepmc.org/article/PPR/PPR302424; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR302424&type=FILE&fileName=EMS120789-pdf.pdf&mimeType=application/pdf @@ -368,8 +368,8 @@ PPR538641,https://doi.org/10.1101/2022.08.29.22279351,Insights into COVID-19 epi PPR204757,https://doi.org/10.1101/2020.08.21.20167965,Implications of the school-household network structure on SARS-CoV-2 transmission under different school reopening strategies in England,"Munday JD, Sherratt K, Meakin S, Endo A, Pearson CAB, Hellewell J, Abbott S, Bosse NI, Atkins KE, Wallinga J, Edmunds WJ, van Hoek AJ, Funk S, CMMID COVID 1-9 Working Group.",,No Journal Info,2020,2020-08-24,Y,,,,"

Background

School closures are a well-established non-pharmaceutical intervention in the event of infectious disease outbreaks, and have been implemented in many countries across the world, including the UK, to slow down the spread of SARS-CoV-2. As governments begin to relax restrictions on public life there is a need to understand the potential impact that reopening schools may have on transmission.

Methods

We used data provided by the UK Department for Education to construct a network of English schools, connected through pairs of pupils resident at the same address. We used the network to evaluate the potential for transmission between schools, and for long range propagation across the network, under different reopening scenarios.

Results

Amongst the options evaluated we found that reopening only Reception, Year 1 and Year 6 (4-6 and 10-11 year olds) resulted in the lowest risk of transmission between schools, with outbreaks within a single school unlikely to result in outbreaks in adjacent schools in the network. The additional reopening of Years 10 and 12 (14-15 and 16-17 year olds) resulted in an increase in the risk of transmission between schools comparable to reopening all primary school years (4-11 year olds). However, the majority of schools presented low risk of initiating widespread transmission through the school system. Reopening all secondary school years (11-18 year olds) resulted in large potential outbreak clusters putting up to 50% of households connected to schools at risk of infection if sustained transmission within schools was possible.

Conclusions

Reopening secondary school years is likely to have a greater impact on community transmission than reopening primary schools in England. Keeping transmission within schools limited is essential for reducing the risk of large outbreaks amongst school-aged children and their household members.",,pdf:https://www.nature.com/articles/s41467-021-22213-0.pdf; doi:https://doi.org/10.1101/2020.08.21.20167965; html:https://europepmc.org/article/PPR/PPR204757; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR204757&type=FILE&fileName=EMS95596-pdf.pdf&mimeType=application/pdf PPR530179,https://doi.org/10.1101/2022.08.08.22278493,Inequalities in colorectal cancer screening uptake in Wales: an examination of the impact of the temporary suspension of the screening programme during the COVID-19 pandemic,"Bright D, Hillier S, Song J, Huws DW, Greene G, Hodgson K, Akbari A, Griffiths R, Davies AR, Gjini A.",,No Journal Info,2022,2022-08-09,Y,,,,"

Background

Response to the early stages of the COVID-19 pandemic resulted in the temporary disruption of cancer screening in the UK, and strong public messaging to stay safe and to protect NHS capacity. Following reintroduction in services, we explored the impact on inequalities in uptake of the Bowel Screening Wales (BSW) programme to identify groups who may benefit from tailored interventions.

Methods

Records within the BSW were linked to electronic health records (EHR) and administrative data within the Secured Anonymised Information Linkage (SAIL) Databank. Ethnic group was obtained from a linked data method available within SAIL. We examined uptake for the first 3 months of invitations (August to October) following the reintroduction of BSW programme in 2020, compared to the same period in the preceding 3 years. Uptake was measured across a 6 month follow-up period. Logistic models were conducted to analyse variations in uptake by sex, age group, income deprivation quintile, urban/rural location, ethnic group, and clinically extremely vulnerable (CEV) status in each period; and to compare uptake within sociodemographic groups between different periods.

Results

Uptake during August to October 2020 (period 2020/21; 60.4%) declined compared to the same period in 2019/20 (62.7%) but remained above the 60% Welsh standard. Variation by sex, age, income deprivation, and ethnic groups was observed in all periods studied. Compared to the pre-pandemic period in 2019/20, uptake declined for most demographic groups, except for older individuals (70-74 years) and those in the most income deprived group. Uptake continues to be lower in males, younger individuals, people living in the most income deprived areas and those of Asian and unknown ethnic backgrounds.

Conclusions

Our findings are encouraging with overall uptake achieving the 60% Welsh standard during the first three months after the programme restarted in 2020 despite the disruption. Inequalities did not worsen after the programme resumed activities but variations in CRC screening in Wales associated with sex, age, deprivation and ethnicity remain. This needs to be considered in targeting strategies to improve uptake and informed choice in CRC screening to avoid exacerbating disparities in CRC outcomes as screening services recover from the pandemic.",,pdf:https://orca.cardiff.ac.uk/id/eprint/157897/1/12889_2023_Article_15345.pdf; doi:https://doi.org/10.1101/2022.08.08.22278493; html:https://europepmc.org/article/PPR/PPR530179; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR530179&type=FILE&fileName=EMS152515-pdf.pdf&mimeType=application/pdf PPR393011,https://doi.org/10.1101/2021.09.03.21262888,Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune modifying therapies: a nationwide cohort study in the OpenSAFELY platform,"MacKenna B, Kennedy NA, Mehkar A, Rowan A, Galloway J, Mansfield KE, Bechman K, Matthewman J, Yates M, Brown J, Schultze A, Norton S, Walker AJ, Morton CE, Harrison D, Bhaskaran K, Rentsch CT, Williamson E, Croker R, Bacon S, Hickman G, Ward T, Davy S, Green A, Fisher L, Hulme W, Bates C, Curtis HJ, Tazare J, Eggo RM, Evans D, Inglesby P, Cockburn J, McDonald HI, Tomlinson LA, Mathur R, Wong AY, Forbes H, Parry J, Hester F, Harper S, Douglas IJ, Smeeth L, Lees CW, Evans SJ, Goldacre B, Smith C, Langan SM.",,No Journal Info,2021,2021-09-10,N,,,,"

ABSTRACT

Background

It is unclear if people with immune-mediated inflammatory diseases (IMIDs) (joint, bowel and skin) and on immune modifying therapy have increased risk of serious COVID-19 outcomes.

Methods

With the approval of NHS England we conducted a cohort study, using OpenSAFELY, analysingroutinely-collected primary care data linked to hospital admission, death and previously unavailable hospital prescription data. We used Cox regression (adjusting for confounders) to estimate hazard ratios (HR) comparing risk of COVID-19-death, death/critical care admission, and hospitalisation (March to September 2020) in: 1) people with IMIDs compared to the general population; and 2) people with IMIDs on targeted immune modifying drugs (e.g., biologics) compared to standard systemic treatment (e.g., methotrexate).

Findings

We identified 17,672,065 adults; of 1,163,438 (7%) with IMIDs, 19,119 people received targeted immune modifying drugs, and 200,813 received standard systemics. We saw evidence of increased COVID-19-death (HR 1.23, 95%CI 1.20, 1.27), and COVID-19 hospitalisation (HR 1.32, 95%CI 1.29, 1.35) in individuals with IMIDs overall compared to individuals without IMIDs of the same age, sex, deprivation and smoking status. We saw no evidence of increased COVID-19 deaths with targeted compared to standard systemic treatments (HR 1.03, 95%CI 0.80, 1.33). There was no evidence of increased COVID-19-related death in those prescribed TNF inhibitors, IL-12/23, IL7, IL-6 or JAK inhibitors compared to standard systemics. Rituximab was associated with increased COVID-19 death (HR 1.68, 95%CI 1.11, 2.56); however, this finding may relate to confounding.

Interpretation

COVID-19 death and hospitalisation was higher in people with IMIDs. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune modifying drugs for IMIDs compared to standard systemics.

RESEARCH IN CONTEXT

Evidence before this study

We searched PubMed on May 19 th , 2021, using the terms “COVID-19”, “SARS-CoV-2” and “rheumatoid arthritis”, “psoriatic arthritis” “ankylosing spondylitis”, “Crohn’s disease” “ulcerative colitis” “hidradenitis suppurativa” and “psoriasis”, to identify primary research articles examining severe COVID-19 outcome risk in individuals with immune-mediated inflammatory diseases (IMIDs) and those on immune modifying therapy. The studies identified (including matched cohort studies and studies in disease-specific registries) were limited by small sample sizes and number of outcomes. Most studies did not show a signal of increased adverse COVID-19 outcomes in those on targeted therapies, with the exception of rituximab. Additionally, disease-specific registries are subject to selection bias and lack denominator populations.

Added value of the study

In our large population-based study of 17 million individuals, including 1 million people with IMIDs and just under 200,000 receiving immune modifying medications, we saw evidence that people with IMIDs had an increased risk of COVID-19-related death compared to the general population after adjusting for potential confounders (age, sex, deprivation, smoking status) (HR 1.23, 95%CI 1.20, 1.27). We saw differences by IMID type, with COVID-19-related death being increased by the most in people with inflammatory joint disease (HR 1.47, 95%CI 1.40, 1.54). We also saw some evidence that those with IMIDs were more likely, compared to the general population, to have COVID-19-related critical care admission/death (HR 1.24, 95%CI 1.21, 1.28) and hospitalisation (HR 1.32, 95%CI 1.29, 1.35). Compared to people with IMIDs taking standard systemics, we saw no evidence of differences in severe COVID-19-related outcomes with TNF inhibitors, IL-17 inhibitors, IL-12/23 inhibitors, IL-6 inhibitors and JAK inhibitors. However, there was some evidence that rituximab was associated with an increased risk of COVID-19-related death (HR 1.68, 95%CI 1.11, 2.56) and death/critical care admission (HR 1.92, 95%CI 1.31, 2.81). We also saw evidence of an increase in COVID-19-related hospital admissions in people prescribed rituximab (HR 1.59, 95%CI 1.16, 2.18) or JAK inhibition (HR 1.81, 95%CI 1.09, 3.01) compared to those on standard systemics, although this could be related to worse underlying health rather than the drugs themselves, and numbers of events were small. This is the first study to our knowledge to use high-cost drug data on medicines supplied by hospitals at a national scale in England (to identify targeted therapies). The availability of these data fills an important gap in the medication record of those with more specialist conditions treated by hospitals creating an important opportunity to generate insights to these conditions and these medications

Implications of all of the available evidence

Our study offers insights into future risk mitigation strategies and SARS-CoV-2 vaccination priorities for individuals with IMIDs, as it highlights that those with IMIDs and those taking rituximab may be at risk of severe COVID-19 outcomes. Critically, our study does not show a link between most targeted immune modifying medications compared to standard systemics and severe COVID-19 outcomes. However, the increased risk of adverse COVID-19 outcomes that we saw in people with IMIDs and those treated with rituximab merits further study.",,pdf:https://qmro.qmul.ac.uk/xmlui/bitstream/123456789/83106/2/Mathur%20Risk%20of%20severe%20COVID-19%20outcomes%20associated%20with%20immune-mediated%20inflammatory%20diseases%20and%20immune-modifying%20therapies%3a%20a%20nationwide%20cohort%20study%20in%20the%20OpenSAFELY%20platform%202022%20Published.pdf; doi:https://doi.org/10.1101/2021.09.03.21262888; html:https://europepmc.org/article/PPR/PPR393011; doi:https://doi.org/10.1101/2021.09.03.21262888 -PPR609122,https://doi.org/10.1101/2023.01.25.23285005,Call detail record aggregation methodology impacts infectious disease models informed by human mobility,"Gibbs H, Musah A, Seidu O, Ampofo W, Asiedu-Bekoe F, Gray J, Adewole WA, Cheshire J, Marks M, Eggo RM.",,No Journal Info,2023,2023-01-28,Y,,,,"This paper demonstrates how two different methods used to calculate population-level mobility from Call Detail Records (CDR) produce varying predictions of the spread of epidemics informed by these data. Our findings are based on one CDR dataset describing inter-district movement in Ghana in 2021, produced using two different aggregation methodologies. One methodology, “all pairs,” is designed to retain long distance network connections while the other, “sequential” methodology is designed to accurately reflect the volume of travel between locations. We show how the choice of methodology feeds through models of human mobility to the predictions of a metapopulation SEIR model of disease transmission. We also show that this impact varies depending on the location of pathogen introduction and transmissibility. For central locations or highly transmissible diseases, we do not observe significant differences between aggregation methodologies on the predicted spread of disease. For less transmissible diseases or those introduced into remote locations, we find that the choice of aggregation methodology influences the speed of spatial spread as well as the size of the peak number of infections in individual districts. Our findings can help researchers and users of epidemiological models to understand how methodological choices at the level of model inputs may influence the results of models of infectious disease transmission, as well as the circumstances in which these choices do not alter model predictions.

Author Summary

Predicting the sub-national spread of infectious disease requires accurate measurements of inter-regional travel networks. Often, this information is derived from the patterns of mobile device connections to the cellular network. This travel data is then used as an input to epidemiological models of infection transmission, defining the likelihood that disease is “exported” between regions. In this paper, we use one mobile device dataset collected in Ghana in 2021, aggregated according to two different methodologies which represent different aspects of inter-regional travel. We show how the choice of aggregation methodology leads to different predicted epidemics, and highlight the conditions under which models of infection transmission may be influenced by methodological choices in the aggregation of travel data used to parameterize these models. For example, we show how aggregation methodology changes predicted epidemics for less-transmissible infections and under certain models of human movement. We also highlight areas of relative stability, where aggregation choices do not alter predicted epidemics, such as cases where an infection is highly transmissible or is introduced into a central location.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1011368&type=printable; doi:https://doi.org/10.1101/2023.01.25.23285005; html:https://europepmc.org/article/PPR/PPR609122; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR609122&type=FILE&fileName=EMS163650-pdf.pdf&mimeType=application/pdf PPR602738,https://doi.org/10.2139/ssrn.4023214,Challenging the Cultures of Racism at Work in the UK's Healthcare Sector,"Ramamurthy A, Bhabhbro S, Bruce F, Gumber A, Fero K.",,No Journal Info,2022,2022-02-01,N,,,,"Background: In UK’s health care sector, racism is rampant. It impacts Black and Brown staff working in NHS at all levels. We aimed to explore and understand the stories and experiences of Black and Brown health care staff during the pandemic and previously in their working lives.

Methods: We conducted a questionnaire survey and qualitative interviews with Black and Brown nurses, midwives and other healthcare staff. 308 respondents completed an online survey, and 45 people participated in the narrative interviews. Interviewees were contacted through meetings organised with several BME health and social care professional networks and the survey. In total, 353 Black and Brown staff members participated. The Critical Race Theory informed the data collection and analysis of the study.

Findings: The study findings report that racism is prevalent in the health and social care sector, and it is usually unreported. Most participants worked during the pandemic and reported experiences of racism before and during it. Our survey findings revealed that 52.6% of the Black and Brown staff experienced unfair treatment in the pandemic concerning Covid deployment, PPE or risk assessment provision. Similarly, 59% had experienced racism during their working lives, making it difficult to do their job; thus, 36% had left a job. Most participants reported that exclusion and neglect as a form of bullying were among the most widely recounted experiences that took a toll on their lives; for example, 53% said racism had impacted their mental health.

Interpretation: Our research underscores that the endemic culture of racism is a fundamental factor that must be recognised and called out. Colourblindness exacerbates racist practices. We argue that only implementing an active zero tolerance to racism policy with penalties for organisations that do not comply can change the status quo.

Funding Information: This work was supported by the Arts and Humanities Research Council, UK [AH/V008714/1, 2020].

Declaration of Interests: All authors declare no conflict of interest.

Ethics Approval Statement: Ethics approval was obtained by Sheffield Hallam University Research Ethics Committee.
",,pdf:http://shura.shu.ac.uk/30208/1/SSRN-id4023214%20%281%29.pdf; doi:https://doi.org/10.2139/ssrn.4023214; html:https://europepmc.org/article/PPR/PPR602738; doi:https://doi.org/10.2139/ssrn.4023214 +PPR609122,https://doi.org/10.1101/2023.01.25.23285005,Call detail record aggregation methodology impacts infectious disease models informed by human mobility,"Gibbs H, Musah A, Seidu O, Ampofo W, Asiedu-Bekoe F, Gray J, Adewole WA, Cheshire J, Marks M, Eggo RM.",,No Journal Info,2023,2023-01-28,Y,,,,"This paper demonstrates how two different methods used to calculate population-level mobility from Call Detail Records (CDR) produce varying predictions of the spread of epidemics informed by these data. Our findings are based on one CDR dataset describing inter-district movement in Ghana in 2021, produced using two different aggregation methodologies. One methodology, “all pairs,” is designed to retain long distance network connections while the other, “sequential” methodology is designed to accurately reflect the volume of travel between locations. We show how the choice of methodology feeds through models of human mobility to the predictions of a metapopulation SEIR model of disease transmission. We also show that this impact varies depending on the location of pathogen introduction and transmissibility. For central locations or highly transmissible diseases, we do not observe significant differences between aggregation methodologies on the predicted spread of disease. For less transmissible diseases or those introduced into remote locations, we find that the choice of aggregation methodology influences the speed of spatial spread as well as the size of the peak number of infections in individual districts. Our findings can help researchers and users of epidemiological models to understand how methodological choices at the level of model inputs may influence the results of models of infectious disease transmission, as well as the circumstances in which these choices do not alter model predictions.

Author Summary

Predicting the sub-national spread of infectious disease requires accurate measurements of inter-regional travel networks. Often, this information is derived from the patterns of mobile device connections to the cellular network. This travel data is then used as an input to epidemiological models of infection transmission, defining the likelihood that disease is “exported” between regions. In this paper, we use one mobile device dataset collected in Ghana in 2021, aggregated according to two different methodologies which represent different aspects of inter-regional travel. We show how the choice of aggregation methodology leads to different predicted epidemics, and highlight the conditions under which models of infection transmission may be influenced by methodological choices in the aggregation of travel data used to parameterize these models. For example, we show how aggregation methodology changes predicted epidemics for less-transmissible infections and under certain models of human movement. We also highlight areas of relative stability, where aggregation choices do not alter predicted epidemics, such as cases where an infection is highly transmissible or is introduced into a central location.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1011368&type=printable; doi:https://doi.org/10.1101/2023.01.25.23285005; html:https://europepmc.org/article/PPR/PPR609122; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR609122&type=FILE&fileName=EMS163650-pdf.pdf&mimeType=application/pdf PPR290155,https://doi.org/10.1101/2021.02.25.21252402,Racial and ethnic differences in COVID-19 vaccine hesitancy and uptake,"Nguyen LH, Joshi AD, Drew DA, Merino J, Ma W, Lo C, Kwon S, Wang K, Graham MS, Polidori L, Menni C, Sudre CH, Anyane-Yeboa A, Astley CM, Warner ET, Hu CY, Selvachandran S, Davies R, Nash D, Franks PW, Wolf J, Ourselin S, Steves CJ, Spector TD, Chan AT.",,No Journal Info,2021,2021-02-28,Y,,,,"

Background

Racial and ethnic minorities have been disproportionately impacted by COVID-19. In the initial phase of population-based vaccination in the United States (U.S.) and United Kingdom (U.K.), vaccine hesitancy and limited access may result in disparities in uptake.

Methods

We performed a cohort study among U.S. and U.K. participants in the smartphone-based COVID Symptom Study (March 24, 2020-February 16, 2021). We used logistic regression to estimate odds ratios (ORs) of COVID-19 vaccine hesitancy (unsure/not willing) and receipt.

Results

In the U.S. ( n =87,388), compared to White non-Hispanic participants, the multivariable ORs of vaccine hesitancy were 3.15 (95% CI: 2.86 to 3.47) for Black participants, 1.42 (1.28 to 1.58) for Hispanic participants, 1.34 (1.18 to 1.52) for Asian participants, and 2.02 (1.70 to 2.39) for participants reporting more than one race/other. In the U.K. ( n =1,254,294), racial and ethnic minorities had similarly elevated hesitancy: compared to White participants, their corresponding ORs were 2.84 (95% CI: 2.69 to 2.99) for Black participants, 1.66 (1.57 to 1.76) for South Asian participants, 1.84 (1.70 to 1.98) for Middle East/East Asian participants, and 1.48 (1.39 to 1.57) for participants reporting more than one race/other. Among U.S. participants, the OR of vaccine receipt was 0.71 (0.64 to 0.79) for Black participants, a disparity that persisted among individuals who specifically endorsed a willingness to obtain a vaccine. In contrast, disparities in uptake were not observed in the U.K.

Conclusions

COVID-19 vaccine hesitancy was greater among racial and ethnic minorities, and Black participants living in the U.S. were less likely to receive a vaccine than White participants. Lower uptake among Black participants in the U.S. during the initial vaccine rollout is attributable to both hesitancy and disparities in access.",,pdf:https://www.nature.com/articles/s41467-022-28200-3.pdf; doi:https://doi.org/10.1101/2021.02.25.21252402; html:https://europepmc.org/article/PPR/PPR290155; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR290155&type=FILE&fileName=EMS117911-pdf.pdf&mimeType=application/pdf PPR170310,https://doi.org/10.1101/2020.05.27.20083287,Estimating excess mortality in people with cancer and multimorbidity in the COVID-19 emergency,"Lai AG, Pasea L, Banerjee A, Denaxas S, Katsoulis M, Chang WH, Williams B, Pillay D, Noursadeghi M, Linch D, Hughes D, Forster MD, Turnbull C, Fitzpatrick NK, Boyd K, Foster GR, Cooper M, Jones M, Pritchard-Jones K, Sullivan R, Hall G, Davie C, Lawler M, Hemingway H.",,No Journal Info,2020,2020-06-01,Y,,,,"

Background:

Cancer and multiple non-cancer conditions are considered by the Centers for Disease Control and Prevention (CDC) as high risk conditions in the COVID-19 emergency. Professional societies have recommended changes in cancer service provision to minimize COVID-19 risks to cancer patients and health care workers. However, we do not know the extent to which cancer patients, in whom multi-morbidity is common, may be at higher overall risk of mortality as a net result of multiple factors including COVID-19 infection, changes in health services, and socioeconomic factors.

Methods:

We report multi-center, weekly cancer diagnostic referrals and chemotherapy treatments until April 2020 in England and Northern Ireland. We analyzed population-based health records from 3,862,012 adults in England to estimate 1-year mortality in 24 cancer sites and 15 non-cancer comorbidity clusters (40 conditions) recognized by CDC as high-risk. We estimated overall (direct and indirect) effects of COVID-19 emergency on mortality under different Relative Impact of the Emergency (RIE) and different Proportions of the population Affected by the Emergency (PAE). We applied the same model to the US, using Surveillance, Epidemiology, and End Results (SEER) program data.

Results:

Weekly data until April 2020 demonstrate significant falls in admissions for chemotherapy (45-66% reduction) and urgent referrals for early cancer diagnosis (70-89% reduction), compared to pre-emergency levels. Under conservative assumptions of the emergency affecting only people with newly diagnosed cancer (incident cases) at COVID-19 PAE of 40%, and an RIE of 1.5, the model estimated 6,270 excess deaths at 1 year in England and 33,890 excess deaths in the US. In England, the proportion of patients with incident cancer with ≥1 comorbidity was 65.2%. The number of comorbidities was strongly associated with cancer mortality risk. Across a range of model assumptions, and across incident and prevalent cancer cases, 78% of excess deaths occur in cancer patients with ≥1 comorbidity.

Conclusion:

We provide the first estimates of potential excess mortality among people with cancer and multimorbidity due to the COVID-19 emergency and demonstrate dramatic changes in cancer services. To better inform prioritization of cancer care and guide policy change, there is an urgent need for weekly data on cause-specific excess mortality, cancer diagnosis and treatment provision and better intelligence on the use of effective treatments for comorbidities.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/06/01/2020.05.27.20083287.full.pdf; doi:https://doi.org/10.1101/2020.05.27.20083287; html:https://europepmc.org/article/PPR/PPR170310; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR170310&type=FILE&fileName=EMS91512-pdf.pdf&mimeType=application/pdf PPR116550,https://doi.org/10.1101/2020.03.05.20031773,Estimating the infection and case fatality ratio for COVID-19 using age-adjusted data from the outbreak on the Diamond Princess cruise ship,"Russell TW, Hellewell J, Jarvis CI, Van Zandvoort K, Abbott S, Ratnayake R, Flasche S, Eggo RM, Edmunds WJ, Kucharski AJ, CMMID COVID-19 working group.",,No Journal Info,2020,2020-03-08,Y,,,,"Adjusting for delay from confirmation-to-death, we estimated case and infection fatality ratios (CFR, IFR) for COVID-19 on the Diamond Princess ship as 2.3% (0.75%–5.3%) and 1.2% (0.38–2.7%). Comparing deaths onboard with expected deaths based on naive CFR estimates using China data, we estimate IFR and CFR in China to be 0.5% (95% CI: 0.2–1.2%) and 1.1% (95% CI: 0.3–2.4%) respectively.

Aim

To estimate the infection and case fatality ratio of COVID-19, using data from passengers of the Diamond Princess cruise ship while correcting for delays between confirmation-and-death, and age-structure of the population.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/12/eurosurv-25-12-3.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.12.2000256&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.1101/2020.03.05.20031773; html:https://europepmc.org/article/PPR/PPR116550; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR116550&type=FILE&fileName=EMS89041-pdf.pdf&mimeType=application/pdf @@ -383,10 +383,10 @@ PPR269227,https://doi.org/10.1101/2021.01.15.21249756,Factors associated with de PPR450186,https://doi.org/10.1101/2022.02.03.22270306,Mental health in a diverse sample of healthcare workers during the COVID-19 pandemic: cross-sectional analysis of the UK-REACH study,"Melbourne CA, Guyatt AL, Nellums L, Papineni P, Papineni P, Gupta A, Qureshi I, Martin CA, Bryant L, John C, Gogoi M, Wobi F, Al-Oraibi A, Chaloner J, Aujayeb A, Gregary B, Lagrata S, Reza R, Simpson S, Zingwe S, Tobin M, Carr S, Khunti K, Gray LJ, McManus IC, Woolf K, Pareek M.",,No Journal Info,2022,2022-02-03,Y,,,,"

Objectives

To investigate how ethnicity and other sociodemographic, work, and physical health factors are related to mental health in UK healthcare and ancillary workers (HCWs), and how structural inequities in these factors may contribute to differences in mental health by ethnicity.

Design

Cross-sectional analysis of baseline data from the UK-REACH national cohort study

Setting

HCWs across UK healthcare settings.

Participants

11,695 HCWs working between December 2020-March 2021.

Main outcome measures

Anxiety or depression symptoms (4-item Patient Health Questionnaire, cut-off >3), and Post-Traumatic Stress Disorder (PTSD) symptoms (3-item civilian PTSD Checklist, cut-off >5).

Results

Asian, Black, Mixed/multiple and Other ethnic groups had greater odds of PTSD than the White ethnic group. Differences in anxiety/depression were less pronounced. Younger, female HCWs, and those who were not doctors had increased odds of symptoms of both PTSD and anxiety/depression. Ethnic minority HCWs were more likely to experience the following work factors that were also associated with mental ill-health: workplace discrimination, feeling insecure in raising workplace concerns, seeing more patients with COVID-19, reporting lack of access to personal protective equipment (PPE), and working longer hours and night shifts. Ethnic minority HCWs were also more likely to live in a deprived area and have experienced bereavement due to COVID-19. After adjusting for sociodemographic and work factors, ethnic differences in PTSD were less pronounced and ethnic minority HCWs had lower odds of anxiety/depression compared to White HCWs.

Conclusions

Ethnic minority HCWs were more likely to experience PTSD and disproportionately experienced work and sociodemographic factors associated with PTSD, anxiety and depression. These findings could help inform future work to develop workplace strategies to safeguard HCWs’ mental health. This will only be possible with adequate investment in staff recruitment and retention, alongside concerted efforts to address inequities due to structural discrimination.

Summary box

What is already known on this topic

The pandemic is placing healthcare workers under immense pressure, and there is currently a mental health crisis amongst NHS staff Ethnic inequities in health outcomes are driven by structural discrimination, which occurs inside and outside the workplace Investigating ethnic inequities in the mental health of healthcare workers requires large diverse studies, of which few exist

What this study adds

In UK-REACH (N=11,695), ethnic minority staff had higher odds of Post-Traumatic Stress Disorder symptoms; we report many other factors associated with mental-ill health, including those experienced disproportionately by ethnic minority staff, such as workplace discrimination, contact with more patients with COVID-19, and bereavement due to COVID-19 These findings underline the moral and practical need to care for staff mental health and wellbeing, which includes tackling structural inequities in the workplace; improving staff mental health may also reduce workforce understaffing due to absence and attrition",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/02/03/2022.02.03.22270306.full.pdf; doi:https://doi.org/10.1101/2022.02.03.22270306; html:https://europepmc.org/article/PPR/PPR450186; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR450186&type=FILE&fileName=EMS143503-pdf.pdf&mimeType=application/pdf PPR430732,https://doi.org/10.1101/2021.12.08.21267421,"Vaccine hesitancy for COVID-19 explored in a phenomic study of 259 socio-cognitive-behavioural measures in the UK-REACH study of 12,431 UK healthcare workers","McManus IC, Woolf K, Martin CA, Nellums LB, Guyatt AL, Melbourne C, Bryant L, Gupta A, John C, Tobin MD, Carr S, Simpson S, Gregary B, Aujayeb A, Zingwe S, Reza R, Gray LJ, Khunti K, Pareek M.",,No Journal Info,2021,2021-12-09,Y,,,,"

Background

Vaccination is key to successful prevention of COVID-19 particularly nosocomial acquired infection in health care workers (HCWs). ‘Vaccine hesitancy’ is common in the population and in HCWs, and like COVID-19 itself, hesitancy is more frequent in ethnic minority groups. UK-REACH (United Kingdom Research study into Ethnicity and COVID-19 outcomes) is a large-scale study of COVID-19 in UK HCWs from diverse ethnic backgrounds, which includes measures of vaccine hesitancy. The present study explores predictors of vaccine hesitancy using a ‘phenomic approach’, considering several hundred questionnaire-based measures.

Methods

UK-REACH includes a questionnaire study encompassing 12,431 HCWs who were recruited from December 2020 to March 2021 and completed a lengthy online questionnaire (785 raw items; 392 derived measures; 260 final measures). Ethnicity was classified using the Office for National Statistics’ five (ONS5) and eighteen (ONS18) categories. Missing data were handled by multiple imputation. Variable selection used the islasso package in R , which provides standard errors so that results from imputations could be combined using Rubin’s rules. The data were modelled using path analysis, so that predictors, and predictors of predictors could be assessed. Significance testing used the Bayesian approach of Kass and Raftery, a ‘very strong’ Bayes Factor of 150, N=12,431, and a Bonferroni correction giving a criterion of p<4.02 × 10 −8 for the main regression, and p<3.11 × 10 −10 for variables in the path analysis.

Results

At the first step of the phenomic analysis, six variables were direct predictors of greater vaccine hesitancy: Lower pro-vaccination attitudes; no flu vaccination in 2019-20; pregnancy; higher COVID-19 conspiracy beliefs; younger age; and lower optimism the roll-out of population vaccination. Overall 44 lower variables in total were direct or indirect predictors of hesitancy, with the remaining 215 variables in the phenomic analysis not independently predicting vaccine hesitancy. Key variables for predicting hesitancy were belief in conspiracy theories of COVID-19 infection, and a low belief in vaccines in general. Conspiracy beliefs had two main sets of influences: Higher Fatalism, which was influenced a) by high external and chance locus of control and higher need for closure, which in turn were associated with neuroticism, conscientiousness, extraversion and agreeableness; and b) by religion being important in everyday life, and being Muslim. receiving information via social media, not having higher education, and perceiving greater risks to self, the latter being influenced by higher concerns about spreading COVID, greater exposure to COVID-19, and financial concerns. There were indirect effects of ethnicity, mediated by religion. Religion was more important for Pakistani and African HCWs, and less important for White and Chinese groups. Lower age had a direct effect on hesitancy, and age and female sex also had several indirect effects on hesitancy.

Conclusions

The phenomic approach, coupled with a path analysis revealed a complex network of social, cognitive, and behavioural influences on SARS-Cov-2 vaccine hesitancy from 44 measures, 6 direct and 38 indirect, with the remaining 215 measures not having direct or indirect effects on hesitancy. It is likely that issues of trust underpin many associations with hesitancy. Understanding such a network of influences may help in tailoring interventions to address vaccine concerns and facilitate uptake in more hesistant groups.

Funding

UKMRI-MRC and NIHR",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/12/09/2021.12.08.21267421.full.pdf; doi:https://doi.org/10.1101/2021.12.08.21267421; html:https://europepmc.org/article/PPR/PPR430732; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR430732&type=FILE&fileName=EMS141669-pdf.pdf&mimeType=application/pdf PPR370776,https://doi.org/10.1101/2021.07.12.21260385,Estimating the effectiveness of first dose of COVID-19 vaccine against mortality in England: a quasi-experimental study,"Bermingham C, Morgan J, Ayoubkhani D, Glickman M, Islam N, Sheikh A, Sterne J, Walker AS, Nafilyan V.",,No Journal Info,2021,2021-07-16,Y,,,,"

Background

Estimating real-world vaccine effectiveness is vital to assess the impact of the vaccination programme on the pandemic and inform the ongoing policy response. However, estimating vaccine effectiveness using observational data is inherently challenging because of the non-randomised design and the potential for unmeasured confounding.

Methods

We used a Regression Discontinuity Design (RDD) to estimate vaccine effectiveness against COVID-19 mortality in England, exploiting the discontinuity in vaccination rates resulting from the UK’s age-based vaccination priority groups. We used the fact that people aged 80 or over were prioritised for the vaccine roll-out in the UK to compare the risk of COVID-19 and non-COVID-19 death in people aged 75–79 and 80–84.

Findings

The prioritisation of vaccination of people aged 80 or above led to a large discrepancy in vaccination rates in people 80–84 compared to those 75–79 at the beginning of the vaccination campaign. We found a corresponding difference in COVID-19 mortality, but not in non-COVID-19 mortality, suggesting that our approach appropriately addresses the issue of unmeasured confounding factors. Our results suggest that the first vaccine dose reduced the risk of COVID-19 death by 52.6% (95% Cl 26.6–84.2) in those aged 80.

Interpretations

Our results support existing evidence that a first dose of a COVID-19 vaccine has a strong protective effect against COVID-19 mortality in older adults. The RDD estimate of vaccine effectiveness is comparable to previously published studies using different methods, suggesting that unmeasured confounding factors are unlikely to substantially bias these studies.

Funding

Office for National Statistics.

Research in Context

Evidence before this study

We searched PubMed for studies reporting on the ‘real-world’ effectiveness of the COVID-19 vaccination on risk of death using terms such as “COVID-19”, “vaccine effectiveness”, “mortality” and “death”. The relevant published studies on this topic report vaccine effectiveness estimates against risk of death ranging from 64.2% to 98.7%, for varying times post-vaccination. All of these are observational studies and therefore potentially subject to bias from unmeasured confounding. We found no studies that used a quasi-experimental method such as regression discontinuity design, which is not subject to bias from unmeasured confounding, to calculate the effectiveness of the COVID-19 vaccination on risk of COVID-19 death, or on other outcomes such as hospitalisation or infection.

Added value of this study

The estimates of vaccine effectiveness based on observational data may be biased by unmeasured confounding. This study uses a regression discontinuity design to estimate vaccine effectiveness, exploiting the fact that the vaccination campaign in the UK was rolled out following age-based priority groups. This enables the calculation of an unbiased estimate of the effectiveness of the COVID-19 vaccine against risk of death. The vaccine effectiveness estimate of 52.6% (95% Cl 26.6–84.2) is slightly lower but similar to previously published estimates, therefore suggesting that these estimates are not substantially affected by unmeasured confounding factors and confirming the effectiveness of the COVID-19 vaccine against risk of COVID-19 death.

Implications of all the available evidence

Obtaining an unbiased estimate of COVID-19 vaccine effectiveness is of vital importance in informing policy for lifting COVID-19 related measures. The regression discontinuity design provides confidence that the existing estimates from observational studies are unlikely to be substantially biased by unmeasured confounding.",,pdf:https://research-information.bris.ac.uk/ws/files/345909877/kwac157.pdf; doi:https://doi.org/10.1101/2021.07.12.21260385; html:https://europepmc.org/article/PPR/PPR370776; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR370776&type=FILE&fileName=EMS130767-pdf.pdf&mimeType=application/pdf -PPR558613,https://doi.org/10.1101/2022.10.17.22281058,Eleven key measures for monitoring general practice clinical activity during COVID-19 using federated analytics on 48 million adults’ primary care records through OpenSAFELY,"Fisher L, Curtis HJ, Croker R, Wiedemann M, Speed V, Wood C, Brown A, Hopcroft LE, Higgins R, Massey J, Inglesby P, Morton CE, Walker AJ, Morley J, Mehrkar A, Bacon S, Hickman G, Macdonald O, Lewis T, Wood M, Myers M, Samuel M, Conibere R, Baqir W, Sood H, Drury C, Collison K, Bates C, Evans D, Dillingham I, Ward T, Davy S, Smith RM, Hulme W, Green A, Parry J, Hester F, Harper S, Cockburn J, O’Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, MacKenna B, Goldacre B.",,No Journal Info,2022,2022-10-17,Y,,,,"

Background

The COVID-19 pandemic has had a significant impact on delivery of NHS care. We have developed the OpenSAFELY Service Restoration Observatory (SRO) to describe this impact on primary care activity and monitor its recovery.

Objectives

To develop key measures of primary care activity and describe the trends in these measures throughout the COVID-19 pandemic.

Methods

With the approval of NHS England we developed an open source software framework for data management and analysis to describe trends and variation in clinical activity across primary care electronic health record (EHR) data on 48 million adults. We developed SNOMED-CT codelists for key measures of primary care clinical activity selected by a expert clinical advisory group and conducted a population cohort-based study to describe trends and variation in these measures January 2019-December 2021, and pragmatically classified their level of recovery one year into the pandemic using the percentage change in the median practice level rate.

Results

We produced 11 measures reflective of clinical activity in general practice. A substantial drop in activity was observed in all measures at the outset of the COVID-19 pandemic. By April 2021, the median rate had recovered to within 15% of the median rate in April 2019 in six measures. The remaining measures showed a sustained drop, ranging from a 18.5% reduction in medication reviews to a 42.0% reduction in blood pressure monitoring. Three measures continued to show a sustained drop by December 2021.

Conclusions

The COVID-19 pandemic was associated with a substantial change in primary care activity across the measures we developed, with recovery in most measures. We delivered an open source software framework to describe trends and variation in clinical activity across an unprecedented scale of primary care data. We will continue to expand the set of key measures to be routinely monitored using our publicly available NHS OpenSAFELY SRO dashboards with near real-time data.",,doi:https://doi.org/10.1101/2022.10.17.22281058; doi:https://doi.org/10.1101/2022.10.17.22281058; html:https://europepmc.org/article/PPR/PPR558613; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR558613&type=FILE&fileName=EMS155818-pdf.pdf&mimeType=application/pdf PPR291740,https://doi.org/10.1101/2021.03.03.21252737,"Ethnicity and COVID-19 outcomes among healthcare workers in the United Kingdom: UK-REACH ethico-legal research, qualitative research on healthcare workers’ experiences, and stakeholder engagement protocol","Gogoi M, Reed-Berendt R, Al-Oraibi A, Hassan O, Wobi F, Gupta A, Abubakar I, Dove ES, Nellums LB, Pareek M.",,No Journal Info,2021,2021-03-03,Y,,,,"

ABSTRACT

Introduction

As the world continues to grapple with the COVID-19 pandemic, emerging evidence suggests that individuals from ethnic minority backgrounds may be disproportionately affected. The UK-REACH project has been initiated to understand ethnic differentials in COVID-19 outcomes among healthcare workers (HCWs) in the United Kingdom (UK) through five inter-linked work packages. The ethico-legal work package (Work Package 3) aims to understand and address legal, ethical and acceptability issues around big data research; the healthcare workers’ experiences work package (Work Package 4) is a qualitative study exploring healthcare workers’ experiences during COVID-19 and; the stakeholder engagement work package (Work Package 5) aims to provide feedback and support with the formulation and dissemination of the project recommendations.

Methods and Analysis

Work Package 3 has two different research strands: (a) desk-based doctrinal research; and (b) empirical qualitative research with key opinion leaders. For the empirical research, in-depth interviews will be conducted digitally and recorded with participants’ permission. Recordings will be transcribed, coded and analysed using thematic analysis. In Work Package 4, online in-depth interviews and focus groups will be conducted with approximately 150 HCWs, from across the UK, and these will be recorded with participants’ consent. The recordings will be transcribed, coded and data will be analysed using thematic analysis. Work Package 5 will achieve its objectives through regular group meetings and in-group discussions.

Ethics and Dissemination

Ethical approval has been received from the London - Brighton & Sussex Research Ethics Committee of the Health Research Authority (Ref No. 20/HRA/4718). Results of the study will be published in open access journals, and disseminated through conference presentations, project website, stakeholder organisations, media and scientific advisory groups.

Registration Details

Registered with the International Standard Randomised Controlled Trial Number registry ( ISRCTN11811602 ).

STRENGTHS AND LIMITATIONS OF THIS STUDY

The dual approach of doctrinal and empirical research (Work Package 3) on the use of personal data by UK-REACH will give a comprehensive understanding of the ethical and legal implications of the study, and perceptions about its use of data. Qualitative research with healthcare workers in the UK on their experiences during the COVID-19 pandemic (Work Package 4) will provide insight into personal behaviour, perceptions of risk and coping mechanisms adopted both inside and outside of the work environment. Stakeholder engagement (Work Package 5) from professional regulatory bodies and staff groups is embedded within the UK-REACH study to provide feedback on project activities and support with project recommendations. The target participants (key opinion leaders) for Work Package 3 empirical study will likely come from predominantly White backgrounds which may limit the breadth of views obtained in interviews. This limitation will be mitigated by active recruitment of opinion leaders from a wide variety of ethnic backgrounds and active interaction with Work Package 5. Due to the pandemic restrictions, interviews and focus group discussions will be conducted via online methods as a substitute for face-to-face meetings, posing practical and technological challenges for dynamic interaction with participants.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/7/e049611.full.pdf; doi:https://doi.org/10.1101/2021.03.03.21252737; html:https://europepmc.org/article/PPR/PPR291740; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR291740&type=FILE&fileName=EMS118538-pdf.pdf&mimeType=application/pdf -PPR609115,https://doi.org/10.1101/2023.01.25.23284428,Primary care coding activity related to the use of online consultation systems or remote consulting: an analysis of 53 million peoples’ health records using OpenSAFELY,"Fonseca M, MacKenna B, Mehrkar A, Walters CE, Hickman G, Pearson J, Fisher L, Inglesby P, Bacon S, Davy S, Hulme W, Goldacre B, Koffman O, Bakhai M, The OpenSAFELY Collaborative.",,No Journal Info,2023,2023-01-28,Y,,,,"

Background

The pandemic accelerated work by the NHS in England to enable and stimulate use of online consultation systems across all practices, for improved access to primary care.

Objective

We aimed to explore general practice coding activity associated with the use of online consultation systems in terms of trends, COVID-19 effect, variation and quality.

Methods

With the approval of NHS England, OpenSAFELY-TPP and OpenSAFELY-EMIS were used to query and analyse in situ records of electronic health record systems of over 53 million patients in over 6,400 practices, mainly in 2019-2020. SNOMED CT codes relevant to online consultation systems and written online consultations were identified. Coded events were described by volumes, practice coverage, trends pre- and post-COVID-19 and inter-practice and sociodemographic variation.

Results

3,550,762 relevant coding events were found in TPP practices, with code eConsultation detected in 84% of practices. Coding activity related to digital forms of interaction increased rapidly from March 2020 at the onset of the COVID-19 pandemic, though we found large variation in coding instance rates among practices in England. Code instances were more commonly found among females, those aged 18-40, those least deprived or white. eConsultation coded activity was more commonly found recorded among patients with a history of asthma or depression.

Conclusions

We successfully queried general practice coding activity relevant to the use of online consultation systems, showing increased adoption as well as key areas of variation during the COVID-19 pandemic. The work can be expanded to support monitoring of coding quality and underlying activity. In future, large-scale impact evaluation studies can be implemented within the platform, namely looking at resource utilisation and patient outcomes.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/01/28/2023.01.25.23284428.full.pdf; doi:https://doi.org/10.1101/2023.01.25.23284428; html:https://europepmc.org/article/PPR/PPR609115; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR609115&type=FILE&fileName=EMS163624-pdf.pdf&mimeType=application/pdf +PPR558613,https://doi.org/10.1101/2022.10.17.22281058,Eleven key measures for monitoring general practice clinical activity during COVID-19 using federated analytics on 48 million adults’ primary care records through OpenSAFELY,"Fisher L, Curtis HJ, Croker R, Wiedemann M, Speed V, Wood C, Brown A, Hopcroft LE, Higgins R, Massey J, Inglesby P, Morton CE, Walker AJ, Morley J, Mehrkar A, Bacon S, Hickman G, Macdonald O, Lewis T, Wood M, Myers M, Samuel M, Conibere R, Baqir W, Sood H, Drury C, Collison K, Bates C, Evans D, Dillingham I, Ward T, Davy S, Smith RM, Hulme W, Green A, Parry J, Hester F, Harper S, Cockburn J, O’Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, MacKenna B, Goldacre B.",,No Journal Info,2022,2022-10-17,Y,,,,"

Background

The COVID-19 pandemic has had a significant impact on delivery of NHS care. We have developed the OpenSAFELY Service Restoration Observatory (SRO) to describe this impact on primary care activity and monitor its recovery.

Objectives

To develop key measures of primary care activity and describe the trends in these measures throughout the COVID-19 pandemic.

Methods

With the approval of NHS England we developed an open source software framework for data management and analysis to describe trends and variation in clinical activity across primary care electronic health record (EHR) data on 48 million adults. We developed SNOMED-CT codelists for key measures of primary care clinical activity selected by a expert clinical advisory group and conducted a population cohort-based study to describe trends and variation in these measures January 2019-December 2021, and pragmatically classified their level of recovery one year into the pandemic using the percentage change in the median practice level rate.

Results

We produced 11 measures reflective of clinical activity in general practice. A substantial drop in activity was observed in all measures at the outset of the COVID-19 pandemic. By April 2021, the median rate had recovered to within 15% of the median rate in April 2019 in six measures. The remaining measures showed a sustained drop, ranging from a 18.5% reduction in medication reviews to a 42.0% reduction in blood pressure monitoring. Three measures continued to show a sustained drop by December 2021.

Conclusions

The COVID-19 pandemic was associated with a substantial change in primary care activity across the measures we developed, with recovery in most measures. We delivered an open source software framework to describe trends and variation in clinical activity across an unprecedented scale of primary care data. We will continue to expand the set of key measures to be routinely monitored using our publicly available NHS OpenSAFELY SRO dashboards with near real-time data.",,doi:https://doi.org/10.1101/2022.10.17.22281058; doi:https://doi.org/10.1101/2022.10.17.22281058; html:https://europepmc.org/article/PPR/PPR558613; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR558613&type=FILE&fileName=EMS155818-pdf.pdf&mimeType=application/pdf PPR290304,https://doi.org/10.1101/2021.02.27.21252593,Surgical activity in England and Wales during the COVID-19 pandemic: a nationwide observational cohort study,"Dobbs TD, Gibson JAG, Fowler AJ, Abbott TE, Shahid T, Torabi F, Griffiths R, Lyons RA, Pearse RM, Whitaker IS.",,No Journal Info,2021,2021-03-01,Y,,,,"

Objectives

To report the volume of surgical activity and the number of cancelled surgical procedures during the COVID-19 pandemic.

Design and setting

Analysis of electronic health record data from the National Health Service (NHS) in England and Wales.

Methods

We used hospital episode statistics for all adult patients undergoing surgery between 1 st January 2020 and 31 st December 2020. We identified surgical procedures using a previously published list of procedure codes. Procedures were stratified by urgency of surgery as defined by NHS England. We calculated the deficit of surgical activity by comparing the expected number of procedures from the years 2016-2019 with the actual number of procedures in 2020. We estimated the cumulative number of cancelled procedures by 31 st December 2021 according patterns of activity in 2020.

Results

The total number of surgical procedures carried out in England and Wales in 2020 was 3,102,674 compared to the predicted number of 4,671,338. This represents a 33.6% reduction in the national volume of surgical activity. There were 763,730 emergency surgical procedures (13.4% reduction), compared to 2,338,944 elective surgical procedures (38.6% reduction). The cumulative number of cancelled or postponed procedures was 1,568,664. We estimate that this will increase to 2,358,420 by 31 st December 2021.

Conclusions

The volume of surgical activity in England and Wales was reduced by 33.6% in 2020, resulting in over 1,568,664 cancelled operations. This deficit will continue to grow in 2021.

Summary boxes

What is already known on this topic

The COVID-19 pandemic necessitated a rapid change in the provision of care, including the suspension of a large proportion of surgical activity Surgical activity has yet to return to normal and has been further impacted by subsequent waves of the pandemic This will lead to a large backlog of cases

What this study adds

3,102,674 surgical procedures were performed in England and Wales during 2020, a 33.6% reduction on the expected yearly surgical activity Over 1.5 million procedures were not performed, with this deficit likely to continue to grow to 2.3 million by the end of 2021 This deficit is the equivalent of more than 6 months of pre-pandemic surgical activity, requiring a monumental financial and logistic challenge to manage",,pdf:https://qmro.qmul.ac.uk/xmlui/bitstream/123456789/71298/2/Abbott%20Surgical%20activity%20in%20England%202021%20Published.pdf; doi:https://doi.org/10.1101/2021.02.27.21252593; html:https://europepmc.org/article/PPR/PPR290304; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR290304&type=FILE&fileName=EMS117861-pdf.pdf&mimeType=application/pdf +PPR609115,https://doi.org/10.1101/2023.01.25.23284428,Primary care coding activity related to the use of online consultation systems or remote consulting: an analysis of 53 million peoples’ health records using OpenSAFELY,"Fonseca M, MacKenna B, Mehrkar A, Walters CE, Hickman G, Pearson J, Fisher L, Inglesby P, Bacon S, Davy S, Hulme W, Goldacre B, Koffman O, Bakhai M, The OpenSAFELY Collaborative.",,No Journal Info,2023,2023-01-28,Y,,,,"

Background

The pandemic accelerated work by the NHS in England to enable and stimulate use of online consultation systems across all practices, for improved access to primary care.

Objective

We aimed to explore general practice coding activity associated with the use of online consultation systems in terms of trends, COVID-19 effect, variation and quality.

Methods

With the approval of NHS England, OpenSAFELY-TPP and OpenSAFELY-EMIS were used to query and analyse in situ records of electronic health record systems of over 53 million patients in over 6,400 practices, mainly in 2019-2020. SNOMED CT codes relevant to online consultation systems and written online consultations were identified. Coded events were described by volumes, practice coverage, trends pre- and post-COVID-19 and inter-practice and sociodemographic variation.

Results

3,550,762 relevant coding events were found in TPP practices, with code eConsultation detected in 84% of practices. Coding activity related to digital forms of interaction increased rapidly from March 2020 at the onset of the COVID-19 pandemic, though we found large variation in coding instance rates among practices in England. Code instances were more commonly found among females, those aged 18-40, those least deprived or white. eConsultation coded activity was more commonly found recorded among patients with a history of asthma or depression.

Conclusions

We successfully queried general practice coding activity relevant to the use of online consultation systems, showing increased adoption as well as key areas of variation during the COVID-19 pandemic. The work can be expanded to support monitoring of coding quality and underlying activity. In future, large-scale impact evaluation studies can be implemented within the platform, namely looking at resource utilisation and patient outcomes.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/01/28/2023.01.25.23284428.full.pdf; doi:https://doi.org/10.1101/2023.01.25.23284428; html:https://europepmc.org/article/PPR/PPR609115; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR609115&type=FILE&fileName=EMS163624-pdf.pdf&mimeType=application/pdf PPR639769,https://doi.org/10.1101/2023.04.01.23287538,Trends in weight gain recorded in English primary care before and during the Coronavirus-19 pandemic: an observational cohort study using the OpenSAFELY platform,"Samuel M, Park RY, Eastwood SV, Eto F, Morton CE, Stow D, Bacon S, Mehrkar A, Morley J, Dillingham I, Inglesby P, Hulme WJ, Khunti K, Mathur R, Valabhji J, MacKenna B, Finer S, The OpenSAFELY Collaborative.",,No Journal Info,2023,2023-04-03,Y,,,,"

Background

We investigated which clinical and sociodemographic characteristics were associated with unhealthy patterns of weight gain amongst adults living in England during the pandemic.

Methods

With the approval of NHS England we conducted an observational cohort study of Body Mass Index (BMI) changes between March 2015 and March 2022 using the OpenSAFELY-TPP platform. We estimated individual rates of weight gain before and during the pandemic, and identified individuals with rapid weight gain (>0·5kg/m 2 /year) in each period. We also estimated the change in rate of weight gain between the prepandemic and pandemic period and defined extreme-accelerators as the ten percent of individuals with the greatest increase (>1·84kg/m 2 /year). We estimated associations with these outcomes using multivariate logistic regression.

Findings

We extracted data on 17,742,365 adults (50·1% female, 76·1% White British). Median BMI increased from 27·8kg/m 2 [IQR:24·3-32·1] in 2019 (March 2019 to February 2020) to 28·0kg/m 2 [24·4-32·6] in 2021. Rapid pandemic weight gain (n=3,214,155) was associated with female sex (male vs female: aOR 0·76 [95%CI:0·76-0·76]); younger age (50-59-years vs 18–29-years: aOR 0·60 [0·60-0·61]); White British ethnicity (Black Caribbean vs White British: aOR 0·91 [0·89-0·94]); deprivation (least-deprived-IMD-quintile vs most-deprived: aOR 0·77 [0·77-0·78]); and long-term conditions, of which mental health conditions had the greatest effect (e.g. depression (aOR 1·18[1·17-1·18])). Similar characteristics increased risk of extreme acceleration (n=2,768,695).

Interpretation

We found female sex, younger age, deprivation and mental health conditions increased risk of unhealthy patterns of pandemic weight gain. This highlights the need to incorporate sociodemographic, physical, and mental health characteristics when formulating post-pandemic research, policies, and interventions targeting BMI.

Funding

NIHR",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/04/03/2023.04.01.23287538.full.pdf; doi:https://doi.org/10.1101/2023.04.01.23287538; html:https://europepmc.org/article/PPR/PPR639769; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR639769&type=FILE&fileName=EMS173550-pdf.pdf&mimeType=application/pdf PPR195140,https://doi.org/10.1101/2020.07.30.20165464,Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score,"Knight SR, Ho A, Pius R, Buchan I, Carson G, Drake TM, Dunning J, Fairfield CJ, Gamble C, Green CA, Gupta R, Halpin S, Hardwick HE, Holden KA, Horby PW, Jackson C, Mclean KA, Merson L, Nguyen-Van-Tam JS, Norman L, Noursadeghi M, Olliaro PL, Pritchard MG, Russell CD, Shaw CA, Sheikh A, Solomon T, Sudlow C, Swann OV, Turtle LC, Openshaw PJ, Baillie JK, Semple MG, Docherty AB, Harrison EM.",,No Journal Info,2020,2020-08-02,Y,,,,"

Objectives

To develop and validate a pragmatic risk score to predict mortality for patients admitted to hospital with covid-19.

Design

Prospective observational cohort study: ISARIC WHO CCP-UK study (ISARIC Coronavirus Clinical Characterisation Consortium [4C]). Model training was performed on a cohort of patients recruited between 6 February and 20 May 2020, with validation conducted on a second cohort of patients recruited between 21 May and 29 June 2020.

Setting

260 hospitals across England, Scotland, and Wales.

Participants

Adult patients (≥18 years) admitted to hospital with covid-19 admitted at least four weeks before final data extraction.

Main outcome measures

In-hospital mortality.

Results

There were 34 692 patients included in the derivation dataset (mortality rate 31.7%) and 22 454 in the validation dataset (mortality 31.5%). The final 4C Mortality Score included eight variables readily available at initial hospital assessment: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea, and C-reactive protein (score range 0-21 points). The 4C risk stratification score demonstrated high discrimination for mortality (derivation cohort: AUROC 0.79; 95% CI 0.78 − 0.79; validation cohort 0.78, 0.77-0.79) with excellent calibration (slope = 1.0). Patients with a score ≥15 (n = 2310, 17.4%) had a 67% mortality (i.e., positive predictive value 67%) compared with 1.0% mortality for those with a score ≤3 (n = 918, 7%; negative predictive value 99%). Discriminatory performance was higher than 15 pre-existing risk stratification scores (AUROC range 0.60-0.76), with scores developed in other covid-19 cohorts often performing poorly (range 0.63-0.73).

Conclusions

We have developed and validated an easy-to-use risk stratification score based on commonly available parameters at hospital presentation. This outperformed existing scores, demonstrated utility to directly inform clinical decision making, and can be used to stratify inpatients with covid-19 into different management groups. The 4C Mortality Score may help clinicians identify patients with covid-19 at high risk of dying during current and subsequent waves of the pandemic.

Study registration

ISRCTN66726260",,pdf:https://www.bmj.com/content/bmj/370/bmj.m3339.full.pdf; doi:https://doi.org/10.1101/2020.07.30.20165464; html:https://europepmc.org/article/PPR/PPR195140; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR195140&type=FILE&fileName=EMS95810-pdf.pdf&mimeType=application/pdf PPR406625,https://doi.org/10.1101/2021.10.10.21264821,Modelling the effect of COVID-19 mass vaccination on acute admissions in a major English healthcare system,"Booton R, Powell A, Turner K, Wood R.",,No Journal Info,2021,2021-10-13,Y,,,,"

Background

Managing high levels of severe COVID-19 in the acute setting can impact upon the quality of care provided to both affected patients and those requiring other hospital services. Mass vaccination has offered a route to reduce societal restrictions while protecting hospitals from being overwhelmed. Yet, early in the mass vaccination effort, the possible effect on future bed pressures remained subject to considerable uncertainty. This paper provides an account of how, in one healthcare system, operational decision-making and bed planning was supported through modelling the effect of a range of vaccination scenarios on future COVID-19 admissions.

Methods

An epidemiological model of the Susceptible-Exposed-Infectious-Recovered (SEIR) type was fitted to local data for the one-million resident healthcare system located in South West England. Model parameters and vaccination scenarios were calibrated through a system-wide multi-disciplinary working group, comprising public health intelligence specialists, healthcare planners, epidemiologists, and academics. From 4 March 2021 (the time of the study), scenarios assumed incremental relaxations to societal restrictions according to the envisaged UK Government timeline, with all restrictions to be removed by 21 June 2021.

Results

Achieving 95% vaccine uptake in adults by 31 July 2021 would not avert a third wave in autumn 2021 but would produce a median peak bed requirement approximately 6% (IQR: 1% to 24%) of that experienced during the second wave (January 2021). A two-month delay in vaccine rollout would lead to significantly higher peak bed occupancy, at 66% (11% to 146%) of that of the second wave. If only 75% uptake was achieved (the amount typically associated with vaccination campaigns) then the second wave peak for acute and intensive care beds would be exceeded by 4% and 19% respectively, an amount which would seriously pressure hospital capacity.

Conclusion

Modelling provided support to senior managers in setting the number of acute and intensive care beds to make available for COVID-19 patients, as well as highlighting the importance of public health in promoting high vaccine uptake among the population. Forecast accuracy has since been supported by actual data collected following the analysis, with observed peak bed occupancy falling comfortably within the inter-quartile range of modelled projections.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/10/13/2021.10.10.21264821.full.pdf; doi:https://doi.org/10.1101/2021.10.10.21264821; html:https://europepmc.org/article/PPR/PPR406625; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR406625&type=FILE&fileName=EMS136883-pdf.pdf&mimeType=application/pdf @@ -395,8 +395,8 @@ PPR273714,https://doi.org/10.1101/2021.01.25.21250356,Trends and clinical charac PPR178438,https://doi.org/10.1101/2020.06.18.20134742,Racial and ethnic determinants of Covid-19 risk,"Lo C, Nguyen LH, Drew DA, Graham MS, Warner ET, Joshi AD, Astley CM, Guo C, Ma W, Mehta RS, Kwon S, Song M, Davies R, Capdevila J, Lee KA, Lochlainn MN, Varsavsky T, Sudre CH, Wolf J, Cozier YC, Rosenberg L, Wilkens LR, Haiman CA, Le Marchand L, Palmer JR, Spector TD, Ourselin S, Steves CJ, Chan AT.",,No Journal Info,2020,2020-06-20,Y,,,,"

ABSTRACT

Background

Racial and ethnic minorities have disproportionately high hospitalization rates and mortality related to the novel coronavirus disease 2019 (Covid-19). There are comparatively scant data on race and ethnicity as determinants of infection risk.

Methods

We used a smartphone application (beginning March 24, 2020 in the United Kingdom [U.K.] and March 29, 2020 in the United States [U.S.]) to recruit 2,414,601 participants who reported their race/ethnicity through May 25, 2020 and employed logistic regression to determine the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for a positive Covid-19 test among racial and ethnic groups.

Results

We documented 8,858 self-reported cases of Covid-19 among 2,259,841 non-Hispanic white; 79 among 9,615 Hispanic; 186 among 18,176 Black; 598 among 63,316 Asian; and 347 among 63,653 other racial minority participants. Compared with non-Hispanic white participants, the risk for a positive Covid-19 test was increased across racial minorities (aORs ranging from 1.24 to 3.51). After adjustment for socioeconomic indices and Covid-19 exposure risk factors, the associations (aOR [95% CI]) were attenuated but remained significant for Hispanic (1.58 [1.24-2.02]) and Black participants (2.56 [1.93-3.39]) in the U.S. and South Asian (1.52 [1.38-1.67]) and Middle Eastern participants (1.56 [1.25-1.95]) in the U.K. A higher risk of Covid-19 and seeking or receiving treatment was also observed for several racial/ethnic minority subgroups.

Conclusions

Our results demonstrate an increase in Covid-19 risk among racial and ethnic minorities not completely explained by other risk factors for Covid-19, comorbidities, and sociodemographic characteristics. Further research investigating these disparities are needed to inform public health measures.",,pdf:http://www.thelancet.com/article/S2589537021003096/pdf; doi:https://doi.org/10.1101/2020.06.18.20134742; html:https://europepmc.org/article/PPR/PPR178438; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR178438&type=FILE&fileName=EMS88297-pdf.pdf&mimeType=application/pdf PPR139421,https://doi.org/10.1101/2020.04.01.20049908,"The effect of non-pharmaceutical interventions on COVID-19 cases, deaths and demand for hospital services in the UK: a modelling study","Davies NG, Kucharski AJ, Eggo RM, Gimma A, Edmunds WJ, CMMID COVID-19 working group.",,No Journal Info,2020,2020-04-06,Y,,,,"

Background

Non-pharmaceutical interventions have been implemented to reduce transmission of SARS-CoV-2 in the UK. Projecting the size of an unmitigated epidemic and the potential effect of different control measures has been critical to support evidence-based policymaking during the early stages of the epidemic.

Methods

We used a stochastic age-structured transmission model to explore a range of intervention scenarios, including the introduction of school closures, social distancing, shielding of elderly groups, self-isolation of symptomatic cases, and extreme “lockdown”-type restrictions. We simulated different durations of interventions and triggers for introduction, as well as combinations of interventions. For each scenario, we projected estimated new cases over time, patients requiring inpatient and critical care (intensive care unit, ICU) treatment, and deaths.

Findings

We found that mitigation measures aimed at reducing transmission would likely have decreased the reproduction number, but not sufficiently to prevent ICU demand from exceeding NHS availability. To keep ICU bed demand below capacity in the model, more extreme restrictions were necessary. In a scenario where “lockdown”-type interventions were put in place to reduce transmission, these interventions would need to be in place for a large proportion of the coming year in order to prevent healthcare demand exceeding availability.

Interpretation

The characteristics of SARS-CoV-2 mean that extreme measures are likely required to bring the epidemic under control and to prevent very large numbers of deaths and an excess of demand on hospital beds, especially those in ICUs.

Research in Context

Evidence before this study

As countries have moved from early containment efforts to planning for the introduction of large-scale non-pharmaceutical interventions to control COVID-19 outbreaks, epidemic modelling studies have explored the potential for extensive social distancing measures to curb transmission. However, it remains unclear how different combinations of interventions, timings, and triggers for the introduction and lifting of control measures may affect the impact of the epidemic on health services, and what the range of uncertainty associated with these estimates would be.

Added value of this study

Using a stochastic, age-structured epidemic model, we explored how eight different intervention scenarios could influence the number of new cases and deaths, as well as intensive care beds required over the projected course of the epidemic. We also assessed the potential impact of local versus national targeting of interventions, reduction in leisure events, impact of increased childcare by grandparents, and timing of triggers for different control measures. We simulated multiple realisations for each scenario to reflect uncertainty in possible epidemic trajectories.

Implications of all the available evidence

Our results support early modelling findings, and subsequent empirical observations, that in the absence of control measures, a COVID-19 epidemic could quickly overwhelm a healthcare system. We found that even a combination of moderate interventions – such as school closures, shielding of older groups and self-isolation – would be unlikely to prevent an epidemic that would far exceed available ICU capacity in the UK. Intermittent periods of more intensive lockdown-type measures are predicted to be effective for preventing the healthcare system from being overwhelmed.","It is highly important to know the outcome of different scenarios ahead of critical decisions. Davies et al. shed light on various scenarios considering there is no drug or vaccine for the COVID-19. They’ve looked at interventions such as school closure, social distancing, shielding of the elderly, self-isolation of those with symptoms and shown that all of these reduces the total number of cases by 70-75% and delays the peak of epidemic by 3-8 weeks. Social distancing have the greatest impact in total number of cases while elderly shielding had the greatest impact on number of deaths.",doi:https://doi.org/10.1016/s2468-2667(20)30133-x; doi:https://doi.org/10.1101/2020.04.01.20049908; html:https://europepmc.org/article/PPR/PPR139421; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR139421&type=FILE&fileName=EMS89534-pdf.pdf&mimeType=application/pdf PPR237625,https://doi.org/10.1101/2020.11.09.20228015,A time-resolved proteomic and diagnostic map characterizes COVID-19 disease progression and predicts outcome,"Demichev V, Tober-Lau P, Nazarenko T, Thibeault C, Whitwell H, Lemke O, Röhl A, Freiwald A, Szyrwiel L, Ludwig D, Correia-Melo C, Helbig ET, Stubbemann P, Grüning N, Blyuss O, Vernardis S, White M, Messner CB, Joannidis M, Sonnweber T, Klein SJ, Pizzini A, Wohlfarter Y, Sahanic S, Hilbe R, Schaefer B, Wagner S, Mittermaier M, Machleidt F, Garcia C, Ruwwe-Glösenkamp C, Lingscheid T, de Jarcy LB, Stegemann MS, Pfeiffer M, Jürgens L, Denker S, Zickler D, Enghard P, Zelezniak A, Campbell A, Hayward C, Porteous DJ, Marioni RE, Uhrig A, Müller-Redetzky H, Zoller H, Löffler-Ragg J, Keller MA, Tancevski I, Timms JF, Zaikin A, Hippenstiel S, Ramharter M, Witzenrath M, Suttorp N, Lilley K, Mülleder M, Sander LE, Ralser M, Kurth F, PA-COVID-19 Study group.",,No Journal Info,2020,2020-11-12,Y,,,,"COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. There is an urgent need for predictive markers that can guide clinical decision-making, inform about the effect of experimental therapies, and point to novel therapeutic targets. Here, we characterize the time-dependent progression of COVID-19 through different stages of the disease, by measuring 86 accredited diagnostic parameters and plasma proteomes at 687 sampling points, in a cohort of 139 patients during hospitalization. We report that the time-resolved patient molecular phenotypes reflect an initial spike in the systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution and immunomodulation. Further, we show that the early host response is predictive for the disease trajectory and gives rise to proteomic and diagnostic marker signatures that classify the need for supplemental oxygen therapy and mechanical ventilation, and that predict the time to recovery of mildly ill patients. In severely ill patients, the molecular phenotype of the early host response predicts survival, in two independent cohorts and weeks before outcome. We also identify age-specific molecular response to COVID-19, which involves increased inflammation and lipoprotein dysregulation in older patients. Our study provides a deep and time resolved molecular characterization of COVID-19 disease progression, and reports biomarkers for risk-adapted treatment strategies and molecular disease monitoring. Our study demonstrates accurate prognosis of COVID-19 outcome from proteomic signatures recorded weeks earlier.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/11/12/2020.11.09.20228015.full.pdf; doi:https://doi.org/10.1101/2020.11.09.20228015; html:https://europepmc.org/article/PPR/PPR237625; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR237625&type=FILE&fileName=EMS104194-pdf.pdf&mimeType=application/pdf -PPR693212,https://doi.org/10.1101/2023.07.16.23292723,Evaluation of the impact of COVID-19 pandemic on hospital admission related to common infections,"Fahmi A, Palin V, Zhong X, Yang Y, Watts S, Ashcroft DM, Goldacre B, Mackenna B, Fisher L, Massey J, Mehrkar A, Bacon S, Hand K, Staa TPv, OpenSAFELY collaborative.",,No Journal Info,2023,2023-07-18,Y,,,,"

Background

Antimicrobial resistance (AMR) is a multifaceted global challenge, partly driven by inappropriate antibiotic prescribing. The COVID-19 pandemic impacted antibiotic prescribing for common bacterial infections. This highlights the need to examine risk of hospital admissions related to common infections, excluding COVID-19 infections during the pandemic.

Methods

With the approval of NHS England, we accessed electronic health records from The Phoenix Partnership (TPP) through OpenSAFELY platform. We included patients with primary care diagnosis of common infections, including lower respiratory tract infection (LRTI), upper respiratory tract infections (URTI), and lower urinary tract infection (UTI), from January 2019 to August 2022. We excluded patients with a COVID-19 record 90 days before to 30 days after the infection diagnosis. Using Cox proportional-hazard regression models, we predicted risk of infection-related hospital admission in 30 days follow-up period after the diagnosis.

Results

We found 12,745,165 infection diagnoses from January 2019 to August 2022. Of them, 80,395 (2.05%) cases were admitted to hospital in the follow-up period. Counts of hospital admission for infections dropped during COVID-19, e.g., LRTI from 3,950 in December 2019 to 520 in April 2020. Comparing those prescribed an antibiotic to those without, reduction in risk of hospital admission were largest with LRTI (adjusted odds ratio (OR) of 0.35; 95% CI, 0.35-0.36) and UTI (adjusted OR 0.45; 95% CI, 0.44-0.46), compared to URTI (adjusted OR 1.04; 95% CI, 1.03-1.06).

Conclusion

Large effectiveness of antibiotics in preventing complications related to LRTI and UTI can support better targeting of antibiotics to patients with higher complication risks.

Key messages

- The main drivers of infection-related hospital admission are age, Charlson comorbidity index, and history of prior antibiotics. - Antibiotics are more effective in preventing hospital admission related to infections such as lower respiratory tract infection and urinary tract infection, rather than upper respiratory tract infection. - Common antibiotic types are associated with more reduction in the risk of infection-related hospital admission.",,doi:https://doi.org/10.1101/2023.07.16.23292723; html:https://europepmc.org/article/PPR/PPR693212; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR693212&type=FILE&fileName=EMS181508-pdf.pdf&mimeType=application/pdf PPR362420,https://doi.org/10.1101/2021.06.24.21259374,A proteomic survival predictor for COVID-19 patients in intensive care,"Demichev V, Tober-Lau P, Nazarenko T, Aulakh SK, Whitwell H, Lemke O, Röhl A, Freiwald A, Mittermaier M, Szyrwiel L, Ludwig D, Correia-Melo C, Lippert LJ, Helbig ET, Stubbemann P, Olk N, Thibeault C, Grüning N, Blyuss O, Vernardis S, White M, Messner CB, Joannidis M, Sonnweber T, Klein SJ, Pizzini A, Wohlfarter Y, Sahanic S, Hilbe R, Schaefer B, Wagner S, Machleidt F, Garcia C, Ruwwe-Glösenkamp C, Lingscheid T, de Jarcy LB, Stegemann MS, Pfeiffer M, Jürgens L, Denker S, Zickler D, Spies C, Edel A, Müller NB, Enghard P, Zelezniak A, Bellmann-Weiler R, Weiss G, Campbell A, Hayward C, Porteous DJ, Marioni RE, Uhrig A, Zoller H, Löffler-Ragg J, Keller MA, Tancevski I, Timms JF, Zaikin A, Hippenstiel S, Ramharter M, Müller-Redetzky H, Witzenrath M, Suttorp N, Lilley K, Mülleder M, Sander LE, Kurth F, Ralser M, PA-COVID-19 Study group.",,No Journal Info,2021,2021-06-26,N,,,,"Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Comprehensively capturing the host physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index and APACHE II score were poor predictors of survival. Plasma proteomics instead identified 14 proteins that showed concentration trajectories different between survivors and non-survivors. A proteomic predictor trained on single samples obtained at the first time point at maximum treatment level (i.e. WHO grade 7) and weeks before the outcome, achieved accurate classification of survivors in an exploratory (AUROC 0.81) as well as in the independent validation cohort (AUROC of 1.0). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that predictors derived from plasma protein levels have the potential to substantially outperform current prognostic markers in intensive care.

Trial registration

German Clinical Trials Register DRKS00021688",,pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000007&type=printable; doi:https://doi.org/10.1101/2021.06.24.21259374; html:https://europepmc.org/article/PPR/PPR362420; doi:https://doi.org/10.1101/2021.06.24.21259374 +PPR693212,https://doi.org/10.1101/2023.07.16.23292723,Evaluation of the impact of COVID-19 pandemic on hospital admission related to common infections,"Fahmi A, Palin V, Zhong X, Yang Y, Watts S, Ashcroft DM, Goldacre B, Mackenna B, Fisher L, Massey J, Mehrkar A, Bacon S, Hand K, Staa TPv, OpenSAFELY collaborative.",,No Journal Info,2023,2023-07-18,Y,,,,"

Background

Antimicrobial resistance (AMR) is a multifaceted global challenge, partly driven by inappropriate antibiotic prescribing. The COVID-19 pandemic impacted antibiotic prescribing for common bacterial infections. This highlights the need to examine risk of hospital admissions related to common infections, excluding COVID-19 infections during the pandemic.

Methods

With the approval of NHS England, we accessed electronic health records from The Phoenix Partnership (TPP) through OpenSAFELY platform. We included patients with primary care diagnosis of common infections, including lower respiratory tract infection (LRTI), upper respiratory tract infections (URTI), and lower urinary tract infection (UTI), from January 2019 to August 2022. We excluded patients with a COVID-19 record 90 days before to 30 days after the infection diagnosis. Using Cox proportional-hazard regression models, we predicted risk of infection-related hospital admission in 30 days follow-up period after the diagnosis.

Results

We found 12,745,165 infection diagnoses from January 2019 to August 2022. Of them, 80,395 (2.05%) cases were admitted to hospital in the follow-up period. Counts of hospital admission for infections dropped during COVID-19, e.g., LRTI from 3,950 in December 2019 to 520 in April 2020. Comparing those prescribed an antibiotic to those without, reduction in risk of hospital admission were largest with LRTI (adjusted odds ratio (OR) of 0.35; 95% CI, 0.35-0.36) and UTI (adjusted OR 0.45; 95% CI, 0.44-0.46), compared to URTI (adjusted OR 1.04; 95% CI, 1.03-1.06).

Conclusion

Large effectiveness of antibiotics in preventing complications related to LRTI and UTI can support better targeting of antibiotics to patients with higher complication risks.

Key messages

- The main drivers of infection-related hospital admission are age, Charlson comorbidity index, and history of prior antibiotics. - Antibiotics are more effective in preventing hospital admission related to infections such as lower respiratory tract infection and urinary tract infection, rather than upper respiratory tract infection. - Common antibiotic types are associated with more reduction in the risk of infection-related hospital admission.",,doi:https://doi.org/10.1101/2023.07.16.23292723; html:https://europepmc.org/article/PPR/PPR693212; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR693212&type=FILE&fileName=EMS181508-pdf.pdf&mimeType=application/pdf PPR129796,https://doi.org/10.1101/2020.03.24.20043018,Age-dependent effects in the transmission and control of COVID-19 epidemics,"Davies NG, Klepac P, Liu Y, Prem K, Jit M, Eggo RM, CMMID COVID-19 working group.",,No Journal Info,2020,2020-03-27,Y,,,,"The COVID-19 pandemic has shown a markedly low proportion of cases among children. Age disparities in observed cases could be explained by children having lower susceptibility to infection, lower propensity to show clinical symptoms, or both. We evaluate these possibilities by fitting an age-structured mathematical model to epidemic data from six countries. We estimate that clinical symptoms occur in 25% (95% CrI: 19-32%) of infections in 10-19-year-olds, rising to 76% (68-82%) in over-70s, and that susceptibility to infection in under-20s is approximately half that of older adults. Accordingly, we find that interventions aimed at children may have a relatively small impact on total cases, particularly if the transmissibility of subclinical infections is low. The age-specific clinical fraction and susceptibility we have estimated has implications for the expected global burden of COVID-19 because of demographic differences across settings: in younger populations, the expected clinical attack rate would be lower, although it is likely that comorbidities in low-income countries will affect disease severity. Without effective control measures, regions with older populations may see disproportionally more clinical cases, particularly in the later stages of the pandemic.","COVID-19 reported cases amongst young children are low while old people are at higher risk of disease and death. Davies et al. investigated the source of difference in young vs older subgroups. They’ve used mathematical models on data of 6 countries and shown that the probability of getting symptoms, rising from 20% in under 10s to over 70% in older adults. Alternative lay summary: This study aimed to explain the differences in the risk of infection with COVID-19 between people of different ages, using data from 6 countries. The authors found that age was a very important factor in showing signs of infection (20% chance of having symptoms aged <10y, 70% in older adults), but that age may not influence the chance of being infected. These findings are important because they suggest that closing schools may be less effective in preventing spread of infection than for infections like influenza where children play a bigger role in spreading the disease.",pdf:https://www.nature.com/articles/s41591-020-0962-9.pdf; doi:https://doi.org/10.1101/2020.03.24.20043018; html:https://europepmc.org/article/PPR/PPR129796; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR129796&type=FILE&fileName=EMS89351-pdf.pdf&mimeType=application/pdf @@ -419,15 +419,15 @@ PPR185844,https://doi.org/10.1101/2020.07.08.20148965,A case-control and cohort PPR607510,https://doi.org/10.2139/ssrn.4060371,Epidemiologic Information Discovery from Open-Access COVID-19 Case Reports Via Pretrained Language Model,"Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, lin h, Wong ZSY, Xu X, Sun Y.",,No Journal Info,2022,2022-03-17,N,,,,"Although open-access data are increasing common and useful to epidemiological research, curation of such datasets is resource-intensive and time-consuming. Despite a major source of COVID-19 data, the regularly disclosed case reports were often written in natural language with unstructured format. Here we propose a computational framework that can automatically extract epidemiological information from open-access COVID-19 case reports. We develop this framework by coupling language model developed using deep neural networks with training samples compiled using an optimized data annotation strategy. When applying to the COVID-19 case reports collected from mainland China, our novel framework outstrips all other state-of-the-art deep learning models. The information extracted from our approach is highly consistent with that obtained from the gold-standard manual coding, with a matching rate of 80%. To implement our algorithm, we provide an open-access online platform that can accurately estimate epidemiological statistics in real-time with substantially reduced burden in data curation.",,pdf:https://www.repository.cam.ac.uk/bitstream/1810/342099/2/article.pdf; doi:https://doi.org/10.2139/ssrn.4060371; html:https://europepmc.org/article/PPR/PPR607510; doi:https://doi.org/10.2139/ssrn.4060371 PPR764966,https://doi.org/10.1101/2023.11.25.23299014,Genetic determinants of blood gene expression and splicing and their contribution to molecular phenotypes and health outcomes,"Tokolyi A, Persyn E, Nath AP, Burnham KL, Marten J, Vanderstichele T, Tardaguila M, Stacey D, Farr B, Iyer V, Jiang X, Lambert SA, Noell G, Quail MA, Rajan D, Ritchie SC, Sun BB, Thurston SA, Xu Y, Whelan CD, Runz H, Petrovski S, Gaffney DJ, Roberts DJ, Angelantonio ED, Peters JE, Soranzo N, Danesh J, Butterworth AS, Inouye M, Davenport EE, Paul DS.",,No Journal Info,2023,2023-11-27,Y,,,,"

Summary

The biological mechanisms through which most non-protein-coding genetic variants affect disease risk are unknown. To investigate the gene-regulatory cascades that ensue from these variants, we mapped blood gene expression and splicing quantitative trait loci (QTLs) through bulk RNA-sequencing in 4,732 participants, and integrated these data with protein, metabolite and lipid QTLs in the same individuals. We identified cis -QTLs for the expression of 17,233 genes and 29,514 splicing events (in 6,853 genes). Using colocalization analysis, we identified 3,430 proteomic and metabolomic traits with a shared association signal with either gene expression or splicing. We quantified the relative contribution of the genetic effects at loci with shared etiology through statistical mediation, observing 222 molecular phenotypes significantly mediated by gene expression or splicing. We uncovered gene-regulatory mechanisms at GWAS disease loci with therapeutic implications, such as WARS1 in hypertension, IL7R in dermatitis and IFNAR2 in COVID-19. Our study provides an open-access and interactive resource of the shared genetic etiology across transcriptional phenotypes, molecular traits and health outcomes in humans ( https://IntervalRNA.org.uk ).",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/11/27/2023.11.25.23299014.full.pdf; doi:https://doi.org/10.1101/2023.11.25.23299014; html:https://europepmc.org/article/PPR/PPR764966; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR764966&type=FILE&fileName=EMS191802-pdf.pdf&mimeType=application/pdf PPR186560,https://doi.org/10.1101/2020.07.10.20151118,The 4C Initiative (Clinical Care for Cardiovascular disease in the COVID-19 pandemic) – monitoring the indirect impact of the coronavirus pandemic on services for cardiovascular diseases in the UK,"4C Initiative of the CVD-COVID-UK consortium, Ball S, Banerjee A, Berry C, Boyle J, Bray B, Bradlow W, Chaudhry A, Crawley R, Danesh J, Denniston A, Falter F, Figueroa J, Hall C, Hemingway H, Jefferson E, Johnson T, King G, Lee K, McKean P, Mason S, Mills N, Pearson E, Pirmohamed M, Poon M, Priedon R, Shah A, Sofat R, Sterne J, Strachan F, Sudlow C, Szarka Z, Whiteley W, Wyatt M.",,No Journal Info,2020,2020-07-11,Y,,,,"

ABSTRACT

Background

The coronavirus (COVID-19) pandemic affects cardiovascular diseases (CVDs) directly through infection and indirectly through health service reorganisation and public health policy. Real-time data are needed to quantify direct and indirect effects. We aimed to monitor hospital activity for presentation, diagnosis and treatment of CVDs during the pandemic to inform on indirect effects.

Methods

We analysed aggregate data on presentations, diagnoses and treatments or procedures for selected CVDs (acute coronary syndromes, heart failure, stroke and transient ischaemic attack, venous thromboembolism, peripheral arterial disease and aortic aneurysm) in UK hospitals before and during the COVID-19 epidemic. We produced an online visualisation tool to enable near real-time monitoring of trends.

Findings

Nine hospitals across England and Scotland contributed hospital activity data from 28 Oct 2019 (pre-COVID-19) to 10 May 2020 (pre-easing of lockdown), and for the same weeks during 2018-2019. Across all hospitals, total admissions and emergency department (ED) attendances decreased after lockdown (23 March 2020) by 57.9% (57.1-58.6%) and 52.9% (52.2-53.5%) respectively compared with the previous year. Activity for cardiac, cerebrovascular and other vascular conditions started to decline 1-2 weeks before lockdown, and fell by 31-88% after lockdown, with the greatest reductions observed for coronary artery bypass grafts, carotid endarterectomy, aortic aneurysm repair and peripheral arterial disease procedures. Compared with before the first UK COVID-19 (31 January 2020), activity declined across diseases and specialties between the first case and lockdown (total ED attendances RR 0.94, 0.93-0.95; total hospital admissions RR 0.96, 0.95-0.97) and after lockdown (attendances RR 0.63, 0.62-0.64; admissions RR 0.59, 0.57-0.60). There was limited recovery towards usual levels of some activities from mid-April 2020.

Interpretation

Substantial reductions in total and cardiovascular activities are likely to contribute to a major burden of indirect effects of the pandemic, suggesting they should be monitored and mitigated urgently.

Funding

British Heart Foundation, Health Data Research UK",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/07/11/2020.07.10.20151118.full.pdf; doi:https://doi.org/10.1101/2020.07.10.20151118; html:https://europepmc.org/article/PPR/PPR186560; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR186560&type=FILE&fileName=EMS87270-pdf.pdf&mimeType=application/pdf -PPR778471,https://doi.org/10.1101/2023.12.21.23300244,"Genetics, primary care records and lifestyle factors for short-term dynamic risk prediction of colorectal cancer: prospective study of asymptomatic and symptomatic UK Biobank participants","Ip S, Harrison H, Usher-Smith JA, Barclay M, Tyrer J, Dennis J, Yang X, Lush M, Renzi C, Pashayan N, Denaxas S, Lyratzopoulos G, Antoniou AC, Wood A.",,No Journal Info,2023,2023-12-24,Y,,,,"

ABSTRACT

Objectives

To quantify the contributions of polygenic scores, primary care records (presenting symptoms, medical history and common blood tests) and lifestyle factors, for short-term risk prediction of colorectal cancer (CRC) in both all and symptomatic individuals.

Design

Prospective cohort study.

Setting

UK Biobank with follow-up until 2018.

Participants

All participants with linked primary care records (n=160,526), and a subcohort of participants with a presentation of a symptom associated with CRC (n=50,728).

Main outcome measures

Outcome was the first recorded CRC diagnosis within two years. Dynamic risk models with time-varying predictors were derived in a super-landmark framework. Contributions to model discrimination were quantified using novel inclusion-order-agnostic Shapley values of Harrel’s C-index using cross-validation.

Results

C-indices [95% CIs] were 0.74 [0.72-0.75] and 0.71 [0.67-0.77] for the models derived in all and symptomatic participants respectively. The Shapley contributions to model discrimination differed between the two groups of participants for different predictors: 31% (32% in the symptomatic participants) for core predictors (e.g., age, sex, smoking), 16% (12%) for polygenic scores, 27% (30%) for primary care blood tests, 14% (14%) for primary care medical history, 8% (0.5%) for additional lifestyle factors and 4% (12%) for symptoms.

Conclusions

Polygenic scores contribute substantially to short-term risk prediction for CRC in both general and symptomatic populations; however, the contribution of information in primary care records (including presenting symptoms, medical history and common blood tests) is greater. There is, however, only a small contribution by the additional lifestyle risk factors which are not routinely collected in primary care.",,doi:https://doi.org/10.1101/2023.12.21.23300244; html:https://europepmc.org/article/PPR/PPR778471; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR778471&type=FILE&fileName=EMS193037-pdf.pdf&mimeType=application/pdf PPR237477,https://doi.org/10.1101/2020.11.11.20220962,Short-term forecasts to inform the response to the Covid-19 epidemic in the UK,"Funk S, Abbott S, Atkins B, Baguelin M, Baillie J, Birrell P, Blake J, Bosse N, Burton J, Carruthers J, Davies N, De Angelis D, Dyson L, Edmunds W, Eggo R, Ferguson N, Gaythorpe K, Gorsich E, Guyver-Fletcher G, Hellewell J, Hill E, Holmes A, House T, Jewell C, Jit M, Jombart T, Joshi I, Keeling M, Kendall E, Knock E, Kucharski A, Lythgoe K, Meakin S, Munday J, Openshaw P, Overton C, Pagani F, Pearson J, Perez-Guzman P, Pellis L, Scarabel F, Semple M, Sherratt K, Tang M, Tildesley M, Van Leeuwen E, Whittles L, CMMID COVID-19 Working Group, Imperial College COVID-19 Response Team, ISARIC4C Investigators.",,No Journal Info,2020,2020-11-13,Y,,,,"

Background

Short-term forecasts of infectious disease can aid situational awareness and planning for outbreak response. Here, we report on multi-model forecasts of Covid-19 in the UK that were generated at regular intervals starting at the end of March 2020, in order to monitor expected healthcare utilisation and population impacts in real time.

Methods

We evaluated the performance of individual model forecasts generated between 24 March and 14 July 2020, using a variety of metrics including the weighted interval score as well as metrics that assess the calibration, sharpness, bias and absolute error of forecasts separately. We further combined the predictions from individual models into ensemble forecasts using a simple mean as well as a quantile regression average that aimed to maximise performance. We compared model performance to a null model of no change.

Results

In most cases, individual models performed better than the null model, and ensembles models were well calibrated and performed comparatively to the best individual models. The quantile regression average did not noticeably outperform the mean ensemble.

Conclusions

Ensembles of multi-model forecasts can inform the policy response to the Covid-19 pandemic by assessing future resource needs and expected population impact of morbidity and mortality.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/12/04/2020.11.11.20220962.full.pdf; doi:https://doi.org/10.1101/2020.11.11.20220962; html:https://europepmc.org/article/PPR/PPR237477; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR237477&type=FILE&fileName=EMS104159-pdf.pdf&mimeType=application/pdf +PPR778471,https://doi.org/10.1101/2023.12.21.23300244,"Genetics, primary care records and lifestyle factors for short-term dynamic risk prediction of colorectal cancer: prospective study of asymptomatic and symptomatic UK Biobank participants","Ip S, Harrison H, Usher-Smith JA, Barclay M, Tyrer J, Dennis J, Yang X, Lush M, Renzi C, Pashayan N, Denaxas S, Lyratzopoulos G, Antoniou AC, Wood A.",,No Journal Info,2023,2023-12-24,Y,,,,"

ABSTRACT

Objectives

To quantify the contributions of polygenic scores, primary care records (presenting symptoms, medical history and common blood tests) and lifestyle factors, for short-term risk prediction of colorectal cancer (CRC) in both all and symptomatic individuals.

Design

Prospective cohort study.

Setting

UK Biobank with follow-up until 2018.

Participants

All participants with linked primary care records (n=160,526), and a subcohort of participants with a presentation of a symptom associated with CRC (n=50,728).

Main outcome measures

Outcome was the first recorded CRC diagnosis within two years. Dynamic risk models with time-varying predictors were derived in a super-landmark framework. Contributions to model discrimination were quantified using novel inclusion-order-agnostic Shapley values of Harrel’s C-index using cross-validation.

Results

C-indices [95% CIs] were 0.74 [0.72-0.75] and 0.71 [0.67-0.77] for the models derived in all and symptomatic participants respectively. The Shapley contributions to model discrimination differed between the two groups of participants for different predictors: 31% (32% in the symptomatic participants) for core predictors (e.g., age, sex, smoking), 16% (12%) for polygenic scores, 27% (30%) for primary care blood tests, 14% (14%) for primary care medical history, 8% (0.5%) for additional lifestyle factors and 4% (12%) for symptoms.

Conclusions

Polygenic scores contribute substantially to short-term risk prediction for CRC in both general and symptomatic populations; however, the contribution of information in primary care records (including presenting symptoms, medical history and common blood tests) is greater. There is, however, only a small contribution by the additional lifestyle risk factors which are not routinely collected in primary care.",,doi:https://doi.org/10.1101/2023.12.21.23300244; html:https://europepmc.org/article/PPR/PPR778471; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR778471&type=FILE&fileName=EMS193037-pdf.pdf&mimeType=application/pdf PPR602769,https://doi.org/10.2139/ssrn.3615999,Diabetes and COVID-19 Related Mortality in the Critical Care Setting: A Real-Time National Cohort Study in England,"Dennis JM, Mateen BA, Sonabend R, Thomas NJ, Patel KA, Hattersley AT, Denaxas S, McGovern AP, Vollmer SJ.",,No Journal Info,2020,2020-06-05,N,,,,"Background:The importance of diabetes as a prognostic factor in people admitted to hospital critical care with COVID-19 is poorly understood and has not been quantified.

Methods:We used a real-time national database (COVID-19 Hospitalisation in England Surveillance System; CHESS), comprising data on COVID-19 related admissions to hospital in England requiring admission to a high dependency unit (HDU) or intensive care unit (ICU) between March 1, 2020 and May 17, 2020. The objective was to describe the relationship between diabetes and all-cause in-hospital mortality in adults, using Cox proportional hazard models adjusted for age, sex, ethnicity, obesity, and other comorbidities. The primary analysis was restricted to a subset with sufficiently complete comorbidity status recording. Several sensitivity analyses, including on the unrestricted dataset, were carried out to verify the results.

Findings: Diabetes was independently associated with mortality in people admitted to critical care settings with COVID-19 in England; the proportion of 30-day mortality attributable to diabetes, after adjusting for age, sex, ethnicity, obesity, and other comorbidities, was 4·8% (95%CI 2·5-7·0). 14,639 COVID-19 related HDU and ICU admissions were reported during the study period, of which 6,142 were included in primary analysis, including 3,311 HDU (mean age 72), and 2,831 ICU admissions (mean age 58). 1,439 (23·4%) had diabetes. 1,847 individuals (30·1%) died during the study period. 30 day mortality was higher in people with diabetes than without (p < 0·001). People with diabetes were at increased risk of death (adjusted hazard ratio (HR) 1·28 [1·14, 1·42]). Results were consistent in subsets admitted to HDU only (adjusted HR 1·27 [1·09, 1·48]) and ICU (adjusted HR 1·31 [1·12, 1·54]). Sensitivity analyses were consistent with the primary analysis.

Interpretation:Diabetes is an independent prognostic factor for mortality in people with COVID-19 requiring HDU or ICU treatment. Quantification of this diabetes associated risk enables appropriate treatment decisions in people with diabetes and severe COVID-19.

Funding Statement: This study received no funding.

Declaration of Interests: APM declares previous research funding from Eli Lilly and Company, Pfizer, and AstraZeneca. SJV declares funding from IQVIA. All other authors declare no competing interests.

Ethics Approval Statement: The study was reviewed and approved by the Warwick BSREC (BSREC 119/19-20) and sponsorship is being provided by University of Warwick (SOC.28/19-20).",,doi:https://doi.org/10.2139/ssrn.3615999; html:https://europepmc.org/article/PPR/PPR602769; doi:https://doi.org/10.2139/ssrn.3615999 PPR218529,https://doi.org/10.1101/2020.09.24.20200048,Genetic mechanisms of critical illness in Covid-19,"Pairo-Castineira E, Clohisey S, Klaric L, Bretherick A, Rawlik K, Parkinson N, Pasko D, Walker S, Richmond A, Fourman MH, Russell CD, Law A, Furniss J, Gountouna E, Wrobel N, Moutsianas L, Wang B, Meynert A, Yang Z, Zhai R, Zheng C, Griffiths F, Oosthuyzen W, Grimes G, Shih B, Keating S, Zechner M, Haley C, Porteous DJ, Hayward C, Knight J, Summers C, Shankar-Hari M, Klenerman P, Turtle L, Ho A, Hinds C, Horby P, Nichol A, Maslove D, Ling L, McAuley D, Montgomery H, Walsh T, Shen X, Rowan K, Fawkes A, Murphy L, Ponting CP, Tenesa A, Caulfield M, Scott R, Openshaw PJ, Semple MG, Vitart V, Wilson JF, Baillie JK, The GenOMICC Investigators, The ISARIC-4C Investigators, The Covid-19 Human Genetics Initiative.",,No Journal Info,2020,2020-09-25,Y,,,,"The subset of patients who develop critical illness in Covid-19 have extensive inflammation affecting the lungs 1 and are strikingly different from other patients: immunosuppressive therapy benefits critically-ill patients, but may harm some non-critical cases. 2 Since susceptibility to life-threatening infections and immune-mediated diseases are both strongly heritable traits, we reasoned that host genetic variation may identify mechanistic targets for therapeutic development in Covid-19. 3 GenOMICC (Genetics Of Mortality In Critical Care, genomicc.org ) is a global collaborative study to understand the genetic basis of critical illness. Here we report the results of a genome-wide association study (GWAS) in 2244 critically-ill Covid-19 patients from 208 UK intensive care units (ICUs), representing >95% of all ICU beds. Ancestry-matched controls were drawn from the UK Biobank population study and results were confirmed in GWAS comparisons with two other population control groups: the 100,000 genomes project and Generation Scotland. We identify and replicate three novel genome-wide significant associations, at chr19p13.3 (rs2109069, p = 3.98 × 10 −12 ), within the gene encoding dipeptidyl peptidase 9 ( DPP9 ), at chr12q24.13 (rs10735079, p =1.65 × 10 −8 ) in a gene cluster encoding antiviral restriction enzyme activators ( OAS1, OAS2, OAS3 ), and at chr21q22.1 (rs2236757, p = 4.99 × 10 −8 ) in the interferon receptor gene IFNAR2 . Consistent with our focus on extreme disease in younger patients with less comorbidity, we detect a stronger signal at the known 3p21.31 locus than previous studies (rs73064425, p = 4.77 × 10 −30 ). We identify potential targets for repurposing of licensed medications. Using Mendelian randomisation we found evidence in support of a causal link from low expression of IFNAR2 , and high expression of TYK2 , to life-threatening disease. Transcriptome-wide association in lung tissue revealed that high expression of the monocyte/macrophage chemotactic receptor CCR2 is associated with severe Covid-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms, and mediators of inflammatory organ damage in Covid-19. Both mechanisms may be amenable to targeted treatment with existing drugs. Large-scale randomised clinical trials will be essential before any change to clinical practice.",,pdf:https://www.nature.com/articles/s41586-020-03065-y.pdf; doi:https://doi.org/10.1101/2020.09.24.20200048; html:https://europepmc.org/article/PPR/PPR218529; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR218529&type=FILE&fileName=EMS96350-pdf.pdf&mimeType=application/pdf PPR172592,https://doi.org/10.1101/2020.06.05.20121962,TRACKing Excess Deaths (TRACKED) – an interactive online tool to monitor excess deaths associated with COVID-19 pandemic in the United Kingdom,"Poon MT, Brennan PM, Jin K, Figueroa JD, Sudlow CL.",,No Journal Info,2020,2020-06-07,Y,,,,"

Background

We aimed to describe trends of excess mortality in the United Kingdom (UK) stratified by nation and cause of death, and to develop an online tool for reporting the most up to date data on excess mortality.

Methods

Population statistics agencies in the UK including the Office for National Statistics (ONS), National Records of Scotland (NRS), and Northern Ireland Statistics and Research Agency (NISRA) publish weekly data on deaths. We used mortality data up to 22 nd May in the ONS and the NISRA and 24 th May in the NRS. Crude mortality for non-COVID deaths (where there is no mention of COVID-19 on the death certificate) calculated. Excess mortality defined as difference between observed mortality and expected average of mortality from previous 5 years.

Results

There were 56,961 excess deaths and 8,986 were non-COVID excess deaths. England had the highest number of excess deaths per 100,000 population (85) and Northern Ireland the lowest (34). Non-COVID mortality increased from 23rd March and returned to the 5-year average on 10th May. In Scotland, where underlying cause mortality data besides COVID-related deaths was available, the percentage excess over the 8-week period when COVID-related mortality peaked was: dementia 49%, other causes 21%, circulatory diseases 10%, and cancer 5%. We developed an online tool (TRACKing Excess Deaths - TRACKED) to allow dynamic exploration and visualisation of the latest mortality trends ( http://trackingexcessdeaths.com ).

Conclusions

Continuous monitoring of excess mortality trends and further integration of age- and gender-stratified and underlying cause of death data beyond COVID-19 will allow dynamic assessment of the impacts of indirect and direct mortality of the COVID-19 pandemic.",,doi:https://doi.org/10.12688/wellcomeopenres.16058.1; doi:https://doi.org/10.1101/2020.06.05.20121962; html:https://europepmc.org/article/PPR/PPR172592; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR172592&type=FILE&fileName=EMS91985-pdf.pdf&mimeType=application/pdf PPR428677,https://doi.org/10.1101/2021.12.03.21266112,Brain Injury in COVID-19 is Associated with Autoinflammation and Autoimmunity,"Needham E, Ren A, Digby R, Outtrim J, Chatfield D, Manktelow A, Newcombe V, Doffinger R, Barcenas-Morales G, Fonseca C, Taussig M, Burnstein R, Dunai C, Sithole N, Ashton N, Zetterberg H, Gisslen M, Edén A, Marklund E, Griffiths M, Cavanagh J, Breen G, Irani S, Elmer A, Kingston N, Bradley J, Taams L, Michael B, Bullmore E, Smith K, Lyons P, Coles A, Menon D, the Cambridge NeuroCOVID Group, the NIHR COVID-19 BioResource, Cambridge NIHR Clinical Research Facility.",,No Journal Info,2021,2021-12-05,Y,,,,"COVID-19 has been associated with many neurological complications including stroke, delirium and encephalitis. Furthermore, many individuals experience a protracted post-viral syndrome which is dominated by neuropsychiatric symptoms, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of severe COVID-19 more broadly. We sought to investigate the dynamics of, and relationship between, serum markers of brain injury (neurofilament light [NfL], Glial Fibrillary Acidic Protein [GFAP] and total Tau) and markers of dysregulated host response including measures of autoinflammation (proinflammatory cytokines) and autoimmunity. Brain injury biomarkers were measured using the Quanterix Simoa HDx platform, cytokine profiling by Luminex (R&D) and autoantibodies by a custom protein microarray. During hospitalisation, patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependant manner, and there was evidence of ongoing active brain injury at follow-up 4 months later. Raised NfL and GFAP were associated with both elevations of pro-inflammatory cytokines and the presence of autoantibodies; autoantibodies were commonly seen against lung surfactant proteins as well as brain proteins such as myelin associated glycoprotein, but reactivity was seen to a large number of different antigens. Furthermore, a distinct process characterised by elevation of serum total Tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses in the same manner as NfL and GFAP.",,pdf:https://www.repository.cam.ac.uk/bitstream/1810/343727/3/awac321.pdf; doi:https://doi.org/10.1101/2021.12.03.21266112; html:https://europepmc.org/article/PPR/PPR428677; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR428677&type=FILE&fileName=EMS141610-pdf.pdf&mimeType=application/pdf PPR153348,https://doi.org/10.1101/2020.04.18.20064774,"How many are at increased risk of severe COVID-19 disease? Rapid global, regional and national estimates for 2020","Clark A, Jit M, Warren-Gash C, Guthrie B, Wang HH, Mercer SW, Sanderson C, McKee M, Troeger C, Ong KI, Checchi F, Perel P, Joseph S, Gibbs HP, Banerjee A, Eggo RM, CMMID COVID-19 working group.",,No Journal Info,2020,2020-04-22,Y,,,,"

Background

The risk of severe COVID-19 disease is known to be higher in older individuals and those with underlying health conditions. Understanding the number of individuals at increased risk of severe COVID-19 illness, and how this varies between countries may inform the design of possible strategies to shield those at highest risk.

Methods

We estimated the number of individuals at increased risk of severe COVID-19 disease by age (5-year age groups), sex and country (n=188) based on prevalence data from the Global Burden of Disease (GBD) study for 2017 and United Nations population estimates for 2020. We also calculated the number of individuals without an underlying condition that could be considered at-risk because of their age, using thresholds from 50-70 years. The list of underlying conditions relevant to COVID-19 disease was determined by mapping conditions listed in GBD to the guidelines published by WHO and public health agencies in the UK and US. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity.

Results

We estimate that 1.7 (1.0 - 2.4) billion individuals (22% [15-28%] of the global population) are at increased risk of severe COVID-19 disease. The share of the population at increased risk ranges from 16% in Africa to 31% in Europe. Chronic kidney disease (CKD), cardiovascular disease (CVD), diabetes and chronic respiratory disease (CRD) were the most prevalent conditions in males and females aged 50+ years. African countries with a high prevalence of HIV/AIDS and Island countries with a high prevalence of diabetes, also had a high share of the population at increased risk. The prevalence of multimorbidity (>1 underlying conditions) was three times higher in Europe than in Africa (10% vs 3%).

Conclusion

Based on current guidelines and prevalence data from GBD, we estimate that one in five individuals worldwide has a condition that is on the list of those at increased risk of severe COVID-19 disease. However, for many of these individuals the underlying condition will be undiagnosed or not severe enough to be captured in health systems, and in some cases the increase in risk may be quite modest. There is an urgent need for robust analyses of the risks associated with different underlying conditions so that countries can identify the highest risk groups and develop targeted shielding policies to mitigate the effects of the COVID-19 pandemic.

Research in context

Evidence before this study

As the COVID-19 pandemic evolves, countries are considering policies of ‘shielding’ the most vulnerable, but there is currently very limited evidence on the number of individuals that might need to be shielded. Guidelines on who is currently believed to be at increased risk of severe COVID-19 illness have been published online by the WHO and public health agencies in the UK and US. We searched PubMed (“Risk factors” AND “COVID-19”) without language restrictions, from database inception until April 5, 2020, and identified 62 studies published between Feb 15, 2020 and March 20, 2020. Evidence from China, Italy and the USA indicates that older individuals, males and those with underlying conditions, such as CVD, diabetes and CRD, are at greater risk of severe COVID-19 illness and death.

Added value of this study

This study combines evidence from large international databases and new analysis of large multimorbidity studies to inform policymakers about the number of individuals that may be at increased risk of severe COVID-19 illness in different countries. We developed a tool for rapid assessments of the number and percentage of country populations that would need to be targeted under different shielding policies.

Implications of all the available evidence

Quantifying how many and who is at increased risk of severe COVID-19 illness is critical to help countries design more effective interventions to protect vulnerable individuals and reduce pressure on health systems. This information can also inform a broader assessment of the health, social and economic implications of shielding various groups.","""This paper estimates the likely number of global population that would be at increased risk of severe COVID-19 disease. They estimate that 1.7 (1.0 - 2.4) billion individuals (22% [15-28%] of the global population) are at increased risk of severe COVID-19 disease. The share of the population at increased risk ranges from 16% in Africa to 31% in Europe.""",pdf:https://www.medrxiv.org/content/medrxiv/early/2020/04/22/2020.04.18.20064774.full.pdf; doi:https://doi.org/10.1101/2020.04.18.20064774; html:https://europepmc.org/article/PPR/PPR153348; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR153348&type=FILE&fileName=EMS90450-pdf.pdf&mimeType=application/pdf -PPR812457,https://doi.org/10.1101/2024.02.28.24303461,"APOL1 variants G1, G2 and N264K affect APOL1 plasma protein concentration: a UK Biobank study","Adamson WE, Noyes H, Ogunsola J, Parekh RS, Cooper A, MacLeod A.",,No Journal Info,2024,2024-02-29,Y,,,,"

Background

APOL1 variants G1 and G2 are common in populations with recent sub-Saharan African ancestry. They are known to influence health conditions: most notably being associated with protection from human African trypanosomiasis and increased risk of susceptibility to chronic kidney disease. Association studies have often considered G1 and G2 as equivalent, however we recently presented evidence of substantial phenotypic differences between carriers of the two variants. An additional APOL1 variant, N264K, has previously been shown to modify the damaging effect of G2 on the kidney. Here, we examine the influence of these variants on APOL1 protein concentration.

Methods

Using a cohort of 1,050 UK Biobank participants with recent African ancestry, we compared APOL1 protein concentration in carriers of variants G1, G2, and N264K and performed a genome-wide association study to identify additional modifiers of APOL1 concentration. We also compared APOL1 concentration across self-reported ethnicities for all 43,330 UK Biobank participants for whom APOL1 concentration data was available.

Findings

APOL1 G1 and G2 are both associated with increased APOL1 protein concentration, however the effect of G2 is more marked, and it was the only locus that reached genome-wide significance in terms of association with APOL1 concentration (p = 3×10 −155 ). In a G2 background, the presence of N264K is associated with a reduction in APOL1 concentration (p = 6 × 10 −5 ). People with self-reported Black or Black British ethnicity have higher APOL1 concentrations all other self-reported ethnicities in the UK Biobank.

Interpretation

These findings demonstrate the influence of APOL1 variants and APOL1 protein concentration and identify additional phenotypic differences between the G1 and G2, highlighting the value in considering them as distinct in molecular and association studies. This work also provides further detail on the relationship between the G2 and N264K variants, which has significant implications for diagnosis and therapy in kidney disease.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2024/02/29/2024.02.28.24303461.full.pdf; doi:https://doi.org/10.1101/2024.02.28.24303461; html:https://europepmc.org/article/PPR/PPR812457; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR812457&type=FILE&fileName=EMS194386-pdf.pdf&mimeType=application/pdf PPR577327,https://doi.org/10.1101/2022.11.28.22282810,Developing a research ready population-scale linked data ethnicity-spine in Wales,"Akbari A, Torabi F, Bedston S, Lowthian E, Abbasizanjani H, Fry R, Lyons J, Owen RK, Khunti K, Lyons RA.",,No Journal Info,2022,2022-11-29,Y,,,,"

Introduction:

Ethnicity information is recorded routinely in electronic health records (EHRs); however, to date, there is no national standard or framework for harmonisation of the existing records. Methods and analysis The national ethnicity-spine uses anonymised individual-level population-scale ethnicity data from 26 EHR available through the Secure Anonymised Information Linkage (SAIL) Databank. A total of 46 million ethnicity records for 4,297,694 individuals in Wales-UK over 22 years (between 2000 and 2021) have been compiled in a harmonised, deduplicated longitudinal research ready data asset. We serialised this data and compared distribution of records over time for four selection approaches (Latest, Mode, Weighted-Mode and Composite) across age bands, sex, deprivation quintiles, health board, and residential location, against the ONS census 2011. The distribution of the dominant group (White) is minimally affected based on the four different selection approaches. Across all other ethnicity categorisations, the Mixed group was most susceptible to variation in distribution depending on the selection approach used and varied from a 0.6% prevalence across the Latest and Mode approach to a 1.1% prevalence for the Weighted-Mode, compared to the 3.1% prevalence for the Composite approach. Substantial alignment was observed with ONS census with the Latest group method (kappa= 0.68, 95% CI [0.67,0.71]) across all sub-groups. Conclusion We provides a reproducible EHR based resource enabling the investigation and evaluation of health inequalities related to ethnic groups in Wales. This generalisable method informs opportunities for the transferability of this methodology across the UK to platforms with comparable routine data sources. Ethics and dissemination This work was supported by the Con-COV team funded by Medical Research Council, Health Data Research UK, ADR Wales funded by ADR UK through the Economic and Social Research Council, and the Wales COVID-19 Evidence Centre, funded by Health and Care Research Wales.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/11/29/2022.11.28.22282810.full.pdf; doi:https://doi.org/10.1101/2022.11.28.22282810; html:https://europepmc.org/article/PPR/PPR577327; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR577327&type=FILE&fileName=EMS157868-pdf.pdf&mimeType=application/pdf +PPR812457,https://doi.org/10.1101/2024.02.28.24303461,"APOL1 variants G1, G2 and N264K affect APOL1 plasma protein concentration: a UK Biobank study","Adamson WE, Noyes H, Ogunsola J, Parekh RS, Cooper A, MacLeod A.",,No Journal Info,2024,2024-02-29,Y,,,,"

Background

APOL1 variants G1 and G2 are common in populations with recent sub-Saharan African ancestry. They are known to influence health conditions: most notably being associated with protection from human African trypanosomiasis and increased risk of susceptibility to chronic kidney disease. Association studies have often considered G1 and G2 as equivalent, however we recently presented evidence of substantial phenotypic differences between carriers of the two variants. An additional APOL1 variant, N264K, has previously been shown to modify the damaging effect of G2 on the kidney. Here, we examine the influence of these variants on APOL1 protein concentration.

Methods

Using a cohort of 1,050 UK Biobank participants with recent African ancestry, we compared APOL1 protein concentration in carriers of variants G1, G2, and N264K and performed a genome-wide association study to identify additional modifiers of APOL1 concentration. We also compared APOL1 concentration across self-reported ethnicities for all 43,330 UK Biobank participants for whom APOL1 concentration data was available.

Findings

APOL1 G1 and G2 are both associated with increased APOL1 protein concentration, however the effect of G2 is more marked, and it was the only locus that reached genome-wide significance in terms of association with APOL1 concentration (p = 3×10 −155 ). In a G2 background, the presence of N264K is associated with a reduction in APOL1 concentration (p = 6 × 10 −5 ). People with self-reported Black or Black British ethnicity have higher APOL1 concentrations all other self-reported ethnicities in the UK Biobank.

Interpretation

These findings demonstrate the influence of APOL1 variants and APOL1 protein concentration and identify additional phenotypic differences between the G1 and G2, highlighting the value in considering them as distinct in molecular and association studies. This work also provides further detail on the relationship between the G2 and N264K variants, which has significant implications for diagnosis and therapy in kidney disease.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2024/02/29/2024.02.28.24303461.full.pdf; doi:https://doi.org/10.1101/2024.02.28.24303461; html:https://europepmc.org/article/PPR/PPR812457; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR812457&type=FILE&fileName=EMS194386-pdf.pdf&mimeType=application/pdf PPR187554,https://doi.org/10.1101/2020.07.14.20152629,COVID-19 infection and attributable mortality in UK care homes: Cohort study using active surveillance and electronic records (March-June 2020),"Dutey-Magni PF, Williams H, Jhass A, Rait G, Lorencatto F, Hemingway H, Hemingway H, Hayward A, Shallcross L.",,No Journal Info,2020,2020-07-15,Y,,,,"

Background

Epidemiological data on COVID-19 infection in care homes are scarce. We analysed data from a large provider of long-term care for older people to investigate infection and mortality during the first wave of the pandemic.

Methods

Cohort study of 179 UK care homes with 9,339 residents and 11,604 staff.We used manager-reported daily tallies to estimate the incidence of suspected and confirmed infection and mortality in staff and residents. Individual-level electronic health records from 8,713 residents were used to model risk factors for confirmed infection, mortality, and estimate attributable mortality.

Results

2,075/9,339 residents developed COVID-19 symptoms (22.2% [95% confidence interval: 21.4%; 23.1%]), while 951 residents (10.2% [9.6%; 10.8%]) and 585 staff (5.0% [4.7%; 5.5%]) had laboratory-confirmed infections. The incidence of confirmed infection was 152.6 [143.1; 162.6] and 62.3 [57.3; 67.5] per 100,000 person-days in residents and staff respectively. 121/179 (67.6%) care homes had at least one COVID-19 infection or COVID-19-related death. Lower staffing ratios and higher occupancy rates were independent risk factors for infection. 217/607 residents with confirmed infection died (case-fatality rate: 35.7% [31.9%; 39.7%]). Mortality in residents with no direct evidence of infection was two-fold higher in care homes with outbreaks versus those without (adjusted HR 2.2 [1.8; 2.6]).

Conclusions

Findingss:

uggest many deaths occurred in people who were infected with COVID-19, but not tested. Higher occupancy and lower staffing levels were independently associated with risks of infection. Protecting staff and residents from infection requires regular testing for COVID-19 and fundamental changes to staffing and care home occupancy.",,pdf:https://discovery.ucl.ac.uk/10122604/10/Dutey-Magni_afab060.pdf; doi:https://doi.org/10.1101/2020.07.14.20152629; html:https://europepmc.org/article/PPR/PPR187554; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR187554&type=FILE&fileName=EMS87167-pdf.pdf&mimeType=application/pdf PPR450173,https://doi.org/10.1101/2022.02.03.22270391,"Device-assessed sleep and physical activity in individuals recovering from a hospital admission for COVID-19: a prospective, multicentre study",,,No Journal Info,2022,2022-02-03,Y,,,,"

Objectives

To describe physical behaviours following hospital admission for COVID-19 including associations with acute illness severity and ongoing symptoms.

Methods

1077 patients with COVID-19 discharged from hospital between March and November 2020 were recruited. Using a 14-day wear protocol, wrist-worn accelerometers were sent to participants after a five-month follow-up assessment. Acute illness severity was assessed by the WHO clinical progression scale, and the severity of ongoing symptoms was assessed using four previously reported data-driven clinical recovery clusters. Two existing control populations of office workers and type 2 diabetes were comparators.

Results

Valid accelerometer data from 253 women and 462 men were included. Women engaged in a mean±SD of 14.9±14.7 minutes/day of moderate-to-vigorous physical activity (MVPA), with 725.6±104.9 minutes/day spent inactive and 7.22±1.08 hours/day asleep. The values for men were 21.0±22.3 and 755.5±102.8 minutes/day and 6.94±1.14 hours/day, respectively. Over 60% of women and men did not have any days containing a 30-minute bout of MVPA. Variability in sleep timing was approximately 2 hours in men and women. More severe acute illness was associated with lower total activity and MVPA in recovery. The very severe recovery cluster was associated with fewer days/week containing continuous bouts of MVPA, longer sleep duration, and higher variability in sleep timing. Patients post-hospitalisation with COVID-19 had lower levels of physical activity, greater sleep variability, and lower sleep efficiency than a similarly aged cohort of office workers or those with type 2 diabetes.

Conclusions

Physical activity and regulating sleep patterns are potential treatable traits for COVID-19 recovery programmes.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/02/03/2022.02.03.22270391.full.pdf; doi:https://doi.org/10.1101/2022.02.03.22270391; html:https://europepmc.org/article/PPR/PPR450173; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR450173&type=FILE&fileName=EMS143501-pdf.pdf&mimeType=application/pdf PPR263081,https://doi.org/10.1101/2021.01.06.21249352,OpenSAFELY NHS Service Restoration Observatory 1: describing trends and variation in primary care clinical activity for 23.3 million patients in England during the first wave of COVID-19,"The OpenSAFELY Collaborative, Curtis HJ, MacKenna B, MacKenna B, Croker R, Inglesby P, Walker AJ, Morley J, Mehrkar A, Morton CE, Bacon S, Hickman G, Bates C, Morley J, Evans D, Ward T, Cockburn J, Davy S, Bhaskaran K, Schultze A, Rentsch CT, Williamson E, Hulme W, McDonald HI, Tomlinson L, Mathur R, Drysdale H, Eggo RM, Wing K, Wong AY, Forbes H, Parry J, Hester F, Harper S, Evans SJ, Douglas IJ, Smeeth L, Goldacre B.",,No Journal Info,2021,2021-01-08,Y,,,,"

Background

The COVID-19 pandemic has disrupted healthcare activity globally. The NHS in England stopped most non-urgent work by March 2020, but later recommended that services should be restored to near-normal levels before winter where possible. The authors are developing the OpenSAFELY NHS Service Restoration Observatory , using data to describe changes in service activity during COVID-19, and reviewing signals for action with commissioners, researchers and clinicians. Here we report phase one: generating, managing, and describing the data.

Objective

To describe the volume and variation of coded clinical activity in English primary care across 23.8 million patients’ records, taking respiratory disease and laboratory procedures as key examples.

Methods

Working on behalf of NHS England we developed an open source software framework for data management and analysis to describe trends and variation in clinical activity across primary care EHR data on 23.8 million patients; and conducted a population cohort-based study to describe activity using CTV3 coding hierarchy and keyword searches from January 2019-September 2020.

Results

Much activity recorded in general practice declined to some extent during the pandemic, but largely recovered by September 2020, with some exceptions. There was a large drop in coded activity for commonly used laboratory tests, with broad recovery to pre-pandemic levels by September. One exception was blood coagulation tests such as International Normalised Ratio (INR), with a smaller reduction (median tests per 1000 patients in 2020: February 8.0; April 6.2; September 7.0). The overall pattern of recording for respiratory symptoms was less affected, following an expected seasonal pattern and classified as “no change” from the previous year. Respiratory tract infections exhibited a sustained drop compared with pre-pandemic levels, not returning to pre-pandemic levels by September 2020. Various COVID-19 codes increased through the period. We observed a small decline associated with high level codes for long-term respiratory conditions such as chronic obstructive pulmonary disease (COPD) and asthma. Asthma annual reviews experienced a small drop but since recovered, while COPD annual reviews remain below baseline.

Conclusions

We successfully delivered an open source software framework to describe trends and variation in clinical activity across an unprecedented scale of primary care data. The COVD-19 pandemic led to a substantial change in healthcare activity. Most laboratory tests showed substantial reduction, largely recovering to near-normal levels by September 2020, with some important tests less affected. Records of respiratory infections decreased with the exception of codes related to COVID-19, whilst activity of other respiratory disease codes was mixed. We are expanding the NHS Service Restoration Observatory in collaboration with clinicians, commissioners and researchers and welcome feedback.",,pdf:https://bjgp.org/content/bjgp/72/714/e63.full.pdf; doi:https://doi.org/10.1101/2021.01.06.21249352; html:https://europepmc.org/article/PPR/PPR263081; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR263081&type=FILE&fileName=EMS110198-pdf.pdf&mimeType=application/pdf diff --git a/data/covid/papers.csv b/data/covid/papers.csv index 7479d82a..7a3e74f5 100644 --- a/data/covid/papers.csv +++ b/data/covid/papers.csv @@ -13,17 +13,17 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc 36261315,https://doi.org/10.1002/ana.26536,Fewer COVID-19 Neurological Complications with Dexamethasone and Remdesivir.,"Grundmann A, Wu CH, Hardwick M, Baillie JK, Openshaw PJM, Semple MG, Böhning D, Pett S, Michael BD, Thomas RH, Galea I, ISARIC4C investigators.",,Annals of neurology,2023,2022-11-09,Y,,,,"

Objective

The objective of this study was to assess the impact of treatment with dexamethasone, remdesivir or both on neurological complications in acute coronavirus diease 2019 (COVID-19).

Methods

We used observational data from the International Severe Acute and emerging Respiratory Infection Consortium World Health Organization (WHO) Clinical Characterization Protocol, United Kingdom. Hospital inpatients aged ≥18 years with laboratory-confirmed severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection admitted between January 31, 2020, and June 29, 2021, were included. Treatment allocation was non-blinded and performed by reporting clinicians. A propensity scoring methodology was used to minimize confounding. Treatment with remdesivir, dexamethasone, or both was assessed against the standard of care. The primary outcome was a neurological complication occurring at the point of death, discharge, or resolution of the COVID-19 clinical episode.

Results

Out of 89,297 hospital inpatients, 64,088 had severe COVID-19 and 25,209 had non-hypoxic COVID-19. Neurological complications developed in 4.8% and 4.5%, respectively. In both groups, neurological complications were associated with increased mortality, intensive care unit (ICU) admission, worse self-care on discharge, and time to recovery. In patients with severe COVID-19, treatment with dexamethasone (n = 21,129), remdesivir (n = 1,428), and both combined (n = 10,846) were associated with a lower frequency of neurological complications: OR = 0.76 (95% confidence interval [CI] = 0.69-0.83), OR = 0.69 (95% CI = 0.51-0.90), and OR = 0.54 (95% CI = 0.47-0.61), respectively. In patients with non-hypoxic COVID-19, dexamethasone (n = 2,580) was associated with less neurological complications (OR = 0.78, 95% CI = 0.62-0.97), whereas the dexamethasone/remdesivir combination (n = 460) showed a similar trend (OR = 0.63, 95% CI = 0.31-1.15).

Interpretation

Treatment with dexamethasone, remdesivir, or both in patients hospitalized with COVID-19 was associated with a lower frequency of neurological complications in an additive manner, such that the greatest benefit was observed in patients who received both drugs together. ANN NEUROL 2023;93:88-102.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ana.26536; doi:https://doi.org/10.1002/ana.26536; html:https://europepmc.org/articles/PMC9874556; pdf:https://europepmc.org/articles/PMC9874556?pdf=render 35913410,https://doi.org/10.1093/cid/ciac629,Validity of Self-testing at Home With Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Detection by Lateral Flow Immunoassay.,"Atchison CJ, Moshe M, Brown JC, Whitaker M, Wong NCK, Bharath AA, McKendry RA, Darzi A, Ashby D, Donnelly CA, Riley S, Elliott P, Barclay WS, Cooke GS, Ward H.",,Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,2023,2023-02-01,Y,Antibodies; Lateral Flow Immunoassay; Home-testing; Covid-19; Sars-cov-2,,,"

Background

We explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow immunoassay (LFIA) performance under field conditions compared to laboratory-based electrochemiluminescence immunoassay (ECLIA) and live virus neutralization.

Methods

In July 2021, 3758 participants performed, at home, a self-administered Fortress LFIA on finger-prick blood, reported and submitted a photograph of the result, and provided a self-collected capillary blood sample for assessment of immunoglobulin G (IgG) antibodies using the Roche Elecsys® Anti-SARS-CoV-2 ECLIA. We compared the self-reported LFIA result to the quantitative ECLIA and checked the reading of the LFIA result with an automated image analysis (ALFA). In a subsample of 250 participants, we compared the results to live virus neutralization.

Results

Almost all participants (3593/3758, 95.6%) had been vaccinated or reported prior infection. Overall, 2777/3758 (73.9%) were positive on self-reported LFIA, 2811/3457 (81.3%) positive by LFIA when ALFA-reported, and 3622/3758 (96.4%) positive on ECLIA (using the manufacturer reference standard threshold for positivity of 0.8 U mL-1). Live virus neutralization was detected in 169 of 250 randomly selected samples (67.6%); 133/169 were positive with self-reported LFIA (sensitivity 78.7%; 95% confidence interval [CI]: 71.8, 84.6), 142/155 (91.6%; 95% CI: 86.1, 95.5) with ALFA, and 169 (100%; 95% CI: 97.8, 100.0) with ECLIA. There were 81 samples with no detectable virus neutralization; 47/81 were negative with self-reported LFIA (specificity 58.0%; 95% CI: 46.5, 68.9), 34/75 (45.3%; 95% CI: 33.8, 57.3) with ALFA, and 0/81 (0%; 95% CI: 0, 4.5) with ECLIA.

Conclusions

Self-administered LFIA is less sensitive than a quantitative antibody test, but the positivity in LFIA correlates better than the quantitative ECLIA with virus neutralization.",,doi:https://doi.org/10.1093/cid/ciac629; doi:https://doi.org/10.1093/cid/ciac629; html:https://europepmc.org/articles/PMC9384551; pdf:https://europepmc.org/articles/PMC9384551?pdf=render 37656609,https://doi.org/10.1093/aje/kwad179,CHALLENGES IN ESTIMATING THE EFFECTIVENESS OF 2 DOSES OF COVID-19 VACCINE BEYOND 6 MONTHS IN ENGLAND.,"Horne EMF, Hulme WJ, Keogh RH, Palmer TM, Williamson EJ, Parker EPK, Walker VM, Knight R, Wei Y, Taylor K, Fisher L, Morley J, Mehrkar A, Dillingham I, Bacon S, Goldacre B, Sterne JAC, OpenSAFELY Collaborative FT.",,American journal of epidemiology,2024,2024-01-01,Y,,,,,,pdf:https://academic.oup.com/aje/advance-article-pdf/doi/10.1093/aje/kwad179/51329819/kwad179.pdf; doi:https://doi.org/10.1093/aje/kwad179; html:https://europepmc.org/articles/PMC10773473; pdf:https://europepmc.org/articles/PMC10773473?pdf=render -38778017,https://doi.org/10.1038/s41541-024-00878-0,Influence of individuals' determinants including vaccine type on cellular and humoral responses to SARS-CoV-2 vaccination.,"Chambers ES, Cai W, Vivaldi G, Jolliffe DA, Perdek N, Li W, Faustini SE, Gibbons JM, Pade C, Richter AG, Coussens AK, Martineau AR.",,NPJ vaccines,2024,2024-05-22,Y,,,,"Vaccine development targeting SARS-CoV-2 in 2020 was of critical importance in reducing COVID-19 severity and mortality. In the U.K. during the initial roll-out most individuals either received two doses of Pfizer COVID-19 vaccine (BNT162b2) or the adenovirus-based vaccine from Oxford/AstraZeneca (ChAdOx1-nCoV-19). There are conflicting data as to the impact of age, sex and body habitus on cellular and humoral responses to vaccination, and most studies in this area have focused on determinants of mRNA vaccine immunogenicity. Here, we studied a cohort of participants in a population-based longitudinal study (COVIDENCE UK) to determine the influence of age, sex, body mass index (BMI) and pre-vaccination anti-Spike (anti-S) antibody status on vaccine-induced humoral and cellular immune responses to two doses of BNT162b2 or ChAdOx-n-CoV-19 vaccination. Younger age and pre-vaccination anti-S seropositivity were both associated with stronger antibody responses to vaccination. BNT162b2 generated higher neutralising and anti-S antibody titres to vaccination than ChAdOx1-nCoV-19, but cellular responses to the two vaccines were no different. Irrespective of vaccine type, increasing age was also associated with decreased frequency of cytokine double-positive CD4+T cells. Increasing BMI was associated with reduced frequency of SARS-CoV-2-specific TNF+CD8% T cells for both vaccines. Together, our findings demonstrate that increasing age and BMI are associated with attenuated cellular and humoral responses to SARS-CoV-2 vaccination. Whilst both vaccines induced T cell responses, BNT162b2 induced significantly elevated humoral immune response as compared to ChAdOx-n-CoV-19.",,pdf:https://www.nature.com/articles/s41541-024-00878-0.pdf; doi:https://doi.org/10.1038/s41541-024-00878-0; html:https://europepmc.org/articles/PMC11111746; pdf:https://europepmc.org/articles/PMC11111746?pdf=render 37564827,https://doi.org/10.1136/bmjmed-2022-000403,Vaccine effectiveness for prevention of covid-19 related hospital admission during pregnancy in England during the alpha and delta variant dominant periods of the SARS-CoV-2 pandemic: population based cohort study.,"Bosworth ML, Schofield R, Ayoubkhani D, Charlton L, Nafilyan V, Khunti K, Zaccardi F, Gillies C, Akbari A, Knight M, Wood R, Hardelid P, Zuccolo L, Harrison C.",,BMJ medicine,2023,2023-07-10,Y,epidemiology; Public Health; Covid-19,,,"

Objective

To estimate vaccine effectiveness for preventing covid-19 related hospital admission in individuals first infected with the SARS-CoV-2 virus during pregnancy compared with those of reproductive age who were not pregnant when first infected with the virus.

Design

Population based cohort study.

Setting

Office for National Statistics Public Health Data Asset linked dataset, providing national linked census and administrative data in England, 8 December 2020 to 31 August 2021.

Participants

815 477 females aged 18-45 years (mean age 30.4 years) who had documented evidence of a first SARS-CoV-2 infection in the NHS Test and Trace or Hospital Episode Statistics data.

Main outcome measures

Hospital admission where covid-19 was recorded as the primary diagnosis. Cox proportional hazards models, adjusted for calendar time of infection, sociodemographic factors, and pre-existing health conditions related to uptake of the covid-19 vaccine and risk of severe covid-19 outcomes, were used to estimate vaccine effectiveness as the complement of the hazard ratio for hospital admission for covid-19.

Results

Compared with pregnant individuals who were not vaccinated, the adjusted rate of hospital admission for covid-19 was 77% (95% confidence interval 70% to 82%) lower for pregnant individuals who had received one dose and 83% (76% to 89%) lower for those who had received two doses of vaccine. These estimates were similar to those found in the non-pregnant group: 79% (77% to 81%) for one dose and 83% (82% to 85%) for two doses of vaccine. Among those who were vaccinated >90 days before infection, having two doses of vaccine was associated with a greater reduction in risk than one dose.

Conclusions

Covid-19 vaccination was associated with reduced rates of hospital admission in pregnant individuals infected with the SARS-CoV-2 virus, and the reduction in risk was similar to that in non-pregnant individuals. Waning of vaccine effectiveness occurred more quickly after one than after two doses of vaccine.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000403.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000403; html:https://europepmc.org/articles/PMC10410807; pdf:https://europepmc.org/articles/PMC10410807?pdf=render +38778017,https://doi.org/10.1038/s41541-024-00878-0,Influence of individuals' determinants including vaccine type on cellular and humoral responses to SARS-CoV-2 vaccination.,"Chambers ES, Cai W, Vivaldi G, Jolliffe DA, Perdek N, Li W, Faustini SE, Gibbons JM, Pade C, Richter AG, Coussens AK, Martineau AR.",,NPJ vaccines,2024,2024-05-22,Y,,,,"Vaccine development targeting SARS-CoV-2 in 2020 was of critical importance in reducing COVID-19 severity and mortality. In the U.K. during the initial roll-out most individuals either received two doses of Pfizer COVID-19 vaccine (BNT162b2) or the adenovirus-based vaccine from Oxford/AstraZeneca (ChAdOx1-nCoV-19). There are conflicting data as to the impact of age, sex and body habitus on cellular and humoral responses to vaccination, and most studies in this area have focused on determinants of mRNA vaccine immunogenicity. Here, we studied a cohort of participants in a population-based longitudinal study (COVIDENCE UK) to determine the influence of age, sex, body mass index (BMI) and pre-vaccination anti-Spike (anti-S) antibody status on vaccine-induced humoral and cellular immune responses to two doses of BNT162b2 or ChAdOx-n-CoV-19 vaccination. Younger age and pre-vaccination anti-S seropositivity were both associated with stronger antibody responses to vaccination. BNT162b2 generated higher neutralising and anti-S antibody titres to vaccination than ChAdOx1-nCoV-19, but cellular responses to the two vaccines were no different. Irrespective of vaccine type, increasing age was also associated with decreased frequency of cytokine double-positive CD4+T cells. Increasing BMI was associated with reduced frequency of SARS-CoV-2-specific TNF+CD8% T cells for both vaccines. Together, our findings demonstrate that increasing age and BMI are associated with attenuated cellular and humoral responses to SARS-CoV-2 vaccination. Whilst both vaccines induced T cell responses, BNT162b2 induced significantly elevated humoral immune response as compared to ChAdOx-n-CoV-19.",,pdf:https://www.nature.com/articles/s41541-024-00878-0.pdf; doi:https://doi.org/10.1038/s41541-024-00878-0; html:https://europepmc.org/articles/PMC11111746; pdf:https://europepmc.org/articles/PMC11111746?pdf=render 38467603,https://doi.org/10.1038/s41467-024-46497-0,Impact of vaccination on the association of COVID-19 with cardiovascular diseases: An OpenSAFELY cohort study.,"Cezard GI, Denholm RE, Knight R, Wei Y, Teece L, Toms R, Forbes HJ, Walker AJ, Fisher L, Massey J, Hopcroft LEM, Horne EMF, Taylor K, Palmer T, Arab MA, Cuitun Coronado JI, Ip SHY, Davy S, Dillingham I, Bacon S, Mehrkar A, Morton CE, Greaves F, Hyams C, Davey Smith G, Macleod J, Chaturvedi N, Goldacre B, Whiteley WN, Wood AM, Sterne JAC, Walker V, Longitudinal Health and Wellbeing and Data and Connectivity UK COVID-19 National Core Studies, CONVALESCENCE study and the OpenSAFELY collaborative.",,Nature communications,2024,2024-03-11,Y,,,,"Infection with SARS-CoV-2 is associated with an increased risk of arterial and venous thrombotic events, but the implications of vaccination for this increased risk are uncertain. With the approval of NHS England, we quantified associations between COVID-19 diagnosis and cardiovascular diseases in different vaccination and variant eras using linked electronic health records for ~40% of the English population. We defined a 'pre-vaccination' cohort (18,210,937 people) in the wild-type/Alpha variant eras (January 2020-June 2021), and 'vaccinated' and 'unvaccinated' cohorts (13,572,399 and 3,161,485 people respectively) in the Delta variant era (June-December 2021). We showed that the incidence of each arterial thrombotic, venous thrombotic and other cardiovascular outcomes was substantially elevated during weeks 1-4 after COVID-19, compared with before or without COVID-19, but less markedly elevated in time periods beyond week 4. Hazard ratios were higher after hospitalised than non-hospitalised COVID-19 and higher in the pre-vaccination and unvaccinated cohorts than the vaccinated cohort. COVID-19 vaccination reduces the risk of cardiovascular events after COVID-19 infection. People who had COVID-19 before or without being vaccinated are at higher risk of cardiovascular events for at least two years.",,pdf:https://www.nature.com/articles/s41467-024-46497-0.pdf; doi:https://doi.org/10.1038/s41467-024-46497-0; html:https://europepmc.org/articles/PMC10928172; pdf:https://europepmc.org/articles/PMC10928172?pdf=render 37587102,https://doi.org/10.1038/s41467-023-40643-w,"SARS-CoV-2 rapid antibody test results and subsequent risk of hospitalisation and death in 361,801 people.","Whitaker M, Davies B, Atchison C, Barclay W, Ashby D, Darzi A, Riley S, Cooke G, Donnelly CA, Chadeau-Hyam M, Elliott P, Ward H.",,Nature communications,2023,2023-08-16,Y,,,,"The value of SARS-CoV-2 lateral flow immunoassay (LFIA) tests for estimating individual disease risk is unclear. The REACT-2 study in England, UK, obtained self-administered SARS-CoV-2 LFIA test results from 361,801 adults in January-May 2021. Here, we link to routine data on subsequent hospitalisation (to September 2021), and death (to December 2021). Among those who had received one or more vaccines, a negative LFIA is associated with increased risk of hospitalisation with COVID-19 (HR: 2.73 [95% confidence interval: 1.15,6.48]), death (all-cause) (HR: 1.59, 95% CI:1.07, 2.37), and death with COVID-19 as underlying cause (20.6 [1.83,232]). For people designated at high risk from COVID-19, who had received one or more vaccines, there is an additional risk of all-cause mortality of 1.9 per 1000 for those testing antibody negative compared to positive. However, the LFIA does not provide substantial predictive information over and above that which is available from detailed sociodemographic and health-related variables. Nonetheless, this simple test provides a marker which could be a valuable addition to understanding population and individual-level risk.",,doi:https://doi.org/10.1038/s41467-023-40643-w; html:https://europepmc.org/articles/PMC10432566; pdf:https://europepmc.org/articles/PMC10432566?pdf=render 38053867,https://doi.org/10.1016/j.heliyon.2023.e21734,Wastewater-based surveillance models for COVID-19: A focused review on spatio-temporal models.,"Torabi F, Li G, Mole C, Nicholson G, Rowlingson B, Smith CR, Jersakova R, Diggle PJ, Blangiardo M.",,Heliyon,2023,2023-11-08,Y,Wastewater-based Epidemiology; Covid-19; Wastewater-Based Surveillance; Spatio-Temporal Statistical Modelling,,,"The evident shedding of the SARS-CoV-2 RNA particles from infected individuals into the wastewater opened up a tantalizing array of possibilities for prediction of COVID-19 prevalence prior to symptomatic case identification through community testing. Many countries have therefore explored the use of wastewater metrics as a surveillance tool, replacing traditional direct measurement of prevalence with cost-effective approaches based on SARS-CoV-2 RNA concentrations in wastewater samples. Two important aspects in building prediction models are: time over which the prediction occurs and space for which the predicted case numbers is shown. In this review, our main focus was on finding mathematical models which take into the account both the time-varying and spatial nature of wastewater-based metrics into account. We used six main characteristics as our assessment criteria: i) modelling approach; ii) temporal coverage; iii) spatial coverage; iv) sample size; v) wastewater sampling method; and vi) covariates included in the modelling. The majority of studies in the early phases of the pandemic recognized the temporal association of SARS-CoV-2 RNA concentration level in wastewater with the number of COVID-19 cases, ignoring their spatial context. We examined 15 studies up to April 2023, focusing on models considering both temporal and spatial aspects of wastewater metrics. Most early studies correlated temporal SARS-CoV-2 RNA levels with COVID-19 cases but overlooked spatial factors. Linear regression and SEIR models were commonly used (n = 10, 66.6 % of studies), along with machine learning (n = 1, 6.6 %) and Bayesian approaches (n = 1, 6.6 %) in some cases. Three studies employed spatio-temporal modelling approach (n = 3, 20.0 %). We conclude that the development, validation and calibration of further spatio-temporally explicit models should be done in parallel with the advancement of wastewater metrics before the potential of wastewater as a surveillance tool can be fully realised.",,doi:https://doi.org/10.1016/j.heliyon.2023.e21734; html:https://europepmc.org/articles/PMC10694161; pdf:https://europepmc.org/articles/PMC10694161?pdf=render 38491011,https://doi.org/10.1038/s41467-024-46451-0,"Uptake of COVID-19 vaccinations amongst 3,433,483 children and young people: meta-analysis of UK prospective cohorts.","Aldridge SJ, Agrawal U, Murphy S, Millington T, Akbari A, Almaghrabi F, Anand SN, Bedston S, Goudie R, Griffiths R, Joy M, Lowthian E, de Lusignan S, Patterson L, Robertson C, Rudan I, Bradley DT, Lyons RA, Sheikh A, Owen RK.",,Nature communications,2024,2024-03-15,Y,,,,"SARS-CoV-2 infection in children and young people (CYP) can lead to life-threatening COVID-19, transmission within households and schools, and the development of long COVID. Using linked health and administrative data, we investigated vaccine uptake among 3,433,483 CYP aged 5-17 years across all UK nations between 4th August 2021 and 31st May 2022. We constructed national cohorts and undertook multi-state modelling and meta-analysis to identify associations between demographic variables and vaccine uptake. We found that uptake of the first COVID-19 vaccine among CYP was low across all four nations compared to other age groups and diminished with subsequent doses. Age and vaccination status of adults living in the same household were identified as important risk factors associated with vaccine uptake in CYP. For example, 5-11 year-olds were less likely to receive their first vaccine compared to 16-17 year-olds (adjusted Hazard Ratio [aHR]: 0.10 (95%CI: 0.06-0.19)), and CYP in unvaccinated households were less likely to receive their first vaccine compared to CYP in partially vaccinated households (aHR: 0.19, 95%CI 0.13-0.29).",,doi:https://doi.org/10.1038/s41467-024-46451-0; html:https://europepmc.org/articles/PMC10943015; pdf:https://europepmc.org/articles/PMC10943015?pdf=render 38388690,https://doi.org/10.1038/s41597-024-02958-1,"Ethnicity data resource in population-wide health records: completeness, coverage and granularity of diversity.","Pineda-Moncusí M, Allery F, Delmestri A, Bolton T, Nolan J, Thygesen JH, Handy A, Banerjee A, Denaxas S, Tomlinson C, Denniston AK, Sudlow C, Akbari A, Wood A, Collins GS, Petersen I, Coates LC, Khunti K, Prieto-sAlhambra D, Khalid S, CVD-COVID-UK/COVID-IMPACT Consortium.",,Scientific data,2024,2024-02-22,Y,,,,"Intersectional social determinants including ethnicity are vital in health research. We curated a population-wide data resource of self-identified ethnicity data from over 60 million individuals in England primary care, linking it to hospital records. We assessed ethnicity data in terms of completeness, consistency, and granularity and found one in ten individuals do not have ethnicity information recorded in primary care. By linking to hospital records, ethnicity data were completed for 94% of individuals. By reconciling SNOMED-CT concepts and census-level categories into a consistent hierarchy, we organised more than 250 ethnicity sub-groups including and beyond ""White"", ""Black"", ""Asian"", ""Mixed"" and ""Other, and found them to be distributed in proportions similar to the general population. This large observational dataset presents an algorithmic hierarchy to represent self-identified ethnicity data collected across heterogeneous healthcare settings. Accurate and easily accessible ethnicity data can lead to a better understanding of population diversity, which is important to address disparities and influence policy recommendations that can translate into better, fairer health for all.",,pdf:https://www.nature.com/articles/s41597-024-02958-1.pdf; doi:https://doi.org/10.1038/s41597-024-02958-1; html:https://europepmc.org/articles/PMC10883937; pdf:https://europepmc.org/articles/PMC10883937?pdf=render 37243092,https://doi.org/10.3390/vaccines11050988,A Methodological Framework for Assessing the Benefit of SARS-CoV-2 Vaccination following Previous Infection: Case Study of Five- to Eleven-Year-Olds.,"Pagel C, Wilde H, Tomlinson C, Mateen B, Brown K.",,Vaccines,2023,2023-05-16,Y,Health Policy; Mathematical Modelling; Covid-19; Paediatric Vaccines,,,"Vaccination rates against SARS-CoV-2 in children aged five to eleven years remain low in many countries. The current benefit of vaccination in this age group has been questioned given that the large majority of children have now experienced at least one SARS-CoV-2 infection. However, protection from infection, vaccination or both wanes over time. National decisions on offering vaccines to this age group have tended to be made without considering time since infection. There is an urgent need to evaluate the additional benefits of vaccination in previously infected children and under what circumstances those benefits accrue. We present a novel methodological framework for estimating the potential benefits of COVID-19 vaccination in previously infected children aged five to eleven, accounting for waning. We apply this framework to the UK context and for two adverse outcomes: hospitalisation related to SARS-CoV-2 infection and Long Covid. We show that the most important drivers of benefit are: the degree of protection provided by previous infection; the protection provided by vaccination; the time since previous infection; and future attack rates. Vaccination can be very beneficial for previously infected children if future attack rates are high and several months have elapsed since the previous major wave in this group. Benefits are generally larger for Long Covid than hospitalisation, because Long Covid is both more common than hospitalisation and previous infection offers less protection against it. Our framework provides a structure for policy makers to explore the additional benefit of vaccination across a range of adverse outcomes and different parameter assumptions. It can be easily updated as new evidence emerges.",,pdf:https://www.mdpi.com/2076-393X/11/5/988/pdf?version=1684231380; doi:https://doi.org/10.3390/vaccines11050988; html:https://europepmc.org/articles/PMC10220644; pdf:https://europepmc.org/articles/PMC10220644?pdf=render +37118449,https://doi.org/10.1038/s43587-022-00224-w,Robust SARS-CoV-2-specific and heterologous immune responses in vaccine-naïve residents of long-term care facilities who survive natural infection.,"Tut G, Lancaster T, Butler MS, Sylla P, Spalkova E, Bone D, Kaur N, Bentley C, Amin U, Jadir AT, Hulme S, Ayodel M, Dowell AC, Pearce H, Zuo J, Margielewska-Davies S, Verma K, Nicol S, Begum J, Jinks E, Tut E, Bruton R, Krutikov M, Shrotri M, Giddings R, Azmi B, Fuller C, Irwin-Singer A, Hayward A, Copas A, Shallcross L, Moss P.",,Nature aging,2022,2022-05-30,Y,,,,"We studied humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 152 long-term care facility staff and 124 residents over a prospective 4-month period shortly after the first wave of infection in England. We show that residents of long-term care facilities developed high and stable levels of antibodies against spike protein and receptor-binding domain. Nucleocapsid-specific responses were also elevated but waned over time. Antibodies showed stable and equivalent levels of functional inhibition against spike-angiotensin-converting enzyme 2 binding in all age groups with comparable activity against viral variants of concern. SARS-CoV-2 seropositive donors showed high levels of antibodies to other beta-coronaviruses but serostatus did not impact humoral immunity to influenza or other respiratory syncytial viruses. SARS-CoV-2-specific cellular responses were similar across all ages but virus-specific populations showed elevated levels of activation in older donors. Thus, survivors of SARS-CoV-2 infection show a robust and stable immunity against the virus that does not negatively impact responses to other seasonal viruses.",,pdf:https://www.nature.com/articles/s43587-022-00224-w.pdf; doi:https://doi.org/10.1038/s43587-022-00224-w; html:https://europepmc.org/articles/PMC10154219; pdf:https://europepmc.org/articles/PMC10154219?pdf=render 37228015,https://doi.org/10.1371/journal.pbio.3002118,Dynamics of SARS-CoV-2 infection hospitalisation and infection fatality ratios over 23 months in England.,"Eales O, Haw D, Wang H, Atchison C, Ashby D, Cooke GS, Barclay W, Ward H, Darzi A, Donnelly CA, Chadeau-Hyam M, Elliott P, Riley S.",,PLoS biology,2023,2023-05-25,Y,,,,"The relationship between prevalence of infection and severe outcomes such as hospitalisation and death changed over the course of the COVID-19 pandemic. Reliable estimates of the infection fatality ratio (IFR) and infection hospitalisation ratio (IHR) along with the time-delay between infection and hospitalisation/death can inform forecasts of the numbers/timing of severe outcomes and allow healthcare services to better prepare for periods of increased demand. The REal-time Assessment of Community Transmission-1 (REACT-1) study estimated swab positivity for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in England approximately monthly from May 2020 to March 2022. Here, we analyse the changing relationship between prevalence of swab positivity and the IFR and IHR over this period in England, using publicly available data for the daily number of deaths and hospitalisations, REACT-1 swab positivity data, time-delay models, and Bayesian P-spline models. We analyse data for all age groups together, as well as in 2 subgroups: those aged 65 and over and those aged 64 and under. Additionally, we analysed the relationship between swab positivity and daily case numbers to estimate the case ascertainment rate of England's mass testing programme. During 2020, we estimated the IFR to be 0.67% and the IHR to be 2.6%. By late 2021/early 2022, the IFR and IHR had both decreased to 0.097% and 0.76%, respectively. The average case ascertainment rate over the entire duration of the study was estimated to be 36.1%, but there was some significant variation in continuous estimates of the case ascertainment rate. Continuous estimates of the IFR and IHR of the virus were observed to increase during the periods of Alpha and Delta's emergence. During periods of vaccination rollout, and the emergence of the Omicron variant, the IFR and IHR decreased. During 2020, we estimated a time-lag of 19 days between hospitalisation and swab positivity, and 26 days between deaths and swab positivity. By late 2021/early 2022, these time-lags had decreased to 7 days for hospitalisations and 18 days for deaths. Even though many populations have high levels of immunity to SARS-CoV-2 from vaccination and natural infection, waning of immunity and variant emergence will continue to be an upwards pressure on the IHR and IFR. As investments in community surveillance of SARS-CoV-2 infection are scaled back, alternative methods are required to accurately track the ever-changing relationship between infection, hospitalisation, and death and hence provide vital information for healthcare provision and utilisation.",,pdf:https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002118&type=printable; doi:https://doi.org/10.1371/journal.pbio.3002118; html:https://europepmc.org/articles/PMC10212114; pdf:https://europepmc.org/articles/PMC10212114?pdf=render 37056776,https://doi.org/10.3389/fimmu.2023.1146702,"SARS-CoV-2 antibody responses associate with sex, age and disease severity in previously uninfected people admitted to hospital with COVID-19: An ISARIC4C prospective study.","Parker E, Thomas J, Roper KJ, Ijaz S, Edwards T, Marchesin F, Katsanovskaja K, Lett L, Jones C, Hardwick HE, Davis C, Vink E, McDonald SE, Moore SC, Dicks S, Jegatheesan K, Cook NJ, Hope J, Cherepanov P, McClure MO, Baillie JK, Openshaw PJM, Turtle L, Ho A, Semple MG, Paxton WA, Tedder RS, Pollakis G, ISARIC4C Investigators.",,Frontiers in immunology,2023,2023-03-15,Y,Serology; Virus; Disease; immunology; Neutralisation; Covid-19; Sars-cov-2,,,"The SARS-CoV-2 pandemic enables the analysis of immune responses induced against a novel coronavirus infecting immunologically naïve individuals. This provides an opportunity for analysis of immune responses and associations with age, sex and disease severity. Here we measured an array of solid-phase binding antibody and viral neutralising Ab (nAb) responses in participants (n=337) of the ISARIC4C cohort and characterised their correlation with peak disease severity during acute infection and early convalescence. Overall, the responses in a Double Antigen Binding Assay (DABA) for antibody to the receptor binding domain (anti-RBD) correlated well with IgM as well as IgG responses against viral spike, S1 and nucleocapsid protein (NP) antigens. DABA reactivity also correlated with nAb. As we and others reported previously, there is greater risk of severe disease and death in older men, whilst the sex ratio was found to be equal within each severity grouping in younger people. In older males with severe disease (mean age 68 years), peak antibody levels were found to be delayed by one to two weeks compared with women, and nAb responses were delayed further. Additionally, we demonstrated that solid-phase binding antibody responses reached higher levels in males as measured via DABA and IgM binding against Spike, NP and S1 antigens. In contrast, this was not observed for nAb responses. When measuring SARS-CoV-2 RNA transcripts (as a surrogate for viral shedding) in nasal swabs at recruitment, we saw no significant differences by sex or disease severity status. However, we have shown higher antibody levels associated with low nasal viral RNA indicating a role of antibody responses in controlling viral replication and shedding in the upper airway. In this study, we have shown discernible differences in the humoral immune responses between males and females and these differences associate with age as well as with resultant disease severity.",,pdf:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1146702/pdf; doi:https://doi.org/10.3389/fimmu.2023.1146702; html:https://europepmc.org/articles/PMC10087108; pdf:https://europepmc.org/articles/PMC10087108?pdf=render -37118449,https://doi.org/10.1038/s43587-022-00224-w,Robust SARS-CoV-2-specific and heterologous immune responses in vaccine-naïve residents of long-term care facilities who survive natural infection.,"Tut G, Lancaster T, Butler MS, Sylla P, Spalkova E, Bone D, Kaur N, Bentley C, Amin U, Jadir AT, Hulme S, Ayodel M, Dowell AC, Pearce H, Zuo J, Margielewska-Davies S, Verma K, Nicol S, Begum J, Jinks E, Tut E, Bruton R, Krutikov M, Shrotri M, Giddings R, Azmi B, Fuller C, Irwin-Singer A, Hayward A, Copas A, Shallcross L, Moss P.",,Nature aging,2022,2022-05-30,Y,,,,"We studied humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 152 long-term care facility staff and 124 residents over a prospective 4-month period shortly after the first wave of infection in England. We show that residents of long-term care facilities developed high and stable levels of antibodies against spike protein and receptor-binding domain. Nucleocapsid-specific responses were also elevated but waned over time. Antibodies showed stable and equivalent levels of functional inhibition against spike-angiotensin-converting enzyme 2 binding in all age groups with comparable activity against viral variants of concern. SARS-CoV-2 seropositive donors showed high levels of antibodies to other beta-coronaviruses but serostatus did not impact humoral immunity to influenza or other respiratory syncytial viruses. SARS-CoV-2-specific cellular responses were similar across all ages but virus-specific populations showed elevated levels of activation in older donors. Thus, survivors of SARS-CoV-2 infection show a robust and stable immunity against the virus that does not negatively impact responses to other seasonal viruses.",,pdf:https://www.nature.com/articles/s43587-022-00224-w.pdf; doi:https://doi.org/10.1038/s43587-022-00224-w; html:https://europepmc.org/articles/PMC10154219; pdf:https://europepmc.org/articles/PMC10154219?pdf=render 38381822,https://doi.org/10.1126/sciadv.adi9379,"Spontaneous, persistent, T cell-dependent IFN-γ release in patients who progress to Long Covid.","Krishna BA, Lim EY, Metaxaki M, Jackson S, Mactavous L, NIHR BioResource, Lyons PA, Doffinger R, Bradley JR, Smith KGC, Sinclair J, Matheson NJ, Lehner PJ, Sithole N, Wills MR.",,Science advances,2024,2024-02-21,Y,,,,"After acute infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a proportion of patients experience persistent symptoms beyond 12 weeks, termed Long Covid. Understanding the mechanisms that cause this debilitating disease and identifying biomarkers for diagnostic, therapeutic, and monitoring purposes are urgently required. We detected persistently high levels of interferon-γ (IFN-γ) from peripheral blood mononuclear cells of patients with Long Covid using highly sensitive FluoroSpot assays. This IFN-γ release was seen in the absence of ex vivo peptide stimulation and remains persistently elevated in patients with Long Covid, unlike the resolution seen in patients recovering from acute SARS-CoV-2 infection. The IFN-γ release was CD8+ T cell-mediated and dependent on antigen presentation by CD14+ cells. Longitudinal follow-up of our study cohort showed that symptom improvement and resolution correlated with a decrease in IFN-γ production to baseline levels. Our study highlights a potential mechanism underlying Long Covid, enabling the search for biomarkers and therapeutics in patients with Long Covid.",,pdf:https://www.science.org/doi/pdf/10.1126/sciadv.adi9379?download=true; doi:https://doi.org/10.1126/sciadv.adi9379; html:https://europepmc.org/articles/PMC10881041; pdf:https://europepmc.org/articles/PMC10881041?pdf=render 38036541,https://doi.org/10.1038/s41467-023-43661-w,"True prevalence of long-COVID in a nationwide, population cohort study.","Hastie CE, Lowe DJ, McAuley A, Mills NL, Winter AJ, Black C, Scott JT, O'Donnell CA, Blane DN, Browne S, Ibbotson TR, Pell JP.",,Nature communications,2023,2023-11-30,Y,,,,"Long-COVID prevalence estimates vary widely and should take account of symptoms that would have occurred anyway. Here we determine the prevalence of symptoms attributable to SARS-CoV-2 infection, taking account of background rates and confounding, in a nationwide population cohort study of 198,096 Scottish adults. 98,666 (49.8%) had symptomatic laboratory-confirmed SARS-CoV-2 infections and 99,430 (50.2%) were age-, sex-, and socioeconomically-matched and never-infected. While 41,775 (64.5%) reported at least one symptom 6 months following SARS-CoV-2 infection, this was also true of 34,600 (50.8%) of those never-infected. The crude prevalence of one or more symptom attributable to SARS-CoV-2 infection was 13.8% (13.2%,14.3%), 12.8% (11.9%,13.6%), and 16.3% (14.4%,18.2%) at 6, 12, and 18 months respectively. Following adjustment for potential confounders, these figures were 6.6% (6.3%, 6.9%), 6.5% (6.0%, 6.9%) and 10.4% (9.1%, 11.6%) respectively. Long-COVID is characterised by a wide range of symptoms that, apart from altered taste and smell, are non-specific. Care should be taken in attributing symptoms to previous SARS-CoV-2 infection.",,pdf:https://www.nature.com/articles/s41467-023-43661-w.pdf; doi:https://doi.org/10.1038/s41467-023-43661-w; html:https://europepmc.org/articles/PMC10689486; pdf:https://europepmc.org/articles/PMC10689486?pdf=render 37124948,https://doi.org/10.1016/j.lanepe.2023.100638,Severity of Omicron BA.5 variant and protective effect of vaccination: national cohort and matched analyses in Scotland.,"Robertson C, Kerr S, Sheikh A.",,The Lancet regional health. Europe,2023,2023-04-14,Y,,,,,,doi:https://doi.org/10.1016/j.lanepe.2023.100638; doi:https://doi.org/10.1016/j.lanepe.2023.100638; html:https://europepmc.org/articles/PMC10139952; pdf:https://europepmc.org/articles/PMC10139952?pdf=render @@ -52,8 +52,8 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc 38806176,https://doi.org/10.1177/00045632241261274,A SARS-CoV-2 minimum data standard to support national serology reporting.,"Urwin EN, Martin J, Sebire N, Harris A, Johnston J, Masood E, Milligan G, Mairs L, Chuter A, Ferguson M, Quinlan P, Jefferson E.",,Annals of clinical biochemistry,2024,2024-05-28,N,Computers; Laboratory Management; Laboratory Methods; Analytical Systems,,,"

Background

Healthcare laboratory systems produce and capture a vast array of information, yet do not always report all of this to the national infrastructure within the United Kingdom. The global COVID-19 pandemic brought about a much greater need for detailed healthcare data, one such instance being laboratory testing data. The reporting of qualitative laboratory test results (e.g., positive, negative or indeterminate) provides a basic understanding of levels of seropositivity. However, to better understand and interpret seropositivity, how it is determined and other factors that affect its calculation (i.e., levels of antibodies), quantitative laboratory test data are needed.

Method

36 data attributes were collected from 3 NHS laboratories and 20 CO-CONNECT project partner organisations. These were assessed against the need for a minimum dataset to determine data attribute importance. An NHS laboratory feasibility study was undertaken to assess the minimum data standard, together with a literature review of national and international data standards and healthcare reports.

Results

A COVID serology minimum data standard (CSMDS) comprising 12 data attributes was created and verified by 3 NHS laboratories to allow national granular reporting of COVID serology results. To support this, a standardised set of vocabulary terms was developed to represent laboratory analyser systems and laboratory information management systems.

Conclusions

This paper puts forward a minimum viable standard for COVID-19 serology data attributes to enhance its granularity and augment the national reporting of COVID-19 serology laboratory results, with implications for future pandemics.",,doi:https://doi.org/10.1177/00045632241261274 37126810,https://doi.org/10.7326/m21-4269,Challenges in Estimating the Effectiveness of COVID-19 Vaccination Using Observational Data.,"Hulme WJ, Williamson E, Horne EMF, Green A, McDonald HI, Walker AJ, Curtis HJ, Morton CE, MacKenna B, Croker R, Mehrkar A, Bacon S, Evans D, Inglesby P, Davy S, Bhaskaran K, Schultze A, Rentsch CT, Tomlinson L, Douglas IJ, Evans SJW, Smeeth L, Palmer T, Goldacre B, Hernán MA, Sterne JAC.",,Annals of internal medicine,2023,2023-05-02,N,,,,"The COVID-19 vaccines were developed and rigorously evaluated in randomized trials during 2020. However, important questions, such as the magnitude and duration of protection, their effectiveness against new virus variants, and the effectiveness of booster vaccination, could not be answered by randomized trials and have therefore been addressed in observational studies. Analyses of observational data can be biased because of confounding and because of inadequate design that does not consider the evolution of the pandemic over time and the rapid uptake of vaccination. Emulating a hypothetical ""target trial"" using observational data assembled during vaccine rollouts can help manage such potential sources of bias. This article describes 2 approaches to target trial emulation. In the sequential approach, on each day, eligible persons who have not yet been vaccinated are matched to a vaccinated person. The single-trial approach sets a single baseline at the start of the rollout and considers vaccination as a time-varying variable. The nature of the confounding depends on the analysis strategy: Estimating ""per-protocol"" effects (accounting for vaccination of initially unvaccinated persons after baseline) may require adjustment for both baseline and ""time-varying"" confounders. These issues are illustrated by using observational data from 2 780 931 persons in the United Kingdom aged 70 years or older to estimate the effect of a first dose of a COVID-19 vaccine. Addressing the issues discussed in this article should help authors of observational studies provide robust evidence to guide clinical and policy decisions.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10152408; doi:https://doi.org/10.7326/M21-4269; html:https://europepmc.org/articles/PMC10152408; pdf:https://europepmc.org/articles/PMC10152408?pdf=render; doi:https://doi.org/10.7326/m21-4269 36825398,https://doi.org/10.1097/mcp.0000000000000948,Effectiveness and safety of coronavirus disease 2019 vaccines.,"Shi T, Robertson C, Sheikh A.",,Current opinion in pulmonary medicine,2023,2023-02-24,Y,,,,"

Purpose of review

To review and summarise recent evidence on the effectiveness of coronavirus disease 2019 (COVID-19) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 hospitalisation and death in adults as well as in specific population groups, namely pregnant women, and children and adolescents. We also sought to summarise evidence on vaccine safety in relation to cardiovascular and neurological complications. In order to do so, we drew primarily on evidence from two our own data platforms and supplement these with insights from related large population-based studies and systematic reviews.

Recent findings

All studies showed high vaccine effectiveness against confirmed SARS-CoV-2 infection and in particular against COVID-19 hospitalisation and death. However, vaccine effectiveness against symptomatic COVID-19 infection waned over time. These studies also found that booster vaccines would be needed to maintain high vaccine effectiveness against severe COVID-19 outcomes. Rare cardiovascular and neurological complications have been reported in association with COVID-19 vaccines.

Summary

The findings from this paper support current recommendations that vaccination remains the safest way for adults, pregnant women, children and adolescents to be protected against COVID-19. There is a need to continue to monitor the effectiveness and safety of COVID-19 vaccines as these continue to be deployed in the evolving pandemic.",,html:https://journals.lww.com/co-pulmonarymedicine/Fulltext/9900/Effectiveness_and_safety_of_coronavirus_disease.53.aspx; doi:https://doi.org/10.1097/MCP.0000000000000948; html:https://europepmc.org/articles/PMC10090353; pdf:https://europepmc.org/articles/PMC10090353?pdf=render -38106559,https://doi.org/10.1016/j.eclinm.2023.102251,Long-term symptom profiles after COVID-19 vs other acute respiratory infections: an analysis of data from the COVIDENCE UK study.,"Vivaldi G, Pfeffer PE, Talaei M, Basera TJ, Shaheen SO, Martineau AR.",,EClinicalMedicine,2023,2023-10-06,Y,Acute respiratory infections; Sars-cov-2; Long Covid; Post-acute Sequelae,,,"

Background

Long COVID is a well recognised, if heterogeneous, entity. Acute respiratory infections (ARIs) due to other pathogens may cause long-term symptoms, but few studies compare post-acute sequelae between SARS-CoV-2 and other ARIs. We aimed to compare symptom profiles between people with previous SARS-CoV-2 infection, people with previous non-COVID-19 ARIs, and contemporaneous controls, and to identify clusters of long-term symptoms.

Methods

COVIDENCE UK is a prospective, population-based UK study of ARIs in adults. We analysed data for 16 potential long COVID symptoms and health-related quality of life (HRQoL), reported between January 21 and February 15, 2021, by participants unvaccinated against SARS-CoV-2. We classified participants as having previous SARS-CoV-2 infection or previous non-COVID-19 ARI (≥4 weeks prior) or no reported ARI. We compared symptoms by infection status using logistic and fractional regression, and identified symptom clusters using latent class analysis (LCA). This study is registered with ClinicalTrials.gov, NCT04330599.

Findings

We included 10,171 participants (1311 [12.9%] with SARS-CoV-2 infection, 472 [4.6%] with non-COVID-19 ARI). Both types of infection were associated with increased prevalence/severity of most symptoms and decreased HRQoL compared with no infection. Participants with SARS-CoV-2 infection had increased odds of problems with taste/smell (odds ratio 19.74, 95% CI 10.53-37.00) and lightheadedness or dizziness (1.74, 1.18-2.56) compared with participants with non-COVID-19 ARIs. Separate LCA models identified three symptom severity groups for each infection type. In the most severe groups (representing 22% of participants for both SARS-CoV-2 and non-COVID-19 ARI), SARS-CoV-2 infection presented with a higher probability of problems with taste/smell (probability 0.41 vs 0.04), hair loss (0.25 vs 0.16), unusual sweating (0.38 vs 0.25), unusual racing of the heart (0.43 vs 0.33), and memory problems (0.70 vs 0.55) than non-COVID-19 ARI.

Interpretation

Both SARS-CoV-2 and non-COVID-19 ARIs are associated with a wide range of symptoms more than 4 weeks after the acute infection. Research on post-acute sequelae of ARIs should extend from SARS-CoV-2 to include other pathogens.

Funding

Barts Charity.",,doi:https://doi.org/10.1016/j.eclinm.2023.102251; html:https://europepmc.org/articles/PMC10721552; pdf:https://europepmc.org/articles/PMC10721552?pdf=render 34994801,https://doi.org/10.1093/pubmed/fdab400,COVID-19 vaccination uptake amongst ethnic minority communities in England: a linked study exploring the drivers of differential vaccination rates.,"Gaughan CH, Razieh C, Khunti K, Banerjee A, Chudasama YV, Davies MJ, Dolby T, Gillies CL, Lawson C, Mirkes EM, Morgan J, Tingay K, Zaccardi F, Yates T, Nafilyan V.",,"Journal of public health (Oxford, England)",2023,2023-03-01,Y,Vaccination; Cultural; Ethnicity; Social; Sociodemographic Factors; Demographic; Covid-19,,,"

Background

Despite generally high coronavirus disease 2019 (COVID-19) vaccination rates in the UK, vaccination hesitancy and lower take-up rates have been reported in certain ethnic minority communities.

Methods

We used vaccination data from the National Immunisation Management System (NIMS) linked to the 2011 Census and individual health records for subjects aged ≥40 years (n = 24 094 186). We estimated age-standardized vaccination rates, stratified by ethnic group and key sociodemographic characteristics, such as religious affiliation, deprivation, educational attainment, geography, living conditions, country of birth, language skills and health status. To understand the association of ethnicity with lower vaccination rates, we conducted a logistic regression model adjusting for differences in geographic, sociodemographic and health characteristics. ResultsAll ethnic groups had lower age-standardized rates of vaccination compared with the white British population, whose vaccination rate of at least one dose was 94% (95% CI: 94%-94%). Black communities had the lowest rates, with 75% (74-75%) of black African and 66% (66-67%) of black Caribbean individuals having received at least one dose. The drivers of these lower rates were partly explained by accounting for sociodemographic differences. However, modelled estimates showed significant differences remained for all minority ethnic groups, compared with white British individuals.

Conclusions

Lower COVID-19 vaccination rates are consistently observed amongst all ethnic minorities.",,pdf:https://academic.oup.com/jpubhealth/article-pdf/45/1/e65/49527132/fdab400.pdf; doi:https://doi.org/10.1093/pubmed/fdab400; html:https://europepmc.org/articles/PMC8755382; pdf:https://europepmc.org/articles/PMC8755382?pdf=render +38106559,https://doi.org/10.1016/j.eclinm.2023.102251,Long-term symptom profiles after COVID-19 vs other acute respiratory infections: an analysis of data from the COVIDENCE UK study.,"Vivaldi G, Pfeffer PE, Talaei M, Basera TJ, Shaheen SO, Martineau AR.",,EClinicalMedicine,2023,2023-10-06,Y,Acute respiratory infections; Sars-cov-2; Long Covid; Post-acute Sequelae,,,"

Background

Long COVID is a well recognised, if heterogeneous, entity. Acute respiratory infections (ARIs) due to other pathogens may cause long-term symptoms, but few studies compare post-acute sequelae between SARS-CoV-2 and other ARIs. We aimed to compare symptom profiles between people with previous SARS-CoV-2 infection, people with previous non-COVID-19 ARIs, and contemporaneous controls, and to identify clusters of long-term symptoms.

Methods

COVIDENCE UK is a prospective, population-based UK study of ARIs in adults. We analysed data for 16 potential long COVID symptoms and health-related quality of life (HRQoL), reported between January 21 and February 15, 2021, by participants unvaccinated against SARS-CoV-2. We classified participants as having previous SARS-CoV-2 infection or previous non-COVID-19 ARI (≥4 weeks prior) or no reported ARI. We compared symptoms by infection status using logistic and fractional regression, and identified symptom clusters using latent class analysis (LCA). This study is registered with ClinicalTrials.gov, NCT04330599.

Findings

We included 10,171 participants (1311 [12.9%] with SARS-CoV-2 infection, 472 [4.6%] with non-COVID-19 ARI). Both types of infection were associated with increased prevalence/severity of most symptoms and decreased HRQoL compared with no infection. Participants with SARS-CoV-2 infection had increased odds of problems with taste/smell (odds ratio 19.74, 95% CI 10.53-37.00) and lightheadedness or dizziness (1.74, 1.18-2.56) compared with participants with non-COVID-19 ARIs. Separate LCA models identified three symptom severity groups for each infection type. In the most severe groups (representing 22% of participants for both SARS-CoV-2 and non-COVID-19 ARI), SARS-CoV-2 infection presented with a higher probability of problems with taste/smell (probability 0.41 vs 0.04), hair loss (0.25 vs 0.16), unusual sweating (0.38 vs 0.25), unusual racing of the heart (0.43 vs 0.33), and memory problems (0.70 vs 0.55) than non-COVID-19 ARI.

Interpretation

Both SARS-CoV-2 and non-COVID-19 ARIs are associated with a wide range of symptoms more than 4 weeks after the acute infection. Research on post-acute sequelae of ARIs should extend from SARS-CoV-2 to include other pathogens.

Funding

Barts Charity.",,doi:https://doi.org/10.1016/j.eclinm.2023.102251; html:https://europepmc.org/articles/PMC10721552; pdf:https://europepmc.org/articles/PMC10721552?pdf=render 38023948,https://doi.org/10.18332/ejm/171802,A qualitative study exploring healthcare workers' lived experiences of the impacts of COVID-19 policies and guidelines on maternal and reproductive healthcare services in the United Kingdom.,"Chaloner J, Qureshi I, Gogoi M, Ekezie WC, Al-Oraibi A, Wobi F, Agbonmwandolor JO, Nellums LB, Pareek M.",,European journal of midwifery,2023,2023-11-08,Y,Healthcare Workers; Vaccine Hesitancy; Redeployment; Infection Controls; Covid-19; Policies And Guidelines,,,"

Introduction

During the COVID-19 pandemic, pregnant women were regarded as vulnerable to poor health outcomes if infected with the SARS-CoV-2 (COVID-19) virus. To protect the United Kingdom's (UK) National Health Service (NHS) and pregnant patients, strict infection control policies and regulations were implemented. This study aimed to understand the impact of the COVID-19 policies and guidelines on maternal and reproductive health services during the pandemic from the experiences of healthcare workers (HCWs) caring for these patients.

Methods

This qualitative study involved HCWs from the United Kingdom Research study into Ethnicity and COVID-19 outcomes in Healthcare workers (UK-REACH) project. Semi-structured interviews and focus groups were conducted online or by telephone with 44 diverse HCWs. Transcripts were thematically analyzed following Braun and Clarke's principles of qualitative analysis.

Results

Three key themes were identified during analysis. First, infection control policies impacted appointment availability, resulting in many cancellations and delays to treatment. Telemedicine was also used extensively to reduce risks from face-to-face consultations, disadvantaging patients from minoritized ethnicities. Secondly, staff shortages and redeployments reduced availability of consultations, appointments, and sonography scans. Finally, staff and patients reported challenges accessing timely, reliable and accurate information and guidance.

Conclusions

COVID-19 demonstrated how a global health crisis can impact maternal and reproductive health services, leading to reduced service quality and surgical delays due to staff redeployment policies. Our findings underscore the implications of policy and future health crises preparedness. This includes tailored infection control policies, addressing elective surgery backlogs early and improved dissemination of relevant vaccine information.",,pdf:https://www.europeanjournalofmidwifery.eu/pdf-171802-96110?filename=A qualitative study.pdf; doi:https://doi.org/10.18332/ejm/171802; html:https://europepmc.org/articles/PMC10630987; pdf:https://europepmc.org/articles/PMC10630987?pdf=render 35110546,https://doi.org/10.1038/s41467-022-28248-1,"A population-based cohort study of obesity, ethnicity and COVID-19 mortality in 12.6 million adults in England.","Yates T, Summerfield A, Razieh C, Banerjee A, Chudasama Y, Davies MJ, Gillies C, Islam N, Lawson C, Mirkes E, Zaccardi F, Khunti K, Nafilyan V.",,Nature communications,2022,2022-02-02,Y,,,,"Obesity and ethnicity are known risk factors for COVID-19 outcomes, but their combination has not been extensively examined. We investigate the association between body mass index (BMI) and COVID-19 mortality across different ethnic groups using linked national Census, electronic health records and mortality data for adults in England from the start of pandemic (January 2020) to December 2020. There were 30,067 (0.27%), 1,208 (0.29%), 1,831 (0.29%), 845 (0.18%) COVID-19 deaths in white, Black, South Asian and other ethnic minority groups, respectively. Here we show that BMI was more strongly associated with COVID-19 mortality in ethnic minority groups, resulting in an ethnic risk of COVID-19 mortality that was dependant on BMI. The estimated risk of COVID-19 mortality at a BMI of 40 kg/m2 in white ethnicities was equivalent to the risk observed at a BMI of 30.1 kg/m2, 27.0 kg/m2, and 32.2 kg/m2 in Black, South Asian and other ethnic minority groups, respectively.",,pdf:https://www.nature.com/articles/s41467-022-28248-1.pdf; doi:https://doi.org/10.1038/s41467-022-28248-1; html:https://europepmc.org/articles/PMC8810846; pdf:https://europepmc.org/articles/PMC8810846?pdf=render 35796183,https://doi.org/10.1177/01410768221107119,"SARS-CoV-2 infection risk among 77,587 healthcare workers: a national observational longitudinal cohort study in Wales, United Kingdom, April to November 2020.","Hollinghurst J, North L, Szakmany T, Pugh R, Davies GA, Sivakumaran S, Jarvis R, Rolles M, Pickrell WO, Akbari A, Davies G, Griffiths R, Lyons J, Torabi F, Fry R, Gravenor MB, Lyons RA.",,Journal of the Royal Society of Medicine,2022,2022-07-07,Y,Public Health; Healthcare Workers; Infection Risk; Covid-19; Sars-cov-2,,,"

Objectives

To better understand the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among healthcare workers, leading to recommendations for the prioritisation of personal protective equipment, testing, training and vaccination.

Design

Observational, longitudinal, national cohort study.

Setting

Our cohort were secondary care (hospital-based) healthcare workers employed by NHS Wales (United Kingdom) organisations from 1 April 2020 to 30 November 2020.

Participants

We included 577,756 monthly observations among 77,587 healthcare workers. Using linked anonymised datasets, participants were grouped into 20 staff roles. Additionally, each role was deemed either patient-facing, non-patient-facing or undetermined. This was linked to individual demographic details and dates of positive SARS-CoV-2 PCR tests.

Main outcome measures

We used univariable and multivariable logistic regression models to determine odds ratios (ORs) for the risk of a positive SARS-CoV-2 PCR test.

Results

Patient-facing healthcare workers were at the highest risk of SARS-CoV-2 infection with an adjusted OR (95% confidence interval [CI]) of 2.28 (95% CI 2.10-2.47). We found that after adjustment, foundation year doctors (OR 1.83 [95% CI 1.47-2.27]), healthcare support workers [OR 1.36 [95% CI 1.20-1.54]) and hospital nurses (OR 1.27 [95% CI 1.12-1.44]) were at the highest risk of infection among all staff groups. Younger healthcare workers and those living in more deprived areas were at a higher risk of infection. We also observed that infection rates varied over time and by organisation.

Conclusions

These findings have important policy implications for the prioritisation of vaccination, testing, training and personal protective equipment provision for patient-facing roles and the higher risk staff groups.",,doi:https://doi.org/10.1177/01410768221107119; doi:https://doi.org/10.1177/01410768221107119; html:https://europepmc.org/articles/PMC9747896; pdf:https://europepmc.org/articles/PMC9747896?pdf=render @@ -73,8 +73,8 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc 34514500,https://doi.org/10.1093/infdis/jiab459,The Impact of Cocirculating Pathogens on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)/Coronavirus Disease 2019 Surveillance: How Concurrent Epidemics May Introduce Bias and Decrease the Observed SARS-CoV-2 Percentage Positivity.,"Kovacevic A, Eggo RM, Baguelin M, Domenech de Cellès M, Opatowski L.",,The Journal of infectious diseases,2022,2022-01-01,Y,Mathematical Modeling; Multiplex Testing; Sars-cov-2; Covid-19 Surveillance; Cocirculating Respiratory Viruses,,,"

Background

Circulation of seasonal non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) respiratory viruses with syndromic overlap during the coronavirus disease 2019 (COVID-19) pandemic may alter the quality of COVID-19 surveillance, with possible consequences for real-time analysis and delay in implementation of control measures.

Methods

Using a multipathogen susceptible-exposed-infectious-recovered (SEIR) transmission model formalizing cocirculation of SARS-CoV-2 and another respiratory virus, we assessed how an outbreak of secondary virus may affect 2 COVID-19 surveillance indicators: testing demand and positivity. Using simulation, we assessed to what extent the use of multiplex polymerase chain reaction tests on a subsample of symptomatic individuals can help correct the observed SARS-CoV-2 percentage positivity and improve surveillance quality.

Results

We find that a non-SARS-CoV-2 epidemic strongly increases SARS-CoV-2 daily testing demand and artificially reduces the observed SARS-CoV-2 percentage positivity for the duration of the outbreak. We estimate that performing 1 multiplex test for every 1000 COVID-19 tests on symptomatic individuals could be sufficient to maintain surveillance of other respiratory viruses in the population and correct the observed SARS-CoV-2 percentage positivity.

Conclusions

This study showed that cocirculating respiratory viruses can distort SARS-CoV-2 surveillance. Correction of the positivity rate can be achieved by using multiplex polymerase chain reaction tests, and a low number of samples is sufficient to avoid bias in SARS-CoV-2 surveillance.",,pdf:https://academic.oup.com/jid/article-pdf/225/2/199/42224165/jiab459.pdf; doi:https://doi.org/10.1093/infdis/jiab459; html:https://europepmc.org/articles/PMC8763960; pdf:https://europepmc.org/articles/PMC8763960?pdf=render 36874571,https://doi.org/10.12688/wellcomeopenres.17981.1,Settings for non-household transmission of SARS-CoV-2 during the second lockdown in England and Wales - analysis of the Virus Watch household community cohort study.,"Hoskins S, Beale S, Nguyen V, Fragaszy E, Navaratnam AMD, Smith C, French C, Kovar J, Byrne T, Fong WLE, Geismar C, Patel P, Yavlinksy A, Johnson AM, Aldridge RW, Hayward A, Virus Watch Collaborative.",,Wellcome open research,2022,2022-08-03,Y,Transmission; Activities; Pandemic; Work; Public Transport; Shopping; Lockdown; Covid-19; Sars-cov-2,,,"Background: ""Lockdowns"" to control serious respiratory virus pandemics were widely used during the coronavirus disease 2019 (COVID-19) pandemic.  However, there is limited information to understand the settings in which most transmission occurs during lockdowns, to support refinement of similar policies for future pandemics.  Methods: Among Virus Watch household cohort participants we identified those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outside the household.  Using survey activity data, we undertook multivariable logistic regressions assessing the contribution of activities on non-household infection risk.  We calculated adjusted population attributable fractions (APAF) to estimate which activity accounted for the greatest proportion of non-household infections during the pandemic's second wave. Results: Among 10,858 adults, 18% of cases were likely due to household transmission.  Among 10,475 participants (household-acquired cases excluded), including 874 non-household-acquired infections, infection was associated with: leaving home for work or education (AOR 1.20 (1.02 - 1.42), APAF 6.9%); public transport (more than once per week AOR 1.82 (1.49 - 2.23), public transport APAF 12.42%); and shopping (more than once per week AOR 1.69 (1.29 - 2.21), shopping APAF 34.56%).  Other non-household activities were rare and not significantly associated with infection. Conclusions: During lockdown, going to work and using public or shared transport independently increased infection risk, however only a minority did these activities.  Most participants visited shops, accounting for one-third of non-household transmission.  Transmission in restricted hospitality and leisure settings was minimal suggesting these restrictions were effective.   If future respiratory infection pandemics emerge these findings highlight the value of working from home, using forms of transport that minimise exposure to others, minimising exposure to shops and restricting non-essential activities.",,doi:https://doi.org/10.12688/wellcomeopenres.17981.1; html:https://europepmc.org/articles/PMC9975411; pdf:https://europepmc.org/articles/PMC9975411?pdf=render 35140406,https://doi.org/10.1038/s41591-022-01701-w,Vaccine effectiveness of heterologous CoronaVac plus BNT162b2 in Brazil.,"Cerqueira-Silva T, Katikireddi SV, de Araujo Oliveira V, Flores-Ortiz R, Júnior JB, Paixão ES, Robertson C, Penna GO, Werneck GL, Barreto ML, Pearce N, Sheikh A, Barral-Netto M, Boaventura VS.",,Nature medicine,2022,2022-02-09,Y,,,,"There is considerable interest in the waning of effectiveness of coronavirus disease 2019 (COVID-19) vaccines and vaccine effectiveness (VE) of booster doses. Using linked national Brazilian databases, we undertook a test-negative design study involving almost 14 million people (~16 million tests) to estimate VE of CoronaVac over time and VE of BNT162b2 booster vaccination against RT-PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes (hospitalization or death). Compared with unvaccinated individuals, CoronaVac VE at 14-30 d after the second dose was 55.0% (95% confidence interval (CI): 54.3-55.7) against confirmed infection and 82.1% (95% CI: 81.4-82.8) against severe outcomes. VE decreased to 34.7% (95% CI: 33.1-36.2) against infection and 72.5% (95% CI: 70.9-74.0) against severe outcomes over 180 d after the second dose. A BNT162b2 booster, 6 months after the second dose of CoronaVac, improved VE against infection to 92.7% (95% CI: 91.0-94.0) and VE against severe outcomes to 97.3% (95% CI: 96.1-98.1) 14-30 d after the booster. Compared with younger age groups, individuals 80 years of age or older had lower protection after the second dose but similar protection after the booster. Our findings support a BNT162b2 booster vaccine dose after two doses of CoronaVac, particularly for the elderly.",,pdf:https://www.nature.com/articles/s41591-022-01701-w.pdf; doi:https://doi.org/10.1038/s41591-022-01701-w; html:https://europepmc.org/articles/PMC9018414; pdf:https://europepmc.org/articles/PMC9018414?pdf=render -36609574,https://doi.org/10.1038/s41467-022-35771-8,A population-based matched cohort study of major congenital anomalies following COVID-19 vaccination and SARS-CoV-2 infection.,"Calvert C, Carruthers J, Denny C, Donaghy J, Hopcroft LEM, Hopkins L, Goulding A, Lindsay L, McLaughlin T, Moore E, Taylor B, Loane M, Dolk H, Morris J, Auyeung B, Bhaskaran K, Gibbons CL, Katikireddi SV, O'Leary M, McAllister D, Shi T, Simpson CR, Robertson C, Sheikh A, Stock SJ, Wood R.",,Nature communications,2023,2023-01-06,Y,,,,"Evidence on associations between COVID-19 vaccination or SARS-CoV-2 infection and the risk of congenital anomalies is limited. Here we report a national, population-based, matched cohort study using linked electronic health records from Scotland (May 2020-April 2022) to estimate the association between COVID-19 vaccination and, separately, SARS-CoV-2 infection between six weeks pre-conception and 19 weeks and six days gestation and the risk of [1] any major congenital anomaly and [2] any non-genetic major congenital anomaly. Mothers vaccinated in this pregnancy exposure period mostly received an mRNA vaccine (73.7% Pfizer-BioNTech BNT162b2 and 7.9% Moderna mRNA-1273). Of the 6731 babies whose mothers were vaccinated in the pregnancy exposure period, 153 had any anomaly and 120 had a non-genetic anomaly. Primary analyses find no association between any vaccination and any anomaly (adjusted Odds Ratio [aOR] = 1.01, 95% Confidence Interval [CI] = 0.83-1.24) or non-genetic anomalies (aOR = 1.00, 95% CI = 0.81-1.22). Primary analyses also find no association between SARS-CoV-2 infection and any anomaly (aOR = 1.02, 95% CI = 0.66-1.60) or non-genetic anomalies (aOR = 0.94, 95% CI = 0.57-1.54). Findings are robust to sensitivity analyses. These data provide reassurance on the safety of vaccination, in particular mRNA vaccines, just before or in early pregnancy.",,pdf:https://www.nature.com/articles/s41467-022-35771-8.pdf; doi:https://doi.org/10.1038/s41467-022-35771-8; html:https://europepmc.org/articles/PMC9821346; pdf:https://europepmc.org/articles/PMC9821346?pdf=render 35038629,https://doi.org/10.1016/j.puhe.2021.12.010,Investigating the association between COVID-19 vaccination and care home outbreak frequency and duration.,"Bradley DT, Murphy S, McWilliams P, Arnold S, Lavery S, Murphy J, de Lusignan S, Hobbs R, Tsang RSM, Akbari A, Torabi F, Beggs J, Chuter A, Shi T, Vasileiou E, Robertson C, Sheikh A, Reid H, O'Reilly D.",,Public health,2022,2021-12-18,Y,Vaccination; outbreak; Care Homes; Covid-19; Sars-cov-2,,,"

Objectives

At the end of 2020, many countries commenced a vaccination programme against SARS-CoV-2. Public health authorities aim to prevent and interrupt outbreaks of infectious disease in social care settings. We aimed to investigate the association between the introduction of the vaccination programme and the frequency and duration of COVID-19 outbreaks in Northern Ireland (NI).

Study design

We undertook an ecological study using routinely available national data.

Methods

We used Poisson regression to measure the relationship between the number of RT-PCR confirmed COVID-19 outbreaks in care homes, and as a measure of community COVID-19 prevalence, the Office for National Statistics COVID-19 Infection Survey estimated the number of people testing positive for COVID-19 in NI. We estimated the change in this relationship and estimated the expected number of care home outbreaks in the absence of the vaccination programme. A Cox proportional hazards model estimated the hazard ratio of a confirmed COVID-19 care home outbreak closure.

Results

Care home outbreaks reduced by two-thirds compared to expected following the introduction of the vaccination programme, from a projected 1625 COVID-19 outbreaks (95% prediction interval 1553-1694) between 7 December 2020 and 28 October 2021 to an observed 501. We estimated an adjusted hazard ratio of 2.53 of the outbreak closure assuming a 21-day lag for immunity.

Conclusions

These findings describe the association of the vaccination with a reduction in outbreak frequency and duration across NI care homes. This indicates probable reduced harm and disruption from COVID-19 in social care settings following vaccination. Future research using individual level data from care home residents will be needed to investigate the effectiveness of the vaccines and the duration of their effects.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa59048/Download/59048__22075__e4bbc8a7cad6434abac5984eb2422e06.pdf; doi:https://doi.org/10.1016/j.puhe.2021.12.010; html:https://europepmc.org/articles/PMC8683272; pdf:https://europepmc.org/articles/PMC8683272?pdf=render +36609574,https://doi.org/10.1038/s41467-022-35771-8,A population-based matched cohort study of major congenital anomalies following COVID-19 vaccination and SARS-CoV-2 infection.,"Calvert C, Carruthers J, Denny C, Donaghy J, Hopcroft LEM, Hopkins L, Goulding A, Lindsay L, McLaughlin T, Moore E, Taylor B, Loane M, Dolk H, Morris J, Auyeung B, Bhaskaran K, Gibbons CL, Katikireddi SV, O'Leary M, McAllister D, Shi T, Simpson CR, Robertson C, Sheikh A, Stock SJ, Wood R.",,Nature communications,2023,2023-01-06,Y,,,,"Evidence on associations between COVID-19 vaccination or SARS-CoV-2 infection and the risk of congenital anomalies is limited. Here we report a national, population-based, matched cohort study using linked electronic health records from Scotland (May 2020-April 2022) to estimate the association between COVID-19 vaccination and, separately, SARS-CoV-2 infection between six weeks pre-conception and 19 weeks and six days gestation and the risk of [1] any major congenital anomaly and [2] any non-genetic major congenital anomaly. Mothers vaccinated in this pregnancy exposure period mostly received an mRNA vaccine (73.7% Pfizer-BioNTech BNT162b2 and 7.9% Moderna mRNA-1273). Of the 6731 babies whose mothers were vaccinated in the pregnancy exposure period, 153 had any anomaly and 120 had a non-genetic anomaly. Primary analyses find no association between any vaccination and any anomaly (adjusted Odds Ratio [aOR] = 1.01, 95% Confidence Interval [CI] = 0.83-1.24) or non-genetic anomalies (aOR = 1.00, 95% CI = 0.81-1.22). Primary analyses also find no association between SARS-CoV-2 infection and any anomaly (aOR = 1.02, 95% CI = 0.66-1.60) or non-genetic anomalies (aOR = 0.94, 95% CI = 0.57-1.54). Findings are robust to sensitivity analyses. These data provide reassurance on the safety of vaccination, in particular mRNA vaccines, just before or in early pregnancy.",,pdf:https://www.nature.com/articles/s41467-022-35771-8.pdf; doi:https://doi.org/10.1038/s41467-022-35771-8; html:https://europepmc.org/articles/PMC9821346; pdf:https://europepmc.org/articles/PMC9821346?pdf=render 37311808,https://doi.org/10.1038/s41467-023-39193-y,"Natural history of long-COVID in a nationwide, population cohort study.","Hastie CE, Lowe DJ, McAuley A, Mills NL, Winter AJ, Black C, Scott JT, O'Donnell CA, Blane DN, Browne S, Ibbotson TR, Pell JP.",,Nature communications,2023,2023-06-13,Y,,,,"Previous studies on the natural history of long-COVID have been few and selective. Without comparison groups, disease progression cannot be differentiated from symptoms originating from other causes. The Long-COVID in Scotland Study (Long-CISS) is a Scotland-wide, general population cohort of adults who had laboratory-confirmed SARS-CoV-2 infection matched to PCR-negative adults. Serial, self-completed, online questionnaires collected information on pre-existing health conditions and current health six, 12 and 18 months after index test. Of those with previous symptomatic infection, 35% reported persistent incomplete/no recovery, 12% improvement and 12% deterioration. At six and 12 months, one or more symptom was reported by 71.5% and 70.7% respectively of those previously infected, compared with 53.5% and 56.5% of those never infected. Altered taste, smell and confusion improved over time compared to the never infected group and adjusted for confounders. Conversely, late onset dry and productive cough, and hearing problems were more likely following SARS-CoV-2 infection.",,pdf:https://www.nature.com/articles/s41467-023-39193-y.pdf; doi:https://doi.org/10.1038/s41467-023-39193-y; html:https://europepmc.org/articles/PMC10263377; pdf:https://europepmc.org/articles/PMC10263377?pdf=render 38589621,https://doi.org/10.1038/s41590-024-01778-0,Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease.,"Liew F, Efstathiou C, Fontanella S, Richardson M, Saunders R, Swieboda D, Sidhu JK, Ascough S, Moore SC, Mohamed N, Nunag J, King C, Leavy OC, Elneima O, McAuley HJC, Shikotra A, Singapuri A, Sereno M, Harris VC, Houchen-Wolloff L, Greening NJ, Lone NI, Thorpe M, Thompson AAR, Rowland-Jones SL, Docherty AB, Chalmers JD, Ho LP, Horsley A, Raman B, Poinasamy K, Marks M, Kon OM, Howard LS, Wootton DG, Quint JK, de Silva TI, Ho A, Chiu C, Harrison EM, Greenhalf W, Baillie JK, Semple MG, Turtle L, Evans RA, Wain LV, Brightling C, Thwaites RS, Openshaw PJM, PHOSP-COVID collaborative group, ISARIC investigators.",,Nature immunology,2024,2024-04-08,Y,,,,"One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.",,doi:https://doi.org/10.1038/s41590-024-01778-0; html:https://europepmc.org/articles/PMC11003868; pdf:https://europepmc.org/articles/PMC11003868?pdf=render 35387486,https://doi.org/10.1161/circulationaha.121.057888,Genetic Landscape of the ACE2 Coronavirus Receptor.,"Yang Z, Macdonald-Dunlop E, Chen J, Zhai R, Li T, Richmond A, Klarić L, Pirastu N, Ning Z, Zheng C, Wang Y, Huang T, He Y, Guo H, Ying K, Gustafsson S, Prins B, Ramisch A, Dermitzakis ET, Png G, Eriksson N, Haessler J, Hu X, Zanetti D, Boutin T, Hwang SJ, Wheeler E, Pietzner M, Raffield LM, Kalnapenkis A, Peters JE, Viñuela A, Gilly A, Elmståhl S, Dedoussis G, Petrie JR, Polašek O, Folkersen L, Chen Y, Yao C, Võsa U, Pairo-Castineira E, Clohisey S, Bretherick AD, Rawlik K, GenOMICC Consortium†, IMI-DIRECT Consortium†, Esko T, Enroth S, Johansson Å, Gyllensten U, Langenberg C, Levy D, Hayward C, Assimes TL, Kooperberg C, Manichaikul AW, Siegbahn A, Wallentin L, Lind L, Zeggini E, Schwenk JM, Butterworth AS, Michaëlsson K, Pawitan Y, Joshi PK, Baillie JK, Mälarstig A, Reiner AP, Wilson JF, Shen X.",,Circulation,2022,2022-04-07,Y,Cardiovascular diseases; Angiotensin-converting Enzyme 2; Genome-wide Association Study; Covid-19; Sars-cov-2,,,"

Background

SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood.

Methods

We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data.

Results

We identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis-protein quantitative trait loci-based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10-2.42]; P=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; P=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; P=0.02). Tissue- and cell type-specific transcriptomic and epigenomic analysis revealed that the ACE2 regulatory variants were enriched for DNA methylation sites in blood immune cells.

Conclusions

Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.057888; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.057888; html:https://europepmc.org/articles/PMC9047645; pdf:https://europepmc.org/articles/PMC9047645?pdf=render @@ -180,8 +180,8 @@ PMC10929454,https://doi.org/,Optimising data curation pipelines for population-l 35813279,https://doi.org/10.1016/s2666-7568(22)00147-7,"Duration of vaccine effectiveness against SARS-CoV-2 infection, hospitalisation, and death in residents and staff of long-term care facilities in England (VIVALDI): a prospective cohort study.","Shrotri M, Krutikov M, Nacer-Laidi H, Azmi B, Palmer T, Giddings R, Fuller C, Irwin-Singer A, Baynton V, Tut G, Moss P, Hayward A, Copas A, Shallcross L.",,The lancet. Healthy longevity,2022,2022-07-04,Y,,,,"

Background

Residents and staff in long-term care facilities have been prioritised for vaccination against SARS-CoV-2, but data on potential waning of vaccine effectiveness and the effect of booster doses in this vulnerable population are scarce. We aimed to evaluate effectiveness of one, two, and three vaccine doses against infection and severe clinical outcomes in staff and residents of long-term care facilities in England over the first year following vaccine roll-out.

Methods

The VIVALDI study is a prospective cohort study done in 331 long-term care facilities in England. Residents aged 65 years or older and staff aged 18 years or older were eligible for participation. Participants had routine PCR testing throughout the study period between Dec 8, 2020, and Dec 11, 2021. We retrieved all PCR results and cycle threshold values for PCR-positive samples from routine testing in long-term care facilities, and positive PCR results from clinical testing in hospitals through the UK's COVID-19 Datastore. PCR results were linked to participants using pseudo-identifiers based on individuals' unique UK National Health Service (NHS) numbers, which were also used to retrieve vaccination records from the National Immunisation Management Service, hospitalisation records from NHS England, and deaths data from the Office for National Statistics through the COVID-19 Datastore. In a Cox proportional hazards regression, we estimated vaccine effectiveness against SARS-CoV-2 infection, COVID-19-related hospitalisation, and COVID-19-related death after one, two, and three vaccine doses, separately by previous SARS-CoV-2 exposure. This study is registered with the ISRCTN Registry, ISRCTN 14447421.

Findings

80 186 residents and staff of long-term care facilities had records available for the study period, of whom 15 518 eligible residents and 19 515 eligible staff were included in the analysis. For residents without evidence of previous SARS-CoV-2 exposure, vaccine effectiveness decreased from 61·7% (95% CI 35·1 to 77·4) to 22·0% (-14·9 to 47·0) against infection; from 89·0% (70·6 to 95·9) to 56·3% (30·1 to 72·6) against hospitalisation; and from 96·4% (84·3 to 99·2) to 64·4% (36·1 to 80·1) against death, when comparing 14-83 days after dose two and 84 days or more after dose two. For staff without evidence of previous exposure, vaccine effectiveness against infection decreased slightly from 57·9% (43·1 to 68·9) at 14-83 days after dose two to 42·1% (29·9 to 52·2) at 84 days or more after dose two. There were no hospitalisations or deaths among unexposed staff at 14-83 days, but seven hospitalisations (vaccine effectiveness 91·0% [95% CI 74·3 to 96·8]) and one death were observed at 84 days or more after dose two. High vaccine effectiveness was restored following a third vaccine dose, with vaccine effectiveness in unexposed residents of 72·7% (55·8 to 83·1) against infection, 90·1% (80·6 to 95·0) against hospitalisation, and 97·5% (88·1 to 99·5) against death; and vaccine effectiveness in unexposed staff of 78·2% (70·0 to 84·1) against infection and 95·8% (49·9 to 99·6) against hospitalisation. There were no COVID-19-related deaths among unexposed staff after the third vaccine dose.

Interpretation

Our findings showed substantial waning of SARS-CoV-2 vaccine effectiveness against all outcomes in residents of long-term care facilities from 12 weeks after a primary course of ChAdOx1-S or mRNA vaccines. Boosters restored protection, and maximised immunity across all outcomes. These findings show the importance of boosting and the need for ongoing surveillance in this vulnerable cohort.

Funding

UK Government Department of Health and Social Care.",,doi:https://doi.org/10.1016/s2666-7568(22)00147-7; doi:https://doi.org/10.1016/S2666-7568(22)00147-7; html:https://europepmc.org/articles/PMC9252508; pdf:https://europepmc.org/articles/PMC9252508?pdf=render 35572721,https://doi.org/10.1016/j.eclinm.2022.101419,Breakthrough SARS-CoV-2 infections in double and triple vaccinated adults and single dose vaccine effectiveness among children in Autumn 2021 in England: REACT-1 study.,"Chadeau-Hyam M, Eales O, Bodinier B, Wang H, Haw D, Whitaker M, Elliott J, Walters CE, Jonnerby J, Atchison C, Diggle PJ, Page AJ, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly CA, Elliott P.",,EClinicalMedicine,2022,2022-05-06,Y,School-aged children; Vaccine Effectiveness; Booster Dose; Children Vaccination; Sars-cov-2 Prevalence,,,"

Background

Prevalence of SARS-CoV-2 infection with Delta variant was increasing in England in late summer 2021 among children aged 5 to 17 years, and adults who had received two vaccine doses. In September 2021, a third (booster) dose was offered to vaccinated adults aged 50 years and over, vulnerable adults and healthcare/care-home workers, and a single vaccine dose already offered to 16 and 17 year-olds was extended to children aged 12 to 15 years.

Methods

SARS-CoV-2 community prevalence in England was available from self-administered throat and nose swabs using reverse transcriptase polymerase chain reaction (RT-PCR) in round 13 (24 June to 12 July 2021, N = 98,233), round 14 (9 to 27 September 2021, N = 100,527) and round 15 (19 October to 5 November 2021, N = 100,112) from the REACT-1 study randomised community surveys. Linking to National Health Service (NHS) vaccination data for consenting participants, we estimated vaccine effectiveness in children aged 12 to 17 years and compared swab-positivity rates in adults who received a third dose with those who received two doses.

Findings

Weighted SARS-CoV-2 prevalence was 1.57% (1.48%, 1.66%) in round 15 compared with 0.83% (0.76%, 0.89%) in round 14, and the previously observed link between infections and hospitalisations and deaths had weakened. Vaccine effectiveness against infection in children aged 12 to 17 years was estimated (round 15) at 64.0% (50.9%, 70.6%) and 67.7% (53.8%, 77.5%) for symptomatic infections. Adults who received a third vaccine dose were less likely to test positive compared to those who received two doses, with adjusted OR of 0.36 (0.25, 0.53).

Interpretation

Vaccination of children aged 12 to 17 years and third (booster) doses in adults were effective at reducing infection risk. High rates of vaccination, including booster doses, are a key part of the strategy to reduce infection rates in the community.

Funding

Department of Health and Social Care, England.",,pdf:http://www.thelancet.com/article/S2589537022001493/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101419; html:https://europepmc.org/articles/PMC9076030; pdf:https://europepmc.org/articles/PMC9076030?pdf=render 36215226,https://doi.org/10.1136/bmj-2022-071230,Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: phase 3 randomised controlled trial (CORONAVIT).,"Jolliffe DA, Holt H, Greenig M, Talaei M, Perdek N, Pfeffer P, Vivaldi G, Maltby S, Symons J, Barlow NL, Normandale A, Garcha R, Richter AG, Faustini SE, Orton C, Ford D, Lyons RA, Davies GA, Kee F, Griffiths CJ, Norrie J, Sheikh A, Shaheen SO, Relton C, Martineau AR.",,BMJ (Clinical research ed.),2022,2022-09-07,Y,,,,"

Objective

To determine the effect of population level implementation of a test-and-treat approach to correction of suboptimal vitamin D status (25-hydroxyvitamin D (25(OH)D) <75 nmol/L) on risk of all cause acute respiratory tract infection and covid 19.

Design

Phase 3 open label randomised controlled trial.

Setting

United Kingdom.

Participants

6200 people aged ≥16 years who were not taking vitamin D supplements at baseline.

Interventions

Offer of a postal finger prick test of blood 25(OH)D concentration with provision of a six month supply of lower dose vitamin D (800 IU/day, n=1550) or higher dose vitamin D (3200 IU/day, n=1550) to those with blood 25(OH)D concentration <75 nmol/L, compared with no offer of testing or supplementation (n=3100). Follow-up was for six months.

Main outcome measures

The primary outcome was the proportion of participants with at least one swab test or doctor confirmed acute respiratory tract infection of any cause. A secondary outcome was the proportion of participants with swab test confirmed covid-19. Logistic regression was used to calculate odds ratios and associated 95% confidence intervals. The primary analysis was conducted by intention to treat.

Results

Of 3100 participants offered a vitamin D test, 2958 (95.4%) accepted and 2674 (86.3%) had 25(OH)D concentrations <75 nmol/L and received vitamin D supplements (n=1328 lower dose, n=1346 higher dose). Compared with 136/2949 (4.6%) participants in the no offer group, at least one acute respiratory tract infection of any cause occurred in 87/1515 (5.7%) in the lower dose group (odds ratio 1.26, 95% confidence interval 0.96 to 1.66) and 76/1515 (5.0%) in the higher dose group (1.09, 0.82 to 1.46). Compared with 78/2949 (2.6%) participants in the no offer group, 55/1515 (3.6%) developed covid-19 in the lower dose group (1.39, 0.98 to 1.97) and 45/1515 (3.0%) in the higher dose group (1.13, 0.78 to 1.63).

Conclusions

Among people aged 16 years and older with a high baseline prevalence of suboptimal vitamin D status, implementation of a population level test-and-treat approach to vitamin D supplementation was not associated with a reduction in risk of all cause acute respiratory tract infection or covid-19.

Trial registration

ClinicalTrials.gov NCT04579640.",,pdf:https://www.bmj.com/content/bmj/378/bmj-2022-071230.full.pdf; doi:https://doi.org/10.1136/bmj-2022-071230; html:https://europepmc.org/articles/PMC9449358; pdf:https://europepmc.org/articles/PMC9449358?pdf=render -37263685,https://doi.org/10.1136/bmjopen-2022-070637,"Impact of the COVID-19 pandemic on domiciliary care workers in Wales, UK: a data linkage cohort study using the SAIL Databank.","Cannings-John R, Schoenbuchner S, Jones H, Lugg-Widger FV, Akbari A, Brookes-Howell L, Hood K, John A, Thomas DR, Prout H, Robling M.",,BMJ open,2023,2023-06-01,Y,Mental health; Social Medicine; Covid-19,,,"

Objectives

To quantify population health risks for domiciliary care workers (DCWs) in Wales, UK, working during the COVID-19 pandemic.

Design

A population-level retrospective study linking occupational registration data to anonymised electronic health records maintained by the Secure Anonymised Information Linkage Databank in a privacy-protecting trusted research environment.

Setting

Registered DCW population in Wales.

Participants

Records for all linked DCWs from 1 March 2020 to 30 November 2021.

Primary and secondary outcome measures

Our primary outcome was confirmed COVID-19 infection; secondary outcomes included contacts for suspected COVID-19, mental health including self-harm, fit notes, respiratory infections not necessarily recorded as COVID-19, deaths involving COVID-19 and all-cause mortality.

Results

Confirmed and suspected COVID-19 infection rates increased over the study period to 24% by 30 November 2021. Confirmed COVID-19 varied by sex (males: 19% vs females: 24%) and age (>55 years: 19% vs <35 years: 26%) and were higher for care workers employed by local authority social services departments compared with the private sector (27% and 23%, respectively). 34% of DCWs required support for a mental health condition, with mental health-related prescribing increasing in frequency when compared with the prepandemic period. Events for self-harm increased from 0.2% to 0.4% over the study period as did the issuing of fit notes. There was no evidence to suggest a miscoding of COVID-19 infection with non-COVID-19 respiratory conditions. COVID-19-related and all-cause mortality were no greater than for the general population aged 15-64 years in Wales (0.1% and 0.034%, respectively). A comparable DCW workforce in Scotland and England would result in a comparable rate of COVID-19 infection, while the younger workforce in Northern Ireland may result in a greater infection rate.

Conclusions

While initial concerns about excess mortality are alleviated, the substantial pre-existing and increased mental health burden for DCWs will require investment to provide long-term support to the sector's workforce.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/6/e070637.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-070637; html:https://europepmc.org/articles/PMC10255029; pdf:https://europepmc.org/articles/PMC10255029?pdf=render 32873607,https://doi.org/10.1136/bmjresp-2020-000644,Ethnicity and risk of death in patients hospitalised for COVID-19 infection in the UK: an observational cohort study in an urban catchment area.,"Sapey E, Gallier S, Mainey C, Nightingale P, McNulty D, Crothers H, Evison F, Reeves K, Pagano D, Denniston AK, Nirantharakumar K, Diggle P, Ball S, All clinicians and students at University Hospitals Birmingham NHS Foundation Trust.",,BMJ open respiratory research,2020,2020-09-01,Y,Viral infection; respiratory infection; Clinical Epidemiology,,,"

Background

Studies suggest that certain black and Asian minority ethnic groups experience poorer outcomes from COVID-19, but these studies have not provided insight into potential reasons for this. We hypothesised that outcomes would be poorer for those of South Asian ethnicity hospitalised from a confirmed SARS-CoV-2 infection, once confounding factors, health-seeking behaviours and community demographics were considered, and that this might reflect a more aggressive disease course in these patients.

Methods

Patients with confirmed SARS-CoV-2 infection requiring admission to University Hospitals Birmingham NHS Foundation Trust (UHB) in Birmingham, UK between 10 March 2020 and 17 April 2020 were included. Standardised admission ratio (SAR) and standardised mortality ratio (SMR) were calculated using observed COVID-19 admissions/deaths and 2011 census data. Adjusted HR for mortality was estimated using Cox proportional hazard model adjusting and propensity score matching.

Results

All patients admitted to UHB with COVID-19 during the study period were included (2217 in total). 58% were male, 69.5% were white and the majority (80.2%) had comorbidities. 18.5% were of South Asian ethnicity, and these patients were more likely to be younger and have no comorbidities, but twice the prevalence of diabetes than white patients. SAR and SMR suggested more admissions and deaths in South Asian patients than would be predicted and they were more likely to present with severe disease despite no delay in presentation since symptom onset. South Asian ethnicity was associated with an increased risk of death, both by Cox regression (HR 1.4, 95% CI 1.2 to 1.8), after adjusting for age, sex, deprivation and comorbidities, and by propensity score matching, matching for the same factors but categorising ethnicity into South Asian or not (HR 1.3, 95% CI 1.0 to 1.6).

Conclusions

Those of South Asian ethnicity appear at risk of worse COVID-19 outcomes. Further studies need to establish the underlying mechanistic pathways.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/7/1/e000644.full.pdf; doi:https://doi.org/10.1136/bmjresp-2020-000644; html:https://europepmc.org/articles/PMC7467523; pdf:https://europepmc.org/articles/PMC7467523?pdf=render +37263685,https://doi.org/10.1136/bmjopen-2022-070637,"Impact of the COVID-19 pandemic on domiciliary care workers in Wales, UK: a data linkage cohort study using the SAIL Databank.","Cannings-John R, Schoenbuchner S, Jones H, Lugg-Widger FV, Akbari A, Brookes-Howell L, Hood K, John A, Thomas DR, Prout H, Robling M.",,BMJ open,2023,2023-06-01,Y,Mental health; Social Medicine; Covid-19,,,"

Objectives

To quantify population health risks for domiciliary care workers (DCWs) in Wales, UK, working during the COVID-19 pandemic.

Design

A population-level retrospective study linking occupational registration data to anonymised electronic health records maintained by the Secure Anonymised Information Linkage Databank in a privacy-protecting trusted research environment.

Setting

Registered DCW population in Wales.

Participants

Records for all linked DCWs from 1 March 2020 to 30 November 2021.

Primary and secondary outcome measures

Our primary outcome was confirmed COVID-19 infection; secondary outcomes included contacts for suspected COVID-19, mental health including self-harm, fit notes, respiratory infections not necessarily recorded as COVID-19, deaths involving COVID-19 and all-cause mortality.

Results

Confirmed and suspected COVID-19 infection rates increased over the study period to 24% by 30 November 2021. Confirmed COVID-19 varied by sex (males: 19% vs females: 24%) and age (>55 years: 19% vs <35 years: 26%) and were higher for care workers employed by local authority social services departments compared with the private sector (27% and 23%, respectively). 34% of DCWs required support for a mental health condition, with mental health-related prescribing increasing in frequency when compared with the prepandemic period. Events for self-harm increased from 0.2% to 0.4% over the study period as did the issuing of fit notes. There was no evidence to suggest a miscoding of COVID-19 infection with non-COVID-19 respiratory conditions. COVID-19-related and all-cause mortality were no greater than for the general population aged 15-64 years in Wales (0.1% and 0.034%, respectively). A comparable DCW workforce in Scotland and England would result in a comparable rate of COVID-19 infection, while the younger workforce in Northern Ireland may result in a greater infection rate.

Conclusions

While initial concerns about excess mortality are alleviated, the substantial pre-existing and increased mental health burden for DCWs will require investment to provide long-term support to the sector's workforce.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/6/e070637.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-070637; html:https://europepmc.org/articles/PMC10255029; pdf:https://europepmc.org/articles/PMC10255029?pdf=render 35077449,https://doi.org/10.1371/journal.pmed.1003871,"Overall and cause-specific hospitalisation and death after COVID-19 hospitalisation in England: A cohort study using linked primary care, secondary care, and death registration data in the OpenSAFELY platform.","Bhaskaran K, Rentsch CT, Hickman G, Hulme WJ, Schultze A, Curtis HJ, Wing K, Warren-Gash C, Tomlinson L, Bates CJ, Mathur R, MacKenna B, Mahalingasivam V, Wong A, Walker AJ, Morton CE, Grint D, Mehrkar A, Eggo RM, Inglesby P, Douglas IJ, McDonald HI, Cockburn J, Williamson EJ, Evans D, Parry J, Hester F, Harper S, Evans SJ, Bacon S, Smeeth L, Goldacre B.",,PLoS medicine,2022,2022-01-25,Y,,,,"

Background

There is concern about medium to long-term adverse outcomes following acute Coronavirus Disease 2019 (COVID-19), but little relevant evidence exists. We aimed to investigate whether risks of hospital admission and death, overall and by specific cause, are raised following discharge from a COVID-19 hospitalisation.

Methods and findings

With the approval of NHS-England, we conducted a cohort study, using linked primary care and hospital data in OpenSAFELY to compare risks of hospital admission and death, overall and by specific cause, between people discharged from COVID-19 hospitalisation (February to December 2020) and surviving at least 1 week, and (i) demographically matched controls from the 2019 general population; and (ii) people discharged from influenza hospitalisation in 2017 to 2019. We used Cox regression adjusted for age, sex, ethnicity, obesity, smoking status, deprivation, and comorbidities considered potential risk factors for severe COVID-19 outcomes. We included 24,673 postdischarge COVID-19 patients, 123,362 general population controls, and 16,058 influenza controls, followed for ≤315 days. COVID-19 patients had median age of 66 years, 13,733 (56%) were male, and 19,061 (77%) were of white ethnicity. Overall risk of hospitalisation or death (30,968 events) was higher in the COVID-19 group than general population controls (fully adjusted hazard ratio [aHR] 2.22, 2.14 to 2.30, p < 0.001) but slightly lower than the influenza group (aHR 0.95, 0.91 to 0.98, p = 0.004). All-cause mortality (7,439 events) was highest in the COVID-19 group (aHR 4.82, 4.48 to 5.19 versus general population controls [p < 0.001] and 1.74, 1.61 to 1.88 versus influenza controls [p < 0.001]). Risks for cause-specific outcomes were higher in COVID-19 survivors than in general population controls and largely similar or lower in COVID-19 compared with influenza patients. However, COVID-19 patients were more likely than influenza patients to be readmitted or die due to their initial infection or other lower respiratory tract infection (aHR 1.37, 1.22 to 1.54, p < 0.001) and to experience mental health or cognitive-related admission or death (aHR 1.37, 1.02 to 1.84, p = 0.039); in particular, COVID-19 survivors with preexisting dementia had higher risk of dementia hospitalisation or death (age- and sex-adjusted HR 2.47, 1.37 to 4.44, p = 0.002). Limitations of our study were that reasons for hospitalisation or death may have been misclassified in some cases due to inconsistent use of codes, and we did not have data to distinguish COVID-19 variants.

Conclusions

In this study, we observed that people discharged from a COVID-19 hospital admission had markedly higher risks for rehospitalisation and death than the general population, suggesting a substantial extra burden on healthcare. Most risks were similar to those observed after influenza hospitalisations, but COVID-19 patients had higher risks of all-cause mortality, readmission or death due to the initial infection, and dementia death, highlighting the importance of postdischarge monitoring.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003871&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003871; html:https://europepmc.org/articles/PMC8789178; pdf:https://europepmc.org/articles/PMC8789178?pdf=render 36384890,https://doi.org/10.1136/bmj-2022-071932,Comparative effectiveness of sotrovimab and molnupiravir for prevention of severe covid-19 outcomes in patients in the community: observational cohort study with the OpenSAFELY platform.,"Zheng B, Green ACA, Tazare J, Curtis HJ, Fisher L, Nab L, Schultze A, Mahalingasivam V, Parker EPK, Hulme WJ, Bacon SCJ, DeVito NJ, Bates C, Evans D, Inglesby P, Drysdale H, Davy S, Cockburn J, Morton CE, Hickman G, Ward T, Smith RM, Parry J, Hester F, Harper S, Mehrkar A, Eggo RM, Walker AJ, Evans SJW, Douglas IJ, MacKenna B, Goldacre B, Tomlinson LA.",,BMJ (Clinical research ed.),2022,2022-11-16,Y,,,,"

Objective

To compare the effectiveness of sotrovimab (a neutralising monoclonal antibody) with molnupiravir (an antiviral) in preventing severe outcomes of covid-19 in adult patients infected with SARS-CoV-2 in the community and at high risk of severe outcomes from covid-19.

Design

Observational cohort study with the OpenSAFELY platform.

Setting

With the approval of NHS England, a real world cohort study was conducted with the OpenSAFELY-TPP platform (a secure, transparent, open source software platform for analysis of NHS electronic health records), and patient level electronic health record data were obtained from 24 million people registered with a general practice in England that uses TPP software. The primary care data were securely linked with data on SARS-CoV-2 infection and treatments, hospital admission, and death, over a period when both drug treatments were frequently prescribed in community settings.

Participants

Adult patients with covid-19 in the community at high risk of severe outcomes from covid-19, treated with sotrovimab or molnupiravir from 16 December 2021.

Interventions

Sotrovimab or molnupiravir given in the community by covid-19 medicine delivery units.

Main outcome measures

Admission to hospital with covid-19 (ie, with covid-19 as the primary diagnosis) or death from covid-19 (ie, with covid-19 as the underlying or contributing cause of death) within 28 days of the start of treatment.

Results

Between 16 December 2021 and 10 February 2022, 3331 and 2689 patients were treated with sotrovimab and molnupiravir, respectively, with no substantial differences in baseline characteristics. Mean age of all 6020 patients was 52 (standard deviation 16) years; 59% were women, 89% were white, and 88% had received three or more covid-19 vaccinations. Within 28 days of the start of treatment, 87 (1.4%) patients were admitted to hospital or died of infection from SARS-CoV-2 (32 treated with sotrovimab and 55 with molnupiravir). Cox proportional hazards models stratified by area showed that after adjusting for demographic information, high risk cohort categories, vaccination status, calendar time, body mass index, and other comorbidities, treatment with sotrovimab was associated with a substantially lower risk than treatment with molnupiravir (hazard ratio 0.54, 95% confidence interval 0.33 to 0.88, P=0.01). Consistent results were found from propensity score weighted Cox models (0.50, 0.31 to 0.81, P=0.005) and when restricted to people who were fully vaccinated (0.53, 0.31 to 0.90, P=0.02). No substantial effect modifications by other characteristics were detected (all P values for interaction >0.10). The findings were similar in an exploratory analysis of patients treated between 16 February and 1 May 2022 when omicron BA.2 was the predominant variant in England.

Conclusions

In routine care of adult patients in England with covid-19 in the community, at high risk of severe outcomes from covid-19, those who received sotrovimab were at lower risk of severe outcomes of covid-19 than those treated with molnupiravir.",,pdf:https://www.bmj.com/content/bmj/379/bmj-2022-071932.full.pdf; doi:https://doi.org/10.1136/bmj-2022-071932; html:https://europepmc.org/articles/PMC9667468 36901540,https://doi.org/10.3390/ijerph20054534,Socioeconomic Background and Self-Reported Sleep Quality in Older Adults during the COVID-19 Pandemic: An Analysis of the English Longitudinal Study of Ageing (ELSA).,"Collinge AN, Bath PA, Bath PA.",,International journal of environmental research and public health,2023,2023-03-03,Y,Mental health; Health Promotion; Wellness; Physical Health; Health Disparities; Health Behaviors; Older Adults; Sleep Quality; Socioeconomic Background; Covid-19,,,"The COVID-19 pandemic negatively impacted sleep quality. However, research regarding older adults' sleep quality during the pandemic has been limited. This study examined the association between socioeconomic background (SEB) and older adults' sleep quality during the COVID-19 pandemic. Data on 7040 adults aged ≥50 were acquired from a COVID-19 sub-study of the English Longitudinal Study of Ageing (ELSA). SEB was operationalized using educational attainment, previous financial situation, and concern about the future financial situation. Sociodemographic, mental health, physical health, and health behavior variables were included as covariates. Chi-squared tests and binary logistic regression were used to examine associations between SEB and sleep quality. Lower educational attainment and greater financial hardship and concerns were associated with poor sleep quality. The relationship between educational attainment and sleep quality was explained by the financial variables, while the relationship between previous financial difficulties and sleep quality was explained by physical health and health behavior variables. Greater financial concerns about the future, poor mental health, and poor physical health were independent risk factors for poor sleep quality in older adults during the pandemic. Healthcare professionals and service providers should consider these issues when supporting older patients with sleep problems and in promoting health and wellness.",,pdf:https://www.mdpi.com/1660-4601/20/5/4534/pdf?version=1677842613; doi:https://doi.org/10.3390/ijerph20054534; html:https://europepmc.org/articles/PMC10001974; pdf:https://europepmc.org/articles/PMC10001974?pdf=render @@ -193,10 +193,10 @@ PMC10929454,https://doi.org/,Optimising data curation pipelines for population-l 36098502,https://doi.org/10.7554/elife.78427,"Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection: Multicentre, prospective study.","Stirrup O, Blackstone J, Mapp F, MacNeil A, Panca M, Holmes A, Machin N, Shin GY, Mahungu T, Saeed K, Saluja T, Taha Y, Mahida N, Pope C, Chawla A, Cutino-Moguel MT, Tamuri A, Williams R, Darby A, Robertson DL, Flaviani F, Nastouli E, Robson S, Smith D, Loose M, Laing K, Monahan I, Kele B, Haldenby S, George R, Bashton M, Witney AA, Byott M, Coll F, Chapman M, Peacock SJ, COG-UK HOCI Investigators, COVID-19 Genomics UK (COG-UK) consortium, Hughes J, Nebbia G, Partridge DG, Parker M, Price JR, Peters C, Roy S, Snell LB, de Silva TI, Thomson E, Flowers P, Copas A, Breuer J.",,eLife,2022,2022-09-13,Y,Human; Microbiology; Infectious disease; Molecular epidemiology; Infection control; epidemiology; Global Health; Hospital-acquired Infection; Infection Prevention; Viral Genomics; Healthcare-associated Infection; Covid-19,,,"

Background

Viral sequencing of SARS-CoV-2 has been used for outbreak investigation, but there is limited evidence supporting routine use for infection prevention and control (IPC) within hospital settings.

Methods

We conducted a prospective non-randomised trial of sequencing at 14 acute UK hospital trusts. Sites each had a 4-week baseline data collection period, followed by intervention periods comprising 8 weeks of 'rapid' (<48 hr) and 4 weeks of 'longer-turnaround' (5-10 days) sequencing using a sequence reporting tool (SRT). Data were collected on all hospital-onset COVID-19 infections (HOCIs; detected ≥48 hr from admission). The impact of the sequencing intervention on IPC knowledge and actions, and on the incidence of probable/definite hospital-acquired infections (HAIs), was evaluated.

Results

A total of 2170 HOCI cases were recorded from October 2020 to April 2021, corresponding to a period of extreme strain on the health service, with sequence reports returned for 650/1320 (49.2%) during intervention phases. We did not detect a statistically significant change in weekly incidence of HAIs in longer-turnaround (incidence rate ratio 1.60, 95% CI 0.85-3.01; p=0.14) or rapid (0.85, 0.48-1.50; p=0.54) intervention phases compared to baseline phase. However, IPC practice was changed in 7.8 and 7.4% of all HOCI cases in rapid and longer-turnaround phases, respectively, and 17.2 and 11.6% of cases where the report was returned. In a 'per-protocol' sensitivity analysis, there was an impact on IPC actions in 20.7% of HOCI cases when the SRT report was returned within 5 days. Capacity to respond effectively to insights from sequencing was breached in most sites by the volume of cases and limited resources.

Conclusions

While we did not demonstrate a direct impact of sequencing on the incidence of nosocomial transmission, our results suggest that sequencing can inform IPC response to HOCIs, particularly when returned within 5 days.

Funding

COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) (grant code: MC_PC_19027), and Genome Research Limited, operating as the Wellcome Sanger Institute.

Clinical trial number

NCT04405934.",,doi:https://doi.org/10.7554/elife.78427; doi:https://doi.org/10.7554/eLife.78427; html:https://europepmc.org/articles/PMC9596156; pdf:https://europepmc.org/articles/PMC9596156?pdf=render 38049846,https://doi.org/10.1186/s13012-023-01321-z,Implementing Germ Defence digital behaviour change intervention via all primary care practices in England to reduce respiratory infections during the COVID-19 pandemic: an efficient cluster randomised controlled trial using the OpenSAFELY platform.,"Ainsworth B, Horwood J, Walter SR, Miller S, Chalder M, De Vocht F, Denison-Day J, Elwenspoek MMC, Curtis HJ, Bates C, Mehrkar A, Bacon S, Goldacre B, OpenSAFELY Collaborative, Craggs P, Amlôt R, Francis N, Little P, Macleod J, Moore M, Morton K, Rice C, Sterne J, Stuart B, Towler L, Willcox ML, Yardley L.",,Implementation science : IS,2023,2023-12-04,Y,Infection control; Respiratory Tract Infections; Primary Care; Rct; Behaviour Change; Ehealth; Covid-19; Efficient Trial Design; Digital Medicine,,,"

Background

Germ Defence ( www.germdefence.org ) is an evidence-based interactive website that promotes behaviour change for infection control within households. To maximise the potential of Germ Defence to effectively reduce the spread of COVID-19, the intervention needed to be implemented at scale rapidly.

Methods

With NHS England approval, we conducted an efficient two-arm (1:1 ratio) cluster randomised controlled trial (RCT) to examine the effectiveness of randomising implementation of Germ Defence via general practitioner (GP) practices across England, UK, compared with usual care to disseminate Germ Defence to patients. GP practices randomised to the intervention arm (n = 3292) were emailed and asked to disseminate Germ Defence to all adult patients via mobile phone text, email or social media. Usual care arm GP practices (n = 3287) maintained standard management for the 4-month trial period and then asked to share Germ Defence with their adult patients. The primary outcome was the rate of GP presentations for respiratory tract infections (RTI) per patient. Secondary outcomes comprised rates of acute RTIs, confirmed COVID-19 diagnoses and suspected COVID-19 diagnoses, COVID-19 symptoms, gastrointestinal infection diagnoses, antibiotic usage and hospital admissions. The impact of the intervention on outcome rates was assessed using negative binomial regression modelling within the OpenSAFELY platform. The uptake of the intervention by GP practice and by patients was measured via website analytics.

Results

Germ Defence was used 310,731 times. The average website satisfaction score was 7.52 (0-10 not at all to very satisfied, N = 9933). There was no evidence of a difference in the rate of RTIs between intervention and control practices (rate ratio (RR) 1.01, 95% CI 0.96, 1.06, p = 0.70). This was similar to all other eight health outcomes. Patient engagement within intervention arm practices ranged from 0 to 48% of a practice list.

Conclusions

While the RCT did not demonstrate a difference in health outcomes, we demonstrated that rapid large-scale implementation of a digital behavioural intervention is possible and can be evaluated with a novel efficient prospective RCT methodology analysing routinely collected patient data entirely within a trusted research environment.

Trial registration

This trial was registered in the ISRCTN registry (14602359) on 12 August 2020.",,pdf:https://implementationscience.biomedcentral.com/counter/pdf/10.1186/s13012-023-01321-z; doi:https://doi.org/10.1186/s13012-023-01321-z; html:https://europepmc.org/articles/PMC10694966; pdf:https://europepmc.org/articles/PMC10694966?pdf=render 37528841,https://doi.org/10.1016/j.eclinm.2023.102064,Repeated antibiotic exposure and risk of hospitalisation and death following COVID-19 infection (OpenSAFELY): a matched case-control study.,"Yang YT, Wong D, Ashcroft DM, Massey J, MacKenna B, Fisher L, Mehrkar A, Bacon SC, OpenSAFELY collaborative, Hand K, Zhong X, Fahmi A, Goldacre B, van Staa T, Palin V.",,EClinicalMedicine,2023,2023-07-05,Y,Antibiotics; Primary Care; Severe Outcome; Covid-19,,,"

Background

Identifying potential risk factors related to severe COVID-19 outcomes is important. Repeated intermittent antibiotic use is known be associated with adverse outcomes. This study aims to examine whether prior frequent antibiotic exposure is associated with severe COVID-19 outcomes.

Methods

With the approval of NHS England, we used the OpenSAFELY platform, which integrated primary and secondary care, COVID-19 test, and death registration data. This matched case-control study included 0.67 million patients (aged 18-110 years) from an eligible 2.47 million patients with incident COVID-19 by matching with replacement. Inclusion criteria included registration within one general practice for at least 3 years and infection with incident COVID-19. Cases were identified according to different severity of COVID-19 outcomes. Cases and eligible controls were 1:6 matched on age, sex, region of GP practice, and index year and month of COVID-19 infection. Five quintile groups, based on the number of previous 3-year antibiotic prescriptions, were created to indicate the frequency of prior antibiotic exposure. Conditional logistic regression used to compare the differences between case and control groups, adjusting for ethnicity, body mass index, comorbidities, vaccination history, deprivation, and care home status. Sensitivity analyses were done to explore potential confounding and the effects of missing data.

Findings

Based on our inclusion criteria, between February 1, 2020 and December 31, 2021, 98,420 patients were admitted to hospitals and 22,660 died. 55 unique antibiotics were prescribed. A dose-response relationship between number of antibiotic prescriptions and risk of severe COVID-19 outcome was observed. Patients in the highest quintile with history of prior antibiotic exposure had 1.80 times greater odds of hospitalisation compared to patients without antibiotic exposure (adjusted odds ratio [OR] 1.80, 95% Confidence Interval [CI] 1.75-1.84). Similarly, the adjusted OR for hospitalised patients with death outcomes was 1.34 (95% CI 1.28-1.41). Larger number of prior antibiotic type was also associated with more severe COVID-19 related hospital admission. The adjusted OR of quintile 5 exposure (the most frequent) with more than 3 antibiotic types was around 2 times larger than quintile 1 (only 1 type; OR 1.80, 95% CI 1.75-1.84 vs. OR 1.03, 95% CI 1.01-1.05).

Interpretation

Our observational study has provided evidence that antibiotic exposure frequency and diversity may be associated with COVID-19 severity, potentially suggesting adverse effects of repeated intermittent antibiotic use. Future work could work to elucidate causal links and potential mechanisms. Antibiotic stewardship should put more emphasis on long-term antibiotic exposure and its adverse outcome to increase the awareness of appropriate antibiotics use.

Funding

Health Data Research UK and National Institute for Health Research.",,doi:https://doi.org/10.1016/j.eclinm.2023.102064; html:https://europepmc.org/articles/PMC10388579; pdf:https://europepmc.org/articles/PMC10388579?pdf=render -38803829,https://doi.org/10.1136/bmjmed-2023-000791,Incidence and treatment of group A streptococcal infections during covid-19 pandemic and 2022 outbreak: retrospective cohort study in England using OpenSAFELY-TPP.,"Cunningham C, Fisher L, Wood C, Speed V, Brown AD, Curtis H, Higgins R, Croker R, Butler-Cole BF, Evans D, Inglesby P, Dillingham I, Bacon SC, Beech E, Hand K, Davy S, Ward T, Hickman G, Bridges L, O'Dwyer T, Maude S, Smith RM, Mehrkar A, Hart LC, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, MacKenna B.",,BMJ medicine,2024,2024-05-24,Y,Primary Health Care; Infectious Disease Medicine; Covid-19,,,"

Objective

To investigate the effect of the covid-19 pandemic on the number of patients with group A streptococcal infections and related antibiotic prescriptions.

Design

Retrospective cohort study in England using OpenSAFELY-TPP.

Setting

Primary care practices in England that used TPP SystmOne software, 1 January 2018 to 31 March 2023, with the approval of NHS England.

Participants

Patients registered at a TPP practice at the start of each month of the study period. Patients with missing data for sex or age were excluded, resulting in a population of 23 816 470 in January 2018, increasing to 25 541 940 by March 2023.

Main outcome measures

Monthly counts and crude rates of patients with group A streptococcal infections (sore throat or tonsillitis, scarlet fever, and invasive group A streptococcal infections), and recommended firstline, alternative, and reserved antibiotic prescriptions linked with a group A streptococcal infection before (pre-April 2020), during, and after (post-April 2021) covid-19 restrictions. Maximum and minimum count and rate for each infectious season (time from September to August), as well as the rate ratio of the 2022-23 season compared with the last comparably high season (2017-18).

Results

The number of patients with group A streptococcal infections, and antibiotic prescriptions linked to an indication of group A streptococcal infection, peaked in December 2022, higher than the peak in 2017-18. The rate ratios for monthly sore throat or tonsillitis (possible group A streptococcal throat infection), scarlet fever, and invasive group A streptococcal infection in 2022-23 relative to 2017-18 were 1.39 (95% confidence interval (CI) 1.38 to 1.40), 2.68 (2.59 to 2.77), and 4.37 (2.94 to 6.48), respectively. The rate ratio for prescriptions of first line, alternative, and reserved antibiotics to patients with group A streptococcal infections in 2022-23 relative to 2017-18 were 1.37 (95% CI 1.35 to 1.38), 2.30 (2.26 to 2.34), and 2.42 (2.24 to 2.61), respectively. For individual antibiotic prescriptions in 2022-23, azithromycin showed the greatest relative increase versus 2017-18, with a rate ratio of 7.37 (6.22 to 8.74). This finding followed a marked decrease in the recording of patients with group A streptococcal infections and associated prescriptions during the period of covid-19 restrictions where the maximum count and rates were lower than any minimum rates before the covid-19 pandemic.

Conclusions

Recording of rates of scarlet fever, sore throat or tonsillitis, and invasive group A streptococcal infections, and associated antibiotic prescribing, peaked in December 2022. Primary care data can supplement existing infectious disease surveillance through linkages with relevant prescribing data and detailed analysis of clinical and demographic subgroups.",,doi:https://doi.org/10.1136/bmjmed-2023-000791; html:https://europepmc.org/articles/PMC11129040; pdf:https://europepmc.org/articles/PMC11129040?pdf=render PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated with multi-mode transportation networks in China,"Xu X, Liu X, Wang L, Wu Y, Lu X, Wang X, Pei S.",,Fundamental Research,2022,2022-04-22,Y,Complex Network; Spatial Spread; Human Mobility; Transportation Networks; Covid-19,,,"The spatial spread of COVID-19 during early 2020 in China was primarily driven by outbound travelers leaving the epicenter, Wuhan, Hubei province. Existing studies focus on the influence of aggregated out-bound population flows originating from Wuhan; however, the impacts of different modes of transportation and the network structure of transportation systems on the early spread of COVID-19 in China are not well understood. Here, we assess the roles of the road, railway, and air transportation networks in driving the spatial spread of COVID-19 in China. We find that the short-range spread within Hubei province was dominated by ground traffic, notably, the railway transportation. In contrast, long-range spread to cities in other provinces was mediated by multiple factors, including a higher risk of case importation associated with air transportation and a larger outbreak size in hub cities located at the center of transportation networks. We further show that, although the dissemination of SARS-CoV-2 across countries and continents is determined by the worldwide air transportation network, the early geographic dispersal of COVID-19 within China is better predicted by the railway traffic. Given the recent emergence of multiple more transmissible variants of SARS-CoV-2, our findings can support a better assessment of the spread risk of those variants and improve future pandemic preparedness and responses. Graphical abstract Image, graphical abstract.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023380/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023380/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9023380; pdf:https://europepmc.org/articles/PMC9023380?pdf=render -37562853,https://doi.org/10.1136/bmjment-2023-300842,Living alone and mental health: parallel analyses in UK longitudinal population surveys and electronic health records prior to and during the COVID-19 pandemic.,"McElroy E, Herrett E, Patel K, Piehlmaier DM, Gessa GD, Huggins C, Green MJ, Kwong ASF, Thompson EJ, Zhu J, Mansfield KE, Silverwood RJ, Mansfield R, Maddock J, Mathur R, Costello RE, Matthews A, Tazare J, Henderson A, Wing K, Bridges L, Bacon S, Mehrkar A, OpenSAFELY Collaborative, Shaw RJ, Wels J, Katikireddi SV, Chaturvedi N, Tomlinson LA, Patalay P, Longitudinal Health and Wellbeing Collaborative.",,BMJ mental health,2023,2023-08-01,Y,Psychiatry; Anxiety Disorders; Covid-19,,,"

Background

People who live alone experience greater levels of mental illness; however, it is unclear whether the COVID-19 pandemic had a disproportionately negative impact on this demographic.

Objective

To describe the mental health gap between those who live alone and with others in the UK prior to and during the COVID-19 pandemic.

Methods

Self-reported psychological distress and life satisfaction in 10 prospective longitudinal population surveys (LPSs) assessed in the nearest pre-pandemic sweep and three periods during the pandemic. Recorded diagnosis of common and severe mental illnesses between March 2018 and January 2022 in electronic healthcare records (EHRs) within the OpenSAFELY-TPP.

Findings

In 37 544 LPS participants, pooled models showed greater psychological distress (standardised mean difference (SMD): 0.09 (95% CI: 0.04; 0.14); relative risk: 1.25 (95% CI: 1.12; 1.39)) and lower life satisfaction (SMD: -0.22 (95% CI: -0.30; -0.15)) for those living alone pre-pandemic. This gap did not change during the pandemic. In the EHR analysis of c.16 million records, mental health conditions were more common in those who lived alone (eg, depression 26 (95% CI: 18 to 33) and severe mental illness 58 (95% CI: 54 to 62) more cases more per 100 000). For common mental health disorders, the gap in recorded cases in EHRs narrowed during the pandemic.

Conclusions

People living alone have poorer mental health and lower life satisfaction. During the pandemic, this gap in self-reported distress remained; however, there was a narrowing of the gap in service use.

Clinical implications

Greater mental health need and potentially greater barriers to mental healthcare access for those who live alone need to be considered in healthcare planning.",,pdf:https://mentalhealth.bmj.com/content/ebmental/26/1/e300842.full.pdf; doi:https://doi.org/10.1136/bmjment-2023-300842; html:https://europepmc.org/articles/PMC10577768; pdf:https://europepmc.org/articles/PMC10577768?pdf=render 34018481,https://doi.org/10.2807/1560-7917.es.2021.26.20.2100428,The potential for vaccination-induced herd immunity against the SARS-CoV-2 B.1.1.7 variant.,"Hodgson D, Flasche S, Jit M, Kucharski AJ, CMMID COVID-19 Working Group, Centre for Mathematical Modelling of Infectious Disease (CMMID) COVID-19 Working Group.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2021,2021-05-01,Y,Vaccination; Herd immunity; Seroprevalence; Sars-cov-2,,,"We assess the feasibility of reaching the herd immunity threshold against SARS-CoV-2 through vaccination, considering vaccine effectiveness (VE), transmissibility of the virus and the level of pre-existing immunity in populations, as well as their age structure. If highly transmissible variants of concern become dominant in areas with low levels of naturally-acquired immunity and/or in populations with large proportions of < 15 year-olds, control of infection without non-pharmaceutical interventions may only be possible with a VE ≥ 80%, and coverage extended to children.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/26/20/eurosurv-26-20-1.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2021.26.20.2100428&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2021.26.20.2100428; html:https://europepmc.org/articles/PMC8138959; pdf:https://europepmc.org/articles/PMC8138959?pdf=render +38803829,https://doi.org/10.1136/bmjmed-2023-000791,Incidence and treatment of group A streptococcal infections during covid-19 pandemic and 2022 outbreak: retrospective cohort study in England using OpenSAFELY-TPP.,"Cunningham C, Fisher L, Wood C, Speed V, Brown AD, Curtis H, Higgins R, Croker R, Butler-Cole BF, Evans D, Inglesby P, Dillingham I, Bacon SC, Beech E, Hand K, Davy S, Ward T, Hickman G, Bridges L, O'Dwyer T, Maude S, Smith RM, Mehrkar A, Hart LC, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, MacKenna B.",,BMJ medicine,2024,2024-05-24,Y,Primary Health Care; Infectious Disease Medicine; Covid-19,,,"

Objective

To investigate the effect of the covid-19 pandemic on the number of patients with group A streptococcal infections and related antibiotic prescriptions.

Design

Retrospective cohort study in England using OpenSAFELY-TPP.

Setting

Primary care practices in England that used TPP SystmOne software, 1 January 2018 to 31 March 2023, with the approval of NHS England.

Participants

Patients registered at a TPP practice at the start of each month of the study period. Patients with missing data for sex or age were excluded, resulting in a population of 23 816 470 in January 2018, increasing to 25 541 940 by March 2023.

Main outcome measures

Monthly counts and crude rates of patients with group A streptococcal infections (sore throat or tonsillitis, scarlet fever, and invasive group A streptococcal infections), and recommended firstline, alternative, and reserved antibiotic prescriptions linked with a group A streptococcal infection before (pre-April 2020), during, and after (post-April 2021) covid-19 restrictions. Maximum and minimum count and rate for each infectious season (time from September to August), as well as the rate ratio of the 2022-23 season compared with the last comparably high season (2017-18).

Results

The number of patients with group A streptococcal infections, and antibiotic prescriptions linked to an indication of group A streptococcal infection, peaked in December 2022, higher than the peak in 2017-18. The rate ratios for monthly sore throat or tonsillitis (possible group A streptococcal throat infection), scarlet fever, and invasive group A streptococcal infection in 2022-23 relative to 2017-18 were 1.39 (95% confidence interval (CI) 1.38 to 1.40), 2.68 (2.59 to 2.77), and 4.37 (2.94 to 6.48), respectively. The rate ratio for prescriptions of first line, alternative, and reserved antibiotics to patients with group A streptococcal infections in 2022-23 relative to 2017-18 were 1.37 (95% CI 1.35 to 1.38), 2.30 (2.26 to 2.34), and 2.42 (2.24 to 2.61), respectively. For individual antibiotic prescriptions in 2022-23, azithromycin showed the greatest relative increase versus 2017-18, with a rate ratio of 7.37 (6.22 to 8.74). This finding followed a marked decrease in the recording of patients with group A streptococcal infections and associated prescriptions during the period of covid-19 restrictions where the maximum count and rates were lower than any minimum rates before the covid-19 pandemic.

Conclusions

Recording of rates of scarlet fever, sore throat or tonsillitis, and invasive group A streptococcal infections, and associated antibiotic prescribing, peaked in December 2022. Primary care data can supplement existing infectious disease surveillance through linkages with relevant prescribing data and detailed analysis of clinical and demographic subgroups.",,doi:https://doi.org/10.1136/bmjmed-2023-000791; html:https://europepmc.org/articles/PMC11129040; pdf:https://europepmc.org/articles/PMC11129040?pdf=render +37562853,https://doi.org/10.1136/bmjment-2023-300842,Living alone and mental health: parallel analyses in UK longitudinal population surveys and electronic health records prior to and during the COVID-19 pandemic.,"McElroy E, Herrett E, Patel K, Piehlmaier DM, Gessa GD, Huggins C, Green MJ, Kwong ASF, Thompson EJ, Zhu J, Mansfield KE, Silverwood RJ, Mansfield R, Maddock J, Mathur R, Costello RE, Matthews A, Tazare J, Henderson A, Wing K, Bridges L, Bacon S, Mehrkar A, OpenSAFELY Collaborative, Shaw RJ, Wels J, Katikireddi SV, Chaturvedi N, Tomlinson LA, Patalay P, Longitudinal Health and Wellbeing Collaborative.",,BMJ mental health,2023,2023-08-01,Y,Psychiatry; Anxiety Disorders; Covid-19,,,"

Background

People who live alone experience greater levels of mental illness; however, it is unclear whether the COVID-19 pandemic had a disproportionately negative impact on this demographic.

Objective

To describe the mental health gap between those who live alone and with others in the UK prior to and during the COVID-19 pandemic.

Methods

Self-reported psychological distress and life satisfaction in 10 prospective longitudinal population surveys (LPSs) assessed in the nearest pre-pandemic sweep and three periods during the pandemic. Recorded diagnosis of common and severe mental illnesses between March 2018 and January 2022 in electronic healthcare records (EHRs) within the OpenSAFELY-TPP.

Findings

In 37 544 LPS participants, pooled models showed greater psychological distress (standardised mean difference (SMD): 0.09 (95% CI: 0.04; 0.14); relative risk: 1.25 (95% CI: 1.12; 1.39)) and lower life satisfaction (SMD: -0.22 (95% CI: -0.30; -0.15)) for those living alone pre-pandemic. This gap did not change during the pandemic. In the EHR analysis of c.16 million records, mental health conditions were more common in those who lived alone (eg, depression 26 (95% CI: 18 to 33) and severe mental illness 58 (95% CI: 54 to 62) more cases more per 100 000). For common mental health disorders, the gap in recorded cases in EHRs narrowed during the pandemic.

Conclusions

People living alone have poorer mental health and lower life satisfaction. During the pandemic, this gap in self-reported distress remained; however, there was a narrowing of the gap in service use.

Clinical implications

Greater mental health need and potentially greater barriers to mental healthcare access for those who live alone need to be considered in healthcare planning.",,pdf:https://mentalhealth.bmj.com/content/ebmental/26/1/e300842.full.pdf; doi:https://doi.org/10.1136/bmjment-2023-300842; html:https://europepmc.org/articles/PMC10577768; pdf:https://europepmc.org/articles/PMC10577768?pdf=render 36522333,https://doi.org/10.1038/s41467-022-35454-4,Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence.,"Gisby JS, Buang NB, Papadaki A, Clarke CL, Malik TH, Medjeral-Thomas N, Pinheiro D, Mortimer PM, Lewis S, Sandhu E, McAdoo SP, Prendecki MF, Willicombe M, Pickering MC, Botto M, Thomas DC, Peters JE.",,Nature communications,2022,2022-12-15,Y,,,,"Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. Here, we perform longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Supervised learning reveals that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. We show that a decreasing trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, is associated with a more severe clinical course. We observe that two months after the acute infection, patients still display dysregulated gene expression related to vascular, platelet and coagulation pathways, including PF4 (platelet factor 4), which may explain the prolonged thrombotic risk following COVID-19.",,pdf:https://www.nature.com/articles/s41467-022-35454-4.pdf; doi:https://doi.org/10.1038/s41467-022-35454-4; html:https://europepmc.org/articles/PMC9753891; pdf:https://europepmc.org/articles/PMC9753891?pdf=render 35902613,https://doi.org/10.1038/s41467-022-32096-4,Dynamics of competing SARS-CoV-2 variants during the Omicron epidemic in England.,"Eales O, de Oliveira Martins L, Page AJ, Wang H, Bodinier B, Tang D, Haw D, Jonnerby J, Atchison C, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S, Elliott P, Donnelly CA, Chadeau-Hyam M.",,Nature communications,2022,2022-07-28,Y,,,,"The SARS-CoV-2 pandemic has been characterised by the regular emergence of genomic variants. With natural and vaccine-induced population immunity at high levels, evolutionary pressure favours variants better able to evade SARS-CoV-2 neutralising antibodies. The Omicron variant (first detected in November 2021) exhibited a high degree of immune evasion, leading to increased infection rates worldwide. However, estimates of the magnitude of this Omicron wave have often relied on routine testing data, which are prone to several biases. Using data from the REal-time Assessment of Community Transmission-1 (REACT-1) study, a series of cross-sectional surveys assessing prevalence of SARS-CoV-2 infection in England, we estimated the dynamics of England's Omicron wave (from 9 September 2021 to 1 March 2022). We estimate an initial peak in national Omicron prevalence of 6.89% (5.34%, 10.61%) during January 2022, followed by a resurgence in SARS-CoV-2 infections as the more transmissible Omicron sub-lineage, BA.2 replaced BA.1 and BA.1.1. Assuming the emergence of further distinct variants, intermittent epidemics of similar magnitudes may become the 'new normal'.",,pdf:https://www.nature.com/articles/s41467-022-32096-4.pdf; doi:https://doi.org/10.1038/s41467-022-32096-4; html:https://europepmc.org/articles/PMC9330949; pdf:https://europepmc.org/articles/PMC9330949?pdf=render 37182748,https://doi.org/10.1016/j.jinf.2023.05.010,The impact of COVID-19 on antibiotic prescribing in primary care in England: Evaluation and risk prediction of appropriateness of type and repeat prescribing.,"Zhong X, Pate A, Yang YT, Fahmi A, Ashcroft DM, Goldacre B, MacKenna B, Mehrkar A, Bacon SCJ, Massey J, Fisher L, Inglesby P, OpenSAFELY collaborative, Hand K, van Staa T, Palin V.",,The Journal of infection,2023,2023-05-12,Y,Infection; Antibiotics; Primary Care; Antibiotic Stewardship; Covid-19 Pandemic,,,"

Background

This study aimed to predict risks of potentially inappropriate antibiotic type and repeat prescribing and assess changes during COVID-19.

Methods

With the approval of NHS England, we used OpenSAFELY platform to access the TPP SystmOne electronic health record (EHR) system and selected patients prescribed antibiotics from 2019 to 2021. Multinomial logistic regression models predicted patient's probability of receiving inappropriate antibiotic type or repeat antibiotic course for each common infection.

Results

The population included 9.1 million patients with 29.2 million antibiotic prescriptions. 29.1% of prescriptions were identified as repeat prescribing. Those with same day incident infection coded in the EHR had considerably lower rates of repeat prescribing (18.0%) and 8.6% had potentially inappropriate type. No major changes in the rates of repeat antibiotic prescribing during COVID-19 were found. In the 10 risk prediction models, good levels of calibration and moderate levels of discrimination were found.

Conclusions

Our study found no evidence of changes in level of inappropriate or repeat antibiotic prescribing after the start of COVID-19. Repeat antibiotic prescribing was frequent and varied according to regional and patient characteristics. There is a need for treatment guidelines to be developed around antibiotic failure and clinicians provided with individualised patient information.",,pdf:http://www.journalofinfection.com/article/S0163445323002888/pdf; doi:https://doi.org/10.1016/j.jinf.2023.05.010; html:https://europepmc.org/articles/PMC10176893; pdf:https://europepmc.org/articles/PMC10176893?pdf=render @@ -222,8 +222,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 38693557,https://doi.org/10.1186/s12913-024-10931-2,The cost of keeping patients waiting: retrospective treatment-control study of additional healthcare utilisation for UK patients awaiting elective treatment.,"James C, Denholm R, Wood R.",,BMC health services research,2024,2024-04-30,Y,Utilisation; Waiting Times; Waitlist; Elective Recovery; Failure-demand,,,"

Objective

Long waiting times for elective hospital treatments are common in many countries. This study seeks to address a deficit in the literature concerning the effect of long waits on the wider consumption of healthcare resources.

Methods

We carried out a retrospective treatment-control study in a healthcare system in South West England from 15 June 2021 to 15 December 2021. We compared weekly contacts with health services of patients waiting over 18 weeks for treatment ('Treatments') and people not on a waiting list ('Controls'). Controls were matched to Treatments based on age, sex, deprivation and multimorbidity. Treatments were stratified by the clinical specialty of the awaited hospital treatment, with healthcare usage assessed over various healthcare settings. Wilcoxon signed-rank tests assessed whether there was an increase in healthcare utilisation and bootstrap resampling was used to estimate the magnitude of any differences.

Results

A total of 44,616 patients were waiting over 18 weeks (the constitutional target in England) for treatment during the study period. There was an increase (p < 0.0004) in healthcare utilisation for all specialties. Patients in the Cardiothoracic Surgery specialty had the largest increase, with 17.9 [interquartile-range: 4.3, 33.8] additional contacts with secondary care and 17.3 [-1.1, 34.1] additional prescriptions per year.

Conclusion

People waiting for treatment consume higher levels of healthcare than comparable individuals not on a waiting list. These findings are relevant for clinicians and managers in better understanding patient need and reducing harm. Results also highlight the possible 'false economy' in failing to promptly resolve long elective waits.",,doi:https://doi.org/10.1186/s12913-024-10931-2; html:https://europepmc.org/articles/PMC11061904; pdf:https://europepmc.org/articles/PMC11061904?pdf=render 35104687,https://doi.org/10.1016/j.retram.2022.103333,A common TMPRSS2 variant has a protective effect against severe COVID-19.,"David A, Parkinson N, Peacock TP, Pairo-Castineira E, Khanna T, Cobat A, Tenesa A, Sancho-Shimizu V, GenOMICC Consortium, ISARIC4C Investigators, Casanova JL, Abel L, Barclay WS, Baillie JK, Sternberg MJ.",,Current research in translational medicine,2022,2022-01-10,Y,Tmprss2; Covid-19; Sars-cov-2; Targeting The Host To Prevent Covid19 Severity,,,"

Background

The human protein transmembrane protease serine type 2 (TMPRSS2) plays a key role in SARS-CoV-2 infection, as it is required to activate the virus' spike protein, facilitating entry into target cells. We hypothesized that naturally-occurring TMPRSS2 human genetic variants affecting the structure and function of the TMPRSS2 protein may modulate the severity of SARS-CoV-2 infection.

Methods

We focused on the only common TMPRSS2 non-synonymous variant predicted to be damaging (rs12329760 C>T, p.V160M), which has a minor allele frequency ranging from 0.14 in Ashkenazi Jewish to 0.38 in East Asians. We analysed the association between the rs12329760 and COVID-19 severity in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units recruited as part of the GenOMICC (Genetics Of Mortality In Critical Care) study. Logistic regression analyses were adjusted for sex, age and deprivation index. For in vitro studies, HEK293 cells were co-transfected with ACE2 and either TMPRSS2 wild type or mutant (TMPRSS2V160M). A SARS-CoV-2 pseudovirus entry assay was used to investigate the ability of TMPRSS2V160M to promote viral entry.

Results

We show that the T allele of rs12329760 is associated with a reduced likelihood of developing severe COVID-19 (OR 0.87, 95%CI:0.79-0.97, p = 0.01). This association was stronger in homozygous individuals when compared to the general population (OR 0.65, 95%CI:0.50-0.84, p = 1.3 × 10-3). We demonstrate in vitro that this variant, which causes the amino acid substitution valine to methionine, affects the catalytic activity of TMPRSS2 and is less able to support SARS-CoV-2 spike-mediated entry into cells.

Conclusion

TMPRSS2 rs12329760 is a common variant associated with a significantly decreased risk of severe COVID-19. Further studies are needed to assess the expression of TMPRSS2 across different age groups. Moreover, our results identify TMPRSS2 as a promising drug target, with a potential role for camostat mesilate, a drug approved for the treatment of chronic pancreatitis and postoperative reflux esophagitis, in the treatment of COVID-19. Clinical trials are needed to confirm this.",,doi:https://doi.org/10.1016/j.retram.2022.103333; doi:https://doi.org/10.1016/j.retram.2022.103333; html:https://europepmc.org/articles/PMC8743599; pdf:https://europepmc.org/articles/PMC8743599?pdf=render 35192611,https://doi.org/10.1371/journal.pmed.1003916,Uptake of infant and preschool immunisations in Scotland and England during the COVID-19 pandemic: An observational study of routinely collected data.,"McQuaid F, Mulholland R, Sangpang Rai Y, Agrawal U, Bedford H, Cameron JC, Gibbons C, Roy P, Sheikh A, Shi T, Simpson CR, Tait J, Tessier E, Turner S, Villacampa Ortega J, White J, Wood R.",,PLoS medicine,2022,2022-02-22,Y,,,,"

Background

In 2020, the SARS-CoV-2 (COVID-19) pandemic and lockdown control measures threatened to disrupt routine childhood immunisation programmes with early reports suggesting uptake would fall. In response, public health bodies in Scotland and England collected national data for childhood immunisations on a weekly or monthly basis to allow for rapid analysis of trends. The aim of this study was to use these data to assess the impact of different phases of the pandemic on infant and preschool immunisation uptake rates.

Methods and findings

We conducted an observational study using routinely collected data for the year prior to the pandemic (2019) and immediately before (22 January to March 2020), during (23 March to 26 July), and after (27 July to 4 October) the first UK ""lockdown"". Data were obtained for Scotland from the Public Health Scotland ""COVID19 wider impacts on the health care system"" dashboard and for England from ImmForm. Five vaccinations delivered at different ages were evaluated; 3 doses of ""6-in-1"" diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b, and hepatitis B vaccine (DTaP/IPV/Hib/HepB) and 2 doses of measles, mumps, and rubella (MMR) vaccine. This represented 439,754 invitations to be vaccinated in Scotland and 4.1 million for England. Uptake during the 2020 periods was compared to the previous year (2019) using binary logistic regression analysis. For Scotland, uptake within 4 weeks of a child becoming eligible by age was analysed along with geographical region and indices of deprivation. For Scotland and England, we assessed whether immunisations were up-to-date at approximately 6 months (all doses 6-in-1) and 16 to 18 months (first MMR) of age. We found that uptake within 4 weeks of eligibility in Scotland for all the 5 vaccines was higher during lockdown than in 2019. Differences ranged from 1.3% for first dose 6-in-1 vaccine (95.3 versus 94%, odds ratio [OR] compared to 2019 1.28, 95% confidence intervals [CIs] 1.18 to 1.39) to 14.3% for second MMR dose (66.1 versus 51.8%, OR compared to 2019 1.8, 95% CI 1.74 to 1.87). Significant increases in uptake were seen across all deprivation levels. In England, fewer children due to receive their immunisations during the lockdown period were up to date at 6 months (6-in-1) or 18 months (first dose MMR). The fall in percentage uptake ranged from 0.5% for first 6-in-1 (95.8 versus 96.3%, OR compared to 2019 0.89, 95% CI 0.86- to 0.91) to 2.1% for third 6-in-1 (86.6 versus 88.7%, OR compared to 2019 0.82, 95% CI 0.81 to 0.83). The use of routinely collected data used in this study was a limiting factor as detailed information on potential confounding factors were not available and we were unable to eliminate the possibility of seasonal trends in immunisation uptake.

Conclusions

In this study, we observed that the national lockdown in Scotland was associated with an increase in timely childhood immunisation uptake; however, in England, uptake fell slightly. Reasons for the improved uptake in Scotland may include active measures taken to promote immunisation at local and national levels during this period and should be explored further. Promoting immunisation uptake and addressing potential vaccine hesitancy is particularly important given the ongoing pandemic and COVID-19 vaccination campaigns.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003916&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003916; html:https://europepmc.org/articles/PMC8863286; pdf:https://europepmc.org/articles/PMC8863286?pdf=render -36227072,https://doi.org/10.1093/jamia/ocac203,Transforming and evaluating the UK Biobank to the OMOP Common Data Model for COVID-19 research and beyond.,"Papez V, Moinat M, Voss EA, Bazakou S, Van Winzum A, Peviani A, Payralbe S, Kallfelz M, Asselbergs FW, Prieto-Alhambra D, Dobson RJB, Denaxas S.",,Journal of the American Medical Informatics Association : JAMIA,2022,2022-12-01,Y,Phenotyping; Electronic Health Records; Omop; Common Data Model; Medical Ontologies,,,"

Objective

The coronavirus disease 2019 (COVID-19) pandemic has demonstrated the value of real-world data for public health research. International federated analyses are crucial for informing policy makers. Common data models (CDMs) are critical for enabling these studies to be performed efficiently. Our objective was to convert the UK Biobank, a study of 500 000 participants with rich genetic and phenotypic data to the Observational Medical Outcomes Partnership (OMOP) CDM.

Materials and methods

We converted UK Biobank data to OMOP CDM v. 5.3. We transformedparticipant research data on diseases collected at recruitment and electronic health records (EHRs) from primary care, hospitalizations, cancer registrations, and mortality from providers in England, Scotland, and Wales. We performed syntactic and semantic validations and compared comorbidities and risk factors between source and transformed data.

Results

We identified 502 505 participants (3086 with COVID-19) and transformed 690 fields (1 373 239 555 rows) to the OMOP CDM using 8 different controlled clinical terminologies and bespoke mappings. Specifically, we transformed self-reported noncancer illnesses 946 053 (83.91% of all source entries), cancers 37 802 (70.81%), medications 1 218 935 (88.25%), and prescriptions 864 788 (86.96%). In EHR, we transformed 13 028 182 (99.95%) hospital diagnoses, 6 465 399 (89.2%) procedures, 337 896 333 primary care diagnoses (CTV3, SNOMED-CT), 139 966 587 (98.74%) prescriptions (dm+d) and 77 127 (99.95%) deaths (ICD-10). We observed good concordance across demographic, risk factor, and comorbidity factors between source and transformed data.

Discussion and conclusion

Our study demonstrated that the OMOP CDM can be successfully leveraged to harmonize complex large-scale biobanked studies combining rich multimodal phenotypic data. Our study uncovered several challenges when transforming data from questionnaires to the OMOP CDM which require further research. The transformed UK Biobank resource is a valuable tool that can enable federated research, like COVID-19 studies.",,pdf:https://academic.oup.com/jamia/article-pdf/30/1/103/47829607/ocac203.pdf; doi:https://doi.org/10.1093/jamia/ocac203; html:https://europepmc.org/articles/PMC9619789; pdf:https://europepmc.org/articles/PMC9619789?pdf=render 35296643,https://doi.org/10.1038/s41467-022-28517-z,"Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab.","Lin S, Kennedy NA, Saifuddin A, Sandoval DM, Reynolds CJ, Seoane RC, Kottoor SH, Pieper FP, Lin KM, Butler DK, Chanchlani N, Nice R, Chee D, Bewshea C, Janjua M, McDonald TJ, Sebastian S, Alexander JL, Constable L, Lee JC, Murray CD, Hart AL, Irving PM, Jones GR, Kok KB, Lamb CA, Lees CW, Altmann DM, Boyton RJ, Goodhand JR, Powell N, Ahmad T, CLARITY IBD study.",,Nature communications,2022,2022-03-16,Y,,,,"Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p <0.0001; 26.8 days [95% CI 26.2 - 27.5] vs 47.6 days [45.5 - 49.8], p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7 U/mL [5.0] vs 784.0 U/mL [3.5], p <0.0001; 35.9 days [34.9 - 36.8] vs 58.0 days [55.0 - 61.3], p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients.",,pdf:https://www.nature.com/articles/s41467-022-28517-z.pdf; doi:https://doi.org/10.1038/s41467-022-28517-z; html:https://europepmc.org/articles/PMC8927425; pdf:https://europepmc.org/articles/PMC8927425?pdf=render +36227072,https://doi.org/10.1093/jamia/ocac203,Transforming and evaluating the UK Biobank to the OMOP Common Data Model for COVID-19 research and beyond.,"Papez V, Moinat M, Voss EA, Bazakou S, Van Winzum A, Peviani A, Payralbe S, Kallfelz M, Asselbergs FW, Prieto-Alhambra D, Dobson RJB, Denaxas S.",,Journal of the American Medical Informatics Association : JAMIA,2022,2022-12-01,Y,Phenotyping; Electronic Health Records; Omop; Common Data Model; Medical Ontologies,,,"

Objective

The coronavirus disease 2019 (COVID-19) pandemic has demonstrated the value of real-world data for public health research. International federated analyses are crucial for informing policy makers. Common data models (CDMs) are critical for enabling these studies to be performed efficiently. Our objective was to convert the UK Biobank, a study of 500 000 participants with rich genetic and phenotypic data to the Observational Medical Outcomes Partnership (OMOP) CDM.

Materials and methods

We converted UK Biobank data to OMOP CDM v. 5.3. We transformedparticipant research data on diseases collected at recruitment and electronic health records (EHRs) from primary care, hospitalizations, cancer registrations, and mortality from providers in England, Scotland, and Wales. We performed syntactic and semantic validations and compared comorbidities and risk factors between source and transformed data.

Results

We identified 502 505 participants (3086 with COVID-19) and transformed 690 fields (1 373 239 555 rows) to the OMOP CDM using 8 different controlled clinical terminologies and bespoke mappings. Specifically, we transformed self-reported noncancer illnesses 946 053 (83.91% of all source entries), cancers 37 802 (70.81%), medications 1 218 935 (88.25%), and prescriptions 864 788 (86.96%). In EHR, we transformed 13 028 182 (99.95%) hospital diagnoses, 6 465 399 (89.2%) procedures, 337 896 333 primary care diagnoses (CTV3, SNOMED-CT), 139 966 587 (98.74%) prescriptions (dm+d) and 77 127 (99.95%) deaths (ICD-10). We observed good concordance across demographic, risk factor, and comorbidity factors between source and transformed data.

Discussion and conclusion

Our study demonstrated that the OMOP CDM can be successfully leveraged to harmonize complex large-scale biobanked studies combining rich multimodal phenotypic data. Our study uncovered several challenges when transforming data from questionnaires to the OMOP CDM which require further research. The transformed UK Biobank resource is a valuable tool that can enable federated research, like COVID-19 studies.",,pdf:https://academic.oup.com/jamia/article-pdf/30/1/103/47829607/ocac203.pdf; doi:https://doi.org/10.1093/jamia/ocac203; html:https://europepmc.org/articles/PMC9619789; pdf:https://europepmc.org/articles/PMC9619789?pdf=render 33658326,https://doi.org/10.1126/science.abg3055,Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England.,"Davies NG, Abbott S, Barnard RC, Jarvis CI, Kucharski AJ, Munday JD, Pearson CAB, Russell TW, Tully DC, Washburne AD, Wenseleers T, Gimma A, Waites W, Wong KLM, van Zandvoort K, Silverman JD, CMMID COVID-19 Working Group, COVID-19 Genomics UK (COG-UK) Consortium, Diaz-Ordaz K, Keogh R, Eggo RM, Funk S, Jit M, Atkins KE, Edmunds WJ.",,"Science (New York, N.Y.)",2021,2021-03-03,Y,,,,"A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, VOC 202012/01 (lineage B.1.1.7), emerged in southeast England in September 2020 and is rapidly spreading toward fixation. Using a variety of statistical and dynamic modeling approaches, we estimate that this variant has a 43 to 90% (range of 95% credible intervals, 38 to 130%) higher reproduction number than preexisting variants. A fitted two-strain dynamic transmission model shows that VOC 202012/01 will lead to large resurgences of COVID-19 cases. Without stringent control measures, including limited closure of educational institutions and a greatly accelerated vaccine rollout, COVID-19 hospitalizations and deaths across England in the first 6 months of 2021 were projected to exceed those in 2020. VOC 202012/01 has spread globally and exhibits a similar transmission increase (59 to 74%) in Denmark, Switzerland, and the United States.",,pdf:https://www.science.org/cms/asset/9064b3e4-39f9-402c-8fa2-b689efda98b4/pap.pdf; doi:https://doi.org/10.1126/science.abg3055; html:https://europepmc.org/articles/PMC8128288; pdf:https://europepmc.org/articles/PMC8128288?pdf=render 34726481,https://doi.org/10.1126/science.abl9551,"Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant.","Elliott P, Haw D, Wang H, Eales O, Walters CE, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Page AJ, Trotter AJ, Prosolek SJ, COVID-19 Genomics UK (COG-UK) Consortium11‡, Ashby D, Donnelly CA, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S.",,"Science (New York, N.Y.)",2021,2021-12-17,Y,,,,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were rising during early summer 2021 in many countries as a result of the Delta variant. We assessed reverse transcription polymerase chain reaction swab positivity in the Real-time Assessment of Community Transmission–1 (REACT-1) study in England. During June and July 2021, we observed sustained exponential growth with an average doubling time of 25 days, driven by complete replacement of the Alpha variant by Delta and by high prevalence at younger, less-vaccinated ages. Prevalence among unvaccinated people [1.21% (95% credible interval 1.03%, 1.41%)] was three times that among double-vaccinated people [0.40% (95% credible interval 0.34%, 0.48%)]. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination.",,pdf:https://www.science.org/history/7d0b03b2-b465-410e-a40d-7300157d8b54/science.abl9551.v1.pdf; doi:https://doi.org/10.1126/science.abl9551; html:https://europepmc.org/articles/PMC10763627; pdf:https://europepmc.org/articles/PMC10763627?pdf=render 38360481,https://doi.org/10.1016/j.ebiom.2024.105000,Phenome-wide analysis reveals epistatic associations between APOL1 variants and chronic kidney disease and multiple other disorders.,"Adamson WE, Noyes H, Johnson P, Cooper A, Monckton DG, Ogunsola J, Beckett-Hill G, Sullivan M, Mark P, Parekh RS, MacLeod A.",,EBioMedicine,2024,2024-02-14,Y,Chronic Kidney Disease; Phenome; Apol1; Uk Biobank; Covid-19,,,"

Background

APOL1 variants G1 and G2 are common in populations with recent African ancestry. They are associated with protection from African sleeping sickness, however homozygosity or compound heterozygosity for these variants is associated with chronic kidney disease (CKD) and related conditions. What is not clear is the extent of associations with non-kidney-related disorders, and whether there are clusters of diseases associated with individual APOL1 genotypes.

Methods

Using a cohort of 7462 UK Biobank participants with recent African ancestry, we conducted a phenome-wide association study investigating associations between individual APOL1 genotypes and conditions identified by the International Classification of Disease phenotypes.

Findings

We identified 27 potential associations between individual APOL1 genotypes and a diverse range of conditions. G1/G2 compound heterozygotes were specifically associated with 26 of these conditions (all deleteriously), with an over-representation of infectious diseases (including hospitalisation and death resulting from COVID-19). The analysis also exposed complexities in the relationship between APOL1 and CKD that are not evident when risk variants are grouped together: G1 homozygosity, G2 homozygosity, and G1/G2 compound heterozygosity were each shown to be associated with distinct CKD phenotypes. The multi-locus nature of the G1/G2 genotype means that its associations would go undetected in a standard genome-wide association study.

Interpretation

Our findings have implications for understanding health risks and better-targeted detection, intervention, and therapeutic strategies, particularly in populations where APOL1 G1 and G2 are common such as in sub-Saharan Africa and its diaspora.

Funding

This study was funded by the Wellcome Trust (209511/Z/17/Z) and H3Africa (H3A/18/004).",,doi:https://doi.org/10.1016/j.ebiom.2024.105000; html:https://europepmc.org/articles/PMC10944146; pdf:https://europepmc.org/articles/PMC10944146?pdf=render @@ -298,13 +298,13 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 36936265,https://doi.org/10.1136/bmjmed-2022-000276,"Trends, variation, and clinical characteristics of recipients of antiviral drugs and neutralising monoclonal antibodies for covid-19 in community settings: retrospective, descriptive cohort study of 23.4 million people in OpenSAFELY.","Green ACA, Curtis HJ, Higgins R, Nab L, Mahalingasivam V, Smith RM, Mehrkar A, Inglesby P, Drysdale H, DeVito NJ, Croker R, Rentsch CT, Bhaskaran K, Tazare J, Zheng B, Andrews CD, Bacon SCJ, Davy S, Dillingham I, Evans D, Fisher L, Hickman G, Hopcroft LEM, Hulme WJ, Massey J, MacDonald O, Morley J, Morton CE, Park RY, Walker AJ, Ward T, Wiedemann M, Bates C, Cockburn J, Parry J, Hester F, Harper S, Douglas IJ, Evans SJW, Goldacre B, Tomlinson LA, MacKenna B.",,BMJ medicine,2023,2023-01-13,Y,Therapeutics; Community health services; Public Health; Covid-19,,,"

Objective

To ascertain patient eligibility status and describe coverage of antiviral drugs and neutralising monoclonal antibodies (nMAB) as treatment for covid-19 in community settings in England.

Design

Retrospective, descriptive cohort study, approved by NHS England.

Setting

Routine clinical data from 23.4 million people linked to data on covid-19 infection and treatment, within the OpenSAFELY-TPP database.

Participants

Outpatients with covid-19 at high risk of severe outcomes.

Interventions

Nirmatrelvir/ritonavir (paxlovid), sotrovimab, molnupiravir, casirivimab/imdevimab, or remdesivir, used in the community by covid-19 medicine delivery units.

Results

93 870 outpatients with covid-19 were identified between 11 December 2021 and 28 April 2022 to be at high risk of severe outcomes and therefore potentially eligible for antiviral or nMAB treatment (or both). Of these patients, 19 040 (20%) received treatment (sotrovimab, 9660 (51%); molnupiravir, 4620 (24%); paxlovid, 4680 (25%); casirivimab/imdevimab, 50 (<1%); and remdesivir, 30 (<1%)). The proportion of patients treated increased from 9% (190/2220) in the first week of treatment availability to 29% (460/1600) in the latest week. The proportion treated varied by high risk group, being lowest in those with liver disease (16%; 95% confidence interval 15% to 17%); by treatment type, with sotrovimab favoured over molnupiravir and paxlovid in all but three high risk groups (Down's syndrome (35%; 30% to 39%), rare neurological conditions (45%; 43% to 47%), and immune deficiencies (48%; 47% to 50%)); by age, ranging from ≥80 years (13%; 12% to 14%) to 50-59 years (23%; 22% to 23%); by ethnic group, ranging from black (11%; 10% to 12%) to white (21%; 21% to 21%); by NHS region, ranging from 13% (12% to 14%) in Yorkshire and the Humber to 25% (24% to 25%) in the East of England); and by deprivation level, ranging from 15% (14% to 15%) in the most deprived areas to 23% (23% to 24%) in the least deprived areas. Groups that also had lower coverage included unvaccinated patients (7%; 6% to 9%), those with dementia (6%; 5% to 7%), and care home residents (6%; 6% to 7%).

Conclusions

Using the OpenSAFELY platform, we were able to identify patients with covid-19 at high risk of severe outcomes who were potentially eligible to receive treatment and assess the coverage of these new treatments among these patients. In the context of a rapid deployment of a new service, the NHS analytical code used to determine eligibility could have been over-inclusive and some of the eligibility criteria not fully captured in healthcare data. However targeted activity might be needed to resolve apparent lower treatment coverage observed among certain groups, in particular (at present): different NHS regions, ethnic groups, people aged ≥80 years, those living in socioeconomically deprived areas, and care home residents.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000276.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000276; html:https://europepmc.org/articles/PMC9951378; pdf:https://europepmc.org/articles/PMC9951378?pdf=render 35717168,https://doi.org/10.1186/s12879-022-07490-4,The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020.,"Knight GM, Pham TM, Stimson J, Funk S, Jafari Y, Pople D, Evans S, Yin M, Brown CS, Bhattacharya A, Hope R, Semple MG, ISARIC4C Investigators, CMMID COVID-19 Working Group, Read JM, Cooper BS, Robotham JV.",,BMC infectious diseases,2022,2022-06-18,Y,Mathematical Modelling; Nosocomial Transmission; Covid-19; Sars-cov-2,,,"

Background

SARS-CoV-2 is known to transmit in hospital settings, but the contribution of infections acquired in hospitals to the epidemic at a national scale is unknown.

Methods

We used comprehensive national English datasets to determine the number of COVID-19 patients with identified hospital-acquired infections (with symptom onset > 7 days after admission and before discharge) in acute English hospitals up to August 2020. As patients may leave the hospital prior to detection of infection or have rapid symptom onset, we combined measures of the length of stay and the incubation period distribution to estimate how many hospital-acquired infections may have been missed. We used simulations to estimate the total number (identified and unidentified) of symptomatic hospital-acquired infections, as well as infections due to onward community transmission from missed hospital-acquired infections, to 31st July 2020.

Results

In our dataset of hospitalised COVID-19 patients in acute English hospitals with a recorded symptom onset date (n = 65,028), 7% were classified as hospital-acquired. We estimated that only 30% (range across weeks and 200 simulations: 20-41%) of symptomatic hospital-acquired infections would be identified, with up to 15% (mean, 95% range over 200 simulations: 14.1-15.8%) of cases currently classified as community-acquired COVID-19 potentially linked to hospital transmission. We estimated that 26,600 (25,900 to 27,700) individuals acquired a symptomatic SARS-CoV-2 infection in an acute Trust in England before 31st July 2020, resulting in 15,900 (15,200-16,400) or 20.1% (19.2-20.7%) of all identified hospitalised COVID-19 cases.

Conclusions

Transmission of SARS-CoV-2 to hospitalised patients likely caused approximately a fifth of identified cases of hospitalised COVID-19 in the ""first wave"" in England, but less than 1% of all infections in England. Using time to symptom onset from admission for inpatients as a detection method likely misses a substantial proportion (> 60%) of hospital-acquired infections.",,pdf:https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-022-07490-4; doi:https://doi.org/10.1186/s12879-022-07490-4; html:https://europepmc.org/articles/PMC9206097; pdf:https://europepmc.org/articles/PMC9206097?pdf=render 35440469,https://doi.org/10.3399/bjgp.2022.0083,"Colchicine for COVID-19 in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial.","Dorward J, Yu LM, Hayward G, Saville BR, Gbinigie O, Van Hecke O, Ogburn E, Evans PH, Thomas NP, Patel MG, Richards D, Berry N, Detry MA, Saunders C, Fitzgerald M, Harris V, Shanyinde M, de Lusignan S, Andersson MI, Butler CC, Hobbs FR, PRINCIPLE Trial Collaborative Group.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2022,2022-06-30,Y,Colchicine; Community; Primary Health Care; Randomised Controlled Trial; Covid-19,,,"

Background

Colchicine has been proposed as a COVID-19 treatment.

Aim

To determine whether colchicine reduces time to recovery and COVID-19-related admissions to hospital and/or deaths among people in the community.

Design and setting

Prospective, multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial (PRINCIPLE).

Method

Adults aged ≥65 years or ≥18 years with comorbidities or shortness of breath, and unwell for ≤14 days with suspected COVID-19 in the community, were randomised to usual care, usual care plus colchicine (500 µg daily for 14 days), or usual care plus other interventions. The co-primary endpoints were time to first self-reported recovery and admission to hospital/death related to COVID-19, within 28 days, analysed using Bayesian models.

Results

The trial opened on 2 April 2020. Randomisation to colchicine started on 4 March 2021 and stopped on 26 May 2021 because the prespecified time to recovery futility criterion was met. The primary analysis model included 2755 participants who were SARS-CoV-2 positive, randomised to colchicine (n = 156), usual care (n = 1145), and other treatments (n = 1454). Time to first self-reported recovery was similar in the colchicine group compared with usual care with an estimated hazard ratio of 0.92 (95% credible interval (CrI) = 0.72 to 1.16) and an estimated increase of 1.4 days in median time to self-reported recovery for colchicine versus usual care. The probability of meaningful benefit in time to recovery was very low at 1.8%. COVID-19-related admissions to hospital/deaths were similar in the colchicine group versus usual care, with an estimated odds ratio of 0.76 (95% CrI = 0.28 to 1.89) and an estimated difference of -0.4% (95% CrI = -2.7 to 2.4).

Conclusion

Colchicine did not improve time to recovery in people at higher risk of complications with COVID-19 in the community.",,pdf:https://bjgp.org/content/bjgp/72/720/e446.full.pdf; doi:https://doi.org/10.3399/BJGP.2022.0083; html:https://europepmc.org/articles/PMC9037186; pdf:https://europepmc.org/articles/PMC9037186?pdf=render -37346822,https://doi.org/10.12688/wellcomeopenres.18735.2,First dose COVID-19 vaccine coverage amongst adolescents and children in England: an analysis of 3.21 million patients' primary care records in situ using OpenSAFELY.,"Hopcroft LE, Curtis HJ, Brown AD, Hulme WJ, Andrews CD, Morton CE, Inglesby P, Morley J, Mehrkar A, Bacon SC, Eggo RM, Mahalingasivam V, Parker EPK, Tomlinson LA, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, Walker AJ, MacKenna B.",,Wellcome open research,2023,2023-06-09,Y,Vaccine; Primary Health Care; Public Health; Covid-19,,,"Background: The coronavirus disease 2019 (COVID-19) vaccination programme in England was extended to include all adolescents and children by April 2022. The aim of this paper is to describe trends and variation in vaccine coverage in different clinical and demographic groups amongst adolescents and children in England by August 2022. Methods: With the approval of NHS England, a cohort study was conducted of 3.21 million children and adolescents' records in general practice in England,  in situ and within the infrastructure of the electronic health record software vendor TPP using OpenSAFELY. Vaccine coverage across various demographic (sex, deprivation index and ethnicity) and clinical (risk status) populations is described. Results: Coverage is higher amongst adolescents than it is amongst children, with 53.5% adolescents and 10.8% children having received their first dose of the COVID-19 vaccine. Within those groups, coverage varies by ethnicity, deprivation index and risk status; there is no evidence of variation by sex. Conclusion: First dose COVID-19 vaccine coverage is shown to vary amongst various demographic and clinical groups of children and adolescents.",,doi:https://doi.org/10.12688/wellcomeopenres.18735.2; html:https://europepmc.org/articles/PMC10280033; pdf:https://europepmc.org/articles/PMC10280033?pdf=render 36343994,https://doi.org/10.1136/bmjopen-2022-063159,"Demographic, behavioural and occupational risk factors associated with SARS-CoV-2 infection in UK healthcare workers: a retrospective observational study.","Cooper DJ, Lear S, Sithole N, Shaw A, Stark H, Ferris M, CITIID-NIHR BioResource COVID-19 collaboration consortium, Bradley J, Maxwell P, Goodfellow I, Weekes MP, Seaman S, Baker S.",,BMJ open,2022,2022-11-07,Y,Infection control; epidemiology; Public Health; Covid-19,,,"

Objective

Healthcare workers (HCWs) are at higher risk of SARS-CoV-2 infection than the general population. This group is pivotal to healthcare system resilience during the COVID-19, and future, pandemics. We investigated demographic, social, behavioural and occupational risk factors for SARS-CoV-2 infection among HCWs.

Design/setting/participants

HCWs enrolled in a large-scale sero-epidemiological study at a UK university teaching hospital were sent questionnaires spanning a 5-month period from March to July 2020. In a retrospective observational cohort study, univariate logistic regression was used to assess factors associated with SARS-CoV-2 infection. A Least Absolute Shrinkage Selection Operator regression model was used to identify variables to include in a multivariate logistic regression model.

Results

Among 2258 HCWs, highest ORs associated with SARS-CoV-2 antibody seropositivity on multivariate analysis were having a household member previously testing positive for SARS-CoV-2 antibodies (OR 6.94 (95% CI 4.15 to 11.6); p<0.0001) and being of black ethnicity (6.21 (95% CI 2.69 to 14.3); p<0.0001). Occupational factors associated with a higher risk of seropositivity included working as a physiotherapist (OR 2.78 (95% CI 1.21 to 6.36); p=0.015) and working predominantly in acute medicine (OR 2.72 (95% CI 1.57 to 4.69); p<0.0001) or medical subspecialties (not including infectious diseases) (OR 2.33 (95% CI 1.4 to 3.88); p=0.001). Reporting that adequate personal protective equipment (PPE) was 'rarely' available had an OR of 2.83 (95% CI 1.29 to 6.25; p=0.01). Reporting attending a handover where social distancing was not possible had an OR of 1.39 (95% CI 1.02 to 1.9; p=0.038).

Conclusions

The emergence of SARS-CoV-2 variants and potential vaccine escape continue to threaten stability of healthcare systems worldwide, and sustained vigilance against HCW infection remains a priority. Enhanced risk assessments should be considered for HCWs of black ethnicity, physiotherapists and those working in acute medicine or medical subspecialties. Workplace risk reduction measures include ongoing access to high-quality PPE and effective social distancing measures.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e063159.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-063159; html:https://europepmc.org/articles/PMC9644078; pdf:https://europepmc.org/articles/PMC9644078?pdf=render +37346822,https://doi.org/10.12688/wellcomeopenres.18735.2,First dose COVID-19 vaccine coverage amongst adolescents and children in England: an analysis of 3.21 million patients' primary care records in situ using OpenSAFELY.,"Hopcroft LE, Curtis HJ, Brown AD, Hulme WJ, Andrews CD, Morton CE, Inglesby P, Morley J, Mehrkar A, Bacon SC, Eggo RM, Mahalingasivam V, Parker EPK, Tomlinson LA, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, Walker AJ, MacKenna B.",,Wellcome open research,2023,2023-06-09,Y,Vaccine; Primary Health Care; Public Health; Covid-19,,,"Background: The coronavirus disease 2019 (COVID-19) vaccination programme in England was extended to include all adolescents and children by April 2022. The aim of this paper is to describe trends and variation in vaccine coverage in different clinical and demographic groups amongst adolescents and children in England by August 2022. Methods: With the approval of NHS England, a cohort study was conducted of 3.21 million children and adolescents' records in general practice in England,  in situ and within the infrastructure of the electronic health record software vendor TPP using OpenSAFELY. Vaccine coverage across various demographic (sex, deprivation index and ethnicity) and clinical (risk status) populations is described. Results: Coverage is higher amongst adolescents than it is amongst children, with 53.5% adolescents and 10.8% children having received their first dose of the COVID-19 vaccine. Within those groups, coverage varies by ethnicity, deprivation index and risk status; there is no evidence of variation by sex. Conclusion: First dose COVID-19 vaccine coverage is shown to vary amongst various demographic and clinical groups of children and adolescents.",,doi:https://doi.org/10.12688/wellcomeopenres.18735.2; html:https://europepmc.org/articles/PMC10280033; pdf:https://europepmc.org/articles/PMC10280033?pdf=render 37221040,https://doi.org/10.1136/oemed-2022-108700,"Coverage, completion and outcomes of COVID-19 risk assessments in a multi-ethnic nationwide cohort of UK healthcare workers: a cross-sectional analysis from the UK-REACH Study.","Martin CA, Woolf K, Bryant L, Goss C, Gogoi M, Lagrata S, Papineni P, Qureshi I, Wobi F, Nellums L, Khunti K, Pareek M, UK-REACH Study Collaborative Group.",,Occupational and environmental medicine,2023,2023-05-23,Y,Ethnic Groups; risk assessment; Health Personnel; Covid-19,,,"

Introduction

There are limited data on the outcomes of COVID-19 risk assessment in healthcare workers (HCWs) or the association of ethnicity, other sociodemographic and occupational factors with risk assessment outcomes.

Methods

We used questionnaire data from UK-REACH (UK Research study into Ethnicity And COVID-19 outcomes in Healthcare workers), an ethnically diverse, nationwide cohort of UK HCWs. We derived four binary outcomes: (1) offered a risk assessment; (2) completed a risk assessment; (3) working practices changed as a result of the risk assessment; (4) wanted changes to working practices after risk assessment but working practices did not change.We examined the association of ethnicity, other sociodemographic/occupational factors and actual/perceived COVID-19 risk variables on our outcomes using multivariable logistic regression.

Results

8649 HCWs were included in total. HCWs from ethnic minority groups were more likely to report being offered a risk assessment than white HCWs, and those from Asian and black ethnic groups were more likely to report having completed an assessment if offered. Ethnic minority HCWs had lower odds of reporting having their work change as a result of risk assessment. Those from Asian and black ethnic groups were more likely to report no changes to their working practices despite wanting them.Previous SARS-CoV-2 infection was associated with lower odds of being offered a risk assessment and having adjustments made to working practices.

Discussion

We found differences in risk assessment outcomes by ethnicity, other sociodemographic/occupational factors and actual/perceived COVID-19 risk factors. These findings are concerning and warrant further research using actual (rather than reported) risk assessment outcomes in an unselected cohort.",,pdf:https://oem.bmj.com/content/oemed/80/7/399.full.pdf; doi:https://doi.org/10.1136/oemed-2022-108700; html:https://europepmc.org/articles/PMC10314065; pdf:https://europepmc.org/articles/PMC10314065?pdf=render 33220850,https://doi.org/10.1016/s0140-6736(20)32465-x,Urgent actions and policies needed to address COVID-19 among UK ethnic minorities.,"Mathur R, Bear L, Khunti K, Eggo RM.",,"Lancet (London, England)",2020,2020-11-19,Y,,,,,,pdf:http://www.thelancet.com/article/S014067362032465X/pdf; doi:https://doi.org/10.1016/S0140-6736(20)32465-X; html:https://europepmc.org/articles/PMC7831890; pdf:https://europepmc.org/articles/PMC7831890?pdf=render 34708157,https://doi.org/10.12688/wellcomeopenres.16701.3,Estimating the duration of seropositivity of human seasonal coronaviruses using seroprevalence studies.,"Rees EM, Waterlow NR, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Lowe R, Kucharski AJ.",,Wellcome open research,2021,2021-12-21,Y,Catalytic model; Seroprevalence; Waning Immunity; Seasonal Coronavirus,,,"Background: The duration of immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still uncertain, but it is of key clinical and epidemiological importance. Seasonal human coronaviruses (HCoV) have been circulating for longer and, therefore, may offer insights into the long-term dynamics of reinfection for such viruses. Methods: Combining historical seroprevalence data from five studies covering the four circulating HCoVs with an age-structured reverse catalytic model, we estimated the likely duration of seropositivity following seroconversion. Results: We estimated that antibody persistence lasted between 0.9 (95% Credible interval: 0.6 - 1.6) and 3.8 (95% CrI: 2.0 - 7.4) years. Furthermore, we found the force of infection in older children and adults (those over 8.5 [95% CrI: 7.5 - 9.9] years) to be higher compared with young children in the majority of studies. Conclusions: These estimates of endemic HCoV dynamics could provide an indication of the future long-term infection and reinfection patterns of SARS-CoV-2.",,doi:https://doi.org/10.12688/wellcomeopenres.16701.3; html:https://europepmc.org/articles/PMC8517721; pdf:https://europepmc.org/articles/PMC8517721?pdf=render -37726825,https://doi.org/10.1186/s13063-023-07606-4,Correction: Development and evaluation of rapid data-enabled access to routine clinical information to enhance early recruitment to the national clinical platform trial of COVID-19 community treatments.,"Cake C, Ogburn E, Pinches H, Coleman G, Seymour D, Woodard F, Manohar S, Monsur M, Landray M, Dalton G, Morris AD, Chinnery PF, UK COVID-19 National Core Studies Consortium, Hobbs FDR, Butler C.",,Trials,2023,2023-09-19,Y,,,,,,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07606-4; doi:https://doi.org/10.1186/s13063-023-07606-4; html:https://europepmc.org/articles/PMC10507817; pdf:https://europepmc.org/articles/PMC10507817?pdf=render 33185672,https://doi.org/10.1093/jamia/ocaa295,Ensemble learning for poor prognosis predictions: A case study on SARS-CoV-2.,"Wu H, Zhang H, Karwath A, Ibrahim Z, Shi T, Zhang X, Wang K, Sun J, Dhaliwal K, Bean D, Cardoso VR, Li K, Teo JT, Banerjee A, Gao-Smith F, Whitehouse T, Veenith T, Gkoutos GV, Wu X, Dobson R, Guthrie B.",,Journal of the American Medical Informatics Association : JAMIA,2021,2021-03-01,Y,Decision Support; Risk Prediction; Ensemble Learning; Covid-19; Model Synergy,,,"

Objective

Risk prediction models are widely used to inform evidence-based clinical decision making. However, few models developed from single cohorts can perform consistently well at population level where diverse prognoses exist (such as the SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2] pandemic). This study aims at tackling this challenge by synergizing prediction models from the literature using ensemble learning.

Materials and methods

In this study, we selected and reimplemented 7 prediction models for COVID-19 (coronavirus disease 2019) that were derived from diverse cohorts and used different implementation techniques. A novel ensemble learning framework was proposed to synergize them for realizing personalized predictions for individual patients. Four diverse international cohorts (2 from the United Kingdom and 2 from China; N = 5394) were used to validate all 8 models on discrimination, calibration, and clinical usefulness.

Results

Results showed that individual prediction models could perform well on some cohorts while poorly on others. Conversely, the ensemble model achieved the best performances consistently on all metrics quantifying discrimination, calibration, and clinical usefulness. Performance disparities were observed in cohorts from the 2 countries: all models achieved better performances on the China cohorts.

Discussion

When individual models were learned from complementary cohorts, the synergized model had the potential to achieve better performances than any individual model. Results indicate that blood parameters and physiological measurements might have better predictive powers when collected early, which remains to be confirmed by further studies.

Conclusions

Combining a diverse set of individual prediction models, the ensemble method can synergize a robust and well-performing model by choosing the most competent ones for individual patients.",,pdf:https://academic.oup.com/jamia/article-pdf/28/4/791/41182395/ocaa295.pdf; doi:https://doi.org/10.1093/jamia/ocaa295; html:https://europepmc.org/articles/PMC7717299; pdf:https://europepmc.org/articles/PMC7717299?pdf=render +37726825,https://doi.org/10.1186/s13063-023-07606-4,Correction: Development and evaluation of rapid data-enabled access to routine clinical information to enhance early recruitment to the national clinical platform trial of COVID-19 community treatments.,"Cake C, Ogburn E, Pinches H, Coleman G, Seymour D, Woodard F, Manohar S, Monsur M, Landray M, Dalton G, Morris AD, Chinnery PF, UK COVID-19 National Core Studies Consortium, Hobbs FDR, Butler C.",,Trials,2023,2023-09-19,Y,,,,,,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07606-4; doi:https://doi.org/10.1186/s13063-023-07606-4; html:https://europepmc.org/articles/PMC10507817; pdf:https://europepmc.org/articles/PMC10507817?pdf=render 34796246,https://doi.org/10.1093/ofid/ofab496,"Acceptability, Usability, and Performance of Lateral Flow Immunoassay Tests for Severe Acute Respiratory Syndrome Coronavirus 2 Antibodies: REACT-2 Study of Self-Testing in Nonhealthcare Key Workers.","Davies B, Araghi M, Moshe M, Gao H, Bennet K, Jenkins J, Atchison C, Darzi A, Ashby D, Riley S, Barclay W, Elliott P, Ward H, Cooke G.",,Open forum infectious diseases,2021,2021-10-04,Y,Sensitivity and specificity; Antibody testing; Sars-cov-2; Covid-19 Diagnostic Testing,,,"

Background

Seroprevalence studies are essential to understand the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Various technologies, including laboratory assays and point-of-care self-tests, are available for antibody testing. The interpretation of seroprevalence studies requires comparative data on the performance of antibody tests.

Methods

In June 2020, current and former members of the United Kingdom police forces and fire service performed a self-test lateral flow immunoassay (LFIA), had a nurse-performed LFIA, and provided a venous blood sample for enzyme-linked immunosorbent assay (ELISA). We present the prevalence of antibodies to SARS-CoV-2 and the acceptability and usability of self-test LFIAs, and we determine the sensitivity and specificity of LFIAs compared with laboratory ELISA.

Results

In this cohort of 5189 current and former members of the police service and 263 members of the fire service, 7.4% (396 of 5348; 95% confidence interval [CI], 6.7-8.1) were antibody positive. Seroprevalence was 8.9% (95% CI, 6.9-11.4) in those under 40 years, 11.5% (95% CI, 8.8-15.0) in those of nonwhite ethnicity, and 7.8% (95% CI, 7.1-8.7) in those currently working. Self-test LFIA had an acceptability of 97.7% and a usability of 90.0%. There was substantial agreement between within-participant LFIA results (kappa 0.80; 95% CI, 0.77-0.83). The LFIAs had a similar performance: compared with ELISA, sensitivity was 82.1% (95% CI, 77.7-86.0) self-test and 76.4% (95% CI, 71.9-80.5) nurse-performed with specificity of 97.8% (95% CI, 97.3-98.2) and 98.5% (95% CI, 98.1-98.8), respectively.

Conclusions

A greater proportion of this nonhealthcare key worker cohort showed evidence of previous infection with SARS-CoV-2 than the general population at 6.0% (95% CI, 5.8-6.1) after the first wave in England. The high acceptability and usability reported by participants and similar performance of self-test and nurse-performed LFIAs indicate that the self-test LFIA is fit for purpose for home testing in occupational and community prevalence studies.",,pdf:https://academic.oup.com/ofid/article-pdf/8/11/ofab496/41174715/ofab496.pdf; doi:https://doi.org/10.1093/ofid/ofab496; html:https://europepmc.org/articles/PMC8522420; pdf:https://europepmc.org/articles/PMC8522420?pdf=render 34265229,https://doi.org/10.1177/01410768211032850,"Symptoms, complications and management of long COVID: a review.","Aiyegbusi OL, Hughes SE, Turner G, Rivera SC, McMullan C, Chandan JS, Haroon S, Price G, Davies EH, Nirantharakumar K, Sapey E, Calvert MJ, TLC Study Group.",,Journal of the Royal Society of Medicine,2021,2021-07-15,Y,Infectious diseases; epidemiology; Public Health; Respiratory Medicine; Health Service Research; Covid-19; Long Covid; Post-Covid-19 Syndrome; Persistent Covid-19 Symptoms,,,"Globally, there are now over 160 million confirmed cases of COVID-19 and more than 3 million deaths. While the majority of infected individuals recover, a significant proportion continue to experience symptoms and complications after their acute illness. Patients with 'long COVID' experience a wide range of physical and mental/psychological symptoms. Pooled prevalence data showed the 10 most prevalent reported symptoms were fatigue, shortness of breath, muscle pain, joint pain, headache, cough, chest pain, altered smell, altered taste and diarrhoea. Other common symptoms were cognitive impairment, memory loss, anxiety and sleep disorders. Beyond symptoms and complications, people with long COVID often reported impaired quality of life, mental health and employment issues. These individuals may require multidisciplinary care involving the long-term monitoring of symptoms, to identify potential complications, physical rehabilitation, mental health and social services support. Resilient healthcare systems are needed to ensure efficient and effective responses to future health challenges.",,doi:https://doi.org/10.1177/01410768211032850; doi:https://doi.org/10.1177/01410768211032850; html:https://europepmc.org/articles/PMC8450986; pdf:https://europepmc.org/articles/PMC8450986?pdf=render 34750106,https://doi.org/10.3399/bjgp.2021.0376,Trends and clinical characteristics of COVID-19 vaccine recipients: a federated analysis of 57.9 million patients’ primary care records in situ using OpenSAFELY.,"Curtis HJ, Inglesby P, Morton CE, MacKenna B, Green A, Hulme W, Walker AJ, Morley J, Mehrkar A, Bacon S, Hickman G, Bates C, Croker R, Evans D, Ward T, Cockburn J, Davy S, Bhaskaran K, Schultze A, Rentsch CT, Williamson EJ, Rowan A, Fisher L, McDonald HI, Tomlinson L, Mathur R, Drysdale H, Eggo RM, Wing K, Wong AY, Forbes H, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Douglas IJ, Evans SJ, Smeeth L, Goldacre B, (The OpenSAFELY Collaborative).",,The British journal of general practice : the journal of the Royal College of General Practitioners,2022,2021-12-31,Y,Ethnic Groups; Vaccination; General Practice; Nhs England; Covid-19; Sars-cov-2,,,"

Background

On 8 December 2020 NHS England administered the first COVID-19 vaccination.

Aim

To describe trends and variation in vaccine coverage in different clinical and demographic groups in the first 100 days of the vaccine rollout.

Design and setting

With the approval of NHS England, a cohort study was conducted of 57.9 million patient records in general practice in England, in situ and within the infrastructure of the electronic health record software vendors EMIS and TPP using OpenSAFELY.

Method

Vaccine coverage across various subgroups of Joint Committee on Vaccination and Immunisation (JCVI) priority cohorts is described.

Results

A total of 20 852 692 patients (36.0%) received a vaccine between 8 December 2020 and 17 March 2021. Of patients aged ≥80 years not in a care home (JCVI group 2) 94.7% received a vaccine, but with substantial variation by ethnicity (White 96.2%, Black 68.3%) and deprivation (least deprived 96.6%, most deprived 90.7%). Patients with pre-existing medical conditions were more likely to be vaccinated with two exceptions: severe mental illness (89.5%) and learning disability (91.4%). There were 275 205 vaccine recipients who were identified as care home residents (JCVI group 1; 91.2% coverage). By 17 March, 1 257 914 (6.0%) recipients had a second dose.

Conclusion

The NHS rapidly delivered mass vaccination. In this study a data-monitoring framework was deployed using publicly auditable methods and a secure in situ processing model, using linked but pseudonymised patient-level NHS data for 57.9 million patients. Targeted activity may be needed to address lower vaccination coverage observed among certain key groups.",,pdf:https://bjgp.org/content/bjgp/72/714/e51.full.pdf; doi:https://doi.org/10.3399/BJGP.2021.0376; html:https://europepmc.org/articles/PMC8589463; pdf:https://europepmc.org/articles/PMC8589463?pdf=render @@ -335,8 +335,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 34782484,https://doi.org/10.1136/thoraxjnl-2021-217580,External validation of the QCovid risk prediction algorithm for risk of COVID-19 hospitalisation and mortality in adults: national validation cohort study in Scotland.,"Simpson CR, Robertson C, Kerr S, Shi T, Vasileiou E, Moore E, McCowan C, Agrawal U, Docherty A, Mulholland R, Murray J, Ritchie LD, McMenamin J, Hippisley-Cox J, Sheikh A.",,Thorax,2022,2021-11-15,Y,Clinical Epidemiology; Covid-19,,,"

Background

The QCovid algorithm is a risk prediction tool that can be used to stratify individuals by risk of COVID-19 hospitalisation and mortality. Version 1 of the algorithm was trained using data covering 10.5 million patients in England in the period 24 January 2020 to 30 April 2020. We carried out an external validation of version 1 of the QCovid algorithm in Scotland.

Methods

We established a national COVID-19 data platform using individual level data for the population of Scotland (5.4 million residents). Primary care data were linked to reverse-transcription PCR (RT-PCR) virology testing, hospitalisation and mortality data. We assessed the performance of the QCovid algorithm in predicting COVID-19 hospitalisations and deaths in our dataset for two time periods matching the original study: 1 March 2020 to 30 April 2020, and 1 May 2020 to 30 June 2020.

Results

Our dataset comprised 5 384 819 individuals, representing 99% of the estimated population (5 463 300) resident in Scotland in 2020. The algorithm showed good calibration in the first period, but systematic overestimation of risk in the second period, prior to temporal recalibration. Harrell's C for deaths in females and males in the first period was 0.95 (95% CI 0.94 to 0.95) and 0.93 (95% CI 0.92 to 0.93), respectively. Harrell's C for hospitalisations in females and males in the first period was 0.81 (95% CI 0.80 to 0.82) and 0.82 (95% CI 0.81 to 0.82), respectively.

Conclusions

Version 1 of the QCovid algorithm showed high levels of discrimination in predicting the risk of COVID-19 hospitalisations and deaths in adults resident in Scotland for the original two time periods studied, but is likely to need ongoing recalibration prospectively.",,pdf:https://thorax.bmj.com/content/thoraxjnl/77/5/497.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2021-217580; html:https://europepmc.org/articles/PMC8595052; pdf:https://europepmc.org/articles/PMC8595052?pdf=render 36436752,https://doi.org/10.1016/j.ijid.2022.11.024,"Outcomes of laboratory-confirmed SARS-CoV-2 infection during resurgence driven by Omicron lineages BA.4 and BA.5 compared with previous waves in the Western Cape Province, South Africa.","Davies MA, Morden E, Rousseau P, Arendse J, Bam JL, Boloko L, Cloete K, Cohen C, Chetty N, Dane P, Heekes A, Hsiao NY, Hunter M, Hussey H, Jacobs T, Jassat W, Kariem S, Kassanjee R, Laenen I, Roux SL, Lessells R, Mahomed H, Maughan D, Meintjes G, Mendelson M, Mnguni A, Moodley M, Murie K, Naude J, Ntusi NAB, Paleker M, Parker A, Pienaar D, Preiser W, Prozesky H, Raubenheimer P, Rossouw L, Schrueder N, Smith B, Smith M, Solomon W, Symons G, Taljaard J, Wasserman S, Wilkinson RJ, Wolmarans M, Wolter N, Boulle A.",,International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases,2023,2022-11-24,Y,"Covid-19; Omicron; Ba.4; Ba.5; Death, Severe Hospitalization",,,"

Objectives

We aimed to compare the clinical severity of Omicron BA.4/BA.5 infection with BA.1 and earlier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection.

Methods

We included public sector patients aged ≥20 years with laboratory-confirmed COVID-19 between May 01-May 21, 2022 (BA.4/BA.5 wave) and equivalent previous wave periods. We compared the risk between waves of (i) death and (ii) severe hospitalization/death (all within 21 days of diagnosis) using Cox regression adjusted for demographics, comorbidities, admission pressure, vaccination, and previous infection.

Results

Among 3793 patients from the BA.4/BA.5 wave and 190,836 patients from previous waves, the risk of severe hospitalization/death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio [aHR] 1.12; 95% confidence interval [CI] 0.93; 1.34). Both Omicron waves had a lower risk of severe outcomes than previous waves. Previous infection (aHR 0.29, 95% CI 0.24; 0.36) and vaccination (aHR 0.17; 95% CI 0.07; 0.40 for at least three doses vs no vaccine) were protective.

Conclusion

Disease severity was similar among diagnosed COVID-19 cases in the BA.4/BA.5 and BA.1 periods in the context of growing immunity against SARS-CoV-2 due to previous infection and vaccination, both of which were strongly protective.",,doi:https://doi.org/10.1016/j.ijid.2022.11.024; doi:https://doi.org/10.1016/j.ijid.2022.11.024; html:https://europepmc.org/articles/PMC9686046; pdf:https://europepmc.org/articles/PMC9686046?pdf=render 33875444,https://doi.org/10.1136/bmjopen-2020-045077,COVID-19 in patients with hepatobiliary and pancreatic diseases: a single-centre cross-sectional study in East London.,"Dayem Ullah AZM, Sivapalan L, Kocher HM, Chelala C.",,BMJ open,2021,2021-04-19,Y,Pancreatic Disease; Hepatobiliary Disease; Covid-19,,,"

Objective

To explore risk factors associated with COVID-19 susceptibility and survival in patients with pre-existing hepato-pancreato-biliary (HPB) conditions.

Design

Cross-sectional study.

Setting

East London Pancreatic Cancer Epidemiology (EL-PaC-Epidem) Study at Barts Health National Health Service Trust, UK. Linked electronic health records were interrogated on a cohort of participants (age ≥18 years), reported with HPB conditions between 1 April 2008 and 6 March 2020.

Participants

EL-PaC-Epidem Study participants, alive on 12 February 2020, and living in East London within the previous 6 months (n=15 440). The cohort represents a multi-ethnic population with 51.7% belonging to the non-White background.

Main outcome measure

COVID-19 incidence and mortality.

Results

Some 226 (1.5%) participants had confirmed COVID-19 diagnosis between 12 February and 12 June 2020, with increased odds for men (OR 1.56; 95% CI 1.2 to 2.04) and Black ethnicity (2.04; 1.39 to 2.95) as well as patients with moderate to severe liver disease (2.2; 1.35 to 3.59). Each additional comorbidity increased the odds of infection by 62%. Substance misusers were at more risk of infection, so were patients on vitamin D treatment. The higher ORs in patients with chronic pancreatic or mild liver conditions, age >70, and a history of smoking or obesity were due to coexisting comorbidities. Increased odds of death were observed for men (3.54; 1.68 to 7.85) and Black ethnicity (3.77; 1.38 to 10.7). Patients having respiratory complications from COVID-19 without a history of chronic respiratory disease also had higher odds of death (5.77; 1.75 to 19).

Conclusions

In this large population-based study of patients with HPB conditions, men, Black ethnicity, pre-existing moderate to severe liver conditions, six common medical multimorbidities, substance misuse and a history of vitamin D treatment independently posed higher odds of acquiring COVID-19 compared with their respective counterparts. The odds of death were significantly high for men and Black people.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/4/e045077.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-045077; html:https://europepmc.org/articles/PMC8057071; pdf:https://europepmc.org/articles/PMC8057071?pdf=render -38135323,https://doi.org/10.1136/bmjopen-2023-076221,Development and application of simulation modelling for orthopaedic elective resource planning in England.,"Harper A, Monks T, Wilson R, Redaniel MT, Eyles E, Jones T, Penfold C, Elliott A, Keen T, Pitt M, Blom A, Whitehouse MR, Judge A.",,BMJ open,2023,2023-12-22,Y,Information management; Orthopaedic & Trauma Surgery; Organisation Of Health Services; World Wide Web Technology,,,"

Objectives

This study aimed to develop a simulation model to support orthopaedic elective capacity planning.

Methods

An open-source, generalisable discrete-event simulation was developed, including a web-based application. The model used anonymised patient records between 2016 and 2019 of elective orthopaedic procedures from a National Health Service (NHS) Trust in England. In this paper, it is used to investigate scenarios including resourcing (beds and theatres) and productivity (lengths of stay, delayed discharges and theatre activity) to support planning for meeting new NHS targets aimed at reducing elective orthopaedic surgical backlogs in a proposed ring-fenced orthopaedic surgical facility. The simulation is interactive and intended for use by health service planners and clinicians.

Results

A higher number of beds (65-70) than the proposed number (40 beds) will be required if lengths of stay and delayed discharge rates remain unchanged. Reducing lengths of stay in line with national benchmarks reduces bed utilisation to an estimated 60%, allowing for additional theatre activity such as weekend working. Further, reducing the proportion of patients with a delayed discharge by 75% reduces bed utilisation to below 40%, even with weekend working. A range of other scenarios can also be investigated directly by NHS planners using the interactive web app.

Conclusions

The simulation model is intended to support capacity planning of orthopaedic elective services by identifying a balance of capacity across theatres and beds and predicting the impact of productivity measures on capacity requirements. It is applicable beyond the study site and can be adapted for other specialties.",,doi:https://doi.org/10.1136/bmjopen-2023-076221; html:https://europepmc.org/articles/PMC10748981; pdf:https://europepmc.org/articles/PMC10748981?pdf=render 34174193,https://doi.org/10.1016/s1473-3099(21)00289-9,Vaccine effectiveness of the first dose of ChAdOx1 nCoV-19 and BNT162b2 against SARS-CoV-2 infection in residents of long-term care facilities in England (VIVALDI): a prospective cohort study.,"Shrotri M, Krutikov M, Palmer T, Giddings R, Azmi B, Subbarao S, Fuller C, Irwin-Singer A, Davies D, Tut G, Lopez Bernal J, Moss P, Hayward A, Copas A, Shallcross L.",,The Lancet. Infectious diseases,2021,2021-06-23,Y,,,,"

Background

The effectiveness of SARS-CoV-2 vaccines in older adults living in long-term care facilities is uncertain. We investigated the protective effect of the first dose of the Oxford-AstraZeneca non-replicating viral-vectored vaccine (ChAdOx1 nCoV-19; AZD1222) and the Pfizer-BioNTech mRNA-based vaccine (BNT162b2) in residents of long-term care facilities in terms of PCR-confirmed SARS-CoV-2 infection over time since vaccination.

Methods

The VIVALDI study is a prospective cohort study that commenced recruitment on June 11, 2020, to investigate SARS-CoV-2 transmission, infection outcomes, and immunity in residents and staff in long-term care facilities in England that provide residential or nursing care for adults aged 65 years and older. In this cohort study, we included long-term care facility residents undergoing routine asymptomatic SARS-CoV-2 testing between Dec 8, 2020 (the date the vaccine was first deployed in a long-term care facility), and March 15, 2021, using national testing data linked within the COVID-19 Datastore. Using Cox proportional hazards regression, we estimated the relative hazard of PCR-positive infection at 0-6 days, 7-13 days, 14-20 days, 21-27 days, 28-34 days, 35-48 days, and 49 days and beyond after vaccination, comparing unvaccinated and vaccinated person-time from the same cohort of residents, adjusting for age, sex, previous infection, local SARS-CoV-2 incidence, long-term care facility bed capacity, and clustering by long-term care facility. We also compared mean PCR cycle threshold (Ct) values for positive swabs obtained before and after vaccination. The study is registered with ISRCTN, number 14447421.

Findings

10 412 care home residents aged 65 years and older from 310 LTCFs were included in this analysis. The median participant age was 86 years (IQR 80-91), 7247 (69·6%) of 10 412 residents were female, and 1155 residents (11·1%) had evidence of previous SARS-CoV-2 infection. 9160 (88·0%) residents received at least one vaccine dose, of whom 6138 (67·0%) received ChAdOx1 and 3022 (33·0%) received BNT162b2. Between Dec 8, 2020, and March 15, 2021, there were 36 352 PCR results in 670 628 person-days, and 1335 PCR-positive infections (713 in unvaccinated residents and 612 in vaccinated residents) were included. Adjusted hazard ratios (HRs) for PCR-positive infection relative to unvaccinated residents declined from 28 days after the first vaccine dose to 0·44 (95% CI 0·24-0·81) at 28-34 days and 0·38 (0·19-0·77) at 35-48 days. Similar effect sizes were seen for ChAdOx1 (adjusted HR 0·32, 95% CI 0·15-0·66) and BNT162b2 (0·35, 0·17-0·71) vaccines at 35-48 days. Mean PCR Ct values were higher for infections that occurred at least 28 days after vaccination than for those occurring before vaccination (31·3 [SD 8·7] in 107 PCR-positive tests vs 26·6 [6·6] in 552 PCR-positive tests; p<0·0001).

Interpretation

Single-dose vaccination with BNT162b2 and ChAdOx1 vaccines provides substantial protection against infection in older adults from 4-7 weeks after vaccination and might reduce SARS-CoV-2 transmission. However, the risk of infection is not eliminated, highlighting the ongoing need for non-pharmaceutical interventions to prevent transmission in long-term care facilities.

Funding

UK Government Department of Health and Social Care.",,pdf:http://www.thelancet.com/article/S1473309921002899/pdf; doi:https://doi.org/10.1016/S1473-3099(21)00289-9; html:https://europepmc.org/articles/PMC8221738 +38135323,https://doi.org/10.1136/bmjopen-2023-076221,Development and application of simulation modelling for orthopaedic elective resource planning in England.,"Harper A, Monks T, Wilson R, Redaniel MT, Eyles E, Jones T, Penfold C, Elliott A, Keen T, Pitt M, Blom A, Whitehouse MR, Judge A.",,BMJ open,2023,2023-12-22,Y,Information management; Orthopaedic & Trauma Surgery; Organisation Of Health Services; World Wide Web Technology,,,"

Objectives

This study aimed to develop a simulation model to support orthopaedic elective capacity planning.

Methods

An open-source, generalisable discrete-event simulation was developed, including a web-based application. The model used anonymised patient records between 2016 and 2019 of elective orthopaedic procedures from a National Health Service (NHS) Trust in England. In this paper, it is used to investigate scenarios including resourcing (beds and theatres) and productivity (lengths of stay, delayed discharges and theatre activity) to support planning for meeting new NHS targets aimed at reducing elective orthopaedic surgical backlogs in a proposed ring-fenced orthopaedic surgical facility. The simulation is interactive and intended for use by health service planners and clinicians.

Results

A higher number of beds (65-70) than the proposed number (40 beds) will be required if lengths of stay and delayed discharge rates remain unchanged. Reducing lengths of stay in line with national benchmarks reduces bed utilisation to an estimated 60%, allowing for additional theatre activity such as weekend working. Further, reducing the proportion of patients with a delayed discharge by 75% reduces bed utilisation to below 40%, even with weekend working. A range of other scenarios can also be investigated directly by NHS planners using the interactive web app.

Conclusions

The simulation model is intended to support capacity planning of orthopaedic elective services by identifying a balance of capacity across theatres and beds and predicting the impact of productivity measures on capacity requirements. It is applicable beyond the study site and can be adapted for other specialties.",,doi:https://doi.org/10.1136/bmjopen-2023-076221; html:https://europepmc.org/articles/PMC10748981; pdf:https://europepmc.org/articles/PMC10748981?pdf=render 33082154,https://doi.org/10.1136/bmj.m3731,Living risk prediction algorithm (QCOVID) for risk of hospital admission and mortality from coronavirus 19 in adults: national derivation and validation cohort study.,"Clift AK, Coupland CAC, Keogh RH, Diaz-Ordaz K, Williamson E, Harrison EM, Hayward A, Hemingway H, Horby P, Mehta N, Benger J, Khunti K, Spiegelhalter D, Sheikh A, Valabhji J, Lyons RA, Robson J, Semple MG, Kee F, Johnson P, Jebb S, Williams T, Hippisley-Cox J.",,BMJ (Clinical research ed.),2020,2020-10-20,Y,,,,"

Objective

To derive and validate a risk prediction algorithm to estimate hospital admission and mortality outcomes from coronavirus disease 2019 (covid-19) in adults.

Design

Population based cohort study.

Setting and participants

QResearch database, comprising 1205 general practices in England with linkage to covid-19 test results, Hospital Episode Statistics, and death registry data. 6.08 million adults aged 19-100 years were included in the derivation dataset and 2.17 million in the validation dataset. The derivation and first validation cohort period was 24 January 2020 to 30 April 2020. The second temporal validation cohort covered the period 1 May 2020 to 30 June 2020.

Main outcome measures

The primary outcome was time to death from covid-19, defined as death due to confirmed or suspected covid-19 as per the death certification or death occurring in a person with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the period 24 January to 30 April 2020. The secondary outcome was time to hospital admission with confirmed SARS-CoV-2 infection. Models were fitted in the derivation cohort to derive risk equations using a range of predictor variables. Performance, including measures of discrimination and calibration, was evaluated in each validation time period.

Results

4384 deaths from covid-19 occurred in the derivation cohort during follow-up and 1722 in the first validation cohort period and 621 in the second validation cohort period. The final risk algorithms included age, ethnicity, deprivation, body mass index, and a range of comorbidities. The algorithm had good calibration in the first validation cohort. For deaths from covid-19 in men, it explained 73.1% (95% confidence interval 71.9% to 74.3%) of the variation in time to death (R2); the D statistic was 3.37 (95% confidence interval 3.27 to 3.47), and Harrell's C was 0.928 (0.919 to 0.938). Similar results were obtained for women, for both outcomes, and in both time periods. In the top 5% of patients with the highest predicted risks of death, the sensitivity for identifying deaths within 97 days was 75.7%. People in the top 20% of predicted risk of death accounted for 94% of all deaths from covid-19.

Conclusion

The QCOVID population based risk algorithm performed well, showing very high levels of discrimination for deaths and hospital admissions due to covid-19. The absolute risks presented, however, will change over time in line with the prevailing SARS-C0V-2 infection rate and the extent of social distancing measures in place, so they should be interpreted with caution. The model can be recalibrated for different time periods, however, and has the potential to be dynamically updated as the pandemic evolves.",,pdf:https://www.bmj.com/content/bmj/371/bmj.m3731.full.pdf; doi:https://doi.org/10.1136/bmj.m3731; html:https://europepmc.org/articles/PMC7574532; pdf:https://europepmc.org/articles/PMC7574532?pdf=render 33342219,https://doi.org/10.1161/circoutcomes.120.007085,Estimating the Effect of Reduced Attendance at Emergency Departments for Suspected Cardiac Conditions on Cardiac Mortality During the COVID-19 Pandemic.,"Katsoulis M, Gomes M, Lai AG, Henry A, Denaxas S, Lagiou P, Nafilyan V, Humberstone B, Banerjee A, Hemingway H, Lumbers RT.",,Circulation. Cardiovascular quality and outcomes,2021,2020-12-20,Y,"Cardiovascular diseases; Coronavirus; Pandemic; Heart Disease; Death, Sudden, Cardiac",,,,,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCOUTCOMES.120.007085; doi:https://doi.org/10.1161/CIRCOUTCOMES.120.007085; html:https://europepmc.org/articles/PMC7819531; pdf:https://europepmc.org/articles/PMC7819531?pdf=render 36385522,https://doi.org/10.1093/ehjqcco/qcac077,Effects of the COVID-19 pandemic on secondary care for cardiovascular disease in the UK: an electronic health record analysis across three countries.,"Wright FL, Cheema K, Goldacre R, Hall N, Herz N, Islam N, Karim Z, Moreno-Martos D, Morales DR, O'Connell D, Spata E, Akbari A, Ashworth M, Barber M, Briffa N, Canoy D, Denaxas S, Khunti K, Kurdi A, Mamas M, Priedon R, Sudlow C, Morris EJA, Lacey B, Banerjee A.",,European heart journal. Quality of care & clinical outcomes,2023,2023-06-01,Y,,,,"

Background

Although morbidity and mortality from COVID-19 have been widely reported, the indirect effects of the pandemic beyond 2020 on other major diseases and health service activity have not been well described.

Methods and results

Analyses used national administrative electronic hospital records in England, Scotland, and Wales for 2016-21. Admissions and procedures during the pandemic (2020-21) related to six major cardiovascular conditions [acute coronary syndrome (ACS), heart failure (HF), stroke/transient ischaemic attack (TIA), peripheral arterial disease (PAD), aortic aneurysm (AA), and venous thromboembolism(VTE)] were compared with the annual average in the pre-pandemic period (2016-19). Differences were assessed by time period and urgency of care.In 2020, there were 31 064 (-6%) fewer hospital admissions [14 506 (-4%) fewer emergencies, 16 560 (-23%) fewer elective admissions] compared with 2016-19 for the six major cardiovascular diseases (CVDs) combined. The proportional reduction in admissions was similar in all three countries. Overall, hospital admissions returned to pre-pandemic levels in 2021. Elective admissions remained substantially below expected levels for almost all conditions in all three countries [-10 996 (-15%) fewer admissions]. However, these reductions were offset by higher than expected total emergency admissions [+25 878 (+6%) higher admissions], notably for HF and stroke in England, and for VTE in all three countries. Analyses for procedures showed similar temporal variations to admissions.

Conclusion

The present study highlights increasing emergency cardiovascular admissions during the pandemic, in the context of a substantial and sustained reduction in elective admissions and procedures. This is likely to increase further the demands on cardiovascular services over the coming years.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa62054/Download/62054__26063__5453b00901174a7d9a0797547f023fba.pdf; doi:https://doi.org/10.1093/ehjqcco/qcac077; html:https://europepmc.org/articles/PMC10284263; pdf:https://europepmc.org/articles/PMC10284263?pdf=render @@ -369,15 +369,15 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 34173614,https://doi.org/10.1016/s2666-7568(20)30012-x,Evolution and effects of COVID-19 outbreaks in care homes: a population analysis in 189 care homes in one geographical region of the UK.,"Burton JK, Bayne G, Evans C, Garbe F, Gorman D, Honhold N, McCormick D, Othieno R, Stevenson JE, Swietlik S, Templeton KE, Tranter M, Willocks L, Guthrie B.",,The lancet. Healthy longevity,2020,2020-10-20,Y,,,,"

Background

COVID-19 has affected care home residents internationally, but detailed information on outbreaks is scarce. We aimed to describe the evolution of outbreaks of COVID-19 in all care homes in one large health region in Scotland.

Methods

We did a population analysis of testing, cases, and deaths in care homes in the National Health Service (NHS) Lothian health region of the UK. We obtained data for COVID-19 testing (PCR testing of nasopharyngeal swabs for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) and deaths (COVID-19-related and non-COVID-19-related), and we analysed data by several variables including type of care home, number of beds, and locality. Outcome measures were timing of outbreaks, number of confirmed cases of COVID-19 in care home residents, care home characteristics associated with the presence of an outbreak, and deaths of residents in both care homes and hospitals. We calculated excess deaths (both COVID-19-related and non-COVID-19-related), which we defined as the sum of deaths over and above the historical average in the same period over the past 5 years.

Findings

Between March 10 and Aug 2, 2020, residents at 189 care homes (5843 beds) were tested for COVID-19 when symptomatic. A COVID-19 outbreak was confirmed at 69 (37%) care homes, of which 66 (96%) were care homes for older people. The size of care homes for older people was strongly associated with a COVID-19 outbreak (odds ratio per 20-bed increase 3·35, 95% CI 1·99-5·63). 907 confirmed cases of SARS-CoV-2 infection were recorded during the study period, and 432 COVID-19-related deaths. 229 (25%) COVID-19-related cases and 99 (24%) COVID-related deaths occurred in five (3%) of 189 care homes, and 441 (49%) cases and 207 (50%) deaths were in 13 (7%) care homes. 411 (95%) COVID-19-related deaths occurred in the 69 care homes with a confirmed COVID-19 outbreak, 19 (4%) deaths were in hospital, and two (<1%) were in one of the 120 care homes without a confirmed COVID-19 outbreak. At the 69 care homes with a confirmed COVID-19 outbreak, 74 excess non-COVID-19-related deaths were reported, whereas ten non-COVID-19-related excess deaths were observed in the 120 care homes without a confirmed COVID-19 outbreak. 32 fewer non-COVID-19-related deaths than expected were reported among care home residents in hospital.

Interpretation

The effect of COVID-19 on care homes has been substantial but concentrated in care homes with known outbreaks. A key implication from our findings is that, if community incidence of COVID-19 increases again, many care home residents will be susceptible. Shielding care home residents from potential sources of SARS-CoV-2 infection, and ensuring rapid action to minimise outbreak size if infection is introduced, will be important for any second wave.

Funding

None.",,doi:https://doi.org/10.1016/s2666-7568(20)30012-x; doi:https://doi.org/10.1016/S2666-7568(20)30012-X; html:https://europepmc.org/articles/PMC7574931; pdf:https://europepmc.org/articles/PMC7574931?pdf=render 34784292,https://doi.org/10.2196/32587,Investigating the Use of Digital Health Technology to Monitor COVID-19 and Its Effects: Protocol for an Observational Study (Covid Collab Study).,"Stewart C, Ranjan Y, Conde P, Rashid Z, Sankesara H, Bai X, Dobson RJB, Folarin AA.",,JMIR research protocols,2021,2021-12-08,Y,Monitoring; Infectious disease; Recovery; Mobile phone; Feasibility; Surveillance; Data; Mental health; Observational; Smartphone; Wearable; Mobile Health; Wearable Devices; Digital Health; Crowdsourced; Covid-19,,,"

Background

The ubiquity of mobile phones and increasing use of wearable fitness trackers offer a wide-ranging window into people's health and well-being. There are clear advantages in using remote monitoring technologies to gain an insight into health, particularly under the shadow of the COVID-19 pandemic.

Objective

Covid Collab is a crowdsourced study that was set up to investigate the feasibility of identifying, monitoring, and understanding the stratification of SARS-CoV-2 infection and recovery through remote monitoring technologies. Additionally, we will assess the impacts of the COVID-19 pandemic and associated social measures on people's behavior, physical health, and mental well-being.

Methods

Participants will remotely enroll in the study through the Mass Science app to donate historic and prospective mobile phone data, fitness tracking wearable data, and regular COVID-19-related and mental health-related survey data. The data collection period will cover a continuous period (ie, both before and after any reported infections), so that comparisons to a participant's own baseline can be made. We plan to carry out analyses in several areas, which will cover symptomatology; risk factors; the machine learning-based classification of illness; and trajectories of recovery, mental well-being, and activity.

Results

As of June 2021, there are over 17,000 participants-largely from the United Kingdom-and enrollment is ongoing.

Conclusions

This paper introduces a crowdsourced study that will include remotely enrolled participants to record mobile health data throughout the COVID-19 pandemic. The data collected may help researchers investigate a variety of areas, including COVID-19 progression; mental well-being during the pandemic; and the adherence of remote, digitally enrolled participants.

International registered report identifier (irrid)

DERR1-10.2196/32587.",,pdf:https://www.researchprotocols.org/2021/12/e32587/PDF; doi:https://doi.org/10.2196/32587; html:https://europepmc.org/articles/PMC8658240 33611594,https://doi.org/10.1093/eurjpc/zwaa155,Excess deaths in people with cardiovascular diseases during the COVID-19 pandemic.,"Banerjee A, Chen S, Pasea L, Lai AG, Katsoulis M, Denaxas S, Nafilyan V, Williams B, Wong WK, Bakhai A, Khunti K, Pillay D, Noursadeghi M, Wu H, Pareek N, Bromage D, McDonagh TA, Byrne J, Teo JTH, Shah AM, Humberstone B, Tang LV, Shah ASV, Rubboli A, Guo Y, Hu Y, Sudlow CLM, Lip GYH, Hemingway H.",,European journal of preventive cardiology,2021,2021-12-01,Y,Cardiovascular disease; Public Health; Health Policy; Global Health; Coronavirus-2019,,,"

Aims

Cardiovascular diseases (CVDs) increase mortality risk from coronavirus infection (COVID-19). There are also concerns that the pandemic has affected supply and demand of acute cardiovascular care. We estimated excess mortality in specific CVDs, both 'direct', through infection, and 'indirect', through changes in healthcare.

Methods and results

We used (i) national mortality data for England and Wales to investigate trends in non-COVID-19 and CVD excess deaths; (ii) routine data from hospitals in England (n = 2), Italy (n = 1), and China (n = 5) to assess indirect pandemic effects on referral, diagnosis, and treatment services for CVD; and (iii) population-based electronic health records from 3 862 012 individuals in England to investigate pre- and post-COVID-19 mortality for people with incident and prevalent CVD. We incorporated pre-COVID-19 risk (by age, sex, and comorbidities), estimated population COVID-19 prevalence, and estimated relative risk (RR) of mortality in those with CVD and COVID-19 compared with CVD and non-infected (RR: 1.2, 1.5, 2.0, and 3.0).Mortality data suggest indirect effects on CVD will be delayed rather than contemporaneous (peak RR 1.14). CVD service activity decreased by 60-100% compared with pre-pandemic levels in eight hospitals across China, Italy, and England. In China, activity remained below pre-COVID-19 levels for 2-3 months even after easing lockdown and is still reduced in Italy and England. For total CVD (incident and prevalent), at 10% COVID-19 prevalence, we estimated direct impact of 31 205 and 62 410 excess deaths in England (RR 1.5 and 2.0, respectively), and indirect effect of 49 932 to 99 865 deaths.

Conclusion

Supply and demand for CVD services have dramatically reduced across countries with potential for substantial, but avoidable, excess mortality during and after the pandemic.",,pdf:https://academic.oup.com/eurjpc/article-pdf/28/14/1599/41827245/zwaa155.pdf; doi:https://doi.org/10.1093/eurjpc/zwaa155; html:https://europepmc.org/articles/PMC7928969; pdf:https://europepmc.org/articles/PMC7928969?pdf=render -35611160,https://doi.org/10.1016/j.eclinm.2022.101462,Impact of first UK COVID-19 lockdown on hospital admissions: Interrupted time series study of 32 million people.,"Shah SA, Brophy S, Kennedy J, Fisher L, Walker A, Mackenna B, Curtis H, Inglesby P, Davy S, Bacon S, Goldacre B, Agrawal U, Moore E, Simpson CR, Macleod J, Cooksey R, Sheikh A, Katikireddi SV.",,EClinicalMedicine,2022,2022-05-20,Y,Pandemic; Healthcare Inequalities; Healthcare Disruption; Interrupted Time Series Analysis; Covid-19; Sars-cov-2,,,"

Background

Uncontrolled infection and lockdown measures introduced in response have resulted in an unprecedented challenge for health systems internationally. Whether such unprecedented impact was due to lockdown itself and recedes when such measures are lifted is unclear. We assessed the short- and medium-term impacts of the first lockdown measures on hospital care for tracer non-COVID-19 conditions in England, Scotland and Wales across diseases, sexes, and socioeconomic and ethnic groups.

Methods

We used OpenSAFELY (for England), EAVEII (Scotland), and SAIL Databank (Wales) to extract weekly hospital admission rates for cancer, cardiovascular and respiratory conditions (excluding COVID-19) from the pre-pandemic period until 25/10/2020 and conducted a controlled interrupted time series analysis. We undertook stratified analyses and assessed admission rates over seven months during which lockdown restrictions were gradually lifted.

Findings

Our combined dataset included 32 million people who contributed over 74 million person-years. Admission rates for all three conditions fell by 34.2% (Confidence Interval (CI): -43.0, -25.3) in England, 20.9% (CI: -27.8, -14.1) in Scotland, and 24.7% (CI: -36.7, -12.7) in Wales, with falls across every stratum considered. In all three nations, cancer-related admissions fell the most while respiratory-related admissions fell the least (e.g., rates fell by 40.5% (CI: -47.4, -33.6), 21.9% (CI: -35.4, -8.4), and 19.0% (CI: -30.6, -7.4) in England for cancer, cardiovascular-related, and respiratory-related admissions respectively). Unscheduled admissions rates fell more in the most than the least deprived quintile across all three nations. Some ethnic minority groups experienced greater falls in admissions (e.g., in England, unscheduled admissions fell by 9.5% (CI: -20.2, 1.2) for Whites, but 44.3% (CI: -71.0, -17.6), 34.6% (CI: -63.8, -5.3), and 25.6% (CI: -45.0, -6.3) for Mixed, Other and Black ethnic groups respectively). Despite easing of restrictions, the overall admission rates remained lower in England, Scotland, and Wales by 20.8%, 21.6%, and 22.0%, respectively when compared to the same period (August-September) during the pre-pandemic years. This corresponds to a reduction of 26.2, 23.8 and 30.2 admissions per 100,000 people in England, Scotland, and Wales respectively.

Interpretation

Hospital care for non-COVID diseases fell substantially across England, Scotland, and Wales during the first lockdown, with reductions persisting for at least six months. The most deprived and minority ethnic groups were impacted more severely.

Funding

This work was funded by the Medical Research Council as part of the Lifelong Health and Wellbeing study as part of National Core Studies (MC_PC_20030). SVK acknowledges funding from the Medical Research Council (MC_UU_00022/2), and the Scottish Government Chief Scientist Office (SPHSU17). EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE - The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. BG has received research funding from the NHS National Institute for Health Research (NIHR), the Wellcome Trust, Health Data Research UK, Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme.",,pdf:http://www.thelancet.com/article/S2589537022001924/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101462; html:https://europepmc.org/articles/PMC9121886; pdf:https://europepmc.org/articles/PMC9121886?pdf=render 34645794,https://doi.org/10.1038/s41467-021-25914-8,A cross-sectional analysis of meteorological factors and SARS-CoV-2 transmission in 409 cities across 26 countries.,"Sera F, Armstrong B, Abbott S, Meakin S, O'Reilly K, von Borries R, Schneider R, Royé D, Hashizume M, Pascal M, Tobias A, Vicedo-Cabrera AM, MCC Collaborative Research Network, CMMID COVID-19 Working Group, Gasparrini A, Lowe R.",,Nature communications,2021,2021-10-13,Y,,,,"There is conflicting evidence on the influence of weather on COVID-19 transmission. Our aim is to estimate weather-dependent signatures in the early phase of the pandemic, while controlling for socio-economic factors and non-pharmaceutical interventions. We identify a modest non-linear association between mean temperature and the effective reproduction number (Re) in 409 cities in 26 countries, with a decrease of 0.087 (95% CI: 0.025; 0.148) for a 10 °C increase. Early interventions have a greater effect on Re with a decrease of 0.285 (95% CI 0.223; 0.347) for a 5th - 95th percentile increase in the government response index. The variation in the effective reproduction number explained by government interventions is 6 times greater than for mean temperature. We find little evidence of meteorological conditions having influenced the early stages of local epidemics and conclude that population behaviour and government interventions are more important drivers of transmission.",,pdf:https://www.nature.com/articles/s41467-021-25914-8.pdf; doi:https://doi.org/10.1038/s41467-021-25914-8; html:https://europepmc.org/articles/PMC8514574; pdf:https://europepmc.org/articles/PMC8514574?pdf=render +35611160,https://doi.org/10.1016/j.eclinm.2022.101462,Impact of first UK COVID-19 lockdown on hospital admissions: Interrupted time series study of 32 million people.,"Shah SA, Brophy S, Kennedy J, Fisher L, Walker A, Mackenna B, Curtis H, Inglesby P, Davy S, Bacon S, Goldacre B, Agrawal U, Moore E, Simpson CR, Macleod J, Cooksey R, Sheikh A, Katikireddi SV.",,EClinicalMedicine,2022,2022-05-20,Y,Pandemic; Healthcare Inequalities; Healthcare Disruption; Interrupted Time Series Analysis; Covid-19; Sars-cov-2,,,"

Background

Uncontrolled infection and lockdown measures introduced in response have resulted in an unprecedented challenge for health systems internationally. Whether such unprecedented impact was due to lockdown itself and recedes when such measures are lifted is unclear. We assessed the short- and medium-term impacts of the first lockdown measures on hospital care for tracer non-COVID-19 conditions in England, Scotland and Wales across diseases, sexes, and socioeconomic and ethnic groups.

Methods

We used OpenSAFELY (for England), EAVEII (Scotland), and SAIL Databank (Wales) to extract weekly hospital admission rates for cancer, cardiovascular and respiratory conditions (excluding COVID-19) from the pre-pandemic period until 25/10/2020 and conducted a controlled interrupted time series analysis. We undertook stratified analyses and assessed admission rates over seven months during which lockdown restrictions were gradually lifted.

Findings

Our combined dataset included 32 million people who contributed over 74 million person-years. Admission rates for all three conditions fell by 34.2% (Confidence Interval (CI): -43.0, -25.3) in England, 20.9% (CI: -27.8, -14.1) in Scotland, and 24.7% (CI: -36.7, -12.7) in Wales, with falls across every stratum considered. In all three nations, cancer-related admissions fell the most while respiratory-related admissions fell the least (e.g., rates fell by 40.5% (CI: -47.4, -33.6), 21.9% (CI: -35.4, -8.4), and 19.0% (CI: -30.6, -7.4) in England for cancer, cardiovascular-related, and respiratory-related admissions respectively). Unscheduled admissions rates fell more in the most than the least deprived quintile across all three nations. Some ethnic minority groups experienced greater falls in admissions (e.g., in England, unscheduled admissions fell by 9.5% (CI: -20.2, 1.2) for Whites, but 44.3% (CI: -71.0, -17.6), 34.6% (CI: -63.8, -5.3), and 25.6% (CI: -45.0, -6.3) for Mixed, Other and Black ethnic groups respectively). Despite easing of restrictions, the overall admission rates remained lower in England, Scotland, and Wales by 20.8%, 21.6%, and 22.0%, respectively when compared to the same period (August-September) during the pre-pandemic years. This corresponds to a reduction of 26.2, 23.8 and 30.2 admissions per 100,000 people in England, Scotland, and Wales respectively.

Interpretation

Hospital care for non-COVID diseases fell substantially across England, Scotland, and Wales during the first lockdown, with reductions persisting for at least six months. The most deprived and minority ethnic groups were impacted more severely.

Funding

This work was funded by the Medical Research Council as part of the Lifelong Health and Wellbeing study as part of National Core Studies (MC_PC_20030). SVK acknowledges funding from the Medical Research Council (MC_UU_00022/2), and the Scottish Government Chief Scientist Office (SPHSU17). EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE - The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. BG has received research funding from the NHS National Institute for Health Research (NIHR), the Wellcome Trust, Health Data Research UK, Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme.",,pdf:http://www.thelancet.com/article/S2589537022001924/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101462; html:https://europepmc.org/articles/PMC9121886; pdf:https://europepmc.org/articles/PMC9121886?pdf=render 38512523,https://doi.org/10.1007/s00415-024-12284-6,Prevalence and temporal relationship of clinical co-morbidities in idiopathic dystonia: a UK linkage-based study.,"Bailey GA, Rawlings A, Torabi F, Pickrell WO, Peall KJ.",,Journal of neurology,2024,2024-03-21,Y,epidemiology; Dystonia; Co-morbidity; Linked Clinical Data,,,"While motor and psychiatric phenotypes in idiopathic dystonia are increasingly well understood, a few studies have examined the rate, type, and temporal pattern of other clinical co-morbidities in dystonia. Here, we determine the rates of clinical diagnoses across 13 broad systems-based diagnostic groups, comparing an overall idiopathic dystonia cohort, and sub-cohorts of cervical dystonia, blepharospasm, and dystonic tremor, to a matched-control cohort. Using the SAIL databank, we undertook a longitudinal population-based cohort study (January 1st 1994-December 31st 2017) using anonymised electronic healthcare records for individuals living in Wales (UK), identifying those diagnosed with dystonia through use of a previously validated algorithm. Clinical co-morbid diagnoses were identified from primary health care records, with a 10% prevalence threshold required for onward analysis. Using this approach, 54,166 dystonia cases were identified together with 216,574 matched controls. Within this cohort, ten of the main ICD-10 diagnostic codes exceeded the 10% prevalence threshold over the 20-year period (infection, neurological, respiratory, gastrointestinal, genitourinary, dermatological, musculoskeletal, circulatory, neoplastic, and endocrinological). In the overall dystonia cohort, musculoskeletal (aOR: 1.89, aHR: 1.74), respiratory (aOR: 1.84; aHR: 1.65), and gastrointestinal (aOR: 1.72; aHR: 1.6) disorders had the strongest associations both pre- and post-dystonia diagnosis. However, variation in the rate of association of individual clinical co-morbidities was observed across the cervical, blepharospasm, and tremor dystonia groups. This study suggests an increased rate of specific co-morbid clinical disorders both pre- and post-dystonia diagnosis which should be considered during clinical assessment of those with dystonia to enable optimum symptomatic management.",,pdf:https://link.springer.com/content/pdf/10.1007/s00415-024-12284-6.pdf; doi:https://doi.org/10.1007/s00415-024-12284-6; html:https://europepmc.org/articles/PMC11136734; pdf:https://europepmc.org/articles/PMC11136734?pdf=render 35698725,https://doi.org/10.1016/s2665-9913(22)00098-4,Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform.,"MacKenna B, Kennedy NA, Mehrkar A, Rowan A, Galloway J, Matthewman J, Mansfield KE, Bechman K, Yates M, Brown J, Schultze A, Norton S, Walker AJ, Morton CE, Harrison D, Bhaskaran K, Rentsch CT, Williamson E, Croker R, Bacon S, Hickman G, Ward T, Davy S, Green A, Fisher L, Hulme W, Bates C, Curtis HJ, Tazare J, Eggo RM, Evans D, Inglesby P, Cockburn J, McDonald HI, Tomlinson LA, Mathur R, Wong AYS, Forbes H, Parry J, Hester F, Harper S, Douglas IJ, Smeeth L, Lees CW, Evans SJW, Goldacre B, Smith CH, Langan SM.",,The Lancet. Rheumatology,2022,2022-06-09,Y,,,,"

Background

The risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases and on immune-modifying drugs might not be fully mediated by comorbidities and might vary by factors such as ethnicity. We aimed to assess the risk of severe COVID-19 in adults with immune-mediated inflammatory diseases and in those on immune-modifying therapies.

Methods

We did a cohort study, using OpenSAFELY (an analytics platform for electronic health records) and TPP (a software provider for general practitioners), analysing routinely collected primary care data linked to hospital admission, death, and previously unavailable hospital prescription data. We included people aged 18 years or older on March 1, 2020, who were registered with TPP practices with at least 12 months of primary care records before March, 2020. We used Cox regression (adjusting for confounders and mediators) to estimate hazard ratios (HRs) comparing the risk of COVID-19-related death, critical care admission or death, and hospital admission (from March 1 to Sept 30, 2020) in people with immune-mediated inflammatory diseases compared with the general population, and in people with immune-mediated inflammatory diseases on targeted immune-modifying drugs (eg, biologics) compared with those on standard systemic treatment (eg, methotrexate).

Findings

We identified 17 672 065 adults; 1 163 438 adults (640 164 [55·0%] women and 523 274 [45·0%] men, and 827 457 [71·1%] of White ethnicity) had immune-mediated inflammatory diseases, and 16 508 627 people (8 215 020 [49·8%] women and 8 293 607 [50·2%] men, and 10 614 096 [64·3%] of White ethnicity) were included as the general population. Of 1 163 438 adults with immune-mediated inflammatory diseases, 19 119 (1·6%) received targeted immune-modifying therapy and 181 694 (15·6%) received standard systemic therapy. Compared with the general population, adults with immune-mediated inflammatory diseases had an increased risk of COVID-19-related death after adjusting for confounders (age, sex, deprivation, and smoking status; HR 1·23, 95% CI 1·20-1·27) and further adjusting for mediators (body-mass index [BMI], cardiovascular disease, diabetes, and current glucocorticoid use; 1·15, 1·11-1·18). Adults with immune-mediated inflammatory diseases also had an increased risk of COVID-19-related critical care admission or death (confounder-adjusted HR 1·24, 95% CI 1·21-1·28; mediator-adjusted 1·16, 1·12-1·19) and hospital admission (confounder-adjusted 1·32, 1·29-1·35; mediator-adjusted 1·20, 1·17-1·23). In post-hoc analyses, the risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases was higher in non-White ethnic groups than in White ethnic groups (as it was in the general population). We saw no evidence of increased COVID-19-related death in adults on targeted, compared with those on standard systemic, therapy after adjusting for confounders (age, sex, deprivation, BMI, immune-mediated inflammatory diseases [bowel, joint, and skin], cardiovascular disease, cancer [excluding non-melanoma skin cancer], stroke, and diabetes (HR 1·03, 95% CI 0·80-1·33), and after additionally adjusting for current glucocorticoid use (1·01, 0·78-1·30). There was no evidence of increased COVID-19-related death in adults prescribed tumour necrosis factor inhibitors, interleukin (IL)-12/IL‑23 inhibitors, IL-17 inhibitors, IL-6 inhibitors, or Janus kinase inhibitors compared with those on standard systemic therapy. Rituximab was associated with increased COVID-19-related death (HR 1·68, 95% CI 1·11-2·56), with some attenuation after excluding people with haematological malignancies or organ transplants (1·54, 0·95-2·49).

Interpretation

COVID-19 deaths and hospital admissions were higher in people with immune-mediated inflammatory diseases. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune-modifying drugs for immune-mediated inflammatory diseases compared with those on standard systemic therapy.

Funding

UK Medical Research Council, NIHR Biomedical Research Centre at King's College London and Guy's and St Thomas' NHS Foundation Trust, and Wellcome Trust.",,pdf:http://www.thelancet.com/article/S2665991322000984/pdf; doi:https://doi.org/10.1016/S2665-9913(22)00098-4; html:https://europepmc.org/articles/PMC9179144; pdf:https://europepmc.org/articles/PMC9179144?pdf=render 34935001,https://doi.org/10.1016/s2666-7568(21)00282-8,Prevalence and duration of detectable SARS-CoV-2 nucleocapsid antibodies in staff and residents of long-term care facilities over the first year of the pandemic (VIVALDI study): prospective cohort study in England.,"Krutikov M, Palmer T, Tut G, Fuller C, Azmi B, Giddings R, Shrotri M, Kaur N, Sylla P, Lancaster T, Irwin-Singer A, Hayward A, Moss P, Copas A, Shallcross L.",,The lancet. Healthy longevity,2022,2021-12-16,Y,,,,"

Background

Long-term care facilities (LTCFs) have reported high SARS-CoV-2 infection rates and related mortality, but the proportion of infected people among those who have survived, and duration of the antibody response to natural infection, is unknown. We determined the prevalence and stability of nucleocapsid antibodies (the standard assay for detection of previous infection) in staff and residents in LTCFs in England.

Methods

This was a prospective cohort study of residents 65 years or older and of staff 65 years or younger in 201 LTCFs in England between March 1, 2020, and May 7, 2021. Participants were linked to a unique pseudo-identifier based on their UK National Health Service identification number. Serial blood samples were tested for IgG antibodies against SARS-CoV-2 nucleocapsid protein using the Abbott ARCHITECT i-system (Abbott, Maidenhead, UK) immunoassay. Primary endpoints were prevalence and cumulative incidence of antibody positivity, which were weighted to the LTCF population. Incidence rate of loss of antibodies (seroreversion) was estimated from Kaplan-Meier curves.

Findings

9488 samples were included, 8636 (91·0%) of which could be individually linked to 1434 residents and 3288 staff members. The cumulative incidence of nucleocapsid seropositivity was 34·6% (29·6-40·0) in residents and 26·1% (23·0-29·5) in staff over 11 months. 239 (38·6%) residents and 503 women (81·3%) were included in the antibody-waning analysis, and median follow-up was 149 days (IQR 107-169). The incidence rate of seroreversion was 2·1 per 1000 person-days at risk, and median time to reversion was 242·5 days.

Interpretation

At least a quarter of staff and a third of surviving residents were infected with SAR-CoV-2 during the first two waves of the pandemic in England. Nucleocapsid-specific antibodies often become undetectable within the first year following infection, which is likely to lead to marked underestimation of the true proportion of people with previous infection. Given that natural infection might act to boost vaccine responses, better assays to identify natural infection should be developed.

Funding

UK Government Department of Health and Social Care.",,pdf:http://www.thelancet.com/article/S2666756821002828/pdf; doi:https://doi.org/10.1016/S2666-7568(21)00282-8; html:https://europepmc.org/articles/PMC8676418 35459950,https://doi.org/10.1093/intqhc/mzac031,Modelling the effect of COVID-19 mass vaccination on acute hospital admissions.,"Booton RD, Powell AL, Turner KME, Wood RM.",,International journal for quality in health care : journal of the International Society for Quality in Health Care,2022,2022-05-01,N,Vaccination; Coronavirus; Mathematical Modelling; Bed Management; Hospital Capacity; Covid-19,,,"

Background

Managing high levels of acute COVID-19 bed occupancy can affect the quality of care provided to both affected patients and those requiring other hospital services. Mass vaccination has offered a route to reduce societal restrictions while protecting hospitals from being overwhelmed. Yet, early in the mass vaccination effort, the possible impact on future bed pressures remained subject to considerable uncertainty.

Objective

The aim of this study was to model the effect of vaccination on projections of acute and intensive care bed demand within a 1 million resident healthcare system located in South West England.

Methods

An age-structured epidemiological model of the susceptible-exposed-infectious-recovered type was fitted to local data up to the time of the study, in early March 2021. Model parameters and vaccination scenarios were calibrated through a system-wide multidisciplinary working group, comprising public health intelligence specialists, healthcare planners, epidemiologists and academics. Scenarios assumed incremental relaxations to societal restrictions according to the envisaged UK Government timeline, with all restrictions to be removed by 21 June 2021.

Results

Achieving 95% vaccine uptake in adults by 31 July 2021 would not avert the third wave in autumn 2021 but would produce a median peak bed requirement ∼6% (IQR: 1-24%) of that experienced during the second wave (January 2021). A 2-month delay in vaccine rollout would lead to significantly higher peak bed occupancy, at 66% (11-146%) of that of the second wave. If only 75% uptake was achieved (the amount typically associated with vaccination campaigns), then the second wave peak for acute and intensive care beds would be exceeded by 4% and 19%, respectively, an amount which would seriously pressure hospital capacity.

Conclusion

Modelling influenced decision-making among senior managers in setting COVID-19 bed capacity levels, as well as highlighting the importance of public health in promoting high vaccine uptake among the population. Forecast accuracy has since been supported by actual data collected following the analysis, with observed peak bed occupancy falling comfortably within the inter-quartile range of modelled projections.",,pdf:https://academic.oup.com/intqhc/article-pdf/34/2/mzac031/43704475/mzac031.pdf; doi:https://doi.org/10.1093/intqhc/mzac031 36374585,https://doi.org/10.1177/01410768221131897,Using national electronic health records for pandemic preparedness: validation of a parsimonious model for predicting excess deaths among those with COVID-19-a data-driven retrospective cohort study.,"Mizani MA, Dashtban A, Pasea L, Lai AG, Thygesen J, Tomlinson C, Handy A, Mamza JB, Morris T, Khalid S, Zaccardi F, Macleod MJ, Torabi F, Canoy D, Akbari A, Berry C, Bolton T, Nolan J, Khunti K, Denaxas S, Hemingway H, Sudlow C, Banerjee A, CVD-COVID-UK Consortium.",,Journal of the Royal Society of Medicine,2023,2022-11-14,N,Infectious diseases; Clinical; epidemiology; Public Health; Health Informatics,,,"

Objectives

To use national, pre- and post-pandemic electronic health records (EHR) to develop and validate a scenario-based model incorporating baseline mortality risk, infection rate (IR) and relative risk (RR) of death for prediction of excess deaths.

Design

An EHR-based, retrospective cohort study.

Setting

Linked EHR in Clinical Practice Research Datalink (CPRD); and linked EHR and COVID-19 data in England provided in NHS Digital Trusted Research Environment (TRE).

Participants

In the development (CPRD) and validation (TRE) cohorts, we included 3.8 million and 35.1 million individuals aged ≥30 years, respectively.

Main outcome measures

One-year all-cause excess deaths related to COVID-19 from March 2020 to March 2021.

Results

From 1 March 2020 to 1 March 2021, there were 127,020 observed excess deaths. Observed RR was 4.34% (95% CI, 4.31-4.38) and IR was 6.27% (95% CI, 6.26-6.28). In the validation cohort, predicted one-year excess deaths were 100,338 compared with the observed 127,020 deaths with a ratio of predicted to observed excess deaths of 0.79.

Conclusions

We show that a simple, parsimonious model incorporating baseline mortality risk, one-year IR and RR of the pandemic can be used for scenario-based prediction of excess deaths in the early stages of a pandemic. Our analyses show that EHR could inform pandemic planning and surveillance, despite limited use in emergency preparedness to date. Although infection dynamics are important in the prediction of mortality, future models should take greater account of underlying conditions.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/01410768221131897; doi:https://doi.org/10.1177/01410768221131897; html:https://europepmc.org/articles/PMC9909113; pdf:https://europepmc.org/articles/PMC9909113?pdf=render; doi:https://doi.org/10.1177/01410768221131897 -37303488,https://doi.org/10.1136/bmjmed-2022-000392,"Changes in medication safety indicators in England throughout the covid-19 pandemic using OpenSAFELY: population based, retrospective cohort study of 57 million patients using federated analytics.","Fisher L, Hopcroft LE, Rodgers S, Barrett J, Oliver K, Avery AJ, Evans D, Curtis H, Croker R, Macdonald O, Morley J, Mehrkar A, Bacon S, Davy S, Dillingham I, Evans D, Hickman G, Inglesby P, Morton CE, Smith B, Ward T, Hulme W, Green A, Massey J, Walker AJ, Bates C, Cockburn J, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Goldacre B, MacKenna B.",,BMJ medicine,2023,2023-05-11,Y,Primary Health Care; Medical Informatics; Covid-19,,,"

Objective

To implement complex, PINCER (pharmacist led information technology intervention) prescribing indicators, on a national scale with general practice data to describe the impact of the covid-19 pandemic on safe prescribing.

Design

Population based, retrospective cohort study using federated analytics.

Setting

Electronic general practice health record data from 56.8 million NHS patients by use of the OpenSAFELY platform, with the approval of the National Health Service (NHS) England.

Participants

NHS patients (aged 18-120 years) who were alive and registered at a general practice that used TPP or EMIS computer systems and were recorded as at risk of at least one potentially hazardous PINCER indicator.

Main outcome measure

Between 1 September 2019 and 1 September 2021, monthly trends and between practice variation for compliance with 13 PINCER indicators, as calculated on the first of every month, were reported. Prescriptions that do not adhere to these indicators are potentially hazardous and can cause gastrointestinal bleeds; are cautioned against in specific conditions (specifically heart failure, asthma, and chronic renal failure); or require blood test monitoring. The percentage for each indicator is formed of a numerator of patients deemed to be at risk of a potentially hazardous prescribing event and the denominator is of patients for which assessment of the indicator is clinically meaningful. Higher indicator percentages represent potentially poorer performance on medication safety.

Results

The PINCER indicators were successfully implemented across general practice data for 56.8 million patient records from 6367 practices in OpenSAFELY. Hazardous prescribing remained largely unchanged during the covid-19 pandemic, with no evidence of increases in indicators of harm as captured by the PINCER indicators. The percentage of patients at risk of potentially hazardous prescribing, as defined by each PINCER indicator, at mean quarter 1 (Q1) 2020 (representing before the pandemic) ranged from 1.11% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 36.20% (amiodarone and no thyroid function test), while Q1 2021 (representing after the pandemic) percentages ranged from 0.75% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 39.23% (amiodarone and no thyroid function test). Transient delays occurred in blood test monitoring for some medications, particularly angiotensin-converting enzyme inhibitors (where blood monitoring worsened from a mean of 5.16% in Q1 2020 to 12.14% in Q1 2021, and began to recover in June 2021). All indicators substantially recovered by September 2021. We identified 1 813 058 patients (3.1%) at risk of at least one potentially hazardous prescribing event.

Conclusion

NHS data from general practices can be analysed at national scale to generate insights into service delivery. Potentially hazardous prescribing was largely unaffected by the covid-19 pandemic in primary care health records in England.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000392.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000392; html:https://europepmc.org/articles/PMC10254692; pdf:https://europepmc.org/articles/PMC10254692?pdf=render 33617936,https://doi.org/10.1016/j.jhin.2021.02.012,Global and national estimates of the number of healthcare workers at high risk of SARS-CoV-2 infection.,"McCarthy CV, Sandmann FG, CMMID COVID-19 Working Group, Jit M.",,The Journal of hospital infection,2021,2021-02-20,Y,,,,,,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4660358/1/Global%20and%20national%20estimates%20of%20the%20number%20of%20healthcare%20workers%20at%20high%20risk%20of%20SARS-CoV-2%20infection.pdf; doi:https://doi.org/10.1016/j.jhin.2021.02.012; html:https://europepmc.org/articles/PMC7896121; pdf:https://europepmc.org/articles/PMC7896121?pdf=render +37303488,https://doi.org/10.1136/bmjmed-2022-000392,"Changes in medication safety indicators in England throughout the covid-19 pandemic using OpenSAFELY: population based, retrospective cohort study of 57 million patients using federated analytics.","Fisher L, Hopcroft LE, Rodgers S, Barrett J, Oliver K, Avery AJ, Evans D, Curtis H, Croker R, Macdonald O, Morley J, Mehrkar A, Bacon S, Davy S, Dillingham I, Evans D, Hickman G, Inglesby P, Morton CE, Smith B, Ward T, Hulme W, Green A, Massey J, Walker AJ, Bates C, Cockburn J, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Goldacre B, MacKenna B.",,BMJ medicine,2023,2023-05-11,Y,Primary Health Care; Medical Informatics; Covid-19,,,"

Objective

To implement complex, PINCER (pharmacist led information technology intervention) prescribing indicators, on a national scale with general practice data to describe the impact of the covid-19 pandemic on safe prescribing.

Design

Population based, retrospective cohort study using federated analytics.

Setting

Electronic general practice health record data from 56.8 million NHS patients by use of the OpenSAFELY platform, with the approval of the National Health Service (NHS) England.

Participants

NHS patients (aged 18-120 years) who were alive and registered at a general practice that used TPP or EMIS computer systems and were recorded as at risk of at least one potentially hazardous PINCER indicator.

Main outcome measure

Between 1 September 2019 and 1 September 2021, monthly trends and between practice variation for compliance with 13 PINCER indicators, as calculated on the first of every month, were reported. Prescriptions that do not adhere to these indicators are potentially hazardous and can cause gastrointestinal bleeds; are cautioned against in specific conditions (specifically heart failure, asthma, and chronic renal failure); or require blood test monitoring. The percentage for each indicator is formed of a numerator of patients deemed to be at risk of a potentially hazardous prescribing event and the denominator is of patients for which assessment of the indicator is clinically meaningful. Higher indicator percentages represent potentially poorer performance on medication safety.

Results

The PINCER indicators were successfully implemented across general practice data for 56.8 million patient records from 6367 practices in OpenSAFELY. Hazardous prescribing remained largely unchanged during the covid-19 pandemic, with no evidence of increases in indicators of harm as captured by the PINCER indicators. The percentage of patients at risk of potentially hazardous prescribing, as defined by each PINCER indicator, at mean quarter 1 (Q1) 2020 (representing before the pandemic) ranged from 1.11% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 36.20% (amiodarone and no thyroid function test), while Q1 2021 (representing after the pandemic) percentages ranged from 0.75% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 39.23% (amiodarone and no thyroid function test). Transient delays occurred in blood test monitoring for some medications, particularly angiotensin-converting enzyme inhibitors (where blood monitoring worsened from a mean of 5.16% in Q1 2020 to 12.14% in Q1 2021, and began to recover in June 2021). All indicators substantially recovered by September 2021. We identified 1 813 058 patients (3.1%) at risk of at least one potentially hazardous prescribing event.

Conclusion

NHS data from general practices can be analysed at national scale to generate insights into service delivery. Potentially hazardous prescribing was largely unaffected by the covid-19 pandemic in primary care health records in England.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000392.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000392; html:https://europepmc.org/articles/PMC10254692; pdf:https://europepmc.org/articles/PMC10254692?pdf=render 35189575,https://doi.org/10.1016/j.ebiom.2022.103878,The impact of hypoxia on B cells in COVID-19.,"Kotagiri P, Mescia F, Hanson AL, Turner L, Bergamaschi L, Peñalver A, Richoz N, Moore SD, Ortmann BM, Dunmore BJ, Morgan MD, Tuong ZK, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, Göttgens B, Toshner M, Hess C, Maxwell PH, Clatworthy MR, Nathan JA, Bradley JR, Lyons PA, Burrows N, Smith KGC.",,EBioMedicine,2022,2022-02-19,Y,Hypoxia; B cells; Lymphopenia; Covid-19,,,"

Background

Prominent early features of COVID-19 include severe, often clinically silent, hypoxia and a pronounced reduction in B cells, the latter important in defence against SARS-CoV-2. This presentation resembles the phenotype of mice with VHL-deficient B cells, in which Hypoxia-Inducible Factors are constitutively active, suggesting hypoxia might drive B cell abnormalities in COVID-19.

Methods

Detailed B cell phenotyping was undertaken by flow-cytometry on longitudinal samples from patients with COVID-19 across a range of severities (NIHR Cambridge BioResource). The impact of hypoxia on the transcriptome was assessed by single-cell and whole blood RNA sequencing analysis. The direct effect of hypoxia on B cells was determined through immunisation studies in genetically modified and hypoxia-exposed mice.

Findings

We demonstrate the breadth of early and persistent defects in B cell subsets in moderate/severe COVID-19, including reduced marginal zone-like, memory and transitional B cells, changes also observed in B cell VHL-deficient mice. These findings were associated with hypoxia-related transcriptional changes in COVID-19 patient B cells, and similar B cell abnormalities were seen in mice kept in hypoxic conditions.

Interpretation

Hypoxia may contribute to the pronounced and persistent B cell pathology observed in acute COVID-19 pneumonia. Assessment of the impact of early oxygen therapy on these immune defects should be considered, as their correction could contribute to improved outcomes.

Funding

Evelyn Trust, Addenbrooke's Charitable Trust, UKRI/NIHR, Wellcome Trust.",,pdf:http://www.thelancet.com/article/S2352396422000627/pdf; doi:https://doi.org/10.1016/j.ebiom.2022.103878; html:https://europepmc.org/articles/PMC8856886; pdf:https://europepmc.org/articles/PMC8856886?pdf=render 34972825,https://doi.org/10.1038/s41564-021-01029-0,Improving local prevalence estimates of SARS-CoV-2 infections using a causal debiasing framework.,"Nicholson G, Lehmann B, Padellini T, Pouwels KB, Jersakova R, Lomax J, King RE, Mallon AM, Diggle PJ, Richardson S, Blangiardo M, Holmes C.",,Nature microbiology,2022,2021-12-31,Y,,,,"Global and national surveillance of SARS-CoV-2 epidemiology is mostly based on targeted schemes focused on testing individuals with symptoms. These tested groups are often unrepresentative of the wider population and exhibit test positivity rates that are biased upwards compared with the true population prevalence. Such data are routinely used to infer infection prevalence and the effective reproduction number, Rt, which affects public health policy. Here, we describe a causal framework that provides debiased fine-scale spatiotemporal estimates by combining targeted test counts with data from a randomized surveillance study in the United Kingdom called REACT. Our probabilistic model includes a bias parameter that captures the increased probability of an infected individual being tested, relative to a non-infected individual, and transforms observed test counts to debiased estimates of the true underlying local prevalence and Rt. We validated our approach on held-out REACT data over a 7-month period. Furthermore, our local estimates of Rt are indicative of 1-week- and 2-week-ahead changes in SARS-CoV-2-positive case numbers. We also observed increases in estimated local prevalence and Rt that reflect the spread of the Alpha and Delta variants. Our results illustrate how randomized surveys can augment targeted testing to improve statistical accuracy in monitoring the spread of emerging and ongoing infectious disease.",,pdf:https://www.nature.com/articles/s41564-021-01029-0.pdf; doi:https://doi.org/10.1038/s41564-021-01029-0; html:https://europepmc.org/articles/PMC8727294; pdf:https://europepmc.org/articles/PMC8727294?pdf=render 34308406,https://doi.org/10.1016/j.lanepe.2021.100180,Ethnic differences in SARS-CoV-2 vaccine hesitancy in United Kingdom healthcare workers: Results from the UK-REACH prospective nationwide cohort study.,"Woolf K, McManus IC, Martin CA, Nellums LB, Guyatt AL, Melbourne C, Bryant L, Gogoi M, Wobi F, Al-Oraibi A, Hassan O, Gupta A, John C, Tobin MD, Carr S, Simpson S, Gregary B, Aujayeb A, Zingwe S, Reza R, Gray LJ, Khunti K, Pareek M, UK-REACH Study Collaborative Group.",,The Lancet regional health. Europe,2021,2021-07-19,Y,,,,"

Background

In most countries, healthcare workers (HCWs) represent a priority group for vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) due to their elevated risk of COVID-19 and potential contribution to nosocomial SARS-CoV-2 transmission. Concerns have been raised that HCWs from ethnic minority groups are more likely to be vaccine hesitant (defined by the World Health Organisation as refusing or delaying a vaccination) than those of White ethnicity, but there are limited data on SARS-CoV-2 vaccine hesitancy and its predictors in UK HCWs.

Methods

Nationwide prospective cohort study and qualitative study in a multi-ethnic cohort of clinical and non-clinical UK HCWs. We analysed ethnic differences in SARS-CoV-2 vaccine hesitancy adjusting for demographics, vaccine trust, and perceived risk of COVID-19. We explored reasons for hesitancy in qualitative data using a framework analysis.

Findings

11,584 HCWs were included in the cohort analysis. 23% (2704) reported vaccine hesitancy. Compared to White British HCWs (21.3% hesitant), HCWs from Black Caribbean (54.2%), Mixed White and Black Caribbean (38.1%), Black African (34.4%), Chinese (33.1%), Pakistani (30.4%), and White Other (28.7%) ethnic groups were significantly more likely to be hesitant. In adjusted analysis, Black Caribbean (aOR 3.37, 95% CI 2.11 - 5.37), Black African (aOR 2.05, 95% CI 1.49 - 2.82), White Other ethnic groups (aOR 1.48, 95% CI 1.19 - 1.84) were significantly more likely to be hesitant. Other independent predictors of hesitancy were younger age, female sex, higher score on a COVID-19 conspiracy beliefs scale, lower trust in employer, lack of influenza vaccine uptake in the previous season, previous COVID-19, and pregnancy. Qualitative data from 99 participants identified the following contributors to hesitancy: lack of trust in government and employers, safety concerns due to the speed of vaccine development, lack of ethnic diversity in vaccine studies, and confusing and conflicting information. Participants felt uptake in ethnic minority communities might be improved through inclusive communication, involving HCWs in the vaccine rollout, and promoting vaccination through trusted networks.

Interpretation

Despite increased risk of COVID-19, HCWs from some ethnic minority groups are more likely to be vaccine hesitant than their White British colleagues. Strategies to build trust and dispel myths surrounding the COVID-19 vaccine in these communities are urgently required. Emphasis should be placed on the safety and benefit of SARS-CoV-2 vaccination in pregnancy and in those with previous COVID-19. Public health communications should be inclusive, non-stigmatising and utilise trusted networks.

Funding

UKRI-MRC and NIHR.",,doi:https://doi.org/10.1016/j.lanepe.2021.100180; doi:https://doi.org/10.1016/j.lanepe.2021.100180; html:https://europepmc.org/articles/PMC8287519; pdf:https://europepmc.org/articles/PMC8287519?pdf=render @@ -387,8 +387,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 33328453,https://doi.org/10.1038/s41467-020-19996-z,Genetic architecture of host proteins involved in SARS-CoV-2 infection.,"Pietzner M, Wheeler E, Carrasco-Zanini J, Raffler J, Kerrison ND, Oerton E, Auyeung VPW, Luan J, Finan C, Casas JP, Ostroff R, Williams SA, Kastenmüller G, Ralser M, Gamazon ER, Wareham NJ, Hingorani AD, Langenberg C.",,Nature communications,2020,2020-12-16,Y,,,,"Understanding the genetic architecture of host proteins interacting with SARS-CoV-2 or mediating the maladaptive host response to COVID-19 can help to identify new or repurpose existing drugs targeting those proteins. We present a genetic discovery study of 179 such host proteins among 10,708 individuals using an aptamer-based technique. We identify 220 host DNA sequence variants acting in cis (MAF 0.01-49.9%) and explaining 0.3-70.9% of the variance of 97 of these proteins, including 45 with no previously known protein quantitative trait loci (pQTL) and 38 encoding current drug targets. Systematic characterization of pQTLs across the phenome identified protein-drug-disease links and evidence that putative viral interaction partners such as MARK3 affect immune response. Our results accelerate the evaluation and prioritization of new drug development programmes and repurposing of trials to prevent, treat or reduce adverse outcomes. Rapid sharing and detailed interrogation of results is facilitated through an interactive webserver ( https://omicscience.org/apps/covidpgwas/ ).",,pdf:https://www.nature.com/articles/s41467-020-19996-z.pdf; doi:https://doi.org/10.1038/s41467-020-19996-z; html:https://europepmc.org/articles/PMC7744536; pdf:https://europepmc.org/articles/PMC7744536?pdf=render 36447940,https://doi.org/10.1016/s2665-9913(22)00305-8,Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY.,"Russell MD, Galloway JB, Andrews CD, MacKenna B, Goldacre B, Mehrkar A, Curtis HJ, Butler-Cole B, O'Dwyer T, Qureshi S, Ledingham JM, Mahto A, Rutherford AI, Adas MA, Alveyn E, Norton S, Cope AP, Bechman K, OpenSAFELY Collaborative.",,The Lancet. Rheumatology,2022,2022-11-03,Y,,,,"

Background

The impact of the COVID-19 pandemic on the incidence and management of inflammatory arthritis is not understood. Routinely captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how care for patients with inflammatory arthritis was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for inflammatory arthritis in England and to replicate key metrics from the National Early Inflammatory Arthritis Audit.

Methods

In this population-level cohort study, we used primary care and hospital data for 17·7 million adults registered with general practices using TPP health record software, to explore the following outcomes between April 1, 2019, and March 31, 2022: (1) incidence of inflammatory arthritis diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and undifferentiated inflammatory arthritis) recorded in primary care; (2) time to first rheumatology assessment; (3) time to first prescription of a disease-modifying antirheumatic drug (DMARD) in primary care; and (4) choice of first DMARD.

Findings

Among 17 683 500 adults, there were 31 280 incident inflammatory arthritis diagnoses recorded between April 1, 2019, and March 31, 2022. The mean age of diagnosed patients was 55·4 years (SD 16·6), 18 615 (59·5%) were female, 12 665 (40·5%) were male, and 22 925 (88·3%) of 25 960 with available ethnicity data were White. New inflammatory arthritis diagnoses decreased by 20·3% in the year commencing April, 2020, relative to the preceding year (5·1 vs 6·4 diagnoses per 10 000 adults). The median time to first rheumatology assessment was shorter during the pandemic (18 days; IQR 8-35) than before (21 days; 9-41). The proportion of patients prescribed DMARDs in primary care was similar before and during the pandemic; however, during the pandemic, fewer people were prescribed methotrexate or leflunomide, and more were prescribed sulfasalazine or hydroxychloroquine.

Interpretation

Inflammatory arthritis diagnoses decreased markedly during the early phase of the pandemic. The impact on rheumatology assessment times and DMARD prescribing in primary care was less marked than might have been anticipated. This study demonstrates the feasibility of using routinely captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection.

Funding

None.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4669009/1/Russell_etal_2022_Incidence-and-management-of-inflammatory.pdf; doi:https://doi.org/10.1016/S2665-9913(22)00305-8; html:https://europepmc.org/articles/PMC9691150; pdf:https://europepmc.org/articles/PMC9691150?pdf=render 34210356,https://doi.org/10.1186/s13059-021-02395-y,CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance.,"Nicholls SM, Poplawski R, Bull MJ, Underwood A, Chapman M, Abu-Dahab K, Taylor B, Colquhoun RM, Rowe WPM, Jackson B, Hill V, O'Toole Á, Rey S, Southgate J, Amato R, Livett R, Gonçalves S, Harrison EM, Peacock SJ, Aanensen DM, Rambaut A, Connor TR, Loman NJ, COVID-19 Genomics UK (COG-UK) Consortium.",,Genome biology,2021,2021-07-01,Y,,,,"In response to the ongoing SARS-CoV-2 pandemic in the UK, the COVID-19 Genomics UK (COG-UK) consortium was formed to rapidly sequence SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of CLIMB-COVID, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network.",,pdf:https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-021-02395-y; doi:https://doi.org/10.1186/s13059-021-02395-y; html:https://europepmc.org/articles/PMC8247108; pdf:https://europepmc.org/articles/PMC8247108?pdf=render -36029521,https://doi.org/10.1093/ije/dyac171,Cohort Profile: The United Kingdom Research study into Ethnicity and COVID-19 outcomes in Healthcare workers (UK-REACH).,"Bryant L, Free RC, Woolf K, Melbourne C, Guyatt AL, John C, Gupta A, Gray LJ, Nellums L, Martin CA, McManus IC, Garwood C, Modhawdia V, Carr S, Wain LV, Tobin MD, Khunti K, Akubakar I, Pareek M, UK-REACH Collaborative Group+.",,International journal of epidemiology,2023,2023-02-01,Y,,,,,,pdf:https://academic.oup.com/ije/article-pdf/52/1/e38/49127215/dyac171.pdf; doi:https://doi.org/10.1093/ije/dyac171; html:https://europepmc.org/articles/PMC9452183; pdf:https://europepmc.org/articles/PMC9452183?pdf=render 32781946,https://doi.org/10.1098/rspb.2020.1405,Key questions for modelling COVID-19 exit strategies.,"Thompson RN, Hollingsworth TD, Isham V, Arribas-Bel D, Ashby B, Britton T, Challenor P, Chappell LHK, Clapham H, Cunniffe NJ, Dawid AP, Donnelly CA, Eggo RM, Funk S, Gilbert N, Glendinning P, Gog JR, Hart WS, Heesterbeek H, House T, Keeling M, Kiss IZ, Kretzschmar ME, Lloyd AL, McBryde ES, McCaw JM, McKinley TJ, Miller JC, Morris M, O'Neill PD, Parag KV, Pearson CAB, Pellis L, Pulliam JRC, Ross JV, Tomba GS, Silverman BW, Struchiner CJ, Tildesley MJ, Trapman P, Webb CR, Mollison D, Restif O.",,Proceedings. Biological sciences,2020,2020-08-12,Y,Uncertainty; Mathematical Modelling; Epidemic Control; Exit Strategy; Covid-19; Sars-cov-2,,,"Combinations of intense non-pharmaceutical interventions (lockdowns) were introduced worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement exit strategies that relax restrictions while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute 'Models for an exit strategy' workshop (11-15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, would allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. This roadmap requires a global collaborative effort from the scientific community and policymakers, and has three parts: (i) improve estimation of key epidemiological parameters; (ii) understand sources of heterogeneity in populations; and (iii) focus on requirements for data collection, particularly in low-to-middle-income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health.",,doi:https://doi.org/10.1098/rspb.2020.1405; doi:https://doi.org/10.1098/rspb.2020.1405; html:https://europepmc.org/articles/PMC7575516; pdf:https://europepmc.org/articles/PMC7575516?pdf=render +36029521,https://doi.org/10.1093/ije/dyac171,Cohort Profile: The United Kingdom Research study into Ethnicity and COVID-19 outcomes in Healthcare workers (UK-REACH).,"Bryant L, Free RC, Woolf K, Melbourne C, Guyatt AL, John C, Gupta A, Gray LJ, Nellums L, Martin CA, McManus IC, Garwood C, Modhawdia V, Carr S, Wain LV, Tobin MD, Khunti K, Akubakar I, Pareek M, UK-REACH Collaborative Group+.",,International journal of epidemiology,2023,2023-02-01,Y,,,,,,pdf:https://academic.oup.com/ije/article-pdf/52/1/e38/49127215/dyac171.pdf; doi:https://doi.org/10.1093/ije/dyac171; html:https://europepmc.org/articles/PMC9452183; pdf:https://europepmc.org/articles/PMC9452183?pdf=render 37192798,https://doi.org/10.1136/bmjopen-2022-066398,Impact of pausing elective hip and knee replacement surgery during winter 2017 on subsequent service provision at a major NHS Trust: a descriptive observational study using interrupted time series.,"Jones T, Penfold C, Redaniel MT, Eyles E, Keen T, Elliott A, Blom AW, Judge A.",,BMJ open,2023,2023-05-16,Y,Knee; Hip; Human Resource Management; Orthopaedic & Trauma Surgery,,,"

Objectives

To explore the impact of a temporary cancellation of elective surgery in winter 2017 on trends in primary hip and knee replacement at a major National Health Service (NHS) Trust, and whether lessons can be learnt about efficient surgery provision.

Design and setting

Observational descriptive study using interrupted time series analysis of hospital records to explore trends in primary hip and knee replacement surgery at a major NHS Trust, as well as patient characteristics, 2016-2019.

Intervention

A temporary cancellation of elective services for 2 months in winter 2017.

Outcomes

NHS-funded hospital admissions for primary hip or knee replacement, length of stay and bed occupancy. Additionally, we explored the ratio of elective to emergency admissions at the Trust as a measure of elective capacity, and the ratio of public to private provision of NHS-funded hip and knee surgery.

Results

After winter 2017, there was a sustained reduction in the number of knee replacements, a decrease in the proportion of most deprived people having knee replacements and an increase in average age for knee replacement and comorbidity for both types of surgery. The ratio of public to private provision dropped after winter 2017, and elective capacity generally has reduced over time. There was clear seasonality in provision of elective surgery, with less complex patients admitted during winter.

Conclusions

Declining elective capacity and seasonality has a marked effect on the provision of joint replacement, despite efficiency improvements in hospital treatment. The Trust has outsourced less complex patients to independent providers, and/or treated them during winter when capacity is most limited. There is a need to explore whether these are strategies that could be used explicitly to maximise the use of limited elective capacity, provide benefit to patients and value for money for taxpayers.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/5/e066398.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-066398; html:https://europepmc.org/articles/PMC10193088; pdf:https://europepmc.org/articles/PMC10193088?pdf=render 37088955,https://doi.org/10.1177/02692163231167212,"Deaths at home, area-based deprivation and the effect of the Covid-19 pandemic: An analysis of mortality data across four nations.","Leniz J, Davies JM, Bone AE, Hocaoglu M, Verne J, Barclay S, Murtagh FEM, Fraser LK, Higginson IJ, Sleeman KE.",,Palliative medicine,2023,2023-04-23,Y,Mortality; Palliative care; Terminal Care; Inequalities; Place Of Death; Deprivation; Pandemics; Socio-economic Position; Covid-19,,,"

Background

The number and proportion of home deaths in the UK increased during the Covid-19 pandemic. It is not known whether these changes were experienced disproportionately by people from different socioeconomic groups.

Aim

To examine the association between home death and socioeconomic position during the Covid-19 pandemic, and how this changed between 2019 and 2020.

Design

Retrospective cohort study using population-based individual-level mortality data.

Setting/participants

All registered deaths in England, Wales, Scotland and Northern Ireland. The proportion of home deaths between 28th March and 31st December 2020 was compared with the same period in 2019. We used Poisson regression models to evaluate the association between decedent's area-based level of deprivation and risk of home death, as well as the interaction between deprivation and year of death, for each nation separately.

Results

Between the 28th March and 31st December 2020, 409,718 deaths were recorded in England, 46,372 in Scotland, 26,410 in Wales and 13,404 in Northern Ireland. All four nations showed an increase in the adjusted proportion of home deaths between 2019 and 2020, ranging from 21 to 28%. This increase was lowest for people living in the most deprived areas in all nations, with evidence of a deprivation gradient in England.

Conclusions

The Covid-19 pandemic exacerbated a previously described socioeconomic inequality in place of death in the UK. Further research to understand the reasons for this change and if this inequality has been sustained is needed.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10125882; doi:https://doi.org/10.1177/02692163231167212; html:https://europepmc.org/articles/PMC10125882; pdf:https://europepmc.org/articles/PMC10125882?pdf=render 35144240,https://doi.org/10.2196/32543,Artificial Intelligence-Enabled Social Media Analysis for Pharmacovigilance of COVID-19 Vaccinations in the United Kingdom: Observational Study.,"Hussain Z, Sheikh Z, Tahir A, Dashtipour K, Gogate M, Sheikh A, Hussain A.",,JMIR public health and surveillance,2022,2022-05-27,Y,Artificial intelligence; Vaccination; Public Health; Health Informatics; Natural Language Processing; Facebook; Social Media; Twitter; Sentiment Analysis; Infodemiology; Deep Learning; Covid-19,,,"

Background

The rollout of vaccines for COVID-19 in the United Kingdom started in December 2020. Uptake has been high, and there has been a subsequent reduction in infections, hospitalizations, and deaths among vaccinated individuals. However, vaccine hesitancy remains a concern, in particular relating to adverse effects following immunization (AEFIs). Social media analysis has the potential to inform policy makers about AEFIs being discussed by the public as well as public attitudes toward the national immunization campaign.

Objective

We sought to assess the frequency and nature of AEFI-related mentions on social media in the United Kingdom and to provide insights on public sentiments toward COVID-19 vaccines.

Methods

We extracted and analyzed over 121,406 relevant Twitter and Facebook posts, from December 8, 2020, to April 30, 2021. These were thematically filtered using a 2-step approach, initially using COVID-19-related keywords and then using vaccine- and manufacturer-related keywords. We identified AEFI-related keywords and modeled their word frequency to monitor their trends over 2-week periods. We also adapted and utilized our recently developed hybrid ensemble model, which combines state-of-the-art lexicon rule-based and deep learning-based approaches, to analyze sentiment trends relating to the main vaccines available in the United Kingdom.

Results

Our COVID-19 AEFI search strategy identified 46,762 unique Facebook posts by 14,346 users and 74,644 tweets (excluding retweets) by 36,446 users over the 4-month period. We identified an increasing trend in the number of mentions for each AEFI on social media over the study period. The most frequent AEFI mentions were found to be symptoms related to appetite (n=79,132, 14%), allergy (n=53,924, 9%), injection site (n=56,152, 10%), and clots (n=43,907, 8%). We also found some rarely reported AEFIs such as Bell palsy (n=11,909, 2%) and Guillain-Barre syndrome (n=9576, 2%) being discussed as frequently as more well-known side effects like headache (n=10,641, 2%), fever (n=12,707, 2%), and diarrhea (n=16,559, 3%). Overall, we found public sentiment toward vaccines and their manufacturers to be largely positive (58%), with a near equal split between negative (22%) and neutral (19%) sentiments. The sentiment trend was relatively steady over time and had minor variations, likely based on political and regulatory announcements and debates.

Conclusions

The most frequently discussed COVID-19 AEFIs on social media were found to be broadly consistent with those reported in the literature and by government pharmacovigilance. We also detected potential safety signals from our analysis that have been detected elsewhere and are currently being investigated. As such, we believe our findings support the use of social media analysis to provide a complementary data source to conventional knowledge sources being used for pharmacovigilance purposes.",,pdf:https://publichealth.jmir.org/2022/5/e32543/PDF; doi:https://doi.org/10.2196/32543; html:https://europepmc.org/articles/PMC9150729 @@ -418,8 +418,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 36476601,https://doi.org/10.1186/s12911-022-02055-6,Neural-signature methods for structured EHR prediction.,"Vauvelle A, Creed P, Denaxas S.",,BMC medical informatics and decision making,2022,2022-12-07,Y,Machine Learning; Electronic Healthcare Records; Signature Methods,,,"Models that can effectively represent structured Electronic Healthcare Records (EHR) are central to an increasing range of applications in healthcare. Due to the sequential nature of health data, Recurrent Neural Networks have emerged as the dominant component within state-of-the-art architectures. The signature transform represents an alternative modelling paradigm for sequential data. This transform provides a non-learnt approach to creating a fixed vector representation of temporal features and has shown strong performances across an increasing number of domains, including medical data. However, the signature method has not yet been applied to structured EHR data. To this end, we follow recent work that enables the signature to be used as a differentiable layer within a neural architecture enabling application in high dimensional domains where calculation would have previously been intractable. Using a heart failure prediction task as an exemplar, we provide an empirical evaluation of different variations of the signature method and compare against state-of-the-art baselines. This first application of neural-signature methods in real-world healthcare data shows a competitive performance when compared to strong baselines and thus warrants further investigation within the health domain.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-022-02055-6; doi:https://doi.org/10.1186/s12911-022-02055-6; html:https://europepmc.org/articles/PMC9730578; pdf:https://europepmc.org/articles/PMC9730578?pdf=render 32835195,https://doi.org/10.1016/s2589-7500(20)30134-5,The effects of physical distancing on population mobility during the COVID-19 pandemic in the UK.,"Drake TM, Docherty AB, Weiser TG, Yule S, Sheikh A, Harrison EM.",,The Lancet. Digital health,2020,2020-06-12,Y,,,,,,doi:https://doi.org/10.1016/s2589-7500(20)30134-5; doi:https://doi.org/10.1016/S2589-7500(20)30134-5; html:https://europepmc.org/articles/PMC7292602; pdf:https://europepmc.org/articles/PMC7292602?pdf=render 35231023,https://doi.org/10.1371/journal.pmed.1003907,Changes in social contacts in England during the COVID-19 pandemic between March 2020 and March 2021 as measured by the CoMix survey: A repeated cross-sectional study.,"Gimma A, Munday JD, Wong KLM, Coletti P, van Zandvoort K, Prem K, CMMID COVID-19 working group, Klepac P, Rubin GJ, Funk S, Edmunds WJ, Jarvis CI.",,PLoS medicine,2022,2022-03-01,Y,,,,"

Background

During the Coronavirus Disease 2019 (COVID-19) pandemic, the United Kingdom government imposed public health policies in England to reduce social contacts in hopes of curbing virus transmission. We conducted a repeated cross-sectional study to measure contact patterns weekly from March 2020 to March 2021 to estimate the impact of these policies, covering 3 national lockdowns interspersed by periods of less restrictive policies.

Methods and findings

The repeated cross-sectional survey data were collected using online surveys of representative samples of the UK population by age and gender. Survey participants were recruited by the online market research company Ipsos MORI through internet-based banner and social media ads and email campaigns. The participant data used for this analysis are restricted to those who reported living in England. We calculated the mean daily contacts reported using a (clustered) bootstrap and fitted a censored negative binomial model to estimate age-stratified contact matrices and estimate proportional changes to the basic reproduction number under controlled conditions using the change in contacts as a scaling factor. To put the findings in perspective, we discuss contact rates recorded throughout the year in terms of previously recorded rates from the POLYMOD study social contact study. The survey recorded 101,350 observations from 19,914 participants who reported 466,710 contacts over 53 weeks. We observed changes in social contact patterns in England over time and by participants' age, personal risk factors, and perception of risk. The mean reported contacts for adults 18 to 59 years old ranged between 2.39 (95% confidence interval [CI] 2.20 to 2.60) contacts and 4.93 (95% CI 4.65 to 5.19) contacts during the study period. The mean contacts for school-age children (5 to 17 years old) ranged from 3.07 (95% CI 2.89 to 3.27) to 15.11 (95% CI 13.87 to 16.41). This demonstrates a sustained decrease in social contacts compared to a mean of 11.08 (95% CI 10.54 to 11.57) contacts per participant in all age groups combined as measured by the POLYMOD social contact study in 2005 to 2006. Contacts measured during periods of lockdowns were lower than in periods of eased social restrictions. The use of face coverings outside the home has remained high since the government mandated use in some settings in July 2020. The main limitations of this analysis are the potential for selection bias, as participants are recruited through internet-based campaigns, and recall bias, in which participants may under- or overreport the number of contacts they have made.

Conclusions

In this study, we observed that recorded contacts reduced dramatically compared to prepandemic levels (as measured in the POLYMOD study), with changes in reported contacts correlated with government interventions throughout the pandemic. Despite easing of restrictions in the summer of 2020, the mean number of reported contacts only returned to about half of that observed prepandemic at its highest recorded level. The CoMix survey provides a unique repeated cross-sectional data set for a full year in England, from the first day of the first lockdown, for use in statistical analyses and mathematical modelling of COVID-19 and other diseases.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003907&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003907; html:https://europepmc.org/articles/PMC8887739; pdf:https://europepmc.org/articles/PMC8887739?pdf=render -38238056,https://doi.org/10.1136/bmjopen-2023-076711,"Cohort profile: Born in Wales-a birth cohort with maternity, parental and child data linkage for life course research in Wales, UK.","Jones H, Seaborne MJ, Kennedy NL, James M, Dredge S, Bandyopadhyay A, Battaglia A, Davies S, Brophy S.",,BMJ open,2024,2024-01-18,Y,epidemiology; Public Health; Community Child Health; Surveys And Questionnaires,,,"

Purpose

Using Wales's national dataset for maternity and births as a core dataset, we have linked related datasets to create a more complete and comprehensive entire country birth cohort. Data of anonymised identified persons are linked on the individual level to data from health, social care and education data within the Secure Anonymised Information Linkage (SAIL) Databank. Each individual is assigned an encrypted Anonymised Linking Field; this field is used to link anonymised individuals across datasets. We present the descriptive data available in the core dataset, and the future expansion plans for the database beyond its initial development stage.

Participants

Descriptive information from 2011 to 2023 has been gathered from the National Community Child Health Database (NCCHD) in SAIL. This comprehensive dataset comprises over 400 000 child electronic records. Additionally, survey responses about health and well-being from a cross-section of the population including 2500 parents and 30 000 primary school children have been collected for enriched personal responses and linkage to the data spine.

Findings to date

The electronic cohort comprises all children born in Wales since 2011, with follow-up conducted until they finish primary school at age 11. The child cohort is 51%: 49% female: male, and 7.8% are from ethnic minority backgrounds. When considering age distribution, 26.8% of children are under the age of 5, while 63.2% fall within the age range of 5-11.

Future plans

Born in Wales will expand by 30 000 new births annually in Wales (in NCCHD), while including follow-up data of children and parents already in the database. Supplementary datasets complement the existing linkage, including primary care, hospital data, educational attainment and social care. Future research includes exploring the long-term implications of COVID-19 on child health and development, and examining the impact of parental work environment on child health and development.",,pdf:https://bmjopen.bmj.com/content/bmjopen/14/1/e076711.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-076711; html:https://europepmc.org/articles/PMC10806724; pdf:https://europepmc.org/articles/PMC10806724?pdf=render 33419870,https://doi.org/10.1136/bmjhci-2020-100254,Network graph representation of COVID-19 scientific publications to aid knowledge discovery.,"Cernile G, Heritage T, Sebire NJ, Gordon B, Schwering T, Kazemlou S, Borecki Y.",,BMJ health & care informatics,2021,2021-01-01,Y,Health care; Medical Informatics; Information Science; Bmj Health Informatics,,,"

Introduction

Numerous scientific journal articles related to COVID-19 have been rapidly published, making navigation and understanding of relationships difficult.

Methods

A graph network was constructed from the publicly available COVID-19 Open Research Dataset (CORD-19) of COVID-19-related publications using an engine leveraging medical knowledge bases to identify discrete medical concepts and an open-source tool (Gephi) to visualise the network.

Results

The network shows connections between diseases, medications and procedures identified from the title and abstract of 195 958 COVID-19-related publications (CORD-19 Dataset). Connections between terms with few publications, those unconnected to the main network and those irrelevant were not displayed. Nodes were coloured by knowledge base and the size of the node related to the number of publications containing the term. The data set and visualisations were made publicly accessible via a webtool.

Conclusion

Knowledge management approaches (text mining and graph networks) can effectively allow rapid navigation and exploration of entity inter-relationships to improve understanding of diseases such as COVID-19.",,pdf:https://informatics.bmj.com/content/bmjhci/28/1/e100254.full.pdf; doi:https://doi.org/10.1136/bmjhci-2020-100254; html:https://europepmc.org/articles/PMC7798427; pdf:https://europepmc.org/articles/PMC7798427?pdf=render +38238056,https://doi.org/10.1136/bmjopen-2023-076711,"Cohort profile: Born in Wales-a birth cohort with maternity, parental and child data linkage for life course research in Wales, UK.","Jones H, Seaborne MJ, Kennedy NL, James M, Dredge S, Bandyopadhyay A, Battaglia A, Davies S, Brophy S.",,BMJ open,2024,2024-01-18,Y,epidemiology; Public Health; Community Child Health; Surveys And Questionnaires,,,"

Purpose

Using Wales's national dataset for maternity and births as a core dataset, we have linked related datasets to create a more complete and comprehensive entire country birth cohort. Data of anonymised identified persons are linked on the individual level to data from health, social care and education data within the Secure Anonymised Information Linkage (SAIL) Databank. Each individual is assigned an encrypted Anonymised Linking Field; this field is used to link anonymised individuals across datasets. We present the descriptive data available in the core dataset, and the future expansion plans for the database beyond its initial development stage.

Participants

Descriptive information from 2011 to 2023 has been gathered from the National Community Child Health Database (NCCHD) in SAIL. This comprehensive dataset comprises over 400 000 child electronic records. Additionally, survey responses about health and well-being from a cross-section of the population including 2500 parents and 30 000 primary school children have been collected for enriched personal responses and linkage to the data spine.

Findings to date

The electronic cohort comprises all children born in Wales since 2011, with follow-up conducted until they finish primary school at age 11. The child cohort is 51%: 49% female: male, and 7.8% are from ethnic minority backgrounds. When considering age distribution, 26.8% of children are under the age of 5, while 63.2% fall within the age range of 5-11.

Future plans

Born in Wales will expand by 30 000 new births annually in Wales (in NCCHD), while including follow-up data of children and parents already in the database. Supplementary datasets complement the existing linkage, including primary care, hospital data, educational attainment and social care. Future research includes exploring the long-term implications of COVID-19 on child health and development, and examining the impact of parental work environment on child health and development.",,pdf:https://bmjopen.bmj.com/content/bmjopen/14/1/e076711.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-076711; html:https://europepmc.org/articles/PMC10806724; pdf:https://europepmc.org/articles/PMC10806724?pdf=render 33758017,https://doi.org/10.1126/science.abf9648,The impact of population-wide rapid antigen testing on SARS-CoV-2 prevalence in Slovakia.,"Pavelka M, Van-Zandvoort K, Abbott S, Sherratt K, Majdan M, CMMID COVID-19 working group, Inštitút Zdravotných Analýz, Jarčuška P, Krajčí M, Flasche S, Funk S.",,"Science (New York, N.Y.)",2021,2021-03-23,Y,,,,"Slovakia conducted multiple rounds of population-wide rapid antigen testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2020, combined with a period of additional contact restrictions. Observed prevalence decreased by 58% (95% confidence interval: 57 to 58%) within 1 week in the 45 counties that were subject to two rounds of mass testing, an estimate that remained robust when adjusting for multiple potential confounders. Adjusting for epidemic growth of 4.4% (1.1 to 6.9%) per day preceding the mass testing campaign, the estimated decrease in prevalence compared with a scenario of unmitigated growth was 70% (67 to 73%). Modeling indicated that this decrease could not be explained solely by infection control measures but required the addition of the isolation and quarantine of household members of those testing positive.",,pdf:https://www.science.org/cms/asset/e974db95-138d-4a9f-aa91-2f8f6c705f36/pap.pdf; doi:https://doi.org/10.1126/science.abf9648; html:https://europepmc.org/articles/PMC8139426; pdf:https://europepmc.org/articles/PMC8139426?pdf=render 38434747,https://doi.org/10.12688/wellcomeopenres.19858.1,"Interpreting pathology test result values with comparators (<, >) in Electronic Health Records research: an OpenSAFELY short data report.","Curtis HJ, Fisher L, Evans D, OpenSAFELY Collaborative, Bacon S, Mehrkar A, Goldacre B, MacKenna B.",,Wellcome open research,2023,2023-11-22,Y,Pathology; Kidney function tests; Electronic Health Records,,,"

Background

Numeric results of pathology tests are sometimes returned as a range rather than a precise value, e.g. ""<10"". In health data research, test result values above or below clinical threshold values are often used to categorise patients into groups; however comparators (<, > etc) are typically stored separately to the numeric values and often ignored, but may influence interpretation.

Methods

With the approval of NHS England we used routine clinical data from 24 million patients in OpenSAFELY to identify pathology tests with comparators commonly attached to result values. For each test we report: the proportion returned with comparators present, split by comparator type and geographic region; the specific numeric result values returned with comparators, and the associated reference limits.

Results

We identified 11 common test codes where at least one in four results had comparators. Three codes related to glomerular filtration rate (GFR) tests/calculations, with 31-45% of results returned with ""≥"" comparators. At least 90% of tests with numeric values 60 and 90 represented ranges (≥60 and ≥90 respectively) rather than exact values. The other tests - four blood tests (Nucleated red blood cell count, Plasma C reactive protein, Tissue transglutaminase immunoglobulin A, and Rheumatoid factor), two urine tests (albumin/microalbumin) and two faecal tests (calprotectin and quantitative faecal immunochemical test) - were returned with ""≤"" comparators (29-86%).

Conclusions

Comparators appear commonly in certain pathology tests in electronic health records. For most common affected tests, we expect there to be minimal implications for researchers for most use-cases. However, care should be taken around whether results falling exactly on clinical threshold values should be considered ""normal"" or ""abnormal"". Results from GFR tests/calculations cannot reliably distinguish between mild kidney disease (60-<90) versus healthy kidney function (90+). More broadly, health data researchers using numeric test result values should consider the impact of comparators.",,doi:https://doi.org/10.12688/wellcomeopenres.19858.1; html:https://europepmc.org/articles/PMC10904973; pdf:https://europepmc.org/articles/PMC10904973?pdf=render 36426419,https://doi.org/10.1111/hsc.14109,"""I don't mean to be rude, but could you put a mask on while I'm here?"" A qualitative study of risks experienced by domiciliary care workers in Wales during the COVID-19 pandemic.","Prout H, Lugg-Widger FV, Brookes-Howell L, Cannings-John R, Akbari A, John A, Thomas DR, Robling M.",,Health & social care in the community,2022,2022-11-24,Y,Qualitative; risk; Social Care; Covid-19; Domiciliary Care Workers,,,"Domiciliary care workers (DCWs) continued to provide care to adults in their own homes throughout the COVID-19 pandemic. The evidence of the impact of COVID-19 on health outcomes of DCWs is currently mixed. The OSCAR study will quantify the impact of COVID-19 upon health outcomes of DCWs in Wales, explore causes of variation and extrapolate to the rest of the UK DCW population. An embedded qualitative study aimed to explore DCW experiences during the pandemic, including factors that may have varied risk of exposure to COVID-19 and adverse health and wellbeing outcomes. Registered DCWs working throughout Wales were invited to participate in a semi-structured telephone interview. 24 DCWs were interviewed between February and July 2021. Themes were identified through inductive analysis using thematic coding. Several themes emerged relating to risk of exposure to COVID-19. First, general changes to the role of the DCW during the pandemic were identified. Second, practical challenges for DCWs in the workplace were reported, including staff shortages, clients and families not following safety procedures, initial shortages of personal protective equipment (PPE), DCW criticism of standard use PPE, client difficulty with PPE and management of rapid antigen testing. Third, lack of government/employer preparation for a pandemic was described, including the reorganisation of staff clients and services, inadequate or confusing information for many DCWs, COVID-19 training and the need for improved practical instruction and limited official standard risk assessments for DCWs. Pressure to attend work and perceptions of COVID-19 risk and vaccination was also reported. In summary, this paper describes the risk factors associated with working during the pandemic. We have mapped recommendations for each problem using these qualitative findings including tailored training and better support for isolated team members and identified the required changes at several socio-ecological levels.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/hsc.14109; doi:https://doi.org/10.1111/hsc.14109; html:https://europepmc.org/articles/PMC10100139; pdf:https://europepmc.org/articles/PMC10100139?pdf=render @@ -444,8 +444,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 32814572,https://doi.org/10.1186/s12916-020-01712-9,The effect of travel restrictions on the geographical spread of COVID-19 between large cities in China: a modelling study.,"Quilty BJ, Diamond C, Liu Y, Gibbs H, Russell TW, Jarvis CI, Prem K, Pearson CAB, Clifford S, Flasche S, CMMID COVID-19 working group, Klepac P, Eggo RM, Jit M.",,BMC medicine,2020,2020-08-19,Y,China; Wuhan; Mobility; Delay; Outbreaks; Modelling; Travel Restrictions; Covid-19; Sars-cov-2; Cordon Sanitaire,,,"

Background

To contain the spread of COVID-19, a cordon sanitaire was put in place in Wuhan prior to the Lunar New Year, on 23 January 2020. We assess the efficacy of the cordon sanitaire to delay the introduction and onset of local transmission of COVID-19 in other major cities in mainland China.

Methods

We estimated the number of infected travellers from Wuhan to other major cities in mainland China from November 2019 to February 2020 using previously estimated COVID-19 prevalence in Wuhan and publicly available mobility data. We focused on Beijing, Chongqing, Hangzhou, and Shenzhen as four representative major cities to identify the potential independent contribution of the cordon sanitaire and holiday travel. To do this, we simulated outbreaks generated by infected arrivals in these destination cities using stochastic branching processes. We also modelled the effect of the cordon sanitaire in combination with reduced transmissibility scenarios to simulate the effect of local non-pharmaceutical interventions.

Results

We find that in the four cities, given the potentially high prevalence of COVID-19 in Wuhan between December 2019 and early January 2020, local transmission may have been seeded as early as 1-8 January 2020. By the time the cordon sanitaire was imposed, infections were likely in the thousands. The cordon sanitaire alone did not substantially affect the epidemic progression in these cities, although it may have had some effect in smaller cities. Reduced transmissibility resulted in a notable decrease in the incidence of infection in the four studied cities.

Conclusions

Our results indicate that sustained transmission was likely occurring several weeks prior to the implementation of the cordon sanitaire in four major cities of mainland China and that the observed decrease in incidence was likely attributable to other non-pharmaceutical, transmission-reducing interventions.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01712-9; doi:https://doi.org/10.1186/s12916-020-01712-9; html:https://europepmc.org/articles/PMC7437104; pdf:https://europepmc.org/articles/PMC7437104?pdf=render 33012285,https://doi.org/10.1186/s12916-020-01779-4,The impact of COVID-19 control measures on social contacts and transmission in Kenyan informal settlements.,"Quaife M, van Zandvoort K, Gimma A, Shah K, McCreesh N, Prem K, Barasa E, Mwanga D, Kangwana B, Pinchoff J, CMMID COVID-19 Working Group, Edmunds WJ, Jarvis CI, Austrian K.",,BMC medicine,2020,2020-10-05,Y,Social Contacts; Covid-19; Sars-cov-2; Physical Distancing,,,"

Background

Many low- and middle-income countries have implemented control measures against coronavirus disease 2019 (COVID-19). However, it is not clear to what extent these measures explain the low numbers of recorded COVID-19 cases and deaths in Africa. One of the main aims of control measures is to reduce respiratory pathogen transmission through direct contact with others. In this study, we collect contact data from residents of informal settlements around Nairobi, Kenya, to assess if control measures have changed contact patterns, and estimate the impact of changes on the basic reproduction number (R0).

Methods

We conducted a social contact survey with 213 residents of five informal settlements around Nairobi in early May 2020, 4 weeks after the Kenyan government introduced enhanced physical distancing measures and a curfew between 7 pm and 5 am. Respondents were asked to report all direct physical and non-physical contacts made the previous day, alongside a questionnaire asking about the social and economic impact of COVID-19 and control measures. We examined contact patterns by demographic factors, including socioeconomic status. We described the impact of COVID-19 and control measures on income and food security. We compared contact patterns during control measures to patterns from non-pandemic periods to estimate the change in R0.

Results

We estimate that control measures reduced physical contacts by 62% and non-physical contacts by either 63% or 67%, depending on the pre-COVID-19 comparison matrix used. Masks were worn by at least one person in 92% of contacts. Respondents in the poorest socioeconomic quintile reported 1.5 times more contacts than those in the richest. Eighty-six percent of respondents reported a total or partial loss of income due to COVID-19, and 74% reported eating less or skipping meals due to having too little money for food.

Conclusion

COVID-19 control measures have had a large impact on direct contacts and therefore transmission, but have also caused considerable economic and food insecurity. Reductions in R0 are consistent with the comparatively low epidemic growth in Kenya and other sub-Saharan African countries that implemented similar, early control measures. However, negative and inequitable impacts on economic and food security may mean control measures are not sustainable in the longer term.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01779-4; doi:https://doi.org/10.1186/s12916-020-01779-4; html:https://europepmc.org/articles/PMC7533154; pdf:https://europepmc.org/articles/PMC7533154?pdf=render 32997638,https://doi.org/10.1109/jbhi.2020.3027987,A Novel Intelligent Computational Approach to Model Epidemiological Trends and Assess the Impact of Non-Pharmacological Interventions for COVID-19.,"Ren J, Yan Y, Zhao H, Ma P, Zabalza J, Hussain Z, Luo S, Dai Q, Zhao S, Sheikh A, Hussain A, Li H.",,IEEE journal of biomedical and health informatics,2020,2020-12-04,Y,,,,"The novel coronavirus disease 2019 (COVID-19) pandemic has led to a worldwide crisis in public health. It is crucial we understand the epidemiological trends and impact of non-pharmacological interventions (NPIs), such as lockdowns for effective management of the disease and control of its spread. We develop and validate a novel intelligent computational model to predict epidemiological trends of COVID-19, with the model parameters enabling an evaluation of the impact of NPIs. By representing the number of daily confirmed cases (NDCC) as a time-series, we assume that, with or without NPIs, the pattern of the pandemic satisfies a series of Gaussian distributions according to the central limit theorem. The underlying pandemic trend is first extracted using a singular spectral analysis (SSA) technique, which decomposes the NDCC time series into the sum of a small number of independent and interpretable components such as a slow varying trend, oscillatory components and structureless noise. We then use a mixture of Gaussian fitting (GF) to derive a novel predictive model for the SSA extracted NDCC incidence trend, with the overall model termed SSA-GF. Our proposed model is shown to accurately predict the NDCC trend, peak daily cases, the length of the pandemic period, the total confirmed cases and the associated dates of the turning points on the cumulated NDCC curve. Further, the three key model parameters, specifically, the amplitude (alpha), mean (mu), and standard deviation (sigma) are linked to the underlying pandemic patterns, and enable a directly interpretable evaluation of the impact of NPIs, such as strict lockdowns and travel restrictions. The predictive model is validated using available data from China and South Korea, and new predictions are made, partially requiring future validation, for the cases of Italy, Spain, the UK and the USA. Comparative results demonstrate that the introduction of consistent control measures across countries can lead to development of similar parametric models, reflected in particular by relative variations in their underlying sigma, alpha and mu values. The paper concludes with a number of open questions and outlines future research directions.",,pdf:https://ieeexplore.ieee.org/ielx7/6221020/9281055/09210178.pdf; doi:https://doi.org/10.1109/JBHI.2020.3027987; html:https://europepmc.org/articles/PMC8545177; pdf:https://europepmc.org/articles/PMC8545177?pdf=render -35476839,https://doi.org/10.1371/journal.pone.0266967,"Healthcare contacts with self-harm during COVID-19: An e-cohort whole-population-based study using individual-level linked routine electronic health records in Wales, UK, 2016-March 2021.","DelPozo-Banos M, Lee SC, Friedmann Y, Akbari A, Torabi F, Lloyd K, Lyons RA, John A.",,PloS one,2022,2022-04-27,Y,,,,"

Introduction

Reduced rates of help seeking by those who self-harmed during the COVID-19 pandemic have been reported.

Objectives

To understand changes in healthcare service contacts for self-harm during the COVID-19 pandemic across primary, emergency and secondary care.

Methods

This retrospective cohort study used routine electronic healthcare data for Wales, United Kingdom, from 2016 to March 14, 2021. Population-based data from primary care, emergency departments and hospital admissions were linked at individual-level. All Welsh residents aged ≥10 years over the study period were included in the study. Primary, emergency and secondary care contacts with self-harm at any time between 2016 and March 14, 2021 were identified. Outcomes were counts, incidence, prevalence and proportion of self-harm contacts relative to all contacts in each and all settings, as well as the proportion of people contacting one or more settings with self-harm. Weekly trends were modelled using generalised estimated equations, with differences between 2020 (to March 2021) and comparison years 2016-2018 (to March 2017-2019) quantified using difference in differences, from which mean rate of odds ratios (μROR) across years was reported.

Results

The study included 3,552,210 individuals over the study period. Self-harm contacts reduced across services in March and December 2020 compared to previous years. Primary care contacts with self-harm reduced disproportionately compared to non-self-harm contacts (μROR = 0.7, p<0.05), while their proportion increased in emergency departments during April 2020 (μROR = 1.3, p<0.05 in 2/3 comparison years) and hospital admissions during April-May 2020 (μROR = 1.2, p<0.05 in 2/3 comparison years). Despite this, those who self-harmed in April 2020 were more likely to be seen in primary care than other settings compared to previous years (μROR = 1.2, p<0.05). A lower proportion of those with self-harm contacts in emergency departments were subsequently admitted to hospital in December 2020 compared to previous years (μROR = 0.5, p<0.05).

Conclusions

These findings suggest that those who self-harmed during the COVID-19 pandemic may have been less likely to seek help, and those who did so faced more stringent criteria for admission. Communications encouraging those who self-harm to seek help during pandemics may be beneficial. However, this needs to be supported by maintained provision of mental health services.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0266967&type=printable; doi:https://doi.org/10.1371/journal.pone.0266967; html:https://europepmc.org/articles/PMC9045644; pdf:https://europepmc.org/articles/PMC9045644?pdf=render 32371477,https://doi.org/10.1126/science.abc0473,Rapid implementation of mobile technology for real-time epidemiology of COVID-19.,"Drew DA, Nguyen LH, Steves CJ, Menni C, Freydin M, Varsavsky T, Sudre CH, Cardoso MJ, Ourselin S, Wolf J, Spector TD, Chan AT, COPE Consortium.",,"Science (New York, N.Y.)",2020,2020-05-05,Y,,,,"The rapid pace of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents challenges to the robust collection of population-scale data to address this global health crisis. We established the COronavirus Pandemic Epidemiology (COPE) Consortium to unite scientists with expertise in big data research and epidemiology to develop the COVID Symptom Study, previously known as the COVID Symptom Tracker, mobile application. This application-which offers data on risk factors, predictive symptoms, clinical outcomes, and geographical hotspots-was launched in the United Kingdom on 24 March 2020 and the United States on 29 March 2020 and has garnered more than 2.8 million users as of 2 May 2020. Our initiative offers a proof of concept for the repurposing of existing approaches to enable rapidly scalable epidemiologic data collection and analysis, which is critical for a data-driven response to this public health challenge.","Drew et al. decribe the use of a smart-phone App to track Covid-19 symptoms reported by users to track, in real time, information on newly infected individuals. It has been launched in the UK and US and has 2.8 million users and is used to rapidly identify emerging hot spots for infection.",pdf:https://www.science.org/cms/asset/fb31d61b-4be3-483a-b040-2ee970dfb432/pap.pdf; doi:https://doi.org/10.1126/science.abc0473; html:https://europepmc.org/articles/PMC7200009; pdf:https://europepmc.org/articles/PMC7200009?pdf=render +35476839,https://doi.org/10.1371/journal.pone.0266967,"Healthcare contacts with self-harm during COVID-19: An e-cohort whole-population-based study using individual-level linked routine electronic health records in Wales, UK, 2016-March 2021.","DelPozo-Banos M, Lee SC, Friedmann Y, Akbari A, Torabi F, Lloyd K, Lyons RA, John A.",,PloS one,2022,2022-04-27,Y,,,,"

Introduction

Reduced rates of help seeking by those who self-harmed during the COVID-19 pandemic have been reported.

Objectives

To understand changes in healthcare service contacts for self-harm during the COVID-19 pandemic across primary, emergency and secondary care.

Methods

This retrospective cohort study used routine electronic healthcare data for Wales, United Kingdom, from 2016 to March 14, 2021. Population-based data from primary care, emergency departments and hospital admissions were linked at individual-level. All Welsh residents aged ≥10 years over the study period were included in the study. Primary, emergency and secondary care contacts with self-harm at any time between 2016 and March 14, 2021 were identified. Outcomes were counts, incidence, prevalence and proportion of self-harm contacts relative to all contacts in each and all settings, as well as the proportion of people contacting one or more settings with self-harm. Weekly trends were modelled using generalised estimated equations, with differences between 2020 (to March 2021) and comparison years 2016-2018 (to March 2017-2019) quantified using difference in differences, from which mean rate of odds ratios (μROR) across years was reported.

Results

The study included 3,552,210 individuals over the study period. Self-harm contacts reduced across services in March and December 2020 compared to previous years. Primary care contacts with self-harm reduced disproportionately compared to non-self-harm contacts (μROR = 0.7, p<0.05), while their proportion increased in emergency departments during April 2020 (μROR = 1.3, p<0.05 in 2/3 comparison years) and hospital admissions during April-May 2020 (μROR = 1.2, p<0.05 in 2/3 comparison years). Despite this, those who self-harmed in April 2020 were more likely to be seen in primary care than other settings compared to previous years (μROR = 1.2, p<0.05). A lower proportion of those with self-harm contacts in emergency departments were subsequently admitted to hospital in December 2020 compared to previous years (μROR = 0.5, p<0.05).

Conclusions

These findings suggest that those who self-harmed during the COVID-19 pandemic may have been less likely to seek help, and those who did so faced more stringent criteria for admission. Communications encouraging those who self-harm to seek help during pandemics may be beneficial. However, this needs to be supported by maintained provision of mental health services.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0266967&type=printable; doi:https://doi.org/10.1371/journal.pone.0266967; html:https://europepmc.org/articles/PMC9045644; pdf:https://europepmc.org/articles/PMC9045644?pdf=render 35151397,https://doi.org/10.1016/s0140-6736(22)00163-5,"Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2022,2022-02-01,Y,,,,"

Background

Casirivimab and imdevimab are non-competing monoclonal antibodies that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike glycoprotein, blocking viral entry into host cells. We aimed to evaluate the efficacy and safety of casirivimab and imdevimab administered in combination in patients admitted to hospital with COVID-19.

Methods

RECOVERY is a randomised, controlled, open-label platform trial comparing several possible treatments with usual care in patients admitted to hospital with COVID-19. 127 UK hospitals took part in the evaluation of casirivimab and imdevimab. Eligible participants were any patients aged at least 12 years admitted to hospital with clinically suspected or laboratory-confirmed SARS-CoV-2 infection. Participants were randomly assigned (1:1) to either usual standard of care alone or usual care plus casirivimab 4 g and imdevimab 4 g administered together in a single intravenous infusion. Investigators and data assessors were masked to analyses of the outcome data during the trial. The primary outcome was 28-day all-cause mortality assessed by intention to treat, first only in patients without detectable antibodies to SARS-CoV-2 infection at randomisation (ie, those who were seronegative) and then in the overall population. Safety was assessed in all participants who received casirivimab and imdevimab. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between Sept 18, 2020, and May 22, 2021, 9785 patients enrolled in RECOVERY were eligible for casirivimab and imdevimab, of which 4839 were randomly assigned to casirivimab and imdevimab plus usual care and 4946 to usual care alone. 3153 (32%) of 9785 patients were seronegative, 5272 (54%) were seropositive, and 1360 (14%) had unknown baseline antibody status. 812 (8%) patients were known to have received at least one dose of a SARS-CoV-2 vaccine. In the primary efficacy population of seronegative patients, 396 (24%) of 1633 patients allocated to casirivimab and imdevimab versus 452 (30%) of 1520 patients allocated to usual care died within 28 days (rate ratio [RR] 0·79, 95% CI 0·69-0·91; p=0·0009). In an analysis of all randomly assigned patients (regardless of baseline antibody status), 943 (19%) of 4839 patients allocated to casirivimab and imdevimab versus 1029 (21%) of 4946 patients allocated to usual care died within 28 days (RR 0·94, 95% CI 0·86-1·02; p=0·14). The proportional effect of casirivimab and imdevimab on mortality differed significantly between seropositive and seronegative patients (p value for heterogeneity=0·002). There were no deaths attributed to the treatment, or meaningful between-group differences in the pre-specified safety outcomes of cause-specific mortality, cardiac arrhythmia, thrombosis, or major bleeding events. Serious adverse reactions reported in seven (<1%) participants were believed by the local investigator to be related to treatment with casirivimab and imdevimab.

Interpretation

In patients admitted to hospital with COVID-19, the monoclonal antibody combination of casirivimab and imdevimab reduced 28-day mortality in patients who were seronegative (and therefore had not mounted their own humoral immune response) at baseline but not in those who were seropositive at baseline.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/95149/5/1-s2.0-S0140673622001635-main.pdf; doi:https://doi.org/10.1016/S0140-6736(22)00163-5; html:https://europepmc.org/articles/PMC8830904 32502389,https://doi.org/10.1016/s2468-2667(20)30133-x,"Effects of non-pharmaceutical interventions on COVID-19 cases, deaths, and demand for hospital services in the UK: a modelling study.","Davies NG, Kucharski AJ, Eggo RM, Gimma A, Edmunds WJ, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 working group.",,The Lancet. Public health,2020,2020-06-02,Y,,,,"

Background

Non-pharmaceutical interventions have been implemented to reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the UK. Projecting the size of an unmitigated epidemic and the potential effect of different control measures has been crucial to support evidence-based policy making during the early stages of the epidemic. This study assesses the potential impact of different control measures for mitigating the burden of COVID-19 in the UK.

Methods

We used a stochastic age-structured transmission model to explore a range of intervention scenarios, tracking 66·4 million people aggregated to 186 county-level administrative units in England, Wales, Scotland, and Northern Ireland. The four base interventions modelled were school closures, physical distancing, shielding of people aged 70 years or older, and self-isolation of symptomatic cases. We also modelled the combination of these interventions, as well as a programme of intensive interventions with phased lockdown-type restrictions that substantially limited contacts outside of the home for repeated periods. We simulated different triggers for the introduction of interventions, and estimated the impact of varying adherence to interventions across counties. For each scenario, we projected estimated new cases over time, patients requiring inpatient and critical care (ie, admission to the intensive care units [ICU]) treatment, and deaths, and compared the effect of each intervention on the basic reproduction number, R0.

Findings

We projected a median unmitigated burden of 23 million (95% prediction interval 13-30) clinical cases and 350 000 deaths (170 000-480 000) due to COVID-19 in the UK by December, 2021. We found that the four base interventions were each likely to decrease R0, but not sufficiently to prevent ICU demand from exceeding health service capacity. The combined intervention was more effective at reducing R0, but only lockdown periods were sufficient to bring R0 near or below 1; the most stringent lockdown scenario resulted in a projected 120 000 cases (46 000-700 000) and 50 000 deaths (9300-160 000). Intensive interventions with lockdown periods would need to be in place for a large proportion of the coming year to prevent health-care demand exceeding availability.

Interpretation

The characteristics of SARS-CoV-2 mean that extreme measures are probably required to bring the epidemic under control and to prevent very large numbers of deaths and an excess of demand on hospital beds, especially those in ICUs.

Funding

Medical Research Council.","The paper identifies the following; This paper identifies the influence of different interventions on COVID on cases, deaths, and demands for hospital services in the UK. This was achieved utilising modelling techniques. The paper concludes that the characteristics of SARS-CoV-2 mean that extreme measures are probably required to bring the epidemic under control and to prevent very large numbers of deaths and an excess of demand on hospital beds, especially those in ICUs. However, Biobank is not very representative of age, ethniticity and deprivation.",pdf:https://europepmc.org/articles/pmc7266572?pdf=render; doi:https://doi.org/10.1016/S2468-2667(20)30133-X; html:https://europepmc.org/articles/PMC7266572; pdf:https://europepmc.org/articles/PMC7266572?pdf=render 37124165,https://doi.org/10.1016/j.ufug.2023.127934,"Effects of the onset of the COVID-19 pandemic restrictions on park crime in London, England: An interrupted time series analysis.","Hajna S, Cummins S.",,Urban forestry & urban greening,2023,2023-04-11,Y,Parks; Crimes; Covid-19,,,"

Introduction

Park crimes may have increased during the COVID-19 pandemic as a result of lockdowns that limited the number of capable guardians in public spaces. Despite this, the impacts of the lockdowns on park crimes remain unknown. To help us understand the societal impacts of policies implemented during this period, we assessed how the onset of the COVID-19 restrictions impacted urban park crime levels in London, England.

Methods

We identified crimes that occurred in publicly accessible parks and gardens in the Greater London Authority (England, UK) between March 1, 2019 and February 28, 2021 by overlaying open-access crime data with greenspace data supplied by the Greater Information for Greater London service. Using interrupted time series analyses, we estimated seasonality-adjusted associations between the onset of COVID-19 restrictions and park crimes.

Results

Overall (1565.7, 95% confidence intervals [CI] 1021.9 to 2109.5) and antisocial behaviour crimes (1772.7, 95% CI 823.6-2721.7) increased in London parks during the first full month of COVID-19 restrictions (April 2020). There were no notable trends in park crimes in London prior to the onset of restrictions, but overall and antisocial behaviour crimes decreased after the onset of restrictions at a rate of 156.4 (95% CI -220.25 to -92.51) and 164.7 (95% CI -280.68 to -48.74) crimes/months, respectively.

Conclusions

Overall park crimes increased during the first full month of the COVID-19 restrictions, largely driven by an increase in antisocial behaviours. Additional research is needed to identify the specific misdemeanours that accounted for this rise in antisocial behaviours and to investigate their downstream impacts (e.g. increases in policing costs or decreases in perceived park safety).",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10088280; doi:https://doi.org/10.1016/j.ufug.2023.127934; html:https://europepmc.org/articles/PMC10088280; pdf:https://europepmc.org/articles/PMC10088280?pdf=render @@ -592,8 +592,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 36093379,https://doi.org/10.1016/j.isci.2022.105079,Epidemiologic information discovery from open-access COVID-19 case reports via pretrained language model.,"Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wong ZSY, Xu XK, Sun Y.",,iScience,2022,2022-09-05,Y,Artificial intelligence; Virology; Machine Learning; Health Sciences,,,"Although open-access data are increasingly common and useful to epidemiological research, the curation of such datasets is resource-intensive and time-consuming. Despite the existence of a major source of COVID-19 data, the regularly disclosed case reports were often written in natural language with an unstructured format. Here, we propose a computational framework that can automatically extract epidemiological information from open-access COVID-19 case reports. We develop this framework by coupling a language model developed using deep neural networks with training samples compiled using an optimized data annotation strategy. When applied to the COVID-19 case reports collected from mainland China, our framework outperforms all other state-of-the-art deep learning models. The information extracted from our approach is highly consistent with that obtained from the gold-standard manual coding, with a matching rate of 80%. To disseminate our algorithm, we provide an open-access online platform that is able to estimate key epidemiological statistics in real time, with much less effort for data curation.",,pdf:http://www.cell.com/article/S2589004222013517/pdf; doi:https://doi.org/10.1016/j.isci.2022.105079; html:https://europepmc.org/articles/PMC9441477; pdf:https://europepmc.org/articles/PMC9441477?pdf=render 34053260,https://doi.org/10.1098/rstb.2020.0283,Exploring surveillance data biases when estimating the reproduction number: with insights into subpopulation transmission of COVID-19 in England.,"Sherratt K, Abbott S, Meakin SR, Hellewell J, Munday JD, Bosse N, CMMID COVID-19 Working Group, Jit M, Funk S.",,"Philosophical transactions of the Royal Society of London. Series B, Biological sciences",2021,2021-05-31,Y,Transmission; Surveillance; Bias; Covid-19; Sars-cov-2; Time-varying Reproduction Number,,,"The time-varying reproduction number (Rt: the average number of secondary infections caused by each infected person) may be used to assess changes in transmission potential during an epidemic. While new infections are not usually observed directly, they can be estimated from data. However, data may be delayed and potentially biased. We investigated the sensitivity of Rt estimates to different data sources representing COVID-19 in England, and we explored how this sensitivity could track epidemic dynamics in population sub-groups. We sourced public data on test-positive cases, hospital admissions and deaths with confirmed COVID-19 in seven regions of England over March through August 2020. We estimated Rt using a model that mapped unobserved infections to each data source. We then compared differences in Rt with the demographic and social context of surveillance data over time. Our estimates of transmission potential varied for each data source, with the relative inconsistency of estimates varying across regions and over time. Rt estimates based on hospital admissions and deaths were more spatio-temporally synchronous than when compared to estimates from all test positives. We found these differences may be linked to biased representations of subpopulations in each data source. These included spatially clustered testing, and where outbreaks in hospitals, care homes, and young age groups reflected the link between age and severity of the disease. We highlight that policy makers could better target interventions by considering the source populations of Rt estimates. Further work should clarify the best way to combine and interpret Rt estimates from different data sources based on the desired use. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.",,doi:https://doi.org/10.1098/rstb.2020.0283; doi:https://doi.org/10.1098/rstb.2020.0283; html:https://europepmc.org/articles/PMC8165604; pdf:https://europepmc.org/articles/PMC8165604?pdf=render 36434299,https://doi.org/10.1007/s00127-022-02393-w,Adverse outcomes associated with recorded victimization in mental health electronic records during the first UK COVID-19 lockdown.,"Kadra-Scalzo G, Kornblum D, Stewart R, Howard LM.",,Social psychiatry and psychiatric epidemiology,2023,2022-11-24,Y,Mental health; Domestic Violence; Victimisation; Adverse Outcomes; Covid-19,,,"

Purpose

The impact of COVID-19 pandemic policies on vulnerable groups such as people with mental health problems who experience violence remains unknown. This study aimed to investigate the prevalence of victimization recorded in mental healthcare records during the first UK lockdown, and associations with subsequent adverse outcomes.

Methods

Using a large mental healthcare database, we identified all adult patients receiving services between 16.12.2019 and 15.06.2020 and extracted records of victimisation between 16.03.2020 and 15.06.2020 (first UK COVID-19 lockdown). We investigated adverse outcomes including acute care, emergency department referrals and all-cause mortality in the year following the lockdown (16.06.2020- 01.11.2021). Multivariable Cox regressions models were constructed, adjusting for socio-demographic, socioeconomic, clinical, and service use factors.

Results

Of 21,037 adults receiving mental healthcare over the observation period, 3,610 (17.2%) had victimisation mentioned between 16.03.2020 and 15.06.2020 (first UK COVID-19 lockdown). Service users with mentions of victimisation in their records had an elevated risk for all outcomes: acute care (adjusted HR: 2.1; 95%CI 1.9-2.3, p < 0.001), emergency department referrals (aHR: 2.0; 95%CI 1.8-2.2; p < 0.001), and all-cause mortality (aHR: 1.5; 95%CI 1.1-1.9; p = 0.003), when compared to service users with no recorded victimisation. We did not observe a statistically significant interaction with gender; however, after adjusting for possible confounders, men had slightly higher hazard ratios for all-cause mortality and emergency department referrals than women.

Conclusion

Patients with documented victimisation during the first UK lockdown were at increased risk for acute care, emergency department referrals and all-cause mortality. Further research is needed into mediating mechanisms.",,pdf:https://link.springer.com/content/pdf/10.1007/s00127-022-02393-w.pdf; doi:https://doi.org/10.1007/s00127-022-02393-w; html:https://europepmc.org/articles/PMC9702612; pdf:https://europepmc.org/articles/PMC9702612?pdf=render -37865101,https://doi.org/10.1016/s2213-8587(23)00253-x,"Empagliflozin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,The lancet. Diabetes & endocrinology,2023,2023-10-18,Y,,,,"

Background

Empagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic, and haemodynamic effects. The RECOVERY trial aimed to assess its safety and efficacy in patients admitted to hospital with COVID-19.

Methods

In the randomised, controlled, open-label RECOVERY trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. In this analysis, we assess eligible and consenting adults who were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus oral empagliflozin 10 mg once daily for 28 days or until discharge (whichever came first) using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. On March 3, 2023 the independent data monitoring committee recommended that the investigators review the data and recruitment was consequently stopped on March 7, 2023. The ongoing RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between July 28, 2021 and March 6, 2023, 4271 patients were randomly allocated to receive either empagliflozin (2113 patients) or usual care alone (2158 patients). Primary and secondary outcome data were known for greater than 99% of randomly assigned patients. Overall, 289 (14%) of 2113 patients allocated to empagliflozin and 307 (14%) of 2158 patients allocated to usual care died within 28 days (rate ratio 0·96 [95% CI 0·82-1·13]; p=0·64). There was no evidence of significant differences in duration of hospitalisation (median 8 days for both groups) or the proportion of patients discharged from hospital alive within 28 days (1678 [79%] in the empagliflozin group vs 1677 [78%] in the usual care group; rate ratio 1·03 [95% CI 0·96-1·10]; p=0·44). Among those not on invasive mechanical ventilation at baseline, there was no evidence of a significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (338 [16%] of 2084 vs 371 [17%] of 2143; risk ratio 0·95 [95% CI 0·84-1·08]; p=0·44). Two serious adverse events believed to be related to empagliflozin were reported: both were ketosis without acidosis.

Interpretation

In adults hospitalised with COVID-19, empagliflozin was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death so is not indicated for the treatment of such patients unless there is an established indication due to a different condition such as diabetes.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (MC_PC_19056), and Wellcome Trust (222406/Z/20/Z).

Translations

For the Nepali, Hindi, Indonesian (Bahasa) and Vietnamese translations of the abstract see Supplementary Materials section.",,doi:https://doi.org/10.1016/S2213-8587(23)00253-X; html:https://europepmc.org/articles/PMC10957483; pdf:https://europepmc.org/articles/PMC10957483?pdf=render 34661663,https://doi.org/10.1001/jamanetworkopen.2021.29639,Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19.,"Izadi Z, Brenner EJ, Mahil SK, Dand N, Yiu ZZN, Yates M, Ungaro RC, Zhang X, Agrawal M, Colombel JF, Gianfrancesco MA, Hyrich KL, Strangfeld A, Carmona L, Mateus EF, Lawson-Tovey S, Klingberg E, Cuomo G, Caprioli M, Cruz-Machado AR, Mazeda Pereira AC, Hasseli R, Pfeil A, Lorenz HM, Hoyer BF, Trupin L, Rush S, Katz P, Schmajuk G, Jacobsohn L, Seet AM, Al Emadi S, Wise L, Gilbert EL, Duarte-García A, Valenzuela-Almada MO, Isnardi CA, Quintana R, Soriano ER, Hsu TY, D'Silva KM, Sparks JA, Patel NJ, Xavier RM, Marques CDL, Kakehasi AM, Flipo RM, Claudepierre P, Cantagrel A, Goupille P, Wallace ZS, Bhana S, Costello W, Grainger R, Hausmann JS, Liew JW, Sirotich E, Sufka P, Robinson PC, Machado PM, Griffiths CEM, Barker JN, Smith CH, Yazdany J, Kappelman MD, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect); the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD); and the COVID-19 Global Rheumatology Allianc, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect); the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD); and the COVID-19 Global Rheumatology Alliance (GRA).",,JAMA network open,2021,2021-10-01,Y,,,,"

Importance

Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood.

Objective

To examine the association between the receipt of TNF inhibitor monotherapy and the risk of COVID-19-associated hospitalization or death compared with other commonly prescribed immunomodulatory treatment regimens among adult patients with IMIDs.

Design, setting, and participants

This cohort study was a pooled analysis of data from 3 international COVID-19 registries comprising individuals with rheumatic diseases, inflammatory bowel disease, and psoriasis from March 12, 2020, to February 1, 2021. Clinicians directly reported COVID-19 outcomes as well as demographic and clinical characteristics of individuals with IMIDs and confirmed or suspected COVID-19 using online data entry portals. Adults (age ≥18 years) with a diagnosis of inflammatory arthritis, inflammatory bowel disease, or psoriasis were included.

Exposures

Treatment exposure categories included TNF inhibitor monotherapy (reference treatment), TNF inhibitors in combination with methotrexate therapy, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, and Janus kinase (Jak) inhibitor monotherapy.

Main outcomes and measures

The main outcome was COVID-19-associated hospitalization or death. Registry-level analyses and a pooled analysis of data across the 3 registries were conducted using multilevel multivariable logistic regression models, adjusting for demographic and clinical characteristics and accounting for country, calendar month, and registry-level correlations.

Results

A total of 6077 patients from 74 countries were included in the analyses; of those, 3215 individuals (52.9%) were from Europe, 3563 individuals (58.6%) were female, and the mean (SD) age was 48.8 (16.5) years. The most common IMID diagnoses were rheumatoid arthritis (2146 patients [35.3%]) and Crohn disease (1537 patients [25.3%]). A total of 1297 patients (21.3%) were hospitalized, and 189 patients (3.1%) died. In the pooled analysis, compared with patients who received TNF inhibitor monotherapy, higher odds of hospitalization or death were observed among those who received a TNF inhibitor in combination with azathioprine/6-mercaptopurine therapy (odds ratio [OR], 1.74; 95% CI, 1.17-2.58; P = .006), azathioprine/6-mercaptopurine monotherapy (OR, 1.84; 95% CI, 1.30-2.61; P = .001), methotrexate monotherapy (OR, 2.00; 95% CI, 1.57-2.56; P < .001), and Jak inhibitor monotherapy (OR, 1.82; 95% CI, 1.21-2.73; P = .004) but not among those who received a TNF inhibitor in combination with methotrexate therapy (OR, 1.18; 95% CI, 0.85-1.63; P = .33). Similar findings were obtained in analyses that accounted for potential reporting bias and sensitivity analyses that excluded patients with a COVID-19 diagnosis based on symptoms alone.

Conclusions and relevance

In this cohort study, TNF inhibitor monotherapy was associated with a lower risk of adverse COVID-19 outcomes compared with other commonly prescribed immunomodulatory treatment regimens among individuals with IMIDs.",,pdf:https://jamanetwork.com/journals/jamanetworkopen/articlepdf/2785080/izadi_2021_oi_210864_1633624160.94853.pdf; doi:https://doi.org/10.1001/jamanetworkopen.2021.29639; html:https://europepmc.org/articles/PMC8524310 +37865101,https://doi.org/10.1016/s2213-8587(23)00253-x,"Empagliflozin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,The lancet. Diabetes & endocrinology,2023,2023-10-18,Y,,,,"

Background

Empagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic, and haemodynamic effects. The RECOVERY trial aimed to assess its safety and efficacy in patients admitted to hospital with COVID-19.

Methods

In the randomised, controlled, open-label RECOVERY trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. In this analysis, we assess eligible and consenting adults who were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus oral empagliflozin 10 mg once daily for 28 days or until discharge (whichever came first) using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. On March 3, 2023 the independent data monitoring committee recommended that the investigators review the data and recruitment was consequently stopped on March 7, 2023. The ongoing RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between July 28, 2021 and March 6, 2023, 4271 patients were randomly allocated to receive either empagliflozin (2113 patients) or usual care alone (2158 patients). Primary and secondary outcome data were known for greater than 99% of randomly assigned patients. Overall, 289 (14%) of 2113 patients allocated to empagliflozin and 307 (14%) of 2158 patients allocated to usual care died within 28 days (rate ratio 0·96 [95% CI 0·82-1·13]; p=0·64). There was no evidence of significant differences in duration of hospitalisation (median 8 days for both groups) or the proportion of patients discharged from hospital alive within 28 days (1678 [79%] in the empagliflozin group vs 1677 [78%] in the usual care group; rate ratio 1·03 [95% CI 0·96-1·10]; p=0·44). Among those not on invasive mechanical ventilation at baseline, there was no evidence of a significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (338 [16%] of 2084 vs 371 [17%] of 2143; risk ratio 0·95 [95% CI 0·84-1·08]; p=0·44). Two serious adverse events believed to be related to empagliflozin were reported: both were ketosis without acidosis.

Interpretation

In adults hospitalised with COVID-19, empagliflozin was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death so is not indicated for the treatment of such patients unless there is an established indication due to a different condition such as diabetes.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (MC_PC_19056), and Wellcome Trust (222406/Z/20/Z).

Translations

For the Nepali, Hindi, Indonesian (Bahasa) and Vietnamese translations of the abstract see Supplementary Materials section.",,doi:https://doi.org/10.1016/S2213-8587(23)00253-X; html:https://europepmc.org/articles/PMC10957483; pdf:https://europepmc.org/articles/PMC10957483?pdf=render 36280346,https://doi.org/10.1136/heartjnl-2022-321492,Cardiovascular disease and mortality sequelae of COVID-19 in the UK Biobank.,"Raisi-Estabragh Z, Cooper J, Salih A, Raman B, Lee AM, Neubauer S, Harvey NC, Petersen SE.",,Heart (British Cardiac Society),2022,2022-12-22,Y,epidemiology; Covid-19,,,"

Objective

To examine association of COVID-19 with incident cardiovascular events in 17 871 UK Biobank cases between March 2020 and 2021.

Methods

COVID-19 cases were defined using health record linkage. Each case was propensity score-matched to two uninfected controls on age, sex, deprivation, body mass index, ethnicity, diabetes, prevalent ischaemic heart disease (IHD), smoking, hypertension and high cholesterol. We included the following incident outcomes: myocardial infarction, stroke, heart failure, atrial fibrillation, venous thromboembolism (VTE), pericarditis, all-cause death, cardiovascular death, IHD death. Cox proportional hazards regression was used to estimate associations of COVID-19 with each outcome over an average of 141 days (range 32-395) of prospective follow-up.

Results

Non-hospitalised cases (n=14 304) had increased risk of incident VTE (HR 2.74 (95% CI 1.38 to 5.45), p=0.004) and death (HR 10.23 (95% CI 7.63 to 13.70), p<0.0001). Individuals with primary COVID-19 hospitalisation (n=2701) had increased risk of all outcomes considered. The largest effect sizes were with VTE (HR 27.6 (95% CI 14.5 to 52.3); p<0.0001), heart failure (HR 21.6 (95% CI 10.9 to 42.9); p<0.0001) and stroke (HR 17.5 (95% CI 5.26 to 57.9); p<0.0001). Those hospitalised with COVID-19 as a secondary diagnosis (n=866) had similarly increased cardiovascular risk. The associated risks were greatest in the first 30 days after infection but remained higher than controls even after this period.

Conclusions

Individuals hospitalised with COVID-19 have increased risk of incident cardiovascular events across a range of disease and mortality outcomes. The risk of most events is highest in the early postinfection period. Individuals not requiring hospitalisation have increased risk of VTE, but not of other cardiovascular-specific outcomes.",,pdf:https://heart.bmj.com/content/heartjnl/109/2/119.full.pdf; doi:https://doi.org/10.1136/heartjnl-2022-321492; html:https://europepmc.org/articles/PMC9811071; pdf:https://europepmc.org/articles/PMC9811071?pdf=render 36526319,https://doi.org/10.1136/bmjopen-2022-064910,Performance of scoring systems in selecting short stay medical admissions suitable for assessment in same day emergency care: an analysis of diagnostic accuracy in a UK hospital setting.,"Atkin C, Gallier S, Wallin E, Reddy-Kolanu V, Sapey E.",,BMJ open,2022,2022-12-16,Y,Internal Medicine; General Medicine (See Internal Medicine); Organisation Of Health Services,,,"

Objectives

To assess the performance of the Amb score and Glasgow Admission Prediction Score (GAPS) in identifying acute medical admissions suitable for same day emergency care (SDEC) in a large urban secondary centre.

Design

Retrospective assessment of routinely collected data from electronic healthcare records.

Setting

Single large urban tertiary care centre.

Participants

All unplanned admissions to general medicine on Monday-Friday, episodes starting 08:00-16:59 hours and lasting up to 48 hours, between 1 April 2019 and 9 March 2020.

Main outcome measures

Sensitivity, specificity, positive and negative predictive value of the Amb score and GAPS in identifying patients discharged within 12 hours of arrival.

Results

7365 episodes were assessed. 94.6% of episodes had an Amb score suggesting suitability for SDEC. The positive predictive value of the Amb score in identifying those discharged within 12 hours was 54.5% (95% CI 53.3% to 55.8%). The area under the receiver operating characteristic curve (AUROC) for the Amb score was 0.612 (95% CI 0.599 to 0.625).42.4% of episodes had a GAPS suggesting suitability for SDEC. The positive predictive value of the GAPS in identifying those discharged within 12 hours was 50.5% (95% CI 48.4% to 52.7%). The AUROC for the GAPS was 0.606 (95% CI 0.590 to 0.622).41.4% of the population had both an Amb and GAPS score suggestive of suitability for SDEC and 5.7% of the population had both and Amb and GAPS score suggestive of a lack of suitability for SDEC.

Conclusions

The Amb score and GAPS had poor discriminatory ability to identify acute medical admissions suitable for discharge within 12 hours, limiting their utility in selecting patients for assessment within SDEC services within this diverse patient population.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e064910.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-064910; html:https://europepmc.org/articles/PMC9764605; pdf:https://europepmc.org/articles/PMC9764605?pdf=render 38066209,https://doi.org/10.1038/s41591-023-02665-1,A toolkit for capturing a representative and equitable sample in health research.,"Retzer A, Ciytak B, Khatsuria F, El-Awaisi J, Harris IM, Chapman L, Kelly T, Richards J, Lam E, Newsome PN, Calvert M, NIHR Birmingham Biomedical Research Centre REP-EQUITY Group.",,Nature medicine,2023,2023-12-08,Y,,,,"Research participants often do not represent the general population. Systematic exclusion of particular groups from research limits the generalizability of research findings and perpetuates health inequalities. Groups considered underserved by research include those whose inclusion is lower than expected based on population estimates, those with a high healthcare burden but limited research participation opportunities and those whose healthcare engagement is less than others. The REP-EQUITY toolkit guides representative and equitable inclusion in research. The toolkit was developed through a methodological systematic review and synthesis and finalized in a consensus workshop with 24 participants. The REP-EQUITY toolkit describes seven steps for investigators to consider in facilitating representative and equitable sample selection. This includes clearly defining (1) the relevant underserved groups, (2) the aims relating to equity and representativeness, (3) the sample proportion of individuals with characteristics associated with being underserved by research, (4) the recruitment goals, (5) the strategies by which external factors will be managed, (6) the methods by which representation in the final sample will be evaluated and (7) the legacy of having used the toolkit. Using the REP-EQUITY toolkit could promote trust between communities and research institutions, increase diverse participation in research and improve the generalizability of health research. National Institute for Health and Care Research PROSPERO identifier: CRD42022355391.",,doi:https://doi.org/10.1038/s41591-023-02665-1; html:https://europepmc.org/articles/PMC10719102; pdf:https://europepmc.org/articles/PMC10719102?pdf=render @@ -640,8 +640,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 33531015,https://doi.org/10.1186/s12916-021-01906-9,The importance of supplementary immunisation activities to prevent measles outbreaks during the COVID-19 pandemic in Kenya.,"Mburu CN, Ojal J, Chebet R, Akech D, Karia B, Tuju J, Sigilai A, Abbas K, Jit M, Funk S, Smits G, van Gageldonk PGM, van der Klis FRM, Tabu C, Nokes DJ, LSHTM CMMID COVID-19 Working Group, Scott J, Flasche S, Adetifa I.",,BMC medicine,2021,2021-02-03,Y,outbreak; Measles; Vaccination Coverage; Supplementary Immunisation Activities; Covid-19,,,"

Background

The COVID-19 pandemic has disrupted routine measles immunisation and supplementary immunisation activities (SIAs) in most countries including Kenya. We assessed the risk of measles outbreaks during the pandemic in Kenya as a case study for the African Region.

Methods

Combining measles serological data, local contact patterns, and vaccination coverage into a cohort model, we predicted the age-adjusted population immunity in Kenya and estimated the probability of outbreaks when contact-reducing COVID-19 interventions are lifted. We considered various scenarios for reduced measles vaccination coverage from April 2020.

Results

In February 2020, when a scheduled SIA was postponed, population immunity was close to the herd immunity threshold and the probability of a large outbreak was 34% (8-54). As the COVID-19 contact restrictions are nearly fully eased, from December 2020, the probability of a large measles outbreak will increase to 38% (19-54), 46% (30-59), and 54% (43-64) assuming a 15%, 50%, and 100% reduction in measles vaccination coverage. By December 2021, this risk increases further to 43% (25-56), 54% (43-63), and 67% (59-72) for the same coverage scenarios respectively. However, the increased risk of a measles outbreak following the lifting of all restrictions can be overcome by conducting a SIA with ≥ 95% coverage in under-fives.

Conclusion

While contact restrictions sufficient for SAR-CoV-2 control temporarily reduce measles transmissibility and the risk of an outbreak from a measles immunity gap, this risk rises rapidly once these restrictions are lifted. Implementing delayed SIAs will be critical for prevention of measles outbreaks given the roll-back of contact restrictions in Kenya.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-01906-9; doi:https://doi.org/10.1186/s12916-021-01906-9; html:https://europepmc.org/articles/PMC7854026; pdf:https://europepmc.org/articles/PMC7854026?pdf=render 37358897,https://doi.org/10.2196/45849,Development of a Corpus Annotated With Mentions of Pain in Mental Health Records: Natural Language Processing Approach.,"Chaturvedi J, Chance N, Mirza L, Vernugopan V, Velupillai S, Stewart R, Roberts A.",,JMIR formative research,2023,2023-06-26,Y,Pain; Mental health; Annotation; Information Extraction; Natural Language Processing,,,"

Background

Pain is a widespread issue, with 20% of adults (1 in 5) experiencing it globally. A strong association has been demonstrated between pain and mental health conditions, and this association is known to exacerbate disability and impairment. Pain is also known to be strongly related to emotions, which can lead to damaging consequences. As pain is a common reason for people to access health care facilities, electronic health records (EHRs) are a potential source of information on this pain. Mental health EHRs could be particularly beneficial since they can show the overlap of pain with mental health. Most mental health EHRs contain the majority of their information within the free-text sections of the records. However, it is challenging to extract information from free text. Natural language processing (NLP) methods are therefore required to extract this information from the text.

Objective

This research describes the development of a corpus of manually labeled mentions of pain and pain-related entities from the documents of a mental health EHR database, for use in the development and evaluation of future NLP methods.

Methods

The EHR database used, Clinical Record Interactive Search, consists of anonymized patient records from The South London and Maudsley National Health Service Foundation Trust in the United Kingdom. The corpus was developed through a process of manual annotation where pain mentions were marked as relevant (ie, referring to physical pain afflicting the patient), negated (ie, indicating absence of pain), or not relevant (ie, referring to pain affecting someone other than the patient, or metaphorical and hypothetical mentions). Relevant mentions were also annotated with additional attributes such as anatomical location affected by pain, pain character, and pain management measures, if mentioned.

Results

A total of 5644 annotations were collected from 1985 documents (723 patients). Over 70% (n=4028) of the mentions found within the documents were annotated as relevant, and about half of these mentions also included the anatomical location affected by the pain. The most common pain character was chronic pain, and the most commonly mentioned anatomical location was the chest. Most annotations (n=1857, 33%) were from patients who had a primary diagnosis of mood disorders (International Classification of Diseases-10th edition, chapter F30-39).

Conclusions

This research has helped better understand how pain is mentioned within the context of mental health EHRs and provided insight into the kind of information that is typically mentioned around pain in such a data source. In future work, the extracted information will be used to develop and evaluate a machine learning-based NLP application to automatically extract relevant pain information from EHR databases.",,pdf:https://formative.jmir.org/2023/1/e45849/PDF; doi:https://doi.org/10.2196/45849; html:https://europepmc.org/articles/PMC10337440; pdf:https://europepmc.org/articles/PMC10337440?pdf=render 36593100,https://doi.org/10.1136/heartjnl-2022-322124,Response to: Correspondence on 'Cardiovascular disease and mortality sequelae of COVID-19 in the UK Biobank' by Jolobe.,"Raisi-Estabragh Z, Harvey NC, Petersen SE.",,Heart (British Cardiac Society),2023,2023-01-02,N,epidemiology; acute coronary syndrome; Covid-19,,,,,doi:https://doi.org/10.1136/heartjnl-2022-322124 -33545096,https://doi.org/10.1016/s0140-6736(21)00149-5,"Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2021,2021-02-02,Y,,,,"

Background

Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.

Methods

In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospital with COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once per day by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatment groups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment and were twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants and local study staff were not masked to the allocated treatment, but all others involved in the trial were masked to the outcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.

Findings

Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) were eligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was 65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomly allocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall, 561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days (rate ratio 0·97, 95% CI 0·87-1·07; p=0·50). No significant difference was seen in duration of hospital stay (median 10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 1·04, 95% CI 0·98-1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, no significant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (risk ratio 0·95, 95% CI 0·87-1·03; p=0·24).

Interpretation

In patients admitted to hospital with COVID-19, azithromycin did not improve survival or other prespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restricted to patients in whom there is a clear antimicrobial indication.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,pdf:http://www.thelancet.com/article/S0140673621001495/pdf; doi:https://doi.org/10.1016/S0140-6736(21)00149-5; html:https://europepmc.org/articles/PMC7884931; pdf:https://europepmc.org/articles/PMC7884931?pdf=render 33075408,https://doi.org/10.1016/j.jaci.2020.10.007,Factors associated with adverse COVID-19 outcomes in patients with psoriasis-insights from a global registry-based study.,"Mahil SK, Dand N, Mason KJ, Yiu ZZN, Tsakok T, Meynell F, Coker B, McAteer H, Moorhead L, Mackenzie T, Rossi MT, Rivera R, Mahe E, Carugno A, Magnano M, Rech G, Balogh EA, Feldman SR, De La Cruz C, Choon SE, Naldi L, Lambert J, Spuls P, Jullien D, Bachelez H, McMahon DE, Freeman EE, Gisondi P, Puig L, Warren RB, Di Meglio P, Langan SM, Capon F, Griffiths CEM, Barker JN, Smith CH, PsoProtect study group.",,The Journal of allergy and clinical immunology,2021,2020-10-16,Y,Psoriasis; Immunosuppressants; risk factors; Hospitalization; Biologics; Covid-19,,,"

Background

The multimorbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse outcomes of coronavirus disease 2019 (COVID-19), but the data are limited.

Objective

Our aim was to characterize the course of COVID-19 in patients with psoriasis and identify factors associated with hospitalization.

Methods

Clinicians reported patients with psoriasis with confirmed/suspected COVID-19 via an international registry, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection. Multiple logistic regression was used to assess the association between clinical and/or demographic characteristics and hospitalization. A separate patient-facing registry characterized risk-mitigating behaviors.

Results

Of 374 clinician-reported patients from 25 countries, 71% were receiving a biologic, 18% were receiving a nonbiologic, and 10% were not receiving any systemic treatment for psoriasis. In all, 348 patients (93%) were fully recovered from COVID-19, 77 (21%) were hospitalized, and 9 (2%) died. Increased hospitalization risk was associated with older age (multivariable-adjusted odds ratio [OR] = 1.59 per 10 years; 95% CI = 1.19-2.13), male sex (OR = 2.51; 95% CI = 1.23-5.12), nonwhite ethnicity (OR = 3.15; 95% CI = 1.24-8.03), and comorbid chronic lung disease (OR = 3.87; 95% CI = 1.52-9.83). Hospitalization was more frequent in patients using nonbiologic systemic therapy than in those using biologics (OR = 2.84; 95% CI = 1.31-6.18). No significant differences were found between classes of biologics. Independent patient-reported data (n = 1626 across 48 countries) suggested lower levels of social isolation in individuals receiving nonbiologic systemic therapy than in those receiving biologics (OR = 0.68; 95% CI = 0.50-0.94).

Conclusion

In this international case series of patients with moderate-to-severe psoriasis, biologic use was associated with lower risk of COVID-19-related hospitalization than with use of nonbiologic systemic therapies; however, further investigation is warranted on account of potential selection bias and unmeasured confounding. Established risk factors (being older, being male, being of nonwhite ethnicity, and having comorbidities) were associated with higher hospitalization rates.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4659367/1/Factors%20associated%20with%20adverse%20COVID-19%20outcomes%20in%20patients%20with%20psoriasis-insights%20from%20a%20global%20registry-based%20study.pdf; doi:https://doi.org/10.1016/j.jaci.2020.10.007; html:https://europepmc.org/articles/PMC7566694; pdf:https://europepmc.org/articles/PMC7566694?pdf=render +33545096,https://doi.org/10.1016/s0140-6736(21)00149-5,"Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2021,2021-02-02,Y,,,,"

Background

Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.

Methods

In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospital with COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once per day by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatment groups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment and were twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants and local study staff were not masked to the allocated treatment, but all others involved in the trial were masked to the outcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.

Findings

Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) were eligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was 65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomly allocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall, 561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days (rate ratio 0·97, 95% CI 0·87-1·07; p=0·50). No significant difference was seen in duration of hospital stay (median 10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 1·04, 95% CI 0·98-1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, no significant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (risk ratio 0·95, 95% CI 0·87-1·03; p=0·24).

Interpretation

In patients admitted to hospital with COVID-19, azithromycin did not improve survival or other prespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restricted to patients in whom there is a clear antimicrobial indication.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,pdf:http://www.thelancet.com/article/S0140673621001495/pdf; doi:https://doi.org/10.1016/S0140-6736(21)00149-5; html:https://europepmc.org/articles/PMC7884931; pdf:https://europepmc.org/articles/PMC7884931?pdf=render 32845538,https://doi.org/10.1634/theoncologist.2020-0572,Cancer and Risk of COVID-19 Through a General Community Survey.,"Lee KA, Ma W, Sikavi DR, Drew DA, Nguyen LH, Bowyer RCE, Cardoso MJ, Fall T, Freidin MB, Gomez M, Graham M, Guo CG, Joshi AD, Kwon S, Lo CH, Lochlainn MN, Menni C, Murray B, Mehta R, Song M, Sudre CH, Bataille V, Varsavsky T, Visconti A, Franks PW, Wolf J, Steves CJ, Ourselin S, Spector TD, Chan AT, COPE consortium.",,The oncologist,2021,2020-09-07,Y,,,,"Individuals with cancer may be at high risk for coronavirus disease 2019 (COVID-19) and adverse outcomes. However, evidence from large population-based studies examining whether cancer and cancer-related therapy exacerbates the risk of COVID-19 infection is still limited. Data were collected from the COVID Symptom Study smartphone application since March 29 through May 8, 2020. Among 23,266 participants with cancer and 1,784,293 without cancer, we documented 10,404 reports of a positive COVID-19 test. Compared with participants without cancer, those living with cancer had a 60% increased risk of a positive COVID-19 test. Among patients with cancer, current treatment with chemotherapy or immunotherapy was associated with a 2.2-fold increased risk of a positive test. The association between cancer and COVID-19 infection was stronger among participants >65 years and males. Future studies are needed to identify subgroups by tumor types and treatment regimens who are particularly at risk for COVID-19 infection and adverse outcomes.",,pdf:https://academic.oup.com/oncolo/article-pdf/26/1/e182/41923952/oncolo_26_1_n_a.pdf; doi:https://doi.org/10.1634/theoncologist.2020-0572; html:https://europepmc.org/articles/PMC7460944; pdf:https://europepmc.org/articles/PMC7460944?pdf=render 37147628,https://doi.org/10.1186/s12911-023-02181-9,Ontology-driven and weakly supervised rare disease identification from clinical notes.,"Dong H, Suárez-Paniagua V, Zhang H, Wang M, Casey A, Davidson E, Chen J, Alex B, Whiteley W, Wu H.",,BMC medical informatics and decision making,2023,2023-05-05,Y,Phenotyping; Natural Language Processing; Rare Diseases; Ontology Matching; Clinical Notes; Weak Supervision,,,"

Background

Computational text phenotyping is the practice of identifying patients with certain disorders and traits from clinical notes. Rare diseases are challenging to be identified due to few cases available for machine learning and the need for data annotation from domain experts.

Methods

We propose a method using ontologies and weak supervision, with recent pre-trained contextual representations from Bi-directional Transformers (e.g. BERT). The ontology-driven framework includes two steps: (i) Text-to-UMLS, extracting phenotypes by contextually linking mentions to concepts in Unified Medical Language System (UMLS), with a Named Entity Recognition and Linking (NER+L) tool, SemEHR, and weak supervision with customised rules and contextual mention representation; (ii) UMLS-to-ORDO, matching UMLS concepts to rare diseases in Orphanet Rare Disease Ontology (ORDO). The weakly supervised approach is proposed to learn a phenotype confirmation model to improve Text-to-UMLS linking, without annotated data from domain experts. We evaluated the approach on three clinical datasets, MIMIC-III discharge summaries, MIMIC-III radiology reports, and NHS Tayside brain imaging reports from two institutions in the US and the UK, with annotations.

Results

The improvements in the precision were pronounced (by over 30% to 50% absolute score for Text-to-UMLS linking), with almost no loss of recall compared to the existing NER+L tool, SemEHR. Results on radiology reports from MIMIC-III and NHS Tayside were consistent with the discharge summaries. The overall pipeline processing clinical notes can extract rare disease cases, mostly uncaptured in structured data (manually assigned ICD codes).

Conclusion

The study provides empirical evidence for the task by applying a weakly supervised NLP pipeline on clinical notes. The proposed weak supervised deep learning approach requires no human annotation except for validation and testing, by leveraging ontologies, NER+L tools, and contextual representations. The study also demonstrates that Natural Language Processing (NLP) can complement traditional ICD-based approaches to better estimate rare diseases in clinical notes. We discuss the usefulness and limitations of the weak supervision approach and propose directions for future studies.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-023-02181-9; doi:https://doi.org/10.1186/s12911-023-02181-9; html:https://europepmc.org/articles/PMC10162001; pdf:https://europepmc.org/articles/PMC10162001?pdf=render 35749561,https://doi.org/10.1371/journal.pcbi.1010234,"Evidence for influenza and RSV interaction from 10 years of enhanced surveillance in Nha Trang, Vietnam, a modelling study.","Waterlow NR, Toizumi M, van Leeuwen E, Thi Nguyen HA, Myint-Yoshida L, Eggo RM, Flasche S.",,PLoS computational biology,2022,2022-06-24,Y,,,,"Influenza and Respiratory Syncytial Virus (RSV) interact within their host posing the concern for impacts on heterologous viruses following vaccination. We aimed to estimate the population level impact of their interaction. We developed a dynamic age-stratified two-pathogen mathematical model that includes pathogen interaction through competition for infection and enhanced severity of dual infections. We used parallel tempering to fit its parameters to 11 years of enhanced hospital-based surveillance for acute respiratory illnesses (ARI) in children under 5 years old in Nha Trang, Vietnam. The data supported either a 41% (95%CrI: 36-54) reduction in susceptibility following infection and for 10.0 days (95%CrI 7.1-12.8) thereafter, or no change in susceptibility following infection. We estimate that co-infection increased the probability for an infection in <2y old children to be reported 7.2 fold (95%CrI 5.0-11.4); or 16.6 fold (95%CrI 14.5-18.4) in the moderate or low interaction scenarios. Absence of either pathogen was not to the detriment of the other. We find stronger evidence for severity enhancing than for acquisition limiting interaction. In this setting vaccination against either pathogen is unlikely to have a major detrimental effect on the burden of disease caused by the other.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1010234&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1010234; html:https://europepmc.org/articles/PMC9262224; pdf:https://europepmc.org/articles/PMC9262224?pdf=render @@ -682,13 +682,13 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 35866236,https://doi.org/10.7189/jogh.12.05033,The road to recovery: an interrupted time series analysis of policy intervention to restore essential health services in Mexico during the COVID-19 pandemic.,"Doubova SV, Arsenault C, Contreras-Sánchez SE, Borrayo-Sánchez G, Leslie HH.",,Journal of global health,2022,2022-07-23,Y,,,,"

Background

Recovery of health services disrupted by the COVID-19 pandemic represents a significant challenge in low- and middle-income countries. In April 2021, the Mexican Institute of Social Security (IMSS), which provides health care to 68.5 million people, launched the National Strategy for Health Services Recovery (Recovery policy). The study objective was to evaluate whether the Recovery policy addressed COVID-related declines in maternal, child health, and non-communicable diseases (NCDs) services.

Methods

We analysed the data of 35 IMSS delegations from January 2019 to November 2021 on contraceptive visits, antenatal care consultations, deliveries, caesarean sections, sick children's consultations, child vaccination, breast and cervical cancer screening, diabetes and hypertension consultations, and control. We focused on the period before (April 2020 - March 2021) and during (April 2021 - November 2021) the Recovery policy and used an interrupted time series design and Poisson Generalized Estimating Equation models to estimate the association of this policy with service use and outcomes and change in their trends.

Results

Despite the third wave of the pandemic in 2021, service utilization increased in the Recovery period, reaching (at minimum) 49% of pre-pandemic levels for sick children's consultations and (at maximum) 106% of pre-pandemic levels for breast cancer screenings. Evidence for the Recovery policy role was mixed: the policy was associated with increased facility deliveries (IRR = 1.15, 95%CI = 1.11-1.19) with a growing trend over time (IRR = 1.04, 95%CI = 1.03-1.05); antenatal care and child health services saw strong level effects but decrease over time. Additionally, the Recovery policy was associated with diabetes and hypertension control. Services recovery varied across delegations.

Conclusions

Health service utilization and NCDs control demonstrated important gains in 2021, but evidence suggests the policy had inconsistent effects across services and decreasing impact over time. Further efforts to strengthen essential health services and ensure consistent recovery across delegations are warranted.",,pdf:https://jogh.org/wp-content/uploads/2022/07/jogh-12-05033.pdf; doi:https://doi.org/10.7189/jogh.12.05033; html:https://europepmc.org/articles/PMC9304921; pdf:https://europepmc.org/articles/PMC9304921?pdf=render 36456017,https://doi.org/10.1136/bmjopen-2022-066288,"Impact of the COVID-19 pandemic on timeliness and equity of measles, mumps and rubella vaccinations in North East London: a longitudinal study using electronic health records.","Firman N, Marszalek M, Gutierrez A, Homer K, Williams C, Harper G, Dostal I, Ahmed Z, Robson J, Dezateux C.",,BMJ open,2022,2022-12-01,Y,Public Health; Primary Care; Paediatric Infectious Disease & Immunisation; Covid-19,,,"

Objectives

To quantify the effect of the COVID-19 pandemic on the timeliness of, and geographical and sociodemographic inequalities in, receipt of first measles, mumps and rubella (MMR) vaccination.

Design

Longitudinal study using primary care electronic health records.

Setting

285 general practices in North East London.

Participants

Children born between 23 August 2017 and 22 September 2018 (pre-pandemic cohort) or between 23 March 2019 and 1 May 2020 (pandemic cohort).

Main outcome measure

Receipt of timely MMR vaccination between 12 and 18 months of age.

Methods

We used logistic regression to estimate the ORs (95% CIs) of receipt of a timely vaccination adjusting for sex, deprivation, ethnic background and Clinical Commissioning Group. We plotted choropleth maps of the proportion receiving timely vaccinations.

Results

Timely MMR receipt fell by 4.0% (95% CI: 3.4% to 4.6%) from 79.2% (78.8% to 79.6%) to 75.2% (74.7% to 75.7%) in the pre-pandemic (n=33 226; 51.3% boys) and pandemic (n=32 446; 51.4%) cohorts, respectively. After adjustment, timely vaccination was less likely in the pandemic cohort (0.79; 0.76 to 0.82), children from black (0.70; 0.65 to 0.76), mixed/other (0.77; 0.72 to 0.82) or with missing (0.77; 0.74 to 0.81) ethnic background, and more likely in girls (1.07; 1.03 to 1.11) and those from South Asian backgrounds (1.39; 1.30 to 1.48). Children living in the least deprived areas were more likely to receive a timely MMR (2.09; 1.78 to 2.46) but there was no interaction between cohorts and deprivation (Wald statistic: 3.44; p=0.49). The proportion of neighbourhoods where less than 60% of children received timely vaccination increased from 7.5% to 12.7% during the pandemic.

Conclusions

The COVID-19 pandemic was associated with a significant fall in timely MMR receipt and increased geographical clustering of measles susceptibility in an area of historically low and inequitable MMR coverage. Immediate action is needed to avert measles outbreaks and support primary care to deliver timely and equitable vaccinations.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e066288.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-066288; html:https://europepmc.org/articles/PMC9723415; pdf:https://europepmc.org/articles/PMC9723415?pdf=render 35443953,https://doi.org/10.1136/bmjopen-2021-056523,Can we accurately forecast non-elective bed occupancy and admissions in the NHS? A time-series MSARIMA analysis of longitudinal data from an NHS Trust.,"Eyles E, Redaniel MT, Jones T, Prat M, Keen T.",,BMJ open,2022,2022-04-20,Y,epidemiology; Statistics & Research Methods; Health Services Administration & Management; Accident & Emergency Medicine,,,"

Objectives

The main objective of the study was to develop more accurate and precise short-term forecasting models for admissions and bed occupancy for an NHS Trust located in Bristol, England. Subforecasts for the medical and surgical specialties, and for different lengths of stay were realised DESIGN: Autoregressive integrated moving average models were specified on a training dataset of daily count data, then tested on a 6-week forecast horizon. Explanatory variables were included in the models: day of the week, holiday days, lagged temperature and precipitation.

Setting

A secondary care hospital in an NHS Trust in South West England.

Participants

Hospital admissions between September 2016 and March 2020, comprising 1291 days.

Primary and secondary outcome measures

The accuracy of the forecasts was assessed through standard measures, as well as compared with the actual data using accuracy thresholds of 10% and 20% of the mean number of admissions or occupied beds.

Results

The overall Autoregressive Integrated Moving Average (ARIMA) admissions forecast was compared with the Trust's forecast, and found to be more accurate, namely, being closer to the actual value 95.6% of the time. Furthermore, it was more precise than the Trust's. The subforecasts, as well as those for bed occupancy, tended to be less accurate compared with the overall forecasts. All of the explanatory variables improved the forecasts.

Conclusions

ARIMA models can forecast non-elective admissions in an NHS Trust accurately on a 6-week horizon, which is an improvement on the current predictive modelling in the Trust. These models can be readily applied to other contexts, improving patient flow.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e056523.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-056523; html:https://europepmc.org/articles/PMC9021768; pdf:https://europepmc.org/articles/PMC9021768?pdf=render -35726508,https://doi.org/10.1177/10398562221103117,Improving quantification of anticholinergic burden using the Anticholinergic Effect on Cognition Scale - a healthcare improvement study in a geriatric ward setting.,"Balasundaram B, Ang WST, Stewart R, Bishara D, Ooi CH, Li F, Akram F, Eu Kwek AB.",,Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists,2022,2022-06-21,Y,Dementia; Delirium; Anticholinergic drugs; Anticholinergic Burden Scales; Anticholinergic Effect On Cognition Scale,,,"

Objective

Anticholinergic burden refers to the cumulative effects of taking multiple medications with anticholinergic effects. This study was carried out in a public hospital in Singapore, aimed to improve and achieve a 100% comprehensive identification and review of measured, anticholinergic burden in a geriatric psychiatry liaison service to geriatric wards. We evaluated changes in pre-to post-assessment anticholinergic burden scores and trainee feedback.

Method

Plan Do Study Act methodology was employed, and Anticholinergic Effect on Cognition scale (AEC) was implemented as the study intervention. A survey instrument evaluated trainee feedback.

Results

There was no measured anticholinergic burden in a baseline of 170 assessments. 75 liaison psychiatry assessments were conducted between June and November 2021 in two cycles. 94.7% of pre-assessments (at the time of assessment) and 71.1% of post-assessments (following assessment) had a record of AEC scores in clinical documentation in cycle one, improving in the second cycle to 100%, 94.6%, respectively. A high post-assessment AEC score of 3 and over reduced from 15.8% in cycle one to 5.4% in cycle two. The trainee feedback suggested an enriching educational experience.

Conclusions

Using the AEC scale, the findings support the feasibility of comprehensive identification and review of measured anticholinergic burden in older people with neurocognitive disorders.",,doi:https://doi.org/10.1177/10398562221103117; doi:https://doi.org/10.1177/10398562221103117; html:https://europepmc.org/articles/PMC9379386; pdf:https://europepmc.org/articles/PMC9379386?pdf=render 33628949,https://doi.org/10.12688/wellcomeopenres.16020.2,The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Questionnaire data capture April-May 2020.,"Northstone K, Howarth S, Smith D, Bowring C, Wells N, Timpson NJ.",,Wellcome open research,2020,2020-11-20,Y,Coronavirus; Mental health; Alspac; Birth Cohort Study; Online Questionnaire; Children Of The 90S; Covid-19,,,"The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992. The resource provides an informative and efficient setting for collecting data on the current coronavirus 2019 (COVID-19) pandemic. In early March 2020, a questionnaire was developed in collaboration with other longitudinal population studies to ensure cross-cohort comparability. It targeted retrospective and current COVID-19 infection information (exposure assessment, symptom tracking and reported clinical outcomes) and the impact of both disease and mitigating measures implemented to manage the COVID-19 crisis more broadly. Data were collected on symptoms of COVID-19 and seasonal flu, travel prior to the pandemic, mental health and social, behavioural and lifestyle factors. The online questionnaire was deployed across parent (G0) and offspring (G1) generations between 9 th April and 15 th May 2020. 6807 participants completed the questionnaire (2706 original mothers, 1014 original fathers/partners, 2973 offspring (mean age ~28 years) and 114 offspring partners). Eight (0.01%) participants (4 G0 and 4 G1) reported a positive test for COVID-19, 77 (1.13%; 28 G0 and 49 G1) reported that they had been told by a doctor they likely had COVID-19 and 865 (12.7%; 426 G0 and 439 G1) suspected that they have had COVID-19.  Using algorithmically defined cases, we estimate that the predicted proportion of COVID-19 cases ranged from 1.03% - 4.19% depending on timing during the period of reporting (October 2019-March 2020). Data from this first questionnaire will be complemented with at least two more follow-up questionnaires, linkage to health records and results of biological testing as they become available. Data has been released as: 1) a standard dataset containing all participant responses with key sociodemographic factors and 2) as a composite release coordinating data from the existing resource, thus enabling bespoke research across all areas supported by the study.",,doi:https://doi.org/10.12688/wellcomeopenres.16020.2; html:https://europepmc.org/articles/PMC7883314; pdf:https://europepmc.org/articles/PMC7883314?pdf=render +35726508,https://doi.org/10.1177/10398562221103117,Improving quantification of anticholinergic burden using the Anticholinergic Effect on Cognition Scale - a healthcare improvement study in a geriatric ward setting.,"Balasundaram B, Ang WST, Stewart R, Bishara D, Ooi CH, Li F, Akram F, Eu Kwek AB.",,Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists,2022,2022-06-21,Y,Dementia; Delirium; Anticholinergic drugs; Anticholinergic Burden Scales; Anticholinergic Effect On Cognition Scale,,,"

Objective

Anticholinergic burden refers to the cumulative effects of taking multiple medications with anticholinergic effects. This study was carried out in a public hospital in Singapore, aimed to improve and achieve a 100% comprehensive identification and review of measured, anticholinergic burden in a geriatric psychiatry liaison service to geriatric wards. We evaluated changes in pre-to post-assessment anticholinergic burden scores and trainee feedback.

Method

Plan Do Study Act methodology was employed, and Anticholinergic Effect on Cognition scale (AEC) was implemented as the study intervention. A survey instrument evaluated trainee feedback.

Results

There was no measured anticholinergic burden in a baseline of 170 assessments. 75 liaison psychiatry assessments were conducted between June and November 2021 in two cycles. 94.7% of pre-assessments (at the time of assessment) and 71.1% of post-assessments (following assessment) had a record of AEC scores in clinical documentation in cycle one, improving in the second cycle to 100%, 94.6%, respectively. A high post-assessment AEC score of 3 and over reduced from 15.8% in cycle one to 5.4% in cycle two. The trainee feedback suggested an enriching educational experience.

Conclusions

Using the AEC scale, the findings support the feasibility of comprehensive identification and review of measured anticholinergic burden in older people with neurocognitive disorders.",,doi:https://doi.org/10.1177/10398562221103117; doi:https://doi.org/10.1177/10398562221103117; html:https://europepmc.org/articles/PMC9379386; pdf:https://europepmc.org/articles/PMC9379386?pdf=render 35337642,https://doi.org/10.1016/s2589-7500(22)00018-8,"Implementation of corticosteroids in treatment of COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK: prospective, cohort study.","Närhi F, Moonesinghe SR, Shenkin SD, Drake TM, Mulholland RH, Donegan C, Dunning J, Fairfield CJ, Girvan M, Hardwick HE, Ho A, Leeming G, Nguyen-Van-Tam JS, Pius R, Russell CD, Shaw CA, Spencer RG, Turtle L, Openshaw PJM, Baillie JK, Harrison EM, Semple MG, Docherty AB, ISARIC4C investigators.",,The Lancet. Digital health,2022,2022-04-01,Y,,,,"

Background

Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care.

Methods

We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260.

Findings

Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70-0·89], p=0·0001, for 70-79 years; 0·52 [0·46-0·58], p<0·0001, for >80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75-80% in January, 2021.

Interpretation

Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered.

Funding

UK National Institute for Health Research and UK Medical Research Council.",,pdf:http://www.thelancet.com/article/S2589750022000188/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00018-8; html:https://europepmc.org/articles/PMC8940185 34000257,https://doi.org/10.1016/s0140-6736(21)00897-7,"Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2021,2021-05-14,Y,,,,"

Background

Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19.

Methods

This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.

Findings

Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93-1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94-1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93-1·05; p=0·79).

Interpretation

In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,pdf:http://www.thelancet.com/article/S0140673621008977/pdf; doi:https://doi.org/10.1016/S0140-6736(21)00897-7; html:https://europepmc.org/articles/PMC8121538 37474660,https://doi.org/10.1038/s41591-023-02445-x,Considerations for patient and public involvement and engagement in health research.,"Aiyegbusi OL, McMullan C, Hughes SE, Turner GM, Subramanian A, Hotham R, Davies EH, Frost C, Alder Y, Agyen L, Buckland L, Camaradou J, Chong A, Jeyes F, Kumar S, Matthews KL, Moore P, Ormerod J, Price G, Saint-Cricq M, Stanton D, Walker A, Haroon S, Denniston AK, Calvert MJ, TLC Study Group.",,Nature medicine,2023,2023-07-20,N,,,,"Patient and public involvement and engagement (PPIE) can provide valuable insights into the experiences of those living with and affected by a disease or health condition. Inclusive collaboration between patients, the public and researchers can lead to productive relationships, ensuring that health research addresses patient needs. Guidelines are available to support effective PPIE; however, evaluation of the impact of PPIE strategies in health research is limited. In this Review, we evaluate the impact of PPIE in the 'Therapies for Long COVID in non-hospitalised individuals' (TLC) Study, using a combination of group discussions and interviews with patient partners and researchers. We identify areas of good practice and reflect on areas for improvement. Using these insights and the results of a survey, we synthesize two checklists of considerations for PPIE, and we propose that research teams use these checklists to optimize the impact of PPIE for both patients and researchers in future studies.",,doi:https://doi.org/10.1038/s41591-023-02445-x -35104366,https://doi.org/10.1111/bjd.21042,Vaccine hesitancy and access to psoriasis care during the COVID-19 pandemic: findings from a global patient-reported cross-sectional survey.,"Bechman K, Cook ES, Dand N, Yiu ZZN, Tsakok T, Meynell F, Coker B, Vincent A, Bachelez H, Barbosa I, Brown MA, Capon F, Contreras CR, De La Cruz C, Meglio PD, Gisondi P, Jullien D, Kelly J, Lambert J, Lancelot C, Langan SM, Mason KJ, McAteer H, Moorhead L, Naldi L, Norton S, Puig L, Spuls PI, Torres T, Urmston D, Vesty A, Warren RB, Waweru H, Weinman J, Griffiths CEM, Barker JN, Smith CH, Galloway JB, Mahil SK, PsoProtect study group.",,The British journal of dermatology,2022,2022-05-03,Y,,,,,,pdf:https://biblio.ugent.be/publication/8757812/file/8757816.pdf; doi:https://doi.org/10.1111/bjd.21042; html:https://europepmc.org/articles/PMC9545500; pdf:https://europepmc.org/articles/PMC9545500?pdf=render 34319235,https://doi.org/10.2196/28873,Remote Assessment of Lung Disease and Impact on Physical and Mental Health (RALPMH): Protocol for a Prospective Observational Study.,"Ranjan Y, Althobiani M, Jacob J, Orini M, Dobson RJ, Porter J, Hurst J, Folarin AA.",,JMIR research protocols,2021,2021-10-07,Y,Lung diseases; Mental health; Remote Monitoring; Respiratory Health; Internet Of Things; Mhealth; Mobile Health; Wearables; Cardiopulmonary Diseases; Covid-19,,,"

Background

Chronic lung disorders like chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are characterized by exacerbations. They are unpleasant for patients and sometimes severe enough to cause hospital admission and death. Moreover, due to the COVID-19 pandemic, vulnerable populations with these disorders are at high risk, and their routine care cannot be done properly. Remote monitoring offers a low cost and safe solution for gaining visibility into the health of people in their daily lives, making it useful for vulnerable populations.

Objective

The primary objective is to assess the feasibility and acceptability of remote monitoring using wearables and mobile phones in patients with pulmonary diseases. The secondary objective is to provide power calculations for future studies centered around understanding the number of exacerbations according to sample size and duration.

Methods

Twenty participants will be recruited in each of three cohorts (COPD, IPF, and posthospitalization COVID). Data collection will be done remotely using the RADAR-Base (Remote Assessment of Disease And Relapse) mobile health (mHealth) platform for different devices, including Garmin wearable devices and smart spirometers, mobile app questionnaires, surveys, and finger pulse oximeters. Passive data include wearable-derived continuous heart rate, oxygen saturation, respiration rate, activity, and sleep. Active data include disease-specific patient-reported outcome measures, mental health questionnaires, and symptom tracking to track disease trajectory. Analyses will assess the feasibility of lung disorder remote monitoring (including data quality, data completeness, system usability, and system acceptability). We will attempt to explore disease trajectory, patient stratification, and identification of acute clinical events such as exacerbations. A key aspect is understanding the potential of real-time data collection. We will simulate an intervention to acquire responses at the time of the event to assess model performance for exacerbation identification.

Results

The Remote Assessment of Lung Disease and Impact on Physical and Mental Health (RALPMH) study provides a unique opportunity to assess the use of remote monitoring in the evaluation of lung disorders. The study started in the middle of June 2021. The data collection apparatus, questionnaires, and wearable integrations were setup and tested by the clinical teams prior to the start of recruitment. While recruitment is ongoing, real-time exacerbation identification models are currently being constructed. The models will be pretrained daily on data of previous days, but the inference will be run in real time.

Conclusions

The RALPMH study will provide a reference infrastructure for remote monitoring of lung diseases. It specifically involves information regarding the feasibility and acceptability of remote monitoring and the potential of real-time data collection and analysis in the context of chronic lung disorders. It will help plan and inform decisions in future studies in the area of respiratory health.

Trial registration

ISRCTN Registry ISRCTN16275601; https://www.isrctn.com/ISRCTN16275601.

International registered report identifier (irrid)

PRR1-10.2196/28873.",,pdf:https://jmir.org/api/download?alt_name=resprot_v10i10e28873_app2.pdf&filename=4dda9f18456291d5d5d6facee1b77a71.pdf; doi:https://doi.org/10.2196/28873; html:https://europepmc.org/articles/PMC8500349 +35104366,https://doi.org/10.1111/bjd.21042,Vaccine hesitancy and access to psoriasis care during the COVID-19 pandemic: findings from a global patient-reported cross-sectional survey.,"Bechman K, Cook ES, Dand N, Yiu ZZN, Tsakok T, Meynell F, Coker B, Vincent A, Bachelez H, Barbosa I, Brown MA, Capon F, Contreras CR, De La Cruz C, Meglio PD, Gisondi P, Jullien D, Kelly J, Lambert J, Lancelot C, Langan SM, Mason KJ, McAteer H, Moorhead L, Naldi L, Norton S, Puig L, Spuls PI, Torres T, Urmston D, Vesty A, Warren RB, Waweru H, Weinman J, Griffiths CEM, Barker JN, Smith CH, Galloway JB, Mahil SK, PsoProtect study group.",,The British journal of dermatology,2022,2022-05-03,Y,,,,,,pdf:https://biblio.ugent.be/publication/8757812/file/8757816.pdf; doi:https://doi.org/10.1111/bjd.21042; html:https://europepmc.org/articles/PMC9545500; pdf:https://europepmc.org/articles/PMC9545500?pdf=render 34240696,https://doi.org/10.2807/1560-7917.es.2021.26.27.2000004,"Nanopore metagenomic sequencing of influenza virus directly from respiratory samples: diagnosis, drug resistance and nosocomial transmission, United Kingdom, 2018/19 influenza season.","Xu Y, Lewandowski K, Downs LO, Kavanagh J, Hender T, Lumley S, Jeffery K, Foster D, Sanderson ND, Vaughan A, Morgan M, Vipond R, Carroll M, Peto T, Crook D, Walker AS, Matthews PC, Pullan ST.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2021,2021-07-01,Y,Genetic diversity; Influenza; Diagnosis; Metagenomics; Antiviral Drug Resistance; Nanopore; Respiratory Viruses; Nosocomial Transmission,,,"BackgroundInfluenza virus presents a considerable challenge to public health by causing seasonal epidemics and occasional pandemics. Nanopore metagenomic sequencing has the potential to be deployed for near-patient testing, providing rapid infection diagnosis, rationalising antimicrobial therapy, and supporting infection-control interventions.AimTo evaluate the applicability of this sequencing approach as a routine laboratory test for influenza in clinical settings.MethodsWe conducted Oxford Nanopore Technologies (Oxford, United Kingdom (UK)) metagenomic sequencing for 180 respiratory samples from a UK hospital during the 2018/19 influenza season, and compared results to routine molecular diagnostic standards (Xpert Xpress Flu/RSV assay; BioFire FilmArray Respiratory Panel 2 assay). We investigated drug resistance, genetic diversity, and nosocomial transmission using influenza sequence data.ResultsCompared to standard testing, Nanopore metagenomic sequencing was 83% (75/90) sensitive and 93% (84/90) specific for detecting influenza A viruses. Of 59 samples with haemagglutinin subtype determined, 40 were H1 and 19 H3. We identified an influenza A(H3N2) genome encoding the oseltamivir resistance S331R mutation in neuraminidase, potentially associated with an emerging distinct intra-subtype reassortant. Whole genome phylogeny refuted suspicions of a transmission cluster in a ward, but identified two other clusters that likely reflected nosocomial transmission, associated with a predominant community-circulating strain. We also detected other potentially pathogenic viruses and bacteria from the metagenome.ConclusionNanopore metagenomic sequencing can detect the emergence of novel variants and drug resistance, providing timely insights into antimicrobial stewardship and vaccine design. Full genome generation can help investigate and manage nosocomial outbreaks.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/26/27/eurosurv-26-27-4.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2021.26.27.2000004&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2021.26.27.2000004; html:https://europepmc.org/articles/PMC8268652; pdf:https://europepmc.org/articles/PMC8268652?pdf=render 35634533,https://doi.org/10.12688/wellcomeopenres.17360.1,A comprehensive high cost drugs dataset from the NHS in England - An OpenSAFELY-TPP Short Data Report.,"Rowan A, Bates C, Hulme W, Evans D, Davy S, A Kennedy N, Galloway J, E Mansfield K, Bechman K, Matthewman J, Yates M, Brown J, Schultze A, Norton S, J Walker A, E Morton C, Bhaskaran K, T Rentsch C, Williamson E, Croker R, Bacon S, Hickman G, Ward T, Green A, Fisher L, J Curtis H, Tazare J, M Eggo R, Inglesby P, Cockburn J, I McDonald H, Mathur R, Ys Wong A, Forbes H, Parry J, Hester F, Harper S, J Douglas I, Smeeth L, A Tomlinson L, W Lees C, Evans S, Smith C, M Langan S, Mehkar A, MacKenna B, Goldacre B.",,Wellcome open research,2021,2021-12-22,Y,Medications; Biosimilars; Healthcare Administration; Opensafely,,,"Background: At the outset of the COVID-19 pandemic, there was no routine comprehensive hospital medicines data from the UK available to researchers. These records can be important for many analyses including the effect of certain medicines on the risk of severe COVID-19 outcomes. With the approval of NHS England, we set out to obtain data on one specific group of medicines, ""high-cost drugs"" (HCD) which are typically specialist medicines for the management of long-term conditions, prescribed by hospitals to patients. Additionally, we aimed to make these data available to all approved researchers in OpenSAFELY-TPP. This report is intended to support all studies carried out in OpenSAFELY-TPP, and those elsewhere, working with this dataset or similar data. Methods: Working with the North East Commissioning Support Unit and NHS Digital, we arranged for collation of a single national HCD dataset to help inform responses to the COVID-19 pandemic. The dataset was developed from payment submissions from hospitals to commissioners. Results: In the financial year (FY) 2018/19 there were 2.8 million submissions for 1.1 million unique patient IDs recorded in the HCD. The average number of submissions per patient over the year was 2.6. In FY 2019/20 there were 4.0 million submissions for 1.3 million unique patient IDs. The average number of submissions per patient over the year was 3.1. Of the 21 variables in the dataset, three are now available for analysis in OpenSafely-TPP: Financial year and month of drug being dispensed; drug name; and a description of the drug dispensed. Conclusions: We have described the process for sourcing a national HCD dataset, making these data available for COVID-19-related analysis through OpenSAFELY-TPP and provided information on the variables included in the dataset, data coverage and an initial descriptive analysis.",,doi:https://doi.org/10.12688/wellcomeopenres.17360.1; html:https://europepmc.org/articles/PMC9120928; pdf:https://europepmc.org/articles/PMC9120928?pdf=render 32935062,https://doi.org/10.23889/ijpds.v5i2.1383,Prospective data linkage to facilitate COVID-19 trials - A call to action.,"Paprica PA, Sydes MR, McGrail KM, Morris AD, Schull MJ, Walker R.",,International journal of population data science,2020,2020-08-11,Y,,,,,,pdf:https://ijpds.org/article/download/1383/2566; doi:https://doi.org/10.23889/ijpds.v5i2.1383; html:https://europepmc.org/articles/PMC7473253; pdf:https://europepmc.org/articles/PMC7473253?pdf=render @@ -712,8 +712,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 38479735,https://doi.org/10.1136/bmjopen-2023-081926,"HFE genotypes, haemochromatosis diagnosis and clinical outcomes at age 80 years: a prospective cohort study in the UK Biobank.","Lucas MR, Atkins JL, Pilling LC, Shearman JD, Melzer D.",,BMJ open,2024,2024-03-13,Y,"Genetics; Mortality; Hepatology; Other Metabolic, E.g. Iron, Porphyria",,,"

Objectives

HFE haemochromatosis genetic variants have an uncertain clinical penetrance, especially to older ages and in undiagnosed groups. We estimated p.C282Y and p.H63D variant cumulative incidence of multiple clinical outcomes in a large community cohort.

Design

Prospective cohort study.

Setting

22 assessment centres across England, Scotland, and Wales in the UK Biobank (2006-2010).

Participants

451 270 participants genetically similar to the 1000 Genomes European reference population, with a mean of 13.3-year follow-up through hospital inpatient, cancer registries and death certificate data.

Main outcome measures

Cox proportional HRs of incident clinical outcomes and mortality in those with HFE p.C282Y/p.H63D mutations compared with those with no variants, stratified by sex and adjusted for age, assessment centre and genetic stratification. Cumulative incidences were estimated from age 40 years to 80 years.

Results

12.1% of p.C282Y+/+ males had baseline (mean age 57 years) haemochromatosis diagnoses, with a cumulative incidence of 56.4% at age 80 years. 33.1% died vs 25.4% without HFE variants (HR 1.29, 95% CI: 1.12 to 1.48, p=4.7×10-4); 27.9% vs 17.1% had joint replacements, 20.3% vs 8.3% had liver disease, and there were excess delirium, dementia, and Parkinson's disease but not depression. Associations, including excess mortality, were similar in the group undiagnosed with haemochromatosis. 3.4% of women with p.C282Y+/+ had baseline haemochromatosis diagnoses, with a cumulative incidence of 40.5% at age 80 years. There were excess incident liver disease (8.9% vs 6.8%; HR 1.62, 95% CI: 1.27 to 2.05, p=7.8×10-5), joint replacements and delirium, with similar results in the undiagnosed. p.C282Y/p.H63D and p.H63D+/+ men or women had no statistically significant excess fatigue or depression at baseline and no excess incident outcomes.

Conclusions

Male and female p.C282Y homozygotes experienced greater excess morbidity than previously documented, including those undiagnosed with haemochromatosis in the community. As haemochromatosis diagnosis rates were low at baseline despite treatment being considered effective, trials of screening to identify people with p.C282Y homozygosity early appear justified.",,doi:https://doi.org/10.1136/bmjopen-2023-081926; html:https://europepmc.org/articles/PMC10936495; pdf:https://europepmc.org/articles/PMC10936495?pdf=render 36777997,https://doi.org/10.1016/j.xgen.2022.100181,Leveraging global multi-ancestry meta-analysis in the study of idiopathic pulmonary fibrosis genetics.,"Partanen JJ, Häppölä P, Zhou W, Lehisto AA, Ainola M, Sutinen E, Allen RJ, Stockwell AD, Leavy OC, Oldham JM, Guillen-Guio B, Cox NJ, Hirbo JB, Schwartz DA, Fingerlin TE, Flores C, Noth I, Yaspan BL, Jenkins RG, Wain LV, Ripatti S, Pirinen M, International IPF Genetics Consortium, Global Biobank Meta-Analysis Initiative (GBMI), Laitinen T, Kaarteenaho R, Myllärniemi M, Daly MJ, Koskela JT.",,Cell genomics,2022,2022-10-12,Y,Meta-analysis; idiopathic pulmonary fibrosis; Gwas; Ancestry; Muc5b; Fine-mapping; Cross-population Analysis; Covid-19; Global Biobank Meta-Analysis Initiative,,,"The research of rare and devastating orphan diseases, such as idiopathic pulmonary fibrosis (IPF) has been limited by the rarity of the disease itself. The prognosis is poor-the prevalence of IPF is only approximately four times the incidence, limiting the recruitment of patients to trials and studies of the underlying biology. Global biobanking efforts can dramatically alter the future of IPF research. We describe a large-scale meta-analysis of IPF, with 8,492 patients and 1,355,819 population controls from 13 biobanks around the globe. Finally, we combine this meta-analysis with the largest available meta-analysis of IPF, reaching 11,160 patients and 1,364,410 population controls. We identify seven novel genome-wide significant loci, only one of which would have been identified if the analysis had been limited to European ancestry individuals. We observe notable pleiotropy across IPF susceptibility and severe COVID-19 infection and note an unexplained sex-heterogeneity effect at the strongest IPF locus MUC5B.",,pdf:https://helda.helsinki.fi/bitstream/10138/355828/1/Leveraging_global_multi_ancestry_meta_a...pdf; doi:https://doi.org/10.1016/j.xgen.2022.100181; html:https://europepmc.org/articles/PMC9903787; pdf:https://europepmc.org/articles/PMC9903787?pdf=render 34693751,https://doi.org/10.1177/14799731211053332,The diagnosis of asthma. Can physiological tests of small airways function help?,"Almeshari MA, Stockley J, Sapey E.",,Chronic respiratory disease,2021,2021-01-01,Y,Diagnosis; Asthma; Spirometry; Oscillometry; Small Airways Function,,,"Asthma is a common, chronic, and heterogeneous disease with a global impact and substantial economic costs. It is also associated with significant mortality and morbidity and the burden of undiagnosed asthma is significant. Asthma can be difficult to diagnose as there is no gold standard test and, while spirometry is central in diagnosing asthma, it may not be sufficient to confirm or exclude the diagnosis. The most commonly reported spirometric measures (forced expiratory volume in one second (FEV1) and forced vital capacity assess function in the larger airways. However, small airway dysfunction is highly prevalent in asthma and some studies suggest small airway involvement is one of the earliest disease manifestations. Moreover, there are new inhaled therapies with ultrafine particles that are specifically designed to target the small airways. Potentially, tests of small airways may more accurately diagnose early or mild asthma and assess the response to treatment than spirometry. Furthermore, some assessment techniques do not rely on forced ventilatory manoeuvres and may, therefore, be easier for certain groups to perform. This review discusses the current evidence of small airways tests in asthma and future research that may be needed to further assess their utility.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/14799731211053332; doi:https://doi.org/10.1177/14799731211053332; html:https://europepmc.org/articles/PMC8543738; pdf:https://europepmc.org/articles/PMC8543738?pdf=render -37596262,https://doi.org/10.1038/s41467-023-40679-y,A genome-wide association study of blood cell morphology identifies cellular proteins implicated in disease aetiology.,"Akbari P, Vuckovic D, Stefanucci L, Jiang T, Kundu K, Kreuzhuber R, Bao EL, Collins JH, Downes K, Grassi L, Guerrero JA, Kaptoge S, Knight JC, Meacham S, Sambrook J, Seyres D, Stegle O, Verboon JM, Walter K, Watkins NA, Danesh J, Roberts DJ, Di Angelantonio E, Sankaran VG, Frontini M, Burgess S, Kuijpers T, Peters JE, Butterworth AS, Ouwehand WH, Soranzo N, Astle WJ.",,Nature communications,2023,2023-08-18,Y,,,,"Blood cells contain functionally important intracellular structures, such as granules, critical to immunity and thrombosis. Quantitative variation in these structures has not been subjected previously to large-scale genetic analysis. We perform genome-wide association studies of 63 flow-cytometry derived cellular phenotypes-including cell-type specific measures of granularity, nucleic acid content and reactivity-in 41,515 participants in the INTERVAL study. We identify 2172 distinct variant-trait associations, including associations near genes coding for proteins in organelles implicated in inflammatory and thrombotic diseases. By integrating with epigenetic data we show that many intracellular structures are likely to be determined in immature precursor cells. By integrating with proteomic data we identify the transcription factor FOG2 as an early regulator of platelet formation and α-granularity. Finally, we show that colocalisation of our associations with disease risk signals can suggest aetiological cell-types-variants in IL2RA and ITGA4 respectively mirror the known effects of daclizumab in multiple sclerosis and vedolizumab in inflammatory bowel disease.",,doi:https://doi.org/10.1038/s41467-023-40679-y; html:https://europepmc.org/articles/PMC10439125; pdf:https://europepmc.org/articles/PMC10439125?pdf=render 36050271,https://doi.org/10.1016/s2589-7500(22)00151-0,CODE-EHR best-practice framework for the use of structured electronic health-care records in clinical research.,"Kotecha D, Asselbergs FW, Achenbach S, Anker SD, Atar D, Baigent C, Banerjee A, Beger B, Brobert G, Casadei B, Ceccarelli C, Cowie MR, Crea F, Cronin M, Denaxas S, Derix A, Fitzsimons D, Fredriksson M, Gale CP, Gkoutos GV, Goettsch W, Hemingway H, Ingvar M, Jonas A, Kazmierski R, Løgstrup S, Lumbers RT, Lüscher TF, McGreavy P, Piña IL, Roessig L, Steinbeisser C, Sundgren M, Tyl B, Thiel GV, Bochove KV, Vardas PE, Villanueva T, Vrana M, Weber W, Weidinger F, Windecker S, Wood A, Grobbee DE, Innovative Medicines Initiative BigData@Heart Consortium, European Society of Cardiology, and CODE-EHR International Consensus Group.",,The Lancet. Digital health,2022,2022-08-29,N,,,,"Big data is important to new developments in global clinical science that aim to improve the lives of patients. Technological advances have led to the regular use of structured electronic health-care records with the potential to address key deficits in clinical evidence that could improve patient care. The COVID-19 pandemic has shown this potential in big data and related analytics but has also revealed important limitations. Data verification, data validation, data privacy, and a mandate from the public to conduct research are important challenges to effective use of routine health-care data. The European Society of Cardiology and the BigData@Heart consortium have brought together a range of international stakeholders, including representation from patients, clinicians, scientists, regulators, journal editors, and industry members. In this Review, we propose the CODE-EHR minimum standards framework to be used by researchers and clinicians to improve the design of studies and enhance transparency of study methods. The CODE-EHR framework aims to develop robust and effective utilisation of health-care data for research purposes.",,doi:https://doi.org/10.1016/s2589-7500(22)00151-0; doi:https://doi.org/10.1016/S2589-7500(22)00151-0 +37596262,https://doi.org/10.1038/s41467-023-40679-y,A genome-wide association study of blood cell morphology identifies cellular proteins implicated in disease aetiology.,"Akbari P, Vuckovic D, Stefanucci L, Jiang T, Kundu K, Kreuzhuber R, Bao EL, Collins JH, Downes K, Grassi L, Guerrero JA, Kaptoge S, Knight JC, Meacham S, Sambrook J, Seyres D, Stegle O, Verboon JM, Walter K, Watkins NA, Danesh J, Roberts DJ, Di Angelantonio E, Sankaran VG, Frontini M, Burgess S, Kuijpers T, Peters JE, Butterworth AS, Ouwehand WH, Soranzo N, Astle WJ.",,Nature communications,2023,2023-08-18,Y,,,,"Blood cells contain functionally important intracellular structures, such as granules, critical to immunity and thrombosis. Quantitative variation in these structures has not been subjected previously to large-scale genetic analysis. We perform genome-wide association studies of 63 flow-cytometry derived cellular phenotypes-including cell-type specific measures of granularity, nucleic acid content and reactivity-in 41,515 participants in the INTERVAL study. We identify 2172 distinct variant-trait associations, including associations near genes coding for proteins in organelles implicated in inflammatory and thrombotic diseases. By integrating with epigenetic data we show that many intracellular structures are likely to be determined in immature precursor cells. By integrating with proteomic data we identify the transcription factor FOG2 as an early regulator of platelet formation and α-granularity. Finally, we show that colocalisation of our associations with disease risk signals can suggest aetiological cell-types-variants in IL2RA and ITGA4 respectively mirror the known effects of daclizumab in multiple sclerosis and vedolizumab in inflammatory bowel disease.",,doi:https://doi.org/10.1038/s41467-023-40679-y; html:https://europepmc.org/articles/PMC10439125; pdf:https://europepmc.org/articles/PMC10439125?pdf=render 38198570,https://doi.org/10.1126/scitranslmed.adf4428,Prospective study design and data analysis in UK Biobank.,"Allen NE, Lacey B, Lawlor DA, Pell JP, Gallacher J, Smeeth L, Elliott P, Matthews PM, Lyons RA, Whetton AD, Lucassen A, Hurles ME, Chapman M, Roddam AW, Fitzpatrick NK, Hansell AL, Hardy R, Marioni RE, O'Donnell VB, Williams J, Lindgren CM, Effingham M, Sellors J, Danesh J, Collins R.",,Science translational medicine,2024,2024-01-10,N,,,,"Population-based prospective studies, such as UK Biobank, are valuable for generating and testing hypotheses about the potential causes of human disease. We describe how UK Biobank's study design, data access policies, and approaches to statistical analysis can help to minimize error and improve the interpretability of research findings, with implications for other population-based prospective studies being established worldwide.",,pdf:https://www.pure.ed.ac.uk/ws/files/405264227/scitranslmed.adf4428.pdf; doi:https://doi.org/10.1126/scitranslmed.adf4428; html:https://europepmc.org/articles/PMC11127744; pdf:https://europepmc.org/articles/PMC11127744?pdf=render; doi:https://doi.org/10.1126/scitranslmed.adf4428 37817277,https://doi.org/10.1186/s13063-023-07656-8,"e-Consent in UK academic-led clinical trials: current practice, challenges and the need for more evidence.","Mitchell EJ, Appelbe D, Bravery A, Culliford L, Evans H, Farrin AJ, Gillies K, Hood K, Love SB, Sydes MR, Williamson PR, Wakefield N, as part of the e-Consent collaborative group.",,Trials,2023,2023-10-10,Y,Consent; Clinical Trial; E-consent,,,"

Background

During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent.

Methods

A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April-June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research.

Results

Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions.

Conclusion

e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent.",,doi:https://doi.org/10.1186/s13063-023-07656-8; html:https://europepmc.org/articles/PMC10565982; pdf:https://europepmc.org/articles/PMC10565982?pdf=render 38633019,https://doi.org/10.1002/lrh2.10391,ROAD2H: Development and evaluation of an open-source explainable artificial intelligence approach for managing co-morbidity and clinical guidelines.,"Domínguez J, Prociuk D, Marović B, Čyras K, Cocarascu O, Ruiz F, Mi E, Mi E, Ramtale C, Rago A, Darzi A, Toni F, Curcin V, Delaney B.",,Learning health systems,2024,2023-09-12,Y,Clinical Decision Support Systems; Argumentation; Fhir; Cds Hooks; Co‐morbidity; Transition‐based Medical Recommendation Model,,,"

Introduction

Clinical decision support (CDS) systems (CDSSs) that integrate clinical guidelines need to reflect real-world co-morbidity. In patient-specific clinical contexts, transparent recommendations that allow for contraindications and other conflicts arising from co-morbidity are a requirement. In this work, we develop and evaluate a non-proprietary, standards-based approach to the deployment of computable guidelines with explainable argumentation, integrated with a commercial electronic health record (EHR) system in Serbia, a middle-income country in West Balkans.

Methods

We used an ontological framework, the Transition-based Medical Recommendation (TMR) model, to represent, and reason about, guideline concepts, and chose the 2017 International global initiative for chronic obstructive lung disease (GOLD) guideline and a Serbian hospital as the deployment and evaluation site, respectively. To mitigate potential guideline conflicts, we used a TMR-based implementation of the Assumptions-Based Argumentation framework extended with preferences and Goals (ABA+G). Remote EHR integration of computable guidelines was via a microservice architecture based on HL7 FHIR and CDS Hooks. A prototype integration was developed to manage chronic obstructive pulmonary disease (COPD) with comorbid cardiovascular or chronic kidney diseases, and a mixed-methods evaluation was conducted with 20 simulated cases and five pulmonologists.

Results

Pulmonologists agreed 97% of the time with the GOLD-based COPD symptom severity assessment assigned to each patient by the CDSS, and 98% of the time with one of the proposed COPD care plans. Comments were favourable on the principles of explainable argumentation; inclusion of additional co-morbidities was suggested in the future along with customisation of the level of explanation with expertise.

Conclusion

An ontological model provided a flexible means of providing argumentation and explainable artificial intelligence for a long-term condition. Extension to other guidelines and multiple co-morbidities is needed to test the approach further.",,doi:https://doi.org/10.1002/lrh2.10391; html:https://europepmc.org/articles/PMC11019374; pdf:https://europepmc.org/articles/PMC11019374?pdf=render @@ -750,8 +750,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 32838035,https://doi.org/10.1002/lrh2.10236,Rapid translation of clinical guidelines into executable knowledge: A case study of COVID-19 and online demonstration.,"Fox J, Khan O, Curtis H, Wright A, Pal C, Cockburn N, Cooper J, Chandan JS, Nirantharakumar K.",,Learning health systems,2021,2020-07-14,Y,Artificial intelligence; Covid‐19; Rapid Learning Systems,,,"

Introduction

We report a pathfinder study of AI/knowledge engineering methods to rapidly formalise COVID-19 guidelines into an executable model of decision making and care pathways. The knowledge source for the study was material published by BMJ Best Practice in March 2020.

Methods

The PROforma guideline modelling language and OpenClinical.net authoring and publishing platform were used to create a data model for care of COVID-19 patients together with executable models of rules, decisions and plans that interpret patient data and give personalised care advice.

Results

PROforma and OpenClinical.net proved to be an effective combination for rapidly creating the COVID-19 model; the Pathfinder 1 demonstrator is available for assessment at https://www.openclinical.net/index.php?id=746.

Conclusions

This is believed to be the first use of AI/knowledge engineering methods for disseminating best-practice in COVID-19 care. It demonstrates a novel and promising approach to the rapid translation of clinical guidelines into point of care services, and a foundation for rapid learning systems in many areas of healthcare.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/lrh2.10236; doi:https://doi.org/10.1002/lrh2.10236; html:https://europepmc.org/articles/PMC7323421; pdf:https://europepmc.org/articles/PMC7323421?pdf=render 37798805,https://doi.org/10.1186/s13063-023-07576-7,"Medicines and Healthcare products Regulatory Agency's ""Consultation on proposals for legislative changes for clinical trials"": a response from the Trials Methodology Research Partnership Adaptive Designs Working Group, with a focus on data sharing.","Law M, Couturier DL, Choodari-Oskooei B, Crout P, Gamble C, Jacko P, Pallmann P, Pilling M, Robertson DS, Robling M, Sydes MR, Villar SS, Wason J, Wheeler G, Williamson SF, Yap C, Jaki T.",,Trials,2023,2023-10-05,Y,Legislation; data sharing; Consultation,,,"In the UK, the Medicines and Healthcare products Regulatory Agency consulted on proposals ""to improve and strengthen the UK clinical trials legislation to help us make the UK the best place to research and develop safe and innovative medicines"". The purpose of the consultation was to help finalise the proposals and contribute to the drafting of secondary legislation. We discussed these proposals as members of the Trials Methodology Research Partnership Adaptive Designs Working Group, which is jointly funded by the Medical Research Council and the National Institute for Health and Care Research. Two topics arose frequently in the discussion: the emphasis on legislation, and the absence of questions on data sharing. It is our opinion that the proposals rely heavily on legislation to change practice. However, clinical trials are heterogeneous, and as a result some trials will struggle to comply with all of the proposed legislation. Furthermore, adaptive design clinical trials are even more heterogeneous than their non-adaptive counterparts, and face more challenges. Consequently, it is possible that increased legislation could have a greater negative impact on adaptive designs than non-adaptive designs. Overall, we are sceptical that the introduction of legislation will achieve the desired outcomes, with some exceptions. Meanwhile the topic of data sharing - making anonymised individual-level clinical trial data available to other investigators for further use - is entirely absent from the proposals and the consultation in general. However, as an aspect of the wider concept of open science and reproducible research, data sharing is an increasingly important aspect of clinical trials. The benefits of data sharing include faster innovation, improved surveillance of drug safety and effectiveness and decreasing participant exposure to unnecessary risk. There are already a number of UK-focused documents that discuss and encourage data sharing, for example, the Concordat on Open Research Data and the Medical Research Council's Data Sharing Policy. We strongly suggest that data sharing should be the norm rather than the exception, and hope that the forthcoming proposals on clinical trials invite discussion on this important topic.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07576-7; doi:https://doi.org/10.1186/s13063-023-07576-7; html:https://europepmc.org/articles/PMC10552399; pdf:https://europepmc.org/articles/PMC10552399?pdf=render 36810190,https://doi.org/10.1136/bmjebm-2023-112253,Digitally enabled decentralised research: opportunities to improve the efficiency of clinical trials and observational studies.,"Aiyegbusi OL, Davies EH, Myles P, Williams T, Frost C, Haroon S, Hughes SE, Wilson R, McMullan C, Subramanian A, Nirantharakumar K, Calvert MJ.",,BMJ evidence-based medicine,2023,2023-02-21,Y,information technology; drug discovery; Drug Development; Covid-19,,,,,pdf:https://ebm.bmj.com/content/ebmed/early/2023/02/20/bmjebm-2023-112253.full.pdf; doi:https://doi.org/10.1136/bmjebm-2023-112253; html:https://europepmc.org/articles/PMC10579468; pdf:https://europepmc.org/articles/PMC10579468?pdf=render -37367415,https://doi.org/10.3390/jcdd10060250,Risk Factors of Secondary Cardiovascular Events in a Multi-Ethnic Asian Population with Acute Myocardial Infarction: A Retrospective Cohort Study from Malaysia.,"Ismail SR, Mohammad MSF, Butterworth AS, Chowdhury R, Danesh J, Di Angelantonio E, Griffin SJ, Pennells L, Wood AM, Md Noh MF, Shah SA.",,Journal of cardiovascular development and disease,2023,2023-06-09,Y,Myocardial infarction; risk factors; Asian; Cardiovascular Mortality; Major Adverse Cardiovascular Events,,,"This retrospective cohort study investigated the incidence and risk factors of major adverse cardiovascular events (MACE) after 1 year of first-documented myocardial infarctions (MIs) in a multi-ethnic Asian population. Secondary MACE were observed in 231 (14.3%) individuals, including 92 (5.7%) cardiovascular-related deaths. Both histories of hypertension and diabetes were associated with secondary MACE after adjustment for age, sex, and ethnicity (HR 1.60 [95%CI 1.22-2.12] and 1.46 [95%CI 1.09-1.97], respectively). With further adjustments for traditional risk factors, individuals with conduction disturbances demonstrated higher risks of MACE: new left-bundle branch block (HR 2.86 [95%CI 1.15-6.55]), right-bundle branch block (HR 2.09 [95%CI 1.02-4.29]), and second-degree heart block (HR 2.45 [95%CI 0.59-10.16]). These associations were broadly similar across different age, sex, and ethnicity groups, although somewhat greater for history of hypertension and BMI among women versus men, for HbA1c control in individuals aged >50 years, and for LVEF ≤ 40% in those with Indian versus Chinese or Bumiputera ethnicities. Several traditional and cardiac risk factors are associated with a higher risk of secondary major adverse cardiovascular events. In addition to hypertension and diabetes, the identification of conduction disturbances in individuals with first-onset MI may be useful for the risk stratification of high-risk individuals.",,pdf:https://www.mdpi.com/2308-3425/10/6/250/pdf?version=1686288586; doi:https://doi.org/10.3390/jcdd10060250; html:https://europepmc.org/articles/PMC10299045; pdf:https://europepmc.org/articles/PMC10299045?pdf=render 33939619,https://doi.org/10.2196/29072,Predicting Risk of Hospital Admission in Patients With Suspected COVID-19 in a Community Setting: Protocol for Development and Validation of a Multivariate Risk Prediction Tool.,"Espinosa-Gonzalez AB, Neves AL, Fiorentino F, Prociuk D, Husain L, Ramtale SC, Mi E, Mi E, Macartney J, Anand SN, Sherlock J, Saravanakumar K, Mayer E, de Lusignan S, Greenhalgh T, Delaney BC.",,JMIR research protocols,2021,2021-05-25,Y,Primary Care; Hospital Admission; Electronic Health Records; Early Warning Score; Risk Prediction Tool; Covid-19 Severity,,,"

Background

During the pandemic, remote consultations have become the norm for assessing patients with signs and symptoms of COVID-19 to decrease the risk of transmission. This has intensified the clinical uncertainty already experienced by primary care clinicians when assessing patients with suspected COVID-19 and has prompted the use of risk prediction scores, such as the National Early Warning Score (NEWS2), to assess severity and guide treatment. However, the risk prediction tools available have not been validated in a community setting and are not designed to capture the idiosyncrasies of COVID-19 infection.

Objective

The objective of this study is to produce a multivariate risk prediction tool, RECAP-V1 (Remote COVID-19 Assessment in Primary Care), to support primary care clinicians in the identification of those patients with COVID-19 that are at higher risk of deterioration and facilitate the early escalation of their treatment with the aim of improving patient outcomes.

Methods

The study follows a prospective cohort observational design, whereby patients presenting in primary care with signs and symptoms suggestive of COVID-19 will be followed and their data linked to hospital outcomes (hospital admission and death). Data collection will be carried out by primary care clinicians in four arms: North West London Clinical Commissioning Groups (NWL CCGs), Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC), Covid Clinical Assessment Service (CCAS), and South East London CCGs (Doctaly platform). The study involves the use of an electronic template that incorporates a list of items (known as RECAP-V0) thought to be associated with disease outcome according to previous qualitative work. Data collected will be linked to patient outcomes in highly secure environments. We will then use multivariate logistic regression analyses for model development and validation.

Results

Recruitment of participants started in October 2020. Initially, only the NWL CCGs and RCGP RSC arms were active. As of March 24, 2021, we have recruited a combined sample of 3827 participants in these two arms. CCAS and Doctaly joined the study in February 2021, with CCAS starting the recruitment process on March 15, 2021. The first part of the analysis (RECAP-V1 model development) is planned to start in April 2021 using the first half of the NWL CCGs and RCGP RSC combined data set. Posteriorly, the model will be validated with the rest of the NWL CCGs and RCGP RSC data as well as the CCAS and Doctaly data sets. The study was approved by the Research Ethics Committee on May 27, 2020 (Integrated Research Application System number: 283024, Research Ethics Committee reference number: 20/NW/0266) and badged as National Institute of Health Research Urgent Public Health Study on October 14, 2020.

Conclusions

We believe the validated RECAP-V1 early warning score will be a valuable tool for the assessment of severity in patients with suspected COVID-19 in the community, either in face-to-face or remote consultations, and will facilitate the timely escalation of treatment with the potential to improve patient outcomes.

Trial registration

ISRCTN registry ISRCTN13953727; https://www.isrctn.com/ISRCTN13953727.

International registered report identifier (irrid)

DERR1-10.2196/29072.",,pdf:https://jmir.org/api/download?alt_name=resprot_v10i5e29072_app1.pdf&filename=e079f888f9036dd40808005eb7b49b6f.pdf; doi:https://doi.org/10.2196/29072; html:https://europepmc.org/articles/PMC8153031 +37367415,https://doi.org/10.3390/jcdd10060250,Risk Factors of Secondary Cardiovascular Events in a Multi-Ethnic Asian Population with Acute Myocardial Infarction: A Retrospective Cohort Study from Malaysia.,"Ismail SR, Mohammad MSF, Butterworth AS, Chowdhury R, Danesh J, Di Angelantonio E, Griffin SJ, Pennells L, Wood AM, Md Noh MF, Shah SA.",,Journal of cardiovascular development and disease,2023,2023-06-09,Y,Myocardial infarction; risk factors; Asian; Cardiovascular Mortality; Major Adverse Cardiovascular Events,,,"This retrospective cohort study investigated the incidence and risk factors of major adverse cardiovascular events (MACE) after 1 year of first-documented myocardial infarctions (MIs) in a multi-ethnic Asian population. Secondary MACE were observed in 231 (14.3%) individuals, including 92 (5.7%) cardiovascular-related deaths. Both histories of hypertension and diabetes were associated with secondary MACE after adjustment for age, sex, and ethnicity (HR 1.60 [95%CI 1.22-2.12] and 1.46 [95%CI 1.09-1.97], respectively). With further adjustments for traditional risk factors, individuals with conduction disturbances demonstrated higher risks of MACE: new left-bundle branch block (HR 2.86 [95%CI 1.15-6.55]), right-bundle branch block (HR 2.09 [95%CI 1.02-4.29]), and second-degree heart block (HR 2.45 [95%CI 0.59-10.16]). These associations were broadly similar across different age, sex, and ethnicity groups, although somewhat greater for history of hypertension and BMI among women versus men, for HbA1c control in individuals aged >50 years, and for LVEF ≤ 40% in those with Indian versus Chinese or Bumiputera ethnicities. Several traditional and cardiac risk factors are associated with a higher risk of secondary major adverse cardiovascular events. In addition to hypertension and diabetes, the identification of conduction disturbances in individuals with first-onset MI may be useful for the risk stratification of high-risk individuals.",,pdf:https://www.mdpi.com/2308-3425/10/6/250/pdf?version=1686288586; doi:https://doi.org/10.3390/jcdd10060250; html:https://europepmc.org/articles/PMC10299045; pdf:https://europepmc.org/articles/PMC10299045?pdf=render 33602244,https://doi.org/10.1186/s12916-021-01924-7,The impact of local and national restrictions in response to COVID-19 on social contacts in England: a longitudinal natural experiment.,"Jarvis CI, Gimma A, van Zandvoort K, Wong KLM, CMMID COVID-19 working group, Edmunds WJ.",,BMC medicine,2021,2021-02-19,Y,Pandemic; England; United Kingdom; Disease Outbreak; Non-pharmaceutical Interventions; Covid-19; Contact Survey; Lockdowns,,,"

Background

England's COVID-19 response transitioned from a national lockdown to localised interventions. In response to rising cases, these were supplemented by national restrictions on contacts (the Rule of Six), then 10 pm closing for bars and restaurants, and encouragement to work from home. These were quickly followed by a 3-tier system applying different restrictions in different localities. As cases continued to rise, a second national lockdown was declared. We used a national survey to quantify the impact of these restrictions on epidemiologically relevant contacts.

Methods

We compared paired measures on setting-specific contacts before and after each restriction started and tested for differences using paired permutation tests on the mean change in contacts and the proportion of individuals decreasing their contacts.

Results

Following the imposition of each measure, individuals tended to report fewer contacts than they had before. However, the magnitude of the changes was relatively small and variable. For instance, although early closure of bars and restaurants appeared to have no measurable effect on contacts, the work from home directive reduced mean daily work contacts by 0.99 (95% confidence interval CI] 0.03-1.94), and the Rule of Six reduced non-work and school contacts by a mean of 0.25 (0.01-0.5) per day. Whilst Tier 3 appeared to also reduce non-work and school contacts, the evidence for an effect of the lesser restrictions (Tiers 1 and 2) was much weaker. There may also have been some evidence of saturation of effects, with those who were in Tier 1 (least restrictive) reducing their contacts markedly when they entered lockdown, which was not reflected in similar changes in those who were already under tighter restrictions (Tiers 2 and 3).

Conclusions

The imposition of various local and national measures in England during the summer and autumn of 2020 has gradually reduced contacts. However, these changes are smaller than the initial lockdown in March. This may partly be because many individuals were already starting from a lower number of contacts.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-01924-7; doi:https://doi.org/10.1186/s12916-021-01924-7; html:https://europepmc.org/articles/PMC7892289; pdf:https://europepmc.org/articles/PMC7892289?pdf=render 37456658,https://doi.org/10.12688/hrbopenres.13667.1,Qualitative data sharing practices in clinical trials in the UK and Ireland: towards the production of good practice guidance.,"McCarthy M, Gillies K, Rousseau N, Wade J, Gamble C, Toomey E, Matvienko-Sikar K, Sydes M, Dowling M, Bryant V, Biesty L, Houghton C.",,HRB open research,2023,2023-02-06,Y,data sharing; Qualitative; trials; Focus Groups,,,"Background: Data sharing enables researchers to conduct novel research with previously collected datasets, thus maximising scientific findings and cost effectiveness, and reducing research waste. The value of sharing, even de-identified, quantitative data from clinical trials is well recognised with a moderated access approach recommended. While substantial challenges to sharing quantitative data remain, there are additional challenges for sharing qualitative data in trials. Incorporating the necessary information about how qualitative data will be shared into already complex trial recruitment and consent processes proves challenging. The aim of this study was to explore whether and how trial teams share qualitative data collected as part of the design, conduct, analysis, or delivery of clinical trials. Methods: Phase 1 involved semi-structured, in-depth qualitative interviews and focus groups with key trial stakeholder groups including trial managers and clinical trialists (n=3), qualitative researchers in trials (n=9), members of research funding bodies (n=2) and trial participants (n=1). Data were analysed using thematic analysis. In Phase 2, we conducted a content analysis of 16 participant information leaflets (PIL) and consent forms (CF) for trials that collected qualitative data. Results: Three key themes were identified from our Phase 1 findings: ' Understanding and experiences of the potential benefits of sharing qualitative data from trials', 'Concerns about qualitative data sharing', and ' Future guidance and funding'. In phase 2, the PILs and CFs received revealed that the benefits of data sharing for participants were only explained in two of the study documents. Conclusions: The value of sharing qualitative data was acknowledged, but there are many uncertainties as to how, when, and where to share this data. In addition, there were ethical concerns in relation to the consent process required for qualitative data sharing in trials. This study provides insight into the existing practice of qualitative data sharing in trials.",,pdf:https://hrbopenresearch.org/articles/6-10/pdf; doi:https://doi.org/10.12688/hrbopenres.13667.1; html:https://europepmc.org/articles/PMC10345597; pdf:https://europepmc.org/articles/PMC10345597?pdf=render 37578823,https://doi.org/10.2196/45233,Challenges in Using mHealth Data From Smartphones and Wearable Devices to Predict Depression Symptom Severity: Retrospective Analysis.,"Sun S, Folarin AA, Zhang Y, Cummins N, Garcia-Dias R, Stewart C, Ranjan Y, Rashid Z, Conde P, Laiou P, Sankesara H, Matcham F, Leightley D, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Simblett S, Nica R, Rintala A, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BWJH, Vairavan S, Narayan VA, Annas P, Hotopf M, Dobson RJB, RADAR-CNS Consortium.",,Journal of medical Internet research,2023,2023-08-14,Y,Depression; Mobile phone; Missing Data; Smartphones; Behavioral Patterns; Digital Phenotypes; Mobile Health; Wearable Devices,,,"

Background

Major depressive disorder (MDD) affects millions of people worldwide, but timely treatment is not often received owing in part to inaccurate subjective recall and variability in the symptom course. Objective and frequent MDD monitoring can improve subjective recall and help to guide treatment selection. Attempts have been made, with varying degrees of success, to explore the relationship between the measures of depression and passive digital phenotypes (features) extracted from smartphones and wearables devices to remotely and continuously monitor changes in symptomatology. However, a number of challenges exist for the analysis of these data. These include maintaining participant engagement over extended time periods and therefore understanding what constitutes an acceptable threshold of missing data; distinguishing between the cross-sectional and longitudinal relationships for different features to determine their utility in tracking within-individual longitudinal variation or screening individuals at high risk; and understanding the heterogeneity with which depression manifests itself in behavioral patterns quantified by the passive features.

Objective

We aimed to address these 3 challenges to inform future work in stratified analyses.

Methods

Using smartphone and wearable data collected from 479 participants with MDD, we extracted 21 features capturing mobility, sleep, and smartphone use. We investigated the impact of the number of days of available data on feature quality using the intraclass correlation coefficient and Bland-Altman analysis. We then examined the nature of the correlation between the 8-item Patient Health Questionnaire (PHQ-8) depression scale (measured every 14 days) and the features using the individual-mean correlation, repeated measures correlation, and linear mixed effects model. Furthermore, we stratified the participants based on their behavioral difference, quantified by the features, between periods of high (depression) and low (no depression) PHQ-8 scores using the Gaussian mixture model.

Results

We demonstrated that at least 8 (range 2-12) days were needed for reliable calculation of most of the features in the 14-day time window. We observed that features such as sleep onset time correlated better with PHQ-8 scores cross-sectionally than longitudinally, whereas features such as wakefulness after sleep onset correlated well with PHQ-8 longitudinally but worse cross-sectionally. Finally, we found that participants could be separated into 3 distinct clusters according to their behavioral difference between periods of depression and periods of no depression.

Conclusions

This work contributes to our understanding of how these mobile health-derived features are associated with depression symptom severity to inform future work in stratified analyses.",,pdf:https://www.jmir.org/2023/1/e45233/PDF; doi:https://doi.org/10.2196/45233; html:https://europepmc.org/articles/PMC10463088 @@ -760,8 +760,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 32553130,https://doi.org/10.1016/s2214-109x(20)30264-3,"Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study.","Clark A, Jit M, Warren-Gash C, Guthrie B, Wang HHX, Mercer SW, Sanderson C, McKee M, Troeger C, Ong KL, Checchi F, Perel P, Joseph S, Gibbs HP, Banerjee A, Eggo RM, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 working group.",,The Lancet. Global health,2020,2020-06-15,Y,,,,"

Background

The risk of severe COVID-19 if an individual becomes infected is known to be higher in older individuals and those with underlying health conditions. Understanding the number of individuals at increased risk of severe COVID-19 and how this varies between countries should inform the design of possible strategies to shield or vaccinate those at highest risk.

Methods

We estimated the number of individuals at increased risk of severe disease (defined as those with at least one condition listed as ""at increased risk of severe COVID-19"" in current guidelines) by age (5-year age groups), sex, and country for 188 countries using prevalence data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 and UN population estimates for 2020. The list of underlying conditions relevant to COVID-19 was determined by mapping the conditions listed in GBD 2017 to those listed in guidelines published by WHO and public health agencies in the UK and the USA. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity. To help interpretation of the degree of risk among those at increased risk, we also estimated the number of individuals at high risk (defined as those that would require hospital admission if infected) using age-specific infection-hospitalisation ratios for COVID-19 estimated for mainland China and making adjustments to reflect country-specific differences in the prevalence of underlying conditions and frailty. We assumed males were twice at likely as females to be at high risk. We also calculated the number of individuals without an underlying condition that could be considered at increased risk because of their age, using minimum ages from 50 to 70 years. We generated uncertainty intervals (UIs) for our estimates by running low and high scenarios using the lower and upper 95% confidence limits for country population size, disease prevalences, multimorbidity fractions, and infection-hospitalisation ratios, and plausible low and high estimates for the degree of clustering, informed by multimorbidity studies.

Findings

We estimated that 1·7 billion (UI 1·0-2·4) people, comprising 22% (UI 15-28) of the global population, have at least one underlying condition that puts them at increased risk of severe COVID-19 if infected (ranging from <5% of those younger than 20 years to >66% of those aged 70 years or older). We estimated that 349 million (186-787) people (4% [3-9] of the global population) are at high risk of severe COVID-19 and would require hospital admission if infected (ranging from <1% of those younger than 20 years to approximately 20% of those aged 70 years or older). We estimated 6% (3-12) of males to be at high risk compared with 3% (2-7) of females. The share of the population at increased risk was highest in countries with older populations, African countries with high HIV/AIDS prevalence, and small island nations with high diabetes prevalence. Estimates of the number of individuals at increased risk were most sensitive to the prevalence of chronic kidney disease, diabetes, cardiovascular disease, and chronic respiratory disease.

Interpretation

About one in five individuals worldwide could be at increased risk of severe COVID-19, should they become infected, due to underlying health conditions, but this risk varies considerably by age. Our estimates are uncertain, and focus on underlying conditions rather than other risk factors such as ethnicity, socioeconomic deprivation, and obesity, but provide a starting point for considering the number of individuals that might need to be shielded or vaccinated as the global pandemic unfolds.

Funding

UK Department for International Development, Wellcome Trust, Health Data Research UK, Medical Research Council, and National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S2214109X20302643/pdf; doi:https://doi.org/10.1016/S2214-109X(20)30264-3; html:https://europepmc.org/articles/PMC7295519 35485805,https://doi.org/10.1017/s003329172200109x,Multimorbidity clusters among people with serious mental illness: a representative primary and secondary data linkage cohort study.,"Ma R, Romano E, Ashworth M, Yadegarfar ME, Dregan A, Ronaldson A, de Oliveira C, Jacobs R, Stewart R, Stubbs B.",,Psychological medicine,2023,2022-04-29,Y,Mortality; Schizophrenia; Psychosis; Physical Health; Multimorbidity,,,"

Background

People with serious mental illness (SMI) experience higher mortality partially attributable to higher long-term condition (LTC) prevalence. However, little is known about multiple LTCs (MLTCs) clustering in this population.

Methods

People from South London with SMI and two or more existing LTCs aged 18+ at diagnosis were included using linked primary and mental healthcare records, 2012-2020. Latent class analysis (LCA) determined MLTC classes and multinominal logistic regression examined associations between demographic/clinical characteristics and latent class membership.

Results

The sample included 1924 patients (mean (s.d.) age 48.2 (17.3) years). Five latent classes were identified: 'substance related' (24.9%), 'atopic' (24.2%), 'pure affective' (30.4%), 'cardiovascular' (14.1%), and 'complex multimorbidity' (6.4%). Patients had on average 7-9 LTCs in each cluster. Males were at increased odds of MLTCs in all four clusters, compared to the 'pure affective'. Compared to the largest cluster ('pure affective'), the 'substance related' and the 'atopic' clusters were younger [odds ratios (OR) per year increase 0.99 (95% CI 0.98-1.00) and 0.96 (0.95-0.97) respectively], and the 'cardiovascular' and 'complex multimorbidity' clusters were older (ORs 1.09 (1.07-1.10) and 1.16 (1.14-1.18) respectively). The 'substance related' cluster was more likely to be White, the 'cardiovascular' cluster more likely to be Black (compared to White; OR 1.75, 95% CI 1.10-2.79), and both more likely to have schizophrenia, compared to other clusters.

Conclusion

The current study identified five latent class MLTC clusters among patients with SMI. An integrated care model for treating MLTCs in this population is recommended to improve multimorbidity care.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/BDE3DC6059EB59B00B2E0CD892963804/S003329172200109Xa.pdf/div-class-title-multimorbidity-clusters-among-people-with-serious-mental-illness-a-representative-primary-and-secondary-data-linkage-cohort-study-div.pdf; doi:https://doi.org/10.1017/S003329172200109X; html:https://europepmc.org/articles/PMC10388332; pdf:https://europepmc.org/articles/PMC10388332?pdf=render 34912046,https://doi.org/10.1038/s41366-021-01048-1,"30-day morbidity and mortality of sleeve gastrectomy, Roux-en-Y gastric bypass and one anastomosis gastric bypass: a propensity score-matched analysis of the GENEVA data.","Singhal R, Cardoso VR, Wiggins T, Super J, Ludwig C, Gkoutos GV, Mahawar K, GENEVA Collaborators.",,International journal of obesity (2005),2022,2021-12-15,Y,,,,"

Background

There is a paucity of data comparing 30-day morbidity and mortality of sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and one anastomosis gastric bypass (OAGB). This study aimed to compare the 30-day safety of SG, RYGB, and OAGB in propensity score-matched cohorts.

Materials and methods

This analysis utilised data collected from the GENEVA study which was a multicentre observational cohort study of bariatric and metabolic surgery (BMS) in 185 centres across 42 countries between 01/05/2022 and 31/10/2020 during the Coronavirus Disease-2019 (COVID-19) pandemic. 30-day complications were categorised according to the Clavien-Dindo classification. Patients receiving SG, RYGB, or OAGB were propensity-matched according to baseline characteristics and 30-day complications were compared between groups.

Results

In total, 6770 patients (SG 3983; OAGB 702; RYGB 2085) were included in this analysis. Prior to matching, RYGB was associated with highest 30-day complication rate (SG 5.8%; OAGB 7.5%; RYGB 8.0% (p = 0.006)). On multivariate regression modelling, Insulin-dependent type 2 diabetes mellitus and hypercholesterolaemia were associated with increased 30-day complications. Being a non-smoker was associated with reduced complication rates. When compared to SG as a reference category, RYGB, but not OAGB, was associated with an increased rate of 30-day complications. A total of 702 pairs of SG and OAGB were propensity score-matched. The complication rate in the SG group was 7.3% (n = 51) as compared to 7.5% (n = 53) in the OAGB group (p = 0.68). Similarly, 2085 pairs of SG and RYGB were propensity score-matched. The complication rate in the SG group was 6.1% (n = 127) as compared to 7.9% (n = 166) in the RYGB group (p = 0.09). And, 702 pairs of OAGB and RYGB were matched. The complication rate in both groups was the same at 7.5 % (n = 53; p = 0.07).

Conclusions

This global study found no significant difference in the 30-day morbidity and mortality of SG, RYGB, and OAGB in propensity score-matched cohorts.",,pdf:https://www.nature.com/articles/s41366-021-01048-1.pdf; doi:https://doi.org/10.1038/s41366-021-01048-1; html:https://europepmc.org/articles/PMC8671878; pdf:https://europepmc.org/articles/PMC8671878?pdf=render -37185641,https://doi.org/10.1136/bmjopen-2022-070022,EXAcerbations of COPD and their OutcomeS on CardioVascular diseases (EXACOS-CV) Programme: protocol of multicountry observational cohort studies.,"Nordon C, Rhodes K, Quint JK, Vogelmeier CF, Simons SO, Hawkins NM, Marshall J, Ouwens M, Garbe E, Müllerová H.",,BMJ open,2023,2023-04-26,Y,epidemiology; Cardiology; Vascular Medicine; Chronic Airways Disease,,,"

Introduction

In patients with chronic obstructive pulmonary disease (COPD), the risk of certain cardiovascular (CV) events is increased by threefold to fivefold in the year following acute exacerbation of COPD (AECOPD), compared with a non-exacerbation period. While the effect of severe AECOPD is well established, the relationship of moderate exacerbation or prior exacerbation to elevated risk of CV events is less clear. We will conduct cohort studies in multiple countries to further characterise the association between AECOPD and CV events.

Methods and analysis

Retrospective longitudinal cohort studies will be conducted within routinely collected electronic healthcare records or claims databases. The study cohorts will include patients meeting inclusion criteria for COPD between 1 January 2014 and 31 December 2018. Moderate exacerbation is defined as an outpatient visit and/or medication dispensation/prescription for exacerbation; severe exacerbation is defined as hospitalisation for COPD. The primary outcomes of interest are the time to (1) first hospitalisation for a CV event (including acute coronary syndrome, heart failure, arrhythmias or cerebral ischaemia) since cohort entry or (2) death. Time-dependent Cox proportional hazards models will compare the hazard of a CV event between exposed periods following exacerbation (split into these periods: 1-7, 8-14, 15-30, 31-180 and 181-365 days) and the unexposed reference time period, adjusted on time-fixed and time-varying confounders.

Ethics and dissemination

Studies have been approved in Canada, Japan, the Netherlands, Spain and the UK, where an institutional review board is mandated. For each study, the results will be published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e070022.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-070022; html:https://europepmc.org/articles/PMC10151875; pdf:https://europepmc.org/articles/PMC10151875?pdf=render 35577541,https://doi.org/10.1136/archdischild-2021-323616,Changes in adolescents' planned hospital care during the COVID-19 pandemic: analysis of linked administrative data.,"Mc Grath-Lone L, Etoori D, Gilbert R, Harron KL, Woodman J, Blackburn R.",,Archives of disease in childhood,2022,2022-09-20,Y,Social Work; Child Health Services; Adolescent Health; Covid-19,,,"

Objective

To describe changes in planned hospital care during the pandemic for vulnerable adolescents receiving children's social care (CSC) services or special educational needs (SEN) support, relative to their peers.

Design

Observational cohort in the Education and Child Health Insights from Linked Data database (linked de-identified administrative health, education and social care records of all children in England).

Study population

All secondary school pupils in years 7-11 in academic year 2019/2020 (N=3 030 235).

Main exposure

Receiving SEN support or CSC services.

Main outcomes

Changes in outpatient attendances and planned hospital admissions during the first 9 months of the pandemic (23 March-31 December 2020), estimated by comparing predicted with observed numbers and rates per 1000 child-years.

Results

A fifth of pupils (20.5%) received some form of statutory support: 14.2% received SEN support only, 3.6% received CSC services only and 2.7% received both. Decreases in planned hospital care were greater for these vulnerable adolescents than their peers: -290 vs -225 per 1000 child-years for outpatient attendances and -36 vs -16 per 1000 child-years for planned admissions. Overall, 21% of adolescents who were vulnerable disproportionately bore 25% of the decrease in outpatient attendances and 37% of the decrease in planned hospital admissions. Vulnerable adolescents were less likely than their peers to have face-to-face outpatient care.

Conclusion

These findings indicate that socially vulnerable groups of children have high health needs, which may need to be prioritised to ensure equitable provision, including for catch-up of planned care postpandemic.",,pdf:https://adc.bmj.com/content/archdischild/107/10/e29.full.pdf; doi:https://doi.org/10.1136/archdischild-2021-323616; html:https://europepmc.org/articles/PMC9157329; pdf:https://europepmc.org/articles/PMC9157329?pdf=render +37185641,https://doi.org/10.1136/bmjopen-2022-070022,EXAcerbations of COPD and their OutcomeS on CardioVascular diseases (EXACOS-CV) Programme: protocol of multicountry observational cohort studies.,"Nordon C, Rhodes K, Quint JK, Vogelmeier CF, Simons SO, Hawkins NM, Marshall J, Ouwens M, Garbe E, Müllerová H.",,BMJ open,2023,2023-04-26,Y,epidemiology; Cardiology; Vascular Medicine; Chronic Airways Disease,,,"

Introduction

In patients with chronic obstructive pulmonary disease (COPD), the risk of certain cardiovascular (CV) events is increased by threefold to fivefold in the year following acute exacerbation of COPD (AECOPD), compared with a non-exacerbation period. While the effect of severe AECOPD is well established, the relationship of moderate exacerbation or prior exacerbation to elevated risk of CV events is less clear. We will conduct cohort studies in multiple countries to further characterise the association between AECOPD and CV events.

Methods and analysis

Retrospective longitudinal cohort studies will be conducted within routinely collected electronic healthcare records or claims databases. The study cohorts will include patients meeting inclusion criteria for COPD between 1 January 2014 and 31 December 2018. Moderate exacerbation is defined as an outpatient visit and/or medication dispensation/prescription for exacerbation; severe exacerbation is defined as hospitalisation for COPD. The primary outcomes of interest are the time to (1) first hospitalisation for a CV event (including acute coronary syndrome, heart failure, arrhythmias or cerebral ischaemia) since cohort entry or (2) death. Time-dependent Cox proportional hazards models will compare the hazard of a CV event between exposed periods following exacerbation (split into these periods: 1-7, 8-14, 15-30, 31-180 and 181-365 days) and the unexposed reference time period, adjusted on time-fixed and time-varying confounders.

Ethics and dissemination

Studies have been approved in Canada, Japan, the Netherlands, Spain and the UK, where an institutional review board is mandated. For each study, the results will be published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e070022.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-070022; html:https://europepmc.org/articles/PMC10151875; pdf:https://europepmc.org/articles/PMC10151875?pdf=render 36525457,https://doi.org/10.1371/journal.pone.0279250,Undergoing radical treatment for prostate cancer and its impact on wellbeing: A qualitative study exploring men's experiences.,"Vyas N, Brunckhorst O, Fox L, Van Hemelrijck M, Muir G, Stewart R, Dasgupta P, Ahmed K.",,PloS one,2022,2022-12-16,Y,,,,"

Introduction

Quality of life in prostate cancer survivorship is becoming increasingly important, with mental and social wellbeing recognised as key components. However, limited global evaluation of psychosocial challenges experienced after treatment exists. Therefore, we aimed to explore the lived experiences of men who underwent radical treatment, and its psychosocial impact.

Material and methods

This qualitative study was conducted using 19 men who had undergone radical treatment (prostatectomy or radiotherapy) for their cancer. Semi-structured interviews were conducted exploring lived experiences of men after treatment. A Structured thematic analysis of collected data was undertaken, with an inductive co-construction of themes through the lens of the biopsychosocial model. Themes generated were considered within a psychological, social, and physical wellbeing framework.

Results

An initial knowledge gap meant mental wellbeing was strongly impacted initially leading to a 'Diagnostic Blow and the Search for Clarity'. Doubt over individuals' future resulted in 'An Uncertain Future' in many men. Once treatment was completed a 'Reflective journey' began, with men considering their outcomes and decisions made. Social wellbeing was also impacted with many identifying the 'Emotional Repercussions' on their relationships and the impact their diagnosis had on their partner and family. Many subsequently sought to increase their support through 'The Social Network and Advocacy', while physical changes led to an increased need for 'Social Planning'. Finally, physical wellbeing was highlighted by a continual acknowledgement of the 'Natural process of ageing' leading to a reluctancy to seek help, whilst simultaneously attempting to improve existing health via 'The Health Kick'.

Conclusions

Radical treatments have a considerable impact on mental and social wellbeing of individuals. Anxiety after diagnosis and significant uncertainty over individual futures exist, with physical complications of treatment leading to social repercussions. Future research should aim to identify forms of support to improve quality of life of these men.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279250&type=printable; doi:https://doi.org/10.1371/journal.pone.0279250; html:https://europepmc.org/articles/PMC9757548; pdf:https://europepmc.org/articles/PMC9757548?pdf=render 38383544,https://doi.org/10.1038/s41467-024-45761-7,The plasmidome associated with Gram-negative bloodstream infections: A large-scale observational study using complete plasmid assemblies.,"Lipworth S, Matlock W, Shaw L, Vihta KD, Rodger G, Chau K, Barker L, George S, Kavanagh J, Davies T, Vaughan A, Andersson M, Jeffery K, Oakley S, Morgan M, Hopkins S, Peto T, Crook D, Walker AS, Stoesser N.",,Nature communications,2024,2024-02-22,Y,,,,"Plasmids carry genes conferring antimicrobial resistance and other clinically important traits, and contribute to the rapid dissemination of such genes. Previous studies using complete plasmid assemblies, which are essential for reliable inference, have been small and/or limited to plasmids carrying antimicrobial resistance genes (ARGs). In this study, we sequenced 1,880 complete plasmids from 738 isolates from bloodstream infections in Oxfordshire, UK. The bacteria had been originally isolated in 2009 (194 isolates) and 2018 (368 isolates), plus a stratified selection from intervening years (176 isolates). We demonstrate that plasmids are largely, but not entirely, constrained to a single host species, although there is substantial overlap between species of plasmid gene-repertoire. Most ARGs are carried by a relatively small number of plasmid groups with biological features that are predictable. Plasmids carrying ARGs (including those encoding carbapenemases) share a putative 'backbone' of core genes with those carrying no such genes. These findings suggest that future surveillance should, in addition to tracking plasmids currently associated with clinically important genes, focus on identifying and monitoring the dissemination of high-risk plasmid groups with the potential to rapidly acquire and disseminate these genes.",,doi:https://doi.org/10.1038/s41467-024-45761-7; html:https://europepmc.org/articles/PMC10881496; pdf:https://europepmc.org/articles/PMC10881496?pdf=render 34800427,https://doi.org/10.1016/s0140-6736(21)01825-0,"Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2022,2021-11-17,Y,,,,"

Background

Aspirin has been proposed as a treatment for COVID-19 on the basis of its anti-thrombotic properties. We aimed to evaluate the efficacy and safety of aspirin in patients admitted to hospital with COVID-19.

Methods

In this randomised, controlled, open-label, platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. The trial took place at 177 hospitals in the UK, two hospitals in Indonesia, and two hospitals in Nepal. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care plus 150 mg aspirin once per day until discharge or usual standard of care alone using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28 day mortality. All analyses were done by intention to treat. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between Nov 1, 2020, and March 21, 2021, 14 892 (66%) of 22 560 patients enrolled into the RECOVERY trial were eligible to be randomly allocated to aspirin. 7351 patients were randomly allocated (1:1) to receive aspirin and 7541 patients to receive usual care alone. Overall, 1222 (17%) of 7351 patients allocated to aspirin and 1299 (17%) of 7541 patients allocated to usual care died within 28 days (rate ratio 0·96, 95% CI 0·89-1·04; p=0·35). Consistent results were seen in all prespecified subgroups of patients. Patients allocated to aspirin had a slightly shorter duration of hospitalisation (median 8 days, IQR 5 to >28, vs 9 days, IQR 5 to >28) and a higher proportion were discharged from hospital alive within 28 days (75% vs 74%; rate ratio 1·06, 95% CI 1·02-1·10; p=0·0062). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs 22%; risk ratio 0·96, 95% CI 0·90-1·03; p=0·23). Aspirin use was associated with a reduction in thrombotic events (4·6% vs 5·3%; absolute reduction 0·6%, SE 0·4%) and an increase in major bleeding events (1·6% vs 1·0%; absolute increase 0·6%, SE 0·2%).

Interpretation

In patients hospitalised with COVID-19, aspirin was not associated with reductions in 28 day mortality or in the risk of progressing to invasive mechanical ventilation or death, but was associated with a small increase in the rate of being discharged alive within 28 days.

Funding

UK Research and Innovation (Medical Research Council), National Institute of Health Research, and the Wellcome Trust through the COVID-19 Therapeutics Accelerator.",,doi:https://doi.org/10.1016/s0140-6736(21)01825-0; doi:https://doi.org/10.1016/S0140-6736(21)01825-0; html:https://europepmc.org/articles/PMC8598213 @@ -791,24 +791,24 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 36654802,https://doi.org/10.1002/lrh2.10315,"A framework for understanding, designing, developing and evaluating learning health systems.","Foley T, Vale L.",,Learning health systems,2023,2022-05-20,Y,Quality improvement; Informatics; Implementation Science; Learning Health Systems; Learning Healthcare Systems,,,"

Introduction

A Learning Health System is not a technical project. It is the evolution of an existing health system into one capable of learning from every patient. This paper outlines a recently published framework intended to aid the understanding, design, development and evaluation of Learning Health Systems.

Methods

This work extended an existing repository of Learning Health System evidence, adding five more workshops. The total was subjected to thematic analysis, yielding a framework of elements important to understanding, designing, developing and evaluating Learning Health Systems. Purposeful literature reviews were conducted on each element. The findings were revised following a review by a group of international experts.

Results

The resulting framework was arranged around four questions:What is our rationale for developing a Learning Health System?There can be many reasons for developing a Learning Health System. Understanding these will guide its development.What sources of complexity exist at the system and the intervention level?An understanding of complexity is central to making Learning Health Systems work. The non-adoption, abandonment, scale-up, spread and sustainability framework was utilised to help understand and manage it.What strategic approaches to change do we need to consider?A range of strategic issues must be addressed to enable successful change in a Learning Health System. These include, strategy, organisational structure, culture, workforce, implementation science, behaviour change, co-design and evaluation.What technical building blocks will we need?A Learning Health System must capture data from practice, turn it into knowledge and apply it back into practice. There are many methods to achieve this and a range of platforms to help.

Discussion

The results form a framework for understanding, designing, developing and evaluating Learning Health Systems at any scale.

Conclusion

It is hoped that this framework will evolve with use and feedback.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9835047; doi:https://doi.org/10.1002/lrh2.10315; html:https://europepmc.org/articles/PMC9835047; pdf:https://europepmc.org/articles/PMC9835047?pdf=render 37828025,https://doi.org/10.1038/s41467-023-41876-5,ADRA2A and IRX1 are putative risk genes for Raynaud's phenomenon.,"Hartmann S, Yasmeen S, Jacobs BM, Denaxas S, Pirmohamed M, Gamazon ER, Caulfield MJ, Genes & Health Research Team, Hemingway H, Pietzner M, Langenberg C.",,Nature communications,2023,2023-10-12,Y,,,,"Raynaud's phenomenon (RP) is a common vasospastic disorder that causes severe pain and ulcers, but despite its high reported heritability, no causal genes have been robustly identified. We conducted a genome-wide association study including 5,147 RP cases and 439,294 controls, based on diagnoses from electronic health records, and identified three unreported genomic regions associated with the risk of RP (p < 5 × 10-8). We prioritized ADRA2A (rs7090046, odds ratio (OR) per allele: 1.26; 95%-CI: 1.20-1.31; p < 9.6 × 10-27) and IRX1 (rs12653958, OR: 1.17; 95%-CI: 1.12-1.22, p < 4.8 × 10-13) as candidate causal genes through integration of gene expression in disease relevant tissues. We further identified a likely causal detrimental effect of low fasting glucose levels on RP risk (rG = -0.21; p-value = 2.3 × 10-3), and systematically highlighted drug repurposing opportunities, like the antidepressant mirtazapine. Our results provide the first robust evidence for a strong genetic contribution to RP and highlight a so far underrated role of α2A-adrenoreceptor signalling, encoded at ADRA2A, as a possible mechanism for hypersensitivity to catecholamine-induced vasospasms.",,pdf:https://www.nature.com/articles/s41467-023-41876-5.pdf; doi:https://doi.org/10.1038/s41467-023-41876-5; html:https://europepmc.org/articles/PMC10570309; pdf:https://europepmc.org/articles/PMC10570309?pdf=render 34765951,https://doi.org/10.1016/j.eclinm.2021.101163,Net effects of sodium-glucose co-transporter-2 inhibition in different patient groups: a meta-analysis of large placebo-controlled randomized trials.,"Staplin N, Roddick AJ, Emberson J, Reith C, Riding A, Wonnacott A, Kuverji A, Bhandari S, Baigent C, Haynes R, Herrington WG.",,EClinicalMedicine,2021,2021-10-26,Y,Safety; Heart Failure; Randomized Trials; Ckd; Sodium-glucose Co-transporter 2 Inhibitors,,,"

Background

The net absolute effects of sodium-glucose co-transporter-2 (SGLT-2) inhibitors across different patient groups have not been quantified.

Methods

We performed a meta-analysis of published large (>500 participants/arm) placebo-controlled SGLT-2 inhibitor trials after systematically searching MEDLINE and Embase databases from inception to 28th August 2021 (PROSPERO 2021 CRD42021240468).

Findings

Four heart failure trials (n=15,684 participants), four trials in type 2 diabetes mellitus at high atherosclerotic cardiovascular risk (n=42,568), and three trials in chronic kidney disease (n=19,289) were included. Relative risks (RRs) for all cardiovascular, renal and safety outcomes were broadly similar across these three patient groups, and between people with or without diabetes. Overall, compared to placebo, allocation to SGLT-2 inhibition reduced risk of hospitalization for heart failure or cardiovascular death by 23% (RR=0.77, 95%CI 0.73-0.80; n=6658), cardiovascular death by 14% (0.86, 0.81-0.92; n=3962), major adverse cardiovascular events by 11% (0.89, 0.84-0.94; n=5703), kidney disease progression by 36% (0.64, 0.59-0.70; n=2275), acute kidney injury by 30% (0.70, 0.62-0.79; n=1013 events) and severe hypoglycaemia by 13% (0.87, 0.79-0.97; n=1484). There was no effect of SGLT-2 inhibition on risk of non-cardiovascular death (0.93, 0.86-1.01; n=2226), but a net 12% reduction in all-cause mortality remained evident (0.88, 0.84-0.93; n=6188). However, the risk of ketoacidosis was 2-times higher among those allocated SGLT-2 inhibitors compared to placebo (2.03, 1.41-2.93; n=159; absolute excess in people with diabetes ∼0.3/1000 patient years). A small increased risk of urinary tract infection was evident (1.07, 1.02-1.13; n=5384) alongside a known increased risk of mycotic genital infections. Overall, risk of lower limb amputations was increased by 16% (1.16, 1.02-1.31; n=1074), but this risk was largely driven by a single outlying trial (CANVAS).

Interpretations

The relative effects of SGLT-2 inhibition on key safety and efficacy outcomes are consistent across the different studied groups of patient. Consequently, absolute benefits and harms are determined by the absolute baseline risk of particular outcomes, with absolute benefits on mortality and on non-fatal serious cardiac/renal outcomes substantially exceeding the risks of amputation and ketoacidosis in the main patient groups studied to date.

Funding

MRC-UK & KRUK.",,doi:https://doi.org/10.1016/j.eclinm.2021.101163; doi:https://doi.org/10.1016/j.eclinm.2021.101163; html:https://europepmc.org/articles/PMC8571171; pdf:https://europepmc.org/articles/PMC8571171?pdf=render -37812323,https://doi.org/10.1186/s41687-023-00634-3,Development and usability testing of an electronic patient-reported outcome (ePRO) solution for patients with inflammatory diseases in an Advanced Therapy Medicinal Product (ATMP) basket trial.,"McMullan C, Retzer A, Hughes SE, Aiyegbusi OL, Bathurst C, Boyd A, Coleman J, Davies EH, Denniston AK, Dunster H, Frost C, Harding R, Hunn A, Kyte D, Malpass R, McNamara G, Mitchell S, Mittal S, Newsome PN, Price G, Rowe A, van Reil W, Walker A, Wilson R, Calvert M.",,Journal of patient-reported outcomes,2023,2023-10-09,Y,Inflammatory Conditions; Usability Testing; Cognitive Interviews; Electronic Patient Reported Outcomes; Early Phase Advanced Therapy Trial,,,"

Background

Electronic patient-reported outcome (ePRO) systems are increasingly used in clinical trials to provide evidence of efficacy and tolerability of treatment from the patient perspective. The aim of this study is twofold: (1) to describe how we developed an electronic platform for patients to report their symptoms, and (2) to develop and undertake usability testing of an ePRO solution for use in a study of cell therapy seeking to provide early evidence of efficacy and tolerability of treatment and test the feasibility of the system for use in later phase studies.

Methods

An ePRO system was designed to be used in a single arm, multi-centre, phase II basket trial investigating the safety and activity of the use of ORBCEL-C™ in the treatment of patients with inflammatory conditions. ORBCEL-C™ is an enriched Mesenchymal Stromal Cells product isolated from human umbilical cord tissue using CD362+ cell selection. Usability testing sessions were conducted using cognitive interviews and the 'Think Aloud' method with patient advisory group members and Research Nurses to assess the usability of the system.

Results

Nine patient partners and seven research nurses took part in one usability testing session. Measures of fatigue and health-related quality of life, the PRO-CTCAE™ and FACT-GP5 global tolerability question were included in the ePRO system. Alert notifications to the clinical team were triggered by PRO-CTCAE™ and FACT-GP5 scores. Patient participants liked the simplicity and responsiveness of the patient-facing app. Two patients were unable to complete the testing session, due to technical issues. Research Nurses suggested minor modifications to improve functionality and the layout of the clinician dashboard and the training materials.

Conclusion

By testing the effectiveness, efficiency, and satisfaction of our novel ePRO system (PROmicsR), we learnt that most people with an inflammatory condition found it easy to report their symptoms using an app on their own device. Their experiences using the PROmicsR ePRO system within a trial environment will be further explored in our upcoming feasibility testing. Research nurses were also positive and found the clinical dashboard easy-to-use. Using ePROs in early phase trials is important in order to provide evidence of therapeutic responses and tolerability, increase the evidence based, and inform methodology development.

Trial registration

ISRCTN, ISRCTN80103507. Registered 01 April 2022, https://www.isrctn.com/ISRCTN80103507.",,pdf:https://jpro.springeropen.com/counter/pdf/10.1186/s41687-023-00634-3; doi:https://doi.org/10.1186/s41687-023-00634-3; html:https://europepmc.org/articles/PMC10562321; pdf:https://europepmc.org/articles/PMC10562321?pdf=render 34514354,https://doi.org/10.1093/jamiaopen/ooab001,Transforming and evaluating electronic health record disease phenotyping algorithms using the OMOP common data model: a case study in heart failure.,"Papez V, Moinat M, Payralbe S, Asselbergs FW, Lumbers RT, Hemingway H, Dobson R, Denaxas S.",,JAMIA open,2021,2021-02-04,Y,Phenotyping; Heart Failure; Algorithms; Ehr; Omop,,,"

Objective

The aim of the study was to transform a resource of linked electronic health records (EHR) to the OMOP common data model (CDM) and evaluate the process in terms of syntactic and semantic consistency and quality when implementing disease and risk factor phenotyping algorithms.

Materials and methods

Using heart failure (HF) as an exemplar, we represented three national EHR sources (Clinical Practice Research Datalink, Hospital Episode Statistics Admitted Patient Care, Office for National Statistics) into the OMOP CDM 5.2. We compared the original and CDM HF patient population by calculating and presenting descriptive statistics of demographics, related comorbidities, and relevant clinical biomarkers.

Results

We identified a cohort of 502 536 patients with the incident and prevalent HF and converted 1 099 195 384 rows of data from 216 581 914 encounters across three EHR sources to the OMOP CDM. The largest percentage (65%) of unmapped events was related to medication prescriptions in primary care. The average coverage of source vocabularies was >98% with the exception of laboratory tests recorded in primary care. The raw and transformed data were similar in terms of demographics and comorbidities with the largest difference observed being 3.78% in the prevalence of chronic obstructive pulmonary disease (COPD).

Conclusion

Our study demonstrated that the OMOP CDM can successfully be applied to convert EHR linked across multiple healthcare settings and represent phenotyping algorithms spanning multiple sources. Similar to previous research, challenges mapping primary care prescriptions and laboratory measurements still persist and require further work. The use of OMOP CDM in national UK EHR is a valuable research tool that can enable large-scale reproducible observational research.",,pdf:https://academic.oup.com/jamiaopen/article-pdf/4/3/ooab001/40325375/ooab001.pdf; doi:https://doi.org/10.1093/jamiaopen/ooab001; html:https://europepmc.org/articles/PMC8423424; pdf:https://europepmc.org/articles/PMC8423424?pdf=render +37812323,https://doi.org/10.1186/s41687-023-00634-3,Development and usability testing of an electronic patient-reported outcome (ePRO) solution for patients with inflammatory diseases in an Advanced Therapy Medicinal Product (ATMP) basket trial.,"McMullan C, Retzer A, Hughes SE, Aiyegbusi OL, Bathurst C, Boyd A, Coleman J, Davies EH, Denniston AK, Dunster H, Frost C, Harding R, Hunn A, Kyte D, Malpass R, McNamara G, Mitchell S, Mittal S, Newsome PN, Price G, Rowe A, van Reil W, Walker A, Wilson R, Calvert M.",,Journal of patient-reported outcomes,2023,2023-10-09,Y,Inflammatory Conditions; Usability Testing; Cognitive Interviews; Electronic Patient Reported Outcomes; Early Phase Advanced Therapy Trial,,,"

Background

Electronic patient-reported outcome (ePRO) systems are increasingly used in clinical trials to provide evidence of efficacy and tolerability of treatment from the patient perspective. The aim of this study is twofold: (1) to describe how we developed an electronic platform for patients to report their symptoms, and (2) to develop and undertake usability testing of an ePRO solution for use in a study of cell therapy seeking to provide early evidence of efficacy and tolerability of treatment and test the feasibility of the system for use in later phase studies.

Methods

An ePRO system was designed to be used in a single arm, multi-centre, phase II basket trial investigating the safety and activity of the use of ORBCEL-C™ in the treatment of patients with inflammatory conditions. ORBCEL-C™ is an enriched Mesenchymal Stromal Cells product isolated from human umbilical cord tissue using CD362+ cell selection. Usability testing sessions were conducted using cognitive interviews and the 'Think Aloud' method with patient advisory group members and Research Nurses to assess the usability of the system.

Results

Nine patient partners and seven research nurses took part in one usability testing session. Measures of fatigue and health-related quality of life, the PRO-CTCAE™ and FACT-GP5 global tolerability question were included in the ePRO system. Alert notifications to the clinical team were triggered by PRO-CTCAE™ and FACT-GP5 scores. Patient participants liked the simplicity and responsiveness of the patient-facing app. Two patients were unable to complete the testing session, due to technical issues. Research Nurses suggested minor modifications to improve functionality and the layout of the clinician dashboard and the training materials.

Conclusion

By testing the effectiveness, efficiency, and satisfaction of our novel ePRO system (PROmicsR), we learnt that most people with an inflammatory condition found it easy to report their symptoms using an app on their own device. Their experiences using the PROmicsR ePRO system within a trial environment will be further explored in our upcoming feasibility testing. Research nurses were also positive and found the clinical dashboard easy-to-use. Using ePROs in early phase trials is important in order to provide evidence of therapeutic responses and tolerability, increase the evidence based, and inform methodology development.

Trial registration

ISRCTN, ISRCTN80103507. Registered 01 April 2022, https://www.isrctn.com/ISRCTN80103507.",,pdf:https://jpro.springeropen.com/counter/pdf/10.1186/s41687-023-00634-3; doi:https://doi.org/10.1186/s41687-023-00634-3; html:https://europepmc.org/articles/PMC10562321; pdf:https://europepmc.org/articles/PMC10562321?pdf=render 33971933,https://doi.org/10.1186/s13063-021-05295-5,Accessing routinely collected health data to improve clinical trials: recent experience of access.,"Macnair A, Love SB, Murray ML, Gilbert DC, Parmar MKB, Denwood T, Carpenter J, Sydes MR, Langley RE, Cafferty FH.",,Trials,2021,2021-05-10,Y,Clinical Trials; Electronic Health Records; Data Accessibility; Routinely Collected Data,,,"

Background

Routinely collected electronic health records (EHRs) have the potential to enhance randomised controlled trials (RCTs) by facilitating recruitment and follow-up. Despite this, current EHR use is minimal in UK RCTs, in part due to ongoing concerns about the utility (reliability, completeness, accuracy) and accessibility of the data. The aim of this manuscript is to document the process, timelines and challenges of the application process to help improve the service both for the applicants and data holders.

Methods

This is a qualitative paper providing a descriptive narrative from one UK clinical trials unit (MRC CTU at UCL) on the experience of two trial teams' application process to access data from three large English national datasets: National Cancer Registration and Analysis Service (NCRAS), National Institute for Cardiovascular Outcomes Research (NICOR) and NHS Digital to establish themes for discussion. The underpinning reason for applying for the data was to compare EHRs with data collected through case report forms in two RCTs, Add-Aspirin (ISRCTN 74358648) and PATCH (ISRCTN 70406718).

Results

The Add-Aspirin trial, which had a pre-planned embedded sub-study to assess EHR, received data from NCRAS 13 months after the first application. In the PATCH trial, the decision to request data was made whilst the trial was recruiting. The study received data after 8 months from NICOR and 15 months for NHS Digital following final application submission. This concluded in May 2020. Prior to application submission, significant time and effort was needed particularly in relation to the PATCH trial where negotiations over consent and data linkage took many years.

Conclusions

Our experience demonstrates that data access can be a prolonged and complex process. This is compounded if multiple data sources are required for the same project. This needs to be factored in when planning to use EHR within RCTs and is best considered prior to conception of the trial. Data holders and researchers are endeavouring to simplify and streamline the application process so that the potential of EHR can be realised for clinical trials.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-021-05295-5; doi:https://doi.org/10.1186/s13063-021-05295-5; html:https://europepmc.org/articles/PMC8108438; pdf:https://europepmc.org/articles/PMC8108438?pdf=render -37263751,https://doi.org/10.1183/13993003.01667-2022,Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection.,"Packer RJ, Shrine N, Hall R, Melbourne CA, Thompson R, Williams AT, Paynton ML, Guyatt AL, Allen RJ, Lee PH, John C, Campbell A, Hayward C, de Vries M, Vonk JM, Davitte J, Hessel E, Michalovich D, Betts JC, Sayers I, Yeo A, Hall IP, Tobin MD, Wain LV.",,The European respiratory journal,2023,2023-06-15,Y,,,,"

Background

Chronic sputum production impacts on quality of life and is a feature of many respiratory diseases. Identification of the genetic variants associated with chronic sputum production in a disease agnostic sample could improve understanding of its causes and identify new molecular targets for treatment.

Methods

We conducted a genome-wide association study (GWAS) of chronic sputum production in UK Biobank. Signals meeting genome-wide significance (p<5×10-8) were investigated in additional independent studies, were fine-mapped and putative causal genes identified by gene expression analysis. GWASs of respiratory traits were interrogated to identify whether the signals were driven by existing respiratory disease among the cases and variants were further investigated for wider pleiotropic effects using phenome-wide association studies (PheWASs).

Results

From a GWAS of 9714 cases and 48 471 controls, we identified six novel genome-wide significant signals for chronic sputum production including signals in the human leukocyte antigen (HLA) locus, chromosome 11 mucin locus (containing MUC2, MUC5AC and MUC5B) and FUT2 locus. The four common variant associations were supported by independent studies with a combined sample size of up to 2203 cases and 17 627 controls. The mucin locus signal had previously been reported for association with moderate-to-severe asthma. The HLA signal was fine-mapped to an amino acid change of threonine to arginine (frequency 36.8%) in HLA-DRB1 (HLA-DRB1*03:147). The signal near FUT2 was associated with expression of several genes including FUT2, for which the direction of effect was tissue dependent. Our PheWAS identified a wide range of associations including blood cell traits, liver biomarkers, infections, gastrointestinal and thyroid-associated diseases, and respiratory disease.

Conclusions

Novel signals at the FUT2 and mucin loci suggest that mucin fucosylation may be a driver of chronic sputum production even in the absence of diagnosed respiratory disease and provide genetic support for this pathway as a target for therapeutic intervention.",,pdf:https://erj.ersjournals.com/content/erj/61/6/2201667.full.pdf; doi:https://doi.org/10.1183/13993003.01667-2022; html:https://europepmc.org/articles/PMC10284065; pdf:https://europepmc.org/articles/PMC10284065?pdf=render 35143670,https://doi.org/10.1093/molbev/msac034,The Carbon Footprint of Bioinformatics.,"Grealey J, Lannelongue L, Saw WY, Marten J, Méric G, Ruiz-Carmona S, Inouye M.",,Molecular biology and evolution,2022,2022-03-01,Y,Bioinformatics; Genomics; Carbon Footprint; Green Algorithms,,,"Bioinformatic research relies on large-scale computational infrastructures which have a nonzero carbon footprint but so far, no study has quantified the environmental costs of bioinformatic tools and commonly run analyses. In this work, we estimate the carbon footprint of bioinformatics (in kilograms of CO2 equivalent units, kgCO2e) using the freely available Green Algorithms calculator (www.green-algorithms.org, last accessed 2022). We assessed 1) bioinformatic approaches in genome-wide association studies (GWAS), RNA sequencing, genome assembly, metagenomics, phylogenetics, and molecular simulations, as well as 2) computation strategies, such as parallelization, CPU (central processing unit) versus GPU (graphics processing unit), cloud versus local computing infrastructure, and geography. In particular, we found that biobank-scale GWAS emitted substantial kgCO2e and simple software upgrades could make it greener, for example, upgrading from BOLT-LMM v1 to v2.3 reduced carbon footprint by 73%. Moreover, switching from the average data center to a more efficient one can reduce carbon footprint by approximately 34%. Memory over-allocation can also be a substantial contributor to an algorithm's greenhouse gas emissions. The use of faster processors or greater parallelization reduces running time but can lead to greater carbon footprint. Finally, we provide guidance on how researchers can reduce power consumption and minimize kgCO2e. Overall, this work elucidates the carbon footprint of common analyses in bioinformatics and provides solutions which empower a move toward greener research.",,pdf:https://academic.oup.com/mbe/article-pdf/39/3/msac034/42692776/msac034.pdf; doi:https://doi.org/10.1093/molbev/msac034; html:https://europepmc.org/articles/PMC8892942; pdf:https://europepmc.org/articles/PMC8892942?pdf=render -38400634,https://doi.org/10.1093/ageing/afae021,Adherence to the Atrial fibrillation Better Care pathway and the risk of adverse health outcomes in older care home residents with atrial fibrillation: a retrospective data linkage study 2003-18.,"Ritchie LA, Harrison SL, Penson PE, Akbari A, Torabi F, Hollinghurst J, Harris D, Oke OB, Akpan A, Halcox JP, Rodgers SE, Lip GYH, Lane DA.",,Age and ageing,2024,2024-02-01,Y,Atrial fibrillation; Older People; Care Homes; Integrated Care; Health Outcomes,,,"

Background

The Atrial fibrillation Better Care (ABC) pathway is the gold-standard approach to atrial fibrillation (AF) management, but the effect of implementation on health outcomes in care home residents is unknown.

Objective

To examine associations between ABC pathway adherence and stroke, transient ischaemic attack, cardiovascular hospitalisation, major bleeding, mortality and a composite of all these outcomes in care home residents.

Methods

A retrospective cohort study of older care home residents (≥65 years) in Wales with AF was conducted between 1 January 2003 and 31 December 2018 using the Secure Anonymised Information Linkage Databank. Adherence to the ABC pathway was assessed at care home entry using pre-specified definitions. Cox proportional hazard and competing risk models were used to estimate the risk of health outcomes according to ABC adherence.

Results

From 14,493 residents (median [interquartile range] age 87.0 [82.6-91.2] years, 35.2% male) with AF, 5,531 (38.2%) were ABC pathway adherent. Pathway adherence was not significantly associated with risk of the composite outcome (adjusted hazard ratio, 95% confidence interval [CI]: 1.01 [0.97-1.05]). There was a significant independent association observed between ABC pathway adherence and a reduced risk of myocardial infarction (0.70 [0.50-0.98]), but a higher risk of haemorrhagic stroke (1.59 [1.06-2.39]). ABC pathway adherence was not significantly associated with any other individual health outcomes examined.

Conclusion

An ABC adherent approach in care home residents was not consistently associated with improved health outcomes. Findings should be interpreted with caution owing to difficulties in defining pathway adherence using routinely collected data and an individualised approach is recommended.",,doi:https://doi.org/10.1093/ageing/afae021; html:https://europepmc.org/articles/PMC10891424; pdf:https://europepmc.org/articles/PMC10891424?pdf=render +37263751,https://doi.org/10.1183/13993003.01667-2022,Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection.,"Packer RJ, Shrine N, Hall R, Melbourne CA, Thompson R, Williams AT, Paynton ML, Guyatt AL, Allen RJ, Lee PH, John C, Campbell A, Hayward C, de Vries M, Vonk JM, Davitte J, Hessel E, Michalovich D, Betts JC, Sayers I, Yeo A, Hall IP, Tobin MD, Wain LV.",,The European respiratory journal,2023,2023-06-15,Y,,,,"

Background

Chronic sputum production impacts on quality of life and is a feature of many respiratory diseases. Identification of the genetic variants associated with chronic sputum production in a disease agnostic sample could improve understanding of its causes and identify new molecular targets for treatment.

Methods

We conducted a genome-wide association study (GWAS) of chronic sputum production in UK Biobank. Signals meeting genome-wide significance (p<5×10-8) were investigated in additional independent studies, were fine-mapped and putative causal genes identified by gene expression analysis. GWASs of respiratory traits were interrogated to identify whether the signals were driven by existing respiratory disease among the cases and variants were further investigated for wider pleiotropic effects using phenome-wide association studies (PheWASs).

Results

From a GWAS of 9714 cases and 48 471 controls, we identified six novel genome-wide significant signals for chronic sputum production including signals in the human leukocyte antigen (HLA) locus, chromosome 11 mucin locus (containing MUC2, MUC5AC and MUC5B) and FUT2 locus. The four common variant associations were supported by independent studies with a combined sample size of up to 2203 cases and 17 627 controls. The mucin locus signal had previously been reported for association with moderate-to-severe asthma. The HLA signal was fine-mapped to an amino acid change of threonine to arginine (frequency 36.8%) in HLA-DRB1 (HLA-DRB1*03:147). The signal near FUT2 was associated with expression of several genes including FUT2, for which the direction of effect was tissue dependent. Our PheWAS identified a wide range of associations including blood cell traits, liver biomarkers, infections, gastrointestinal and thyroid-associated diseases, and respiratory disease.

Conclusions

Novel signals at the FUT2 and mucin loci suggest that mucin fucosylation may be a driver of chronic sputum production even in the absence of diagnosed respiratory disease and provide genetic support for this pathway as a target for therapeutic intervention.",,pdf:https://erj.ersjournals.com/content/erj/61/6/2201667.full.pdf; doi:https://doi.org/10.1183/13993003.01667-2022; html:https://europepmc.org/articles/PMC10284065; pdf:https://europepmc.org/articles/PMC10284065?pdf=render 36538350,https://doi.org/10.2196/41200,Identifying Patterns of Clinical Interest in Clinicians' Treatment Preferences: Hypothesis-free Data Science Approach to Prioritizing Prescribing Outliers for Clinical Review.,"MacKenna B, Curtis HJ, Hopcroft LEM, Walker AJ, Croker R, Macdonald O, Evans SJW, Inglesby P, Evans D, Morley J, Bacon SCJ, Goldacre B.",,JMIR medical informatics,2022,2022-12-20,Y,Prescribing; Clinical Audit; Antipsychotics; Pericyazine; Data Science; Nhs England; Promazine Hydrochloride,,,"

Background

Data analysis is used to identify signals suggestive of variation in treatment choice or clinical outcome. Analyses to date have generally focused on a hypothesis-driven approach.

Objective

This study aimed to develop a hypothesis-free approach to identify unusual prescribing behavior in primary care data. We aimed to apply this methodology to a national data set in a cross-sectional study to identify chemicals with significant variation in use across Clinical Commissioning Groups (CCGs) for further clinical review, thereby demonstrating proof of concept for prioritization approaches.

Methods

Here we report a new data-driven approach to identify unusual prescribing behaviour in primary care data. This approach first applies a set of filtering steps to identify chemicals with prescribing rate distributions likely to contain outliers, then applies two ranking approaches to identify the most extreme outliers amongst those candidates. This methodology has been applied to three months of national prescribing data (June-August 2017).

Results

Our methodology provides rankings for all chemicals by administrative region. We provide illustrative results for 2 antipsychotic drugs of particular clinical interest: promazine hydrochloride and pericyazine, which rank highly by outlier metrics. Specifically, our method identifies that, while promazine hydrochloride and pericyazine are barely used by most clinicians (with national prescribing rates of 11.1 and 6.2 per 1000 antipsychotic prescriptions, respectively), they make up a substantial proportion of antipsychotic prescribing in 2 small geographic regions in England during the study period (with maximum regional prescribing rates of 298.7 and 241.1 per 1000 antipsychotic prescriptions, respectively).

Conclusions

Our hypothesis-free approach is able to identify candidates for audit and review in clinical practice. To illustrate this, we provide 2 examples of 2 very unusual antipsychotics used disproportionately in 2 small geographic areas of England.",,pdf:https://medinform.jmir.org/2022/12/e41200/PDF; doi:https://doi.org/10.2196/41200; html:https://europepmc.org/articles/PMC9812268 +38400634,https://doi.org/10.1093/ageing/afae021,Adherence to the Atrial fibrillation Better Care pathway and the risk of adverse health outcomes in older care home residents with atrial fibrillation: a retrospective data linkage study 2003-18.,"Ritchie LA, Harrison SL, Penson PE, Akbari A, Torabi F, Hollinghurst J, Harris D, Oke OB, Akpan A, Halcox JP, Rodgers SE, Lip GYH, Lane DA.",,Age and ageing,2024,2024-02-01,Y,Atrial fibrillation; Older People; Care Homes; Integrated Care; Health Outcomes,,,"

Background

The Atrial fibrillation Better Care (ABC) pathway is the gold-standard approach to atrial fibrillation (AF) management, but the effect of implementation on health outcomes in care home residents is unknown.

Objective

To examine associations between ABC pathway adherence and stroke, transient ischaemic attack, cardiovascular hospitalisation, major bleeding, mortality and a composite of all these outcomes in care home residents.

Methods

A retrospective cohort study of older care home residents (≥65 years) in Wales with AF was conducted between 1 January 2003 and 31 December 2018 using the Secure Anonymised Information Linkage Databank. Adherence to the ABC pathway was assessed at care home entry using pre-specified definitions. Cox proportional hazard and competing risk models were used to estimate the risk of health outcomes according to ABC adherence.

Results

From 14,493 residents (median [interquartile range] age 87.0 [82.6-91.2] years, 35.2% male) with AF, 5,531 (38.2%) were ABC pathway adherent. Pathway adherence was not significantly associated with risk of the composite outcome (adjusted hazard ratio, 95% confidence interval [CI]: 1.01 [0.97-1.05]). There was a significant independent association observed between ABC pathway adherence and a reduced risk of myocardial infarction (0.70 [0.50-0.98]), but a higher risk of haemorrhagic stroke (1.59 [1.06-2.39]). ABC pathway adherence was not significantly associated with any other individual health outcomes examined.

Conclusion

An ABC adherent approach in care home residents was not consistently associated with improved health outcomes. Findings should be interpreted with caution owing to difficulties in defining pathway adherence using routinely collected data and an individualised approach is recommended.",,doi:https://doi.org/10.1093/ageing/afae021; html:https://europepmc.org/articles/PMC10891424; pdf:https://europepmc.org/articles/PMC10891424?pdf=render 35023833,https://doi.org/10.7554/elife.71802,Epigenetic scores for the circulating proteome as tools for disease prediction.,"Gadd DA, Hillary RF, McCartney DL, Zaghlool SB, Stevenson AJ, Cheng Y, Fawns-Ritchie C, Nangle C, Campbell A, Flaig R, Harris SE, Walker RM, Shi L, Tucker-Drob EM, Gieger C, Peters A, Waldenberger M, Graumann J, McRae AF, Deary IJ, Porteous DJ, Hayward C, Visscher PM, Cox SR, Evans KL, McIntosh AM, Suhre K, Marioni RE.",,eLife,2022,2022-01-13,Y,Human; Prediction; Aging; Genetics; Proteomics; Genomics; Biomarker; epidemiology; Global Health; Epigenetic; Morbiditiy,,,"Protein biomarkers have been identified across many age-related morbidities. However, characterising epigenetic influences could further inform disease predictions. Here, we leverage epigenome-wide data to study links between the DNA methylation (DNAm) signatures of the circulating proteome and incident diseases. Using data from four cohorts, we trained and tested epigenetic scores (EpiScores) for 953 plasma proteins, identifying 109 scores that explained between 1% and 58% of the variance in protein levels after adjusting for known protein quantitative trait loci (pQTL) genetic effects. By projecting these EpiScores into an independent sample (Generation Scotland; n = 9537) and relating them to incident morbidities over a follow-up of 14 years, we uncovered 137 EpiScore-disease associations. These associations were largely independent of immune cell proportions, common lifestyle and health factors, and biological aging. Notably, we found that our diabetes-associated EpiScores highlighted previous top biomarker associations from proteome-wide assessments of diabetes. These EpiScores for protein levels can therefore be a valuable resource for disease prediction and risk stratification.",,doi:https://doi.org/10.7554/elife.71802; doi:https://doi.org/10.7554/eLife.71802; html:https://europepmc.org/articles/PMC8880990; pdf:https://europepmc.org/articles/PMC8880990?pdf=render 35523486,https://doi.org/10.1136/bmjopen-2021-059258,Using digital health tools for the Remote Assessment of Treatment Prognosis in Depression (RAPID): a study protocol for a feasibility study.,"de Angel V, Lewis S, Munir S, Matcham F, Dobson R, Hotopf M.",,BMJ open,2022,2022-05-06,Y,Mental health; Anxiety Disorders; Health Informatics; Depression & Mood Disorders,,,"

Introduction

Digital health tools such as smartphones and wearable devices could improve psychological treatment outcomes in depression through more accurate and comprehensive measures of patient behaviour. However, in this emerging field, most studies are small and based on student populations outside of a clinical setting. The current study aims to determine the feasibility and acceptability of using smartphones and wearable devices to collect behavioural and clinical data in people undergoing therapy for depressive disorders and establish the extent to which they can be potentially useful biomarkers of depression and recovery after treatment.

Methods and analysis

This is an observational, prospective cohort study of 65 people attending psychological therapy for depression in multiple London-based sites. It will collect continuous passive data from smartphone sensors and a Fitbit fitness tracker, and deliver questionnaires, speech tasks and cognitive assessments through smartphone-based apps. Objective data on sleep, physical activity, location, Bluetooth contact, smartphone use and heart rate will be gathered for 7 months, and compared with clinical and contextual data. A mixed methods design, including a qualitative interview of patient experiences, will be used to evaluate key feasibility indicators, digital phenotypes of depression and therapy prognosis. Patient and public involvement was sought for participant-facing documents and the study design of the current research proposal.

Ethics and dissemination

Ethical approval has been obtained from the London Westminster Research Ethics Committee, and the Health Research Authority, Integrated Research Application System (project ID: 270918). Privacy and confidentiality will be guaranteed and the procedures for handling, processing, storage and destruction of the data will comply with the General Data Protection Regulation. Findings from this study will form part of a doctoral thesis, will be presented at national and international meetings or academic conferences and will generate manuscripts to be submitted to peer-reviewed journals.

Trial registration number

https://doi.org/10.17605/OSF.IO/PMYTA.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/5/e059258.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-059258; html:https://europepmc.org/articles/PMC9083394; pdf:https://europepmc.org/articles/PMC9083394?pdf=render 34481555,https://doi.org/10.1016/s2213-8587(21)00207-2,"Identifying adults at high-risk for change in weight and BMI in England: a longitudinal, large-scale, population-based cohort study using electronic health records.","Katsoulis M, Lai AG, Diaz-Ordaz K, Gomes M, Pasea L, Banerjee A, Denaxas S, Tsilidis K, Lagiou P, Misirli G, Bhaskaran K, Wannamethee G, Dobson R, Batterham RL, Kipourou DK, Lumbers RT, Wen L, Wareham N, Langenberg C, Hemingway H.",,The lancet. Diabetes & endocrinology,2021,2021-09-02,Y,,,,"

Background

Targeted obesity prevention policies would benefit from the identification of population groups with the highest risk of weight gain. The relative importance of adult age, sex, ethnicity, geographical region, and degree of social deprivation on weight gain is not known. We aimed to identify high-risk groups for changes in weight and BMI using electronic health records (EHR).

Methods

In this longitudinal, population-based cohort study we used linked EHR data from 400 primary care practices (via the Clinical Practice Research Datalink) in England, accessed via the CALIBER programme. Eligible participants were aged 18-74 years, were registered at a general practice clinic, and had BMI and weight measurements recorded between Jan 1, 1998, and June 30, 2016, during the period when they had eligible linked data with at least 1 year of follow-up time. We calculated longitudinal changes in BMI over 1, 5, and 10 years, and investigated the absolute risk and odds ratios (ORs) of transitioning between BMI categories (underweight, normal weight, overweight, obesity class 1 and 2, and severe obesity [class 3]), as defined by WHO. The associations of demographic factors with BMI transitions were estimated by use of logistic regression analysis, adjusting for baseline BMI, family history of cardiovascular disease, use of diuretics, and prevalent chronic conditions.

Findings

We included 2 092 260 eligible individuals with more than 9 million BMI measurements in our study. Young adult age was the strongest risk factor for weight gain at 1, 5, and 10 years of follow-up. Compared with the oldest age group (65-74 years), adults in the youngest age group (18-24 years) had the highest OR (4·22 [95% CI 3·86-4·62]) and greatest absolute risk (37% vs 24%) of transitioning from normal weight to overweight or obesity at 10 years. Likewise, adults in the youngest age group with overweight or obesity at baseline were also at highest risk to transition to a higher BMI category; OR 4·60 (4·06-5·22) and absolute risk (42% vs 18%) of transitioning from overweight to class 1 and 2 obesity, and OR 5·87 (5·23-6·59) and absolute risk (22% vs 5%) of transitioning from class 1 and 2 obesity to class 3 obesity. Other demographic factors were consistently less strongly associated with these transitions; for example, the OR of transitioning from normal weight to overweight or obesity in people living in the most socially deprived versus least deprived areas was 1·23 (1·18-1·27), for men versus women was 1·12 (1·08-1·16), and for Black individuals versus White individuals was 1·13 (1·04-1·24). We provide an open access online risk calculator, and present high-resolution obesity risk charts over a 1-year, 5-year, and 10-year follow-up period.

Interpretation

A radical shift in policy is required to focus on individuals at the highest risk of weight gain (ie, young adults aged 18-24 years) for individual-level and population-level prevention of obesity and its long-term consequences for health and health care.

Funding

The British Hearth Foundation, Health Data Research UK, the UK Medical Research Council, and the National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S2213858721002072/pdf; doi:https://doi.org/10.1016/S2213-8587(21)00207-2; html:https://europepmc.org/articles/PMC8440227; pdf:https://europepmc.org/articles/PMC8440227?pdf=render 36208161,https://doi.org/10.1093/eurheartj/ehac426,CODE-EHR best practice framework for the use of structured electronic healthcare records in clinical research.,"Kotecha D, Asselbergs FW, Achenbach S, Anker SD, Atar D, Baigent C, Banerjee A, Beger B, Brobert G, Casadei B, Ceccarelli C, Cowie MR, Crea F, Cronin M, Denaxas S, Derix A, Fitzsimons D, Fredriksson M, Gale CP, Gkoutos GV, Goettsch W, Hemingway H, Ingvar M, Jonas A, Kazmierski R, Løgstrup S, Thomas Lumbers R, Lüscher TF, McGreavy P, Piña IL, Roessig L, Steinbeisser C, Sundgren M, Tyl B, van Thiel G, van Bochove K, Vardas PE, Villanueva T, Vrana M, Weber W, Weidinger F, Windecker S, Wood A, Grobbee DE, Innovative Medicines Initiative BigData@Heart Consortium, European Society of Cardiology, CODE-EHR international consensus group.",,European heart journal,2022,2022-10-01,Y,,,,"Big data is central to new developments in global clinical science aiming to improve the lives of patients. Technological advances have led to the routine use of structured electronic healthcare records with the potential to address key gaps in clinical evidence. The covid-19 pandemic has demonstrated the potential of big data and related analytics, but also important pitfalls. Verification, validation, and data privacy, as well as the social mandate to undertake research are key challenges. The European Society of Cardiology and the BigData@Heart consortium have brought together a range of international stakeholders, including patient representatives, clinicians, scientists, regulators, journal editors and industry. We propose the CODE-EHR Minimum Standards Framework as a means to improve the design of studies, enhance transparency and develop a roadmap towards more robust and effective utilisation of healthcare data for research purposes.",,pdf:https://academic.oup.com/eurheartj/article-pdf/43/37/3578/46535456/ehac426.pdf; doi:https://doi.org/10.1093/eurheartj/ehac426; html:https://europepmc.org/articles/PMC9452067; pdf:https://europepmc.org/articles/PMC9452067?pdf=render -37381004,https://doi.org/10.1186/s12913-023-09545-x,A qualitative descriptive study exploring clinicians' perspectives of the management of older trauma care in rural Australia.,"Ferrah N, Parker C, Ibrahim J, Gabbe B, Cameron P.",,BMC health services research,2023,2023-06-28,Y,Trauma; Rural; Interview; Older Adults,,,"

Background

For older trauma patients who sustain trauma in rural areas, the risk of adverse outcomes associated with advancing age, is compounded by the challenges encountered in rural healthcare such as geographic isolation, lack of resources, and accessibility. Little is known of the experience and challenges faced by rural clinicians who manage trauma in older adults. An understanding of stakeholders' views is paramount to the effective development and implementation of a trauma system inclusive of rural communities. The aim of this descriptive qualitative study was to explore the perspectives of clinicians who provide care to older trauma patients in rural settings.

Method

We conducted semi-structured interviews of health professionals (medical doctors, nurses, paramedics, and allied health professionals) who provide care to older trauma patients in rural Queensland, Australia. A thematic analysis consisting of both inductive and deductive coding approaches, was used to identify and develop themes from interviews.

Results

Fifteen participants took part in the interviews. Three key themes were identified: enablers of trauma care, barriers, and changes to improve trauma care of older people. The resilience of rural residents, and breadth of experience of rural clinicians were strengths identified by participants. The perceived systemic lack of resources, both material and in the workforce, and fragmentation of the health system across the state were barriers to the provision of trauma care to older rural patients. Some changes proposed by participants included tailored education programs that would be taught in rural centres, a dedicated case coordinator for older trauma patients from rural areas, and a centralised system designed to streamline the management of older trauma patients coming from rural regions.

Conclusions

Rural clinicians are important stakeholders who should be included in discussions on adapting trauma guidelines to the rural setting. In this study, participants formulated pertinent and concrete recommendations that should be weighed against the current evidence, and tested in rural centres.",,pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-023-09545-x; doi:https://doi.org/10.1186/s12913-023-09545-x; html:https://europepmc.org/articles/PMC10308762; pdf:https://europepmc.org/articles/PMC10308762?pdf=render 33644414,https://doi.org/10.23889/ijpds.v5i3.1371,Public involvement & engagement in the work of a data safe haven: a case study of the SAIL Databank.,"Jones KH, Heys S, Thompson R, Cross L, Ford D.",,International journal of population data science,2020,2020-08-24,Y,Public Engagement; Data Safe Haven,,,"

Background

The SAIL Databank is a data safe haven established in 2007 at Swansea University (Wales). It was set up to create new opportunities for research using routinely-collected health and other public service datasets in linkable anonymised form. SAIL forms the bedrock of other Population Data Science initiatives made possible by the data and safe haven environment.

Aim

The aim of this paper is to provide an overview of public involvement & engagement in connection with the SAIL Databank and related Population Data Science initiatives.

Approach

We have a public involvement & engagement policy for SAIL in the context of Population Data Science. We established a Consumer Panel to provide advice on the work of SAIL and associated initiatives, including on proposed uses of SAIL data. We reviewed the topics discussed and provide examples of advice to researchers. We carried out a survey with members on their experiences of being on the Panel and their perceptions of the work of SAIL. We have a programme of wider public engagement and provide illustrations of this work.

Discussion

We summarise what this paper adds and some lessons learned. In the rapidly developing area of Population Data Science it is important that people feel welcome, that they are encouraged to ask questions and are provided with digestible information and adequate consideration time. Citizens have provided us with valuable anticipated and unanticipated opinions and novel viewpoints. We seek to take a pragmatic approach, prioritising the communication modes that allow maximum public input commensurate with the purpose of the activity.

Conclusion

This paper has set out our policy, rationale, scope and practical approaches to public involvement & engagement for SAIL and our related Population Data Science initiatives. Although there will be jurisdictional, cultural and organizational differences, we believe that the material covered in this paper will be of interest to other data focused enterprises across the world.",,pdf:https://ijpds.org/article/download/1371/2815; doi:https://doi.org/10.23889/ijpds.v5i3.1371; html:https://europepmc.org/articles/PMC7893854; pdf:https://europepmc.org/articles/PMC7893854?pdf=render +37381004,https://doi.org/10.1186/s12913-023-09545-x,A qualitative descriptive study exploring clinicians' perspectives of the management of older trauma care in rural Australia.,"Ferrah N, Parker C, Ibrahim J, Gabbe B, Cameron P.",,BMC health services research,2023,2023-06-28,Y,Trauma; Rural; Interview; Older Adults,,,"

Background

For older trauma patients who sustain trauma in rural areas, the risk of adverse outcomes associated with advancing age, is compounded by the challenges encountered in rural healthcare such as geographic isolation, lack of resources, and accessibility. Little is known of the experience and challenges faced by rural clinicians who manage trauma in older adults. An understanding of stakeholders' views is paramount to the effective development and implementation of a trauma system inclusive of rural communities. The aim of this descriptive qualitative study was to explore the perspectives of clinicians who provide care to older trauma patients in rural settings.

Method

We conducted semi-structured interviews of health professionals (medical doctors, nurses, paramedics, and allied health professionals) who provide care to older trauma patients in rural Queensland, Australia. A thematic analysis consisting of both inductive and deductive coding approaches, was used to identify and develop themes from interviews.

Results

Fifteen participants took part in the interviews. Three key themes were identified: enablers of trauma care, barriers, and changes to improve trauma care of older people. The resilience of rural residents, and breadth of experience of rural clinicians were strengths identified by participants. The perceived systemic lack of resources, both material and in the workforce, and fragmentation of the health system across the state were barriers to the provision of trauma care to older rural patients. Some changes proposed by participants included tailored education programs that would be taught in rural centres, a dedicated case coordinator for older trauma patients from rural areas, and a centralised system designed to streamline the management of older trauma patients coming from rural regions.

Conclusions

Rural clinicians are important stakeholders who should be included in discussions on adapting trauma guidelines to the rural setting. In this study, participants formulated pertinent and concrete recommendations that should be weighed against the current evidence, and tested in rural centres.",,pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-023-09545-x; doi:https://doi.org/10.1186/s12913-023-09545-x; html:https://europepmc.org/articles/PMC10308762; pdf:https://europepmc.org/articles/PMC10308762?pdf=render 36712153,https://doi.org/10.1093/ehjdh/ztac046,Systematic approach to outcome assessment from coded electronic healthcare records in the DaRe2THINK NHS-embedded randomized trial.,"Wang X, Mobley AR, Tica O, Okoth K, Ghosh RE, Myles P, Williams T, Haynes S, Nirantharakumar K, Shukla D, Kotecha D, DaRe2THINK Trial Committees .",,European heart journal. Digital health,2022,2022-09-16,Y,Coding; Anticoagulation; Atrial fibrillation; Randomized controlled trial; Primary Care; Secondary Care; Electronic Healthcare Record,,,"

Aims

Improving the efficiency of clinical trials is key to their continued importance in directing evidence-based patient care. Digital innovations, in particular the use of electronic healthcare records (EHRs), allow for large-scale screening and follow up of participants. However, it is critical these developments are accompanied by robust and transparent methods that can support high-quality and high clinical value research.

Methods and results

The DaRe2THINK trial includes a series of novel processes, including nationwide pseudonymized pre screening of the primary-care EHR across England, digital enrolment, remote e-consent, and 'no-visit' follow up by linking all primary- and secondary-care health data with patient-reported outcomes. DaRe2THINK is a pragmatic, healthcare-embedded randomized trial testing whether earlier use of direct oral anticoagulants in patients with prior or current atrial fibrillation can prevent thromboembolic events and cognitive decline (www.birmingham.ac.uk/dare2think). This study outlines the systematic approach and methodology employed to define patient information and outcome events. This includes transparency on all medical code lists and phenotypes used in the trial across a variety of national data sources, including Clinical Practice Research Datalink Aurum (primary care), Hospital Episode Statistics (secondary care), and the Office for National Statistics (mortality).

Conclusion

Co-designed by a patient and public involvement team, DaRe2THINK presents an opportunity to transform the approach to randomized trials in the setting of routine healthcare, providing high-quality evidence generation in populations representative of the community at risk.",,pdf:https://academic.oup.com/ehjdh/article-pdf/3/3/426/47117043/ztac046.pdf; doi:https://doi.org/10.1093/ehjdh/ztac046; html:https://europepmc.org/articles/PMC9708037; pdf:https://europepmc.org/articles/PMC9708037?pdf=render 37731935,https://doi.org/10.1016/j.eclinm.2023.102193,"Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019.",GBD 2019 IMID Collaborators.,,EClinicalMedicine,2023,2023-09-09,Y,Trend; incidence; Immune-mediated Inflammatory Disease; Global Burden Of Disease Study,,,"

Background

The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019.

Methods

We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends.

Findings

In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of -0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = -0.41), inflammatory bowel disease (AAPC = -0.72), multiple sclerosis (AAPC = -0.26), psoriasis (AAPC = -0.77), and atopic dermatitis (AAPC = -0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR.

Interpretation

The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively.

Funding

The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38).",,pdf:http://www.thelancet.com/article/S258953702300370X/pdf; doi:https://doi.org/10.1016/j.eclinm.2023.102193; html:https://europepmc.org/articles/PMC10507198; pdf:https://europepmc.org/articles/PMC10507198?pdf=render 35238940,https://doi.org/10.1093/ndt/gfac040,"Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial.",EMPA-KIDNEY Collaborative Group.,,"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",2022,2022-06-01,Y,"Cardiovascular disease; Empagliflozin; Sodium-glucose Co-transporter 2 Inhibitor; Ckd, Clinical Trial",,,"

Background

The effects of the sodium-glucose co-transporter 2 inhibitor empagliflozin on renal and cardiovascular disease have not been tested in a dedicated population of people with chronic kidney disease (CKD).

Methods

The EMPA-KIDNEY trial is an international randomized, double-blind, placebo-controlled trial assessing whether empagliflozin 10 mg daily decreases the risk of kidney disease progression or cardiovascular death in people with CKD. People with or without diabetes mellitus (DM) were eligible provided they had an estimated glomerular filtration rate (eGFR) ≥20 but <45 mL/min/1.73 m2 or an eGFR ≥45 but <90 mL/min/1.73 m2 with a urinary albumin:creatinine ratio (uACR) ≥200 mg/g. The trial design is streamlined, as extra work for collaborating sites is kept to a minimum and only essential information is collected.

Results

Between 15 May 2019 and 16 April 2021, 6609 people from eight countries in Europe, North America and East Asia were randomized. The mean age at randomization was 63.8 years [standard deviation (SD) 13.9)], 2192 (33%) were female and 3570 (54%) had no prior history of DM. The mean eGFR was 37.5 mL/min/1.73 m2 (SD 14.8), including 5185 (78%) with an eGFR <45 mL/min/1.73 m2. The median uACR was 412 mg/g) (quartile 1-quartile 3 94-1190), with a uACR <300 mg/g in 3194 (48%). The causes of kidney disease included diabetic kidney disease [n = 2057 (31%)], glomerular disease [n = 1669 (25%)], hypertensive/renovascular disease [n = 1445 (22%)], other [n = 808 (12%)] and unknown causes [n = 630 (10%)].

Conclusions

EMPA-KIDNEY will evaluate the efficacy and safety of empagliflozin in a widely generalizable population of people with CKD at risk of kidney disease progression. Results are anticipated in 2022.",,pdf:https://academic.oup.com/ndt/article-pdf/37/7/1317/44138360/gfac040.pdf; doi:https://doi.org/10.1093/ndt/gfac040; html:https://europepmc.org/articles/PMC9217655; pdf:https://europepmc.org/articles/PMC9217655?pdf=render -36932161,https://doi.org/10.1038/s41433-023-02478-z,Evaluating patient-reported outcome measures (PROMs) for future clinical trials in adult patients with optic neuritis.,"Panthagani J, O'Donovan C, Aiyegbusi OL, Liu X, Bayliss S, Calvert M, Pesudovs K, Denniston AK, Moore DJ, Braithwaite T.",,"Eye (London, England)",2023,2023-03-17,Y,,,,"

Objective

To search for and critically appraise the psychometric quality of patient-reported outcome measures (PROMs) developed or validated in optic neuritis, in order to support high-quality research and care.

Methods

We systematically searched MEDLINE(Ovid), Embase(Ovid), PsycINFO(Ovid) and CINAHLPlus(EBSCO), and additional grey literature to November 2021, to identify PROM development or validation studies applicable to optic neuritis associated with any systemic or neurologic disease in adults. We included instruments developed using classic test theory or Rasch analysis approaches. We used established quality criteria to assess content development, validity, reliability, and responsiveness, grading multiple domains from A (high quality) to C (low quality).

Results

From 3142 screened abstracts we identified five PROM instruments potentially applicable to optic neuritis: three differing versions of the National Eye Institute (NEI)-Visual Function Questionnaire (VFQ): the 51-item VFQ; the 25-item VFQ and a 10-item neuro-ophthalmology supplement; and the Impact of Visual Impairment Scale (IVIS), a constituent of the Multiple Sclerosis Quality of Life Inventory (MSQLI) handbook, derived from the Functional Assessment of Multiple Sclerosis (FAMS). Psychometric appraisal revealed the NEI-VFQ-51 and 10-item neuro module had some relevant content development but weak psychometric development, and the FAMS had stronger psychometric development using Rasch Analysis, but was only somewhat relevant to optic neuritis. We identified no content or psychometric development for IVIS.

Conclusion

There is unmet need for a PROM with strong content and psychometric development applicable to optic neuritis for use in virtual care pathways and clinical trials to support drug marketing authorisation.",,pdf:https://www.nature.com/articles/s41433-023-02478-z.pdf; doi:https://doi.org/10.1038/s41433-023-02478-z; html:https://europepmc.org/articles/PMC10022552; pdf:https://europepmc.org/articles/PMC10022552?pdf=render 37293269,https://doi.org/10.1140/epjds/s13688-023-00394-6,Do poverty and wealth look the same the world over? A comparative study of 12 cities from five high-income countries using street images.,"Suel E, Muller E, Bennett JE, Blakely T, Doyle Y, Lynch J, Mackenbach JD, Middel A, Mizdrak A, Nathvani R, Brauer M, Ezzati M.",,EPJ data science,2023,2023-06-07,Y,Computer vision; Visual Similarity; Urban Inequalities; Street Images,,,"Urbanization and inequalities are two of the major policy themes of our time, intersecting in large cities where social and economic inequalities are particularly pronounced. Large scale street-level images are a source of city-wide visual information and allow for comparative analyses of multiple cities. Computer vision methods based on deep learning applied to street images have been shown to successfully measure inequalities in socioeconomic and environmental features, yet existing work has been within specific geographies and have not looked at how visual environments compare across different cities and countries. In this study, we aim to apply existing methods to understand whether, and to what extent, poor and wealthy groups live in visually similar neighborhoods across cities and countries. We present novel insights on similarity of neighborhoods using street-level images and deep learning methods. We analyzed 7.2 million images from 12 cities in five high-income countries, home to more than 85 million people: Auckland (New Zealand), Sydney (Australia), Toronto and Vancouver (Canada), Atlanta, Boston, Chicago, Los Angeles, New York, San Francisco, and Washington D.C. (United States of America), and London (United Kingdom). Visual features associated with neighborhood disadvantage are more distinct and unique to each city than those associated with affluence. For example, from what is visible from street images, high density poor neighborhoods located near the city center (e.g., in London) are visually distinct from poor suburban neighborhoods characterized by lower density and lower accessibility (e.g., in Atlanta). This suggests that differences between two cities is also driven by historical factors, policies, and local geography. Our results also have implications for image-based measures of inequality in cities especially when trained on data from cities that are visually distinct from target cities. We showed that these are more prone to errors for disadvantaged areas especially when transferring across cities, suggesting more attention needs to be paid to improving methods for capturing heterogeneity in poor environment across cities around the world.

Supplementary information

The online version contains supplementary material available at 10.1140/epjds/s13688-023-00394-6.",,pdf:https://epjdatascience.springeropen.com/counter/pdf/10.1140/epjds/s13688-023-00394-6; doi:https://doi.org/10.1140/epjds/s13688-023-00394-6; html:https://europepmc.org/articles/PMC10245348; pdf:https://europepmc.org/articles/PMC10245348?pdf=render +36932161,https://doi.org/10.1038/s41433-023-02478-z,Evaluating patient-reported outcome measures (PROMs) for future clinical trials in adult patients with optic neuritis.,"Panthagani J, O'Donovan C, Aiyegbusi OL, Liu X, Bayliss S, Calvert M, Pesudovs K, Denniston AK, Moore DJ, Braithwaite T.",,"Eye (London, England)",2023,2023-03-17,Y,,,,"

Objective

To search for and critically appraise the psychometric quality of patient-reported outcome measures (PROMs) developed or validated in optic neuritis, in order to support high-quality research and care.

Methods

We systematically searched MEDLINE(Ovid), Embase(Ovid), PsycINFO(Ovid) and CINAHLPlus(EBSCO), and additional grey literature to November 2021, to identify PROM development or validation studies applicable to optic neuritis associated with any systemic or neurologic disease in adults. We included instruments developed using classic test theory or Rasch analysis approaches. We used established quality criteria to assess content development, validity, reliability, and responsiveness, grading multiple domains from A (high quality) to C (low quality).

Results

From 3142 screened abstracts we identified five PROM instruments potentially applicable to optic neuritis: three differing versions of the National Eye Institute (NEI)-Visual Function Questionnaire (VFQ): the 51-item VFQ; the 25-item VFQ and a 10-item neuro-ophthalmology supplement; and the Impact of Visual Impairment Scale (IVIS), a constituent of the Multiple Sclerosis Quality of Life Inventory (MSQLI) handbook, derived from the Functional Assessment of Multiple Sclerosis (FAMS). Psychometric appraisal revealed the NEI-VFQ-51 and 10-item neuro module had some relevant content development but weak psychometric development, and the FAMS had stronger psychometric development using Rasch Analysis, but was only somewhat relevant to optic neuritis. We identified no content or psychometric development for IVIS.

Conclusion

There is unmet need for a PROM with strong content and psychometric development applicable to optic neuritis for use in virtual care pathways and clinical trials to support drug marketing authorisation.",,pdf:https://www.nature.com/articles/s41433-023-02478-z.pdf; doi:https://doi.org/10.1038/s41433-023-02478-z; html:https://europepmc.org/articles/PMC10022552; pdf:https://europepmc.org/articles/PMC10022552?pdf=render 36719715,https://doi.org/10.2196/41248,Patterns in the Use of Heart Failure Telemonitoring: Post Hoc Analysis of the e-Vita Heart Failure Trial.,"Brons M, Ten Klooster I, van Gemert-Pijnen L, Jaarsma T, Asselbergs FW, Oerlemans MIFJ, Koudstaal S, Rutten FH.",,JMIR cardio,2023,2023-01-31,Y,Adherence; Heart Failure; Patient Monitoring; Remote Monitoring; Telemonitoring; Ehealth; Electronic Personal Health Record,,,"

Background

Research on the use of home telemonitoring data and adherence to it can provide new insights into telemonitoring for the daily management of patients with heart failure (HF).

Objective

We described the use of a telemonitoring platform-including remote patient monitoring of blood pressure, pulse, and weight-and the use of the electronic personal health record. Patient characteristics were assessed in both adherent and nonadherent patients to weight transmissions.

Methods

We used the data of the e-Vita HF study, a 3-arm parallel randomized trial performed in stable patients with HF managed in outpatient clinics in the Netherlands. In this study, data were analyzed from the participants in the intervention arm (ie, e-Vita HF platform). Adherence to weight transmissions was defined as transmitting weight ≥3 times per week for at least 42 weeks during a year.

Results

Data from 150 patients (mean age 67, SD 11 years; n=37, 25% female; n=123, 82% self-assessed New York Heart Association class I-II) were analyzed. One-year adherence to weight transmissions was 74% (n=111). Patients adherent to weight transmissions were less often hospitalized for HF in the 6 months before enrollment in the study compared to those who were nonadherent (n=9, 8% vs n=9, 23%; P=.02). The percentage of patients visiting the personal health record dropped steadily over time (n=140, 93% vs n=59, 39% at one year). With univariable analyses, there was no significant correlation between patient characteristics and adherence to weight transmissions.

Conclusions

Adherence to remote patient monitoring was high among stable patients with HF and best for weighing; however, adherence decreased over time. Clinical and demographic variables seem not related to adherence to transmitting weight.

Trial registration

ClinicalTrials.gov NCT01755988; https://clinicaltrials.gov/ct2/show/NCT01755988.",,pdf:https://cardio.jmir.org/2023/1/e41248/PDF; doi:https://doi.org/10.2196/41248; html:https://europepmc.org/articles/PMC9929726; pdf:https://europepmc.org/articles/PMC9929726?pdf=render 33017023,https://doi.org/10.1001/jamaneurol.2020.3502,Trends in Optic Neuritis Incidence and Prevalence in the UK and Association With Systemic and Neurologic Disease.,"Braithwaite T, Subramanian A, Petzold A, Galloway J, Adderley NJ, Mollan SP, Plant GT, Nirantharakumar K, Denniston AK.",,JAMA neurology,2020,2020-12-01,N,,,,"

Importance

Epidemiologic data on optic neuritis (ON) incidence and associations with immune-mediated inflammatory diseases (IMIDs) are sparse.

Objective

To estimate 22-year trends in ON prevalence and incidence and association with IMIDs in the United Kingdom.

Design, setting, and participants

This cohort study analyzed data from The Health Improvement Network from January 1, 1995, to September 1, 2019. The study included 10 937 511 patients 1 year or older with 75.2 million person-years' follow-up. Annual ON incidence rates were estimated yearly (January 1, 1997, to December 31, 2018), and annual ON prevalence was estimated by performing sequential cross-sectional studies on data collected on January 1 each year for the same period. Data for 1995, 1996, and 2019 were excluded as incomplete. Risk factors for ON were explored in a cohort analysis from January 1, 1997, to December 31, 2018. Matched case-control and retrospective cohort studies were performed using data from January 1, 1995, to September 1, 2019, to explore the odds of antecedent diagnosis and hazard of incident diagnosis of 66 IMIDs in patients compared with controls.

Exposures

Optic neuritis.

Main outcomes and measures

Annual point prevalence and incidence rates of ON, adjusted incident rate ratios (IRRs) for risk factors, and adjusted odds ratios (ORs) and adjusted hazard ratios (HRs) for 66 IMIDs.

Results

A total of 10 937 511 patients (median [IQR] age at cohort entry, 32.6 [18.0-50.4] years; 5 571 282 [50.9%] female) were studied. A total of 1962 of 2826 patients (69.4%) with incident ON were female and 1192 of 1290 92.4%) were White, with a mean (SD) age of 35.6 (15.6) years. Overall incidence across 22 years was stable at 3.7 (95% CI, 3.6-3.9) per 100 000 person-years. Annual point prevalence (per 100 000 population) increased with database maturity, from 69.3 (95% CI, 57.2-81.3) in 1997 to 114.8 (95% CI, 111.0-118.6) in 2018. The highest risk of incident ON was associated with female sex, obesity, reproductive age, smoking, and residence at higher latitude, with significantly lower risk in South Asian or mixed race/ethnicity compared with White people. Patients with ON had significantly higher odds of prior multiple sclerosis (MS) (OR, 98.22; 95% CI, 65.40-147.52), syphilis (OR, 5.76; 95% CI, 1.39-23.96), Mycoplasma (OR, 3.90; 95% CI, 1.09-13.93), vasculitis (OR, 3.70; 95% CI, 1.68-8.15), sarcoidosis (OR, 2.50; 95% CI, 1.21-5.18), Epstein-Barr virus (OR, 2.29; 95% CI, 1.80-2.92), Crohn disease (OR, 1.97; 95% CI, 1.13-3.43), and psoriasis (OR, 1.28; 95% CI, 1.03-1.58). Patients with ON had a significantly higher hazard of incident MS (HR, 284.97; 95% CI, 167.85-483.81), Behçet disease (HR, 17.39; 95% CI, 1.55-195.53), sarcoidosis (HR, 14.80; 95% CI, 4.86-45.08), vasculitis (HR, 4.89; 95% CI, 1.82-13.10), Sjögren syndrome (HR, 3.48; 95% CI, 1.38-8.76), and herpetic infection (HR, 1.68; 95% CI, 1.24-2.28).

Conclusions and relevance

The UK incidence of ON is stable. Even though predominantly associated with MS, ON has numerous other associations with IMIDs. Although individually rare, together these associations outnumber MS-associated ON and typically require urgent management to preserve sight.",,pdf:http://pure-oai.bham.ac.uk/ws/files/100688542/NEU20_1602R_Merged_PDF.pdf; doi:https://doi.org/10.1001/jamaneurol.2020.3502; html:https://europepmc.org/articles/PMC7536630; doi:https://doi.org/10.1001/jamaneurol.2020.3502 36529816,https://doi.org/10.1038/s41598-022-26357-x,Novel multimorbidity clusters in people with eczema and asthma: a population-based cluster analysis.,"Mulick AR, Henderson AD, Prieto-Merino D, Mansfield KE, Matthewman J, Quint JK, Lyons RA, Sheikh A, McAllister DA, Nitsch D, Langan SM.",,Scientific reports,2022,2022-12-18,Y,,,,"Eczema and asthma are allergic diseases and two of the commonest chronic conditions in high-income countries. Their co-existence with other allergic conditions is common, but little research exists on wider multimorbidity with these conditions. We set out to identify and compare clusters of multimorbidity in people with eczema or asthma and people without. Using routinely-collected primary care data from the U.K. Clinical Research Practice Datalink GOLD, we identified adults ever having eczema (or asthma), and comparison groups never having eczema (or asthma). We derived clusters of multimorbidity from hierarchical cluster analysis of Jaccard distances between pairs of diagnostic categories estimated from mixed-effects logistic regressions. We analysed 434,422 individuals with eczema (58% female, median age 47 years) and 1,333,281 individuals without (55% female, 47 years), and 517,712 individuals with asthma (53% female, 44 years) and 1,601,210 individuals without (53% female, 45 years). Age at first morbidity, sex and having eczema/asthma affected the scope of multimorbidity, with women, older age and eczema/asthma being associated with larger morbidity clusters. Injuries, digestive, nervous system and mental health disorders were more commonly seen in eczema and asthma than control clusters. People with eczema and asthma of all ages and both sexes may experience greater multimorbidity than people without eczema and asthma, including conditions not previously recognised as contributing to their disease burden. This work highlights areas where there is a critical need for research addressing the burden and drivers of multimorbidity in order to inform strategies to reduce poor health outcomes.",,pdf:https://www.nature.com/articles/s41598-022-26357-x.pdf; doi:https://doi.org/10.1038/s41598-022-26357-x; html:https://europepmc.org/articles/PMC9760185; pdf:https://europepmc.org/articles/PMC9760185?pdf=render @@ -866,8 +866,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 36697134,https://doi.org/10.1016/j.jacc.2022.10.034,Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis.,"Ćorović A, Wall C, Nus M, Gopalan D, Huang Y, Imaz M, Zulcinski M, Peverelli M, Uryga A, Lambert J, Bressan D, Maughan RT, Pericleous C, Dubash S, Jordan N, Jayne DR, Hoole SP, Calvert PA, Dean AF, Rassl D, Barwick T, Iles M, Frontini M, Hannon G, Manavaki R, Fryer TD, Aloj L, Graves MJ, Gilbert FJ, Dweck MR, Newby DE, Fayad ZA, Reynolds G, Morgan AW, Aboagye EO, Davenport AP, Jørgensen HF, Mallat Z, Bennett MR, Peters JE, Rudd JHF, Mason JC, Tarkin JM.",,Journal of the American College of Cardiology,2023,2023-01-01,Y,Atherosclerosis; Inflammation; Molecular Imaging; Giant Cell Arteritis; Takayasu Arteritis; Somatostatin Receptor,,,"

Background

Assessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures.

Objectives

We aimed to investigate somatostatin receptor 2 (SST2) as a novel inflammation-specific molecular imaging target in LVV.

Methods

In a prospective, observational cohort study, in vivo arterial SST2 expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using 68Ga-DOTATATE and 18F-FET-βAG-TOCA. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy; imaging mass cytometry; and bulk, single-cell, and single-nucleus RNA sequencing.

Results

Sixty-one participants (LVV: n = 27; recent atherosclerotic myocardial infarction of ≤2 weeks: n = 25; control subjects with an oncologic indication for imaging: n = 9) were included. Index vessel SST2 maximum tissue-to-blood ratio was 61.8% (P < 0.0001) higher in active/grumbling LVV than inactive LVV and 34.6% (P = 0.0002) higher than myocardial infarction, with good diagnostic accuracy (area under the curve: ≥0.86; P < 0.001 for both). Arterial SST2 signal was not elevated in any of the control subjects. SST2 PET/MRI was generally consistent with 18F-fluorodeoxyglucose PET/computed tomography imaging in LVV patients with contemporaneous clinical scans but with very low background signal in the brain and heart, allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. Clinically effective treatment for LVV was associated with a 0.49 ± 0.24 (standard error of the mean [SEM]) (P = 0.04; 22.3%) reduction in the SST2 maximum tissue-to-blood ratio after 9.3 ± 3.2 months. SST2 expression was localized to macrophages, pericytes, and perivascular adipocytes in vasculitis specimens, with specific receptor binding confirmed by autoradiography. SSTR2-expressing macrophages coexpressed proinflammatory markers.

Conclusions

SST2 PET/MRI holds major promise for diagnosis and therapeutic monitoring in LVV. (PET Imaging of Giant Cell and Takayasu Arteritis [PITA], NCT04071691; Residual Inflammation and Plaque Progression Long-Term Evaluation [RIPPLE], NCT04073810).",,doi:https://doi.org/10.1016/j.jacc.2022.10.034; doi:https://doi.org/10.1016/j.jacc.2022.10.034; html:https://europepmc.org/articles/PMC9883634; pdf:https://europepmc.org/articles/PMC9883634?pdf=render 36449515,https://doi.org/10.1371/journal.pcbi.1010726,Cluster detection with random neighbourhood covering: Application to invasive Group A Streptococcal disease.,"Cavallaro M, Coelho J, Ready D, Decraene V, Lamagni T, McCarthy ND, Todkill D, Keeling MJ.",,PLoS computational biology,2022,2022-11-30,Y,,,,"The rapid detection of outbreaks is a key step in the effective control and containment of infectious diseases. In particular, the identification of cases which might be epidemiologically linked is crucial in directing outbreak-containment efforts and shaping the intervention of public health authorities. Often this requires the detection of clusters of cases whose numbers exceed those expected by a background of sporadic cases. Quantifying exceedances rapidly is particularly challenging when only few cases are typically reported in a precise location and time. To address such important public health concerns, we present a general method which can detect spatio-temporal deviations from a Poisson point process and estimate the odds of an isolate being part of a cluster. This method can be applied to diseases where detailed geographical information is available. In addition, we propose an approach to explicitly take account of delays in microbial typing. As a case study, we considered invasive group A Streptococcus infection events as recorded and typed by Public Health England from 2015 to 2020.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1010726&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1010726; html:https://europepmc.org/articles/PMC9744322; pdf:https://europepmc.org/articles/PMC9744322?pdf=render 35193912,https://doi.org/10.1136/bmjopen-2021-053884,"Variation in health visiting contacts for children in England: cross-sectional analysis of the 2-2½ year review using administrative data (Community Services Dataset, CSDS).","Fraser C, Harron K, Barlow J, Bennett S, Woods G, Shand J, Kendall S, Woodman J.",,BMJ open,2022,2022-02-22,Y,Public Health; Community Child Health; Child Protection; Organisation Of Health Services,,,"

Objective

The 2-2½ year universal health visiting review in England is a key time point for assessing child development and promoting school readiness. We aimed to ascertain which children were least likely to receive their 2-2½ year review and whether there were additional non-mandated contacts for children who missed this review.

Design, setting, participants

Cross-sectional analysis of the 2-2½ year review and additional health visiting contacts for 181 130 children aged 2 in England 2018/2019, stratified by ethnicity, deprivation, safeguarding vulnerability indicator and Looked After Child status.

Analysis

We used data from 33 local authorities submitting highly complete data on health visiting contacts to the Community Services Dataset. We calculated the percentage of children with a recorded 2-2½ year review and/or any additional health visiting contacts and average number of contacts, by child characteristic.

Results

The most deprived children were slightly less likely to receive a 2-2½ year review than the least deprived children (72% vs 78%) and Looked After Children much less likely, compared with other children (44% vs 69%). When all additional contacts were included, the pattern was reversed (deprivation) or disappeared (Looked After children). A substantial proportion of all children (24%), children with a 'safeguarding vulnerability' (22%) and Looked After children (29%) did not have a record of either a 2-2½ year review or any other face-to-face contact in the year.

Conclusions

A substantial minority of children aged 2 with known vulnerabilities did not see the health visiting team at all in the year. Some higher need children (eg, deprived and Looked After) appeared to be seeing the health visiting team but not receiving their mandated health review. Further work is needed to establish the reasons for this, and potential solutions. There is an urgent need to improve the quality of national health visiting data.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e053884.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-053884; html:https://europepmc.org/articles/PMC8867374; pdf:https://europepmc.org/articles/PMC8867374?pdf=render -36351458,https://doi.org/10.1016/s0140-6736(22)02074-8,Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials.,"Nuffield Department of Population Health Renal Studies Group, SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium.",,"Lancet (London, England)",2022,2022-11-06,Y,,,,"

Background

Large trials have shown that sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart failure or chronic kidney disease, or with type 2 diabetes and high risk of atherosclerotic cardiovascular disease. None of the trials recruiting patients with and without diabetes were designed to assess outcomes separately in patients without diabetes.

Methods

We did a systematic review and meta-analysis of SGLT2 inhibitor trials. We searched the MEDLINE and Embase databases for trials published from database inception to Sept 5, 2022. SGLT2 inhibitor trials that were double-blind, placebo-controlled, performed in adults (age ≥18 years), large (≥500 participants per group), and at least 6 months in duration were included. Summary-level data used for analysis were extracted from published reports or provided by trial investigators, and inverse-variance-weighted meta-analyses were conducted to estimate treatment effects. The main efficacy outcomes were kidney disease progression (standardised to a definition of a sustained ≥50% decrease in estimated glomerular filtration rate [eGFR] from randomisation, a sustained low eGFR, end-stage kidney disease, or death from kidney failure), acute kidney injury, and a composite of cardiovascular death or hospitalisation for heart failure. Other outcomes were death from cardiovascular and non-cardiovascular disease considered separately, and the main safety outcomes were ketoacidosis and lower limb amputation. This study is registered with PROSPERO, CRD42022351618.

Findings

We identified 13 trials involving 90 413 participants. After exclusion of four participants with uncertain diabetes status, we analysed 90 409 participants (74 804 [82·7%] participants with diabetes [>99% with type 2 diabetes] and 15 605 [17·3%] without diabetes; trial-level mean baseline eGFR range 37-85 mL/min per 1·73 m2). Compared with placebo, allocation to an SGLT2 inhibitor reduced the risk of kidney disease progression by 37% (relative risk [RR] 0·63, 95% CI 0·58-0·69) with similar RRs in patients with and without diabetes. In the four chronic kidney disease trials, RRs were similar irrespective of primary kidney diagnosis. SGLT2 inhibitors reduced the risk of acute kidney injury by 23% (0·77, 0·70-0·84) and the risk of cardiovascular death or hospitalisation for heart failure by 23% (0·77, 0·74-0·81), again with similar effects in those with and without diabetes. SGLT2 inhibitors also reduced the risk of cardiovascular death (0·86, 0·81-0·92) but did not significantly reduce the risk of non-cardiovascular death (0·94, 0·88-1·02). For these mortality outcomes, RRs were similar in patients with and without diabetes. For all outcomes, results were broadly similar irrespective of trial mean baseline eGFR. Based on estimates of absolute effects, the absolute benefits of SGLT2 inhibition outweighed any serious hazards of ketoacidosis or amputation.

Interpretation

In addition to the established cardiovascular benefits of SGLT2 inhibitors, the randomised data support their use for modifying risk of kidney disease progression and acute kidney injury, not only in patients with type 2 diabetes at high cardiovascular risk, but also in patients with chronic kidney disease or heart failure irrespective of diabetes status, primary kidney disease, or kidney function.

Funding

UK Medical Research Council and Kidney Research UK.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613836; doi:https://doi.org/10.1016/S0140-6736(22)02074-8; html:https://europepmc.org/articles/PMC7613836 35189842,https://doi.org/10.1186/s12888-022-03753-1,"Remote Assessment of Disease and Relapse in Major Depressive Disorder (RADAR-MDD): recruitment, retention, and data availability in a longitudinal remote measurement study.","Matcham F, Leightley D, Siddi S, Lamers F, White KM, Annas P, de Girolamo G, Difrancesco S, Haro JM, Horsfall M, Ivan A, Lavelle G, Li Q, Lombardini F, Mohr DC, Narayan VA, Oetzmann C, Penninx BWJH, Bruce S, Nica R, Simblett SK, Wykes T, Brasen JC, Myin-Germeys I, Rintala A, Conde P, Dobson RJB, Folarin AA, Stewart C, Ranjan Y, Rashid Z, Cummins N, Manyakov NV, Vairavan S, Hotopf M, RADAR-CNS consortium.",,BMC psychiatry,2022,2022-02-21,Y,Cohort study; Longitudinal; Major Depressive Disorder; Multicentre; Remote Measurement Technologies,,,"

Background

Major Depressive Disorder (MDD) is prevalent, often chronic, and requires ongoing monitoring of symptoms to track response to treatment and identify early indicators of relapse. Remote Measurement Technologies (RMT) provide an opportunity to transform the measurement and management of MDD, via data collected from inbuilt smartphone sensors and wearable devices alongside app-based questionnaires and tasks. A key question for the field is the extent to which participants can adhere to research protocols and the completeness of data collected. We aimed to describe drop out and data completeness in a naturalistic multimodal longitudinal RMT study, in people with a history of recurrent MDD. We further aimed to determine whether those experiencing a depressive relapse at baseline contributed less complete data.

Methods

Remote Assessment of Disease and Relapse - Major Depressive Disorder (RADAR-MDD) is a multi-centre, prospective observational cohort study conducted as part of the Remote Assessment of Disease and Relapse - Central Nervous System (RADAR-CNS) program. People with a history of MDD were provided with a wrist-worn wearable device, and smartphone apps designed to: a) collect data from smartphone sensors; and b) deliver questionnaires, speech tasks, and cognitive assessments. Participants were followed-up for a minimum of 11 months and maximum of 24 months.

Results

Individuals with a history of MDD (n = 623) were enrolled in the study,. We report 80% completion rates for primary outcome assessments across all follow-up timepoints. 79.8% of people participated for the maximum amount of time available and 20.2% withdrew prematurely. We found no evidence of an association between the severity of depression symptoms at baseline and the availability of data. In total, 110 participants had > 50% data available across all data types.

Conclusions

RADAR-MDD is the largest multimodal RMT study in the field of mental health. Here, we have shown that collecting RMT data from a clinical population is feasible. We found comparable levels of data availability in active and passive forms of data collection, demonstrating that both are feasible in this patient group.",,pdf:https://bmcpsychiatry.biomedcentral.com/track/pdf/10.1186/s12888-022-03753-1; doi:https://doi.org/10.1186/s12888-022-03753-1; html:https://europepmc.org/articles/PMC8860359; pdf:https://europepmc.org/articles/PMC8860359?pdf=render +36351458,https://doi.org/10.1016/s0140-6736(22)02074-8,Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials.,"Nuffield Department of Population Health Renal Studies Group, SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium.",,"Lancet (London, England)",2022,2022-11-06,Y,,,,"

Background

Large trials have shown that sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart failure or chronic kidney disease, or with type 2 diabetes and high risk of atherosclerotic cardiovascular disease. None of the trials recruiting patients with and without diabetes were designed to assess outcomes separately in patients without diabetes.

Methods

We did a systematic review and meta-analysis of SGLT2 inhibitor trials. We searched the MEDLINE and Embase databases for trials published from database inception to Sept 5, 2022. SGLT2 inhibitor trials that were double-blind, placebo-controlled, performed in adults (age ≥18 years), large (≥500 participants per group), and at least 6 months in duration were included. Summary-level data used for analysis were extracted from published reports or provided by trial investigators, and inverse-variance-weighted meta-analyses were conducted to estimate treatment effects. The main efficacy outcomes were kidney disease progression (standardised to a definition of a sustained ≥50% decrease in estimated glomerular filtration rate [eGFR] from randomisation, a sustained low eGFR, end-stage kidney disease, or death from kidney failure), acute kidney injury, and a composite of cardiovascular death or hospitalisation for heart failure. Other outcomes were death from cardiovascular and non-cardiovascular disease considered separately, and the main safety outcomes were ketoacidosis and lower limb amputation. This study is registered with PROSPERO, CRD42022351618.

Findings

We identified 13 trials involving 90 413 participants. After exclusion of four participants with uncertain diabetes status, we analysed 90 409 participants (74 804 [82·7%] participants with diabetes [>99% with type 2 diabetes] and 15 605 [17·3%] without diabetes; trial-level mean baseline eGFR range 37-85 mL/min per 1·73 m2). Compared with placebo, allocation to an SGLT2 inhibitor reduced the risk of kidney disease progression by 37% (relative risk [RR] 0·63, 95% CI 0·58-0·69) with similar RRs in patients with and without diabetes. In the four chronic kidney disease trials, RRs were similar irrespective of primary kidney diagnosis. SGLT2 inhibitors reduced the risk of acute kidney injury by 23% (0·77, 0·70-0·84) and the risk of cardiovascular death or hospitalisation for heart failure by 23% (0·77, 0·74-0·81), again with similar effects in those with and without diabetes. SGLT2 inhibitors also reduced the risk of cardiovascular death (0·86, 0·81-0·92) but did not significantly reduce the risk of non-cardiovascular death (0·94, 0·88-1·02). For these mortality outcomes, RRs were similar in patients with and without diabetes. For all outcomes, results were broadly similar irrespective of trial mean baseline eGFR. Based on estimates of absolute effects, the absolute benefits of SGLT2 inhibition outweighed any serious hazards of ketoacidosis or amputation.

Interpretation

In addition to the established cardiovascular benefits of SGLT2 inhibitors, the randomised data support their use for modifying risk of kidney disease progression and acute kidney injury, not only in patients with type 2 diabetes at high cardiovascular risk, but also in patients with chronic kidney disease or heart failure irrespective of diabetes status, primary kidney disease, or kidney function.

Funding

UK Medical Research Council and Kidney Research UK.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613836; doi:https://doi.org/10.1016/S0140-6736(22)02074-8; html:https://europepmc.org/articles/PMC7613836 34755628,https://doi.org/10.1016/s0140-6736(21)01546-4,"Global, regional, and national mortality among young people aged 10-24 years, 1950-2019: a systematic analysis for the Global Burden of Disease Study 2019.",GBD 2019 Adolescent Mortality Collaborators.,,"Lancet (London, England)",2021,2021-10-28,Y,,,,"

Background

Documentation of patterns and long-term trends in mortality in young people, which reflect huge changes in demographic and social determinants of adolescent health, enables identification of global investment priorities for this age group. We aimed to analyse data on the number of deaths, years of life lost, and mortality rates by sex and age group in people aged 10-24 years in 204 countries and territories from 1950 to 2019 by use of estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019.

Methods

We report trends in estimated total numbers of deaths and mortality rate per 100 000 population in young people aged 10-24 years by age group (10-14 years, 15-19 years, and 20-24 years) and sex in 204 countries and territories between 1950 and 2019 for all causes, and between 1980 and 2019 by cause of death. We analyse variation in outcomes by region, age group, and sex, and compare annual rate of change in mortality in young people aged 10-24 years with that in children aged 0-9 years from 1990 to 2019. We then analyse the association between mortality in people aged 10-24 years and socioeconomic development using the GBD Socio-demographic Index (SDI), a composite measure based on average national educational attainment in people older than 15 years, total fertility rate in people younger than 25 years, and income per capita. We assess the association between SDI and all-cause mortality in 2019, and analyse the ratio of observed to expected mortality by SDI using the most recent available data release (2017).

Findings

In 2019 there were 1·49 million deaths (95% uncertainty interval 1·39-1·59) worldwide in people aged 10-24 years, of which 61% occurred in males. 32·7% of all adolescent deaths were due to transport injuries, unintentional injuries, or interpersonal violence and conflict; 32·1% were due to communicable, nutritional, or maternal causes; 27·0% were due to non-communicable diseases; and 8·2% were due to self-harm. Since 1950, deaths in this age group decreased by 30·0% in females and 15·3% in males, and sex-based differences in mortality rate have widened in most regions of the world. Geographical variation has also increased, particularly in people aged 10-14 years. Since 1980, communicable and maternal causes of death have decreased sharply as a proportion of total deaths in most GBD super-regions, but remain some of the most common causes in sub-Saharan Africa and south Asia, where more than half of all adolescent deaths occur. Annual percentage decrease in all-cause mortality rate since 1990 in adolescents aged 15-19 years was 1·3% in males and 1·6% in females, almost half that of males aged 1-4 years (2·4%), and around a third less than in females aged 1-4 years (2·5%). The proportion of global deaths in people aged 0-24 years that occurred in people aged 10-24 years more than doubled between 1950 and 2019, from 9·5% to 21·6%.

Interpretation

Variation in adolescent mortality between countries and by sex is widening, driven by poor progress in reducing deaths in males and older adolescents. Improving global adolescent mortality will require action to address the specific vulnerabilities of this age group, which are being overlooked. Furthermore, indirect effects of the COVID-19 pandemic are likely to jeopardise efforts to improve health outcomes including mortality in young people aged 10-24 years. There is an urgent need to respond to the changing global burden of adolescent mortality, address inequities where they occur, and improve the availability and quality of primary mortality data in this age group.

Funding

Bill & Melinda Gates Foundation.",,pdf:http://www.thelancet.com/article/S0140673621015464/pdf; doi:https://doi.org/10.1016/S0140-6736(21)01546-4; html:https://europepmc.org/articles/PMC8576274; pdf:https://europepmc.org/articles/PMC8576274?pdf=render 35072136,https://doi.org/10.1016/j.xgen.2021.100029,GA4GH: International policies and standards for data sharing across genomic research and healthcare.,"Rehm HL, Page AJH, Smith L, Adams JB, Alterovitz G, Babb LJ, Barkley MP, Baudis M, Beauvais MJS, Beck T, Beckmann JS, Beltran S, Bernick D, Bernier A, Bonfield JK, Boughtwood TF, Bourque G, Bowers SR, Brookes AJ, Brudno M, Brush MH, Bujold D, Burdett T, Buske OJ, Cabili MN, Cameron DL, Carroll RJ, Casas-Silva E, Chakravarty D, Chaudhari BP, Chen SH, Cherry JM, Chung J, Cline M, Clissold HL, Cook-Deegan RM, Courtot M, Cunningham F, Cupak M, Davies RM, Denisko D, Doerr MJ, Dolman LI, Dove ES, Dursi LJ, Dyke SOM, Eddy JA, Eilbeck K, Ellrott KP, Fairley S, Fakhro KA, Firth HV, Fitzsimons MS, Fiume M, Flicek P, Fore IM, Freeberg MA, Freimuth RR, Fromont LA, Fuerth J, Gaff CL, Gan W, Ghanaim EM, Glazer D, Green RC, Griffith M, Griffith OL, Grossman RL, Groza T, Auvil JMG, Guigó R, Gupta D, Haendel MA, Hamosh A, Hansen DP, Hart RK, Hartley DM, Haussler D, Hendricks-Sturrup RM, Ho CWL, Hobb AE, Hoffman MM, Hofmann OM, Holub P, Hsu JS, Hubaux JP, Hunt SE, Husami A, Jacobsen JO, Jamuar SS, Janes EL, Jeanson F, Jené A, Johns AL, Joly Y, Jones SJM, Kanitz A, Kato K, Keane TM, Kekesi-Lafrance K, Kelleher J, Kerry G, Khor SS, Knoppers BM, Konopko MA, Kosaki K, Kuba M, Lawson J, Leinonen R, Li S, Lin MF, Linden M, Liu X, Udara Liyanage I, Lopez J, Lucassen AM, Lukowski M, Mann AL, Marshall J, Mattioni M, Metke-Jimenez A, Middleton A, Milne RJ, Molnár-Gábor F, Mulder N, Munoz-Torres MC, Nag R, Nakagawa H, Nasir J, Navarro A, Nelson TH, Niewielska A, Nisselle A, Niu J, Nyrönen TH, O'Connor BD, Oesterle S, Ogishima S, Wang VO, Paglione LAD, Palumbo E, Parkinson HE, Philippakis AA, Pizarro AD, Prlic A, Rambla J, Rendon A, Rider RA, Robinson PN, Rodarmer KW, Rodriguez LL, Rubin AF, Rueda M, Rushton GA, Ryan RS, Saunders GI, Schuilenburg H, Schwede T, Scollen S, Senf A, Sheffield NC, Skantharajah N, Smith AV, Sofia HJ, Spalding D, Spurdle AB, Stark Z, Stein LD, Suematsu M, Tan P, Tedds JA, Thomson AA, Thorogood A, Tickle TL, Tokunaga K, Törnroos J, Torrents D, Upchurch S, Valencia A, Guimera RV, Vamathevan J, Varma S, Vears DF, Viner C, Voisin C, Wagner AH, Wallace SE, Walsh BP, Williams MS, Winkler EC, Wold BJ, Wood GM, Woolley JP, Yamasaki C, Yates AD, Yung CK, Zass LJ, Zaytseva K, Zhang J, Goodhand P, North K, Birney E.",,Cell genomics,2021,2021-11-01,Y,,,,"The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits.",,doi:https://doi.org/10.1016/j.xgen.2021.100029; html:https://europepmc.org/articles/PMC8774288; pdf:https://europepmc.org/articles/PMC8774288?pdf=render 34416195,https://doi.org/10.1016/s0140-6736(21)01207-1,"Global, regional, and national progress towards Sustainable Development Goal 3.2 for neonatal and child health: all-cause and cause-specific mortality findings from the Global Burden of Disease Study 2019.",GBD 2019 Under-5 Mortality Collaborators.,,"Lancet (London, England)",2021,2021-08-17,Y,,,,"

Background

Sustainable Development Goal 3.2 has targeted elimination of preventable child mortality, reduction of neonatal death to less than 12 per 1000 livebirths, and reduction of death of children younger than 5 years to less than 25 per 1000 livebirths, for each country by 2030. To understand current rates, recent trends, and potential trajectories of child mortality for the next decade, we present the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 findings for all-cause mortality and cause-specific mortality in children younger than 5 years of age, with multiple scenarios for child mortality in 2030 that include the consideration of potential effects of COVID-19, and a novel framework for quantifying optimal child survival.

Methods

We completed all-cause mortality and cause-specific mortality analyses from 204 countries and territories for detailed age groups separately, with aggregated mortality probabilities per 1000 livebirths computed for neonatal mortality rate (NMR) and under-5 mortality rate (U5MR). Scenarios for 2030 represent different potential trajectories, notably including potential effects of the COVID-19 pandemic and the potential impact of improvements preferentially targeting neonatal survival. Optimal child survival metrics were developed by age, sex, and cause of death across all GBD location-years. The first metric is a global optimum and is based on the lowest observed mortality, and the second is a survival potential frontier that is based on stochastic frontier analysis of observed mortality and Healthcare Access and Quality Index.

Findings

Global U5MR decreased from 71·2 deaths per 1000 livebirths (95% uncertainty interval [UI] 68·3-74·0) in 2000 to 37·1 (33·2-41·7) in 2019 while global NMR correspondingly declined more slowly from 28·0 deaths per 1000 live births (26·8-29·5) in 2000 to 17·9 (16·3-19·8) in 2019. In 2019, 136 (67%) of 204 countries had a U5MR at or below the SDG 3.2 threshold and 133 (65%) had an NMR at or below the SDG 3.2 threshold, and the reference scenario suggests that by 2030, 154 (75%) of all countries could meet the U5MR targets, and 139 (68%) could meet the NMR targets. Deaths of children younger than 5 years totalled 9·65 million (95% UI 9·05-10·30) in 2000 and 5·05 million (4·27-6·02) in 2019, with the neonatal fraction of these deaths increasing from 39% (3·76 million [95% UI 3·53-4·02]) in 2000 to 48% (2·42 million; 2·06-2·86) in 2019. NMR and U5MR were generally higher in males than in females, although there was no statistically significant difference at the global level. Neonatal disorders remained the leading cause of death in children younger than 5 years in 2019, followed by lower respiratory infections, diarrhoeal diseases, congenital birth defects, and malaria. The global optimum analysis suggests NMR could be reduced to as low as 0·80 (95% UI 0·71-0·86) deaths per 1000 livebirths and U5MR to 1·44 (95% UI 1·27-1·58) deaths per 1000 livebirths, and in 2019, there were as many as 1·87 million (95% UI 1·35-2·58; 37% [95% UI 32-43]) of 5·05 million more deaths of children younger than 5 years than the survival potential frontier.

Interpretation

Global child mortality declined by almost half between 2000 and 2019, but progress remains slower in neonates and 65 (32%) of 204 countries, mostly in sub-Saharan Africa and south Asia, are not on track to meet either SDG 3.2 target by 2030. Focused improvements in perinatal and newborn care, continued and expanded delivery of essential interventions such as vaccination and infection prevention, an enhanced focus on equity, continued focus on poverty reduction and education, and investment in strengthening health systems across the development spectrum have the potential to substantially improve U5MR. Given the widespread effects of COVID-19, considerable effort will be required to maintain and accelerate progress.

Funding

Bill & Melinda Gates Foundation.",,pdf:http://www.thelancet.com/article/S0140673621012071/pdf; doi:https://doi.org/10.1016/S0140-6736(21)01207-1; html:https://europepmc.org/articles/PMC8429803; pdf:https://europepmc.org/articles/PMC8429803?pdf=render diff --git a/data/papers.csv b/data/papers.csv index 36e43368..f6ac672f 100644 --- a/data/papers.csv +++ b/data/papers.csv @@ -119,8 +119,8 @@ PMC10929454,https://doi.org/,Optimising data curation pipelines for population-l 35356660,https://doi.org/10.7189/jogh.12.05008,"BNT162b2 and ChAdOx1 nCoV-19 vaccinations, incidence of SARS-CoV-2 infections and COVID-19 hospitalisations in Scotland in the Delta era.","Shah SA, Robertson C, Rudan I, Murray JL, McCowan C, Grange Z, Buelo A, Sullivan C, Simpson CR, Ritchie LD, Sheikh A.",,Journal of global health,2022,2022-03-26,Y,,,,"

Background

The emergence of the B.1.617.2 Delta variant of concern was associated with increasing numbers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and COVID-19 hospital admissions. We aim to study national population level SARS-CoV-2 infections and COVID-19 associated hospitalisations by vaccination status to provide insight into the association of vaccination on temporal trends during the time in which the SARS-CoV-2 Delta variant became dominant in Scotland.

Methods

We used the Scotland-wide Early Pandemic Evaluation and Enhanced Surveillance (EAVE II) platform, covering the period when Delta was pervasive (May 01 to October 23, 2021). We performed a cohort analysis of every vaccine-eligible individual aged 20 or over from across Scotland. We determined the vaccination coverage, SARS-CoV-2 incidence rate and COVID-19 associated hospitalisations incidence rate. We then stratified those rates by age group, vaccination status (defined as ""unvaccinated"", ""partially vaccinated"" (1 dose), or ""fully vaccinated"" (2 doses)), vaccine type (BNT162b2 or ChAdOx1 nCoV-19), and coexisting conditions known to be associated with severe COVID-19 outcomes.

Results

During the follow-up of 4 183 022 individuals, there were 407 405 SARS-CoV-2 positive cases with 10 441 (2.6%) associated with a hospital admission. Those vaccinated with two doses (defined as fully vaccinated in the current study) of either vaccine had lower incidence rates of SARS-CoV-2 infections and much lower incidence rates of COVID-19 associated hospitalisations than those unvaccinated in the Delta era in Scotland. Younger age groups were substantially more likely to get infected. In contrast, older age groups were much more likely to be hospitalised. The incidence rates stratified by coexisting conditions were broadly comparable with the overall age group patterns.

Conclusions

This study suggests that national population level vaccination was associated with a reduction in SARS-CoV-2 infections and COVID-19 associated hospitalisation in Scotland throughout the Delta era.",,doi:https://doi.org/10.7189/jogh.12.05008; doi:https://doi.org/10.7189/jogh.12.05008; html:https://europepmc.org/articles/PMC8942298; pdf:https://europepmc.org/articles/PMC8942298?pdf=render 35609019,https://doi.org/10.1371/journal.pone.0267176,Population birth outcomes in 2020 and experiences of expectant mothers during the COVID-19 pandemic: A 'born in Wales' mixed methods study using routine data.,"Jones H, Seaborne M, Cowley L, Odd D, Paranjothy S, Akbari A, Brophy S.",,PloS one,2022,2022-05-24,Y,,,,"

Background

Pregnancy can be a stressful time and the COVID-19 pandemic has affected all aspects of life. This study aims to investigate the pandemic impact on pregnancy experience, rates of primary childhood immunisations and the differences in birth outcomes in during 2020 to those of previous years.

Methods

Self-reported pregnancy experience: 215 expectant mothers (aged 16+) in Wales completed an online survey about their experiences of pregnancy during the pandemic. The qualitative survey data was analysed using codebook thematic analysis. Population-level birth outcomes in Wales: Stillbirths, prematurity, birth weight and Caesarean section births before (2016-2019) and during (2020) the pandemic were compared using anonymised individual-level, population-scale routine data held in the Secure Anonymised Information Linkage (SAIL) Databank. Uptake of the first three scheduled primary childhood immunisations were compared between 2019 and 2020.

Findings

The pandemic had a negative impact on the mental health of 71% of survey respondents, who reported anxiety, stress and loneliness; this was associated with attending scans without their partner, giving birth alone, and minimal contact with midwives. There was no significant difference in annual outcomes including gestation and birth weight, stillbirths, and Caesarean sections for infants born in 2020 compared to 2016-2019. There was an increase in late term births (≥42 weeks gestation) during the first lockdown (OR: 1.28, p = 0.019) and a decrease in moderate to late preterm births (32-36 weeks gestation) during the second lockdown (OR: 0.74, p = 0.001). Fewer babies were born in 2020 (N = 29,031) compared to 2016-2019 (average N = 32,582). All babies received their immunisations in 2020, but there were minor delays in the timings of immunisations. Those due at 8-weeks were 8% less likely to be on time (within 28-days) and at 16-weeks, they were 19% less likely to be on time.

Interpretation

Whilst the pandemic had a negative impact on mothers' experiences of pregnancy. Population-level data suggests that this did not translate to adverse birth outcomes for babies born during the pandemic.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0267176&type=printable; doi:https://doi.org/10.1371/journal.pone.0267176; html:https://europepmc.org/articles/PMC9129046; pdf:https://europepmc.org/articles/PMC9129046?pdf=render 37192798,https://doi.org/10.1136/bmjopen-2022-066398,Impact of pausing elective hip and knee replacement surgery during winter 2017 on subsequent service provision at a major NHS Trust: a descriptive observational study using interrupted time series.,"Jones T, Penfold C, Redaniel MT, Eyles E, Keen T, Elliott A, Blom AW, Judge A.",,BMJ open,2023,2023-05-16,Y,Knee; Hip; Human Resource Management; Orthopaedic & Trauma Surgery,,,"

Objectives

To explore the impact of a temporary cancellation of elective surgery in winter 2017 on trends in primary hip and knee replacement at a major National Health Service (NHS) Trust, and whether lessons can be learnt about efficient surgery provision.

Design and setting

Observational descriptive study using interrupted time series analysis of hospital records to explore trends in primary hip and knee replacement surgery at a major NHS Trust, as well as patient characteristics, 2016-2019.

Intervention

A temporary cancellation of elective services for 2 months in winter 2017.

Outcomes

NHS-funded hospital admissions for primary hip or knee replacement, length of stay and bed occupancy. Additionally, we explored the ratio of elective to emergency admissions at the Trust as a measure of elective capacity, and the ratio of public to private provision of NHS-funded hip and knee surgery.

Results

After winter 2017, there was a sustained reduction in the number of knee replacements, a decrease in the proportion of most deprived people having knee replacements and an increase in average age for knee replacement and comorbidity for both types of surgery. The ratio of public to private provision dropped after winter 2017, and elective capacity generally has reduced over time. There was clear seasonality in provision of elective surgery, with less complex patients admitted during winter.

Conclusions

Declining elective capacity and seasonality has a marked effect on the provision of joint replacement, despite efficiency improvements in hospital treatment. The Trust has outsourced less complex patients to independent providers, and/or treated them during winter when capacity is most limited. There is a need to explore whether these are strategies that could be used explicitly to maximise the use of limited elective capacity, provide benefit to patients and value for money for taxpayers.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/5/e066398.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-066398; html:https://europepmc.org/articles/PMC10193088; pdf:https://europepmc.org/articles/PMC10193088?pdf=render -34817387,https://doi.org/10.2196/29532,Introduction of Systematized Nomenclature of Medicine-Clinical Terms Coding Into an Electronic Health Record and Evaluation of its Impact: Qualitative and Quantitative Study.,"Pankhurst T, Evison F, Atia J, Gallier S, Coleman J, Ball S, McKee D, Ryan S, Black R.",,JMIR medical informatics,2021,2021-11-23,Y,Research; Diagnoses; data sharing; Clinical Decision Support; Population Health; Electronic Health Records; Coding Standards; Problem List; Health Data Exchange; Clinician Led Design; International Classification Of Diseases Version 10 (Icd-10); National Health Service Blueprint; Systematized Nomenclature Of Medicine–clinical Terms (Snomed-ct); Clinician Reported Experience; Electronic Health Record Standards; Patient Diagnoses; Use Of Electronic Health Data; User-led Design; Clinical Usability; Health Data Research,,,"

Background

This study describes the conversion within an existing electronic health record (EHR) from the International Classification of Diseases, Tenth Revision coding system to the SNOMED-CT (Systematized Nomenclature of Medicine-Clinical Terms) for the collection of patient histories and diagnoses. The setting is a large acute hospital that is designing and building its own EHR. Well-designed EHRs create opportunities for continuous data collection, which can be used in clinical decision support rules to drive patient safety. Collected data can be exchanged across health care systems to support patients in all health care settings. Data can be used for research to prevent diseases and protect future populations.

Objective

The aim of this study was to migrate a current EHR, with all relevant patient data, to the SNOMED-CT coding system to optimize clinical use and clinical decision support, facilitate data sharing across organizational boundaries for national programs, and enable remodeling of medical pathways.

Methods

The study used qualitative and quantitative data to understand the successes and gaps in the project, clinician attitudes toward the new tool, and the future use of the tool.

Results

The new coding system (tool) was well received and immediately widely used in all specialties. This resulted in increased, accurate, and clinically relevant data collection. Clinicians appreciated the increased depth and detail of the new coding, welcomed the potential for both data sharing and research, and provided extensive feedback for further development.

Conclusions

Successful implementation of the new system aligned the University Hospitals Birmingham NHS Foundation Trust with national strategy and can be used as a blueprint for similar projects in other health care settings.",,pdf:https://medinform.jmir.org/2021/11/e29532/PDF; doi:https://doi.org/10.2196/29532; html:https://europepmc.org/articles/PMC8663536 36216011,https://doi.org/10.1016/s2213-2600(22)00360-5,Pregnancy outcomes after SARS-CoV-2 infection in periods dominated by delta and omicron variants in Scotland: a population-based cohort study.,"Stock SJ, Moore E, Calvert C, Carruthers J, Denny C, Donaghy J, Hillman S, Hopcroft LEM, Hopkins L, Goulding A, Lindsay L, McLaughlin T, Taylor B, Auyeung B, Katikireddi SV, McCowan C, Ritchie LD, Rudan I, Simpson CR, Robertson C, Sheikh A, Wood R.",,The Lancet. Respiratory medicine,2022,2022-10-07,Y,,,,"

Background

Evidence suggests that the SARS-CoV-2 omicron (B.1·1.529) is associated with lower risks of adverse outcomes than the delta (B.1.617.2) variant among the general population. However, little is known about outcomes after omicron infection in pregnancy. We aimed to assess and compare short-term pregnancy outcomes after SARS-CoV-2 delta and omicron infection in pregnancy.

Methods

We did a national population-based cohort study of women who had SARS-CoV-2 infection in pregnancy between May 17, 2021, and Jan 31, 2022. The primary maternal outcome was admission to critical care within 21 days of infection or death within 28 days of date of infection. Pregnancy outcomes were preterm birth and stillbirth within 28 days of infection. Neonatal outcomes were death within 28 days of birth, and low Apgar score (<7 of 10, for babies born at term) or neonatal SARS-CoV-2 infection in births occurring within 28 days of maternal infection. We used periods when variants were dominant in the general Scottish population, based on 50% or more of cases being S-gene positive (delta variant, from May 17 to Dec 14, 2021) or S-gene negative (omicron variant, from Dec 15, 2021, to Jan 31, 2022) as surrogates for variant infections. Analyses used logistic regression, adjusting for maternal age, deprivation quintile, ethnicity, weeks of gestation, and vaccination status. Sensitivity analyses included restricting the analysis to those with first confirmed SARS-CoV-2 infection and using periods when delta or omicron had 90% or more predominance.

Findings

Between May 17, 2021, and Jan 31, 2022, there were 9923 SARS-CoV-2 infections in 9823 pregnancies, in 9817 women in Scotland. Compared with infections in the delta-dominant period, SARS-CoV-2 infections in pregnancy in the omicron-dominant period were associated with lower maternal critical care admission risk (0·3% [13 of 4968] vs 1·8% [89 of 4955]; adjusted odds ratio 0·25, 95% CI 0·14-0·44) and lower preterm birth within 28 days of infection (1·8% [37 of 2048] vs 4·2% [98 of 2338]; 0·57, 95% CI 0·38-0·87). There were no maternal deaths within 28 days of infection. Estimates of low Apgar scores were imprecise due to low numbers (5 [1·2%] of 423 with omicron vs 11 [2·1%] of 528 with delta, adjusted odds ratio 0·72, 0·23-2·32). There were fewer stillbirths in the omicron-dominant period than in the delta-dominant period (4·3 [2 of 462] per 1000 births vs 20·3 [13 of 639] per 1000) and no neonatal deaths during the omicron-dominant period (0 [0 of 460] per 1000 births vs 6·3 [4 of 626] per 1000 births), thus numbers were too small to support adjusted analyses. Rates of neonatal infection were low in births within 28 days of maternal SARS-CoV-2 infection, with 11 cases of neonatal SARS-CoV-2 in the delta-dominant period, and 1 case in the omicron-dominant period. Of the 15 stillbirths, 12 occurred in women who had not received two or more doses of COVID-19 vaccination at the time of SARS-CoV-2 infection in pregnancy. All 12 cases of neonatal SARS-CoV-2 infection occurred in women who had not received two or more doses of vaccine at the time of maternal infection. Findings in sensitivity analyses were similar to those in the main analyses.

Interpretation

Pregnant women infected with SARS-CoV-2 were substantially less likely to have a preterm birth or maternal critical care admission during the omicron-dominant period than during the delta-dominant period.

Funding

Wellcome Trust, Tommy's charity, Medical Research Council, UK Research and Innovation, Health Data Research UK, National Core Studies-Data and Connectivity, Public Health Scotland, Scottish Government Health and Social Care, Scottish Government Chief Scientist Office, National Research Scotland.",,doi:https://doi.org/10.1016/s2213-2600(22)00360-5; doi:https://doi.org/10.1016/S2213-2600(22)00360-5; html:https://europepmc.org/articles/PMC9708088; pdf:https://europepmc.org/articles/PMC9708088?pdf=render +34817387,https://doi.org/10.2196/29532,Introduction of Systematized Nomenclature of Medicine-Clinical Terms Coding Into an Electronic Health Record and Evaluation of its Impact: Qualitative and Quantitative Study.,"Pankhurst T, Evison F, Atia J, Gallier S, Coleman J, Ball S, McKee D, Ryan S, Black R.",,JMIR medical informatics,2021,2021-11-23,Y,Research; Diagnoses; data sharing; Clinical Decision Support; Population Health; Electronic Health Records; Coding Standards; Problem List; Health Data Exchange; Clinician Led Design; International Classification Of Diseases Version 10 (Icd-10); National Health Service Blueprint; Systematized Nomenclature Of Medicine–clinical Terms (Snomed-ct); Clinician Reported Experience; Electronic Health Record Standards; Patient Diagnoses; Use Of Electronic Health Data; User-led Design; Clinical Usability; Health Data Research,,,"

Background

This study describes the conversion within an existing electronic health record (EHR) from the International Classification of Diseases, Tenth Revision coding system to the SNOMED-CT (Systematized Nomenclature of Medicine-Clinical Terms) for the collection of patient histories and diagnoses. The setting is a large acute hospital that is designing and building its own EHR. Well-designed EHRs create opportunities for continuous data collection, which can be used in clinical decision support rules to drive patient safety. Collected data can be exchanged across health care systems to support patients in all health care settings. Data can be used for research to prevent diseases and protect future populations.

Objective

The aim of this study was to migrate a current EHR, with all relevant patient data, to the SNOMED-CT coding system to optimize clinical use and clinical decision support, facilitate data sharing across organizational boundaries for national programs, and enable remodeling of medical pathways.

Methods

The study used qualitative and quantitative data to understand the successes and gaps in the project, clinician attitudes toward the new tool, and the future use of the tool.

Results

The new coding system (tool) was well received and immediately widely used in all specialties. This resulted in increased, accurate, and clinically relevant data collection. Clinicians appreciated the increased depth and detail of the new coding, welcomed the potential for both data sharing and research, and provided extensive feedback for further development.

Conclusions

Successful implementation of the new system aligned the University Hospitals Birmingham NHS Foundation Trust with national strategy and can be used as a blueprint for similar projects in other health care settings.",,pdf:https://medinform.jmir.org/2021/11/e29532/PDF; doi:https://doi.org/10.2196/29532; html:https://europepmc.org/articles/PMC8663536 35918098,https://doi.org/10.1136/bmj-2022-070695,Risk of covid-19 related deaths for SARS-CoV-2 omicron (B.1.1.529) compared with delta (B.1.617.2): retrospective cohort study.,"Ward IL, Bermingham C, Ayoubkhani D, Gethings OJ, Pouwels KB, Yates T, Khunti K, Hippisley-Cox J, Banerjee A, Walker AS, Nafilyan V.",,BMJ (Clinical research ed.),2022,2022-08-02,Y,,,,"

Objective

To assess the risk of covid-19 death after infection with omicron BA.1 compared with delta (B.1.617.2).

Design

Retrospective cohort study.

Setting

England, United Kingdom, from 1 December 2021 to 30 December 2021.

Participants

1 035 149 people aged 18-100 years who tested positive for SARS-CoV-2 under the national surveillance programme and had an infection identified as omicron BA.1 or delta compatible.

Main outcome measures

The main outcome measure was covid-19 death as identified from death certification records. The exposure of interest was the SARS-CoV-2 variant identified from NHS Test and Trace PCR positive tests taken in the community (pillar 2) and analysed by Lighthouse laboratories. Cause specific Cox proportional hazard regression models (censoring non-covid-19 deaths) were adjusted for sex, age, vaccination status, previous infection, calendar time, ethnicity, index of multiple deprivation rank, household deprivation, university degree, keyworker status, country of birth, main language, region, disability, and comorbidities. Interactions between variant and sex, age, vaccination status, and comorbidities were also investigated.

Results

The risk of covid-19 death was 66% lower (95% confidence interval 54% to 75%) for omicron BA.1 compared with delta after adjusting for a wide range of potential confounders. The reduction in the risk of covid-19 death for omicron compared with delta was more pronounced in people aged 18-59 years (number of deaths: delta=46, omicron=11; hazard ratio 0.14, 95% confidence interval 0.07 to 0.27) than in those aged ≥70 years (number of deaths: delta=113, omicron=135; hazard ratio 0.44, 95% confidence interval 0.32 to 0.61, P<0.0001). No evidence of a difference in risk was found between variant and number of comorbidities.

Conclusions

The results support earlier studies showing a reduction in severity of infection with omicron BA.1 compared with delta in terms of hospital admission. This study extends the research to also show a reduction in the risk of covid-19 death for the omicron variant compared with the delta variant.",,pdf:https://www.bmj.com/content/bmj/378/bmj-2022-070695.full.pdf; doi:https://doi.org/10.1136/bmj-2022-070695; html:https://europepmc.org/articles/PMC9344192; pdf:https://europepmc.org/articles/PMC9344192?pdf=render 38537901,https://doi.org/10.1016/j.cct.2024.107514,Getting our ducks in a row: The need for data utility comparisons of healthcare systems data for clinical trials.,"Sydes MR, Murray ML, Ahmed S, Apostolidou S, Bliss JM, Bloomfield C, Cannings-John R, Carpenter J, Clayton T, Clout M, Cosgriff R, Farrin AJ, Gentry-Maharaj A, Gilbert DC, Harper C, James ND, Langley RE, Lessels S, Lugg-Widger F, Mackenzie IS, Mafham M, Menon U, Mintz H, Pinches H, Robling M, Wright-Hughes A, Yorke-Edwards V, Love SB.",,Contemporary clinical trials,2024,2024-03-26,N,DUCKS; Health Policy; Electronic Health Records; Rcts; Data Utility; Real World Data; Routinely-Collected Data; Healthcare Systems Data; Routinely-collected Healthcare Data; Data Utility Comparison Studies,,,"

Background

Better use of healthcare systems data, collected as part of interactions between patients and the healthcare system, could transform planning and conduct of randomised controlled trials. Multiple challenges to widespread use include whether healthcare systems data captures sufficiently well the data traditionally captured on case report forms. ""Data Utility Comparison Studies"" (DUCkS) assess the utility of healthcare systems data for RCTs by comparison to data collected by the trial. Despite their importance, there are few published UK examples of DUCkS.

Methods-and-results

Building from ongoing and selected recent examples of UK-led DUCkS in the literature, we set out experience-based considerations for the conduct of future DUCkS. Developed through informal iterative discussions in many forums, considerations are offered for planning, protocol development, data, analysis and reporting, with comparisons at ""patient-level"" or ""trial-level"", depending on the item of interest and trial status.

Discussion

DUCkS could be a valuable tool in assessing where healthcare systems data can be used for trials and in which trial teams can play a leading role. There is a pressing need for trials to be more efficient in their delivery and research waste must be reduced. Trials have been making inconsistent use of healthcare systems data, not least because of an absence of evidence of utility. DUCkS can also help to identify challenges in using healthcare systems data, such as linkage (access and timing) and data quality. We encourage trial teams to incorporate and report DUCkS in trials and funders and data providers to support them.",,doi:https://doi.org/10.1016/j.cct.2024.107514 35275994,https://doi.org/10.2337/dc21-1709,Admission Blood Glucose Level and Its Association With Cardiovascular and Renal Complications in Patients Hospitalized With COVID-19.,"Norris T, Razieh C, Yates T, Zaccardi F, Gillies CL, Chudasama YV, Rowlands A, Davies MJ, McCann GP, Banerjee A, Docherty AB, Openshaw PJM, Baillie JK, Semple MG, Lawson CA, Khunti K.",,Diabetes care,2022,2022-05-01,N,,,,"

Objective

To investigate the association between admission blood glucose levels and risk of in-hospital cardiovascular and renal complications.

Research design and methods

In this multicenter prospective study of 36,269 adults hospitalized with COVID-19 between 6 February 2020 and 16 March 2021 (N = 143,266), logistic regression models were used to explore associations between admission glucose level (mmol/L and mg/dL) and odds of in-hospital complications, including heart failure, arrhythmia, cardiac ischemia, cardiac arrest, coagulation complications, stroke, and renal injury. Nonlinearity was investigated using restricted cubic splines. Interaction models explored whether associations between glucose levels and complications were modified by clinically relevant factors.

Results

Cardiovascular and renal complications occurred in 10,421 (28.7%) patients; median admission glucose level was 6.7 mmol/L (interquartile range 5.8-8.7) (120.6 mg/dL [104.4-156.6]). While accounting for confounders, for all complications except cardiac ischemia and stroke, there was a nonlinear association between glucose and cardiovascular and renal complications. For example, odds of heart failure, arrhythmia, coagulation complications, and renal injury decreased to a nadir at 6.4 mmol/L (115 mg/dL), 4.9 mmol/L (88.2 mg/dL), 4.7 mmol/L (84.6 mg/dL), and 5.8 mmol/L (104.4 mg/dL), respectively, and increased thereafter until 26.0 mmol/L (468 mg/dL), 50.0 mmol/L (900 mg/dL), 8.5 mmol/L (153 mg/dL), and 32.4 mmol/L (583.2 mg/dL). Compared with 5 mmol/L (90 mg/dL), odds ratios at these glucose levels were 1.28 (95% CI 0.96, 1.69) for heart failure, 2.23 (1.03, 4.81) for arrhythmia, 1.59 (1.36, 1.86) for coagulation complications, and 2.42 (2.01, 2.92) for renal injury. For most complications, a modifying effect of age was observed, with higher odds of complications at higher glucose levels for patients age <69 years. Preexisting diabetes status had a similar modifying effect on odds of complications, but evidence was strongest for renal injury, cardiac ischemia, and any cardiovascular/renal complication.

Conclusions

Increased odds of cardiovascular or renal complications were observed for admission glucose levels indicative of both hypo- and hyperglycemia. Admission glucose could be used as a marker for risk stratification of high-risk patients. Further research should evaluate interventions to optimize admission glucose on improving COVID-19 outcomes.",,pdf:https://diabetesjournals.org/care/article-pdf/45/5/1132/678515/dc211709.pdf; doi:https://doi.org/10.2337/dc21-1709; html:https://europepmc.org/articles/PMC9174963; pdf:https://europepmc.org/articles/PMC9174963?pdf=render; doi:https://doi.org/10.2337/dc21-1709 @@ -151,8 +151,8 @@ PMC10929454,https://doi.org/,Optimising data curation pipelines for population-l 36332519,https://doi.org/10.1016/j.ijmedinf.2022.104905,Creation of a core competency framework for clinical informatics: From genesis to maintaining relevance.,"Davies A, Hassey A, Williams J, Moulton G.",,International journal of medical informatics,2022,2022-10-30,N,Informatics; Core Competencies; Competency Framework; Healthcare Workforce; Informaticians,,,"

Background

The United Kingdom's Faculty of Clinical Informatics (FCI) embarked on the creation of a core competency framework in response to the need to provide support to those working in clinical and health and social care that also hold informatics roles.

Methods

The work spanned several phases and utilised a mixed-methods approach consisting of interviews, surveys, job listing analysis, expert discussions and a systematic literature review. The work presented here explores the lessons learnt from the process of creating the framework and the next steps for ensuring its use and continued relevance.

Results

A core competency framework was generated with six domains, 36 sub-domains and 111 individual competency statements. A discussion and eight key recommendations are presented based on the development of this framework.

Conclusion

Definition of the target audience is important to manage scope and define purpose. The use of robust reproducible methods helps to establish a strong evidence base. Competency frameworks should be living documents, ideally presented in an accessible digital form to enable easy use and embedding in other tools (e.g. for accreditation or to search competencies).",,doi:https://doi.org/10.1016/j.ijmedinf.2022.104905 34544601,https://doi.org/10.1016/j.vaccine.2021.09.019,"Inequalities in coverage of COVID-19 vaccination: A population register based cross-sectional study in Wales, UK.","Perry M, Akbari A, Cottrell S, Gravenor MB, Roberts R, Lyons RA, Bedston S, Torabi F, Griffiths L.",,Vaccine,2021,2021-09-08,Y,Ethnic Groups; Vaccination; Socioeconomic Factors; Immunisation; Covid-19 Vaccines,,,"The COVID-19 pandemic has highlighted existing health inequalities for ethnic minority groups and those living in more socioeconomically deprived areas in the UK. With higher levels of severe outcomes in these groups, equitable vaccination coverage should be prioritised. The aim of this study was to identify inequalities in coverage of COVID-19 vaccination in Wales, UK and to highlight areas which may benefit from routine enhanced surveillance and targeted interventions. Records within the Wales Immunisation System (WIS) population register were linked to the Welsh Demographic Service Dataset (WDSD) and central list of shielding patients, held within the Secure Anonymised Information Linkage (SAIL) Databank. Ethnic group was derived from the 2011 census and over 20 administrative electronic health record (EHR) data sources. Uptake of first dose of any COVID-19 vaccine was analysed over time, with the odds of being vaccinated as at 25th April 2021 by sex, health board of residence, rural/urban classification, deprivation quintile and ethnic group presented. Using logistic regression models, analyses were adjusted for age group, care home resident status, health and social care worker status and shielding status. This study included 1,256,412 individuals aged 50 years and over. Vaccine coverage increased steadily from 8th December 2020 until mid-April 2021. Overall uptake of first dose of COVID-19 vaccine in this group was 92.1%. After adjustment the odds of being vaccinated were lower for individuals who were male, resident in the most deprived areas, resident in an urban area and an ethnic group other than White. The largest inequality was seen between ethnic groups, with the odds of being vaccinated 0.22 (95 %CI 0.21-0.24) if in any Black ethnic group compared to any White ethnic group. Ongoing monitoring of inequity in uptake of vaccinations is required, with better targeted interventions and engagement with deprived and ethnic communities to improve vaccination uptake.",,doi:https://doi.org/10.1016/j.vaccine.2021.09.019; doi:https://doi.org/10.1016/j.vaccine.2021.09.019; html:https://europepmc.org/articles/PMC8423991 36447940,https://doi.org/10.1016/s2665-9913(22)00305-8,Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY.,"Russell MD, Galloway JB, Andrews CD, MacKenna B, Goldacre B, Mehrkar A, Curtis HJ, Butler-Cole B, O'Dwyer T, Qureshi S, Ledingham JM, Mahto A, Rutherford AI, Adas MA, Alveyn E, Norton S, Cope AP, Bechman K, OpenSAFELY Collaborative.",,The Lancet. Rheumatology,2022,2022-11-03,Y,,,,"

Background

The impact of the COVID-19 pandemic on the incidence and management of inflammatory arthritis is not understood. Routinely captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how care for patients with inflammatory arthritis was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for inflammatory arthritis in England and to replicate key metrics from the National Early Inflammatory Arthritis Audit.

Methods

In this population-level cohort study, we used primary care and hospital data for 17·7 million adults registered with general practices using TPP health record software, to explore the following outcomes between April 1, 2019, and March 31, 2022: (1) incidence of inflammatory arthritis diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and undifferentiated inflammatory arthritis) recorded in primary care; (2) time to first rheumatology assessment; (3) time to first prescription of a disease-modifying antirheumatic drug (DMARD) in primary care; and (4) choice of first DMARD.

Findings

Among 17 683 500 adults, there were 31 280 incident inflammatory arthritis diagnoses recorded between April 1, 2019, and March 31, 2022. The mean age of diagnosed patients was 55·4 years (SD 16·6), 18 615 (59·5%) were female, 12 665 (40·5%) were male, and 22 925 (88·3%) of 25 960 with available ethnicity data were White. New inflammatory arthritis diagnoses decreased by 20·3% in the year commencing April, 2020, relative to the preceding year (5·1 vs 6·4 diagnoses per 10 000 adults). The median time to first rheumatology assessment was shorter during the pandemic (18 days; IQR 8-35) than before (21 days; 9-41). The proportion of patients prescribed DMARDs in primary care was similar before and during the pandemic; however, during the pandemic, fewer people were prescribed methotrexate or leflunomide, and more were prescribed sulfasalazine or hydroxychloroquine.

Interpretation

Inflammatory arthritis diagnoses decreased markedly during the early phase of the pandemic. The impact on rheumatology assessment times and DMARD prescribing in primary care was less marked than might have been anticipated. This study demonstrates the feasibility of using routinely captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection.

Funding

None.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4669009/1/Russell_etal_2022_Incidence-and-management-of-inflammatory.pdf; doi:https://doi.org/10.1016/S2665-9913(22)00305-8; html:https://europepmc.org/articles/PMC9691150; pdf:https://europepmc.org/articles/PMC9691150?pdf=render -35909577,https://doi.org/10.23889/ijpds.v7i1.1725,Educational achievements of children aged 10-11 years with cystic fibrosis. A data linkage study in Wales.,"Schlüter DK, Griffiths R, Akbari A, Taylor-Robinson D.",,International journal of population data science,2022,2022-06-27,Y,Education; Cystic Fibrosis; Data Linkage; Sail Databank,,,"

Introduction

As people with cystic fibrosis (CF) lead longer, healthier lives, educational qualifications and employment prospects are increasingly important. However, little is known about the social consequences of CF, in particular, any impact on educational achievements and the support children with CF receive in schools.

Objectives

To assess the educational achievements of children with CF in Wales compared to the general Welsh population, and the additional learning support children with CF receive in schools.

Methods

We conducted a population-scale data linkage study of all children born in Wales using the Secure Anonymised Information Linkage (SAIL) Databank. We used anonymised individual-level population-scale health and administrative data sources to identify children with CF born between 2000 - 2015, linked to educational attainment records. We calculated the percentage of children that reached expected levels in statutory assessment at age 10-11, Key Stage 2 (KS2), and compared this to educational outcomes in the general population. We also assessed the percentage of children with CF that received extra learning support.

Results

Out of 150 eligible children, 119 had KS2 results. 77% (95% CI: 69%-84%) of children achieved expected levels in English, 81% (95% CI: 73% -87%) in Mathematics and 82% (95% CI: 75% - 88%) in Science. In the comparable general Welsh population, 83.4% to 91.1% achieved the expected level in English, 84.9% to 91.6% in Maths, and 87.1% to 92.2% in Science across the years of the study. 70% of children with CF received extra learning support.

Conclusions

Children with CF in Wales may have worse educational achievements than the general population. More research is needed to inform policies and interventions to better support children with CF to reach their full educational potential and employment opportunities.",,pdf:https://ijpds.org/article/download/1725/3455; doi:https://doi.org/10.23889/ijpds.v7i1.1725; html:https://europepmc.org/articles/PMC9284509; pdf:https://europepmc.org/articles/PMC9284509?pdf=render 34148733,https://doi.org/10.1016/j.bja.2021.05.018,Mortality after surgery with SARS-CoV-2 infection in England: a population-wide epidemiological study.,"Abbott TEF, Fowler AJ, Dobbs TD, Gibson J, Shahid T, Dias P, Akbari A, Whitaker IS, Pearse RM.",,British journal of anaesthesia,2021,2021-06-11,Y,Surgery; Anaesthesia; epidemiology; Public Policy; Covid-19,,,"

Background

The COVID-19 pandemic has heavily impacted elective and emergency surgery around the world. We aimed to confirm the incidence of perioperative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated mortality after surgery.

Methods

Analysis of routine electronic health record data from NHS hospitals in England. We extracted data from Hospital Episode Statistics in England describing adult patients undergoing surgery between January 1, 2020 and February 28, 2021. The exposure was SARS-CoV-2 infection defined by International Classification of Diseases (ICD)-10 codes. The primary outcome measure was 90 day in-hospital mortality. Data were analysed using multivariable logistic regression adjusted for age, sex, Charlson Comorbidity Index, Index of Multiple Deprivation, presence of cancer, surgical procedure type and admission acuity. Results are presented as n (%) and odds ratios (OR) with 95% confidence intervals (CI).

Results

We identified 2 666 978 patients undergoing surgery of whom 28 777 (1.1%) had SARS-CoV-2 infection. In total, 26 364 (1.0%) patients died in hospital. SARS-CoV-2 infection was associated with a much greater risk of death (SARS-CoV-2: 6153/28 777 [21.4%] vs no SARS-CoV-2: 20 211/2 638 201 [0.8%]; OR=5.7 [95% CI, 5.5-5.9]; P<0.001). Amongst patients undergoing elective surgery, 2412/1 857 586 (0.1%) had SARS-CoV-2, of whom 172/2412 (7.1%) died, compared with 1414/1 857 586 (0.1%) patients without SARS-CoV-2 (OR=25.8 [95% CI, 21.7-30.9]; P<0.001). Amongst patients undergoing emergency surgery, 22 918/582 292 (3.9%) patients had SARS-CoV-2, of whom 5752/22 918 (25.1%) died, compared with 18 060/559 374 (3.4%) patients without SARS-CoV-2 (OR=5.5 [95% CI, 5.3-5.7]; P<0.001).

Conclusions

The low incidence of SARS-CoV-2 infection in NHS surgical pathways suggests current infection prevention and control policies are highly effective. However, the high mortality amongst patients with SARS-CoV-2 suggests these precautions cannot be safely relaxed.",,pdf:http://www.bjanaesthesia.org/article/S0007091221003123/pdf; doi:https://doi.org/10.1016/j.bja.2021.05.018; html:https://europepmc.org/articles/PMC8192173; pdf:https://europepmc.org/articles/PMC8192173?pdf=render +35909577,https://doi.org/10.23889/ijpds.v7i1.1725,Educational achievements of children aged 10-11 years with cystic fibrosis. A data linkage study in Wales.,"Schlüter DK, Griffiths R, Akbari A, Taylor-Robinson D.",,International journal of population data science,2022,2022-06-27,Y,Education; Cystic Fibrosis; Data Linkage; Sail Databank,,,"

Introduction

As people with cystic fibrosis (CF) lead longer, healthier lives, educational qualifications and employment prospects are increasingly important. However, little is known about the social consequences of CF, in particular, any impact on educational achievements and the support children with CF receive in schools.

Objectives

To assess the educational achievements of children with CF in Wales compared to the general Welsh population, and the additional learning support children with CF receive in schools.

Methods

We conducted a population-scale data linkage study of all children born in Wales using the Secure Anonymised Information Linkage (SAIL) Databank. We used anonymised individual-level population-scale health and administrative data sources to identify children with CF born between 2000 - 2015, linked to educational attainment records. We calculated the percentage of children that reached expected levels in statutory assessment at age 10-11, Key Stage 2 (KS2), and compared this to educational outcomes in the general population. We also assessed the percentage of children with CF that received extra learning support.

Results

Out of 150 eligible children, 119 had KS2 results. 77% (95% CI: 69%-84%) of children achieved expected levels in English, 81% (95% CI: 73% -87%) in Mathematics and 82% (95% CI: 75% - 88%) in Science. In the comparable general Welsh population, 83.4% to 91.1% achieved the expected level in English, 84.9% to 91.6% in Maths, and 87.1% to 92.2% in Science across the years of the study. 70% of children with CF received extra learning support.

Conclusions

Children with CF in Wales may have worse educational achievements than the general population. More research is needed to inform policies and interventions to better support children with CF to reach their full educational potential and employment opportunities.",,pdf:https://ijpds.org/article/download/1725/3455; doi:https://doi.org/10.23889/ijpds.v7i1.1725; html:https://europepmc.org/articles/PMC9284509; pdf:https://europepmc.org/articles/PMC9284509?pdf=render 33319712,https://doi.org/10.1186/s12911-020-01336-2,Towards semantic interoperability: finding and repairing hidden contradictions in biomedical ontologies.,"Slater LT, Gkoutos GV, Hoehndorf R.",,BMC medical informatics and decision making,2020,2020-12-15,Y,Automated Reasoning; Ontology Interoperability,,,"

Background

Ontologies are widely used throughout the biomedical domain. These ontologies formally represent the classes and relations assumed to exist within a domain. As scientific domains are deeply interlinked, so too are their representations. While individual ontologies can be tested for consistency and coherency using automated reasoning methods, systematically combining ontologies of multiple domains together may reveal previously hidden contradictions.

Methods

We developed a method that tests for hidden unsatisfiabilities in an ontology that arise when combined with other ontologies. For this purpose, we combined sets of ontologies and use automated reasoning to determine whether unsatisfiable classes are present. In addition, we designed and implemented a novel algorithm that can determine justifications for contradictions across extremely large and complicated ontologies, and use these justifications to semi-automatically repair ontologies by identifying a small set of axioms that, when removed, result in a consistent and coherent set of ontologies.

Results

We tested the mutual consistency of the OBO Foundry and the OBO ontologies and find that the combined OBO Foundry gives rise to at least 636 unsatisfiable classes, while the OBO ontologies give rise to more than 300,000 unsatisfiable classes. We also applied our semi-automatic repair algorithm to each combination of OBO ontologies that resulted in unsatisfiable classes, finding that only 117 axioms could be removed to account for all cases of unsatisfiability across all OBO ontologies.

Conclusions

We identified a large set of hidden unsatisfiability across a broad range of biomedical ontologies, and we find that this large set of unsatisfiable classes is the result of a relatively small amount of axiomatic disagreements. Our results show that hidden unsatisfiability is a serious problem in ontology interoperability; however, our results also provide a way towards more consistent ontologies by addressing the issues we identified.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-020-01336-2; doi:https://doi.org/10.1186/s12911-020-01336-2; html:https://europepmc.org/articles/PMC7736131; pdf:https://europepmc.org/articles/PMC7736131?pdf=render 38331807,https://doi.org/10.1186/s12916-024-03271-9,Childhood maltreatment and risk of endocrine diseases: an exploration of mediating pathways using sequential mediation analysis.,"Wen S, Zhu J, Han X, Li Y, Liu H, Yang H, Hou C, Xu S, Wang J, Hu Y, Qu Y, Liu D, Aspelund T, Fang F, Valdimarsdóttir UA, Song H.",,BMC medicine,2024,2024-02-08,Y,Endocrine diseases; Childhood Maltreatment; Sequential Mediation Analysis; Psychological Adversities,,,"

Background

Adverse childhood experiences (ACEs), including childhood maltreatment, have been linked with increased risk of diabetes and obesity during adulthood. A comprehensive assessment on the associations between childhood maltreatment and all major endocrine diseases, as well as the relative importance of different proposed mechanistic pathways on these associations, is currently lacking.

Methods

Based on the UK Biobank, we constructed a cohort including 151,659 participants with self-reported data on childhood maltreatment who were 30 years of age or older on/after January 1, 1985. All participants were followed from the index date (i.e., January 1, 1985, or their 30th birthday, whichever came later) until the first diagnosis of any or specific (12 individual diagnoses and 9 subtypes) endocrine diseases, death, or the end of follow-up (December 31, 2019), whichever occurred first. We used Cox models to examine the association of childhood maltreatment, treated as continuous (i.e., the cumulative number of experienced childhood maltreatment), ordinal (i.e., 0, 1 and ≥ 2), or binary (< 2 and ≥ 2) variable, with any and specific endocrine diseases, adjusted for multiple covariates. We further examined the risk of having multiple endocrine diseases using Linear or Logistic Regression models. Then, sequential mediation analyses were performed to assess the contribution of four possible mechanisms (i.e., suboptimal socioeconomic status (SES), psychological adversities, unfavorable lifestyle, and biological alterations) on the observed associations.

Results

During an average follow-up of 30.8 years, 20,885 participants received a diagnosis of endocrine diseases. We observed an association between the cumulative number of experienced childhood maltreatment and increased risk of being diagnosed with any endocrine disease (adjusted hazard ratio (HR) = 1.10, 95% confidence interval 1.09-1.12). The HR was 1.26 (1.22-1.30) when comparing individuals ≥ 2 with those with < 2 experienced childhood maltreatment. We further noted the most pronounced associations for type 2 diabetes (1.40 (1.33-1.48)) and hypothalamic-pituitary-adrenal (HPA)-axis-related endocrine diseases (1.38 (1.17-1.62)), and the association was stronger for having multiple endocrine diseases, compared to having one (odds ratio (95% CI) = 1.24 (1.19-1.30), 1.35 (1.27-1.44), and 1.52 (1.52-1.53) for 1, 2, and ≥ 3, respectively). Sequential mediation analyses showed that the association between childhood maltreatment and endocrine diseases was consistently and most distinctly mediated by psychological adversities (15.38 ~ 44.97%), while unfavorable lifestyle (10.86 ~ 25.32%) was additionally noted for type 2 diabetes whereas suboptimal SES (14.42 ~ 39.33%) for HPA-axis-related endocrine diseases.

Conclusions

Our study demonstrates that adverse psychological sequel of childhood maltreatment constitutes the main pathway to multiple endocrine diseases, particularly type 2 diabetes and HPA-axis-related endocrine diseases. Therefore, increased access to evidence-based mental health services may also be pivotal in reducing the risk of endocrine diseases among childhood maltreatment-exposed individuals.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-024-03271-9; doi:https://doi.org/10.1186/s12916-024-03271-9; html:https://europepmc.org/articles/PMC10854183; pdf:https://europepmc.org/articles/PMC10854183?pdf=render 35796183,https://doi.org/10.1177/01410768221107119,"SARS-CoV-2 infection risk among 77,587 healthcare workers: a national observational longitudinal cohort study in Wales, United Kingdom, April to November 2020.","Hollinghurst J, North L, Szakmany T, Pugh R, Davies GA, Sivakumaran S, Jarvis R, Rolles M, Pickrell WO, Akbari A, Davies G, Griffiths R, Lyons J, Torabi F, Fry R, Gravenor MB, Lyons RA.",,Journal of the Royal Society of Medicine,2022,2022-07-07,Y,Public Health; Healthcare Workers; Infection Risk; Covid-19; Sars-cov-2,,,"

Objectives

To better understand the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among healthcare workers, leading to recommendations for the prioritisation of personal protective equipment, testing, training and vaccination.

Design

Observational, longitudinal, national cohort study.

Setting

Our cohort were secondary care (hospital-based) healthcare workers employed by NHS Wales (United Kingdom) organisations from 1 April 2020 to 30 November 2020.

Participants

We included 577,756 monthly observations among 77,587 healthcare workers. Using linked anonymised datasets, participants were grouped into 20 staff roles. Additionally, each role was deemed either patient-facing, non-patient-facing or undetermined. This was linked to individual demographic details and dates of positive SARS-CoV-2 PCR tests.

Main outcome measures

We used univariable and multivariable logistic regression models to determine odds ratios (ORs) for the risk of a positive SARS-CoV-2 PCR test.

Results

Patient-facing healthcare workers were at the highest risk of SARS-CoV-2 infection with an adjusted OR (95% confidence interval [CI]) of 2.28 (95% CI 2.10-2.47). We found that after adjustment, foundation year doctors (OR 1.83 [95% CI 1.47-2.27]), healthcare support workers [OR 1.36 [95% CI 1.20-1.54]) and hospital nurses (OR 1.27 [95% CI 1.12-1.44]) were at the highest risk of infection among all staff groups. Younger healthcare workers and those living in more deprived areas were at a higher risk of infection. We also observed that infection rates varied over time and by organisation.

Conclusions

These findings have important policy implications for the prioritisation of vaccination, testing, training and personal protective equipment provision for patient-facing roles and the higher risk staff groups.",,doi:https://doi.org/10.1177/01410768221107119; doi:https://doi.org/10.1177/01410768221107119; html:https://europepmc.org/articles/PMC9747896; pdf:https://europepmc.org/articles/PMC9747896?pdf=render @@ -213,8 +213,8 @@ PMC10929454,https://doi.org/,Optimising data curation pipelines for population-l 36918541,https://doi.org/10.1038/s41467-023-36997-w,Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease.,"Young WJ, Haessler J, Benjamins JW, Repetto L, Yao J, Isaacs A, Harper AR, Ramirez J, Garnier S, van Duijvenboden S, Baldassari AR, Concas MP, Duong T, Foco L, Isaksen JL, Mei H, Noordam R, Nursyifa C, Richmond A, Santolalla ML, Sitlani CM, Soroush N, Thériault S, Trompet S, Aeschbacher S, Ahmadizar F, Alonso A, Brody JA, Campbell A, Correa A, Darbar D, De Luca A, Deleuze JF, Ellervik C, Fuchsberger C, Goel A, Grace C, Guo X, Hansen T, Heckbert SR, Jackson RD, Kors JA, Lima-Costa MF, Linneberg A, Macfarlane PW, Morrison AC, Navarro P, Porteous DJ, Pramstaller PP, Reiner AP, Risch L, Schotten U, Shen X, Sinagra G, Soliman EZ, Stoll M, Tarazona-Santos E, Tinker A, Trajanoska K, Villard E, Warren HR, Whitsel EA, Wiggins KL, Arking DE, Avery CL, Conen D, Girotto G, Grarup N, Hayward C, Jukema JW, Mook-Kanamori DO, Olesen MS, Padmanabhan S, Psaty BM, Pattaro C, Ribeiro ALP, Rotter JI, Stricker BH, van der Harst P, van Duijn CM, Verweij N, Wilson JG, Orini M, Charron P, Watkins H, Kooperberg C, Lin HJ, Wilson JF, Kanters JK, Sotoodehnia N, Mifsud B, Lambiase PD, Tereshchenko LG, Munroe PB.",,Nature communications,2023,2023-03-14,Y,,,,"The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction.",,pdf:https://www.nature.com/articles/s41467-023-36997-w.pdf; doi:https://doi.org/10.1038/s41467-023-36997-w; html:https://europepmc.org/articles/PMC10015012; pdf:https://europepmc.org/articles/PMC10015012?pdf=render 36638616,https://doi.org/10.1016/j.compbiomed.2022.106425,Klarigi: Characteristic explanations for semantic biomedical data.,"Slater K, Williams JA, Schofield PN, Russell S, Pendleton SC, Karwath A, Fanning H, Ball S, Hoehndorf R, Gkoutos GV.",,Computers in biology and medicine,2023,2022-12-22,N,Phenotypes; Ontology; Enrichment Analysis; Semantic Analysis; Explicability; Phenotype Profiles; Semantic Explanation,,,"Annotation of biomedical entities with ontology classes provides for formal semantic analysis and mobilisation of background knowledge in determining their relationships. To date, enrichment analysis has been routinely employed to identify classes that are over-represented in annotations across sets of groups, such as biosample gene expression profiles or patient phenotypes, and is useful for a range of tasks including differential diagnosis and causative variant prioritisation. These approaches, however, usually consider only univariate relationships, make limited use of the semantic features of ontologies, and provide limited information and evaluation of the explanatory power of both singular and grouped candidate classes. Moreover, they are not designed to solve the problem of deriving cohesive, characteristic, and discriminatory sets of classes for entity groups. We have developed a new tool, called Klarigi, which introduces multiple scoring heuristics for identification of classes that are both compositional and discriminatory for groups of entities annotated with ontology classes. The tool includes a novel algorithm for derivation of multivariable semantic explanations for entity groups, makes use of semantic inference through live use of an ontology reasoner, and includes a classification method for identifying the discriminatory power of candidate sets, in addition to significance testing apposite to traditional enrichment approaches. We describe the design and implementation of Klarigi, including its scoring and explanation determination methods, and evaluate its use in application to two test cases with clinical significance, comparing and contrasting methods and results with literature-based and enrichment analysis methods. We demonstrate that Klarigi produces characteristic and discriminatory explanations for groups of biomedical entities in two settings. We also show that these explanations recapitulate and extend the knowledge held in existing biomedical databases and literature for several diseases. We conclude that Klarigi provides a distinct and valuable perspective on biomedical datasets when compared with traditional enrichment methods, and therefore constitutes a new method by which biomedical datasets can be explored, contributing to improved insight into semantic data.",,doi:https://doi.org/10.1016/j.compbiomed.2022.106425; doi:https://doi.org/10.1016/j.compbiomed.2022.106425 37475157,https://doi.org/10.1093/cvr/cvad106,A machine learning based approach to identify carotid subclinical atherosclerosis endotypes.,"Chen QS, Bergman O, Ziegler L, Baldassarre D, Veglia F, Tremoli E, Strawbridge RJ, Gallo A, Pirro M, Smit AJ, Kurl S, Savonen K, Lind L, Eriksson P, Gigante B.",,Cardiovascular research,2023,2023-12-01,Y,Atherosclerosis; Artificial intelligence; biological markers; Endotype; Progression Of Atherosclerosis; Ascvd,,,"

Aims

To define endotypes of carotid subclinical atherosclerosis.

Methods and results

We integrated demographic, clinical, and molecular data (n = 124) with ultrasonographic carotid measurements from study participants in the IMPROVE cohort (n = 3340). We applied a neural network algorithm and hierarchical clustering to identify carotid atherosclerosis endotypes. A measure of carotid subclinical atherosclerosis, the c-IMTmean-max, was used to extract atherosclerosis-related features and SHapley Additive exPlanations (SHAP) to reveal endotypes. The association of endotypes with carotid ultrasonographic measurements at baseline, after 30 months, and with the 3-year atherosclerotic cardiovascular disease (ASCVD) risk was estimated by linear (β, SE) and Cox [hazard ratio (HR), 95% confidence interval (CI)] regression models. Crude estimates were adjusted by common cardiovascular risk factors, and baseline ultrasonographic measures. Improvement in ASCVD risk prediction was evaluated by C-statistic and by net reclassification improvement with reference to SCORE2, c-IMTmean-max, and presence of carotid plaques. An ensemble stacking model was used to predict endotypes in an independent validation cohort, the PIVUS (n = 1061). We identified four endotypes able to differentiate carotid atherosclerosis risk profiles from mild (endotype 1) to severe (endotype 4). SHAP identified endotype-shared variables (age, biological sex, and systolic blood pressure) and endotype-specific biomarkers. In the IMPROVE, as compared to endotype 1, endotype 4 associated with the thickest c-IMT at baseline (β, SE) 0.36 (0.014), the highest number of plaques 1.65 (0.075), the fastest c-IMT progression 0.06 (0.013), and the highest ASCVD risk (HR, 95% CI) (1.95, 1.18-3.23). Baseline and progression measures of carotid subclinical atherosclerosis and ASCVD risk were associated with the predicted endotypes in the PIVUS. Endotypes consistently improved measures of ASCVD risk discrimination and reclassification in both study populations.

Conclusions

We report four replicable subclinical carotid atherosclerosis-endotypes associated with progression of atherosclerosis and ASCVD risk in two independent populations. Our approach based on endotypes can be applied for precision medicine in ASCVD prevention.",,pdf:https://academic.oup.com/cardiovascres/advance-article-pdf/doi/10.1093/cvr/cvad106/50910161/cvad106.pdf; doi:https://doi.org/10.1093/cvr/cvad106; html:https://europepmc.org/articles/PMC10730242; pdf:https://europepmc.org/articles/PMC10730242?pdf=render -36769519,https://doi.org/10.3390/jcm12030872,Patterns of Healthcare Resource Utilisation of Critical Care Survivors between 2006 and 2017 in Wales: A Population-Based Study.,"Alsallakh M, Tan L, Pugh R, Akbari A, Bailey R, Griffiths R, Lyons RA, Szakmany T.",,Journal of clinical medicine,2023,2023-01-21,Y,Wales; Healthcare Resource Utilisation; Critical Care Survivorship,,,"In this retrospective cohort study, we used the Secure Anonymised Information Linkage (SAIL) Databank to characterise and identify predictors of the one-year post-discharge healthcare resource utilisation (HRU) of adults who were admitted to critical care units in Wales between 1 April 2006 and 31 December 2017. We modelled one-year post-critical-care HRU using negative binomial models and used linear models for the difference from one-year pre-critical-care HRU. We estimated the association between critical illness and post-hospitalisation HRU using multilevel negative binomial models among people hospitalised in 2015. We studied 55,151 patients. Post-critical-care HRU was 11-87% greater than pre-critical-care levels, whereas emergency department (ED) attendances decreased by 30%. Age ≥50 years was generally associated with greater post-critical-care HRU; those over 80 had three times longer hospital readmissions than those younger than 50 (incidence rate ratio (IRR): 2.96, 95% CI: 2.84, 3.09). However, ED attendances were higher in those younger than 50. High comorbidity was associated with 22-62% greater post-critical-care HRU than no or low comorbidity. The most socioeconomically deprived quintile was associated with 24% more ED attendances (IRR: 1.24 [1.16, 1.32]) and 13% longer hospital stays (IRR: 1.13 [1.09, 1.17]) than the least deprived quintile. Critical care survivors had greater 1-year post-discharge HRU than non-critical inpatients, including 68% longer hospital stays (IRR: 1.68 [1.63, 1.74]). Critical care survivors, particularly those with older ages, high comorbidity, and socioeconomic deprivation, used significantly more primary and secondary care resources after discharge compared with their baseline and non-critical inpatients. Interventions are needed to ensure that key subgroups are identified and adequately supported.",,pdf:https://www.mdpi.com/2077-0383/12/3/872/pdf?version=1674984751; doi:https://doi.org/10.3390/jcm12030872; html:https://europepmc.org/articles/PMC9917699; pdf:https://europepmc.org/articles/PMC9917699?pdf=render 36035235,https://doi.org/10.1212/nxg.0000000000200015,"Frequency and Phenotype Associations of Rare Variants in 5 Monogenic Cerebral Small Vessel Disease Genes in 200,000 UK Biobank Participants.","Ferguson AC, Thrippleton S, Henshall D, Whittaker E, Conway B, MacLeod M, Malik R, Rawlik K, Tenesa A, Sudlow C, Rannikmae K.",,Neurology. Genetics,2022,2022-08-24,Y,,,,"

Background and objectives

Based on previous case reports and disease-based cohorts, a minority of patients with cerebral small vessel disease (cSVD) have a monogenic cause, with many also manifesting extracerebral phenotypes. We investigated the frequency, penetrance, and phenotype associations of putative pathogenic variants in cSVD genes in the UK Biobank (UKB), a large population-based study.

Methods

We used a systematic review of previous literature and ClinVar to identify putative pathogenic rare variants in CTSA, TREX1, HTRA1, and COL4A1/2. We mapped phenotypes previously attributed to these variants (phenotypes-of-interest) to disease coding systems used in the UKB's linked health data from UK hospital admissions, death records, and primary care. Among 199,313 exome-sequenced UKB participants, we assessed the following: the proportion of participants carrying ≥1 variant(s); phenotype-of-interest penetrance; and the association between variant carrier status and phenotypes-of-interest using a binary (any phenotype present/absent) and phenotype burden (linear score of the number of phenotypes a participant possessed) approach.

Results

Among UKB participants, 0.5% had ≥1 variant(s) in studied genes. Using hospital admission and death records, 4%-20% of variant carriers per gene had an associated phenotype. This increased to 7%-55% when including primary care records. Only COL4A1 variant carrier status was significantly associated with having ≥1 phenotype-of-interest and a higher phenotype score (OR = 1.29, p = 0.006).

Discussion

While putative pathogenic rare variants in monogenic cSVD genes occur in 1:200 people in the UKB population, only approximately half of variant carriers have a relevant disease phenotype recorded in their linked health data. We could not replicate most previously reported gene-phenotype associations, suggesting lower penetrance rates, overestimated pathogenicity, and/or limited statistical power.",,pdf:https://ng.neurology.org/content/nng/8/5/e200015.full.pdf; doi:https://doi.org/10.1212/NXG.0000000000200015; html:https://europepmc.org/articles/PMC9403885; pdf:https://europepmc.org/articles/PMC9403885?pdf=render +36769519,https://doi.org/10.3390/jcm12030872,Patterns of Healthcare Resource Utilisation of Critical Care Survivors between 2006 and 2017 in Wales: A Population-Based Study.,"Alsallakh M, Tan L, Pugh R, Akbari A, Bailey R, Griffiths R, Lyons RA, Szakmany T.",,Journal of clinical medicine,2023,2023-01-21,Y,Wales; Healthcare Resource Utilisation; Critical Care Survivorship,,,"In this retrospective cohort study, we used the Secure Anonymised Information Linkage (SAIL) Databank to characterise and identify predictors of the one-year post-discharge healthcare resource utilisation (HRU) of adults who were admitted to critical care units in Wales between 1 April 2006 and 31 December 2017. We modelled one-year post-critical-care HRU using negative binomial models and used linear models for the difference from one-year pre-critical-care HRU. We estimated the association between critical illness and post-hospitalisation HRU using multilevel negative binomial models among people hospitalised in 2015. We studied 55,151 patients. Post-critical-care HRU was 11-87% greater than pre-critical-care levels, whereas emergency department (ED) attendances decreased by 30%. Age ≥50 years was generally associated with greater post-critical-care HRU; those over 80 had three times longer hospital readmissions than those younger than 50 (incidence rate ratio (IRR): 2.96, 95% CI: 2.84, 3.09). However, ED attendances were higher in those younger than 50. High comorbidity was associated with 22-62% greater post-critical-care HRU than no or low comorbidity. The most socioeconomically deprived quintile was associated with 24% more ED attendances (IRR: 1.24 [1.16, 1.32]) and 13% longer hospital stays (IRR: 1.13 [1.09, 1.17]) than the least deprived quintile. Critical care survivors had greater 1-year post-discharge HRU than non-critical inpatients, including 68% longer hospital stays (IRR: 1.68 [1.63, 1.74]). Critical care survivors, particularly those with older ages, high comorbidity, and socioeconomic deprivation, used significantly more primary and secondary care resources after discharge compared with their baseline and non-critical inpatients. Interventions are needed to ensure that key subgroups are identified and adequately supported.",,pdf:https://www.mdpi.com/2077-0383/12/3/872/pdf?version=1674984751; doi:https://doi.org/10.3390/jcm12030872; html:https://europepmc.org/articles/PMC9917699; pdf:https://europepmc.org/articles/PMC9917699?pdf=render 36609574,https://doi.org/10.1038/s41467-022-35771-8,A population-based matched cohort study of major congenital anomalies following COVID-19 vaccination and SARS-CoV-2 infection.,"Calvert C, Carruthers J, Denny C, Donaghy J, Hopcroft LEM, Hopkins L, Goulding A, Lindsay L, McLaughlin T, Moore E, Taylor B, Loane M, Dolk H, Morris J, Auyeung B, Bhaskaran K, Gibbons CL, Katikireddi SV, O'Leary M, McAllister D, Shi T, Simpson CR, Robertson C, Sheikh A, Stock SJ, Wood R.",,Nature communications,2023,2023-01-06,Y,,,,"Evidence on associations between COVID-19 vaccination or SARS-CoV-2 infection and the risk of congenital anomalies is limited. Here we report a national, population-based, matched cohort study using linked electronic health records from Scotland (May 2020-April 2022) to estimate the association between COVID-19 vaccination and, separately, SARS-CoV-2 infection between six weeks pre-conception and 19 weeks and six days gestation and the risk of [1] any major congenital anomaly and [2] any non-genetic major congenital anomaly. Mothers vaccinated in this pregnancy exposure period mostly received an mRNA vaccine (73.7% Pfizer-BioNTech BNT162b2 and 7.9% Moderna mRNA-1273). Of the 6731 babies whose mothers were vaccinated in the pregnancy exposure period, 153 had any anomaly and 120 had a non-genetic anomaly. Primary analyses find no association between any vaccination and any anomaly (adjusted Odds Ratio [aOR] = 1.01, 95% Confidence Interval [CI] = 0.83-1.24) or non-genetic anomalies (aOR = 1.00, 95% CI = 0.81-1.22). Primary analyses also find no association between SARS-CoV-2 infection and any anomaly (aOR = 1.02, 95% CI = 0.66-1.60) or non-genetic anomalies (aOR = 0.94, 95% CI = 0.57-1.54). Findings are robust to sensitivity analyses. These data provide reassurance on the safety of vaccination, in particular mRNA vaccines, just before or in early pregnancy.",,pdf:https://www.nature.com/articles/s41467-022-35771-8.pdf; doi:https://doi.org/10.1038/s41467-022-35771-8; html:https://europepmc.org/articles/PMC9821346; pdf:https://europepmc.org/articles/PMC9821346?pdf=render 34071236,https://doi.org/10.3390/ijms22115763,"Integration of the Microbiome, Metabolome and Transcriptomics Data Identified Novel Metabolic Pathway Regulation in Colorectal Cancer.","Bisht V, Nash K, Xu Y, Agarwal P, Bosch S, Gkoutos GV, Acharjee A.",,International journal of molecular sciences,2021,2021-05-28,Y,Microbiota; Biomarkers; Transcriptome; Metabolomics; Colorectal Neoplasms; Omics Integration,,,"Integrative multiomics data analysis provides a unique opportunity for the mechanistic understanding of colorectal cancer (CRC) in addition to the identification of potential novel therapeutic targets. In this study, we used public omics data sets to investigate potential associations between microbiome, metabolome, bulk transcriptomics and single cell RNA sequencing datasets. We identified multiple potential interactions, for example 5-aminovalerate interacting with Adlercreutzia; cholesteryl ester interacting with bacterial genera Staphylococcus, Blautia and Roseburia. Using public single cell and bulk RNA sequencing, we identified 17 overlapping genes involved in epithelial cell pathways, with particular significance of the oxidative phosphorylation pathway and the ACAT1 gene that indirectly regulates the esterification of cholesterol. These findings demonstrate that the integration of multiomics data sets from diverse populations can help us in untangling the colorectal cancer pathogenesis as well as postulate the disease pathology mechanisms and therapeutic targets.",,pdf:https://www.mdpi.com/1422-0067/22/11/5763/pdf?version=1622194941; doi:https://doi.org/10.3390/ijms22115763; html:https://europepmc.org/articles/PMC8198673; pdf:https://europepmc.org/articles/PMC8198673?pdf=render 36000189,https://doi.org/10.1515/dx-2022-0052,The diagnostic potential and barriers of microbiome based therapeutics.,"Acharjee A, Singh U, Choudhury SP, Gkoutos GV.",,"Diagnosis (Berlin, Germany)",2022,2022-08-25,N,Microbiota; Biomarker; Diagnostics; Machine Learning,,,"High throughput technological innovations in the past decade have accelerated research into the trillions of commensal microbes in the gut. The 'omics' technologies used for microbiome analysis are constantly evolving, and large-scale datasets are being produced. Despite of the fact that much of the research is still in its early stages, specific microbial signatures have been associated with the promotion of cancer, as well as other diseases such as inflammatory bowel disease, neurogenerative diareses etc. It has been also reported that the diversity of the gut microbiome influences the safety and efficacy of medicines. The availability and declining sequencing costs has rendered the employment of RNA-based diagnostics more common in the microbiome field necessitating improved data-analytical techniques so as to fully exploit all the resulting rich biological datasets, while accounting for their unique characteristics, such as their compositional nature as well their heterogeneity and sparsity. As a result, the gut microbiome is increasingly being demonstrating as an important component of personalised medicine since it not only plays a role in inter-individual variability in health and disease, but it also represents a potentially modifiable entity or feature that may be addressed by treatments in a personalised way. In this context, machine learning and artificial intelligence-based methods may be able to unveil new insights into biomedical analyses through the generation of models that may be used to predict category labels, and continuous values. Furthermore, diagnostic aspects will add value in the identification of the non invasive markers in the critical diseases like cancer.",,pdf:https://www.degruyter.com/document/doi/10.1515/dx-2022-0052/pdf; doi:https://doi.org/10.1515/dx-2022-0052 @@ -263,8 +263,8 @@ PMC10929454,https://doi.org/,Optimising data curation pipelines for population-l 35155637,https://doi.org/10.3389/fcvm.2022.822269,Generalizable Framework for Atrial Volume Estimation for Cardiac CT Images Using Deep Learning With Quality Control Assessment.,"Abdulkareem M, Brahier MS, Zou F, Taylor A, Thomaides A, Bergquist PJ, Srichai MB, Lee AM, Vargas JD, Petersen SE.",,Frontiers in cardiovascular medicine,2022,2022-01-28,Y,Quality control; CT; Left Atrial Volume; Left Atrium; Deep Learning,,,"

Objectives

Cardiac computed tomography (CCT) is a common pre-operative imaging modality to evaluate pulmonary vein anatomy and left atrial appendage thrombus in patients undergoing catheter ablation (CA) for atrial fibrillation (AF). These images also allow for full volumetric left atrium (LA) measurement for recurrence risk stratification, as larger LA volume (LAV) is associated with higher recurrence rates. Our objective is to apply deep learning (DL) techniques to fully automate the computation of LAV and assess the quality of the computed LAV values.

Methods

Using a dataset of 85,477 CCT images from 337 patients, we proposed a framework that consists of several processes that perform a combination of tasks including the selection of images with LA from all other images using a ResNet50 classification model, the segmentation of images with LA using a UNet image segmentation model, the assessment of the quality of the image segmentation task, the estimation of LAV, and quality control (QC) assessment.

Results

Overall, the proposed LAV estimation framework achieved accuracies of 98% (precision, recall, and F1 score metrics) in the image classification task, 88.5% (mean dice score) in the image segmentation task, 82% (mean dice score) in the segmentation quality prediction task, and R 2 (the coefficient of determination) value of 0.968 in the volume estimation task. It correctly identified 9 out of 10 poor LAV estimations from a total of 337 patients as poor-quality estimates.

Conclusions

We proposed a generalizable framework that consists of DL models and computational methods for LAV estimation. The framework provides an efficient and robust strategy for QC assessment of the accuracy for DL-based image segmentation and volume estimation tasks, allowing high-throughput extraction of reproducible LAV measurements to be possible.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2022.822269/pdf; doi:https://doi.org/10.3389/fcvm.2022.822269; html:https://europepmc.org/articles/PMC8831539; pdf:https://europepmc.org/articles/PMC8831539?pdf=render 36441117,https://doi.org/10.1111/acps.13523,Predictors of hospital readmission for patients diagnosed with delirium: An electronic health record data analysis.,"Friedrich ME, Perera G, Leutgeb L, Haardt D, Frey R, Stewart R, Mueller C.",,Acta psychiatrica Scandinavica,2023,2022-12-28,Y,Dementia; risk factors; Delirium; Readmission,,,"

Introduction

Delirium is an acute and fluctuating change in attention and cognition that increases the risk of functional decline, institutionalisation and death in hospitalised patients. After delirium, patients have a significantly higher risk of readmission to hospital. Our aim was to investigate factors associated with hospital readmission in people with delirium.

Methods

We carried out an observational retrospective cohort study using linked mental health care and hospitalisation records from South London. Logistic regression models were used to predict the odds of 30-day readmission and Cox proportional hazard models to calculate readmission risks when not restricting follow-up time.

Results

Of 2814 patients (mean age 78.9 years SD ±11.8) discharged from hospital after an episode of delirium, 823 (29.3%) were readmitted within 30 days. Depressed mood (odds ratio (OR) 1.34 (95% confidence interval (CI) 1.08-1.66)), moderate-to-severe physical health problems (OR 1.67 (95% CI 1.18-2.2.36)) and a history of serious circulatory disease (OR 1.29 (95% CI 1.07-1.55)) were associated with higher odds of hospital readmission, whereas a diagnosis of delirium superimposed on dementia (OR 0.67 (95% CI 0.53-0.84)) and problematic alcohol/substance (OR 0.54 (95% CI 0.33-0.89)) use were associated with lower odds. Cox proportionate hazard models showed similar results.

Conclusion

Almost one-third of patients with delirium were readmitted within a short period of time, a more detailed understanding of the underlying risk factors could help prevent readmissions. Our findings indicate that the aetiology (as alcohol-related delirium), the recognition that delirium occurred in the context of dementia, as well as potentially modifiable factors, as depressed mood affect readmission risk, and should be assessed in clinical settings.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/acps.13523; doi:https://doi.org/10.1111/acps.13523; html:https://europepmc.org/articles/PMC10463092; pdf:https://europepmc.org/articles/PMC10463092?pdf=render 37254630,https://doi.org/10.1111/acel.13808,"Mid-life leukocyte telomere length and dementia risk: An observational and mendelian randomization study of 435,046 UK Biobank participants.","Liu R, Xiang M, Pilling LC, Melzer D, Wang L, Manning KJ, Steffens DC, Bowden J, Fortinsky RH, Kuchel GA, Rhee TG, Diniz BS, Kuo CL.",,Aging cell,2023,2023-05-30,Y,Cognition; Alzheimer's disease; Vascular dementia; Brain Magnetic Resonance Imaging; Hallmarks Of Biological Aging,,,"Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging-related diseases, including Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD). The objective of this study was to assess associations of leukocyte telomere length (TL) with AD/ADRD and early markers of AD/ADRD, including cognitive performance and brain magnetic resonance imaging (MRI) phenotypes. Data from European-ancestry participants in the UK Biobank (n = 435,046) were used to evaluate whether mid-life leukocyte TL is associated with incident AD/ADRD over a mean follow-up of 12.2 years. In a subsample without AD/ADRD and with brain imaging data (n = 43,390), we associated TL with brain MRI phenotypes related to AD or vascular dementia pathology. Longer TL was associated with a lower risk of incident AD/ADRD (adjusted Hazard Ratio [aHR] per SD = 0.93, 95% CI 0.90-0.96, p = 3.37 × 10-7 ). Longer TL also was associated with better cognitive performance in specific cognitive domains, larger hippocampus volume, lower total volume of white matter hyperintensities, and higher fractional anisotropy and lower mean diffusivity in the fornix. In conclusion, longer TL is inversely associated with AD/ADRD, cognitive impairment, and brain structural lesions toward the development of AD/ADRD. However, the relationships between genetically determined TL and the outcomes above were not statistically significant based on the results from Mendelian randomization analysis results. Our findings add to the literature of prioritizing risk for AD/ADRD. The causality needs to be ascertained in mechanistic studies.",,doi:https://doi.org/10.1111/acel.13808; doi:https://doi.org/10.1111/acel.13808; html:https://europepmc.org/articles/PMC10352557; pdf:https://europepmc.org/articles/PMC10352557?pdf=render -38751343,https://doi.org/10.1093/ced/llae196,Disagreement concerning atopic dermatitis subtypes between an English prospective cohort (ALSPAC) and linked electronic health records.,"Matthewman J, Mulick A, Dand N, Major-Smith D, Henderson A, Pearce N, Denaxas S, Iskandar R, Roberts A, Cornish RP, Brown SJ, Paternoster L, Langan SM.",,Clinical and experimental dermatology,2024,2024-05-16,N,,,,"

Background

Subtypes of atopic dermatitis (AD) have been derived from the Avon Longitudinal Study of Parents and Children (ALSPAC) based on presence and severity of symptoms reported in questionnaires (Severe-Frequent, Moderate-Frequent, Moderate-Declining, Mild-Intermittent, Unaffected/Rare). Good agreement between ALSPAC and linked electronic health records (EHRs) would increase trust in the clinical validity of these subtypes and allow inferring subtypes from EHRs alone, which would enable their study in large primary care databases.

Objectives

1. Explore if presence and number of AD records in EHRs agrees with AD symptom and severity reports from ALSPAC; 2. Explore if EHRs agree with ALSPAC-derived AD subtypes; 3. Construct models to classify ALSPAC-derived AD subtype using EHRs.

Methods

We used data from the ALSPAC prospective cohort study from 11 timepoints until age 14 years (1991-2008), linked to local general practice EHRs. We assessed how far ALSPAC questionnaire responses and derived subtypes agreed with AD as established in EHRs using different AD definitions (e.g., diagnosis and/or prescription) and other AD-related records. We classified AD subtypes using EHRs, fitting multinomial logistic regression models tuning hyperparameters and evaluating performance in the testing set (ROC AUC, accuracy, sensitivity, and specificity).

Results

8,828 individuals out of a total 13,898 had both been assigned an AD subtype and had linked EHRs. The number of AD-related codes in EHRs generally increased with severity of AD subtype, however not all with the Severe-Frequent subtypes had AD in EHRs, and many with the Unaffected/Rare subtype did have AD in EHRs. When predicting ALSPAC AD subtype using EHRs, the best tuned model had ROC AUC of 0.65, sensitivity of 0.29 and specificity of 0.83 (both macro averaged); when different sets of predictors were used, individuals with missing EHR coverage excluded, and subtypes combined, sensitivity was not considerably improved.

Conclusions

ALSPAC and EHRs disagreed not just on AD subtypes, but also on whether children had AD or not. Researchers should be aware that individuals considered as having AD in one source may not be considered as having AD in another.",,doi:https://doi.org/10.1093/ced/llae196; doi:https://doi.org/10.1093/ced/llae196 31783849,https://doi.org/10.1186/s12911-019-0953-2,Developing a standardised approach to the aggregation of inpatient episodes into person-based spells in all specialties and psychiatric specialties.,"Rees S, Akbari A, Collins H, Lee SC, Marchant A, Rees A, Thayer D, Wang T, Wood S, John A.",,BMC medical informatics and decision making,2019,2019-11-29,Y,Data Quality; Data Linkage; Electronic Healthcare Record; Spells; Hospital Inpatient Episodes; Routine Health Data,Improving Public Health,,"

Background

Electronic health record (EHR) data are available for research in all UK nations and cross-nation comparative studies are becoming more common. All UK inpatient EHRs are based around episodes, but episode-based analysis may not sufficiently capture the patient journey. There is no UK-wide method for aggregating episodes into standardised person-based spells. This study identifies two data quality issues affecting the creation of person-based spells, and tests four methods to create these spells, for implementation across all UK nations.

Methods

Welsh inpatient EHRs from 2013 to 2017 were analysed. Phase one described two data quality issues; transfers of care and episode sequencing. Phase two compared four methods for creating person spells. Measures were mean length of stay (LOS, expressed in days) and number of episodes per person spell for each method.

Results

3.5% of total admissions were transfers-in and 3.1% of total discharges were transfers-out. 68.7% of total transfers-in and 48.7% of psychiatric transfers-in had an identifiable preceding transfer-out, and 78.2% of total transfers-out and 59.0% of psychiatric transfers-out had an identifiable subsequent transfer-in. 0.2% of total episodes and 4.0% of psychiatric episodes overlapped with at least one other episode of any specialty. Method one (no evidence of transfer required; overlapping episodes grouped together) resulted in the longest mean LOS (4.0 days for all specialties; 48.5 days for psychiatric specialties) and the fewest single episode person spells (82.4% of all specialties; 69.7% for psychiatric specialties). Method three (evidence of transfer required; overlapping episodes separated) resulted in the shortest mean LOS (3.7 days for all specialties; 45.8 days for psychiatric specialties) and the most single episode person spells; (86.9% for all specialties; 86.3% for psychiatric specialties).

Conclusions

Transfers-in appear better recorded than transfers-out. Transfer coding is incomplete, particularly for psychiatric specialties. The proportion of episodes that overlap is small but psychiatric episodes are disproportionately affected. The most successful method for grouping episodes into person spells aggregated overlapping episodes and required no evidence of transfer from admission source/method or discharge destination codes. The least successful method treated overlapping episodes as distinct and required transfer coding. The impact of all four methods was greater for psychiatric specialties.","Rees et al used a Welsh database to examine inpatient episode/transfer coding coding for psychiatric patients. They identified deficiencies in the existing coding system for psychitatrics transfers and unexplained coding mistakes/problems, then they presesnt several different methods for constructing the inpatient spell to improve coding and avoid misclassification.",pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-019-0953-2; doi:https://doi.org/10.1186/s12911-019-0953-2; html:https://europepmc.org/articles/PMC6884917; pdf:https://europepmc.org/articles/PMC6884917?pdf=render +38751343,https://doi.org/10.1093/ced/llae196,Disagreement concerning atopic dermatitis subtypes between an English prospective cohort (ALSPAC) and linked electronic health records.,"Matthewman J, Mulick A, Dand N, Major-Smith D, Henderson A, Pearce N, Denaxas S, Iskandar R, Roberts A, Cornish RP, Brown SJ, Paternoster L, Langan SM.",,Clinical and experimental dermatology,2024,2024-05-16,N,,,,"

Background

Subtypes of atopic dermatitis (AD) have been derived from the Avon Longitudinal Study of Parents and Children (ALSPAC) based on presence and severity of symptoms reported in questionnaires (Severe-Frequent, Moderate-Frequent, Moderate-Declining, Mild-Intermittent, Unaffected/Rare). Good agreement between ALSPAC and linked electronic health records (EHRs) would increase trust in the clinical validity of these subtypes and allow inferring subtypes from EHRs alone, which would enable their study in large primary care databases.

Objectives

1. Explore if presence and number of AD records in EHRs agrees with AD symptom and severity reports from ALSPAC; 2. Explore if EHRs agree with ALSPAC-derived AD subtypes; 3. Construct models to classify ALSPAC-derived AD subtype using EHRs.

Methods

We used data from the ALSPAC prospective cohort study from 11 timepoints until age 14 years (1991-2008), linked to local general practice EHRs. We assessed how far ALSPAC questionnaire responses and derived subtypes agreed with AD as established in EHRs using different AD definitions (e.g., diagnosis and/or prescription) and other AD-related records. We classified AD subtypes using EHRs, fitting multinomial logistic regression models tuning hyperparameters and evaluating performance in the testing set (ROC AUC, accuracy, sensitivity, and specificity).

Results

8,828 individuals out of a total 13,898 had both been assigned an AD subtype and had linked EHRs. The number of AD-related codes in EHRs generally increased with severity of AD subtype, however not all with the Severe-Frequent subtypes had AD in EHRs, and many with the Unaffected/Rare subtype did have AD in EHRs. When predicting ALSPAC AD subtype using EHRs, the best tuned model had ROC AUC of 0.65, sensitivity of 0.29 and specificity of 0.83 (both macro averaged); when different sets of predictors were used, individuals with missing EHR coverage excluded, and subtypes combined, sensitivity was not considerably improved.

Conclusions

ALSPAC and EHRs disagreed not just on AD subtypes, but also on whether children had AD or not. Researchers should be aware that individuals considered as having AD in one source may not be considered as having AD in another.",,doi:https://doi.org/10.1093/ced/llae196; doi:https://doi.org/10.1093/ced/llae196 36997856,https://doi.org/10.1186/s12882-023-03126-0,A clinical frailty scale obtained from MDT discussion performs poorly in assessing frailty in haemodialysis recipients.,"Anderson BM, Qasim M, Correa G, Evison F, Gallier S, Ferro CJ, Jackson TA, Sharif A.",,BMC nephrology,2023,2023-03-30,Y,Mortality; Frailty; Haemodialysis; Hospitalisation; Clinical Frailty Scale,,,"

Background

The Clinical Frailty Scale (CFS) is a commonly utilised frailty screening tool that has been associated with hospitalisation and mortality in haemodialysis recipients, but is subject to heterogenous methodologies including subjective clinician opinion. The aims of this study were to (i) examine the accuracy of a subjective, multidisciplinary assessment of CFS at haemodialysis Quality Assurance (QA) meetings (CFS-MDT), compared with a standard CFS score via clinical interview, and (ii) ascertain the associations of these scores with hospitalisation and mortality.

Methods

We performed a prospective cohort study of prevalent haemodialysis recipients linked to national datasets for outcomes including mortality and hospitalisation. Frailty was assessed using the CFS after structured clinical interview. The CFS-MDT was derived from consensus at haemodialysis QA meetings, involving dialysis nurses, dietitians, and nephrologists.

Results

453 participants were followed-up for a median of 685 days (IQR 544-812), during which there were 96 (21.2%) deaths and 1136 hospitalisations shared between 327 (72.1%) participants. Frailty was identified in 246 (54.3%) participants via CFS, but only 120 (26.5%) via CFS-MDT. There was weak correlation (Spearman Rho 0.485, P < 0.001) on raw frailty scores and minimal agreement (Cohen's κ = 0.274, P < 0.001) on categorisation of frail, vulnerable and robust between the CFS and CFS-MDT. Increasing frailty was associated with higher rates of hospitalisation for the CFS (IRR 1.26, 95% C.I. 1.17-1.36, P = 0.016) and CFS-MDT (IRR 1.10, 1.02-1.19, P = 0.02), but only the CFS-MDT was associated with nights spent in hospital (IRR 1.22, 95% C.I. 1.08-1.38, P = 0.001). Both scores were associated with mortality (CFS HR 1.31, 95% C.I. 1.09-1.57, P = 0.004; CFS-MDT HR 1.36, 95% C.I. 1.16-1.59, P < 0.001).

Conclusions

Assessment of CFS is deeply affected by the underlying methodology, with the potential to profoundly affect decision-making. The CFS-MDT appears to be a weak alternative to conventional CFS. Standardisation of CFS use is of paramount importance in clinical and research practice in haemodialysis.

Trial registration

Clinicaltrials.gov : NCT03071107 registered 06/03/2017.",,pdf:https://bmcnephrol.biomedcentral.com/counter/pdf/10.1186/s12882-023-03126-0; doi:https://doi.org/10.1186/s12882-023-03126-0; html:https://europepmc.org/articles/PMC10062243; pdf:https://europepmc.org/articles/PMC10062243?pdf=render 36350946,https://doi.org/10.1093/bjsopen/zrac130,Major adverse cardiovascular events and all-cause mortality after emergency general surgery among kidney failure patients.,"Anderson B, Zou X, Evison F, Gallier S, Inston N, Sharif A.",,BJS open,2022,2022-11-01,Y,,,,"

Background

Emergency general surgery (EGS) is associated with increased mortality, with kidney failure a contributing risk, but comparative outcomes between patients with kidney failure and the general population are lacking.

Methods

In this retrospective population-cohort study, data were analysed for all EGS procedures performed in England between 1 April 2004 and 31 March 2019. EGS was defined as partial colectomy, small bowel resection, cholecystectomy, appendicectomy, lysis of peritoneal adhesions, surgery for peptic ulcer, or laparotomy. The main outcome measure was major adverse cardiovascular events (MACEs) and all-cause mortality after surgery.

Results

From 691 064 procedures, 0.16 per cent (n = 1097) and 0.23 per cent (n = 1567) were performed on kidney transplant and dialysis recipients respectively. Laparotomy was the most frequent EGS procedure for kidney transplant (46 per cent of procedures, n = 507) and dialysis (45 per cent of procedures, n = 704) recipients, with the highest 30-day and 1-year mortality. In logistic regression analysis, both kidney failure cohorts had higher risk for experiencing MACEs in the postoperative interval after emergency laparotomy; within 3 months (dialysis; OR 2.44 (95 per cent c.i. 2.08 to 2.87), P < 0.001 and transplant; OR 2.05 (95 per cent c.i. 1.57 to 2.68), P < 0.001) and within 1 year (dialysis; OR 2.39 (95 per cent c.i. 2.06 to 2.77), P < 0.001 and transplant; OR 2.21 (95 per cent c.i. 1.76 to 2.77), P < 0.001); however, in a propensity-score-matched cohort, increased risk for MACEs was observed among dialysis patients after emergency laparotomy (HR 2.10 (95 per cent c.i. 1.82 to 2.43), P < 0.001) but not kidney transplant recipients (HR 1.17 (95 per cent c.i. 0.97 to 1.41), P = 0.096).

Conclusion

Mortality after emergency surgery is higher for patients with kidney failure and dialysis is worse than kidney transplantation, with cardiovascular deaths more common than the general population.",,pdf:https://academic.oup.com/bjsopen/article-pdf/6/6/zrac130/46906578/zrac130.pdf; doi:https://doi.org/10.1093/bjsopen/zrac130; html:https://europepmc.org/articles/PMC9645564; pdf:https://europepmc.org/articles/PMC9645564?pdf=render 36580462,https://doi.org/10.1371/journal.pone.0279381,Investigating the potential impact of PCSK9-inhibitors on mood disorders using eQTL-based Mendelian randomization.,"Aman A, Slob EAW, Ward J, Cullen B, Graham N, Lyall DM, Sattar N, Strawbridge RJ.",,PloS one,2022,2022-12-29,Y,,,,"Prescription of PCSK9-inhibitors has increased in recent years but not much is known about its off-target effects. PCSK9-expression is evident in non-hepatic tissues, notably the brain, and genetic variation in the PCSK9 locus has recently been shown to be associated with mood disorder-related traits. We investigated whether PCSK9 inhibition, proxied by a genetic reduction in expression of PCSK9 mRNA, might have a causal adverse effect on mood disorder-related traits. We used genetic variants in the PCSK9 locus associated with reduced PCSK9 expression (eQTLs) in the European population from GTEx v8 and examined the effect on PCSK9 protein levels and three mood disorder-related traits (major depressive disorder, mood instability, and neuroticism), using summary statistics from the largest European ancestry genome-wide association studies. We conducted summary-based Mendelian randomization analyses to estimate the causal effects, and attempted replication using data from eQTLGen, Brain-eMETA, and the CAGE consortium. We found that genetically reduced PCSK9 gene-expression levels were significantly associated with reduced PCSK9 protein levels but not with increased risk of mood disorder-related traits. Further investigation of nearby genes demonstrated that reduced USP24 gene-expression levels was significantly associated with increased risk of mood instability (p-value range = 5.2x10-5-0.03), and neuroticism score (p-value range = 2.9x10-5-0.02), but not with PCSK9 protein levels. Our results suggest that genetic variation in this region acts on mood disorders through a PCSK9-independent pathway, and therefore PCSK9-inhibitors are unlikely to have an adverse impact on mood disorder-related traits.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279381&type=printable; doi:https://doi.org/10.1371/journal.pone.0279381; html:https://europepmc.org/articles/PMC9799310; pdf:https://europepmc.org/articles/PMC9799310?pdf=render @@ -278,8 +278,8 @@ PMC10929454,https://doi.org/,Optimising data curation pipelines for population-l 33893241,https://doi.org/10.1126/science.abf0874,Resurgence of SARS-CoV-2: Detection by community viral surveillance.,"Riley S, Ainslie KEC, Eales O, Walters CE, Wang H, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P.",,"Science (New York, N.Y.)",2021,2021-04-23,Y,,,,"Surveillance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has mainly relied on case reporting, which is biased by health service performance, test availability, and test-seeking behaviors. We report a community-wide national representative surveillance program in England based on self-administered swab results from ~594,000 individuals tested for SARS-CoV-2, regardless of symptoms, between May and the beginning of September 2020. The epidemic declined between May and July 2020 but then increased gradually from mid-August, accelerating into early September 2020 at the start of the second wave. When compared with cases detected through routine surveillance, we report here a longer period of decline and a younger age distribution. Representative community sampling for SARS-CoV-2 can substantially improve situational awareness and feed into the public health response even at low prevalence.",,pdf:https://www.science.org/cms/asset/00326f17-60ca-4c01-8814-727df6504005/pap.pdf; doi:https://doi.org/10.1126/science.abf0874; html:https://europepmc.org/articles/PMC8158959; pdf:https://europepmc.org/articles/PMC8158959?pdf=render 31566668,https://doi.org/10.1093/ageing/afz110,External validation of the electronic Frailty Index using the population of Wales within the Secure Anonymised Information Linkage Databank.,"Hollinghurst J, Fry R, Akbari A, Clegg A, Lyons RA, Watkins A, Rodgers SE.",,Age and ageing,2019,2019-11-01,Y,Frailty; Older People; Primary Care; Electronic Health Record; Cumulative Deficit; Electronic Frailty Index,Improving Public Health,,"

Background

frailty has major implications for health and social care services internationally. The development, validation and national implementation of the electronic Frailty Index (eFI) using routine primary care data has enabled change in the care of older people living with frailty in England.

Aims

to externally validate the eFI in Wales and assess new frailty-related outcomes.

Study design and setting

retrospective cohort study using the Secure Anonymised Information Linkage (SAIL) Databank, comprising 469,000 people aged 65-95, registered with a SAIL contributing general practice on 1 January 2010.

Methods

four categories (fit; mild; moderate and severe) of frailty were constructed using recognised cut points from the eFI. We calculated adjusted hazard ratios (HRs) from Cox regression models for validation of existing outcomes: 1-, 3- and 5-year mortality, hospitalisation, and care home admission for validation. We also analysed, as novel outcomes, 1-year mortality following hospitalisation and frailty transition times.

Results

HR trends for the validation outcomes in SAIL followed the original results from ResearchOne and THIN databases. Relative to the fit category, adjusted HRs in SAIL (95% CI) for 1-year mortality following hospitalisation were 1.05 (95% CI 1.03-1.08) for mild frailty, 1.24 (95% CI 1.21-1.28) for moderate frailty and 1.51 (95% CI 1.45-1.57) for severe frailty. The median time (lower and upper quartile) between frailty categories was 2,165 days (lower and upper quartiles: 1,510 and 2,831) from fit to mild, 1,155 days (lower and upper quartiles: 756 and 1,610) from mild to moderate and 898 days (lower and upper quartiles: 584 and 1,275) from moderate to severe.

Conclusions

further validation of the eFI showed robust predictive validity and utility for new outcomes.",,pdf:https://academic.oup.com/ageing/article-pdf/48/6/922/30302589/afz110.pdf; doi:https://doi.org/10.1093/ageing/afz110; html:https://europepmc.org/articles/PMC6814149; pdf:https://europepmc.org/articles/PMC6814149?pdf=render 37247403,https://doi.org/10.1093/ageing/afad077,Attainment of NICE blood pressure targets among older people with newly diagnosed hypertension: nationwide linked electronic health records cohort study.,"Todd O, Johnson O, Wilkinson C, Hollinghurst J, Dondo TB, Yadegarfar ME, Sheppard JP, McManus RJ, Gale CP, Clegg A.",,Age and ageing,2023,2023-05-01,Y,Hypertension; Blood pressure; Frailty; Older People; Treatment Target,,,"

Background

it is not known if clinical practice reflects guideline recommendations for the management of hypertension in older people and whether guideline adherence varies according to overall health status.

Aims

to describe the proportion of older people attaining National Institute for Health and Care Excellence (NICE) guideline blood pressure targets within 1 year of hypertension diagnosis and determine predictors of target attainment.

Methods

a nationwide cohort study of Welsh primary care data from the Secure Anonymised Information Linkage databank including patients aged ≥65 years newly diagnosed with hypertension between 1st June 2011 and 1st June 2016. The primary outcome was attainment of NICE guideline blood pressure targets as measured by the latest blood pressure recording up to 1 year after diagnosis. Predictors of target attainment were investigated using logistic regression.

Results

there were 26,392 patients (55% women, median age 71 [IQR 68-77] years) included, of which 13,939 (52.8%) attained a target blood pressure within a median follow-up of 9 months. Success in attaining target blood pressure was associated with a history of atrial fibrillation (OR 1.26, 95% CI 1.11, 1.43), heart failure (OR 1.25, 95% CI 1.06, 1.49) and myocardial infarction (OR 1.20, 95% CI 1.10, 1.32), all compared to no history of each, respectively. Care home residence, the severity of frailty, and increasing co-morbidity were not associated with target attainment following adjustment for confounder variables.

Conclusions

blood pressure remains insufficiently controlled 1 year after diagnosis in nearly half of older people with newly diagnosed hypertension, but target attainment appears unrelated to baseline frailty, multi-morbidity or care home residence.",,doi:https://doi.org/10.1093/ageing/afad077; doi:https://doi.org/10.1093/ageing/afad077; html:https://europepmc.org/articles/PMC10226747; pdf:https://europepmc.org/articles/PMC10226747?pdf=render -37789603,https://doi.org/10.1002/pon.6225,Prognostic factors for mental wellbeing in prostate cancer: A systematic review and meta-analysis.,"Vyas N, Brunckhorst O, Fanshawe JB, Stewart R, Dasgupta P, Ahmed K.",,Psycho-oncology,2023,2023-10-03,Y,Cancer; Depression; Quality of life; Anxiety; Oncology; prostate cancer; Body Image; Masculinity; Mental Wellbeing; Fear Of Cancer Recurrence,,,"

Objectives

To evaluate the evidence base for patient, oncological, and treatment prognostic factors associated with multiple mental wellbeing outcomes in prostate cancer patients.

Methods

We performed a literature search of MEDLINE, EMBASE, and CINAHL databases including studies evaluating patient, oncological, or treatment factors against one of five mental wellbeing outcomes; depression, anxiety, fear of cancer recurrence, masculinity, and body image perception. Data synthesis included a random effects meta-analysis for the prognostic effect of individual factors if sufficient homogenous data was available, with a structured narrative synthesis where this was not possible.

Results

A final 62 articles were included. Older age was associated with a reducing odds of depression (OR 0.97, p = 0.04), with little evidence of effect for other outcomes. Additionally, baseline mental health status was related to depression and increasing time since diagnosis was associated with reducing fear of recurrence, albeith with low certainty of evidence. However, few other patient or oncological factors demonstrated any coherent relationship with any wellbeing outcome. Androgen deprivation therapy was associated with increased depression (HR 1.65, 95% CI 1.41-1.92, p < 0.01) and anxiety, however, little difference was seen between other treatment options. Overall, whilst numerous factors were identified, most were evaluated by single studies with few evaluating masculinity and body image outcomes.

Conclusion

We highlight the existing evidence for prognostic factors in mental wellbeing outcomes in prostate cancer, allowing us to consider high-risk groups of patients for preventative and treatment measures. However, the current evidence is heterogenous with further work required exploring less conclusive factors and outcomes.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pon.6225; doi:https://doi.org/10.1002/pon.6225; html:https://europepmc.org/articles/PMC10946963; pdf:https://europepmc.org/articles/PMC10946963?pdf=render 36322788,https://doi.org/10.2196/40035,A Hybrid Architecture (CO-CONNECT) to Facilitate Rapid Discovery and Access to Data Across the United Kingdom in Response to the COVID-19 Pandemic: Development Study.,"Jefferson E, Cole C, Mumtaz S, Cox S, Giles TC, Adejumo S, Urwin E, Lea D, Macdonald C, Best J, Masood E, Milligan G, Johnston J, Horban S, Birced I, Hall C, Jackson AS, Collins C, Rising S, Dodsley C, Hampton J, Hadfield A, Santos R, Tarr S, Panagi V, Lavagna J, Jackson T, Chuter A, Beggs J, Martinez-Queipo M, Ward H, von Ziegenweidt J, Burns F, Martin J, Sebire N, Morris C, Bradley D, Baxter R, Ahonen-Bishopp A, Smith P, Shoemark A, Valdes AM, Ollivere B, Manisty C, Eyre D, Gallant S, Joy G, McAuley A, Connell D, Northstone K, Jeffery K, Di Angelantonio E, McMahon A, Walker M, Semple MG, Sims JM, Lawrence E, Davies B, Baillie JK, Tang M, Leeming G, Power L, Breeze T, Murray D, Orton C, Pierce I, Hall I, Ladhani S, Gillson N, Whitaker M, Shallcross L, Seymour D, Varma S, Reilly G, Morris A, Hopkins S, Sheikh A, Quinlan P.",,Journal of medical Internet research,2022,2022-12-27,Y,Meta-analysis; Health care; Public Health; Clinical Care; Data Extraction; Data Privacy; Health Data; Federated Network; Data Governance; Infrastructure Model; Covid-19; Health Care Record,,,"

Background

COVID-19 data have been generated across the United Kingdom as a by-product of clinical care and public health provision, as well as numerous bespoke and repurposed research endeavors. Analysis of these data has underpinned the United Kingdom's response to the pandemic, and informed public health policies and clinical guidelines. However, these data are held by different organizations, and this fragmented landscape has presented challenges for public health agencies and researchers as they struggle to find relevant data to access and interrogate the data they need to inform the pandemic response at pace.

Objective

We aimed to transform UK COVID-19 diagnostic data sets to be findable, accessible, interoperable, and reusable (FAIR).

Methods

A federated infrastructure model (COVID - Curated and Open Analysis and Research Platform [CO-CONNECT]) was rapidly built to enable the automated and reproducible mapping of health data partners' pseudonymized data to the Observational Medical Outcomes Partnership Common Data Model without the need for any data to leave the data controllers' secure environments, and to support federated cohort discovery queries and meta-analysis.

Results

A total of 56 data sets from 19 organizations are being connected to the federated network. The data include research cohorts and COVID-19 data collected through routine health care provision linked to longitudinal health care records and demographics. The infrastructure is live, supporting aggregate-level querying of data across the United Kingdom.

Conclusions

CO-CONNECT was developed by a multidisciplinary team. It enables rapid COVID-19 data discovery and instantaneous meta-analysis across data sources, and it is researching streamlined data extraction for use in a Trusted Research Environment for research and public health analysis. CO-CONNECT has the potential to make UK health data more interconnected and better able to answer national-level research questions while maintaining patient confidentiality and local governance procedures.",,pdf:https://www.jmir.org/2022/12/e40035/PDF; doi:https://doi.org/10.2196/40035; html:https://europepmc.org/articles/PMC9822177 +37789603,https://doi.org/10.1002/pon.6225,Prognostic factors for mental wellbeing in prostate cancer: A systematic review and meta-analysis.,"Vyas N, Brunckhorst O, Fanshawe JB, Stewart R, Dasgupta P, Ahmed K.",,Psycho-oncology,2023,2023-10-03,Y,Cancer; Depression; Quality of life; Anxiety; Oncology; prostate cancer; Body Image; Masculinity; Mental Wellbeing; Fear Of Cancer Recurrence,,,"

Objectives

To evaluate the evidence base for patient, oncological, and treatment prognostic factors associated with multiple mental wellbeing outcomes in prostate cancer patients.

Methods

We performed a literature search of MEDLINE, EMBASE, and CINAHL databases including studies evaluating patient, oncological, or treatment factors against one of five mental wellbeing outcomes; depression, anxiety, fear of cancer recurrence, masculinity, and body image perception. Data synthesis included a random effects meta-analysis for the prognostic effect of individual factors if sufficient homogenous data was available, with a structured narrative synthesis where this was not possible.

Results

A final 62 articles were included. Older age was associated with a reducing odds of depression (OR 0.97, p = 0.04), with little evidence of effect for other outcomes. Additionally, baseline mental health status was related to depression and increasing time since diagnosis was associated with reducing fear of recurrence, albeith with low certainty of evidence. However, few other patient or oncological factors demonstrated any coherent relationship with any wellbeing outcome. Androgen deprivation therapy was associated with increased depression (HR 1.65, 95% CI 1.41-1.92, p < 0.01) and anxiety, however, little difference was seen between other treatment options. Overall, whilst numerous factors were identified, most were evaluated by single studies with few evaluating masculinity and body image outcomes.

Conclusion

We highlight the existing evidence for prognostic factors in mental wellbeing outcomes in prostate cancer, allowing us to consider high-risk groups of patients for preventative and treatment measures. However, the current evidence is heterogenous with further work required exploring less conclusive factors and outcomes.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pon.6225; doi:https://doi.org/10.1002/pon.6225; html:https://europepmc.org/articles/PMC10946963; pdf:https://europepmc.org/articles/PMC10946963?pdf=render 37765085,https://doi.org/10.3390/ph16091277,The Effects of CYP2C19 Genotype on Proxies of SSRI Antidepressant Response in the UK Biobank.,"Wong WLE, Fabbri C, Laplace B, Li D, van Westrhenen R, Lewis CM, Dawe GS, Young AH.",,"Pharmaceuticals (Basel, Switzerland)",2023,2023-09-11,Y,Cytochrome p450; Antidepressants; Pharmacogenetics; Treatment Response,,,"Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used psychopharmaceutical treatment for major depressive disorder (MDD), but individual responses to SSRIs vary greatly. CYP2C19 is a key enzyme involved in the metabolism of several drugs, including SSRIs. Variations in the CYP2C19 gene are associated with differential metabolic activity, and thus differential SSRI exposure; accordingly, the CYP2C19 genotype may affect the therapeutic response and clinical outcomes, though existing evidence of this link is not entirely consistent. Therefore, we analysed data from the UK Biobank, a large, deeply phenotyped prospective study, to investigate the effects of CYP2C19 metaboliser phenotypes on several clinical outcomes derived from primary care records, including multiple measures of antidepressant switching, discontinuation, duration, and side effects. In this dataset, 24,729 individuals were prescribed citalopram, 3012 individuals were prescribed escitalopram, and 12,544 individuals were prescribed sertraline. Consistent with pharmacological expectations, CYP2C19 poor metabolisers on escitalopram were more likely to switch antidepressants, have side effects following first prescription, and be on escitalopram for a shorter duration compared to normal metabolisers. CYP2C19 poor and intermediate metabolisers on citalopram also exhibited increased odds of discontinuation and shorter durations relative to normal metabolisers. Generally, no associations were found between metabolic phenotypes and proxies of response to sertraline. Sensitivity analyses in a depression subgroup and metabolic activity scores corroborated results from the primary analysis. In summary, our findings suggest that CYP2C19 genotypes, and thus metabolic phenotypes, may have utility in determining clinical responses to SSRIs, particularly escitalopram and citalopram, though further investigation of such a relationship is warranted.",,doi:https://doi.org/10.3390/ph16091277; html:https://europepmc.org/articles/PMC10535191; pdf:https://europepmc.org/articles/PMC10535191?pdf=render 37148584,https://doi.org/10.1016/j.ebiom.2023.104588,Association of HLA diversity with the risk of 25 cancers in the UK Biobank.,"Wang QL, Wang TM, Deng CM, Zhang WL, He YQ, Xue WQ, Liao Y, Yang DW, Zheng MQ, Jia WH.",,EBioMedicine,2023,2023-05-04,Y,Cancer susceptibility; Uk Biobank; Hla Evolutionary Divergence; Hla Heterozygosity,,,"

Background

The human leukocyte antigen (HLA) is a highly polymorphic region, and HLA diversity may play a role in presenting tumour-associated peptides and inducing immune responses. However, the effect of HLA diversity on cancers has not been fully assessed. We aimed to explore the role of HLA diversity on cancer development.

Methods

A pan-cancer analysis was performed to evaluate the effect of HLA diversity, measured by HLA heterozygosity and HLA evolutionary divergence (HED), on the susceptibility of 25 cancers in the UK Biobank.

Findings

We observed that the diversity of HLA class II locus was associated with a lower risk of lung cancer (ORhetero = 0.94, 95% CI = 0.90-0.97, P = 1.29 × 10-4) and head and neck cancer (ORhetero = 0.91, 95% CI = 0.86-0.96, P = 1.56 × 10-3). Besides, a lower risk of non-Hodgkin lymphoma was associated with an increased diversity of HLA class I (ORhetero = 0.92, 95% CI = 0.87-0.98, P = 8.38 × 10-3) and class II locus (ORhetero = 0.89, 95% CI = 0.86-0.92, P = 1.65 × 10-10). A lower risk of Hodgkin lymphoma was associated with the HLA class I diversity (ORhetero = 0.85, 95% CI = 0.75-0.96, P = 0.011). The protective effect of HLA diversity was mainly observed in pathological subtypes with higher tumour mutation burden, such as lung squamous cell carcinoma (P = 9.39 × 10-3) and diffuse large B cell lymphoma (Pclass I = 4.12 × 10-4; Pclass Ⅱ = 4.71 × 10-5), as well as the smoking subgroups of lung cancer (P = 7.45 × 10-5) and head and neck cancer (P = 4.55 × 10-3).

Interpretation

We provided a systematic insight into the effect of HLA diversity on cancers, which might help to understand the etiological role of HLA on cancer development.

Funding

This study was supported by grants from the National Natural Science Foundation of China (82273705, 82003520); the Basic and Applied Basic Research Foundation of Guangdong Province, China (2021B1515420007); the Science and Technology Planning Project of Guangzhou, China (201804020094); Sino-Sweden Joint Research Programme (81861138006); the National Natural Science Foundation of China (81973131, 81903395, 81803319, 81802708).",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189092; doi:https://doi.org/10.1016/j.ebiom.2023.104588; html:https://europepmc.org/articles/PMC10189092; pdf:https://europepmc.org/articles/PMC10189092?pdf=render 38336700,https://doi.org/10.1186/s12916-023-03179-w,Peripheral vertigo and subsequent risk of depression and anxiety disorders: a prospective cohort study using the UK Biobank.,"Chen X, Wei D, Fang F, Song H, Yin L, Kaijser M, Gurholt TP, Andreassen OA, Valdimarsdóttir U, Hu K, Duan M.",,BMC medicine,2024,2024-02-09,Y,Psychiatric disorders; Fractional Anisotropy; Peripheral Vertigo; Frontal-limbic Network,,,"

Background

Peripheral vertigo is often comorbid with psychiatric disorders. However, no longitudinal study has quantified the association between peripheral vertigo and risk of psychiatric disorders. Furthermore, it remains unknown how the white matter integrity of frontal-limbic network relates to the putative peripheral vertigo-psychiatric disorder link.

Methods

We conducted a cohort study including 452,053 participants of the UK Biobank with a follow-up from 2006 through 2021. We assessed the risks of depression and anxiety disorders in relation to a hospitalization episode involving peripheral vertigo using Cox proportional hazards models. We also examined the associations of peripheral vertigo, depression, and anxiety with MRI fractional anisotropy (FA) in a subsample with brain MRI data (N = 36,087), using multivariable linear regression.

Results

Individuals with an inpatient diagnosis of peripheral vertigo had elevated risks of incident depression (hazard ratio (HR) 2.18; 95% confidence interval (CI) 1.79-2.67) and anxiety (HR 2.11; 95% CI 1.71-2.61), compared to others, particularly within 2 years after hospitalization (HR for depression 2.91; 95% CI 2.04-4.15; HR for anxiety 4.92; 95% CI 3.62-6.69). Depression was associated with lower FA in most studied white matter regions, whereas anxiety and peripheral vertigo did not show statistically significant associations with FA.

Conclusions

Individuals with an inpatient diagnosis of peripheral vertigo have increased subsequent risks of depression and anxiety disorders, especially within 2 years after hospitalization. Our findings further indicate a link between depression and lower microstructural connectivity as well as integrity beyond the frontal-limbic network.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-03179-w; doi:https://doi.org/10.1186/s12916-023-03179-w; html:https://europepmc.org/articles/PMC10858592; pdf:https://europepmc.org/articles/PMC10858592?pdf=render @@ -310,16 +310,16 @@ PMC10929454,https://doi.org/,Optimising data curation pipelines for population-l 36369736,https://doi.org/10.1080/19490976.2022.2139979,"Integration of stool microbiota, proteome and amino acid profiles to discriminate patients with adenomas and colorectal cancer.","Bosch S, Acharjee A, Quraishi MN, Bijnsdorp IV, Rojas P, Bakkali A, Jansen EE, Stokkers P, Kuijvenhoven J, Pham TV, Beggs AD, Jimenez CR, Struys EA, Gkoutos GV, de Meij TG, de Boer NK.",,Gut microbes,2022,2022-01-01,Y,Screening; Biomarker; Adenoma; Colon cancer; Data integration; stool; Multi Omics,,,"

Background

Screening for colorectal cancer (CRC) reduces its mortality but has limited sensitivity and specificity. Aims We aimed to explore potential biomarker panels for CRC and adenoma detection and to gain insight into the interaction between gut microbiota and human metabolism in the presence of these lesions.

Methods

This multicenter case-control cohort was performed between February 2016 and November 2019. Consecutive patients ≥18 years with a scheduled colonoscopy were asked to participate and divided into three age, gender, body-mass index and smoking status-matched subgroups: CRC (n = 12), adenomas (n = 21) and controls (n = 20). Participants collected fecal samples prior to bowel preparation on which proteome (LC-MS/MS), microbiota (16S rRNA profiling) and amino acid (HPLC) composition were assessed. Best predictive markers were combined to create diagnostic biomarker panels. Pearson correlation-based analysis on selected markers was performed to create networks of all platforms.

Results

Combining omics platforms provided new panels which outperformed hemoglobin in this cohort, currently used for screening (AUC 0.98, 0.95 and 0.87 for CRC vs controls, adenoma vs controls and CRC vs adenoma, respectively). Integration of data sets revealed markers associated with increased blood excretion, stress- and inflammatory responses and pointed toward downregulation of epithelial integrity.

Conclusions

Integrating fecal microbiota, proteome and amino acids platforms provides for new biomarker panels that may improve noninvasive screening for adenomas and CRC, and may subsequently lead to lower incidence and mortality of colon cancer.",,doi:https://doi.org/10.1080/19490976.2022.2139979; doi:https://doi.org/10.1080/19490976.2022.2139979; html:https://europepmc.org/articles/PMC9662191; pdf:https://europepmc.org/articles/PMC9662191?pdf=render 35973468,https://doi.org/10.1016/j.jviromet.2022.114607,Evaluation of the impact of pre-analytical conditions on sample stability for the detection of SARS-CoV-2 RNA.,"Mosscrop L, Watber P, Elliot P, Cooke G, Barclay W, Freemont PS, Rosadas C, Taylor GP.",,Journal of virological methods,2022,2022-08-13,Y,RNA; Diagnosis; Rt-qpcr; Sample Stability; Sars-cov-2,,,"Demand for accurate SARS-CoV-2 diagnostics is high. Most samples in the UK are collected in the community and rely on the postal service for delivery to the laboratories. The current recommendation remains that swabs should be collected in Viral Transport Media (VTM) and transported with a cold chain to the laboratory for RNA extraction and RT-qPCR. This is not always possible. We aimed to test the stability of SARS-CoV-2 RNA subjected to different pre-analytical conditions. Swabs were dipped into PBS containing cultured SARS-CoV-2 and placed in either a dry tube or a tube containing either normal saline or VTM. The tubes were then stored at different temperatures (20-50 °C) for variable periods (8 h to 5 days). Samples were tested by RT-qPCR targeting SARS-CoV-2 E gene. VTM outperformed swabs in saline and dry swabs in all conditions. Samples in VTM were stable, independent of a cold chain, for 5 days, with a maximum increase in cycle threshold (Ct) of 1.34 when held at 40 °C. Using normal saline as the transport media resulted in a loss of sensitivity (increased Ct) over time and with increasing temperature (up to 7.8 cycles compared to VTM). SARS-CoV-2 was not detected in 3/9 samples in normal saline when tested after 120 h incubation. Transportation of samples in VTM provides a high level of confidence in the results despite the potential for considerable, uncontrolled variation in temperature and longer transportation periods. False negative results may be seen after 96 h in saline and viral loads will appear lower.",,doi:https://doi.org/10.1016/j.jviromet.2022.114607; doi:https://doi.org/10.1016/j.jviromet.2022.114607; html:https://europepmc.org/articles/PMC9374597; pdf:https://europepmc.org/articles/PMC9374597?pdf=render 33228632,https://doi.org/10.1186/s12920-020-00826-6,A random forest based biomarker discovery and power analysis framework for diagnostics research.,"Acharjee A, Larkman J, Xu Y, Cardoso VR, Gkoutos GV.",,BMC medical genomics,2020,2020-11-23,Y,Biomarker; Feature Selection; Random Forest; Power Study,,,"

Background

Biomarker identification is one of the major and important goal of functional genomics and translational medicine studies. Large scale -omics data are increasingly being accumulated and can provide vital means for the identification of biomarkers for the early diagnosis of complex disease and/or for advanced patient/diseases stratification. These tasks are clearly interlinked, and it is essential that an unbiased and stable methodology is applied in order to address them. Although, recently, many, primarily machine learning based, biomarker identification approaches have been developed, the exploration of potential associations between biomarker identification and the design of future experiments remains a challenge.

Methods

In this study, using both simulated and published experimentally derived datasets, we assessed the performance of several state-of-the-art Random Forest (RF) based decision approaches, namely the Boruta method, the permutation based feature selection without correction method, the permutation based feature selection with correction method, and the backward elimination based feature selection method. Moreover, we conducted a power analysis to estimate the number of samples required for potential future studies.

Results

We present a number of different RF based stable feature selection methods and compare their performances using simulated, as well as published, experimentally derived, datasets. Across all of the scenarios considered, we found the Boruta method to be the most stable methodology, whilst the Permutation (Raw) approach offered the largest number of relevant features, when allowed to stabilise over a number of iterations. Finally, we developed and made available a web interface ( https://joelarkman.shinyapps.io/PowerTools/ ) to streamline power calculations thereby aiding the design of potential future studies within a translational medicine context.

Conclusions

We developed a RF-based biomarker discovery framework and provide a web interface for our framework, termed PowerTools, that caters the design of appropriate and cost-effective subsequent future omics study.",,pdf:https://bmcmedgenomics.biomedcentral.com/track/pdf/10.1186/s12920-020-00826-6; doi:https://doi.org/10.1186/s12920-020-00826-6; html:https://europepmc.org/articles/PMC7685541; pdf:https://europepmc.org/articles/PMC7685541?pdf=render -37949372,https://doi.org/10.1016/j.jhin.2023.10.021,COVID-19-related mortality and hospital admissions in the VIVALDI study cohort: October 2020 to March 2023.,"Stirrup O, Krutikov M, Azmi B, Monakhov I, Hayward A, Copas A, Shallcross L.",,The Journal of hospital infection,2024,2023-11-08,Y,Care Homes; Covid-19; Sars-cov-2; Infection Fatality Ratio; Infection Hospitalization Ratio,,,"

Background

Long-term-care facilities (LTCFs) were heavily affected by COVID-19 early in the pandemic, but the impact of the virus has reduced over time with vaccination campaigns and build-up of immunity from prior infection.

Objectives

To evaluate the mortality and hospital admissions associated with SARS-CoV-2 in LTCFs in England over the course of the VIVALDI study, from October 2020 to March 2023.

Methods

We included residents aged ≥65 years from participating LTCFs who had available follow-up time within the analysis period. We calculated incidence rates (IRs) of COVID-19-linked mortality and hospital admissions per calendar quarter, along with infection fatality ratios (IFRs, within 28 days) and infection hospitalization ratios (IHRs, within 14 days) following positive SARS-CoV-2 test.

Results

A total of 26,286 residents were included, with at least one positive test for SARS-CoV-2 in 8513 (32.4%). The IR of COVID-19-related mortality peaked in the first quarter (Q1) of 2021 at 0.47 per 1000 person-days (1 kpd) (around a third of all deaths), in comparison with 0.10 per 1 kpd for Q1 2023 which had a similar IR of SARS-CoV-2 infections. There was a fall in observed IFR for SARS-CoV-2 infections from 24.9% to 6.7% between these periods, with a fall in IHR from 12.1% to 8.8%. The population had high overall IRs for mortality for each quarter evaluated, corresponding to annual mortality probability of 28.8-41.3%.

Conclusions

Standardized real-time monitoring of hospitalization and mortality following infection in LTCFs could inform policy on the need for non-pharmaceutical interventions to prevent transmission.",,pdf:http://www.journalofhospitalinfection.com/article/S0195670123003572/pdf; doi:https://doi.org/10.1016/j.jhin.2023.10.021; html:https://europepmc.org/articles/PMC10927615; pdf:https://europepmc.org/articles/PMC10927615?pdf=render 31469943,https://doi.org/10.1002/cnm.3255,Computational instantaneous wave-free ratio (IFR) for patient-specific coronary artery stenoses using 1D network models.,"Carson JM, Roobottom C, Alcock R, Nithiarasu P.",,International journal for numerical methods in biomedical engineering,2019,2019-11-01,Y,Coronary Arteries; Ffr; Ifr; Haemodynamic Modelling,,cardiovascular,"In this work, we estimate the diagnostic threshold of the instantaneous wave-free ratio (iFR) through the use of a one-dimensional haemodynamic framework. To this end, we first compared the computed fractional flow reserve (cFFR) predicted from a 1D computational framework with invasive clinical measurements. The framework shows excellent promise and utilises minimal patient data from a cohort of 52 patients with a total of 66 stenoses. The diagnostic accuracy of the cFFR model was 75.76%, with a sensitivity of 71.43%, a specificity of 77.78%, a positive predictive value of 60%, and a negative predictive value of 85.37%. The validated model was then used to estimate the diagnostic threshold of iFR. The model determined a quadratic relationship between cFFR and the ciFR. The iFR diagnostic threshold was determined to be 0.8910 from a receiver operating characteristic curve that is in the range of 0.89 to 0.9 that is normally reported in clinical studies.",This study aimed to measure how well an algorithm using data from non-invasive tests was able to predict early signs of heart disease.,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cnm.3255; doi:https://doi.org/10.1002/cnm.3255; html:https://europepmc.org/articles/PMC7003475; pdf:https://europepmc.org/articles/PMC7003475?pdf=render +37949372,https://doi.org/10.1016/j.jhin.2023.10.021,COVID-19-related mortality and hospital admissions in the VIVALDI study cohort: October 2020 to March 2023.,"Stirrup O, Krutikov M, Azmi B, Monakhov I, Hayward A, Copas A, Shallcross L.",,The Journal of hospital infection,2024,2023-11-08,Y,Care Homes; Covid-19; Sars-cov-2; Infection Fatality Ratio; Infection Hospitalization Ratio,,,"

Background

Long-term-care facilities (LTCFs) were heavily affected by COVID-19 early in the pandemic, but the impact of the virus has reduced over time with vaccination campaigns and build-up of immunity from prior infection.

Objectives

To evaluate the mortality and hospital admissions associated with SARS-CoV-2 in LTCFs in England over the course of the VIVALDI study, from October 2020 to March 2023.

Methods

We included residents aged ≥65 years from participating LTCFs who had available follow-up time within the analysis period. We calculated incidence rates (IRs) of COVID-19-linked mortality and hospital admissions per calendar quarter, along with infection fatality ratios (IFRs, within 28 days) and infection hospitalization ratios (IHRs, within 14 days) following positive SARS-CoV-2 test.

Results

A total of 26,286 residents were included, with at least one positive test for SARS-CoV-2 in 8513 (32.4%). The IR of COVID-19-related mortality peaked in the first quarter (Q1) of 2021 at 0.47 per 1000 person-days (1 kpd) (around a third of all deaths), in comparison with 0.10 per 1 kpd for Q1 2023 which had a similar IR of SARS-CoV-2 infections. There was a fall in observed IFR for SARS-CoV-2 infections from 24.9% to 6.7% between these periods, with a fall in IHR from 12.1% to 8.8%. The population had high overall IRs for mortality for each quarter evaluated, corresponding to annual mortality probability of 28.8-41.3%.

Conclusions

Standardized real-time monitoring of hospitalization and mortality following infection in LTCFs could inform policy on the need for non-pharmaceutical interventions to prevent transmission.",,pdf:http://www.journalofhospitalinfection.com/article/S0195670123003572/pdf; doi:https://doi.org/10.1016/j.jhin.2023.10.021; html:https://europepmc.org/articles/PMC10927615; pdf:https://europepmc.org/articles/PMC10927615?pdf=render 37120260,https://doi.org/10.1016/s2468-2667(23)00079-8,Changes in COVID-19-related mortality across key demographic and clinical subgroups in England from 2020 to 2022: a retrospective cohort study using the OpenSAFELY platform.,"Nab L, Parker EPK, Andrews CD, Hulme WJ, Fisher L, Morley J, Mehrkar A, MacKenna B, Inglesby P, Morton CE, Bacon SCJ, Hickman G, Evans D, Ward T, Smith RM, Davy S, Dillingham I, Maude S, Butler-Cole BFC, O'Dwyer T, Stables CL, Bridges L, Bates C, Cockburn J, Parry J, Hester F, Harper S, Zheng B, Williamson EJ, Eggo RM, Evans SJW, Goldacre B, Tomlinson LA, Walker AJ, OpenSAFELY Collaborative.",,The Lancet. Public health,2023,2023-05-01,Y,,,,"

Background

COVID-19 has been shown to differently affect various demographic and clinical population subgroups. We aimed to describe trends in absolute and relative COVID-19-related mortality risks across clinical and demographic population subgroups during successive SARS-CoV-2 pandemic waves.

Methods

We did a retrospective cohort study in England using the OpenSAFELY platform with the approval of National Health Service England, covering the first five SARS-CoV-2 pandemic waves (wave one [wild-type] from March 23 to May 30, 2020; wave two [alpha (B.1.1.7)] from Sept 7, 2020, to April 24, 2021; wave three [delta (B.1.617.2)] from May 28 to Dec 14, 2021; wave four [omicron (B.1.1.529)] from Dec 15, 2021, to April 29, 2022; and wave five [omicron] from June 24 to Aug 3, 2022). In each wave, we included people aged 18-110 years who were registered with a general practice on the first day of the wave and who had at least 3 months of continuous general practice registration up to this date. We estimated crude and sex-standardised and age-standardised wave-specific COVID-19-related death rates and relative risks of COVID-19-related death in population subgroups.

Findings

18 895 870 adults were included in wave one, 19 014 720 in wave two, 18 932 050 in wave three, 19 097 970 in wave four, and 19 226 475 in wave five. Crude COVID-19-related death rates per 1000 person-years decreased from 4·48 deaths (95% CI 4·41-4·55) in wave one to 2·69 (2·66-2·72) in wave two, 0·64 (0·63-0·66) in wave three, 1·01 (0·99-1·03) in wave four, and 0·67 (0·64-0·71) in wave five. In wave one, the standardised COVID-19-related death rates were highest in people aged 80 years or older, people with chronic kidney disease stage 5 or 4, people receiving dialysis, people with dementia or learning disability, and people who had received a kidney transplant (ranging from 19·85 deaths per 1000 person-years to 44·41 deaths per 1000 person-years, compared with from 0·05 deaths per 1000 person-years to 15·93 deaths per 1000 person-years in other subgroups). In wave two compared with wave one, in a largely unvaccinated population, the decrease in COVID-19-related mortality was evenly distributed across population subgroups. In wave three compared with wave one, larger decreases in COVID-19-related death rates were seen in groups prioritised for primary SARS-CoV-2 vaccination, including people aged 80 years or older and people with neurological disease, learning disability, or severe mental illness (90-91% decrease). Conversely, smaller decreases in COVID-19-related death rates were observed in younger age groups, people who had received organ transplants, and people with chronic kidney disease, haematological malignancies, or immunosuppressive conditions (0-25% decrease). In wave four compared with wave one, the decrease in COVID-19-related death rates was smaller in groups with lower vaccination coverage (including younger age groups) and conditions associated with impaired vaccine response, including people who had received organ transplants and people with immunosuppressive conditions (26-61% decrease).

Interpretation

There was a substantial decrease in absolute COVID-19-related death rates over time in the overall population, but demographic and clinical relative risk profiles persisted and worsened for people with lower vaccination coverage or impaired immune response. Our findings provide an evidence base to inform UK public health policy for protecting these vulnerable population subgroups.

Funding

UK Research and Innovation, Wellcome Trust, UK Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10139026; doi:https://doi.org/10.1016/S2468-2667(23)00079-8; html:https://europepmc.org/articles/PMC10139026; pdf:https://europepmc.org/articles/PMC10139026?pdf=render 36174228,https://doi.org/10.1093/ije/dyac189,Cohort Profile: Longitudinal population-based study of COVID-19 in UK adults (COVIDENCE UK).,"Holt H, Relton C, Talaei M, Symons J, Davies MR, Jolliffe DA, Vivaldi G, Tydeman F, Williamson AE, Pfeffer PE, Orton C, Ford DV, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Breen G, Shaheen SO, Martineau AR.",,International journal of epidemiology,2023,2023-02-01,N,,,,,,pdf:https://academic.oup.com/ije/article-pdf/52/1/e46/49127271/dyac189.pdf; doi:https://doi.org/10.1093/ije/dyac189; html:https://europepmc.org/articles/PMC9620716; pdf:https://europepmc.org/articles/PMC9620716?pdf=render; doi:https://doi.org/10.1093/ije/dyac189 35502909,https://doi.org/10.1177/01410768221095239,Impact on emergency and elective hospital-based care in Scotland over the first 12 months of the pandemic: interrupted time-series analysis of national lockdowns.,"Shah SA, Mulholland RH, Wilkinson S, Katikireddi SV, Pan J, Shi T, Kerr S, Agrawal U, Rudan I, Simpson CR, Stock SJ, Macleod J, Murray JL, McCowan C, Ritchie L, Woolhouse M, Sheikh A.",,Journal of the Royal Society of Medicine,2022,2022-05-03,Y,Public Health; Statistics And Research Methods; Population Trends,,,"

Objectives

COVID-19 has resulted in the greatest disruption to National Health Service (NHS) care in its over 70-year history. Building on our previous work, we assessed the ongoing impact of pandemic-related disruption on provision of emergency and elective hospital-based care across Scotland over the first year of the pandemic.

Design

We undertook interrupted time-series analyses to evaluate the impact of ongoing pandemic-related disruption on hospital NHS care provision at national level and across demographics and clinical specialties spanning the period 29 March 2020-28 March 2021.

Setting

Scotland, UK.

Participants

Patients receiving hospital care from NHS Scotland.

Main outcome measures

We used the percentage change of accident and emergency attendances, and emergency and planned hospital admissions during the pandemic compared to the average admission rate for equivalent weeks in 2018-2019.

Results

As restrictions were gradually lifted in Scotland after the first lockdown, hospital-based admissions increased approaching pre-pandemic levels. Subsequent tightening of restrictions in September 2020 were associated with a change in slope of relative weekly admissions rate: -1.98% (-2.38, -1.58) in accident and emergency attendance, -1.36% (-1.68, -1.04) in emergency admissions and -2.31% (-2.95, -1.66) in planned admissions. A similar pattern was seen across sex, socioeconomic status and most age groups, except children (0-14 years) where accident and emergency attendance, and emergency admissions were persistently low over the study period.

Conclusions

We found substantial disruption to urgent and planned inpatient healthcare provision in hospitals across NHS Scotland. There is the need for urgent policy responses to address continuing unmet health needs and to ensure resilience in the context of future pandemics.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/01410768221095239; doi:https://doi.org/10.1177/01410768221095239; html:https://europepmc.org/articles/PMC9723811; pdf:https://europepmc.org/articles/PMC9723811?pdf=render 35290489,https://doi.org/10.1007/s00247-021-05266-7,Dynamic susceptibility-contrast magnetic resonance imaging with contrast agent leakage correction aids in predicting grade in pediatric brain tumours: a multicenter study.,"Withey SB, MacPherson L, Oates A, Powell S, Novak J, Abernethy L, Pizer B, Grundy R, Morgan PS, Bailey S, Mitra D, Arvanitis TN, Auer DP, Avula S, Peet AC.",,Pediatric radiology,2022,2022-03-15,Y,Brain; Tumor; Children; Perfusion; Magnetic Resonance Imaging; Blood volume; Multicenter; Leakage Correction; Dynamic Susceptibility-contrast Magnetic Resonance Imaging,,,"

Background

Relative cerebral blood volume (rCBV) measured using dynamic susceptibility-contrast MRI can differentiate between low- and high-grade pediatric brain tumors. Multicenter studies are required for translation into clinical practice.

Objective

We compared leakage-corrected dynamic susceptibility-contrast MRI perfusion parameters acquired at multiple centers in low- and high-grade pediatric brain tumors.

Materials and methods

Eighty-five pediatric patients underwent pre-treatment dynamic susceptibility-contrast MRI scans at four centers. MRI protocols were variable. We analyzed data using the Boxerman leakage-correction method producing pixel-by-pixel estimates of leakage-uncorrected (rCBVuncorr) and corrected (rCBVcorr) relative cerebral blood volume, and the leakage parameter, K2. Histological diagnoses were obtained. Tumors were classified by high-grade tumor. We compared whole-tumor median perfusion parameters between low- and high-grade tumors and across tumor types.

Results

Forty tumors were classified as low grade, 45 as high grade. Mean whole-tumor median rCBVuncorr was higher in high-grade tumors than low-grade tumors (mean ± standard deviation [SD] = 2.37±2.61 vs. -0.14±5.55; P<0.01). Average median rCBV increased following leakage correction (2.54±1.63 vs. 1.68±1.36; P=0.010), remaining higher in high-grade tumors than low grade-tumors. Low-grade tumors, particularly pilocytic astrocytomas, showed T1-dominant leakage effects; high-grade tumors showed T2*-dominance (mean K2=0.017±0.049 vs. 0.002±0.017). Parameters varied with tumor type but not center. Median rCBVuncorr was higher (mean = 1.49 vs. 0.49; P=0.015) and K2 lower (mean = 0.005 vs. 0.016; P=0.013) in children who received a pre-bolus of contrast agent compared to those who did not. Leakage correction removed the difference.

Conclusion

Dynamic susceptibility-contrast MRI acquired at multiple centers helped distinguish between children's brain tumors. Relative cerebral blood volume was significantly higher in high-grade compared to low-grade tumors and differed among common tumor types. Vessel leakage correction is required to provide accurate rCBV, particularly in low-grade enhancing tumors.",,pdf:https://link.springer.com/content/pdf/10.1007/s00247-021-05266-7.pdf; doi:https://doi.org/10.1007/s00247-021-05266-7; html:https://europepmc.org/articles/PMC9107460; pdf:https://europepmc.org/articles/PMC9107460?pdf=render 35913410,https://doi.org/10.1093/cid/ciac629,Validity of Self-testing at Home With Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Detection by Lateral Flow Immunoassay.,"Atchison CJ, Moshe M, Brown JC, Whitaker M, Wong NCK, Bharath AA, McKendry RA, Darzi A, Ashby D, Donnelly CA, Riley S, Elliott P, Barclay WS, Cooke GS, Ward H.",,Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,2023,2023-02-01,Y,Antibodies; Lateral Flow Immunoassay; Home-testing; Covid-19; Sars-cov-2,,,"

Background

We explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow immunoassay (LFIA) performance under field conditions compared to laboratory-based electrochemiluminescence immunoassay (ECLIA) and live virus neutralization.

Methods

In July 2021, 3758 participants performed, at home, a self-administered Fortress LFIA on finger-prick blood, reported and submitted a photograph of the result, and provided a self-collected capillary blood sample for assessment of immunoglobulin G (IgG) antibodies using the Roche Elecsys® Anti-SARS-CoV-2 ECLIA. We compared the self-reported LFIA result to the quantitative ECLIA and checked the reading of the LFIA result with an automated image analysis (ALFA). In a subsample of 250 participants, we compared the results to live virus neutralization.

Results

Almost all participants (3593/3758, 95.6%) had been vaccinated or reported prior infection. Overall, 2777/3758 (73.9%) were positive on self-reported LFIA, 2811/3457 (81.3%) positive by LFIA when ALFA-reported, and 3622/3758 (96.4%) positive on ECLIA (using the manufacturer reference standard threshold for positivity of 0.8 U mL-1). Live virus neutralization was detected in 169 of 250 randomly selected samples (67.6%); 133/169 were positive with self-reported LFIA (sensitivity 78.7%; 95% confidence interval [CI]: 71.8, 84.6), 142/155 (91.6%; 95% CI: 86.1, 95.5) with ALFA, and 169 (100%; 95% CI: 97.8, 100.0) with ECLIA. There were 81 samples with no detectable virus neutralization; 47/81 were negative with self-reported LFIA (specificity 58.0%; 95% CI: 46.5, 68.9), 34/75 (45.3%; 95% CI: 33.8, 57.3) with ALFA, and 0/81 (0%; 95% CI: 0, 4.5) with ECLIA.

Conclusions

Self-administered LFIA is less sensitive than a quantitative antibody test, but the positivity in LFIA correlates better than the quantitative ECLIA with virus neutralization.",,doi:https://doi.org/10.1093/cid/ciac629; doi:https://doi.org/10.1093/cid/ciac629; html:https://europepmc.org/articles/PMC9384551; pdf:https://europepmc.org/articles/PMC9384551?pdf=render 32634370,https://doi.org/10.1098/rsob.200121,Core regulatory circuitries in defining cancer cell identity across the malignant spectrum.,"Jahangiri L, Tsaprouni L, Trigg RM, Williams JA, Gkoutos GV, Turner SD, Pereira J.",,Open biology,2020,2020-07-08,Y,Cell Identity; Super-enhancers; Core Regulatory Circuitry; Liquid And Solid Cancers,,,"Gene expression programmes driving cell identity are established by tightly regulated transcription factors that auto- and cross-regulate in a feed-forward manner, forming core regulatory circuitries (CRCs). CRC transcription factors create and engage super-enhancers by recruiting acetylation writers depositing permissive H3K27ac chromatin marks. These super-enhancers are largely associated with BET proteins, including BRD4, that influence higher-order chromatin structure. The orchestration of these events triggers accessibility of RNA polymerase machinery and the imposition of lineage-specific gene expression. In cancers, CRCs drive cell identity by superimposing developmental programmes on a background of genetic alterations. Further, the establishment and maintenance of oncogenic states are reliant on CRCs that drive factors involved in tumour development. Hence, the molecular dissection of CRC components driving cell identity and cancer state can contribute to elucidating mechanisms of diversion from pre-determined developmental programmes and highlight cancer dependencies. These insights can provide valuable opportunities for identifying and re-purposing drug targets. In this article, we review the current understanding of CRCs across solid and liquid malignancies and avenues of investigation for drug development efforts. We also review techniques used to understand CRCs and elaborate the indication of discussed CRC transcription factors in the wider context of cancer CRC models.",,pdf:https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.200121; doi:https://doi.org/10.1098/rsob.200121; html:https://europepmc.org/articles/PMC7574545; pdf:https://europepmc.org/articles/PMC7574545?pdf=render -37147628,https://doi.org/10.1186/s12911-023-02181-9,Ontology-driven and weakly supervised rare disease identification from clinical notes.,"Dong H, Suárez-Paniagua V, Zhang H, Wang M, Casey A, Davidson E, Chen J, Alex B, Whiteley W, Wu H.",,BMC medical informatics and decision making,2023,2023-05-05,Y,Phenotyping; Natural Language Processing; Rare Diseases; Ontology Matching; Clinical Notes; Weak Supervision,,,"

Background

Computational text phenotyping is the practice of identifying patients with certain disorders and traits from clinical notes. Rare diseases are challenging to be identified due to few cases available for machine learning and the need for data annotation from domain experts.

Methods

We propose a method using ontologies and weak supervision, with recent pre-trained contextual representations from Bi-directional Transformers (e.g. BERT). The ontology-driven framework includes two steps: (i) Text-to-UMLS, extracting phenotypes by contextually linking mentions to concepts in Unified Medical Language System (UMLS), with a Named Entity Recognition and Linking (NER+L) tool, SemEHR, and weak supervision with customised rules and contextual mention representation; (ii) UMLS-to-ORDO, matching UMLS concepts to rare diseases in Orphanet Rare Disease Ontology (ORDO). The weakly supervised approach is proposed to learn a phenotype confirmation model to improve Text-to-UMLS linking, without annotated data from domain experts. We evaluated the approach on three clinical datasets, MIMIC-III discharge summaries, MIMIC-III radiology reports, and NHS Tayside brain imaging reports from two institutions in the US and the UK, with annotations.

Results

The improvements in the precision were pronounced (by over 30% to 50% absolute score for Text-to-UMLS linking), with almost no loss of recall compared to the existing NER+L tool, SemEHR. Results on radiology reports from MIMIC-III and NHS Tayside were consistent with the discharge summaries. The overall pipeline processing clinical notes can extract rare disease cases, mostly uncaptured in structured data (manually assigned ICD codes).

Conclusion

The study provides empirical evidence for the task by applying a weakly supervised NLP pipeline on clinical notes. The proposed weak supervised deep learning approach requires no human annotation except for validation and testing, by leveraging ontologies, NER+L tools, and contextual representations. The study also demonstrates that Natural Language Processing (NLP) can complement traditional ICD-based approaches to better estimate rare diseases in clinical notes. We discuss the usefulness and limitations of the weak supervision approach and propose directions for future studies.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-023-02181-9; doi:https://doi.org/10.1186/s12911-023-02181-9; html:https://europepmc.org/articles/PMC10162001; pdf:https://europepmc.org/articles/PMC10162001?pdf=render 35354646,https://doi.org/10.1136/thoraxjnl-2021-218629,Relationship between asthma and severe COVID-19: a national cohort study.,"Dolby T, Nafilyan V, Morgan A, Kallis C, Sheikh A, Quint JK.",,Thorax,2023,2022-03-30,Y,Asthma; Covid-19,,,"

Background

We aimed to determine whether children and adults with poorly controlled or more severe asthma have greater risk of hospitalisation and/or death from COVID-19.

Methods

We used individual-level data from the Office for National Statistics Public Health Data Asset, based on the 2011 census in England, and the General Practice Extraction Service data for pandemic planning and research linked to death registration records and Hospital Episode Statistics admission data. Adults were followed from 1 January 2020 to 30 September 2021 for hospitalisation or death from COVID-19. For children, only hospitalisation was included.

Results

Our cohort comprised 35 202 533 adults and 2 996 503 children aged 12-17 years. After controlling for sociodemographic factors, pre-existing health conditions and vaccine status, the risk of death involving COVID-19 for adults with asthma prescribed low dose inhaled corticosteroids (ICS) was not significantly different from those without asthma. Adults with asthma prescribed medium and high dosage ICS had an elevated risk of COVID-19 death; HRs 1.18 (95% CI 1.14 to 1.23) and 1.36 (95% CI 1.28 to 1.44), respectively. A similar pattern was observed for COVID-19 hospitalisation; fully adjusted HRs 1.53 (95% CI 1.50 to 1.56) and 1.52 (95% CI 1.46 to 1.56) for adults with asthma prescribed medium and high-dosage ICS, respectively. Risk of hospitalisation was greater for children with asthma prescribed one (2.58 (95% CI 1.82 to 3.66)) or two or more (3.80 (95% CI 2.41 to 5.95)) courses of oral corticosteroids in the year prior to the pandemic.

Discussion

People with mild and/or well-controlled asthma are neither at significantly increased risk of hospitalisation with nor more likely to die from COVID-19 than adults without asthma.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/03/29/thoraxjnl-2021-218629.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2021-218629; html:https://europepmc.org/articles/PMC8983409; pdf:https://europepmc.org/articles/PMC8983409?pdf=render +37147628,https://doi.org/10.1186/s12911-023-02181-9,Ontology-driven and weakly supervised rare disease identification from clinical notes.,"Dong H, Suárez-Paniagua V, Zhang H, Wang M, Casey A, Davidson E, Chen J, Alex B, Whiteley W, Wu H.",,BMC medical informatics and decision making,2023,2023-05-05,Y,Phenotyping; Natural Language Processing; Rare Diseases; Ontology Matching; Clinical Notes; Weak Supervision,,,"

Background

Computational text phenotyping is the practice of identifying patients with certain disorders and traits from clinical notes. Rare diseases are challenging to be identified due to few cases available for machine learning and the need for data annotation from domain experts.

Methods

We propose a method using ontologies and weak supervision, with recent pre-trained contextual representations from Bi-directional Transformers (e.g. BERT). The ontology-driven framework includes two steps: (i) Text-to-UMLS, extracting phenotypes by contextually linking mentions to concepts in Unified Medical Language System (UMLS), with a Named Entity Recognition and Linking (NER+L) tool, SemEHR, and weak supervision with customised rules and contextual mention representation; (ii) UMLS-to-ORDO, matching UMLS concepts to rare diseases in Orphanet Rare Disease Ontology (ORDO). The weakly supervised approach is proposed to learn a phenotype confirmation model to improve Text-to-UMLS linking, without annotated data from domain experts. We evaluated the approach on three clinical datasets, MIMIC-III discharge summaries, MIMIC-III radiology reports, and NHS Tayside brain imaging reports from two institutions in the US and the UK, with annotations.

Results

The improvements in the precision were pronounced (by over 30% to 50% absolute score for Text-to-UMLS linking), with almost no loss of recall compared to the existing NER+L tool, SemEHR. Results on radiology reports from MIMIC-III and NHS Tayside were consistent with the discharge summaries. The overall pipeline processing clinical notes can extract rare disease cases, mostly uncaptured in structured data (manually assigned ICD codes).

Conclusion

The study provides empirical evidence for the task by applying a weakly supervised NLP pipeline on clinical notes. The proposed weak supervised deep learning approach requires no human annotation except for validation and testing, by leveraging ontologies, NER+L tools, and contextual representations. The study also demonstrates that Natural Language Processing (NLP) can complement traditional ICD-based approaches to better estimate rare diseases in clinical notes. We discuss the usefulness and limitations of the weak supervision approach and propose directions for future studies.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-023-02181-9; doi:https://doi.org/10.1186/s12911-023-02181-9; html:https://europepmc.org/articles/PMC10162001; pdf:https://europepmc.org/articles/PMC10162001?pdf=render 33683514,https://doi.org/10.1007/s10237-021-01437-5,A framework for incorporating 3D hyperelastic vascular wall models in 1D blood flow simulations.,"Coccarelli A, Carson JM, Aggarwal A, Pant S.",,Biomechanics and modeling in mechanobiology,2021,2021-03-08,Y,Pulse wave velocity; Common carotid artery; Hyperelasticity; Tube Law; Axial Stretching; One-dimensional Blood Flow Modelling,,,"We present a novel framework for investigating the role of vascular structure on arterial haemodynamics in large vessels, with a special focus on the human common carotid artery (CCA). The analysis is carried out by adopting a three-dimensional (3D) derived, fibre-reinforced, hyperelastic structural model, which is coupled with an axisymmetric, reduced order model describing blood flow. The vessel transmural pressure and lumen area are related via a Holzapfel-Ogden type of law, and the residual stresses along the thickness and length of the vessel are also accounted for. After a structural characterization of the adopted hyperelastic model, we investigate the link underlying the vascular wall response and blood-flow dynamics by comparing the proposed framework results against a popular tube law. The comparison shows that the behaviour of the model can be captured by the simpler linear surrogate only if a representative value of compliance is applied. Sobol's multi-variable sensitivity analysis is then carried out in order to identify the extent to which the structural parameters have an impact on the CCA haemodynamics. In this case, the local pulse wave velocity (PWV) is used as index for representing the arterial transmission capacity of blood pressure waveforms. The sensitivity analysis suggests that some geometrical factors, such as the stress-free inner radius and opening angle, play a major role on the system's haemodynamics. Subsequently, we quantified the differences in haemodynamic variables obtained from different virtual CCAs, tube laws and flow conditions. Although each artery presents a distinct vascular response, the differences obtained across different flow regimes are not significant. As expected, the linear tube law is unable to accurately capture all the haemodynamic features characterizing the current model. The findings from the sensitivity analysis are further confirmed by investigating the axial stretching effect on the CCA fluid dynamics. This factor does not seem to alter the pressure and flow waveforms. On the contrary, it is shown that, for an axially stretched vessel, the vascular wall exhibits an attenuation in absolute distension and an increase in circumferential stress, corroborating the findings of previous studies. This analysis shows that the new model offers a good balance between computational complexity and physics captured, making it an ideal framework for studies aiming to investigate the profound link between vascular mechanobiology and blood flow.",,pdf:https://link.springer.com/content/pdf/10.1007/s10237-021-01437-5.pdf; doi:https://doi.org/10.1007/s10237-021-01437-5; html:https://europepmc.org/articles/PMC8298378; pdf:https://europepmc.org/articles/PMC8298378?pdf=render 34697502,https://doi.org/10.1038/s41591-021-01556-7,Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection.,"Patone M, Handunnetthi L, Saatci D, Pan J, Katikireddi SV, Razvi S, Hunt D, Mei XW, Dixon S, Zaccardi F, Khunti K, Watkinson P, Coupland CAC, Doidge J, Harrison DA, Ravanan R, Sheikh A, Robertson C, Hippisley-Cox J.",,Nature medicine,2021,2021-10-25,Y,,,,"Emerging reports of rare neurological complications associated with COVID-19 infection and vaccinations are leading to regulatory, clinical and public health concerns. We undertook a self-controlled case series study to investigate hospital admissions from neurological complications in the 28 days after a first dose of ChAdOx1nCoV-19 (n = 20,417,752) or BNT162b2 (n = 12,134,782), and after a SARS-CoV-2-positive test (n = 2,005,280). There was an increased risk of Guillain-Barré syndrome (incidence rate ratio (IRR), 2.90; 95% confidence interval (CI): 2.15-3.92 at 15-21 days after vaccination) and Bell's palsy (IRR, 1.29; 95% CI: 1.08-1.56 at 15-21 days) with ChAdOx1nCoV-19. There was an increased risk of hemorrhagic stroke (IRR, 1.38; 95% CI: 1.12-1.71 at 15-21 days) with BNT162b2. An independent Scottish cohort provided further support for the association between ChAdOx1nCoV and Guillain-Barré syndrome (IRR, 2.32; 95% CI: 1.08-5.02 at 1-28 days). There was a substantially higher risk of all neurological outcomes in the 28 days after a positive SARS-CoV-2 test including Guillain-Barré syndrome (IRR, 5.25; 95% CI: 3.00-9.18). Overall, we estimated 38 excess cases of Guillain-Barré syndrome per 10 million people receiving ChAdOx1nCoV-19 and 145 excess cases per 10 million people after a positive SARS-CoV-2 test. In summary, although we find an increased risk of neurological complications in those who received COVID-19 vaccines, the risk of these complications is greater following a positive SARS-CoV-2 test.",,pdf:https://www.nature.com/articles/s41591-021-01556-7.pdf; doi:https://doi.org/10.1038/s41591-021-01556-7; html:https://europepmc.org/articles/PMC8629105; pdf:https://europepmc.org/articles/PMC8629105?pdf=render 32935051,https://doi.org/10.23889/ijpds.v5i1.1128,A national initiative in data science for health: an evaluation of the UK Farr Institute.,"Hemingway H, Lyons R, Li Q, Buchan I, Ainsworth J, Pell J, Morris A.",,International journal of population data science,2020,2020-04-08,Y,,,,"

Objective

To evaluate the extent to which the inter-institutional, inter-disciplinary mobilisation of data and skills in the Farr Institute contributed to establishing the emerging field of data science for health in the UK.

Design and outcome measures

We evaluated evidence of six domains characterising a new field of science:defining central scientific challenges,demonstrating how the central challenges might be solved,creating novel interactions among groups of scientists,training new types of experts,re-organising universities,demonstrating impacts in society.We carried out citation, network and time trend analyses of publications, and a narrative review of infrastructure, methods and tools.

Setting

Four UK centres in London, North England, Scotland and Wales (23 university partners), 2013-2018.

Results

1. The Farr Institute helped define a central scientific challenge publishing a research corpus, demonstrating insights from electronic health record (EHR) and administrative data at each stage of the translational cycle in 593 papers with at least one Farr Institute author affiliation on PubMed. 2. The Farr Institute offered some demonstrations of how these scientific challenges might be solved: it established the first four ISO27001 certified trusted research environments in the UK, and approved more than 1000 research users, published on 102 unique EHR and administrative data sources, although there was no clear evidence of an increase in novel, sustained record linkages. The Farr Institute established open platforms for the EHR phenotyping algorithms and validations (>70 diseases, CALIBER). Sample sizes showed some evidence of increase but remained less than 10% of the UK population in primary care-hospital care linked studies. 3.The Farr Institute created novel interactions among researchers: the co-author publication network expanded from 944 unique co-authors (based on 67 publications in the first 30 months) to 3839 unique co-authors (545 papers in the final 30 months). 4. Training expanded substantially with 3 new masters courses, training >400 people at masters, short-course and leadership level and 48 PhD students. 5. Universities reorganised with 4/5 Centres established 27 new faculty (tenured) positions, 3 new university institutes. 6. Emerging evidence of impacts included: > 3200 citations for the 10 most cited papers and Farr research informed eight practice-changing clinical guidelines and policies relevant to the health of millions of UK citizens.

Conclusion

The Farr Institute played a major role in establishing and growing the field of data science for health in the UK, with some initial evidence of benefits for health and healthcare. The Farr Institute has now expanded into Health Data Research (HDR) UK but key challenges remain including, how to network such activities internationally.",,pdf:https://ijpds.org/article/download/1128/2865; doi:https://doi.org/10.23889/ijpds.v5i1.1128; html:https://europepmc.org/articles/PMC7480324; pdf:https://europepmc.org/articles/PMC7480324?pdf=render @@ -333,10 +333,10 @@ PMC10929454,https://doi.org/,Optimising data curation pipelines for population-l 37561812,https://doi.org/10.1371/journal.pcbi.1011368,Call detail record aggregation methodology impacts infectious disease models informed by human mobility.,"Gibbs H, Musah A, Seidu O, Ampofo W, Asiedu-Bekoe F, Gray J, Adewole WA, Cheshire J, Marks M, Eggo RM.",,PLoS computational biology,2023,2023-08-10,Y,,,,"This paper demonstrates how two different methods used to calculate population-level mobility from Call Detail Records (CDR) produce varying predictions of the spread of epidemics informed by these data. Our findings are based on one CDR dataset describing inter-district movement in Ghana in 2021, produced using two different aggregation methodologies. One methodology, ""all pairs,"" is designed to retain long distance network connections while the other, ""sequential"" methodology is designed to accurately reflect the volume of travel between locations. We show how the choice of methodology feeds through models of human mobility to the predictions of a metapopulation SEIR model of disease transmission. We also show that this impact varies depending on the location of pathogen introduction and the transmissibility of infections. For central locations or highly transmissible diseases, we do not observe significant differences between aggregation methodologies on the predicted spread of disease. For less transmissible diseases or those introduced into remote locations, we find that the choice of aggregation methodology influences the speed of spatial spread as well as the size of the peak number of infections in individual districts. Our findings can help researchers and users of epidemiological models to understand how methodological choices at the level of model inputs may influence the results of models of infectious disease transmission, as well as the circumstances in which these choices do not alter model predictions.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1011368&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1011368; html:https://europepmc.org/articles/PMC10443843; pdf:https://europepmc.org/articles/PMC10443843?pdf=render 35473737,https://doi.org/10.1136/bmjopen-2021-060413,"Therapies for Long COVID in non-hospitalised individuals: from symptoms, patient-reported outcomes and immunology to targeted therapies (The TLC Study).","Haroon S, Nirantharakumar K, Hughes SE, Subramanian A, Aiyegbusi OL, Davies EH, Myles P, Williams T, Turner G, Chandan JS, McMullan C, Lord J, Wraith DC, McGee K, Denniston AK, Taverner T, Jackson LJ, Sapey E, Gkoutos G, Gokhale K, Leggett E, Iles C, Frost C, McNamara G, Bamford A, Marshall T, Zemedikun DT, Price G, Marwaha S, Simms-Williams N, Brown K, Walker A, Jones K, Matthews K, Camaradou J, Saint-Cricq M, Kumar S, Alder Y, Stanton DE, Agyen L, Baber M, Blaize H, Calvert M.",,BMJ open,2022,2022-04-26,Y,Therapeutics; immunology; Public Health; Covid-19,,,"

Introduction

Individuals with COVID-19 frequently experience symptoms and impaired quality of life beyond 4-12 weeks, commonly referred to as Long COVID. Whether Long COVID is one or several distinct syndromes is unknown. Establishing the evidence base for appropriate therapies is needed. We aim to evaluate the symptom burden and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals and evaluate potential therapies.

Methods and analysis

A cohort of 4000 non-hospitalised individuals with a past COVID-19 diagnosis and 1000 matched controls will be selected from anonymised primary care records from the Clinical Practice Research Datalink, and invited by their general practitioners to participate on a digital platform (Atom5). Individuals will report symptoms, quality of life, work capability and patient-reported outcome measures. Data will be collected monthly for 1 year.Statistical clustering methods will be used to identify distinct Long COVID-19 symptom clusters. Individuals from the four most prevalent clusters and two control groups will be invited to participate in the BioWear substudy which will further phenotype Long COVID symptom clusters by measurement of immunological parameters and actigraphy.We will review existing evidence on interventions for postviral syndromes and Long COVID to map and prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulative evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers for future evaluation.Individuals with lived experience of Long COVID will be involved throughout this programme through a patient and public involvement group.

Ethics and dissemination

Ethical approval was obtained from the Solihull Research Ethics Committee, West Midlands (21/WM/0203). Research findings will be presented at international conferences, in peer-reviewed journals, to Long COVID patient support groups and to policymakers.

Trial registration number

1567490.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e060413.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-060413; html:https://europepmc.org/articles/PMC9044550; pdf:https://europepmc.org/articles/PMC9044550?pdf=render 34445233,https://doi.org/10.3390/ijms22168527,The Contribution of Autophagy and LncRNAs to MYC-Driven Gene Regulatory Networks in Cancers.,"Jahangiri L, Pucci P, Ishola T, Trigg RM, Williams JA, Pereira J, Cavanagh ML, Turner SD, Gkoutos GV, Tsaprouni L.",,International journal of molecular sciences,2021,2021-08-08,Y,MYC; Autophagy; Lncrnas; Gene Regulatory Networks (Grns),,,"MYC is a target of the Wnt signalling pathway and governs numerous cellular and developmental programmes hijacked in cancers. The amplification of MYC is a frequently occurring genetic alteration in cancer genomes, and this transcription factor is implicated in metabolic reprogramming, cell death, and angiogenesis in cancers. In this review, we analyse MYC gene networks in solid cancers. We investigate the interaction of MYC with long non-coding RNAs (lncRNAs). Furthermore, we investigate the role of MYC regulatory networks in inducing changes to cellular processes, including autophagy and mitophagy. Finally, we review the interaction and mutual regulation between MYC and lncRNAs, and autophagic processes and analyse these networks as unexplored areas of targeting and manipulation for therapeutic gain in MYC-driven malignancies.",,pdf:https://www.mdpi.com/1422-0067/22/16/8527/pdf?version=1628431894; doi:https://doi.org/10.3390/ijms22168527; html:https://europepmc.org/articles/PMC8395220; pdf:https://europepmc.org/articles/PMC8395220?pdf=render -34829865,https://doi.org/10.3390/biomedicines9111636,Machine Learning-Based Identification of Potentially Novel Non-Alcoholic Fatty Liver Disease Biomarkers.,"Shafiha R, Bahcivanci B, Gkoutos GV, Acharjee A.",,Biomedicines,2021,2021-11-07,Y,Biomarker; Machine Learning; Lipidomics; Transcriptomics; Nafld,,,"Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that presents a great challenge for treatment and prevention.. This study aims to implement a machine learning approach that employs such datasets to identify potential biomarker targets. We developed a pipeline to identify potential biomarkers for NAFLD that includes five major processes, namely, a pre-processing step, a feature selection and a generation of a random forest model and, finally, a downstream feature analysis and a provision of a potential biological interpretation. The pre-processing step includes data normalising and variable extraction accompanied by appropriate annotations. A feature selection based on a differential gene expression analysis is then conducted to identify significant features and then employ them to generate a random forest model whose performance is assessed based on a receiver operating characteristic curve. Next, the features are subjected to a downstream analysis, such as univariate analysis, a pathway enrichment analysis, a network analysis and a generation of correlation plots, boxplots and heatmaps. Once the results are obtained, the biological interpretation and the literature validation is conducted over the identified features and results. We applied this pipeline to transcriptomics and lipidomic datasets and concluded that the C4BPA gene could play a role in the development of NAFLD. The activation of the complement pathway, due to the downregulation of the C4BPA gene, leads to an increase in triglyceride content, which might further render the lipid metabolism. This approach identified the C4BPA gene, an inhibitor of the complement pathway, as a potential biomarker for the development of NAFLD.",,pdf:https://www.mdpi.com/2227-9059/9/11/1636/pdf?version=1637024773; doi:https://doi.org/10.3390/biomedicines9111636; html:https://europepmc.org/articles/PMC8615894; pdf:https://europepmc.org/articles/PMC8615894?pdf=render 35165107,https://doi.org/10.1136/bmjopen-2021-050062,"Investigating the uptake, effectiveness and safety of COVID-19 vaccines: protocol for an observational study using linked UK national data.","Vasileiou E, Shi T, Kerr S, Robertson C, Joy M, Tsang R, McGagh D, Williams J, Hobbs R, de Lusignan S, de Lusignan S, Bradley D, OReilly D, Murphy S, Chuter A, Beggs J, Ford D, Orton C, Akbari A, Bedston S, Davies G, Griffiths LJ, Griffiths R, Lowthian E, Lyons J, Lyons RA, North L, Perry M, Torabi F, Pickett J, McMenamin J, McCowan C, Agrawal U, Wood R, Stock SJ, Moore E, Henery P, Simpson CR, Sheikh A.",,BMJ open,2022,2022-02-14,Y,epidemiology; Public Health; Respiratory Infections; Covid-19,,,"

Introduction

The novel coronavirus SARS-CoV-2, which emerged in December 2019, has caused millions of deaths and severe illness worldwide. Numerous vaccines are currently under development of which a few have now been authorised for population-level administration by several countries. As of 20 September 2021, over 48 million people have received their first vaccine dose and over 44 million people have received their second vaccine dose across the UK. We aim to assess the uptake rates, effectiveness, and safety of all currently approved COVID-19 vaccines in the UK.

Methods and analysis

We will use prospective cohort study designs to assess vaccine uptake, effectiveness and safety against clinical outcomes and deaths. Test-negative case-control study design will be used to assess vaccine effectiveness (VE) against laboratory confirmed SARS-CoV-2 infection. Self-controlled case series and retrospective cohort study designs will be carried out to assess vaccine safety against mild-to-moderate and severe adverse events, respectively. Individual-level pseudonymised data from primary care, secondary care, laboratory test and death records will be linked and analysed in secure research environments in each UK nation. Univariate and multivariate logistic regression models will be carried out to estimate vaccine uptake levels in relation to various population characteristics. VE estimates against laboratory confirmed SARS-CoV-2 infection will be generated using a generalised additive logistic model. Time-dependent Cox models will be used to estimate the VE against clinical outcomes and deaths. The safety of the vaccines will be assessed using logistic regression models with an offset for the length of the risk period. Where possible, data will be meta-analysed across the UK nations.

Ethics and dissemination

We obtained approvals from the National Research Ethics Service Committee, Southeast Scotland 02 (12/SS/0201), the Secure Anonymised Information Linkage independent Information Governance Review Panel project number 0911. Concerning English data, University of Oxford is compliant with the General Data Protection Regulation and the National Health Service (NHS) Digital Data Security and Protection Policy. This is an approved study (Integrated Research Application ID 301740, Health Research Authority (HRA) Research Ethics Committee 21/HRA/2786). The Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub meets NHS Digital's Data Security and Protection Toolkit requirements. In Northern Ireland, the project was approved by the Honest Broker Governance Board, project number 0064. Findings will be made available to national policy-makers, presented at conferences and published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e050062.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-050062; html:https://europepmc.org/articles/PMC8844955; pdf:https://europepmc.org/articles/PMC8844955?pdf=render -37463814,https://doi.org/10.1136/bmjopen-2022-069635,HbA1c recording in patients following a first diagnosis of serious mental illness: the South London and Maudsley Biomedical Research Centre case register.,"Bell N, Perera G, Chandran D, Stubbs B, Gaughran F, Stewart R.",,BMJ open,2023,2023-07-18,Y,Psychiatry; Mental health; epidemiology; Health Informatics; General Diabetes; Quality In Health Care,,,"

Objectives

To investigate factors associated with the recording of glycated haemoglobin (HbA1c) in people with first diagnoses of serious mental illness (SMI) in a large mental healthcare provider, and factors associated with HbA1c levels, when recorded. To our knowledge this is the first such investigation, although attention to dysglycaemia in SMI is an increasing priority in mental healthcare.

Design

The study was primarily descriptive in nature, seeking to ascertain the frequency of HbA1c recording in the mental healthcare sector for people following first SMI diagnosis.

Settings

A large mental healthcare provider, the South London and Maudsley National Health Service Trust.

Participants

Using electronic mental health records data, we ascertained patients with first SMI diagnoses (schizophrenia, schizoaffective disorder, bipolar disorder) from 2008 to 2018.

Outcome measures

Recording or not of HbA1c level was ascertained from routine local laboratory data and supplemented by a natural language processing (NLP) algorithm for extracting recorded values in text fields (precision 0.89%, recall 0.93%). Age, gender, ethnic group, year of diagnosis, and SMI diagnosis were investigated as covariates in relation to recording or not of HbA1c and first recorded levels.

Results

Of 21 462 patients in the sample (6546 bipolar disorder; 14 916 schizophrenia or schizoaffective disorder; mean age 38.8 years, 49% female), 4106 (19.1%) had at least one HbA1c result recorded from laboratory data, increasing to 6901 (32.2%) following NLP. HbA1c recording was independently more likely in non-white ethnic groups (black compared with white: OR 2.45, 95% CI 2.29 to 2.62), and was negatively associated with age (OR per year increase 0.93, 0.92-0.95), female gender (0.83, 0.78-0.88) and bipolar disorder (0.49, 0.45-0.52).

Conclusions

Over a 10-year period, relatively low level of recording of HbA1c was observed, although this has increased over time and ascertainment was increased with text extraction. It remains important to improve the routine monitoring of dysglycaemia in these at-risk disorders.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/7/e069635.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-069635; html:https://europepmc.org/articles/PMC10357777; pdf:https://europepmc.org/articles/PMC10357777?pdf=render +34829865,https://doi.org/10.3390/biomedicines9111636,Machine Learning-Based Identification of Potentially Novel Non-Alcoholic Fatty Liver Disease Biomarkers.,"Shafiha R, Bahcivanci B, Gkoutos GV, Acharjee A.",,Biomedicines,2021,2021-11-07,Y,Biomarker; Machine Learning; Lipidomics; Transcriptomics; Nafld,,,"Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that presents a great challenge for treatment and prevention.. This study aims to implement a machine learning approach that employs such datasets to identify potential biomarker targets. We developed a pipeline to identify potential biomarkers for NAFLD that includes five major processes, namely, a pre-processing step, a feature selection and a generation of a random forest model and, finally, a downstream feature analysis and a provision of a potential biological interpretation. The pre-processing step includes data normalising and variable extraction accompanied by appropriate annotations. A feature selection based on a differential gene expression analysis is then conducted to identify significant features and then employ them to generate a random forest model whose performance is assessed based on a receiver operating characteristic curve. Next, the features are subjected to a downstream analysis, such as univariate analysis, a pathway enrichment analysis, a network analysis and a generation of correlation plots, boxplots and heatmaps. Once the results are obtained, the biological interpretation and the literature validation is conducted over the identified features and results. We applied this pipeline to transcriptomics and lipidomic datasets and concluded that the C4BPA gene could play a role in the development of NAFLD. The activation of the complement pathway, due to the downregulation of the C4BPA gene, leads to an increase in triglyceride content, which might further render the lipid metabolism. This approach identified the C4BPA gene, an inhibitor of the complement pathway, as a potential biomarker for the development of NAFLD.",,pdf:https://www.mdpi.com/2227-9059/9/11/1636/pdf?version=1637024773; doi:https://doi.org/10.3390/biomedicines9111636; html:https://europepmc.org/articles/PMC8615894; pdf:https://europepmc.org/articles/PMC8615894?pdf=render 34879829,https://doi.org/10.1186/s12911-021-01693-6,Identifying and evaluating clinical subtypes of Alzheimer's disease in care electronic health records using unsupervised machine learning.,"Alexander N, Alexander DC, Barkhof F, Denaxas S.",,BMC medical informatics and decision making,2021,2021-12-08,Y,Alzheimer's disease; Clustering; Subtyping; Ehr; K-means,,,"

Background

Alzheimer's disease (AD) is a highly heterogeneous disease with diverse trajectories and outcomes observed in clinical populations. Understanding this heterogeneity can enable better treatment, prognosis and disease management. Studies to date have mainly used imaging or cognition data and have been limited in terms of data breadth and sample size. Here we examine the clinical heterogeneity of Alzheimer's disease patients using electronic health records (EHR) to identify and characterise disease subgroups using multiple clustering methods, identifying clusters which are clinically actionable.

Methods

We identified AD patients in primary care EHR from the Clinical Practice Research Datalink (CPRD) using a previously validated rule-based phenotyping algorithm. We extracted and included a range of comorbidities, symptoms and demographic features as patient features. We evaluated four different clustering methods (k-means, kernel k-means, affinity propagation and latent class analysis) to cluster Alzheimer's disease patients. We compared clusters on clinically relevant outcomes and evaluated each method using measures of cluster structure, stability, efficiency of outcome prediction and replicability in external data sets.

Results

We identified 7,913 AD patients, with a mean age of 82 and 66.2% female. We included 21 features in our analysis. We observed 5, 2, 5 and 6 clusters in k-means, kernel k-means, affinity propagation and latent class analysis respectively. K-means was found to produce the most consistent results based on four evaluative measures. We discovered a consistent cluster found in three of the four methods composed of predominantly female, younger disease onset (43% between ages 42-73) diagnosed with depression and anxiety, with a quicker rate of progression compared to the average across other clusters.

Conclusion

Each clustering approach produced substantially different clusters and K-Means performed the best out of the four methods based on the four evaluative criteria. However, the consistent appearance of one particular cluster across three of the four methods potentially suggests the presence of a distinct disease subtype that merits further exploration. Our study underlines the variability of the results obtained from different clustering approaches and the importance of systematically evaluating different approaches for identifying disease subtypes in complex EHR.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-021-01693-6; doi:https://doi.org/10.1186/s12911-021-01693-6; html:https://europepmc.org/articles/PMC8653614; pdf:https://europepmc.org/articles/PMC8653614?pdf=render +37463814,https://doi.org/10.1136/bmjopen-2022-069635,HbA1c recording in patients following a first diagnosis of serious mental illness: the South London and Maudsley Biomedical Research Centre case register.,"Bell N, Perera G, Chandran D, Stubbs B, Gaughran F, Stewart R.",,BMJ open,2023,2023-07-18,Y,Psychiatry; Mental health; epidemiology; Health Informatics; General Diabetes; Quality In Health Care,,,"

Objectives

To investigate factors associated with the recording of glycated haemoglobin (HbA1c) in people with first diagnoses of serious mental illness (SMI) in a large mental healthcare provider, and factors associated with HbA1c levels, when recorded. To our knowledge this is the first such investigation, although attention to dysglycaemia in SMI is an increasing priority in mental healthcare.

Design

The study was primarily descriptive in nature, seeking to ascertain the frequency of HbA1c recording in the mental healthcare sector for people following first SMI diagnosis.

Settings

A large mental healthcare provider, the South London and Maudsley National Health Service Trust.

Participants

Using electronic mental health records data, we ascertained patients with first SMI diagnoses (schizophrenia, schizoaffective disorder, bipolar disorder) from 2008 to 2018.

Outcome measures

Recording or not of HbA1c level was ascertained from routine local laboratory data and supplemented by a natural language processing (NLP) algorithm for extracting recorded values in text fields (precision 0.89%, recall 0.93%). Age, gender, ethnic group, year of diagnosis, and SMI diagnosis were investigated as covariates in relation to recording or not of HbA1c and first recorded levels.

Results

Of 21 462 patients in the sample (6546 bipolar disorder; 14 916 schizophrenia or schizoaffective disorder; mean age 38.8 years, 49% female), 4106 (19.1%) had at least one HbA1c result recorded from laboratory data, increasing to 6901 (32.2%) following NLP. HbA1c recording was independently more likely in non-white ethnic groups (black compared with white: OR 2.45, 95% CI 2.29 to 2.62), and was negatively associated with age (OR per year increase 0.93, 0.92-0.95), female gender (0.83, 0.78-0.88) and bipolar disorder (0.49, 0.45-0.52).

Conclusions

Over a 10-year period, relatively low level of recording of HbA1c was observed, although this has increased over time and ascertainment was increased with text extraction. It remains important to improve the routine monitoring of dysglycaemia in these at-risk disorders.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/7/e069635.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-069635; html:https://europepmc.org/articles/PMC10357777; pdf:https://europepmc.org/articles/PMC10357777?pdf=render 38177425,https://doi.org/10.1038/s43588-023-00461-y,GREENER principles for environmentally sustainable computational science.,"Lannelongue L, Aronson HG, Bateman A, Birney E, Caplan T, Juckes M, McEntyre J, Morris AD, Reilly G, Inouye M.",,Nature computational science,2023,2023-06-26,N,,,,"The carbon footprint of scientific computing is substantial, but environmentally sustainable computational science (ESCS) is a nascent field with many opportunities to thrive. To realize the immense green opportunities and continued, yet sustainable, growth of computer science, we must take a coordinated approach to our current challenges, including greater awareness and transparency, improved estimation and wider reporting of environmental impacts. Here, we present a snapshot of where ESCS stands today and introduce the GREENER set of principles, as well as guidance for best practices moving forward.",,doi:https://doi.org/10.1038/s43588-023-00461-y 31799783,https://doi.org/10.1002/cnm.3267,Personalising cardiovascular network models in pregnancy: A two-tiered parameter estimation approach.,"Carson J, Warrander L, Johnstone E, van Loon R.",,International journal for numerical methods in biomedical engineering,2021,2020-01-13,Y,Pregnancy; Parameter estimation; Pre-eclampsia; Personalised Haemodynamic Model; Uterine Artery Waveform,,,"Uterine artery Doppler waveforms are often studied to determine whether a patient is at risk of developing pathologies such as pre-eclampsia. Many uterine waveform indices have been developed, which attempt to relate characteristics of the waveform with the physiological adaptation of the maternal cardiovascular system, and are often suggested to be an indicator of increased placenta resistance and arterial stiffness. Doppler waveforms of four patients, two of whom developed pre-eclampsia, are compared with a comprehensive closed-loop model of pregnancy. The closed-loop model has been previously validated but has been extended to include an improved parameter estimation technique that utilises systolic and diastolic blood pressure, cardiac output, heart rate, and pulse wave velocity measurements to adapt model resistances, compliances, blood volume, and the mean vessel areas in the main systemic arteries. The shape of the model-predicted uterine artery velocity waveforms showed good agreement with the characteristics observed in the patient Doppler waveforms. The personalised models obtained now allow a prediction of the uterine pressure waveforms in addition to the uterine velocity. This allows for a more detailed mechanistic analysis of the waveforms, eg, wave intensity analysis, to study existing clinical indices. The findings indicate that to accurately estimate arterial stiffness, both pulse pressure and pulse wave velocities are required. In addition, the results predict that patients who developed pre-eclampsia later in pregnancy have larger vessel areas in the main systemic arteries compared with the two patients who had normal pregnancy outcomes.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cnm.3267; doi:https://doi.org/10.1002/cnm.3267; html:https://europepmc.org/articles/PMC9286682; pdf:https://europepmc.org/articles/PMC9286682?pdf=render 37346822,https://doi.org/10.12688/wellcomeopenres.18735.2,First dose COVID-19 vaccine coverage amongst adolescents and children in England: an analysis of 3.21 million patients' primary care records in situ using OpenSAFELY.,"Hopcroft LE, Curtis HJ, Brown AD, Hulme WJ, Andrews CD, Morton CE, Inglesby P, Morley J, Mehrkar A, Bacon SC, Eggo RM, Mahalingasivam V, Parker EPK, Tomlinson LA, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, Walker AJ, MacKenna B.",,Wellcome open research,2023,2023-06-09,Y,Vaccine; Primary Health Care; Public Health; Covid-19,,,"Background: The coronavirus disease 2019 (COVID-19) vaccination programme in England was extended to include all adolescents and children by April 2022. The aim of this paper is to describe trends and variation in vaccine coverage in different clinical and demographic groups amongst adolescents and children in England by August 2022. Methods: With the approval of NHS England, a cohort study was conducted of 3.21 million children and adolescents' records in general practice in England,  in situ and within the infrastructure of the electronic health record software vendor TPP using OpenSAFELY. Vaccine coverage across various demographic (sex, deprivation index and ethnicity) and clinical (risk status) populations is described. Results: Coverage is higher amongst adolescents than it is amongst children, with 53.5% adolescents and 10.8% children having received their first dose of the COVID-19 vaccine. Within those groups, coverage varies by ethnicity, deprivation index and risk status; there is no evidence of variation by sex. Conclusion: First dose COVID-19 vaccine coverage is shown to vary amongst various demographic and clinical groups of children and adolescents.",,doi:https://doi.org/10.12688/wellcomeopenres.18735.2; html:https://europepmc.org/articles/PMC10280033; pdf:https://europepmc.org/articles/PMC10280033?pdf=render @@ -359,12 +359,12 @@ PMC10929454,https://doi.org/,Optimising data curation pipelines for population-l 34007894,https://doi.org/10.23889/ijpds.v6i1.1373,Visualisation and optimisation of alcohol-related hospital admissions ICD-10 codes in Welsh e-cohort data.,"Trefan L, Akbari A, Morgan JS, Farewell DM, Fone D, Lyons RA, Jones Hywel M, Moore SC.",,International journal of population data science,2021,2021-03-24,Y,Alcohol; Hospital Admission; Optimisation; Icd-10 Codes; E-Cohort Data,,,"

Introduction

The excessive consumption of alcohol is detrimental to long term health and increases the likelihood of hospital admission. However, definitions of alcohol-related hospital admission vary, giving rise to uncertainty in the effect of alcohol on alcohol-related health care utilization.

Objectives

To compare diagnostic codes on hospital admission and discharge and to determine the ideal combination of codes necessary for an accurate determination of alcohol-related hospital admission.

Methods

Routine population-linked e-cohort data were extracted from the Secure Anonymised Information Linkage (SAIL) Databank containing all alcohol-related hospital admissions (n,= 92,553) from 2006 to 2011 in Wales, United Kingdom. The distributions of the diagnostic codes recorded at admission and discharge were compared. By calculating a misclassification rate (sensitivity-like measure) the appropriate number of coding fields to examine for alcohol-codes was established.

Results

There was agreement between admission and discharge codes. When more than ten coding fields were used the misclassification rate was less than 1%.

Conclusion

With the data at present and alcohol-related codes used, codes recorded at admission and discharge can be used equivalently to identify alcohol-related admissions. The appropriate number of coding fields to examine was established: fewer than ten is likely to lead to under-reporting of alcohol-related admissions. The methods developed here can be applied to other medical conditions that can be described using a certain set of diagnostic codes, each of which can be a known sole cause of the condition and recorded in multiple positions in e-cohort data.",,pdf:https://ijpds.org/article/download/1373/3264; doi:https://doi.org/10.23889/ijpds.v6i1.1373; html:https://europepmc.org/articles/PMC8103565; pdf:https://europepmc.org/articles/PMC8103565?pdf=render 38444664,https://doi.org/10.1183/23120541.00010-2024,Development and evaluation of a tool to optimise inhaler selection prior to hospital discharge following an exacerbation of COPD.,"Price E, Ahmad S, Althobiani MA, Ayoob T, Burgoyne T, De Soyza A, Dobson M, Echevarria C, Martin G, Mendes RG, Preston AM, Rahman NM, Sapey E, Usmani OS, Hurst JR.",,ERJ open research,2024,2024-03-04,N,,,,"

Introduction

Rates of mortality and re-admission after a hospitalised exacerbation of COPD are high and resistant to change. COPD guidelines do not give practical advice about the optimal selection of inhaled drugs and device in this situation. We hypothesised that a failure to optimise inhaled drug and drug delivery prior to discharge from hospital after an exacerbation would be associated with a modifiable increased risk of re-admission and death. We designed a study to 1) develop a practical inhaler selection tool to use at the point of hospital discharge and 2) implement this tool to understand the potential impact on modifying inhaler prescriptions, clinical outcomes, acceptability to clinicians and patients, and the feasibility of delivering a definitive trial to demonstrate potential benefit.

Methods

We iteratively developed an inhaler selection tool for use prior to discharge following a hospitalised exacerbation of COPD using surveys with multiprofessional clinicians and a focus group of people living with COPD. We surveyed clinicians to understand their views on the minimum clinically important difference (MCID) for death and re-admission following a hospitalised exacerbation of COPD. We conducted a mixed-methods implementation feasibility study using the tool at discharge, and collated 30- and 90-day follow-up data including death and re-admissions. Additionally, we observed the tool being used and interviewed clinicians and patients about use of the tool in this setting.

Results

We completed the design of an inhaler selection tool through two rounds of consultations with 94 multiprofessional clinicians, and a focus group of four expert patients. Regarding MCIDs, there was majority consensus for the following reductions from baseline being the MCID: 30-day readmissions 5-10%, 90-day readmissions 10-20%, 30-day mortality 5-10% and 90-day mortality 5-10%. 118 patients were assessed for eligibility and 26 had the tool applied. A change in inhaled medication was recommended in nine (35%) out of 26. Re-admission or death at 30 days was seen in 33% of the switch group and 35% of the no-switch group. Re-admission or death at 90 days was seen in 56% of the switch group and 41% of the no-switch group. Satisfaction with inhalers was generally high, and switching was associated with a small increase in the Feeling of Satisfaction with Inhaler questionnaire of 3 out of 50 points. Delivery of a definitive study would be challenging.

Conclusion

We completed a mixed-methods study to design and implement a tool to aid optimisation of inhaled pharmacotherapy prior to discharge following a hospitalised exacerbation of COPD. This was not associated with fewer re-admissions, but was well received and one-third of people were eligible for a change in inhalers.",,doi:https://doi.org/10.1183/23120541.00010-2024 38283541,https://doi.org/10.1016/j.ssmph.2023.101592,Childhood cognitive ability and self-harm and suicide in later life.,"Iveson MH, Ball EL, Whalley HC, Deary IJ, Cox SR, Batty GD, John A, McIntosh AM.",,SSM - population health,2024,2023-12-29,Y,epidemiology; Suicide; Data Linkage; Self-harm; Older Age; Cognitive Ability,,,"

Background

Self-harm and suicide remain prevalent in later life. For younger adults, higher early-life cognitive ability appears to predict lower self-harm and suicide risk. Comparatively little is known about these associations among middle-aged and older adults.

Methods

This study examined the association between childhood (age 11) cognitive ability and self-harm and suicide risk among a Scotland-wide cohort (N = 53037), using hospital admission and mortality records to follow individuals from age 34 to 85. Multistate models examined the association between childhood cognitive ability and transitions between unaffected, self-harm, and then suicide or non-suicide death.

Results

After adjusting for childhood and adulthood socioeconomic conditions, higher childhood cognitive ability was significantly associated with reduced risk of self-harm among both males (451 events; HR = 0.90, 95% CI [0.82, 0.99]) and females (516 events; HR = 0.89, 95% CI [0.81, 0.98]). Childhood cognitive ability was not significantly associated with suicide risk among those with (Male: 16 events, HR = 1.05, 95% CI [0.61, 1.80]; Female: 13 events, HR = 1.08, 95% CI [0.55, 2.15]) or without self-harm events (Male: 118 events, HR = 1.17, 95% CI [0.84, 1.63]; Female: 31 events, HR = 1.30, 95% CI [0.70, 2.41]).

Limitations

The study only includes self-harm events that result in a hospital admission and does not account for self-harm prior to follow-up.

Conclusions

This extends work on cognitive ability and mental health, demonstrating that these associations can span the life course and into middle and older age.",,doi:https://doi.org/10.1016/j.ssmph.2023.101592; html:https://europepmc.org/articles/PMC10821139; pdf:https://europepmc.org/articles/PMC10821139?pdf=render -37180154,https://doi.org/10.3389/fimmu.2023.1083072,Real-time assessment of neutrophil metabolism and oxidative burst using extracellular flux analysis.,"Grudzinska FS, Jasper A, Sapey E, Thickett DR, Mauro C, Scott A, Barlow J.",,Frontiers in immunology,2023,2023-04-25,Y,Neutrophils; Oxidative burst; glycolysis; Immunometabolism; Extracellular Flux Analysis,,,"Neutrophil responses are critical during inflammatory and infective events, and neutrophil dysregulation has been associated with poor patient outcomes. Immunometabolism is a rapidly growing field that has provided insights into cellular functions in health and disease. Neutrophils are highly glycolytic when activated, with inhibition of glycolysis associated with functional deficits. There is currently very limited data available assessing metabolism in neutrophils. Extracellular flux (XF) analysis assesses real time oxygen consumption and the rate of proton efflux in cells. This technology allows for the automated addition of inhibitors and stimulants to visualise the effect on metabolism. We describe optimised protocols for an XFe96 XF Analyser to (i) probe glycolysis in neutrophils under basal and stimulated conditions, (ii) probe phorbol 12-myristate 13-acetate induced oxidative burst, and (iii) highlight challenges of using XF technology to examine mitochondrial function in neutrophils. We provide an overview of how to analyze XF data and identify pitfalls of probing neutrophil metabolism with XF analysis. In summary we describe robust methods for assessing glycolysis and oxidative burst in human neutrophils and discuss the challenges around using this technique to assess mitochondrial respiration. XF technology is a powerful platform with a user-friendly interface and data analysis templates, however we suggest caution when assessing neutrophil mitochondrial respiration.",,pdf:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1083072/pdf; doi:https://doi.org/10.3389/fimmu.2023.1083072; html:https://europepmc.org/articles/PMC10166867; pdf:https://europepmc.org/articles/PMC10166867?pdf=render 37358897,https://doi.org/10.2196/45849,Development of a Corpus Annotated With Mentions of Pain in Mental Health Records: Natural Language Processing Approach.,"Chaturvedi J, Chance N, Mirza L, Vernugopan V, Velupillai S, Stewart R, Roberts A.",,JMIR formative research,2023,2023-06-26,Y,Pain; Mental health; Annotation; Information Extraction; Natural Language Processing,,,"

Background

Pain is a widespread issue, with 20% of adults (1 in 5) experiencing it globally. A strong association has been demonstrated between pain and mental health conditions, and this association is known to exacerbate disability and impairment. Pain is also known to be strongly related to emotions, which can lead to damaging consequences. As pain is a common reason for people to access health care facilities, electronic health records (EHRs) are a potential source of information on this pain. Mental health EHRs could be particularly beneficial since they can show the overlap of pain with mental health. Most mental health EHRs contain the majority of their information within the free-text sections of the records. However, it is challenging to extract information from free text. Natural language processing (NLP) methods are therefore required to extract this information from the text.

Objective

This research describes the development of a corpus of manually labeled mentions of pain and pain-related entities from the documents of a mental health EHR database, for use in the development and evaluation of future NLP methods.

Methods

The EHR database used, Clinical Record Interactive Search, consists of anonymized patient records from The South London and Maudsley National Health Service Foundation Trust in the United Kingdom. The corpus was developed through a process of manual annotation where pain mentions were marked as relevant (ie, referring to physical pain afflicting the patient), negated (ie, indicating absence of pain), or not relevant (ie, referring to pain affecting someone other than the patient, or metaphorical and hypothetical mentions). Relevant mentions were also annotated with additional attributes such as anatomical location affected by pain, pain character, and pain management measures, if mentioned.

Results

A total of 5644 annotations were collected from 1985 documents (723 patients). Over 70% (n=4028) of the mentions found within the documents were annotated as relevant, and about half of these mentions also included the anatomical location affected by the pain. The most common pain character was chronic pain, and the most commonly mentioned anatomical location was the chest. Most annotations (n=1857, 33%) were from patients who had a primary diagnosis of mood disorders (International Classification of Diseases-10th edition, chapter F30-39).

Conclusions

This research has helped better understand how pain is mentioned within the context of mental health EHRs and provided insight into the kind of information that is typically mentioned around pain in such a data source. In future work, the extracted information will be used to develop and evaluate a machine learning-based NLP application to automatically extract relevant pain information from EHR databases.",,pdf:https://formative.jmir.org/2023/1/e45849/PDF; doi:https://doi.org/10.2196/45849; html:https://europepmc.org/articles/PMC10337440; pdf:https://europepmc.org/articles/PMC10337440?pdf=render +37180154,https://doi.org/10.3389/fimmu.2023.1083072,Real-time assessment of neutrophil metabolism and oxidative burst using extracellular flux analysis.,"Grudzinska FS, Jasper A, Sapey E, Thickett DR, Mauro C, Scott A, Barlow J.",,Frontiers in immunology,2023,2023-04-25,Y,Neutrophils; Oxidative burst; glycolysis; Immunometabolism; Extracellular Flux Analysis,,,"Neutrophil responses are critical during inflammatory and infective events, and neutrophil dysregulation has been associated with poor patient outcomes. Immunometabolism is a rapidly growing field that has provided insights into cellular functions in health and disease. Neutrophils are highly glycolytic when activated, with inhibition of glycolysis associated with functional deficits. There is currently very limited data available assessing metabolism in neutrophils. Extracellular flux (XF) analysis assesses real time oxygen consumption and the rate of proton efflux in cells. This technology allows for the automated addition of inhibitors and stimulants to visualise the effect on metabolism. We describe optimised protocols for an XFe96 XF Analyser to (i) probe glycolysis in neutrophils under basal and stimulated conditions, (ii) probe phorbol 12-myristate 13-acetate induced oxidative burst, and (iii) highlight challenges of using XF technology to examine mitochondrial function in neutrophils. We provide an overview of how to analyze XF data and identify pitfalls of probing neutrophil metabolism with XF analysis. In summary we describe robust methods for assessing glycolysis and oxidative burst in human neutrophils and discuss the challenges around using this technique to assess mitochondrial respiration. XF technology is a powerful platform with a user-friendly interface and data analysis templates, however we suggest caution when assessing neutrophil mitochondrial respiration.",,pdf:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1083072/pdf; doi:https://doi.org/10.3389/fimmu.2023.1083072; html:https://europepmc.org/articles/PMC10166867; pdf:https://europepmc.org/articles/PMC10166867?pdf=render 37650027,https://doi.org/10.23889/ijpds.v7i1.1724,"A methodology to facilitate critical care research using multiple linked electronic, clinical and administrative health records at population scale.","Griffiths R, Herbert L, Akbari A, Bailey R, Hollinghurst J, Pugh R, Szakmany T, Torabi F, Lyons RA.",,International journal of population data science,2022,2022-07-18,Y,Intensive Care; Critical Care; Electronic Health Records; Icnarc; Linkable Research Data,,,"

Introduction

Critical Care is a specialty in medicine providing a service for severely ill and high-risk patients who, due to the nature of their condition, may require long periods recovering after discharge. Consequently, focus on the routine data collection carried out in Intensive Care Units (ICUs) leads to reporting that is confined to the critical care episode and is typically insensitive to variation in individual patient pathways through critical care to recovery.A resource which facilitates efficient research into interactions with healthcare services surrounding critical admissions, capturing the complete patient's healthcare trajectory from primary care to non-acute hospital care prior to ICU, would provide an important longer-term perspective for critical care research.

Objective

To describe and apply a reproducible methodology that demonstrates how both routine administrative and clinically rich critical care data sources can be integrated with primary and secondary healthcare data to create a single dataset that captures a broader view of patient care.

Method

To demonstrate the INTEGRATE methodology, it was applied to routine administrative and clinical healthcare data sources in the Secure Anonymised Data Linking (SAIL) Databank to create a dataset of patients' complete healthcare trajectory prior to critical care admission. SAIL is a national, data safe haven of anonymised linkable datasets about the population of Wales.

Results

When applying the INTEGRATE methodology in SAIL, between 2010 and 2019 we observed 91,582 critical admissions for 76,019 patients. Of these, 90,632 (99%) had an associated non-acute hospital admission, 48,979 (53%) had an emergency admission, and 64,832 (71%) a primary care interaction in the week prior to the critical care admission.

Conclusion

This methodology, at population scale, integrates two critical care data sources into a single dataset together with data sources on healthcare prior to critical admission, thus providing a key research asset to study critical care pathways.",,doi:https://doi.org/10.23889/ijpds.v7i1.1724; html:https://europepmc.org/articles/PMC10464871; pdf:https://europepmc.org/articles/PMC10464871?pdf=render -38192590,https://doi.org/10.1016/j.eclinm.2023.102321,Clinical and health inequality risk factors for non-COVID-related sepsis during the global COVID-19 pandemic: a national case-control and cohort study.,"Zhong X, Ashiru-Oredope D, Pate A, Martin GP, Sharma A, Dark P, Felton T, Lake C, MacKenna B, Mehrkar A, Bacon SCJ, Massey J, Inglesby P, Goldacre B, OpenSAFELY Collaborative, Hand K, Bladon S, Cunningham N, Gilham E, Brown CS, Mirfenderesky M, Palin V, van Staa TP.",,EClinicalMedicine,2023,2023-11-23,Y,Sepsis; Morbidity; Primary Care; Deprivation; Health Inequality; Covid-19 Pandemic,,,"

Background

Sepsis, characterised by significant morbidity and mortality, is intricately linked to socioeconomic disparities and pre-admission clinical histories. This study aspires to elucidate the association between non-COVID-19 related sepsis and health inequality risk factors amidst the pandemic in England, with a secondary focus on their association with 30-day sepsis mortality.

Methods

With the approval of NHS England, we harnessed the OpenSAFELY platform to execute a cohort study and a 1:6 matched case-control study. A sepsis diagnosis was identified from the incident hospital admissions record using ICD-10 codes. This encompassed 248,767 cases with non-COVID-19 sepsis from a cohort of 22.0 million individuals spanning January 1, 2019, to June 31, 2022. Socioeconomic deprivation was gauged using the Index of Multiple Deprivation score, reflecting indicators like income, employment, and education. Hospitalisation-related sepsis diagnoses were categorised as community-acquired or hospital-acquired. Cases were matched to controls who had no recorded diagnosis of sepsis, based on age (stepwise), sex, and calendar month. The eligibility criteria for controls were established primarily on the absence of a recorded sepsis diagnosis. Associations between potential predictors and odds of developing non-COVID-19 sepsis underwent assessment through conditional logistic regression models, with multivariable regression determining odds ratios (ORs) for 30-day mortality.

Findings

The study included 224,361 (10.2%) cases with non-COVID-19 sepsis and 1,346,166 matched controls. The most socioeconomic deprived quintile was associated with higher odds of developing non-COVID-19 sepsis than the least deprived quintile (crude OR 1.80 [95% CI 1.77-1.83]). Other risk factors (after adjusting comorbidities) such as learning disability (adjusted OR 3.53 [3.35-3.73]), chronic liver disease (adjusted OR 3.08 [2.97-3.19]), chronic kidney disease (stage 4: adjusted OR 2.62 [2.55-2.70], stage 5: adjusted OR 6.23 [5.81-6.69]), cancer, neurological disease, immunosuppressive conditions were also associated with developing non-COVID-19 sepsis. The incidence rate of non-COVID-19 sepsis decreased during the COVID-19 pandemic and rebounded to pre-pandemic levels (April 2021) after national lockdowns had been lifted. The 30-day mortality risk in cases with non-COVID-19 sepsis was higher for the most deprived quintile across all periods.

Interpretation

Socioeconomic deprivation, comorbidity and learning disabilities were associated with an increased odds of developing non-COVID-19 related sepsis and 30-day mortality in England. This study highlights the need to improve the prevention of sepsis, including more precise targeting of antimicrobials to higher-risk patients.

Funding

The UK Health Security Agency, Health Data Research UK, and National Institute for Health Research.",,doi:https://doi.org/10.1016/j.eclinm.2023.102321; html:https://europepmc.org/articles/PMC10772239; pdf:https://europepmc.org/articles/PMC10772239?pdf=render -36219788,https://doi.org/10.1093/ije/dyac185,Borrowing strength from clinical trials in analysing longitudinal data from a treated cohort: investigating the effectiveness of acetylcholinesterase inhibitors in the management of dementia.,"Knight R, Stewart R, Khondoker M, Landau S.",,International journal of epidemiology,2023,2023-06-01,Y,Cognition; Dementia; Randomized controlled trial; acetylcholinesterase inhibitors; Electronic Medical Record; Bayesian Modelling,,,"

Background

Health care professionals seek information about effectiveness of treatments in patients who would be offered them in routine clinical practice. Electronic medical records (EMRs) and randomized controlled trials (RCTs) can both provide data on treatment effects; however, each data source has limitations when considered in isolation.

Methods

A novel modelling methodology which incorporates RCT estimates in the analysis of EMR data via informative prior distributions is proposed. A Bayesian mixed modelling approach is used to model outcome trajectories among patients in the EMR dataset receiving the treatment of interest. This model incorporates an estimate of treatment effect based on a meta-analysis of RCTs as an informative prior distribution. This provides a combined estimate of treatment effect based on both data sources.

Results

The superior performance of the novel combined estimator is demonstrated via a simulation study. The new approach is applied to estimate the effectiveness at 12 months after treatment initiation of acetylcholinesterase inhibitors in the management of the cognitive symptoms of dementia in terms of Mini-Mental State Examination scores. This demonstrated that estimates based on either trials data only (1.10, SE = 0.316) or cohort data only (1.56, SE = 0.240) overestimated this compared with the estimate using data from both sources (0.86, SE = 0.327).

Conclusions

It is possible to combine data from EMRs and RCTs in order to provide better estimates of treatment effectiveness.",,pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac185/47708280/dyac185.pdf; doi:https://doi.org/10.1093/ije/dyac185; html:https://europepmc.org/articles/PMC10244047; pdf:https://europepmc.org/articles/PMC10244047?pdf=render 35572721,https://doi.org/10.1016/j.eclinm.2022.101419,Breakthrough SARS-CoV-2 infections in double and triple vaccinated adults and single dose vaccine effectiveness among children in Autumn 2021 in England: REACT-1 study.,"Chadeau-Hyam M, Eales O, Bodinier B, Wang H, Haw D, Whitaker M, Elliott J, Walters CE, Jonnerby J, Atchison C, Diggle PJ, Page AJ, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly CA, Elliott P.",,EClinicalMedicine,2022,2022-05-06,Y,School-aged children; Vaccine Effectiveness; Booster Dose; Children Vaccination; Sars-cov-2 Prevalence,,,"

Background

Prevalence of SARS-CoV-2 infection with Delta variant was increasing in England in late summer 2021 among children aged 5 to 17 years, and adults who had received two vaccine doses. In September 2021, a third (booster) dose was offered to vaccinated adults aged 50 years and over, vulnerable adults and healthcare/care-home workers, and a single vaccine dose already offered to 16 and 17 year-olds was extended to children aged 12 to 15 years.

Methods

SARS-CoV-2 community prevalence in England was available from self-administered throat and nose swabs using reverse transcriptase polymerase chain reaction (RT-PCR) in round 13 (24 June to 12 July 2021, N = 98,233), round 14 (9 to 27 September 2021, N = 100,527) and round 15 (19 October to 5 November 2021, N = 100,112) from the REACT-1 study randomised community surveys. Linking to National Health Service (NHS) vaccination data for consenting participants, we estimated vaccine effectiveness in children aged 12 to 17 years and compared swab-positivity rates in adults who received a third dose with those who received two doses.

Findings

Weighted SARS-CoV-2 prevalence was 1.57% (1.48%, 1.66%) in round 15 compared with 0.83% (0.76%, 0.89%) in round 14, and the previously observed link between infections and hospitalisations and deaths had weakened. Vaccine effectiveness against infection in children aged 12 to 17 years was estimated (round 15) at 64.0% (50.9%, 70.6%) and 67.7% (53.8%, 77.5%) for symptomatic infections. Adults who received a third vaccine dose were less likely to test positive compared to those who received two doses, with adjusted OR of 0.36 (0.25, 0.53).

Interpretation

Vaccination of children aged 12 to 17 years and third (booster) doses in adults were effective at reducing infection risk. High rates of vaccination, including booster doses, are a key part of the strategy to reduce infection rates in the community.

Funding

Department of Health and Social Care, England.",,pdf:http://www.thelancet.com/article/S2589537022001493/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101419; html:https://europepmc.org/articles/PMC9076030; pdf:https://europepmc.org/articles/PMC9076030?pdf=render +36219788,https://doi.org/10.1093/ije/dyac185,Borrowing strength from clinical trials in analysing longitudinal data from a treated cohort: investigating the effectiveness of acetylcholinesterase inhibitors in the management of dementia.,"Knight R, Stewart R, Khondoker M, Landau S.",,International journal of epidemiology,2023,2023-06-01,Y,Cognition; Dementia; Randomized controlled trial; acetylcholinesterase inhibitors; Electronic Medical Record; Bayesian Modelling,,,"

Background

Health care professionals seek information about effectiveness of treatments in patients who would be offered them in routine clinical practice. Electronic medical records (EMRs) and randomized controlled trials (RCTs) can both provide data on treatment effects; however, each data source has limitations when considered in isolation.

Methods

A novel modelling methodology which incorporates RCT estimates in the analysis of EMR data via informative prior distributions is proposed. A Bayesian mixed modelling approach is used to model outcome trajectories among patients in the EMR dataset receiving the treatment of interest. This model incorporates an estimate of treatment effect based on a meta-analysis of RCTs as an informative prior distribution. This provides a combined estimate of treatment effect based on both data sources.

Results

The superior performance of the novel combined estimator is demonstrated via a simulation study. The new approach is applied to estimate the effectiveness at 12 months after treatment initiation of acetylcholinesterase inhibitors in the management of the cognitive symptoms of dementia in terms of Mini-Mental State Examination scores. This demonstrated that estimates based on either trials data only (1.10, SE = 0.316) or cohort data only (1.56, SE = 0.240) overestimated this compared with the estimate using data from both sources (0.86, SE = 0.327).

Conclusions

It is possible to combine data from EMRs and RCTs in order to provide better estimates of treatment effectiveness.",,pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac185/47708280/dyac185.pdf; doi:https://doi.org/10.1093/ije/dyac185; html:https://europepmc.org/articles/PMC10244047; pdf:https://europepmc.org/articles/PMC10244047?pdf=render +38192590,https://doi.org/10.1016/j.eclinm.2023.102321,Clinical and health inequality risk factors for non-COVID-related sepsis during the global COVID-19 pandemic: a national case-control and cohort study.,"Zhong X, Ashiru-Oredope D, Pate A, Martin GP, Sharma A, Dark P, Felton T, Lake C, MacKenna B, Mehrkar A, Bacon SCJ, Massey J, Inglesby P, Goldacre B, OpenSAFELY Collaborative, Hand K, Bladon S, Cunningham N, Gilham E, Brown CS, Mirfenderesky M, Palin V, van Staa TP.",,EClinicalMedicine,2023,2023-11-23,Y,Sepsis; Morbidity; Primary Care; Deprivation; Health Inequality; Covid-19 Pandemic,,,"

Background

Sepsis, characterised by significant morbidity and mortality, is intricately linked to socioeconomic disparities and pre-admission clinical histories. This study aspires to elucidate the association between non-COVID-19 related sepsis and health inequality risk factors amidst the pandemic in England, with a secondary focus on their association with 30-day sepsis mortality.

Methods

With the approval of NHS England, we harnessed the OpenSAFELY platform to execute a cohort study and a 1:6 matched case-control study. A sepsis diagnosis was identified from the incident hospital admissions record using ICD-10 codes. This encompassed 248,767 cases with non-COVID-19 sepsis from a cohort of 22.0 million individuals spanning January 1, 2019, to June 31, 2022. Socioeconomic deprivation was gauged using the Index of Multiple Deprivation score, reflecting indicators like income, employment, and education. Hospitalisation-related sepsis diagnoses were categorised as community-acquired or hospital-acquired. Cases were matched to controls who had no recorded diagnosis of sepsis, based on age (stepwise), sex, and calendar month. The eligibility criteria for controls were established primarily on the absence of a recorded sepsis diagnosis. Associations between potential predictors and odds of developing non-COVID-19 sepsis underwent assessment through conditional logistic regression models, with multivariable regression determining odds ratios (ORs) for 30-day mortality.

Findings

The study included 224,361 (10.2%) cases with non-COVID-19 sepsis and 1,346,166 matched controls. The most socioeconomic deprived quintile was associated with higher odds of developing non-COVID-19 sepsis than the least deprived quintile (crude OR 1.80 [95% CI 1.77-1.83]). Other risk factors (after adjusting comorbidities) such as learning disability (adjusted OR 3.53 [3.35-3.73]), chronic liver disease (adjusted OR 3.08 [2.97-3.19]), chronic kidney disease (stage 4: adjusted OR 2.62 [2.55-2.70], stage 5: adjusted OR 6.23 [5.81-6.69]), cancer, neurological disease, immunosuppressive conditions were also associated with developing non-COVID-19 sepsis. The incidence rate of non-COVID-19 sepsis decreased during the COVID-19 pandemic and rebounded to pre-pandemic levels (April 2021) after national lockdowns had been lifted. The 30-day mortality risk in cases with non-COVID-19 sepsis was higher for the most deprived quintile across all periods.

Interpretation

Socioeconomic deprivation, comorbidity and learning disabilities were associated with an increased odds of developing non-COVID-19 related sepsis and 30-day mortality in England. This study highlights the need to improve the prevention of sepsis, including more precise targeting of antimicrobials to higher-risk patients.

Funding

The UK Health Security Agency, Health Data Research UK, and National Institute for Health Research.",,doi:https://doi.org/10.1016/j.eclinm.2023.102321; html:https://europepmc.org/articles/PMC10772239; pdf:https://europepmc.org/articles/PMC10772239?pdf=render 35296643,https://doi.org/10.1038/s41467-022-28517-z,"Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab.","Lin S, Kennedy NA, Saifuddin A, Sandoval DM, Reynolds CJ, Seoane RC, Kottoor SH, Pieper FP, Lin KM, Butler DK, Chanchlani N, Nice R, Chee D, Bewshea C, Janjua M, McDonald TJ, Sebastian S, Alexander JL, Constable L, Lee JC, Murray CD, Hart AL, Irving PM, Jones GR, Kok KB, Lamb CA, Lees CW, Altmann DM, Boyton RJ, Goodhand JR, Powell N, Ahmad T, CLARITY IBD study.",,Nature communications,2022,2022-03-16,Y,,,,"Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p <0.0001; 26.8 days [95% CI 26.2 - 27.5] vs 47.6 days [45.5 - 49.8], p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7 U/mL [5.0] vs 784.0 U/mL [3.5], p <0.0001; 35.9 days [34.9 - 36.8] vs 58.0 days [55.0 - 61.3], p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients.",,pdf:https://www.nature.com/articles/s41467-022-28517-z.pdf; doi:https://doi.org/10.1038/s41467-022-28517-z; html:https://europepmc.org/articles/PMC8927425; pdf:https://europepmc.org/articles/PMC8927425?pdf=render 36460578,https://doi.org/10.1016/s2589-7500(22)00187-x,Identifying and visualising multimorbidity and comorbidity patterns in patients in the English National Health Service: a population-based study.,"Kuan V, Denaxas S, Patalay P, Nitsch D, Mathur R, Gonzalez-Izquierdo A, Sofat R, Partridge L, Roberts A, Wong ICK, Hingorani M, Chaturvedi N, Hemingway H, Hingorani AD, Multimorbidity Mechanism and Therapeutic Research Collaborative (MMTRC).",,The Lancet. Digital health,2023,2022-11-29,N,,,,"

Background

Globally, there is a paucity of multimorbidity and comorbidity data, especially for minority ethnic groups and younger people. We estimated the frequency of common disease combinations and identified non-random disease associations for all ages in a multiethnic population.

Methods

In this population-based study, we examined multimorbidity and comorbidity patterns stratified by ethnicity or race, sex, and age for 308 health conditions using electronic health records from individuals included on the Clinical Practice Research Datalink linked with the Hospital Episode Statistics admitted patient care dataset in England. We included individuals who were older than 1 year and who had been registered for at least 1 year in a participating general practice during the study period (between April 1, 2010, and March 31, 2015). We identified the most common combinations of conditions and comorbidities for index conditions. We defined comorbidity as the accumulation of additional conditions to an index condition over an individual's lifetime. We used network analysis to identify conditions that co-occurred more often than expected by chance. We developed online interactive tools to explore multimorbidity and comorbidity patterns overall and by subgroup based on ethnicity, sex, and age.

Findings

We collected data for 3 872 451 eligible patients, of whom 1 955 700 (50·5%) were women and girls, 1 916 751 (49·5%) were men and boys, 2 666 234 (68·9%) were White, 155 435 (4·0%) were south Asian, and 98 815 (2·6%) were Black. We found that a higher proportion of boys aged 1-9 years (132 506 [47·8%] of 277 158) had two or more diagnosed conditions than did girls in the same age group (106 982 [40·3%] of 265 179), but more women and girls were diagnosed with multimorbidity than were boys aged 10 years and older and men (1 361 232 [80·5%] of 1 690 521 vs 1 161 308 [70·8%] of 1 639 593). White individuals (2 097 536 [78·7%] of 2 666 234) were more likely to be diagnosed with two or more conditions than were Black (59 339 [60·1%] of 98 815) or south Asian individuals (93 617 [60·2%] of 155 435). Depression commonly co-occurred with anxiety, migraine, obesity, atopic conditions, deafness, soft-tissue disorders, and gastrointestinal disorders across all subgroups. Heart failure often co-occurred with hypertension, atrial fibrillation, osteoarthritis, stable angina, myocardial infarction, chronic kidney disease, type 2 diabetes, and chronic obstructive pulmonary disease. Spinal fractures were most strongly non-randomly associated with malignancy in Black individuals, but with osteoporosis in White individuals. Hypertension was most strongly associated with kidney disorders in those aged 20-29 years, but with dyslipidaemia, obesity, and type 2 diabetes in individuals aged 40 years and older. Breast cancer was associated with different comorbidities in individuals from different ethnic groups. Asthma was associated with different comorbidities between males and females. Bipolar disorder was associated with different comorbidities in younger age groups compared with older age groups.

Interpretation

Our findings and interactive online tools are a resource for: patients and their clinicians, to prevent and detect comorbid conditions; research funders and policy makers, to redesign service provision, training priorities, and guideline development; and biomedical researchers and manufacturers of medicines, to provide leads for research into common or sequential pathways of disease and inform the design of clinical trials.

Funding

UK Research and Innovation, Medical Research Council, National Institute for Health and Care Research, Department of Health and Social Care, Wellcome Trust, British Heart Foundation, and The Alan Turing Institute.",,pdf:http://www.thelancet.com/article/S258975002200187X/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00187-X 38435677,https://doi.org/10.1016/j.abst.2023.10.002,Taurine as a biomarker for aging: A new avenue for translational research.,Acharjee A.,,Advances in biomarker sciences and technology,2023,2023-01-01,Y,Biomarker; Diagnostics; Translational Research,,,"The physiologic and irreversible process of ageing is accompanied by a wide range of structural and functional shifts at multiple different levels. It is also suggested that variations in the blood concentrations of metabolites, hormones, and micronutrients may play a role in the ageing process. Recently, Singh et al. 1,2 investigated a study on Taurine shortage as a driver and biomarker of ageing and its impact on a healthy lifespan.2 They further proposed that functional abnormalities in numerous organs associated with age-related illnesses have been linked to early-life Taurine insufficiency. Taurine deficiency in the elderly and the possible benefits of Taurine supplements One of the reasons for decreasing Taurine concentration is the loss of endogenous synthesis, which may contribute to the decrease in Taurine levels seen in the elderly. While it was previously believed that the liver was responsible for most Taurine synthesis in humans, new research suggests that other organs or common intermediates may play a larger role. The authors experimented with and analysed a life-span examination of various organisms, for example, mice to assess the impacts of Taurine supplementation. They also analysed after the administration of oral Taurine supplementation in conjunction with other interventions using multi-omics data sets (RNA sequencing, metabolomics etc.) across different species.",,doi:https://doi.org/10.1016/j.abst.2023.10.002; html:https://europepmc.org/articles/PMC10901744 @@ -391,13 +391,13 @@ PMC10910267,https://doi.org/,Development and evaluation of a tool to optimise in 35793922,https://doi.org/10.1136/bmjopen-2021-059385,Deriving and validating a risk prediction model for long COVID-19: protocol for an observational cohort study using linked Scottish data.,"Daines L, Mulholland RH, Vasileiou E, Hammersley V, Weatherill D, Katikireddi SV, Kerr S, Moore E, Pesenti E, Quint JK, Shah SA, Shi T, Simpson CR, Robertson C, Sheikh A.",,BMJ open,2022,2022-07-06,Y,Public Health; Protocols & Guidelines; Covid-19,,,"

Introduction

COVID-19 is commonly experienced as an acute illness, yet some people continue to have symptoms that persist for weeks, or months (commonly referred to as 'long-COVID'). It remains unclear which patients are at highest risk of developing long-COVID. In this protocol, we describe plans to develop a prediction model to identify individuals at risk of developing long-COVID.

Methods and analysis

We will use the national Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, a population-level linked dataset of routine electronic healthcare data from 5.4 million individuals in Scotland. We will identify potential indicators for long-COVID by identifying patterns in primary care data linked to information from out-of-hours general practitioner encounters, accident and emergency visits, hospital admissions, outpatient visits, medication prescribing/dispensing and mortality. We will investigate the potential indicators of long-COVID by performing a matched analysis between those with a positive reverse transcriptase PCR (RT-PCR) test for SARS-CoV-2 infection and two control groups: (1) individuals with at least one negative RT-PCR test and never tested positive; (2) the general population (everyone who did not test positive) of Scotland. Cluster analysis will then be used to determine the final definition of the outcome measure for long-COVID. We will then derive, internally and externally validate a prediction model to identify the epidemiological risk factors associated with long-COVID.

Ethics and dissemination

The EAVE II study has obtained approvals from the Research Ethics Committee (reference: 12/SS/0201), and the Public Benefit and Privacy Panel for Health and Social Care (reference: 1920-0279). Study findings will be published in peer-reviewed journals and presented at conferences. Understanding the predictors for long-COVID and identifying the patient groups at greatest risk of persisting symptoms will inform future treatments and preventative strategies for long-COVID.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/7/e059385.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-059385; html:https://europepmc.org/articles/PMC9260199; pdf:https://europepmc.org/articles/PMC9260199?pdf=render 36530697,https://doi.org/10.3389/fpubh.2022.1035415,Associations between air pollution and multimorbidity in the UK Biobank: A cross-sectional study.,"Ronaldson A, Arias de la Torre J, Ashworth M, Hansell AL, Hotopf M, Mudway I, Stewart R, Dregan A, Bakolis I.",,Frontiers in public health,2022,2022-12-02,Y,Air pollution; Nitrogen dioxide; particulate matter; Health Status; Exploratory Factor Analysis; Multimorbidity,,,"

Background

Long-term exposure to air pollution concentrations is known to be adversely associated with a broad range of single non-communicable diseases, but its role in multimorbidity has not been investigated in the UK. We aimed to assess associations between long-term air pollution exposure and multimorbidity status, severity, and patterns using the UK Biobank cohort.

Methods

Multimorbidity status was calculated based on 41 physical and mental conditions. We assessed cross-sectional associations between annual modeled particulate matter (PM)2.5, PMcoarse, PM10, and nitrogen dioxide (NO2) concentrations (μg/m3-modeled to residential address) and multimorbidity status at the baseline assessment (2006-2010) in 364,144 people (mean age: 52.2 ± 8.1 years, 52.6% female). Air pollutants were categorized into quartiles to assess dose-response associations. Among those with multimorbidity (≥2 conditions; n = 156,395) we assessed associations between air pollutant exposure levels and multimorbidity severity and multimorbidity patterns, which were identified using exploratory factor analysis. Associations were explored using generalized linear models adjusted for sociodemographic, behavioral, and environmental indicators.

Results

Higher exposures to PM2.5, and NO2 were associated with multimorbidity status in a dose-dependent manner. These associations were strongest when we compared the highest air pollution quartile (quartile 4: Q4) with the lowest quartile (Q1) [PM2.5: adjusted odds ratio (adjOR) = 1.21 (95% CI = 1.18, 1.24); NO2: adjOR = 1.19 (95 % CI = 1.16, 1.23)]. We also observed dose-response associations between air pollutant exposures and multimorbidity severity scores. We identified 11 multimorbidity patterns. Air pollution was associated with several multimorbidity patterns with strongest associations (Q4 vs. Q1) observed for neurological (stroke, epilepsy, alcohol/substance dependency) [PM2.5: adjOR = 1.31 (95% CI = 1.14, 1.51); NO2: adjOR = 1.33 (95% CI = 1.11, 1.60)] and respiratory patterns (COPD, asthma) [PM2.5: adjOR = 1.24 (95% CI = 1.16, 1.33); NO2: adjOR = 1.26 (95% CI = 1.15, 1.38)].

Conclusions

This cross-sectional study provides evidence that exposure to air pollution might be associated with having multimorbid, multi-organ conditions. Longitudinal studies are needed to further explore these associations.",,pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.1035415/pdf; doi:https://doi.org/10.3389/fpubh.2022.1035415; html:https://europepmc.org/articles/PMC9755180; pdf:https://europepmc.org/articles/PMC9755180?pdf=render 32635913,https://doi.org/10.1186/s12911-020-01169-z,Application of standardised effect sizes to hospital discharge outcomes for people with diabetes.,"Robbins T, Lim Choi Keung SN, Sankar S, Randeva H, Arvanitis TN.",,BMC medical informatics and decision making,2020,2020-07-07,Y,Mortality; Diabetes; Readmission; Effect Size,,,"

Background

Patients with diabetes are at an increased risk of readmission and mortality when discharged from hospital. Existing research identifies statistically significant risk factors that are thought to underpin these outcomes. Increasingly, these risk factors are being used to create risk prediction models, and target risk modifying interventions. These risk factors are typically reported in the literature accompanied by unstandardized effect sizes, which makes comparisons difficult. We demonstrate an assessment of variation between standardised effect sizes for such risk factors across care outcomes and patient cohorts. Such an approach will support development of more rigorous risk stratification tools and better targeting of intervention measures.

Methods

Data was extracted from the electronic health record of a major tertiary referral centre, over a 3-year period, for all patients discharged from hospital with a concurrent diagnosis of diabetes mellitus. Risk factors selected for extraction were pre-specified according to a systematic review of the research literature. Standardised effect sizes were calculated for all statistically significant risk factors, and compared across patient cohorts and both readmission & mortality outcome measures.

Results

Data was extracted for 46,357 distinct admissions patients, creating a large dataset of approximately 10,281,400 data points. The calculation of standardized effect size measures allowed direct comparison. Effect sizes were noted to be larger for mortality compared to readmission, as well as for being larger for surgical and type 1 diabetes cohorts of patients.

Conclusions

The calculation of standardised effect sizes is an important step in evaluating risk factors for healthcare events. This will improve our understanding of risk and support the development of more effective risk stratification tools to support patients to make better informed decisions at discharge from hospital.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-020-01169-z; doi:https://doi.org/10.1186/s12911-020-01169-z; html:https://europepmc.org/articles/PMC7339522; pdf:https://europepmc.org/articles/PMC7339522?pdf=render -38269898,https://doi.org/10.3233/shti231054,Identifying Mentions of Pain in Mental Health Records Text: A Natural Language Processing Approach.,"Chaturvedi J, Velupillai S, Stewart R, Roberts A.",,Studies in health technology and informatics,2024,2024-01-01,N,Pain; Mental health; Electronic Health Records; Natural Language Processing; Transformers,,,"Pain is a common reason for accessing healthcare resources and is a growing area of research, especially in its overlap with mental health. Mental health electronic health records are a good data source to study this overlap. However, much information on pain is held in the free text of these records, where mentions of pain present a unique natural language processing problem due to its ambiguous nature. This project uses data from an anonymised mental health electronic health records database. A machine learning based classification algorithm is trained to classify sentences as discussing patient pain or not. This will facilitate the extraction of relevant pain information from large databases. 1,985 documents were manually triple-annotated for creation of gold standard training data, which was used to train four classification algorithms. The best performing model achieved an F1-score of 0.98 (95% CI 0.98-0.99).",,pdf:https://ebooks.iospress.nl/pdf/doi/10.3233/SHTI231054; doi:https://doi.org/10.3233/SHTI231054 35050151,https://doi.org/10.3390/metabo12010029,Integration of Metabolomic and Clinical Data Improves the Prediction of Intensive Care Unit Length of Stay Following Major Traumatic Injury.,"Acharjee A, Hazeldine J, Bazarova A, Deenadayalu L, Zhang J, Bentley C, Russ D, Lord JM, Gkoutos GV, Young SP, Foster MA.",,Metabolites,2021,2021-12-31,Y,Inflammation; Metabolomics; Omics Integration; Icu Length Of Stay,,,"Recent advances in emergency medicine and the co-ordinated delivery of trauma care mean more critically-injured patients now reach the hospital alive and survive life-saving operations. Indeed, between 2008 and 2017, the odds of surviving a major traumatic injury in the UK increased by nineteen percent. However, the improved survival rates of severely-injured patients have placed an increased burden on the healthcare system, with major trauma a common cause of intensive care unit (ICU) admissions that last ≥10 days. Improved understanding of the factors influencing patient outcomes is now urgently needed. We investigated the serum metabolomic profile of fifty-five major trauma patients across three post-injury phases: acute (days 0-4), intermediate (days 5-14) and late (days 15-112). Using ICU length of stay (LOS) as a clinical outcome, we aimed to determine whether the serum metabolome measured at days 0-4 post-injury for patients with an extended (≥10 days) ICU LOS differed from that of patients with a short (<10 days) ICU LOS. In addition, we investigated whether combining metabolomic profiles with clinical scoring systems would generate a variable that would identify patients with an extended ICU LOS with a greater degree of accuracy than models built on either variable alone. The number of metabolites unique to and shared across each time segment varied across acute, intermediate and late segments. A one-way ANOVA revealed the most variation in metabolite levels across the different time-points was for the metabolites lactate, glucose, anserine and 3-hydroxybutyrate. A total of eleven features were selected to differentiate between <10 days ICU LOS vs. >10 days ICU LOS. New Injury Severity Score (NISS), testosterone, and the metabolites cadaverine, urea, isoleucine, acetoacetate, dimethyl sulfone, syringate, creatinine, xylitol, and acetone form the integrated biomarker set. Using metabolic enrichment analysis, we found valine, leucine and isoleucine biosynthesis, glutathione metabolism, and glycine, serine and threonine metabolism were the top three pathways differentiating ICU LOS with a p < 0.05. A combined model of NISS and testosterone and all nine selected metabolites achieved an AUROC of 0.824. Differences exist in the serum metabolome of major trauma patients who subsequently experience a short or prolonged ICU LOS in the acute post-injury setting. Combining metabolomic data with anatomical scoring systems allowed us to discriminate between these two groups with a greater degree of accuracy than that of either variable alone.",,pdf:https://www.mdpi.com/2218-1989/12/1/29/pdf?version=1642410547; doi:https://doi.org/10.3390/metabo12010029; html:https://europepmc.org/articles/PMC8780653; pdf:https://europepmc.org/articles/PMC8780653?pdf=render +38269898,https://doi.org/10.3233/shti231054,Identifying Mentions of Pain in Mental Health Records Text: A Natural Language Processing Approach.,"Chaturvedi J, Velupillai S, Stewart R, Roberts A.",,Studies in health technology and informatics,2024,2024-01-01,N,Pain; Mental health; Electronic Health Records; Natural Language Processing; Transformers,,,"Pain is a common reason for accessing healthcare resources and is a growing area of research, especially in its overlap with mental health. Mental health electronic health records are a good data source to study this overlap. However, much information on pain is held in the free text of these records, where mentions of pain present a unique natural language processing problem due to its ambiguous nature. This project uses data from an anonymised mental health electronic health records database. A machine learning based classification algorithm is trained to classify sentences as discussing patient pain or not. This will facilitate the extraction of relevant pain information from large databases. 1,985 documents were manually triple-annotated for creation of gold standard training data, which was used to train four classification algorithms. The best performing model achieved an F1-score of 0.98 (95% CI 0.98-0.99).",,pdf:https://ebooks.iospress.nl/pdf/doi/10.3233/SHTI231054; doi:https://doi.org/10.3233/SHTI231054 36217535,https://doi.org/10.1038/s43856-022-00185-6,"Multi-omic phenotyping reveals host-microbe responses to bariatric surgery, glycaemic control and obesity.","Penney NC, Yeung DKT, Garcia-Perez I, Posma JM, Kopytek A, Garratt B, Ashrafian H, Frost G, Marchesi JR, Purkayastha S, Hoyles L, Darzi A, Holmes E.",,Communications medicine,2022,2022-10-07,Y,Obesity; Type 2 diabetes; Dynamical Systems; Microbiome,,,"

Background

Resolution of type 2 diabetes (T2D) is common following bariatric surgery, particularly Roux-en-Y gastric bypass. However, the underlying mechanisms have not been fully elucidated.

Methods

To address this we compare the integrated serum, urine and faecal metabolic profiles of participants with obesity ± T2D (n = 80, T2D = 42) with participants who underwent Roux-en-Y gastric bypass or sleeve gastrectomy (pre and 3-months post-surgery; n = 27), taking diet into account. We co-model these data with shotgun metagenomic profiles of the gut microbiota to provide a comprehensive atlas of host-gut microbe responses to bariatric surgery, weight-loss and glycaemic control at the systems level.

Results

Here we show that bariatric surgery reverses several disrupted pathways characteristic of T2D. The differential metabolite set representative of bariatric surgery overlaps with both diabetes (19.3% commonality) and body mass index (18.6% commonality). However, the percentage overlap between diabetes and body mass index is minimal (4.0% commonality), consistent with weight-independent mechanisms of T2D resolution. The gut microbiota is more strongly correlated to body mass index than T2D, although we identify some pathways such as amino acid metabolism that correlate with changes to the gut microbiota and which influence glycaemic control.

Conclusion

We identify multi-omic signatures associated with responses to surgery, body mass index, and glycaemic control. Improved understanding of gut microbiota - host co-metabolism may lead to novel therapies for weight-loss or diabetes. However, further experiments are required to provide mechanistic insight into the role of the gut microbiota in host metabolism and establish proof of causality.",,pdf:https://www.nature.com/articles/s43856-022-00185-6.pdf; doi:https://doi.org/10.1038/s43856-022-00185-6; html:https://europepmc.org/articles/PMC9546886; pdf:https://europepmc.org/articles/PMC9546886?pdf=render 37363796,https://doi.org/10.1016/j.lanepe.2023.100636,Comparative effectiveness of two- and three-dose COVID-19 vaccination schedules involving AZD1222 and BNT162b2 in people with kidney disease: a linked OpenSAFELY and UK Renal Registry cohort study.,"OpenSAFELY Collaborative, Parker EPK, Horne EMF, Hulme WJ, Tazare J, Zheng B, Carr EJ, Loud F, Lyon S, Mahalingasivam V, MacKenna B, Mehrkar A, Scanlon M, Santhakumaran S, Steenkamp R, Goldacre B, Sterne JAC, Nitsch D, Tomlinson LA, LH&W NCS (or CONVALESCENCE) Collaborative.",,The Lancet regional health. Europe,2023,2023-05-03,Y,Vaccination; Effectiveness; Chronic Kidney Disease; Nhs England; Covid-19; Sars-cov-2,,,"

Background

Kidney disease is a key risk factor for COVID-19-related mortality and suboptimal vaccine response. Optimising vaccination strategies is essential to reduce the disease burden in this vulnerable population. We therefore compared the effectiveness of two- and three-dose schedules involving AZD1222 (AZ; ChAdOx1-S) and BNT162b2 (BNT) among people with kidney disease in England.

Methods

With the approval of NHS England, we performed a retrospective cohort study among people with moderate-to-severe kidney disease. Using linked primary care and UK Renal Registry records in the OpenSAFELY-TPP platform, we identified adults with stage 3-5 chronic kidney disease, dialysis recipients, and kidney transplant recipients. We used Cox proportional hazards models to compare COVID-19-related outcomes and non-COVID-19 death after two-dose (AZ-AZ vs BNT-BNT) and three-dose (AZ-AZ-BNT vs BNT-BNT-BNT) schedules.

Findings

After two doses, incidence during the Delta wave was higher in AZ-AZ (n = 257,580) than BNT-BNT recipients (n = 169,205; adjusted hazard ratios [95% CIs] 1.43 [1.37-1.50], 1.59 [1.43-1.77], 1.44 [1.12-1.85], and 1.09 [1.02-1.17] for SARS-CoV-2 infection, COVID-19-related hospitalisation, COVID-19-related death, and non-COVID-19 death, respectively). Findings were consistent across disease subgroups, including dialysis and transplant recipients. After three doses, there was little evidence of differences between AZ-AZ-BNT (n = 220,330) and BNT-BNT-BNT recipients (n = 157,065) for any outcome during a period of Omicron dominance.

Interpretation

Among individuals with moderate-to-severe kidney disease, two doses of BNT conferred stronger protection than AZ against SARS-CoV-2 infection and severe disease. A subsequent BNT dose levelled the playing field, emphasising the value of heterologous RNA doses in vulnerable populations.

Funding

National Core Studies, Wellcome Trust, MRC, and Health Data Research UK.",,doi:https://doi.org/10.1016/j.lanepe.2023.100636; doi:https://doi.org/10.1016/j.lanepe.2023.100636; html:https://europepmc.org/articles/PMC10155829; pdf:https://europepmc.org/articles/PMC10155829?pdf=render 35909058,https://doi.org/10.1016/s2589-7500(22)00123-6,Remote COVID-19 Assessment in Primary Care (RECAP) risk prediction tool: derivation and real-world validation studies.,"Espinosa-Gonzalez A, Prociuk D, Fiorentino F, Ramtale C, Mi E, Mi E, Glampson B, Neves AL, Okusi C, Husain L, Macartney J, Brown M, Browne B, Warren C, Chowla R, Heaversedge J, Greenhalgh T, de Lusignan S, Mayer E, Delaney BC.",,The Lancet. Digital health,2022,2022-07-28,Y,,,,"

Background

Accurate assessment of COVID-19 severity in the community is essential for patient care and requires COVID-19-specific risk prediction scores adequately validated in a community setting. Following a qualitative phase to identify signs, symptoms, and risk factors, we aimed to develop and validate two COVID-19-specific risk prediction scores. Remote COVID-19 Assessment in Primary Care-General Practice score (RECAP-GP; without peripheral oxygen saturation [SpO2]) and RECAP-oxygen saturation score (RECAP-O2; with SpO2).

Methods

RECAP was a prospective cohort study that used multivariable logistic regression. Data on signs and symptoms (predictors) of disease were collected from community-based patients with suspected COVID-19 via primary care electronic health records and linked with secondary data on hospital admission (outcome) within 28 days of symptom onset. Data sources for RECAP-GP were Oxford-Royal College of General Practitioners Research and Surveillance Centre (RCGP-RSC) primary care practices (development set), northwest London primary care practices (validation set), and the NHS COVID-19 Clinical Assessment Service (CCAS; validation set). The data source for RECAP-O2 was the Doctaly Assist platform (development set and validation set in subsequent sample). The two probabilistic risk prediction models were built by backwards elimination using the development sets and validated by application to the validation datasets. Estimated sample size per model, including the development and validation sets was 2880 people.

Findings

Data were available from 8311 individuals. Observations, such as SpO2, were mostly missing in the northwest London, RCGP-RSC, and CCAS data; however, SpO2 was available for 1364 (70·0%) of 1948 patients who used Doctaly. In the final predictive models, RECAP-GP (n=1863) included sex (male and female), age (years), degree of breathlessness (three point scale), temperature symptoms (two point scale), and presence of hypertension (yes or no); the area under the curve was 0·80 (95% CI 0·76-0·85) and on validation the negative predictive value of a low risk designation was 99% (95% CI 98·1-99·2; 1435 of 1453). RECAP-O2 included age (years), degree of breathlessness (two point scale), fatigue (two point scale), and SpO2 at rest (as a percentage); the area under the curve was 0·84 (0·78-0·90) and on validation the negative predictive value of low risk designation was 99% (95% CI 98·9-99·7; 1176 of 1183).

Interpretation

Both RECAP models are valid tools to assess COVID-19 patients in the community. RECAP-GP can be used initially, without need for observations, to identify patients who require monitoring. If the patient is monitored and SpO2 is available, RECAP-O2 is useful to assess the need for treatment escalation.

Funding

Community Jameel and the Imperial College President's Excellence Fund, the Economic and Social Research Council, UK Research and Innovation, and Health Data Research UK.",,doi:https://doi.org/10.1016/s2589-7500(22)00123-6; doi:https://doi.org/10.1016/S2589-7500(22)00123-6; html:https://europepmc.org/articles/PMC9333950; pdf:https://europepmc.org/articles/PMC9333950?pdf=render -37678881,https://doi.org/10.1093/ageing/afad157,Survival and critical care use among people with dementia in a large English cohort.,"Yorganci E, Sleeman KE, Sampson EL, Stewart R, EMBED-Care Programme.",,Age and ageing,2023,2023-09-01,Y,Survival; Dementia; Intensive Care; Older People; Critical Care; Routine Data,,,"

Background

Admitting people with dementia to critical care units may not always lead to a clear survival benefit. Critical care admissions of people with dementia vary across countries. Little is known about the use and trends of critical care admissions of people with dementia in England.

Objective

To investigate critical care use and survival among people with dementia in a large London catchment area.

Methods

A retrospective cohort study using data from dementia assessment services in south London, UK (2007-20) linked with national hospitalisation data to ascertain critical care admissions. Outcomes included age-sex-standardised critical care use and 1-year post-critical care admission survival by dementia severity (binary: mild versus moderate/severe). We used logistic regression and Kaplan-Meier survival plots for investigating 1-year survival following a critical care admission and linear regressions for time trends.

Results

Of 19,787 people diagnosed with dementia, 726 (3.7%) had ≥1 critical care admission at any time after receiving their dementia diagnosis. The overall 1-year survival of people with dementia, who had a CCA, was 47.5% (n = 345). Dementia severity was not associated with 1-year survival following a critical care admission (mild dementia versus moderate-severe dementia odds of 1-year mortality OR: 0.90, 95% CI [0.66-1.22]). Over the 12-year period from 2008 to 2019, overall critical care use decreased (β = -0.05; 95% CI = -0.01, -0.0003; P = 0.03), while critical care admissions occurring during the last year of life increased (β = 0.11, 95% CI = 0.01, 0.20, P = 0.03).

Conclusions

In this cohort, while critical care use among people with dementia declined overall, its use increased among those in their last year of life. Survival remains comparable to that observed in general older populations.",,doi:https://doi.org/10.1093/ageing/afad157; html:https://europepmc.org/articles/PMC10484725; pdf:https://europepmc.org/articles/PMC10484725?pdf=render 31878916,https://doi.org/10.1186/s12889-019-7919-2,Sustained adherence to a Mediterranean diet and physical activity on all-cause mortality in the Melbourne Collaborative Cohort Study: application of the g-formula.,"Williamson EJ, Polak J, Simpson JA, Giles GG, English DR, Hodge A, Gurrin L, Forbes AB.",,BMC public health,2019,2019-12-26,Y,G-computation; Time-varying Confounding; Parametric G-formula; G-methods,"Improving Public Health, Understanding the Causes of Disease",,"

Background

Adherence to a traditional Mediterranean diet has been associated with lower mortality and cardiovascular disease risk. The relative importance of diet compared to other lifestyle factors and effects of dietary patterns over time remains unknown.

Methods

We used the parametric G-formula to account for time-dependent confounding, in order to assess the relative importance of diet compared to other lifestyle factors and effects of dietary patterns over time. We included healthy Melbourne Collaborative Cohort Study participants attending a visit during 1995-1999. Questionnaires assessed diet and physical activity at each of three study waves. Deaths were identified by linkage to national registries. We estimated mortality risk over approximately 14 years (1995-2011).

Results

Of 22,213 participants, 2163 (9.7%) died during 13.6 years median follow-up. Sustained high physical activity and adherence to a Mediterranean-style diet resulted in an estimated reduction in all-cause mortality of 1.82 per 100 people (95% confidence interval (CI): 0.03, 3.6). The population attributable fraction was 13% (95% CI: 4, 23%) for sustained high physical activity, 7% (95% CI: - 3, 17%) for sustained adherence to a Mediterranean-style diet and 18% (95% CI: 0, 36%) for their combination.

Conclusions

A small reduction in mortality may be achieved by sustained elevated physical activity levels in healthy middle-aged adults, but there may be comparatively little gain from increasing adherence to a Mediterranean-style diet.",This study aimed to calculate the proportion of deaths that could be prevented over a 14 year period through making long-term changes in lifestyle (diet and physical activity). Over 22K people were included in the study and filled out questionnaires about their lifestyle at three different time points. The authors used statistical methods that take into account how lifestyle measurements change over time and estimated the relative impact that different lifestyle factors have on death. The study suggests that being more physically active in middle age is more likely to reduce mortality than maintaining a Mediterranean-style diet.,pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-019-7919-2; doi:https://doi.org/10.1186/s12889-019-7919-2; html:https://europepmc.org/articles/PMC6933918; pdf:https://europepmc.org/articles/PMC6933918?pdf=render +37678881,https://doi.org/10.1093/ageing/afad157,Survival and critical care use among people with dementia in a large English cohort.,"Yorganci E, Sleeman KE, Sampson EL, Stewart R, EMBED-Care Programme.",,Age and ageing,2023,2023-09-01,Y,Survival; Dementia; Intensive Care; Older People; Critical Care; Routine Data,,,"

Background

Admitting people with dementia to critical care units may not always lead to a clear survival benefit. Critical care admissions of people with dementia vary across countries. Little is known about the use and trends of critical care admissions of people with dementia in England.

Objective

To investigate critical care use and survival among people with dementia in a large London catchment area.

Methods

A retrospective cohort study using data from dementia assessment services in south London, UK (2007-20) linked with national hospitalisation data to ascertain critical care admissions. Outcomes included age-sex-standardised critical care use and 1-year post-critical care admission survival by dementia severity (binary: mild versus moderate/severe). We used logistic regression and Kaplan-Meier survival plots for investigating 1-year survival following a critical care admission and linear regressions for time trends.

Results

Of 19,787 people diagnosed with dementia, 726 (3.7%) had ≥1 critical care admission at any time after receiving their dementia diagnosis. The overall 1-year survival of people with dementia, who had a CCA, was 47.5% (n = 345). Dementia severity was not associated with 1-year survival following a critical care admission (mild dementia versus moderate-severe dementia odds of 1-year mortality OR: 0.90, 95% CI [0.66-1.22]). Over the 12-year period from 2008 to 2019, overall critical care use decreased (β = -0.05; 95% CI = -0.01, -0.0003; P = 0.03), while critical care admissions occurring during the last year of life increased (β = 0.11, 95% CI = 0.01, 0.20, P = 0.03).

Conclusions

In this cohort, while critical care use among people with dementia declined overall, its use increased among those in their last year of life. Survival remains comparable to that observed in general older populations.",,doi:https://doi.org/10.1093/ageing/afad157; html:https://europepmc.org/articles/PMC10484725; pdf:https://europepmc.org/articles/PMC10484725?pdf=render 33780469,https://doi.org/10.1371/journal.pone.0248195,Deriving household composition using population-scale electronic health record data-A reproducible methodology.,"Johnson RD, Griffiths LJ, Hollinghurst JP, Akbari A, Lee A, Thompson DA, Lyons RA, Fry R.",,PloS one,2021,2021-03-29,Y,,,,"

Background

Physical housing and household composition have an important role in the lives of individuals and drive health and social outcomes, and inequalities. Most methods to understand housing composition are based on survey or census data, and there is currently no reproducible methodology for creating population-level household composition measures using linked administrative data.

Methods

Using existing, and more recent enhancements to the address-data linkage methods in the SAIL Databank using Residential Anonymised Linking Fields we linked individuals to properties using the anonymised Welsh Demographic Service data in the SAIL Databank. We defined households, household size, and household composition measures based on adult to child relationships, and age differences between residents to create relative age measures.

Results

Two relative age-based algorithms were developed and returned similar results when applied to population and household-level data, describing household composition for 3.1 million individuals within 1.2 million households in Wales. Developed methods describe binary, and count level generational household composition measures.

Conclusions

Improved residential anonymised linkage field methods in SAIL have led to improved property-level data linkage, allowing the design and application of household composition measures that assign individuals to shared residences and allow the description of household composition across Wales. The reproducible methods create longitudinal, household-level composition measures at a population-level using linked administrative data. Such measures are important to help understand more detail about an individual's home and area environment and how that may affect the health and wellbeing of the individual, other residents, and potentially into the wider community.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0248195&type=printable; doi:https://doi.org/10.1371/journal.pone.0248195; html:https://europepmc.org/articles/PMC8007012; pdf:https://europepmc.org/articles/PMC8007012?pdf=render 37795045,https://doi.org/10.1177/26320843221147855,Monitoring metrics over time: Why clinical trialists need to systematically collect site performance metrics.,"Yorke-Edwards V, Diaz-Montana C, Murray ML, Sydes MR, Love SB.",,Research methods in medicine & health sciences,2023,2022-12-21,N,Clinical Trials; Risk-based Monitoring; Central Monitoring; Study-Within-A-Trial (Swat); Centralised Monitoring,,,"

Background

Over the last decade, there has been an increasing interest in risk-based monitoring (RBM) in clinical trials, resulting in a number of guidelines from regulators and its inclusion in ICH GCP. However, there is a lack of detail on how to approach RBM from a practical perspective, and insufficient understanding of best practice.

Purpose

We present a method for clinical trials units to track their metrics within clinical trials using descriptive statistics and visualisations.

Research design

We suggest descriptive statistics and visualisations within a SWAT methodology.

Study sample

We illustrate this method using the metrics from TEMPER, a monitoring study carried out in three trials at the MRC Clinical Trials Unit at UCL.

Data collection

The data collection for TEMPER is described in DOI: 10.1177/1740774518793379.

Results

We show the results and discuss a protocol for a Study-Within-A-Trial (SWAT 167) for those wishing to use the method.

Conclusions

The potential benefits metric tracking brings to clinical trials include enhanced assessment of sites for potential corrective action, improved evaluation and contextualisation of the influence of metrics and their thresholds, and the establishment of best practice in RBM. The standardisation of the collection of such monitoring data would benefit both individual trials and the clinical trials community.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/26320843221147855; doi:https://doi.org/10.1177/26320843221147855; html:https://europepmc.org/articles/PMC7615148; pdf:https://europepmc.org/articles/PMC7615148?pdf=render; doi:https://doi.org/10.1177/26320843221147855 35595824,https://doi.org/10.1038/s41598-022-12517-6,Transmission dynamics of SARS-CoV-2 in a strictly-Orthodox Jewish community in the UK.,"Waites W, Pearson CAB, Gaskell KM, House T, Pellis L, Johnson M, Gould V, Hunt A, Stone NRH, Kasstan B, Chantler T, Lal S, Roberts CH, Goldblatt D, CMMID COVID-19 Working Group, Marks M, Eggo RM.",,Scientific reports,2022,2022-05-20,Y,,,,"Some social settings such as households and workplaces, have been identified as high risk for SARS-CoV-2 transmission. Identifying and quantifying the importance of these settings is critical for designing interventions. A tightly-knit religious community in the UK experienced a very large COVID-19 epidemic in 2020, reaching 64.3% seroprevalence within 10 months, and we surveyed this community both for serological status and individual-level attendance at particular settings. Using these data, and a network model of people and places represented as a stochastic graph rewriting system, we estimated the relative contribution of transmission in households, schools and religious institutions to the epidemic, and the relative risk of infection in each of these settings. All congregate settings were important for transmission, with some such as primary schools and places of worship having a higher share of transmission than others. We found that the model needed a higher general-community transmission rate for women (3.3-fold), and lower susceptibility to infection in children to recreate the observed serological data. The precise share of transmission in each place was related to assumptions about the internal structure of those places. Identification of key settings of transmission can allow public health interventions to be targeted at these locations.",,pdf:https://www.nature.com/articles/s41598-022-12517-6.pdf; doi:https://doi.org/10.1038/s41598-022-12517-6; html:https://europepmc.org/articles/PMC9121858; pdf:https://europepmc.org/articles/PMC9121858?pdf=render @@ -407,8 +407,8 @@ PMC10910267,https://doi.org/,Development and evaluation of a tool to optimise in 32989456,https://doi.org/10.1093/ije/dyaa144,Emulating a target trial in case-control designs: an application to statins and colorectal cancer.,"Dickerman BA, García-Albéniz X, Logan RW, Denaxas S, Hernán MA.",,International journal of epidemiology,2020,2020-10-01,N,Causal Inference; Electronic Health Records; Case-control; Comparative Effectiveness; Target Trial,,,"

Background

Previous case-control studies have reported a strong association between statin use and lower cancer risk. It is unclear whether this association reflects a benefit of statins or is the result of design decisions that cannot be mapped to a (hypothetical) target trial (that would answer the question of interest).

Methods

We outlined the protocol of a target trial to estimate the effect of statins on colorectal cancer incidence among adults with low-density lipoprotein (LDL) cholesterol below 5 mmol/L. We then emulated the target trial using linked electronic health records of 752 469 eligible UK adults (CALIBER 1999-2016) under both a cohort design and a case-control sampling of the cohort. We used pooled logistic regression to estimate intention-to-treat and per-protocol effects of statins on colorectal cancer, with adjustment for baseline and time-varying risk factors via inverse-probability weighting. Finally, we compared our case-control effect estimates with those obtained using previous case-control procedures.

Results

Over the 6-year follow-up, 3596 individuals developed colorectal cancer. Estimated intention-to-treat and per-protocol hazard ratios were 1.00 (95% confidence interval [CI]: 0.87, 1.16) and 0.90 (95% CI: 0.71, 1.12), respectively. As expected, adequate case-control sampling yielded the same estimates. By contrast, previous case-control analytical approaches yielded estimates that appeared strongly protective (odds ratio 0.57, 95% CI: 0.36, 0.91, for ≥5 vs. <5 years of statin use).

Conclusions

Our study demonstrates how to explicitly emulate a target trial using case-control data to reduce discrepancies between observational and randomized trial evidence. This approach may inform future case-control analyses for comparative effectiveness research.",,pdf:https://academic.oup.com/ije/article-pdf/49/5/1637/34947124/dyaa144.pdf; doi:https://doi.org/10.1093/ije/dyaa144; html:https://europepmc.org/articles/PMC7746409; pdf:https://europepmc.org/articles/PMC7746409?pdf=render; doi:https://doi.org/10.1093/ije/dyaa144 35189888,https://doi.org/10.1186/s12916-022-02286-4,Determinants of pre-vaccination antibody responses to SARS-CoV-2: a population-based longitudinal study (COVIDENCE UK).,"Talaei M, Faustini S, Holt H, Jolliffe DA, Vivaldi G, Greenig M, Perdek N, Maltby S, Bigogno CM, Symons J, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Richter AG, Shaheen SO, Martineau AR.",,BMC medicine,2022,2022-02-22,Y,Obesity; Diet; Serology; Alcohol; Exercise; Micronutrients; Lifestyle; Ethnicity; Occupation; Sars-cov-2,,,"

Background

Prospective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking.

Methods

We did a prospective population-based study in SARS-CoV-2 vaccine-naive UK adults recruited between May 1 and November 2, 2020, without a positive swab test result for SARS-CoV-2 prior to enrolment. Information on 88 potential sociodemographic, behavioural, nutritional, clinical and pharmacological risk factors was obtained through online questionnaires, and combined IgG/IgA/IgM responses to SARS-CoV-2 spike glycoprotein were determined in dried blood spots obtained between November 6, 2020, and April 18, 2021. We used logistic and linear regression to estimate adjusted odds ratios (aORs) and adjusted geometric mean ratios (aGMRs) for potential determinants of SARS-CoV-2 seropositivity (all participants) and antibody titres (seropositive participants only), respectively.

Results

Of 11,130 participants, 1696 (15.2%) were seropositive. Factors independently associated with  higher risk of SARS-CoV-2 seropositivity included frontline health/care occupation (aOR 1.86, 95% CI 1.48-2.33), international travel (1.20, 1.07-1.35), number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.29, 1.06-1.57, P-trend = 0.01), body mass index (BMI) ≥ 25 vs. < 25 kg/m2 (1.24, 1.11-1.39), South Asian vs. White ethnicity (1.65, 1.10-2.49) and alcohol consumption ≥15 vs. 0 units/week (1.23, 1.04-1.46). Light physical exercise associated with  lower risk (0.80, 0.70-0.93, for ≥ 10 vs. 0-4 h/week). Among seropositive participants, higher titres of anti-Spike antibodies associated with factors including BMI ≥ 30 vs. < 25 kg/m2 (aGMR 1.10, 1.02-1.19), South Asian vs. White ethnicity (1.22, 1.04-1.44), frontline health/care occupation (1.24, 95% CI 1.11-1.39), international travel (1.11, 1.05-1.16) and number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.12, 1.02-1.23, P-trend = 0.01); these associations were not substantially attenuated by adjustment for COVID-19 disease severity.

Conclusions

Higher alcohol consumption and lower light physical exercise represent new modifiable risk factors for SARS-CoV-2 infection. Recognised associations between South Asian ethnic origin and obesity and higher risk of SARS-CoV-2 seropositivity were independent of other sociodemographic, behavioural, nutritional, clinical, and pharmacological factors investigated. Among seropositive participants, higher titres of anti-Spike antibodies in people of South Asian ancestry and in obese people were not explained by greater COVID-19 disease severity in these groups.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-022-02286-4; doi:https://doi.org/10.1186/s12916-022-02286-4; html:https://europepmc.org/articles/PMC8860623; pdf:https://europepmc.org/articles/PMC8860623?pdf=render 37363797,https://doi.org/10.1016/j.lanepe.2023.100653,Impact of COVID-19 on broad-spectrum antibiotic prescribing for common infections in primary care in England: a time-series analyses using OpenSAFELY and effects of predictors including deprivation.,"Zhong X, Pate A, Yang YT, Fahmi A, Ashcroft DM, Goldacre B, MacKenna B, Mehrkar A, Bacon SC, Massey J, Fisher L, Inglesby P, OpenSAFELY collaborative, Hand K, van Staa T, Palin V.",,The Lancet regional health. Europe,2023,2023-05-16,Y,Antimicrobial resistance; Primary Care; Broad-spectrum Antibiotics; Covid-19 Pandemic,,,"

Background

The COVID-19 pandemic impacted the healthcare systems, adding extra pressure to reduce antimicrobial resistance. Therefore, we aimed to evaluate changes in antibiotic prescription patterns after COVID-19 started.

Methods

With the approval of NHS England, we used the OpenSAFELY platform to access the TPP SystmOne electronic health record (EHR) system in primary care and selected patients prescribed antibiotics from 2019 to 2021. To evaluate the impact of COVID-19 on broad-spectrum antibiotic prescribing, we evaluated prescribing rates and its predictors and used interrupted time series analysis by fitting binomial logistic regression models.

Findings

Over 32 million antibiotic prescriptions were extracted over the study period; 8.7% were broad-spectrum. The study showed increases in broad-spectrum antibiotic prescribing (odds ratio [OR] 1.37; 95% confidence interval [CI] 1.36-1.38) as an immediate impact of the pandemic, followed by a gradual recovery with a 1.1-1.2% decrease in odds of broad-spectrum prescription per month. The same pattern was found within subgroups defined by age, sex, region, ethnicity, and socioeconomic deprivation quintiles. More deprived patients were more likely to receive broad-spectrum antibiotics, which differences remained stable over time. The most significant increase in broad-spectrum prescribing was observed for lower respiratory tract infection (OR 2.33; 95% CI 2.1-2.50) and otitis media (OR 1.96; 95% CI 1.80-2.13).

Interpretation

An immediate reduction in antibiotic prescribing and an increase in the proportion of broad-spectrum antibiotic prescribing in primary care was observed. The trends recovered to pre-pandemic levels, but the consequence of the COVID-19 pandemic on AMR needs further investigation.

Funding

This work was supported by Health Data Research UK and by National Institute for Health Research.",,doi:https://doi.org/10.1016/j.lanepe.2023.100653; doi:https://doi.org/10.1016/j.lanepe.2023.100653; html:https://europepmc.org/articles/PMC10186397; pdf:https://europepmc.org/articles/PMC10186397?pdf=render -36544046,https://doi.org/10.1038/s41746-022-00730-6,A survey on clinical natural language processing in the United Kingdom from 2007 to 2022.,"Wu H, Wang M, Wu J, Francis F, Chang YH, Shavick A, Dong H, Poon MTC, Fitzpatrick N, Levine AP, Slater LT, Handy A, Karwath A, Gkoutos GV, Chelala C, Shah AD, Stewart R, Collier N, Alex B, Whiteley W, Sudlow C, Roberts A, Dobson RJB.",,NPJ digital medicine,2022,2022-12-21,Y,,,,"Much of the knowledge and information needed for enabling high-quality clinical research is stored in free-text format. Natural language processing (NLP) has been used to extract information from these sources at scale for several decades. This paper aims to present a comprehensive review of clinical NLP for the past 15 years in the UK to identify the community, depict its evolution, analyse methodologies and applications, and identify the main barriers. We collect a dataset of clinical NLP projects (n = 94; £ = 41.97 m) funded by UK funders or the European Union's funding programmes. Additionally, we extract details on 9 funders, 137 organisations, 139 persons and 431 research papers. Networks are created from timestamped data interlinking all entities, and network analysis is subsequently applied to generate insights. 431 publications are identified as part of a literature review, of which 107 are eligible for final analysis. Results show, not surprisingly, clinical NLP in the UK has increased substantially in the last 15 years: the total budget in the period of 2019-2022 was 80 times that of 2007-2010. However, the effort is required to deepen areas such as disease (sub-)phenotyping and broaden application domains. There is also a need to improve links between academia and industry and enable deployments in real-world settings for the realisation of clinical NLP's great potential in care delivery. The major barriers include research and development access to hospital data, lack of capable computational resources in the right places, the scarcity of labelled data and barriers to sharing of pretrained models.",,pdf:https://www.nature.com/articles/s41746-022-00730-6.pdf; doi:https://doi.org/10.1038/s41746-022-00730-6; html:https://europepmc.org/articles/PMC9770568; pdf:https://europepmc.org/articles/PMC9770568?pdf=render 34598993,https://doi.org/10.1136/bmjopen-2021-054410,"Changes in neonatal admissions, care processes and outcomes in England and Wales during the COVID-19 pandemic: a whole population cohort study.","Greenbury SF, Longford N, Ougham K, Angelini ED, Battersby C, Uthaya S, Modi N.",,BMJ open,2021,2021-10-01,Y,Public Health; Neonatology; Neonatal Intensive & Critical Care,,,"

Objectives

The COVID-19 pandemic instigated multiple societal and healthcare interventions with potential to affect perinatal practice. We evaluated population-level changes in preterm and full-term admissions to neonatal units, care processes and outcomes.

Design

Observational cohort study using the UK National Neonatal Research Database.

Setting

England and Wales.

Participants

Admissions to National Health Service neonatal units from 2012 to 2020.

Main outcome measures

Admissions by gestational age, ethnicity and Index of Multiple Deprivation, and key care processes and outcomes.

Methods

We calculated differences in numbers and rates between April and June 2020 (spring), the first 3 months of national lockdown (COVID-19 period), and December 2019-February 2020 (winter), prior to introduction of mitigation measures, and compared them with the corresponding differences in the previous 7 years. We considered the COVID-19 period highly unusual if the spring-winter difference was smaller or larger than all previous corresponding differences, and calculated the level of confidence in this conclusion.

Results

Marked fluctuations occurred in all measures over the 8 years with several highly unusual changes during the COVID-19 period. Total admissions fell, having risen over all previous years (COVID-19 difference: -1492; previous 7-year difference range: +100, +1617; p<0.001); full-term black admissions rose (+66; -64, +35; p<0.001) whereas Asian (-137; -14, +101; p<0.001) and white (-319; -235, +643: p<0.001) admissions fell. Transfers to higher and lower designation neonatal units increased (+129; -4, +88; p<0.001) and decreased (-47; -25, +12; p<0.001), respectively. Total preterm admissions decreased (-350; -26, +479; p<0.001). The fall in extremely preterm admissions was most marked in the two lowest socioeconomic quintiles.

Conclusions

Our findings indicate substantial changes occurred in care pathways and clinical thresholds, with disproportionate effects on black ethnic groups, during the immediate COVID-19 period, and raise the intriguing possibility that non-healthcare interventions may reduce extremely preterm births.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/10/e054410.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054410; html:https://europepmc.org/articles/PMC8488283; pdf:https://europepmc.org/articles/PMC8488283?pdf=render +36544046,https://doi.org/10.1038/s41746-022-00730-6,A survey on clinical natural language processing in the United Kingdom from 2007 to 2022.,"Wu H, Wang M, Wu J, Francis F, Chang YH, Shavick A, Dong H, Poon MTC, Fitzpatrick N, Levine AP, Slater LT, Handy A, Karwath A, Gkoutos GV, Chelala C, Shah AD, Stewart R, Collier N, Alex B, Whiteley W, Sudlow C, Roberts A, Dobson RJB.",,NPJ digital medicine,2022,2022-12-21,Y,,,,"Much of the knowledge and information needed for enabling high-quality clinical research is stored in free-text format. Natural language processing (NLP) has been used to extract information from these sources at scale for several decades. This paper aims to present a comprehensive review of clinical NLP for the past 15 years in the UK to identify the community, depict its evolution, analyse methodologies and applications, and identify the main barriers. We collect a dataset of clinical NLP projects (n = 94; £ = 41.97 m) funded by UK funders or the European Union's funding programmes. Additionally, we extract details on 9 funders, 137 organisations, 139 persons and 431 research papers. Networks are created from timestamped data interlinking all entities, and network analysis is subsequently applied to generate insights. 431 publications are identified as part of a literature review, of which 107 are eligible for final analysis. Results show, not surprisingly, clinical NLP in the UK has increased substantially in the last 15 years: the total budget in the period of 2019-2022 was 80 times that of 2007-2010. However, the effort is required to deepen areas such as disease (sub-)phenotyping and broaden application domains. There is also a need to improve links between academia and industry and enable deployments in real-world settings for the realisation of clinical NLP's great potential in care delivery. The major barriers include research and development access to hospital data, lack of capable computational resources in the right places, the scarcity of labelled data and barriers to sharing of pretrained models.",,pdf:https://www.nature.com/articles/s41746-022-00730-6.pdf; doi:https://doi.org/10.1038/s41746-022-00730-6; html:https://europepmc.org/articles/PMC9770568; pdf:https://europepmc.org/articles/PMC9770568?pdf=render 37400731,https://doi.org/10.1007/s10802-023-01086-5,Maternal Mental Health and Children's Problem Behaviours: A Bi-directional Relationship?,"Lowthian E, Bedston S, Kristensen SM, Akbari A, Fry R, Huxley K, Johnson R, Kim HS, Owen RK, Taylor C, Griffiths L.",,Research on child and adolescent psychopathology,2023,2023-07-04,Y,Child Development; Bayesian analysis; Structural Equation Modelling; Maternal Mental Health; Millennium Cohort Study,,,"Transactional theory and the coercive family process model have illustrated how the parent-child relationship is reciprocal. Emerging research using advanced statistical methods has examined these theories, but further investigations are necessary. In this study, we utilised linked health data on maternal mental health disorders and explored their relationship with child problem behaviours via the Strengths and Difficulties Questionnaire for over 13 years. We accessed data from the Millennium Cohort Study, linked to anonymised individual-level population-scale health and administrative data within the Secure Anonymised Information Linkage (SAIL) Databank. We used Bayesian Structural Equation Modelling, specifically Random-Intercept Cross-Lagged Panel Models, to analyse the relationships between mothers and their children. We then explored these models with the addition of time-invariant covariates. We found that a mother's mental health was strongly associated over time, as were children's problem behaviours. We found mixed evidence for bi-directional relationships, with only emotional problems showing bi-directional associations in mid to late childhood. Only child-to-mother pathways were identified for the overall problem behaviour score and peer problems; no associations were found for conduct problems or hyperactivity. All models had strong between-effects and clear socioeconomic and sex differences. We encourage the use of whole family-based support for mental health and problem behaviours, and recommend that socioeconomic, sex and wider differences should be considered as factors in tailoring family-based interventions and support.",,pdf:https://link.springer.com/content/pdf/10.1007/s10802-023-01086-5.pdf; doi:https://doi.org/10.1007/s10802-023-01086-5; html:https://europepmc.org/articles/PMC10628040; pdf:https://europepmc.org/articles/PMC10628040?pdf=render 35413949,https://doi.org/10.1038/s41467-022-29521-z,"Persistent COVID-19 symptoms in a community study of 606,434 people in England.","Whitaker M, Elliott J, Chadeau-Hyam M, Riley S, Darzi A, Cooke G, Ward H, Elliott P.",,Nature communications,2022,2022-04-12,Y,,,,"Long COVID remains a broadly defined syndrome, with estimates of prevalence and duration varying widely. We use data from rounds 3-5 of the REACT-2 study (n = 508,707; September 2020 - February 2021), a representative community survey of adults in England, and replication data from round 6 (n = 97,717; May 2021) to estimate the prevalence and identify predictors of persistent symptoms lasting 12 weeks or more; and unsupervised learning to cluster individuals by reported symptoms. At 12 weeks in rounds 3-5, 37.7% experienced at least one symptom, falling to 21.6% in round 6. Female sex, increasing age, obesity, smoking, vaping, hospitalisation with COVID-19, deprivation, and being a healthcare worker are associated with higher probability of persistent symptoms in rounds 3-5, and Asian ethnicity with lower probability. Clustering analysis identifies a subset of participants with predominantly respiratory symptoms. Managing the long-term sequelae of COVID-19 will remain a major challenge for affected individuals and their families and for health services.",,pdf:https://www.nature.com/articles/s41467-022-29521-z.pdf; doi:https://doi.org/10.1038/s41467-022-29521-z; html:https://europepmc.org/articles/PMC9005552; pdf:https://europepmc.org/articles/PMC9005552?pdf=render 33948220,https://doi.org/10.1177/20552076211007661,Association between glycosylated haemoglobin and outcomes for patients discharged from hospital with diabetes: A health informatics approach.,"Robbins T, Sankaranarayanan S, Randeva H, Keung SNLC, Arvanitis TN.",,Digital health,2021,2021-01-01,Y,Biochemistry; Diabetes; Hospital Discharge; Readmission; Health Informatics,,,"

Aims/objectives

Extensive research considers associations between inpatient glycaemic control and outcomes during hospital admission; this cautions against overly tight glycaemic targets. Little research considers glycaemic control following hospital discharge. This is despite a clear understanding that people with diabetes are at increased risk of negative outcomes, following discharge. We evaluate absolute and relative Hba1c values, and frequency of Hba1c monitoring, on readmission and mortality rates for people discharged from hospital with diabetes.

Methods

All discharges (n = 46,357) with diabetes from a major tertiary referral centre over 3 years were extracted, including biochemistry data. We conducted an evaluation of association between Hba1c, mortality and readmission, statistical significance and standardised Cohen's D effect size calculations.

Results

399 patients had a Hba1c performed during their admission. 3,138 patients had a Hba1c within 1 year of discharge. Mean average Hba1c for readmissions was 57.82 vs 60.39 for not readmitted (p = 0.009, Cohen's D 0.28). Mean average number of days to Hba1c testing in readmitted was 97 vs 113 for those not readmitted (p = 0.00006, Cohen's D 0.39). Further evaluation of mortality outcomes, cohorts of T1DM and T2DM and association of relative change in Hba1c was performed.

Conclusions

Lower Hba1c values following discharge from hospital are significantly associated with increased risk of readmission, as is a shorter duration until testing. Similar patterns observed for mortality. Findings particularly prominent for T1DM. Further research needed to consider underlying causation and design of appropriate risk stratification models.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/20552076211007661; doi:https://doi.org/10.1177/20552076211007661; html:https://europepmc.org/articles/PMC8054217; pdf:https://europepmc.org/articles/PMC8054217?pdf=render @@ -420,8 +420,8 @@ PMC10910267,https://doi.org/,Development and evaluation of a tool to optimise in 34340970,https://doi.org/10.3399/bjgp.2021.0301,Clinical coding of long COVID in English primary care: a federated analysis of 58 million patient records in situ using OpenSAFELY.,"Walker AJ, MacKenna B, Inglesby P, Tomlinson L, Rentsch CT, Curtis HJ, Morton CE, Morley J, Mehrkar A, Bacon S, Hickman G, Bates C, Croker R, Evans D, Ward T, Cockburn J, Davy S, Bhaskaran K, Schultze A, Williamson EJ, Hulme WJ, McDonald HI, Mathur R, Eggo RM, Wing K, Wong AY, Forbes H, Tazare J, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Douglas IJ, Evans SJ, (The OpenSAFELY Collaborative).",,The British journal of general practice : the journal of the Royal College of General Practitioners,2021,2021-10-28,Y,Primary Health Care; General Practice; Electronic Health Records; Covid-19; Long Covid,,,"

Background

Long COVID describes new or persistent symptoms at least 4 weeks after onset of acute COVID-19. Clinical codes to describe this phenomenon were recently created.

Aim

To describe the use of long-COVID codes, and variation of use by general practice, demographic variables, and over time.

Design and setting

Population-based cohort study in English primary care.

Method

Working on behalf of NHS England, OpenSAFELY data were used encompassing 96% of the English population between 1 February 2020 and 25 May 2021. The proportion of people with a recorded code for long COVID was measured overall and by demographic factors, electronic health record software system (EMIS or TPP), and week.

Results

Long COVID was recorded for 23 273 people. Coding was unevenly distributed among practices, with 26.7% of practices having never used the codes. Regional variation ranged between 20.3 per 100 000 people for East of England (95% confidence interval [CI] = 19.3 to 21.4) and 55.6 per 100 000 people in London (95% CI = 54.1 to 57.1). Coding was higher among females (52.1, 95% CI = 51.3 to 52.9) than males (28.1, 95% CI = 27.5 to 28.7), and higher among practices using EMIS (53.7, 95% CI = 52.9 to 54.4) than those using TPP (20.9, 95% CI = 20.3 to 21.4).

Conclusion

Current recording of long COVID in primary care is very low, and variable between practices. This may reflect patients not presenting; clinicians and patients holding different diagnostic thresholds; or challenges with the design and communication of diagnostic codes. Increased awareness of diagnostic codes is recommended to facilitate research and planning of services, and also surveys with qualitative work to better evaluate clinicians' understanding of the diagnosis.",,pdf:https://bjgp.org/content/bjgp/71/712/e806.full.pdf; doi:https://doi.org/10.3399/BJGP.2021.0301; html:https://europepmc.org/articles/PMC8340730; pdf:https://europepmc.org/articles/PMC8340730?pdf=render 35289755,https://doi.org/10.2196/31021,Concept Libraries for Repeatable and Reusable Research: Qualitative Study Exploring the Needs of Users.,"Almowil Z, Zhou SM, Brophy S, Croxall J.",,JMIR human factors,2022,2022-03-15,Y,Electronic Health Records; Record Linkage; Reproducible Research; Clinical Codes; Concept Libraries,,,"

Background

Big data research in the field of health sciences is hindered by a lack of agreement on how to identify and define different conditions and their medications. This means that researchers and health professionals often have different phenotype definitions for the same condition. This lack of agreement makes it difficult to compare different study findings and hinders the ability to conduct repeatable and reusable research.

Objective

This study aims to examine the requirements of various users, such as researchers, clinicians, machine learning experts, and managers, in the development of a data portal for phenotypes (a concept library).

Methods

This was a qualitative study using interviews and focus group discussion. One-to-one interviews were conducted with researchers, clinicians, machine learning experts, and senior research managers in health data science (N=6) to explore their specific needs in the development of a concept library. In addition, a focus group discussion with researchers (N=14) working with the Secured Anonymized Information Linkage databank, a national eHealth data linkage infrastructure, was held to perform a SWOT (strengths, weaknesses, opportunities, and threats) analysis for the phenotyping system and the proposed concept library. The interviews and focus group discussion were transcribed verbatim, and 2 thematic analyses were performed.

Results

Most of the participants thought that the prototype concept library would be a very helpful resource for conducting repeatable research, but they specified that many requirements are needed before its development. Although all the participants stated that they were aware of some existing concept libraries, most of them expressed negative perceptions about them. The participants mentioned several facilitators that would stimulate them to share their work and reuse the work of others, and they pointed out several barriers that could inhibit them from sharing their work and reusing the work of others. The participants suggested some developments that they would like to see to improve reproducible research output using routine data.

Conclusions

The study indicated that most interviewees valued a concept library for phenotypes. However, only half of the participants felt that they would contribute by providing definitions for the concept library, and they reported many barriers regarding sharing their work on a publicly accessible platform. Analysis of interviews and the focus group discussion revealed that different stakeholders have different requirements, facilitators, barriers, and concerns about a prototype concept library.",,doi:https://doi.org/10.2196/31021; doi:https://doi.org/10.2196/31021; html:https://europepmc.org/articles/PMC8965669 34862222,https://doi.org/10.7861/clinmed.2021-0386,'What is the risk to me from COVID-19?': Public involvement in providing mortality risk information for people with 'high-risk' conditions for COVID-19 (OurRisk.CoV).,"Banerjee A, Pasea L, Manohar S, Lai AG, Hemingway E, Sofer I, Katsoulis M, Sood H, Morris A, Cake C, Fitzpatrick NK, Williams B, Denaxas S, Hemingway H, and members of the Health Data Research UK COVID-19 Patient and Public Involvement and Engagement Panel.",,"Clinical medicine (London, England)",2021,2021-11-01,N,Mortality; Coronavirus; Patient And Public Involvement; Risk Information,,,"Patients and public have sought mortality risk information throughout the pandemic, but their needs may not be served by current risk prediction tools. Our mixed methods study involved: (1) systematic review of published risk tools for prognosis, (2) provision and patient testing of new mortality risk estimates for people with high-risk conditions and (3) iterative patient and public involvement and engagement with qualitative analysis. Only one of 53 (2%) previously published risk tools involved patients or the public, while 11/53 (21%) had publicly accessible portals, but all for use by clinicians and researchers.Among people with a wide range of underlying conditions, there has been sustained interest and engagement in accessible and tailored, pre- and postpandemic mortality information. Informed by patient feedback, we provide such information in 'five clicks' (https://covid19-phenomics.org/OurRiskCoV.html), as context for decision making and discussions with health professionals and family members. Further development requires curation and regular updating of NHS data and wider patient and public engagement.",,pdf:https://www.rcpjournals.org/content/clinmedicine/21/6/e620.full.pdf; doi:https://doi.org/10.7861/clinmed.2021-0386; html:https://europepmc.org/articles/PMC8806292; pdf:https://europepmc.org/articles/PMC8806292?pdf=render; doi:https://doi.org/10.7861/clinmed.2021-0386 -38769347,https://doi.org/10.1038/s41746-024-01065-0,Self-supervised learning of accelerometer data provides new insights for sleep and its association with mortality.,"Yuan H, Plekhanova T, Walmsley R, Reynolds AC, Maddison KJ, Bucan M, Gehrman P, Rowlands A, Ray DW, Bennett D, McVeigh J, Straker L, Eastwood P, Kyle SD, Doherty A.",,NPJ digital medicine,2024,2024-05-20,Y,,,,"Sleep is essential to life. Accurate measurement and classification of sleep/wake and sleep stages is important in clinical studies for sleep disorder diagnoses and in the interpretation of data from consumer devices for monitoring physical and mental well-being. Existing non-polysomnography sleep classification techniques mainly rely on heuristic methods developed in relatively small cohorts. Thus, we aimed to establish the accuracy of wrist-worn accelerometers for sleep stage classification and subsequently describe the association between sleep duration and efficiency (proportion of total time asleep when in bed) with mortality outcomes. We developed a self-supervised deep neural network for sleep stage classification using concurrent laboratory-based polysomnography and accelerometry. After exclusion, 1448 participant nights of data were used for training. The difference between polysomnography and the model classifications on the external validation was 34.7 min (95% limits of agreement (LoA): -37.8-107.2 min) for total sleep duration, 2.6 min for REM duration (95% LoA: -68.4-73.4 min) and 32.1 min (95% LoA: -54.4-118.5 min) for NREM duration. The sleep classifier was deployed in the UK Biobank with 100,000 participants to study the association of sleep duration and sleep efficiency with all-cause mortality. Among 66,214 UK Biobank participants, 1642 mortality events were observed. Short sleepers (<6 h) had a higher risk of mortality compared to participants with normal sleep duration of 6-7.9 h, regardless of whether they had low sleep efficiency (Hazard ratios (HRs): 1.58; 95% confidence intervals (CIs): 1.19-2.11) or high sleep efficiency (HRs: 1.45; 95% CIs: 1.16-1.81). Deep-learning-based sleep classification using accelerometers has a fair to moderate agreement with polysomnography. Our findings suggest that having short overnight sleep confers mortality risk irrespective of sleep continuity.",,pdf:https://www.nature.com/articles/s41746-024-01065-0.pdf; doi:https://doi.org/10.1038/s41746-024-01065-0; html:https://europepmc.org/articles/PMC11106264; pdf:https://europepmc.org/articles/PMC11106264?pdf=render 34232969,https://doi.org/10.23889/ijpds.v5i1.1151,How effective are population health surveys for estimating prevalence of chronic conditions compared to anonymised clinical data?,"Whiffen T, Akbari A, Paget T, Lowe S, Lyons R.",,International journal of population data science,2020,2020-06-12,Y,,,,"

Introduction

Population health surveys are used to record person-reported outcome measures for chronic health conditions and provide a useful source of data when evaluating potential disease burdens. The reliability of survey-based prevalence estimates for chronic diseases is unclear nonetheless. This study applied methodological triangulation via a data linkage method to validate prevalence of selected chronic conditions (angina, myocardial infarction, heart failure, and asthma).

Methods

Linked healthcare records were used for a combined cohort of 11,323 adults from the 2013 and 2014 sweeps of the Welsh Health Survey (WHS). The approach utilised consented survey data linked to primary and secondary care electronic health record (EHR) data back to 2002 within the Secure Anonymised Information Linkage (SAIL) Databank.

Results

This descriptive study demonstrates validation of survey and clinical data using data linkage for selected chronic cardiovascular conditions and asthma with varied success. The results indicate that identifying cases for separate cardiovascular conditions was limited without specific medication codes for each condition, but more straightforward for asthma, where there was an extensive list of medications available. For asthma there was better agreement between prevalence estimates based on survey and clinical data as a result.

Conclusion

Whilst the results provide external validity for the WHS as an instrument for estimating the burden of chronic disease, they also indicate that a data linkage appproach can be used to produce comparable prevalence estimates using clinical data if a defined condition-specific set of clinical codes are available.",,pdf:https://ijpds.org/article/download/1151/2553; doi:https://doi.org/10.23889/ijpds.v5i1.1151; html:https://europepmc.org/articles/PMC7473295; pdf:https://europepmc.org/articles/PMC7473295?pdf=render +38769347,https://doi.org/10.1038/s41746-024-01065-0,Self-supervised learning of accelerometer data provides new insights for sleep and its association with mortality.,"Yuan H, Plekhanova T, Walmsley R, Reynolds AC, Maddison KJ, Bucan M, Gehrman P, Rowlands A, Ray DW, Bennett D, McVeigh J, Straker L, Eastwood P, Kyle SD, Doherty A.",,NPJ digital medicine,2024,2024-05-20,Y,,,,"Sleep is essential to life. Accurate measurement and classification of sleep/wake and sleep stages is important in clinical studies for sleep disorder diagnoses and in the interpretation of data from consumer devices for monitoring physical and mental well-being. Existing non-polysomnography sleep classification techniques mainly rely on heuristic methods developed in relatively small cohorts. Thus, we aimed to establish the accuracy of wrist-worn accelerometers for sleep stage classification and subsequently describe the association between sleep duration and efficiency (proportion of total time asleep when in bed) with mortality outcomes. We developed a self-supervised deep neural network for sleep stage classification using concurrent laboratory-based polysomnography and accelerometry. After exclusion, 1448 participant nights of data were used for training. The difference between polysomnography and the model classifications on the external validation was 34.7 min (95% limits of agreement (LoA): -37.8-107.2 min) for total sleep duration, 2.6 min for REM duration (95% LoA: -68.4-73.4 min) and 32.1 min (95% LoA: -54.4-118.5 min) for NREM duration. The sleep classifier was deployed in the UK Biobank with 100,000 participants to study the association of sleep duration and sleep efficiency with all-cause mortality. Among 66,214 UK Biobank participants, 1642 mortality events were observed. Short sleepers (<6 h) had a higher risk of mortality compared to participants with normal sleep duration of 6-7.9 h, regardless of whether they had low sleep efficiency (Hazard ratios (HRs): 1.58; 95% confidence intervals (CIs): 1.19-2.11) or high sleep efficiency (HRs: 1.45; 95% CIs: 1.16-1.81). Deep-learning-based sleep classification using accelerometers has a fair to moderate agreement with polysomnography. Our findings suggest that having short overnight sleep confers mortality risk irrespective of sleep continuity.",,pdf:https://www.nature.com/articles/s41746-024-01065-0.pdf; doi:https://doi.org/10.1038/s41746-024-01065-0; html:https://europepmc.org/articles/PMC11106264; pdf:https://europepmc.org/articles/PMC11106264?pdf=render 34746717,https://doi.org/10.1016/j.eclinm.2021.101100,Paediatric major incident triage: UK military tool offers best performance in predicting the need for time-critical major surgical and resuscitative intervention.,"Malik NS, Chernbumroong S, Xu Y, Vassallo J, Lee J, Moran CG, Newton T, Arul GS, Lord JM, Belli A, Keene D, Foster M, Hodgetts T, Bowley DM, Gkoutos GV.",,EClinicalMedicine,2021,2021-08-23,Y,,,,"

Background

Children are frequently injured during major incidents (MI), including terrorist attacks, conflict and natural disasters. Triage facilitates healthcare resource allocation in order to maximise overall survival. A critical function of MI triage tools is to identify patients needing time-critical major resuscitative and surgical intervention (Priority 1 (P1) status). This study compares the performance of 11 MI triage tools in predicting P1 status in children from the UK Trauma Audit and Research Network (TARN) registry.

Methods

Patients aged <16 years within TARN (January 2008-December 2017) were included. 11 triage tools were applied to patients' first recorded pre-hospital physiology. Patients were retrospectively assigned triage categories (P1, P2, P3, Expectant or Dead) using predefined intervention-based criteria. Tools' performance in <16s were evaluated within four-yearly age subgroups, comparing tool-predicted and intervention-based priority status.

Findings

Amongst 4962 patients, mortality was 1.1% (n = 53); median Injury Severity Score (ISS) was 9 (IQR 9-16). Blunt injuries predominated (94.4%). 1343 (27.1%) met intervention-based criteria for P1, exhibiting greater intensive care requirement (60.2% vs. 8.5%, p < 0.01) and ISS (median 17 vs 9, p < 0.01) compared with P2 patients. The Battlefield Casualty Drills (BCD) Triage Sieve had greatest sensitivity (75.7%) in predicting P1 status in children <16 years, demonstrating a 38.4-49.8% improvement across all subgroups of children <12 years compared with the UK's current Paediatric Triage Tape (PTT). JumpSTART demonstrated low sensitivity in predicting P1 status in 4 to 8 year olds (35.5%) and 0 to 4 year olds (28.5%), and was outperformed by its adult counterpart START (60.6% and 59.6%).

Interpretation

The BCD Triage Sieve had greatest sensitivity in predicting P1 status in this paediatric trauma registry population: we recommend it replaces the PTT in UK practice. Users of JumpSTART may consider alternative tools. We recommend Lerner's triage category definitions when conducting MI evaluations.",,pdf:http://www.thelancet.com/article/S2589537021003801/pdf; doi:https://doi.org/10.1016/j.eclinm.2021.101100; html:https://europepmc.org/articles/PMC8548919; pdf:https://europepmc.org/articles/PMC8548919?pdf=render 38642997,https://doi.org/10.1136/bmjopen-2023-079923,Distributions of recorded pain in mental health records: a natural language processing based study.,"Chaturvedi J, Stewart R, Ashworth M, Roberts A.",,BMJ open,2024,2024-04-19,Y,Chronic pain; Mental health; epidemiology; Electronic Health Records; Natural Language Processing,,,"

Objective

The objective of this study is to determine demographic and diagnostic distributions of physical pain recorded in clinical notes of a mental health electronic health records database by using natural language processing and examine the overlap in recorded physical pain between primary and secondary care.

Design, setting and participants

The data were extracted from an anonymised version of the electronic health records of a large secondary mental healthcare provider serving a catchment of 1.3 million residents in south London. These included patients under active referral, aged 18+ at the index date of 1 July 2018 and having at least one clinical document (≥30 characters) between 1 July 2017 and 1 July 2019. This cohort was compared with linked primary care records from one of the four local government areas.

Outcome

The primary outcome of interest was the presence of recorded physical pain within the clinical notes of the patients, not including psychological or metaphorical pain.

Results

A total of 27 211 patients were retrieved. Of these, 52% (14,202) had narrative text containing relevant mentions of physical pain. Older patients (OR 1.17, 95% CI 1.15 to 1.19), females (OR 1.42, 95% CI 1.35 to 1.49), Asians (OR 1.30, 95% CI 1.16 to 1.45) or black (OR 1.49, 95% CI 1.40 to 1.59) ethnicities, living in deprived neighbourhoods (OR 1.64, 95% CI 1.55 to 1.73) showed higher odds of recorded pain. Patients with severe mental illnesses were found to be less likely to report pain (OR 0.43, 95% CI 0.41 to 0.46, p<0.001). 17% of the cohort from secondary care also had records from primary care.

Conclusion

The findings of this study show sociodemographic and diagnostic differences in recorded pain. Specifically, lower documentation across certain groups indicates the need for better screening protocols and training on recognising varied pain presentations. Additionally, targeting improved detection of pain for minority and disadvantaged groups by care providers can promote health equity.",,doi:https://doi.org/10.1136/bmjopen-2023-079923; html:https://europepmc.org/articles/PMC11033644; pdf:https://europepmc.org/articles/PMC11033644?pdf=render 33079204,https://doi.org/10.1093/ehjqcco/qcaa079,Impact of COVID-19 on cardiac procedure activity in England and associated 30-day mortality.,"Mohamed MO, Banerjee A, Clarke S, de Belder M, Patwala A, Goodwin AT, Kwok CS, Rashid M, Gale CP, Curzen N, Mamas MA.",,European heart journal. Quality of care & clinical outcomes,2021,2021-05-01,Y,Mortality; Cardiac; England; Procedures; Covid-19,,,"

Aims

Limited data exist on the impact of COVID-19 on national changes in cardiac procedure activity, including patient characteristics and clinical outcomes before and during the COVID-19 pandemic.

Methods and results

All major cardiac procedures (n = 374 899) performed between 1 January and 31 May for the years 2018, 2019, and 2020 were analysed, stratified by procedure type and time-period (pre-COVID: January-May 2018 and 2019 and January-February 2020 and COVID: March-May 2020). Multivariable logistic regression was performed to examine the odds ratio (OR) of 30-day mortality for procedures performed in the COVID period. Overall, there was a deficit of 45 501 procedures during the COVID period compared to the monthly averages (March-May) in 2018-2019. Cardiac catheterization and device implantations were the most affected in terms of numbers (n = 19 637 and n = 10 453), whereas surgical procedures such as mitral valve replacement, other valve replacement/repair, atrioseptal defect/ventriculoseptal defect repair, and coronary artery bypass grafting were the most affected as a relative percentage difference (Δ) to previous years' averages. Transcatheter aortic valve replacement was the least affected (Δ -10.6%). No difference in 30-day mortality was observed between pre-COVID and COVID time-periods for all cardiac procedures except cardiac catheterization [OR 1.25 95% confidence interval (CI) 1.07-1.47, P = 0.006] and cardiac device implantation (OR 1.35 95% CI 1.15-1.58, P < 0.001).

Conclusion

Cardiac procedural activity has significantly declined across England during the COVID-19 pandemic, with a deficit in excess of 45 000 procedures, without an increase in risk of mortality for most cardiac procedures performed during the pandemic. Major restructuring of cardiac services is necessary to deal with this deficit, which would inevitably impact long-term morbidity and mortality.",,pdf:https://academic.oup.com/ehjqcco/article-pdf/7/3/247/37776880/qcaa079.pdf; doi:https://doi.org/10.1093/ehjqcco/qcaa079; html:https://europepmc.org/articles/PMC7665465; pdf:https://europepmc.org/articles/PMC7665465?pdf=render @@ -431,8 +431,8 @@ PMC10910267,https://doi.org/,Development and evaluation of a tool to optimise in 37798357,https://doi.org/10.1038/s41598-023-42331-7,"An angiopoietin 2, FGF23, and BMP10 biomarker signature differentiates atrial fibrillation from other concomitant cardiovascular conditions.","Chua W, Cardoso VR, Guasch E, Sinner MF, Al-Taie C, Brady P, Casadei B, Crijns HJGM, Dudink EAMP, Hatem SN, Kääb S, Kastner P, Mont L, Nehaj F, Purmah Y, Reyat JS, Schotten U, Sommerfeld LC, Zeemering S, Ziegler A, Gkoutos GV, Kirchhof P, Fabritz L.",,Scientific reports,2023,2023-10-05,Y,,,,"Early detection of atrial fibrillation (AF) enables initiation of anticoagulation and early rhythm control therapy to reduce stroke, cardiovascular death, and heart failure. In a cross-sectional, observational study, we aimed to identify a combination of circulating biomolecules reflecting different biological processes to detect prevalent AF in patients with cardiovascular conditions presenting to hospital. Twelve biomarkers identified by reviewing literature and patents were quantified on a high-precision, high-throughput platform in 1485 consecutive patients with cardiovascular conditions (median age 69 years [Q1, Q3 60, 78]; 60% male). Patients had either known AF (45%) or AF ruled out by 7-day ECG-monitoring. Logistic regression with backward elimination and a neural network approach considering 7 key clinical characteristics and 12 biomarker concentrations were applied to a randomly sampled discovery cohort (n = 933) and validated in the remaining patients (n = 552). In addition to age, sex, and body mass index (BMI), BMP10, ANGPT2, and FGF23 identified patients with prevalent AF (AUC 0.743 [95% CI 0.712, 0.775]). These circulating biomolecules represent distinct pathways associated with atrial cardiomyopathy and AF. Neural networks identified the same variables as the regression-based approach. The validation using regression yielded an AUC of 0.719 (95% CI 0.677, 0.762), corroborated using deep neural networks (AUC 0.784 [95% CI 0.745, 0.822]). Age, sex, BMI and three circulating biomolecules (BMP10, ANGPT2, FGF23) are associated with prevalent AF in unselected patients presenting to hospital. Findings should be externally validated. Results suggest that age and different disease processes approximated by these three biomolecules contribute to AF in patients. Our findings have the potential to improve screening programs for AF after external validation.",,pdf:https://www.nature.com/articles/s41598-023-42331-7.pdf; doi:https://doi.org/10.1038/s41598-023-42331-7; html:https://europepmc.org/articles/PMC10556075; pdf:https://europepmc.org/articles/PMC10556075?pdf=render 36333839,https://doi.org/10.1002/gps.5834,The impact of the first UK COVID-19 lockdown on presentations with psychosis to mental health services for older adults: An electronic health records study in South London.,"Simkin L, Yung P, Greig F, Perera G, Tsamakis K, Rizos E, Stewart R, Velayudhan L, Mueller C.",,International journal of geriatric psychiatry,2022,2022-10-24,Y,Dementia; Hallucinations; Delusions; Psychosis; Older Adults; Lockdown; Covid-19; Non-white Ethnicity,,,"

Objectives

Social distancing restrictions in the COVID-19 pandemic may have had adverse effects on older adults' mental health. Whereby the impact on mood is well-described, less is known about psychotic symptoms. The aim of this study was to compare characteristics associated with psychotic symptoms during the first UK lockdown and a pre-pandemic comparison period.

Methods

In this retrospective observational study we analysed anonymised records from patients referred to mental health services for older adults in South London in the 16-week period of the UK lockdown starting in March 2020, and in the comparable pre-pandemic period in 2019. We used logistic regression models to compare the associations of different patient characteristics with increased odds of presenting with any psychotic symptom (defined as hallucinations and/or delusion), hallucinations, or delusions, during lockdown and the corresponding pre-pandemic period.

Results

1991 referrals were identified. There were fewer referrals during lockdown but a higher proportion of presentations with any psychotic symptom (48.7% vs. 42.8%, p = 0.018), particularly hallucinations (41.0% vs. 27.8%, p < 0.001). Patients of non-White ethnicity (adjusted odds ratio (OR): 1.83; 95% confidence interval (CI): 1.13-2.99) and patients with dementia (adjusted OR: 3.09; 95% CI: 1.91-4.99) were more likely to be referred with psychotic symptoms during lockdown. While a weaker association between dementia and psychotic symptoms was found in the pre-COVID period (adjusted OR: 1.55; 95% CI: 1.19-2.03), interaction terms indicated higher odds of patients of non-White ethnicity or dementia to present with psychosis during the lockdown period.

Conclusions

During lockdown, referrals to mental health services for adults decreased, but contained a higher proportion with psychotic symptoms. The stronger association with psychotic symptoms in non-White ethnic groups and patients with dementia during lockdown suggests that barriers in accessing care might have increased during the COVID-19 pandemic.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/gps.5834; doi:https://doi.org/10.1002/gps.5834; html:https://europepmc.org/articles/PMC9828419; pdf:https://europepmc.org/articles/PMC9828419?pdf=render 35607618,https://doi.org/10.1016/j.patter.2022.100471,"Relevance, redundancy, and complementarity trade-off (RRCT): A principled, generic, robust feature-selection tool.",Tsanas A.,,"Patterns (New York, N.Y.)",2022,2022-03-31,Y,Information theory; Variable selection; Feature Selection; Statistical Learning; Dimensionality Reduction; Curse Of Dimensionality; Principle Of Parsimony,,,"We present a new heuristic feature-selection (FS) algorithm that integrates in a principled algorithmic framework the three key FS components: relevance, redundancy, and complementarity. Thus, we call it relevance, redundancy, and complementarity trade-off (RRCT). The association strength between each feature and the response and between feature pairs is quantified via an information theoretic transformation of rank correlation coefficients, and the feature complementarity is quantified using partial correlation coefficients. We empirically benchmark the performance of RRCT against 19 FS algorithms across four synthetic and eight real-world datasets in indicative challenging settings evaluating the following: (1) matching the true feature set and (2) out-of-sample performance in binary and multi-class classification problems when presenting selected features into a random forest. RRCT is very competitive in both tasks, and we tentatively make suggestions on the generalizability and application of the best-performing FS algorithms across settings where they may operate effectively.",,pdf:http://www.cell.com/article/S2666389922000514/pdf; doi:https://doi.org/10.1016/j.patter.2022.100471; html:https://europepmc.org/articles/PMC9122960; pdf:https://europepmc.org/articles/PMC9122960?pdf=render -38806176,https://doi.org/10.1177/00045632241261274,A SARS-CoV-2 minimum data standard to support national serology reporting.,"Urwin EN, Martin J, Sebire N, Harris A, Johnston J, Masood E, Milligan G, Mairs L, Chuter A, Ferguson M, Quinlan P, Jefferson E.",,Annals of clinical biochemistry,2024,2024-05-28,N,Computers; Laboratory Management; Laboratory Methods; Analytical Systems,,,"

Background

Healthcare laboratory systems produce and capture a vast array of information, yet do not always report all of this to the national infrastructure within the United Kingdom. The global COVID-19 pandemic brought about a much greater need for detailed healthcare data, one such instance being laboratory testing data. The reporting of qualitative laboratory test results (e.g., positive, negative or indeterminate) provides a basic understanding of levels of seropositivity. However, to better understand and interpret seropositivity, how it is determined and other factors that affect its calculation (i.e., levels of antibodies), quantitative laboratory test data are needed.

Method

36 data attributes were collected from 3 NHS laboratories and 20 CO-CONNECT project partner organisations. These were assessed against the need for a minimum dataset to determine data attribute importance. An NHS laboratory feasibility study was undertaken to assess the minimum data standard, together with a literature review of national and international data standards and healthcare reports.

Results

A COVID serology minimum data standard (CSMDS) comprising 12 data attributes was created and verified by 3 NHS laboratories to allow national granular reporting of COVID serology results. To support this, a standardised set of vocabulary terms was developed to represent laboratory analyser systems and laboratory information management systems.

Conclusions

This paper puts forward a minimum viable standard for COVID-19 serology data attributes to enhance its granularity and augment the national reporting of COVID-19 serology laboratory results, with implications for future pandemics.",,doi:https://doi.org/10.1177/00045632241261274 37006328,https://doi.org/10.1093/braincomms/fcad065,"Infections among individuals with multiple sclerosis, Alzheimer's disease and Parkinson's disease.","Hu Y, Hu K, Song H, Pawitan Y, Piehl F, Fang F.",,Brain communications,2023,2023-03-16,Y,Multiple sclerosis; Alzheimer’s disease; Infections; Parkinson’s Disease,,,"A link between neurodegenerative diseases and infections has been previously reported. However, it is not clear to what extent such link is caused by confounding factors or to what extent it is intimately connected with the underlying conditions. Further, studies on the impact of infections on mortality risk following neurodegenerative diseases are rare. We analysed two data sets with different characteristics: (i) a community-based cohort from the UK Biobank with 2023 patients with multiple sclerosis, 2200 patients with Alzheimer's disease, 3050 patients with Parkinson's disease diagnosed before 1 March 2020 and 5 controls per case who were randomly selected and individually matched to the case; (ii) a Swedish Twin Registry cohort with 230 patients with multiple sclerosis, 885 patients with Alzheimer's disease and 626 patients with Parkinson's disease diagnosed before 31 December 2016 and their disease-free co-twins. The relative risk of infections after a diagnosis of neurodegenerative disease was estimated using stratified Cox models, with adjustment for differences in baseline characteristics. Causal mediation analyses of survival outcomes based on Cox models were performed to assess the impact of infections on mortality. Compared with matched controls or unaffected co-twins, we observed an elevated infection risk after diagnosis of neurodegenerative diseases, with a fully adjusted hazard ratio (95% confidence interval) of 2.45 (2.24-2.69) for multiple sclerosis, 5.06 (4.58-5.59) for Alzheimer's disease and 3.72 (3.44-4.01) for Parkinson's disease in the UK Biobank cohort, and 1.78 (1.21-2.62) for multiple sclerosis, 1.50 (1.19-1.88) for Alzheimer's disease and 2.30 (1.79-2.95) for Parkinson's disease in the twin cohort. Similar risk increases were observed when we analysed infections during the 5 years before diagnosis of the respective disease. Occurrence of infections after diagnosis had, however, relatively little impact on mortality, as mediation of infections on mortality (95% confidence interval) was estimated as 31.89% (26.83-37.11%) for multiple sclerosis, 13.38% (11.49-15.29%) for Alzheimer's disease and 18.85% (16.95-20.97%) for Parkinson's disease in the UK Biobank cohort, whereas it was 6.56% (-3.59 to 16.88%) for multiple sclerosis, -2.21% (-0.21 to 4.65%) for Parkinson's disease and -3.89% (-7.27 to -0.51%) for Alzheimer's disease in the twin cohort. Individuals with studied neurodegenerative diseases display an increased risk of infections independently of genetic and familial environment factors. A similar magnitude of risk increase is present prior to confirmed diagnosis, which may indicate a modulating effect of the studied neurological conditions on immune defences.",,pdf:https://academic.oup.com/braincomms/advance-article-pdf/doi/10.1093/braincomms/fcad065/49588224/fcad065.pdf; doi:https://doi.org/10.1093/braincomms/fcad065; html:https://europepmc.org/articles/PMC10053639; pdf:https://europepmc.org/articles/PMC10053639?pdf=render +38806176,https://doi.org/10.1177/00045632241261274,A SARS-CoV-2 minimum data standard to support national serology reporting.,"Urwin EN, Martin J, Sebire N, Harris A, Johnston J, Masood E, Milligan G, Mairs L, Chuter A, Ferguson M, Quinlan P, Jefferson E.",,Annals of clinical biochemistry,2024,2024-05-28,N,Computers; Laboratory Management; Laboratory Methods; Analytical Systems,,,"

Background

Healthcare laboratory systems produce and capture a vast array of information, yet do not always report all of this to the national infrastructure within the United Kingdom. The global COVID-19 pandemic brought about a much greater need for detailed healthcare data, one such instance being laboratory testing data. The reporting of qualitative laboratory test results (e.g., positive, negative or indeterminate) provides a basic understanding of levels of seropositivity. However, to better understand and interpret seropositivity, how it is determined and other factors that affect its calculation (i.e., levels of antibodies), quantitative laboratory test data are needed.

Method

36 data attributes were collected from 3 NHS laboratories and 20 CO-CONNECT project partner organisations. These were assessed against the need for a minimum dataset to determine data attribute importance. An NHS laboratory feasibility study was undertaken to assess the minimum data standard, together with a literature review of national and international data standards and healthcare reports.

Results

A COVID serology minimum data standard (CSMDS) comprising 12 data attributes was created and verified by 3 NHS laboratories to allow national granular reporting of COVID serology results. To support this, a standardised set of vocabulary terms was developed to represent laboratory analyser systems and laboratory information management systems.

Conclusions

This paper puts forward a minimum viable standard for COVID-19 serology data attributes to enhance its granularity and augment the national reporting of COVID-19 serology laboratory results, with implications for future pandemics.",,doi:https://doi.org/10.1177/00045632241261274 36992188,https://doi.org/10.3390/vaccines11030604,"Household Composition and Inequalities in COVID-19 Vaccination in Wales, UK.","Lench A, Perry M, Johnson RD, Fry R, Richardson G, Lyons RA, Akbari A, Edwards A, Collins B, Joseph-Williams N, Cooper A, Cottrell S.",,Vaccines,2023,2023-03-07,Y,Vaccines; Vaccination; Households; Inequalities; Immunisation; Household Composition; Inequities; Covid-19,,,"The uptake of COVID-19 vaccination in Wales is high at a population level but many inequalities exist. Household composition may be an important factor in COVID-19 vaccination uptake due to the practical, social, and psychological implications associated with different living arrangements. In this study, the role of household composition in the uptake of COVID-19 vaccination in Wales was examined with the aim of identifying areas for intervention to address inequalities. Records within the Wales Immunisation System (WIS) COVID-19 vaccination register were linked to the Welsh Demographic Service Dataset (WDSD; a population register for Wales) held within the Secure Anonymised Information Linkage (SAIL) databank. Eight household types were defined based on household size, the presence or absence of children, and the presence of single or multiple generations. Uptake of the second dose of any COVID-19 vaccine was analysed using logistic regression. Gender, age group, health board, rural/urban residential classification, ethnic group, and deprivation quintile were included as covariates for multivariable regression. Compared to two-adult households, all other household types were associated with lower uptake. The most significantly reduced uptake was observed for large, multigenerational, adult group households (aOR 0.45, 95%CI 0.43-0.46). Comparing multivariable regression with and without incorporation of household composition as a variable produced significant differences in odds of vaccination for health board, age group, and ethnic group categories. These results indicate that household composition is an important factor for the uptake of COVID-19 vaccination and consideration of differences in household composition is necessary to mitigate vaccination inequalities.",,pdf:https://www.mdpi.com/2076-393X/11/3/604/pdf?version=1678670919; doi:https://doi.org/10.3390/vaccines11030604; html:https://europepmc.org/articles/PMC10055803; pdf:https://europepmc.org/articles/PMC10055803?pdf=render 37046692,https://doi.org/10.3390/cancers15072031,"Breast, Prostate, Colorectal, and Lung Cancer Incidence and Risk Factors in Women Who Have Sex with Women and Men Who Have Sex with Men: A Cross-Sectional and Longitudinal Analysis Using UK Biobank.","Underwood S, Lyratzopoulos G, Saunders CL.",,Cancers,2023,2023-03-29,Y,Inequalities; Cancer Incidence; Cancer Risk; Cancer Epidemiology; Sexual Minority Health,,,"

Background

There is limited evidence about cancer incidence for lesbian, gay and bisexual women and men, although the prevalence of cancer risk factors may be higher.

Aim

To describe cancer incidence for four common cancers (breast, lung, colorectal and prostate).

Methods

This project used UK Biobank participant data. We explored risk factor prevalence (age, deprivation, ethnicity, smoking, alcohol intake, obesity, parity, and sexual history), and calculated cancer risk, for six groups defined based on sexual history; women who have sex exclusively with men (WSEM), or women (WSEW), women who have sex with men and women (WSWM); men who have sex exclusively with women (MSEW), or men (MSEM), and men who have sex with women and men (MSWM).

Results

WSEW, WSWM, MSEM, and MSMW were younger, more likely to smoke, and to live in more deprived neighbourhoods. We found no evidence of an association between sexual history and breast, colorectal, or prostate cancer in age-adjusted models. Lung cancer incidence was higher for WSWM compared with WSEM, HR (95%CI) 1.78 (1.28-2.48), p = 0.0005, and MSWM compared with MSEW, 1.43 (1.03-1.99), p = 0.031; after adjustment for smoking, this difference was no longer significant.

Conclusions

Sexual minority groups have a higher risk for lung cancer, due to greater exposure to smoking.",,pdf:https://www.mdpi.com/2072-6694/15/7/2031/pdf?version=1680080044; doi:https://doi.org/10.3390/cancers15072031; html:https://europepmc.org/articles/PMC10093616; pdf:https://europepmc.org/articles/PMC10093616?pdf=render 37528841,https://doi.org/10.1016/j.eclinm.2023.102064,Repeated antibiotic exposure and risk of hospitalisation and death following COVID-19 infection (OpenSAFELY): a matched case-control study.,"Yang YT, Wong D, Ashcroft DM, Massey J, MacKenna B, Fisher L, Mehrkar A, Bacon SC, OpenSAFELY collaborative, Hand K, Zhong X, Fahmi A, Goldacre B, van Staa T, Palin V.",,EClinicalMedicine,2023,2023-07-05,Y,Antibiotics; Primary Care; Severe Outcome; Covid-19,,,"

Background

Identifying potential risk factors related to severe COVID-19 outcomes is important. Repeated intermittent antibiotic use is known be associated with adverse outcomes. This study aims to examine whether prior frequent antibiotic exposure is associated with severe COVID-19 outcomes.

Methods

With the approval of NHS England, we used the OpenSAFELY platform, which integrated primary and secondary care, COVID-19 test, and death registration data. This matched case-control study included 0.67 million patients (aged 18-110 years) from an eligible 2.47 million patients with incident COVID-19 by matching with replacement. Inclusion criteria included registration within one general practice for at least 3 years and infection with incident COVID-19. Cases were identified according to different severity of COVID-19 outcomes. Cases and eligible controls were 1:6 matched on age, sex, region of GP practice, and index year and month of COVID-19 infection. Five quintile groups, based on the number of previous 3-year antibiotic prescriptions, were created to indicate the frequency of prior antibiotic exposure. Conditional logistic regression used to compare the differences between case and control groups, adjusting for ethnicity, body mass index, comorbidities, vaccination history, deprivation, and care home status. Sensitivity analyses were done to explore potential confounding and the effects of missing data.

Findings

Based on our inclusion criteria, between February 1, 2020 and December 31, 2021, 98,420 patients were admitted to hospitals and 22,660 died. 55 unique antibiotics were prescribed. A dose-response relationship between number of antibiotic prescriptions and risk of severe COVID-19 outcome was observed. Patients in the highest quintile with history of prior antibiotic exposure had 1.80 times greater odds of hospitalisation compared to patients without antibiotic exposure (adjusted odds ratio [OR] 1.80, 95% Confidence Interval [CI] 1.75-1.84). Similarly, the adjusted OR for hospitalised patients with death outcomes was 1.34 (95% CI 1.28-1.41). Larger number of prior antibiotic type was also associated with more severe COVID-19 related hospital admission. The adjusted OR of quintile 5 exposure (the most frequent) with more than 3 antibiotic types was around 2 times larger than quintile 1 (only 1 type; OR 1.80, 95% CI 1.75-1.84 vs. OR 1.03, 95% CI 1.01-1.05).

Interpretation

Our observational study has provided evidence that antibiotic exposure frequency and diversity may be associated with COVID-19 severity, potentially suggesting adverse effects of repeated intermittent antibiotic use. Future work could work to elucidate causal links and potential mechanisms. Antibiotic stewardship should put more emphasis on long-term antibiotic exposure and its adverse outcome to increase the awareness of appropriate antibiotics use.

Funding

Health Data Research UK and National Institute for Health Research.",,doi:https://doi.org/10.1016/j.eclinm.2023.102064; html:https://europepmc.org/articles/PMC10388579; pdf:https://europepmc.org/articles/PMC10388579?pdf=render @@ -442,13 +442,13 @@ PMC10910267,https://doi.org/,Development and evaluation of a tool to optimise in 31984360,https://doi.org/10.1093/jamiaopen/ooz009,Annotating and detecting phenotypic information for chronic obstructive pulmonary disease.,"Ju M, Short AD, Thompson P, Bakerly ND, Gkoutos GV, Tsaprouni L, Ananiadou S.",,JAMIA open,2019,2019-04-26,Y,Phenotype; Information Extraction; Natural Language Processing; chronic obstructive pulmonary disease; Text Mining,The Human Phenome,,"

Objectives

Chronic obstructive pulmonary disease (COPD) phenotypes cover a range of lung abnormalities. To allow text mining methods to identify pertinent and potentially complex information about these phenotypes from textual data, we have developed a novel annotated corpus, which we use to train a neural network-based named entity recognizer to detect fine-grained COPD phenotypic information.

Materials and methods

Since COPD phenotype descriptions often mention other concepts within them (proteins, treatments, etc.), our corpus annotations include both outermost phenotype descriptions and concepts nested within them. Our neural layered bidirectional long short-term memory conditional random field (BiLSTM-CRF) network firstly recognizes nested mentions, which are fed into subsequent BiLSTM-CRF layers, to help to recognize enclosing phenotype mentions.

Results

Our corpus of 30 full papers (available at: http://www.nactem.ac.uk/COPD) is annotated by experts with 27 030 phenotype-related concept mentions, most of which are automatically linked to UMLS Metathesaurus concepts. When trained using the corpus, our BiLSTM-CRF network outperforms other popular approaches in recognizing detailed phenotypic information.

Discussion

Information extracted by our method can facilitate efficient location and exploration of detailed information about phenotypes, for example, those specifically concerning reactions to treatments.

Conclusion

The importance of our corpus for developing methods to extract fine-grained information about COPD phenotypes is demonstrated through its successful use to train a layered BiLSTM-CRF network to extract phenotypic information at various levels of granularity. The minimal human intervention needed for training should permit ready adaption to extracting phenotypic information about other diseases.",COPD is linked with a number of lung abnormalities. This study has developed a computer algorithm to extract information about these abnormalities.,pdf:https://academic.oup.com/jamiaopen/article-pdf/2/2/261/32298683/ooz009.pdf; doi:https://doi.org/10.1093/jamiaopen/ooz009; html:https://europepmc.org/articles/PMC6951876; pdf:https://europepmc.org/articles/PMC6951876?pdf=render 34089614,https://doi.org/10.1093/ije/dyab028,Cohort Profile: Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) Database.,"Mulholland RH, Vasileiou E, Simpson CR, Robertson C, Ritchie LD, Agrawal U, Woolhouse M, Murray JL, Stagg HR, Docherty AB, McCowan C, Wood R, Stock SJ, Sheikh A.",,International journal of epidemiology,2021,2021-08-01,N,,,,,,pdf:https://academic.oup.com/ije/article-pdf/50/4/1064/40146583/dyab028.pdf; doi:https://doi.org/10.1093/ije/dyab028; html:https://europepmc.org/articles/PMC8195245; pdf:https://europepmc.org/articles/PMC8195245?pdf=render; doi:https://doi.org/10.1093/ije/dyab028 36606535,https://doi.org/10.1111/jdv.18841,The association between atopic eczema and lymphopenia: Results from a UK cohort study with replication in US survey data.,"Hollestein LM, Ye MYF, Ang KL, Forbes H, Mansfield KE, Abuabara K, Smeeth L, Langan SM.",,Journal of the European Academy of Dermatology and Venereology : JEADV,2023,2023-01-25,Y,,,,"

Background

Lymphocyte skin homing in atopic eczema (AE) may induce lymphopenia.

Objective

To determine if AE is associated with lymphopenia.

Methods

We used UK primary care electronic health records (Clinical Practice Research Datalink GOLD) for a matched cohort study in adults (18 years+) (1997-2015) with at least one recorded lymphocyte count. We matched people with AE to up to five people without. We used multivariable logistic regression to estimate the association between AE and lymphopenia (two low lymphocyte counts within 3 months) and linear mixed effects regression to estimate the association with absolute lymphocyte counts using all available counts. Cox proportional hazard models were used to investigate the effect of lymphopenia on common infections. We replicated the study using US survey data (National Health and Nutrition Examination Survey [NHANES]).

Results

Among 71,731 adults with AE and 126,349 adults without AE, we found an adjusted odds ratio (OR) for lymphopenia of 1.16 (95% CI: 1.09-1.23); the strength of association increased with increasing eczema severity. When comparing all recorded lymphocyte counts from adults with AE (n = 1,497,306) to those of people without AE (n = 4,035,870) we saw a lower mean lymphocyte (adjusted mean difference -0.047 × 109 /L [95% CI: -0.051 to -0.043]) in those with AE. The difference was larger for men, with increasing age, and with increasing AE severity and was present among people with AE not treated with immunosuppressive drugs. In NHANES (n = 22,624), the adjusted OR for lymphopenia in adults with AE was 1.30 (95% CI: 0.80-2.11), and the adjusted mean lymphocyte count difference was -0.03 × 109 /L (95% CI: -0.07 to 0.02). Despite having a lower lymphocyte count, adjusting for time with lymphopenia, did not alter risk estimates of infections.

Conclusion

Atopic eczema, including increasing AE severity, is associated with a decreased lymphocyte count, regardless of immunosuppressive drug use. Whether the lower lymphocyte count has wider health implications for people with severe eczema warrants further investigation.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4668507/1/Hollestein_etal_2023_The-association-between-atopic-eczema.pdf; doi:https://doi.org/10.1111/jdv.18841; html:https://europepmc.org/articles/PMC10947025; pdf:https://europepmc.org/articles/PMC10947025?pdf=render -37536152,https://doi.org/10.1016/j.seizure.2023.07.016,Association of comorbid-socioeconomic clusters with mortality in late onset epilepsy derived through unsupervised machine learning.,"Josephson CB, Gonzalez-Izquierdo A, Engbers JDT, Denaxas S, Delgado-Garcia G, Sajobi TT, Wang M, Keezer MR, Wiebe S.",,Seizure,2023,2023-07-29,N,Epilepsy; Elderly; Cohort study; Electronic Health Records; Unsupervised Machine Learning; Late-onset Epilepsy,,,"

Background and objectives

Late-onset epilepsy is a heterogenous entity associated with specific aetiologies and an elevated risk of premature mortality. Specific multimorbid-socioeconomic profiles and their unique prognostic trajectories have not been described. We sought to determine if specific clusters of late onset epilepsy exist, and whether they have unique hazards of premature mortality.

Methods

We performed a retrospective observational cohort study linking primary and hospital-based UK electronic health records with vital statistics data (covering years 1998-2019) to identify all cases of incident late onset epilepsy (from people aged ≥65) and 1:10 age, sex, and GP practice-matched controls. We applied hierarchical agglomerative clustering using common aetiologies identified at baseline to define multimorbid-socioeconomic profiles, compare hazards of early mortality, and tabulating causes of death stratified by cluster.

Results

From 1,032,129 people aged ≥65, we identified 1048 cases of late onset epilepsy who were matched to 10,259 controls. Median age at epilepsy diagnosis was 68 (interquartile range: 66-72) and 474 (45%) were female. The hazard of premature mortality related to late-onset epilepsy was higher than matched controls (hazard ratio [HR] 1.73; 95% confidence interval [95%CI] 1.51-1.99). Ten unique phenotypic clusters were identified, defined by 'healthy' males and females, ischaemic stroke, intracerebral haemorrhage (ICH), ICH and alcohol misuse, dementia and anxiety, anxiety, depression in males and females, and brain tumours. Cluster-specific hazards were often similar to that derived for late-onset epilepsy as a whole. Clusters that differed significantly from the base late-onset epilepsy hazard were 'dementia and anxiety' (HR 5.36; 95%CI 3.31-8.68), 'brain tumour' (HR 4.97; 95%CI 2.89-8.56), 'ICH and alcohol misuse' (HR 2.91; 95%CI 1.76-4.81), and 'ischaemic stroke' (HR 2.83; 95%CI 1.83-4.04). These cluster-specific risks were also elevated compared to those derived for tumours, dementia, ischaemic stroke, and ICH in the whole population. Seizure-related cause of death was uncommon and restricted to the ICH, ICH and alcohol misuse, and healthy female clusters.

Significance

Late-onset epilepsy is an amalgam of unique phenotypic clusters that can be quantitatively defined. Late-onset epilepsy and cluster-specific comorbid profiles have complex effects on premature mortality above and beyond the base rates attributed to epilepsy and cluster-defining comorbidities alone.",,doi:https://doi.org/10.1016/j.seizure.2023.07.016 32946449,https://doi.org/10.1371/journal.pone.0237676,"Proton pump inhibitors and dementia risk: Evidence from a cohort study using linked routinely collected national health data in Wales, UK.","Cooksey R, Kennedy J, Dennis MS, Escott-Price V, Lyons RA, Seaborne M, Brophy S.",,PloS one,2020,2020-09-18,Y,,,,"

Objectives

Proton pump inhibitors (PPIs) are commonly prescribed for prevention and treatment of gastrointestinal conditions or for gastroprotection from other drugs. Research suggests they are linked to increased dementia risk. We use linked national health data to examine the association between PPI use and the development of incident dementia.

Methods and findings

A population-based study using electronic health-data from the Secure Anonymised Information Linkage (SAIL) Databank, Wales (UK) from 1999 to 2015. Of data available on 3,765,744 individuals, a cohort who had ever been prescribed a PPI was developed (n = 183,968) for people aged 55 years and over and compared to non-PPI exposed individuals (131,110). Those with prior dementia, mild-cognitive-impairment or delirium codes were excluded. Confounding factors included comorbidities and/or drugs associated with them. Comorbidities might include head injury and some examples of medications include antidepressants, antiplatelets and anticoagulants. These commonly prescribed drugs were investigated as it was not feasible to explore all drugs in this study. The main outcome was a diagnosis of incident dementia. Cox proportional hazard regression modelling was used to calculate the Hazard ratio (HR) of developing dementia in PPI-exposed compared to unexposed individuals while controlling for potential confounders. The mean age of the PPI exposed individuals was 69.9 years and 39.8% male while the mean age of the unexposed individuals was 72.1 years and 41.1% male. The rate of PPI usage was 58.4% (183,968) and incident dementia rate was 11.8% (37,148/315,078). PPI use was associated with decreased dementia risk (HR: 0.67, 95% CI: 0.65 to 0.67, p<0.01).

Conclusions

This study, using large-scale, multi-centre health-data was unable to confirm an association between PPI use and increased dementia risk. Previously reported links may be associated with confounders of people using PPI's, such as increased risk of cardiovascular disease and/or depression and their associated medications which may be responsible for any increased risk of developing dementia.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0237676&type=printable; doi:https://doi.org/10.1371/journal.pone.0237676; html:https://europepmc.org/articles/PMC7500586; pdf:https://europepmc.org/articles/PMC7500586?pdf=render +37536152,https://doi.org/10.1016/j.seizure.2023.07.016,Association of comorbid-socioeconomic clusters with mortality in late onset epilepsy derived through unsupervised machine learning.,"Josephson CB, Gonzalez-Izquierdo A, Engbers JDT, Denaxas S, Delgado-Garcia G, Sajobi TT, Wang M, Keezer MR, Wiebe S.",,Seizure,2023,2023-07-29,N,Epilepsy; Elderly; Cohort study; Electronic Health Records; Unsupervised Machine Learning; Late-onset Epilepsy,,,"

Background and objectives

Late-onset epilepsy is a heterogenous entity associated with specific aetiologies and an elevated risk of premature mortality. Specific multimorbid-socioeconomic profiles and their unique prognostic trajectories have not been described. We sought to determine if specific clusters of late onset epilepsy exist, and whether they have unique hazards of premature mortality.

Methods

We performed a retrospective observational cohort study linking primary and hospital-based UK electronic health records with vital statistics data (covering years 1998-2019) to identify all cases of incident late onset epilepsy (from people aged ≥65) and 1:10 age, sex, and GP practice-matched controls. We applied hierarchical agglomerative clustering using common aetiologies identified at baseline to define multimorbid-socioeconomic profiles, compare hazards of early mortality, and tabulating causes of death stratified by cluster.

Results

From 1,032,129 people aged ≥65, we identified 1048 cases of late onset epilepsy who were matched to 10,259 controls. Median age at epilepsy diagnosis was 68 (interquartile range: 66-72) and 474 (45%) were female. The hazard of premature mortality related to late-onset epilepsy was higher than matched controls (hazard ratio [HR] 1.73; 95% confidence interval [95%CI] 1.51-1.99). Ten unique phenotypic clusters were identified, defined by 'healthy' males and females, ischaemic stroke, intracerebral haemorrhage (ICH), ICH and alcohol misuse, dementia and anxiety, anxiety, depression in males and females, and brain tumours. Cluster-specific hazards were often similar to that derived for late-onset epilepsy as a whole. Clusters that differed significantly from the base late-onset epilepsy hazard were 'dementia and anxiety' (HR 5.36; 95%CI 3.31-8.68), 'brain tumour' (HR 4.97; 95%CI 2.89-8.56), 'ICH and alcohol misuse' (HR 2.91; 95%CI 1.76-4.81), and 'ischaemic stroke' (HR 2.83; 95%CI 1.83-4.04). These cluster-specific risks were also elevated compared to those derived for tumours, dementia, ischaemic stroke, and ICH in the whole population. Seizure-related cause of death was uncommon and restricted to the ICH, ICH and alcohol misuse, and healthy female clusters.

Significance

Late-onset epilepsy is an amalgam of unique phenotypic clusters that can be quantitatively defined. Late-onset epilepsy and cluster-specific comorbid profiles have complex effects on premature mortality above and beyond the base rates attributed to epilepsy and cluster-defining comorbidities alone.",,doi:https://doi.org/10.1016/j.seizure.2023.07.016 36882868,https://doi.org/10.1186/s12916-023-02784-z,"Assessing the impacts of COVID-19 vaccination programme's timing and speed on health benefits, cost-effectiveness, and relative affordability in 27 African countries.","Liu Y, Procter SR, Pearson CAB, Montero AM, Torres-Rueda S, Asfaw E, Uzochukwu B, Drake T, Bergren E, Eggo RM, Ruiz F, Ndembi N, Nonvignon J, Jit M, Vassall A.",,BMC medicine,2023,2023-03-08,Y,Mathematical models; Vaccination; Economic evaluation; decision-making; Affordability; Programme Evaluation; Public Health Interventions; Covid-19 | Sars-cov-2,,,"

Background

The COVID-19 vaccine supply shortage in 2021 constrained roll-out efforts in Africa while populations experienced waves of epidemics. As supply improves, a key question is whether vaccination remains an impactful and cost-effective strategy given changes in the timing of implementation.

Methods

We assessed the impact of vaccination programme timing using an epidemiological and economic model. We fitted an age-specific dynamic transmission model to reported COVID-19 deaths in 27 African countries to approximate existing immunity resulting from infection before substantial vaccine roll-out. We then projected health outcomes (from symptomatic cases to overall disability-adjusted life years (DALYs) averted) for different programme start dates (01 January to 01 December 2021, n = 12) and roll-out rates (slow, medium, fast; 275, 826, and 2066 doses/million population-day, respectively) for viral vector and mRNA vaccines by the end of 2022. Roll-out rates used were derived from observed uptake trajectories in this region. Vaccination programmes were assumed to prioritise those above 60 years before other adults. We collected data on vaccine delivery costs, calculated incremental cost-effectiveness ratios (ICERs) compared to no vaccine use, and compared these ICERs to GDP per capita. We additionally calculated a relative affordability measure of vaccination programmes to assess potential nonmarginal budget impacts.

Results

Vaccination programmes with early start dates yielded the most health benefits and lowest ICERs compared to those with late starts. While producing the most health benefits, fast vaccine roll-out did not always result in the lowest ICERs. The highest marginal effectiveness within vaccination programmes was found among older adults. High country income groups, high proportions of populations over 60 years or non-susceptible at the start of vaccination programmes are associated with low ICERs relative to GDP per capita. Most vaccination programmes with small ICERs relative to GDP per capita were also relatively affordable.

Conclusion

Although ICERs increased significantly as vaccination programmes were delayed, programmes starting late in 2021 may still generate low ICERs and manageable affordability measures. Looking forward, lower vaccine purchasing costs and vaccines with improved efficacies can help increase the economic value of COVID-19 vaccination programmes.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02784-z; doi:https://doi.org/10.1186/s12916-023-02784-z; html:https://europepmc.org/articles/PMC9991879; pdf:https://europepmc.org/articles/PMC9991879?pdf=render 38633209,https://doi.org/10.3389/fepid.2024.1326306,Making predictions under interventions: a case study from the PREDICT-CVD cohort in New Zealand primary care.,"Lin L, Poppe K, Wood A, Martin GP, Peek N, Sperrin M.",,Frontiers in epidemiology,2024,2024-04-03,Y,Cardiovascular diseases; Prevention; Treatment; Causal Inference; Clinical Prediction Model,,,"

Background

Most existing clinical prediction models do not allow predictions under interventions. Such predictions allow predicted risk under different proposed strategies to be compared and are therefore useful to support clinical decision making. We aimed to compare methodological approaches for predicting individual level cardiovascular risk under three interventions: smoking cessation, reducing blood pressure, and reducing cholesterol.

Methods

We used data from the PREDICT prospective cohort study in New Zealand to calculate cardiovascular risk in a primary care setting. We compared three strategies to estimate absolute risk under intervention: (a) conditioning on hypothetical interventions in non-causal models; (b) combining existing prediction models with causal effects estimated using observational causal inference methods; and (c) combining existing prediction models with causal effects reported in published literature.

Results

The median absolute cardiovascular risk among smokers was 3.9%; our approaches predicted that smoking cessation reduced this to a median between a non-causal estimate of 2.5% and a causal estimate of 2.8%, depending on estimation methods. For reducing blood pressure, the proposed approaches estimated a reduction of absolute risk from a median of 4.9% to a median between 3.2% and 4.5% (both derived from causal estimation). Reducing cholesterol was estimated to reduce median absolute risk from 3.1% to between 2.2% (non-causal estimate) and 2.8% (causal estimate).

Conclusions

Estimated absolute risk reductions based on non-causal methods were different to those based on causal methods, and there was substantial variation in estimates within the causal methods. Researchers wishing to estimate risk under intervention should be explicit about their causal modelling assumptions and conduct sensitivity analysis by considering a range of possible approaches.",,doi:https://doi.org/10.3389/fepid.2024.1326306; html:https://europepmc.org/articles/PMC11021700; pdf:https://europepmc.org/articles/PMC11021700?pdf=render 37415095,https://doi.org/10.1186/s12889-023-16202-9,Multi-morbidity and its association with common cancer diagnoses: a UK Biobank prospective study.,"Conroy MC, Reeves GK, Allen NE.",,BMC public health,2023,2023-07-06,Y,Cancer Risk; Uk Biobank; Multi-morbidity,,,"

Background

Whilst multi-morbidity is known to be a concern in people with cancer, very little is known about the risk of cancer in multi-morbid patients. This study aims to investigate the risk of being diagnosed with lung, colorectal, breast and prostate cancer associated with multi-morbidity.

Methods

We investigated the association between multi-morbidity and subsequent risk of cancer diagnosis in UK Biobank. Cox models were used to estimate the relative risks of each cancer of interest in multi-morbid participants, using the Cambridge Multimorbidity Score. The extent to which reverse causation, residual confounding and ascertainment bias may have impacted on the findings was robustly investigated.

Results

Of the 436,990 participants included in the study who were cancer-free at baseline, 21.6% (99,965) were multi-morbid (≥ 2 diseases). Over a median follow-up time of 10.9 [IQR 10.0-11.7] years, 9,019 prostate, 7,994 breast, 5,241 colorectal, and 3,591 lung cancers were diagnosed. After exclusion of the first year of follow-up, there was no clear association between multi-morbidity and risk of colorectal, prostate or breast cancer diagnosis. Those with ≥ 4 diseases at recruitment had double the risk of a subsequent lung cancer diagnosis compared to those with no diseases (HR 2.00 [95% CI 1.70-2.35] p for trend < 0.001). These findings were robust to sensitivity analyses aimed at reducing the impact of reverse causation, residual confounding from known cancer risk factors and ascertainment bias.

Conclusions

Individuals with multi-morbidity are at an increased risk of lung cancer diagnosis. While this association did not appear to be due to common sources of bias in observational studies, further research is needed to understand what underlies this association.",,pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-023-16202-9; doi:https://doi.org/10.1186/s12889-023-16202-9; html:https://europepmc.org/articles/PMC10326925; pdf:https://europepmc.org/articles/PMC10326925?pdf=render -37018139,https://doi.org/10.1093/rheumatology/kead150,"COVID-19 infection, admission and death and the impact of corticosteroids among people with rare autoimmune rheumatic disease during the second wave of COVID-19 in England: results from the RECORDER Project.","Rutter M, Lanyon PC, Grainge MJ, Hubbard R, Bythell M, Stilwell P, Aston J, McPhail S, Stevens S, Pearce FA.",,"Rheumatology (Oxford, England)",2023,2023-12-01,Y,Infection; Mortality; Coronavirus; epidemiology; Shielding; Covid-19; Rare Autoimmune Rheumatic Diseases,,,"

Objectives

To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the second wave of the COVID-19 pandemic in England, and describe the impact of corticosteroids on outcomes.

Methods

Hospital Episode Statistics data were used to identify people alive on 1 August 2020 with ICD-10 codes for RAIRD from the whole population of England. Linked national health records were used to calculate rates and rate ratios of COVID-19 infection and death up to 30 April 2021. Primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. NHS Digital and Office for National Statistics general population data were used for comparison. The association between 30-day corticosteroid usage and COVID-19-related death, COVID-19-related hospital admissions and all-cause deaths was also described.

Results

Of 168 330 people with RAIRD, 9961 (5.92%) had a positive COVID-19 PCR test. The age-standardized infection rate ratio between RAIRD and the general population was 0.99 (95% CI: 0.97, 1.00). 1342 (0.80%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardized mortality rate for COVID-19-related death was 2.76 (95% CI: 2.63, 2.89) times higher than in the general population. There was a dose-dependent relationship between 30-day corticosteroid usage and COVID-19-related death. There was no increase in deaths due to other causes.

Conclusions

During the second wave of COVID-19 in England, people with RAIRD had the same risk of COVID-19 infection but a 2.76-fold increased risk of COVID-19-related death compared with the general population, with corticosteroids associated with increased risk.",,pdf:https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/kead150/49769320/kead150.pdf; doi:https://doi.org/10.1093/rheumatology/kead150; html:https://europepmc.org/articles/PMC10691923; pdf:https://europepmc.org/articles/PMC10691923?pdf=render 34582457,https://doi.org/10.1371/journal.pmed.1003777,Predictive symptoms for COVID-19 in the community: REACT-1 study of over 1 million people.,"Elliott J, Whitaker M, Bodinier B, Eales O, Riley S, Ward H, Cooke G, Darzi A, Chadeau-Hyam M, Elliott P.",,PLoS medicine,2021,2021-09-28,Y,,,,"

Background

Rapid detection, isolation, and contact tracing of community COVID-19 cases are essential measures to limit the community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to identify a parsimonious set of symptoms that jointly predict COVID-19 and investigated whether predictive symptoms differ between the B.1.1.7 (Alpha) lineage (predominating as of April 2021 in the US, UK, and elsewhere) and wild type.

Methods and findings

We obtained throat and nose swabs with valid SARS-CoV-2 PCR test results from 1,147,370 volunteers aged 5 years and above (6,450 positive cases) in the REal-time Assessment of Community Transmission-1 (REACT-1) study. This study involved repeated community-based random surveys of prevalence in England (study rounds 2 to 8, June 2020 to January 2021, response rates 22%-27%). Participants were asked about symptoms occurring in the week prior to testing. Viral genome sequencing was carried out for PCR-positive samples with N-gene cycle threshold value < 34 (N = 1,079) in round 8 (January 2021). In univariate analysis, all 26 surveyed symptoms were associated with PCR positivity compared with non-symptomatic people. Stability selection (1,000 penalized logistic regression models with 50% subsampling) among people reporting at least 1 symptom identified 7 symptoms as jointly and positively predictive of PCR positivity in rounds 2-7 (June to December 2020): loss or change of sense of smell, loss or change of sense of taste, fever, new persistent cough, chills, appetite loss, and muscle aches. The resulting model (rounds 2-7) predicted PCR positivity in round 8 with area under the curve (AUC) of 0.77. The same 7 symptoms were selected as jointly predictive of B.1.1.7 infection in round 8, although when comparing B.1.1.7 with wild type, new persistent cough and sore throat were more predictive of B.1.1.7 infection while loss or change of sense of smell was more predictive of the wild type. The main limitations of our study are (i) potential participation bias despite random sampling of named individuals from the National Health Service register and weighting designed to achieve a representative sample of the population of England and (ii) the necessary reliance on self-reported symptoms, which may be prone to recall bias and may therefore lead to biased estimates of symptom prevalence in England.

Conclusions

Where testing capacity is limited, it is important to use tests in the most efficient way possible. We identified a set of 7 symptoms that, when considered together, maximize detection of COVID-19 in the community, including infection with the B.1.1.7 lineage.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003777&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003777; html:https://europepmc.org/articles/PMC8478234; pdf:https://europepmc.org/articles/PMC8478234?pdf=render +37018139,https://doi.org/10.1093/rheumatology/kead150,"COVID-19 infection, admission and death and the impact of corticosteroids among people with rare autoimmune rheumatic disease during the second wave of COVID-19 in England: results from the RECORDER Project.","Rutter M, Lanyon PC, Grainge MJ, Hubbard R, Bythell M, Stilwell P, Aston J, McPhail S, Stevens S, Pearce FA.",,"Rheumatology (Oxford, England)",2023,2023-12-01,Y,Infection; Mortality; Coronavirus; epidemiology; Shielding; Covid-19; Rare Autoimmune Rheumatic Diseases,,,"

Objectives

To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the second wave of the COVID-19 pandemic in England, and describe the impact of corticosteroids on outcomes.

Methods

Hospital Episode Statistics data were used to identify people alive on 1 August 2020 with ICD-10 codes for RAIRD from the whole population of England. Linked national health records were used to calculate rates and rate ratios of COVID-19 infection and death up to 30 April 2021. Primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. NHS Digital and Office for National Statistics general population data were used for comparison. The association between 30-day corticosteroid usage and COVID-19-related death, COVID-19-related hospital admissions and all-cause deaths was also described.

Results

Of 168 330 people with RAIRD, 9961 (5.92%) had a positive COVID-19 PCR test. The age-standardized infection rate ratio between RAIRD and the general population was 0.99 (95% CI: 0.97, 1.00). 1342 (0.80%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardized mortality rate for COVID-19-related death was 2.76 (95% CI: 2.63, 2.89) times higher than in the general population. There was a dose-dependent relationship between 30-day corticosteroid usage and COVID-19-related death. There was no increase in deaths due to other causes.

Conclusions

During the second wave of COVID-19 in England, people with RAIRD had the same risk of COVID-19 infection but a 2.76-fold increased risk of COVID-19-related death compared with the general population, with corticosteroids associated with increased risk.",,pdf:https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/kead150/49769320/kead150.pdf; doi:https://doi.org/10.1093/rheumatology/kead150; html:https://europepmc.org/articles/PMC10691923; pdf:https://europepmc.org/articles/PMC10691923?pdf=render 36755846,https://doi.org/10.1093/ckj/sfac241,"Depression is associated with frailty and lower quality of life in haemodialysis recipients, but not with mortality or hospitalization.","Anderson BM, Qasim M, Correa G, Evison F, Gallier S, Ferro CJ, Jackson TA, Sharif A.",,Clinical kidney journal,2023,2022-10-31,Y,Mortality; Depression; Frailty; Haemodialysis; Hospitalization; Health-related Quality Of Life,,,"

Background

Frailty and depression are highly prevalent in haemodialysis recipients, exhibit a reciprocal relationship, and are associated with increased mortality and hospitalization, and lower quality of life. Despite this, there has been little exploration of the relationship between depression and frailty upon patient outcomes. We aimed to explore the relationship between depression and frailty, and their associations with mortality, hospitalization and quality of life.

Methods

We performed a prospective cohort study of prevalent haemodialysis recipients linked to national datasets for outcomes including mortality and hospitalization. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), frailty using the Clinical Frailty Scale (CFS) and quality of life using the EuroQol 5-Dimension (EQ-5D) Summary Index.

Results

A total of 485 prevalent haemodialysis recipients were recruited, with 111 deaths and 1241 hospitalizations during follow-up. CFS was independently associated with mortality [hazard ratio (HR) 1.31; 95% confidence interval (CI) 1.08, 1.59; P = .006], hospitalization [incidence rate ratio (IRR) 1.13; 95% CI 1.03, 1.25; P = .010] and lower quality of life (Coef. -0.401; 95% CI -0.511, -0.292; P < .001). PHQ-9 score was independently associated with lower quality of life (Coef. -0.042; 95% CI -0.063, -0.021; P < .001), but not mortality (HR 1.00; 95% CI 0.96, 1.04; P = .901) or hospitalization (IRR 0.99; 95% CI 0.97, 1.01; P = .351). In an adjusted model including CFS, moderate depression was associated with reduced hospitalization (IRR 0.72; 95% CI 0.56, 0.93; P = .013).

Conclusions

With the addition of frailty, depression was associated with lower hospital admissions, but poorer quality of life. The relationship between frailty and depression, and their influence on outcomes is complex, requiring further study.",,pdf:https://academic.oup.com/ckj/article-pdf/16/2/342/49100412/sfac241.pdf; doi:https://doi.org/10.1093/ckj/sfac241; html:https://europepmc.org/articles/PMC9900564; pdf:https://europepmc.org/articles/PMC9900564?pdf=render 38459430,https://doi.org/10.1186/s12859-024-05682-0,Bayesian inference for identifying tumour-specific cancer dependencies through integration of ex-vivo drug response assays and drug-protein profiling.,"Xing H, Yau C.",,BMC bioinformatics,2024,2024-03-08,Y,Gaussian Process; Chemical Perturbation; Spike-and-slab Regression; Tumor-specific Molecular Dependencies,,,"The identification of tumor-specific molecular dependencies is essential for the development of effective cancer therapies. Genetic and chemical perturbations are powerful tools for discovering these dependencies. Even though chemical perturbations can be applied to primary cancer samples at large scale, the interpretation of experiment outcomes is often complicated by the fact that one chemical compound can affect multiple proteins. To overcome this challenge, Batzilla et al. (PLoS Comput Biol 18(8): e1010438, 2022) proposed DepInfeR, a regularized multi-response regression model designed to identify and estimate specific molecular dependencies of individual cancers from their ex-vivo drug sensitivity profiles. Inspired by their work, we propose a Bayesian extension to DepInfeR. Our proposed approach offers several advantages over DepInfeR, including e.g. the ability to handle missing values in both protein-drug affinity and drug sensitivity profiles without the need for data pre-processing steps such as imputation. Moreover, our approach uses Gaussian Processes to capture more complex molecular dependency structures, and provides probabilistic statements about whether a protein in the protein-drug affinity profiles is informative to the drug sensitivity profiles. Simulation studies demonstrate that our proposed approach achieves better prediction accuracy, and is able to discover unreported dependency structures.",,pdf:https://bmcbioinformatics.biomedcentral.com/counter/pdf/10.1186/s12859-024-05682-0; doi:https://doi.org/10.1186/s12859-024-05682-0; html:https://europepmc.org/articles/PMC10921766; pdf:https://europepmc.org/articles/PMC10921766?pdf=render 37340474,https://doi.org/10.1186/s12916-023-02877-9,Antidepressant drug prescription and incidence of COVID-19 in mental health outpatients: a retrospective cohort study.,"Glebov OO, Mueller C, Stewart R, Aarsland D, Perera G.",,BMC medicine,2023,2023-06-21,Y,Antidepressants; Ssri; respiratory infection; Drug Repurposing; Covid-19; Sars-cov-2,,,"

Background

Currently, the main pharmaceutical intervention for COVID-19 is vaccination. While antidepressant (AD) drugs have shown some efficacy in treatment of symptomatic COVID-19, their preventative potential remains largely unexplored. Analysis of association between prescription of ADs and COVID-19 incidence in the population would be beneficial for assessing the utility of ADs in COVID-19 prevention.

Methods

Retrospective study of association between AD prescription and COVID-19 diagnosis was performed in a cohort of community-dwelling adult mental health outpatients during the 1st wave of COVID-19 pandemic in the UK. Clinical record interactive search (CRIS) was performed for mentions of ADs within 3 months preceding admission to inpatient care of the South London and Maudsley (SLaM) NHS Foundation Trust. Incidence of positive COVID-19 tests upon admission and during inpatient treatment was the primary outcome measure.

Results

AD mention was associated with approximately 40% lower incidence of positive COVID-19 test results when adjusted for socioeconomic parameters and physical health. This association was also observed for prescription of ADs of the selective serotonin reuptake inhibitor (SSRI) class.

Conclusions

This preliminary study suggests that ADs, and SSRIs in particular, may be of benefit for preventing COVID-19 infection spread in the community. The key limitations of the study are its retrospective nature and the focus on a mental health patient cohort. A more definitive assessment of AD and SSRI preventative potential warrants prospective studies in the wider demographic.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02877-9; doi:https://doi.org/10.1186/s12916-023-02877-9; html:https://europepmc.org/articles/PMC10283271; pdf:https://europepmc.org/articles/PMC10283271?pdf=render @@ -468,14 +468,14 @@ PMC10910267,https://doi.org/,Development and evaluation of a tool to optimise in 35671273,https://doi.org/10.1371/journal.pone.0268837,Optimising the balance of acute and intermediate care capacity for the complex discharge pathway: Computer modelling study during COVID-19 recovery in England.,"Onen-Dumlu Z, Harper AL, Forte PG, Powell AL, Pitt M, Vasilakis C, Wood RM.",,PloS one,2022,2022-06-07,Y,,,,"

Objectives

While there has been significant research on the pressures facing acute hospitals during the COVID-19 pandemic, there has been less interest in downstream community services which have also been challenged in meeting demand. This study aimed to estimate the theoretical cost-optimal capacity requirement for 'step down' intermediate care services within a major healthcare system in England, at a time when considerable uncertainty remained regarding vaccination uptake and the easing of societal restrictions.

Methods

Demand for intermediate care was projected using an epidemiological model (for COVID-19 demand) and regressing upon public mobility (for non-COVID-19 demand). These were inputted to a computer simulation model of patient flow from acute discharge readiness to bedded and home-based Discharge to Assess (D2A) intermediate care services. Cost-optimal capacity was defined as that which yielded the lowest total cost of intermediate care provision and corresponding acute discharge delays.

Results

Increased intermediate care capacity is likely to bring about lower system-level costs, with the additional D2A investment more than offset by substantial reductions in costly acute discharge delays (leading also to improved patient outcome and experience). Results suggest that completely eliminating acute 'bed blocking' is unlikely economical (requiring large amounts of downstream capacity), and that health systems should instead target an appropriate tolerance based upon the specific characteristics of the pathway.

Conclusions

Computer modelling can be a valuable asset for determining optimal capacity allocation along the complex care pathway. With results supporting a Business Case for increased downstream capacity, this study demonstrates how modelling can be applied in practice and provides a blueprint for use alongside the freely-available model code.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0268837&type=printable; doi:https://doi.org/10.1371/journal.pone.0268837; html:https://europepmc.org/articles/PMC9173611; pdf:https://europepmc.org/articles/PMC9173611?pdf=render 36145196,https://doi.org/10.3390/nu14183821,Vitamin D Supplementation Does Not Influence SARS-CoV-2 Vaccine Efficacy or Immunogenicity: Sub-Studies Nested within the CORONAVIT Randomised Controlled Trial.,"Jolliffe DA, Vivaldi G, Chambers ES, Cai W, Li W, Faustini SE, Gibbons JM, Pade C, Coussens AK, Richter AG, McKnight Á, Martineau AR.",,Nutrients,2022,2022-09-16,Y,Interferon gamma; Vitamin D; Antibody; Randomised Controlled Trial; Breakthrough Sars-cov-2 Infection; Bnt162b2 Pfizer; Chadox1 Ncov-19 Oxford–astrazeneca,,,"Vitamin D deficiency has been reported to associate with the impaired development of antigen-specific responses following vaccination. We aimed to determine whether vitamin D supplements might boost the immunogenicity and efficacy of SARS-CoV-2 vaccination by conducting three sub-studies nested within the CORONAVIT randomised controlled trial, which investigated the effects of offering vitamin D supplements at a dose of 800 IU/day or 3200 IU/day vs. no offer on risk of acute respiratory infections in UK adults with circulating 25-hydroxyvitamin D concentrations <75 nmol/L. Sub-study 1 (n = 2808) investigated the effects of vitamin D supplementation on the risk of breakthrough SARS-CoV-2 infection following two doses of SARS-CoV-2 vaccine. Sub-study 2 (n = 1853) investigated the effects of vitamin D supplementation on titres of combined IgG, IgA and IgM (IgGAM) anti-Spike antibodies in eluates of dried blood spots collected after SARS-CoV-2 vaccination. Sub-study 3 (n = 100) investigated the effects of vitamin D supplementation on neutralising antibody and cellular responses in venous blood samples collected after SARS-CoV-2 vaccination. In total, 1945/2808 (69.3%) sub-study 1 participants received two doses of ChAdOx1 nCoV-19 (Oxford−AstraZeneca); the remainder received two doses of BNT162b2 (Pfizer). Mean follow-up 25(OH)D concentrations were significantly elevated in the 800 IU/day vs. no-offer group (82.5 vs. 53.6 nmol/L; mean difference 28.8 nmol/L, 95% CI 22.8−34.8) and in the 3200 IU/day vs. no offer group (105.4 vs. 53.6 nmol/L; mean difference 51.7 nmol/L, 45.1−58.4). Vitamin D supplementation did not influence the risk of breakthrough SARS-CoV-2 infection in vaccinated participants (800 IU/day vs. no offer: adjusted hazard ratio 1.28, 95% CI 0.89 to 1.84; 3200 IU/day vs. no offer: 1.17, 0.81 to 1.70). Neither did it influence IgGAM anti-Spike titres, neutralising antibody titres or IFN-γ concentrations in the supernatants of S peptide-stimulated whole blood. In conclusion, vitamin D replacement at a dose of 800 or 3200 IU/day effectively elevated 25(OH)D concentrations, but it did not influence the protective efficacy or immunogenicity of SARS-CoV-2 vaccination when given to adults who had a sub-optimal vitamin D status at baseline.",,pdf:https://www.mdpi.com/2072-6643/14/18/3821/pdf?version=1663570353; doi:https://doi.org/10.3390/nu14183821; html:https://europepmc.org/articles/PMC9506404; pdf:https://europepmc.org/articles/PMC9506404?pdf=render 37656609,https://doi.org/10.1093/aje/kwad179,CHALLENGES IN ESTIMATING THE EFFECTIVENESS OF 2 DOSES OF COVID-19 VACCINE BEYOND 6 MONTHS IN ENGLAND.,"Horne EMF, Hulme WJ, Keogh RH, Palmer TM, Williamson EJ, Parker EPK, Walker VM, Knight R, Wei Y, Taylor K, Fisher L, Morley J, Mehrkar A, Dillingham I, Bacon S, Goldacre B, Sterne JAC, OpenSAFELY Collaborative FT.",,American journal of epidemiology,2024,2024-01-01,Y,,,,,,pdf:https://academic.oup.com/aje/advance-article-pdf/doi/10.1093/aje/kwad179/51329819/kwad179.pdf; doi:https://doi.org/10.1093/aje/kwad179; html:https://europepmc.org/articles/PMC10773473; pdf:https://europepmc.org/articles/PMC10773473?pdf=render -38191614,https://doi.org/10.1038/s41591-023-02686-w,A common framework for health data governance standards.,"Torabi F, Squires E, Orton C, Heys S, Ford D, Lyons RA, Thompson S.",,Nature medicine,2024,2024-01-01,N,,,,,,doi:https://doi.org/10.1038/s41591-023-02686-w 32723851,https://doi.org/10.1136/bmjhci-2019-100122,HDR UK supporting mobilising computable biomedical knowledge in the UK.,"Sebire NJ, Cake C, Morris AD.",,BMJ health & care informatics,2020,2020-07-01,Y,Health care; Medical Informatics; Information Systems,,,"Computable biomedical knowledge (CBK) represents an evolving area of health informatics, with potential for rapid translational patient benefit. Health Data Research UK (HDR UK) is the national Institute for Health Data Science, whose aim is to unite the UK's health data to enable discoveries that improve people's lives. The three main components include the UK HDR Alliance of data custodians, committed to making health data available for research and innovation purposes for public benefit while ensuring safe use of data and building public trust, the HDR Hubs, as centres of expertise for curating data and providing expert domain-specific services, and the HDR Innovation Gateway ('Gateway'), providing discovery, accessibility, security and interoperability services. To support CBK developments, HDR UK is encouraging use of open data standards for research purposes, with guidance around areas in which standards are emerging, aims to work closely with the international CBK community to support initiatives and aid with evaluation and collaboration, and has established a phenomics workstream to create a national platform for dissemination of machine readable and computable phenotypical algorithms to reduce duplication of effort and improve reproducibility in clinical studies.",,pdf:https://informatics.bmj.com/content/bmjhci/27/2/e100122.full.pdf; doi:https://doi.org/10.1136/bmjhci-2019-100122; html:https://europepmc.org/articles/PMC7388881; pdf:https://europepmc.org/articles/PMC7388881?pdf=render -35534084,https://doi.org/10.1136/bmjopen-2021-054186,Evaluation of freely available data profiling tools for health data research application: a functional evaluation review.,"Gordon B, Fennessy C, Varma S, Barrett J, McCondochie E, Heritage T, Duroe O, Jeffery R, Rajamani V, Earlam K, Banda V, Sebire N.",,BMJ open,2022,2022-05-09,Y,Information management; information technology; Health Informatics,,,"

Objectives

To objectively evaluate freely available data profiling software tools using healthcare data.

Design

Data profiling tools were evaluated for their capabilities using publicly available information and data sheets. From initial assessment, several underwent further detailed evaluation for application on healthcare data using a synthetic dataset of 1000 patients and associated data using a common health data model, and tools scored based on their functionality with this dataset.

Setting

Improving the quality of healthcare data for research use is a priority. Profiling tools can assist by evaluating datasets across a range of quality dimensions. Several freely available software packages with profiling capabilities are available but healthcare organisations often have limited data engineering capability and expertise.

Participants

28 profiling tools, 8 undergoing evaluation on synthetic dataset of 1000 patients.

Results

Of 28 potential profiling tools initially identified, 8 showed high potential for applicability with healthcare datasets based on available documentation, of which two performed consistently well for these purposes across multiple tasks including determination of completeness, consistency, uniqueness, validity, accuracy and provision of distribution metrics.

Conclusions

Numerous freely available profiling tools are serviceable for potential use with health datasets, of which at least two demonstrated high performance across a range of technical data quality dimensions based on testing with synthetic health dataset and common data model. The appropriate tool choice depends on factors including underlying organisational infrastructure, level of data engineering and coding expertise, but there are freely available tools helping profile health datasets for research use and inform curation activity.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/5/e054186.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054186; html:https://europepmc.org/articles/PMC9086620; pdf:https://europepmc.org/articles/PMC9086620?pdf=render +38191614,https://doi.org/10.1038/s41591-023-02686-w,A common framework for health data governance standards.,"Torabi F, Squires E, Orton C, Heys S, Ford D, Lyons RA, Thompson S.",,Nature medicine,2024,2024-01-01,N,,,,,,doi:https://doi.org/10.1038/s41591-023-02686-w 32935048,https://doi.org/10.23889/ijpds.v5i1.1121,The Secure Anonymised Information Linkage databank Dementia e-cohort (SAIL-DeC).,"Schnier C, Wilkinson T, Akbari A, Orton C, Sleegers K, Gallacher J, Lyons RA, Sudlow C.",,International journal of population data science,2020,2020-02-25,Y,,,,"

Introduction

The rising burden of dementia is a global concern, and there is a need to study its causes, natural history and outcomes. The Secure Anonymised Information Linkage (SAIL) Databank contains anonymised, routinely-collected healthcare data for the population of Wales, UK. It has potential to be a valuable resource for dementia research owing to its size, long follow-up time and prospective collection of data during clinical care.

Objectives

We aimed to apply reproducible methods to create the SAIL dementia e-cohort (SAIL-DeC). We created SAIL-DeC with a view to maximising its utility for a broad range of research questions whilst minimising duplication of effort for researchers.

Methods

SAIL contains individual-level, linked primary care, hospital admission, mortality and demographic data. Data are currently available until 2018 and future updates will extend participant follow-up time. We included participants who were born between 1st January 1900 and 1st January 1958 and for whom primary care data were available. We applied algorithms consisting of International Classification of Diseases (versions 9 and 10) and Read (version 2) codes to identify participants with and without all-cause dementia and dementia subtypes. We also created derived variables for comorbidities and risk factors.

Results

From 4.4 million unique participants in SAIL, 1.2 million met the cohort inclusion criteria, resulting in 18.8 million person-years of follow-up. Of these, 129,650 (10%) developed all-cause dementia, with 77,978 (60%) having dementia subtype codes. Alzheimer's disease was the most common subtype diagnosis (62%). Among the dementia cases, the median duration of observation time was 14 years.

Conclusion

We have created a generalisable, national dementia e-cohort, aimed at facilitating epidemiological dementia research.",,pdf:https://ijpds.org/article/download/1121/2984; doi:https://doi.org/10.23889/ijpds.v5i1.1121; html:https://europepmc.org/articles/PMC7473277; pdf:https://europepmc.org/articles/PMC7473277?pdf=render +35534084,https://doi.org/10.1136/bmjopen-2021-054186,Evaluation of freely available data profiling tools for health data research application: a functional evaluation review.,"Gordon B, Fennessy C, Varma S, Barrett J, McCondochie E, Heritage T, Duroe O, Jeffery R, Rajamani V, Earlam K, Banda V, Sebire N.",,BMJ open,2022,2022-05-09,Y,Information management; information technology; Health Informatics,,,"

Objectives

To objectively evaluate freely available data profiling software tools using healthcare data.

Design

Data profiling tools were evaluated for their capabilities using publicly available information and data sheets. From initial assessment, several underwent further detailed evaluation for application on healthcare data using a synthetic dataset of 1000 patients and associated data using a common health data model, and tools scored based on their functionality with this dataset.

Setting

Improving the quality of healthcare data for research use is a priority. Profiling tools can assist by evaluating datasets across a range of quality dimensions. Several freely available software packages with profiling capabilities are available but healthcare organisations often have limited data engineering capability and expertise.

Participants

28 profiling tools, 8 undergoing evaluation on synthetic dataset of 1000 patients.

Results

Of 28 potential profiling tools initially identified, 8 showed high potential for applicability with healthcare datasets based on available documentation, of which two performed consistently well for these purposes across multiple tasks including determination of completeness, consistency, uniqueness, validity, accuracy and provision of distribution metrics.

Conclusions

Numerous freely available profiling tools are serviceable for potential use with health datasets, of which at least two demonstrated high performance across a range of technical data quality dimensions based on testing with synthetic health dataset and common data model. The appropriate tool choice depends on factors including underlying organisational infrastructure, level of data engineering and coding expertise, but there are freely available tools helping profile health datasets for research use and inform curation activity.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/5/e054186.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054186; html:https://europepmc.org/articles/PMC9086620; pdf:https://europepmc.org/articles/PMC9086620?pdf=render 35922409,https://doi.org/10.1038/s41467-022-32121-6,Dynamics of a national Omicron SARS-CoV-2 epidemic during January 2022 in England.,"Elliott P, Eales O, Bodinier B, Tang D, Wang H, Jonnerby J, Haw D, Elliott J, Whitaker M, Walters CE, Atchison C, Diggle PJ, Page AJ, Trotter AJ, Ashby D, Barclay W, Taylor G, Ward H, Darzi A, Cooke GS, Chadeau-Hyam M, Donnelly CA.",,Nature communications,2022,2022-08-03,Y,,,,"Rapid transmission of the SARS-CoV-2 Omicron variant has led to record-breaking case incidence rates around the world. Since May 2020, the REal-time Assessment of Community Transmission-1 (REACT-1) study tracked the spread of SARS-CoV-2 infection in England through RT-PCR of self-administered throat and nose swabs from randomly-selected participants aged 5 years and over. In January 2022, we found an overall weighted prevalence of 4.41% (n = 102,174), three-fold higher than in November to December 2021; we sequenced 2,374 (99.2%) Omicron infections (19 BA.2), and only 19 (0.79%) Delta, with a growth rate advantage for BA.2 compared to BA.1 or BA.1.1. Prevalence was decreasing overall (reproduction number R = 0.95, 95% credible interval [CrI], 0.93, 0.97), but increasing in children aged 5 to 17 years (R = 1.13, 95% CrI, 1.09, 1.18). In England during January 2022, we observed unprecedented levels of SARS-CoV-2 infection, especially among children, driven by almost complete replacement of Delta by Omicron.",,pdf:https://www.nature.com/articles/s41467-022-32121-6.pdf; doi:https://doi.org/10.1038/s41467-022-32121-6; html:https://europepmc.org/articles/PMC9349208; pdf:https://europepmc.org/articles/PMC9349208?pdf=render 35361119,https://doi.org/10.1186/s12859-022-04641-x,classifieR a flexible interactive cloud-application for functional annotation of cancer transcriptomes.,"Quinn GP, Sessler T, Ahmaderaghi B, Lambe S, VanSteenhouse H, Lawler M, Wappett M, Seligmann B, Longley DB, McDade SS.",,BMC bioinformatics,2022,2022-03-31,Y,Gene Expression; Functional Annotation; Cancer Subtype; Shiny Application; Colorectal Shiny Cms Cris Immune,,,"

Background

Transcriptionally informed predictions are increasingly important for sub-typing cancer patients, understanding underlying biology and to inform novel treatment strategies. For instance, colorectal cancers (CRCs) can be classified into four CRC consensus molecular subgroups (CMS) or five intrinsic (CRIS) sub-types that have prognostic and predictive value. Breast cancer (BRCA) has five PAM50 molecular subgroups with similar value, and the OncotypeDX test provides transcriptomic based clinically actionable treatment-risk stratification. However, assigning samples to these subtypes and other transcriptionally inferred predictions is time consuming and requires significant bioinformatics experience. There is no ""universal"" method of using data from diverse assay/sequencing platforms to provide subgroup classification using the established classifier sets of genes (CMS, CRIS, PAM50, OncotypeDX), nor one which in provides additional useful functional annotations such as cellular composition, single-sample Gene Set Enrichment Analysis, or prediction of transcription factor activity.

Results

To address this bottleneck, we developed classifieR, an easy-to-use R-Shiny based web application that supports flexible rapid single sample annotation of transcriptional profiles derived from cancer patient samples form diverse platforms. We demonstrate the utility of the "" classifieR"" framework to applications focused on the analysis of transcriptional profiles from colorectal (classifieRc) and breast (classifieRb). Samples are annotated with disease relevant transcriptional subgroups (CMS/CRIS sub-types in classifieRc and PAM50/inferred OncotypeDX in classifieRb), estimation of cellular composition using MCP-counter and xCell, single-sample Gene Set Enrichment Analysis (ssGSEA) and transcription factor activity predictions with Discriminant Regulon Expression Analysis (DoRothEA).

Conclusions

classifieR provides a framework which enables labs without access to a dedicated bioinformation can get information on the molecular makeup of their samples, providing an insight into patient prognosis, druggability and also as a tool for analysis and discovery. Applications are hosted online at https://generatr.qub.ac.uk/app/classifieRc and https://generatr.qub.ac.uk/app/classifieRb after signing up for an account on https://generatr.qub.ac.uk .",,pdf:https://bmcbioinformatics.biomedcentral.com/track/pdf/10.1186/s12859-022-04641-x; doi:https://doi.org/10.1186/s12859-022-04641-x; html:https://europepmc.org/articles/PMC8974006; pdf:https://europepmc.org/articles/PMC8974006?pdf=render -37408471,https://doi.org/10.1093/eurheartj/ehad424,The CODE-EHR global framework: lifting the veil on health record data.,"Asselbergs FW, Kotecha D.",,European heart journal,2023,2023-09-01,N,,,,,,pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad424/50827856/ehad424.pdf; doi:https://doi.org/10.1093/eurheartj/ehad424 32499256,https://doi.org/10.1136/bmjopen-2019-033424,Point-of-care tests for urinary tract infections: protocol for a systematic review and meta-analysis of diagnostic test accuracy.,"Fraile Navarro D, Sullivan F, Azcoaga-Lorenzo A, Hernandez Santiago V.",,BMJ open,2020,2020-06-03,Y,Urinary tract infections; epidemiology; Molecular Diagnostics; Diagnostic Microbiology,,,"

Introduction

Urinary tract infections (UTIs) are the second most common type of infection worldwide, accounting for a large number of primary care consultations and antibiotic prescribing. Current diagnosis is based on an empirical approach, relying on symptoms and occasional use of urine dipsticks. The diagnostic reference standard is still urine culture, although it is not routinely recommended for uncomplicated UTIs in the community, due to time to diagnosis (48 hours). Faster point-of-care tests have been developed, but their diagnostic accuracy has not been compared. Our objective is to systematically review and meta-analyse the diagnostic accuracy of currently available point-of-care tests for UTIs.

Methods and analysis

Studies evaluating the diagnostic accuracy of point-of-care tests for UTIs will be included. PubMed, Web of Science, Embase and Cochrane Database of Systematic Reviews were searched from inception to 1 June 2019. Data extraction and risk-of-bias assessment will be assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Meta-analysis will be performed depending on data availability and heterogeneity.

Ethics and dissemination

This is a systematic review protocol and therefore formal ethical approval is not required, as no primary, identifiable, personal data will be collected. Patients or the public were not involved in the design of our research. However, the findings from this review will be shared with key stakeholders, including patient groups, clinicians and guideline developers, and will also be presented and national and international conferences.

Prospero registration number

CRD42018112019.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/6/e033424.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-033424; html:https://europepmc.org/articles/PMC7282288; pdf:https://europepmc.org/articles/PMC7282288?pdf=render +37408471,https://doi.org/10.1093/eurheartj/ehad424,The CODE-EHR global framework: lifting the veil on health record data.,"Asselbergs FW, Kotecha D.",,European heart journal,2023,2023-09-01,N,,,,,,pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad424/50827856/ehad424.pdf; doi:https://doi.org/10.1093/eurheartj/ehad424 36536453,https://doi.org/10.1186/s41512-022-00137-7,Protocol for development and validation of postpartum cardiovascular disease (CVD) risk prediction model incorporating reproductive and pregnancy-related candidate predictors.,"Wambua S, Crowe F, Thangaratinam S, O'Reilly D, McCowan C, Brophy S, Yau C, Nirantharakumar K, Riley R, MuM-PreDiCT Group.",,Diagnostic and prognostic research,2022,2022-12-19,Y,Prognosis; Cardiovascular disease; Pregnant women; Pregnancy complications; Prediction Modeling,,,"

Background

Cardiovascular disease (CVD) is a leading cause of death among women. CVD is associated with reduced quality of life, significant treatment and management costs, and lost productivity. Estimating the risk of CVD would help patients at a higher risk of CVD to initiate preventive measures to reduce risk of disease. The Framingham risk score and the QRISK® score are two risk prediction models used to evaluate future CVD risk in the UK. Although the algorithms perform well in the general population, they do not take into account pregnancy complications, which are well known risk factors for CVD in women and have been highlighted in a recent umbrella review. We plan to develop a robust CVD risk prediction model to assess the additional value of pregnancy risk factors in risk prediction of CVD in women postpartum.

Methods

Using candidate predictors from QRISK®-3, the umbrella review identified from literature and from discussions with clinical experts and patient research partners, we will use time-to-event Cox proportional hazards models to develop and validate a 10-year risk prediction model for CVD postpartum using Clinical Practice Research Datalink (CPRD) primary care database for development and internal validation of the algorithm and the Secure Anonymised Information Linkage (SAIL) databank for external validation. We will then assess the value of additional candidate predictors to the QRISK®-3 in our internal and external validations.

Discussion

The developed risk prediction model will incorporate pregnancy-related factors which have been shown to be associated with future risk of CVD but have not been taken into account in current risk prediction models. Our study will therefore highlight the importance of incorporating pregnancy-related risk factors into risk prediction modeling for CVD postpartum.",,pdf:https://diagnprognres.biomedcentral.com/counter/pdf/10.1186/s41512-022-00137-7; doi:https://doi.org/10.1186/s41512-022-00137-7; html:https://europepmc.org/articles/PMC9761974; pdf:https://europepmc.org/articles/PMC9761974?pdf=render 37337233,https://doi.org/10.1186/s12916-023-02921-8,Trajectories of cardiac troponin in the decades before cardiovascular death: a longitudinal cohort study.,"Kimenai DM, Anand A, de Bakker M, Shipley M, Fujisawa T, Lyngbakken MN, Hveem K, Omland T, Valencia-Hernández CA, Lindbohm JV, Kivimaki M, Singh-Manoux A, Strachan FE, Shah ASV, Kardys I, Boersma E, Brunner EJ, Mills NL.",,BMC medicine,2023,2023-06-19,Y,cardiac troponin; risk factors; Outcome; General Population,,,"

Background

High-sensitivity cardiac troponin testing is a promising tool for cardiovascular risk prediction, but whether serial testing can dynamically predict risk is uncertain. We evaluated the trajectory of cardiac troponin I in the years prior to a cardiovascular event in the general population, and determine whether serial measurements could track risk within individuals.

Methods

In the Whitehall II cohort, high-sensitivity cardiac troponin I concentrations were measured on three occasions over a 15-year period. Time trajectories of troponin were constructed in those who died from cardiovascular disease compared to those who survived or died from other causes during follow up and these were externally validated in the HUNT Study. A joint model that adjusts for cardiovascular risk factors was used to estimate risk of cardiovascular death using serial troponin measurements.

Results

In 7,293 individuals (mean 58 ± 7 years, 29.4% women) cardiovascular and non-cardiovascular death occurred in 281 (3.9%) and 914 (12.5%) individuals (median follow-up 21.4 years), respectively. Troponin concentrations increased in those dying from cardiovascular disease with a steeper trajectory compared to those surviving or dying from other causes in Whitehall and HUNT (Pinteraction < 0.05 for both). The joint model demonstrated an independent association between temporal evolution of troponin and risk of cardiovascular death (HR per doubling, 1.45, 95% CI,1.33-1.75).

Conclusions

Cardiac troponin I concentrations increased in those dying from cardiovascular disease compared to those surviving or dying from other causes over the preceding decades. Serial cardiac troponin testing in the general population has potential to track future cardiovascular risk.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02921-8; doi:https://doi.org/10.1186/s12916-023-02921-8; html:https://europepmc.org/articles/PMC10280894; pdf:https://europepmc.org/articles/PMC10280894?pdf=render 37068964,https://doi.org/10.3399/bjgp.2022.0301,OpenSAFELY NHS Service Restoration Observatory 2: changes in primary care clinical activity in England during the COVID-19 pandemic.,"Curtis HJ, MacKenna B, Wiedemann M, Fisher L, Croker R, Morton CE, Inglesby P, Walker AJ, Morley J, Mehrkar A, Bacon SC, Hickman G, Evans D, Ward T, Davy S, Hulme WJ, Macdonald O, Conibere R, Lewis T, Myers M, Wanninayake S, Collison K, Drury C, Samuel M, Sood H, Cipriani A, Fazel S, Sharma M, Baqir W, Bates C, Parry J, Goldacre B, OpenSAFELY Collaborative.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2023,2023-04-27,Y,Primary Health Care; General Practice; Electronic Health Records; Covid-19,,,"

Background

The COVID-19 pandemic has disrupted healthcare activity across a broad range of clinical services. The NHS stopped non-urgent work in March 2020, later recommending services be restored to near-normal levels before winter where possible.

Aim

To describe changes in the volume and variation of coded clinical activity in general practice across six clinical areas: cardiovascular disease, diabetes, mental health, female and reproductive health, screening and related procedures, and processes related to medication.

Design and setting

With the approval of NHS England, a cohort study was conducted of 23.8 million patient records in general practice, in situ using OpenSAFELY.

Method

Common primary care activities were analysed using Clinical Terms Version 3 codes and keyword searches from January 2019 to December 2020, presenting median and deciles of code usage across practices per month.

Results

Substantial and widespread changes in clinical activity in primary care were identified since the onset of the COVID-19 pandemic, with generally good recovery by December 2020. A few exceptions showed poor recovery and warrant further investigation, such as mental health (for example, for 'Depression interim review' the median occurrences across practices in December 2020 was down by 41.6% compared with December 2019).

Conclusion

Granular NHS general practice data at population-scale can be used to monitor disruptions to healthcare services and guide the development of mitigation strategies. The authors are now developing real-time monitoring dashboards for the key measures identified in this study, as well as further studies using primary care data to monitor and mitigate the indirect health impacts of COVID-19 on the NHS.",,pdf:https://bjgp.org/content/bjgp/early/2023/01/31/BJGP.2022.0301.full.pdf; doi:https://doi.org/10.3399/BJGP.2022.0301; html:https://europepmc.org/articles/PMC10131234; pdf:https://europepmc.org/articles/PMC10131234?pdf=render @@ -499,8 +499,8 @@ PMC10910267,https://doi.org/,Development and evaluation of a tool to optimise in 38419826,https://doi.org/10.23889/ijpds.v8i4.2164,Common governance model: a way to avoid data segregation between existing trusted research environment.,"Torabi F, Orton C, Squires E, Heys S, Hier R, Lyons RA, Thompson S.",,International journal of population data science,2023,2023-11-08,Y,Data Protection; Data Governance; Trusted Research Environments,,,"

Background

Trusted Research Environments provide a legitimate basis for data access along with a set of technologies to support implementation of the ""five-safes"" framework for privacy protection. Lack of standard approaches in achieving compliance with the ""five-safes"" framework results in a diversity of approaches across different TREs. Data access and analysis across multiple TREs has a range of benefits including improved precision of analysis due to larger sample sizes and broader availability of out-of-sample records, particularly in the study of rare conditions. Knowledge of governance approaches used across UK-TREs is limited.

Objective

To document key governance features in major UK-TRE contributing to UK wide analysis and to identify elements that would directly facilitate multi TRE collaborations and federated analysis in future.

Method

We summarised three main characteristics across 15 major UK-based TREs: 1) data access environment; 2) data access requests and disclosure control procedures; and 3) governance models. We undertook case studies of collaborative analyses conducted in more than one TRE. We identified an array of TREs operating on an equivalent level of governance. We further identify commonly governed TREs with architectural considerations for achieving an equivalent level of information security management system standards to facilitate multi TRE functionality and federated analytics.

Results

All 15 UK-TREs allow pooling and analysis of aggregated research outputs only when they have passed human-operated disclosure control checks. Data access requests procedures are unique to each TRE. We also observed a variability in disclosure control procedures across various TREs with no or minimal researcher guidance on best practices for file out request procedures. In 2023, six TREs (40.0%) held ISO 20071 accreditation, while 9 TREs (56.2%) participated in four-nation analyses.

Conclusion

Secure analysis of individual-level data from multiple TREs is possible through existing technical solutions but requires development of a well-established governance framework meeting all stakeholder requirements and addressing public and patient concerns. Formation of a standard model could act as the catalyst for evolution of current TREs governance models to a multi TRE ecosystem within the UK and beyond.",,doi:https://doi.org/10.23889/ijpds.v8i4.2164; html:https://europepmc.org/articles/PMC10900179; pdf:https://europepmc.org/articles/PMC10900179?pdf=render 35418418,https://doi.org/10.1136/bmjopen-2021-049441,"Health checks for adults with intellectual disability and association with survival rates: a linked electronic records matched cohort study in Wales, UK.","Kennedy N, Kennedy J, Kerr M, Dredge S, Brophy S.",,BMJ open,2022,2022-04-13,Y,epidemiology; Quality In Health Care; General Medicine (See Internal Medicine),,,"

Objective

To examine if mortality rates are lower in people with intellectual disability who have had a health check compared with those who have not had health checks.

Setting

General practice records of 26 954 people with an intellectual disability in Wales between 2005-2017, of which 7650 (28.4%) with a health check were matched 1:2 with those without a health check.

Primary outcome measure

Office of National Statistics mortality data; a Cox regression was utilised to examine time to death adjusted for comorbidities and gender.

Results

Patients who had a health check were stratified by those who (1) had a confirmed health check, that is, Read Code for a health check (n=7650 (28.4 %)) and (2) had no evidence of receiving a health check in their medical record. Patients with a health check were matched for age at time of health check with two people who did not have a health check. The health check was associated with improved survival for those with autism or Down's Syndrome (HR 0.58 (95% CI 0.37 to 0.91) and HR 0.76 (95% CI 0.64 to 0.91), respectively). There was no evidence of improved survival for those diagnosed with diabetes or cancer. The people who had a health check were more likely to be older, have epilepsy and less likely to have autism or Down's syndrome.

Conclusions

Health checks are likely to influence survival if started before a person is diagnosed with a chronic condition, especially for people with autism or Down's syndrome.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e049441.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049441; html:https://europepmc.org/articles/PMC9013997; pdf:https://europepmc.org/articles/PMC9013997?pdf=render 35927670,https://doi.org/10.1186/s12882-022-02902-8,Pre-operative Waterlow score and outcomes after kidney transplantation.,"Brotherton A, Evison F, Gallier S, Sharif A.",,BMC nephrology,2022,2022-08-04,Y,Mortality; Kidney transplantation; Length Of Stay; Readmission; Surrogate; Waterlow,,,"

Background

Waterlow scoring was introduced in the 1980s as a nursing tool to risk stratify for development of decubitus ulcers (pressure sores) and is commonly used in UK hospitals. Recent interest has focussed on its value as a pre-op surrogate marker for adverse surgical outcomes, but utility after kidney transplantation has never been explored.

Methods

In this single-centre observational study, data was extracted from hospital informatics systems for all kidney allograft recipients transplanted between 1st January 2007 and 30th June 2020. Waterlow scores were categorised as per national standards; 0-9 (low risk), 10-14 (at risk), 15-19 (high risk) and ≥ 20 (very high risk). Multiple imputation was used to replace missing data with substituted values. Primary outcomes of interest were post-operative length of stay, emergency re-admission within 90-days and mortality analysed by linear, logistic or Cox regression models respectively.

Results

Data was available for 2,041 kidney transplant patients, with baseline demographics significantly different across Waterlow categories. As a continuous variable, the median Waterlow score across the study cohort was 10 (interquartile range 8-13). As a categorical variable, Waterlow scores pre-operatively were classified as low risk (n = 557), at risk (n = 543), high risk (n = 120), very high risk (n = 27) and a large proportion of missing data (n = 794). Median length of stay in days varied significantly with pre-op Waterlow category scores, progressively getting longer with increasing severity of Waterlow category. However, no difference was observed in risk for emergency readmission within 90-days of surgery with severity of Waterlow category. Patients with 'very high risk' Waterlow scores had increased risk for mortality at 41.9% versus high risk (23.7%), at risk (17.4%) and low risk (13.4%). In adjusted analyses, 'very high risk' Waterlow group (as a categorical variable) or Waterlow score (as a continuous variable) had an independent association with increase length of stay after transplant surgery only. No association was observed between any Waterlow risk group/score with emergency 90-day readmission rates or post-transplant mortality after adjustment.

Conclusions

Pre-operative Waterlow scoring is a poor surrogate marker to identify kidney transplant patients at risk of emergency readmission or death and should not be utilised outside its intended use.",,pdf:https://bmcnephrol.biomedcentral.com/counter/pdf/10.1186/s12882-022-02902-8; doi:https://doi.org/10.1186/s12882-022-02902-8; html:https://europepmc.org/articles/PMC9351155; pdf:https://europepmc.org/articles/PMC9351155?pdf=render -37927438,https://doi.org/10.1016/j.lanepe.2023.100741,Comparative effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised high-risk patients during Omicron waves: observational cohort study using the OpenSAFELY platform.,"Zheng B, Tazare J, Nab L, Green AC, Curtis HJ, Mahalingasivam V, Herrett EL, Costello RE, Eggo RM, Speed V, Bacon SC, Bates C, Parry J, Cockburn J, Hester F, Harper S, Schaffer AL, Hulme WJ, Mehrkar A, Evans SJ, MacKenna B, Goldacre B, Douglas IJ, Tomlinson LA, OpenSAFELY Collaborative.",,The Lancet regional health. Europe,2023,2023-10-08,Y,Comparative Effectiveness; Real-world Data; Covid-19; Sotrovimab; Paxlovid,,,"

Background

Timely evidence of the comparative effectiveness between COVID-19 therapies in real-world settings is needed to inform clinical care. This study aimed to compare the effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir in preventing severe COVID-19 outcomes in non-hospitalised high-risk COVID-19 adult patients during Omicron waves.

Methods

With the approval of NHS England, we conducted a real-world cohort study using the OpenSAFELY-TPP platform. Patient-level primary care data were obtained from 24 million people in England and were securely linked with data on COVID-19 infection and therapeutics, hospital admission, and death, covering a period where both nirmatrelvir/ritonavir and sotrovimab were first-line treatment options in community settings (February 10, 2022-November 27, 2022). Molnupiravir (third-line option) was used as an exploratory comparator to nirmatrelvir/ritonavir, both of which were antivirals. Cox proportional hazards model stratified by area was used to compare the risk of 28-day COVID-19 related hospitalisation/death across treatment groups.

Findings

A total of 9026 eligible patients treated with nirmatrelvir/ritonavir (n = 5704) and sotrovimab (n = 3322) were included in the main analysis. The mean age was 52.7 (SD = 14.9) years and 93% (8436/9026) had three or more COVID-19 vaccinations. Within 28 days after treatment initiation, 55/9026 (0.61%) COVID-19 related hospitalisations/deaths were observed (34/5704 [0.60%] treated with nirmatrelvir/ritonavir and 21/3322 [0.63%] with sotrovimab). After adjusting for demographics, high-risk cohort categories, vaccination status, calendar time, body mass index and other comorbidities, we observed no significant difference in outcome risk between nirmatrelvir/ritonavir and sotrovimab users (HR = 0.89, 95% CI: 0.48-1.63; P = 0.698). Results from propensity score weighted model also showed non-significant difference between treatment groups (HR = 0.82, 95% CI: 0.45-1.52; P = 0.535). The exploratory analysis comparing nirmatrelvir/ritonavir users with 1041 molnupiravir users (13/1041 [1.25%] COVID-19 related hospitalisations/deaths) showed an association in favour of nirmatrelvir/ritonavir (HR = 0.45, 95% CI: 0.22-0.94; P = 0.033).

Interpretation

In routine care of non-hospitalised high-risk adult patients with COVID-19 in England, no substantial difference in the risk of severe COVID-19 outcomes was observed between those who received nirmatrelvir/ritonavir and sotrovimab between February and November 2022, when Omicron subvariants BA.2, BA.5, or BQ.1 were dominant.

Funding

UK Research and Innovation, Wellcome Trust, UK Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.",,doi:https://doi.org/10.1016/j.lanepe.2023.100741; doi:https://doi.org/10.1016/j.lanepe.2023.100741; html:https://europepmc.org/articles/PMC10624988; pdf:https://europepmc.org/articles/PMC10624988?pdf=render 37248229,https://doi.org/10.1038/s41467-023-38756-3,Evidence-driven spatiotemporal COVID-19 hospitalization prediction with Ising dynamics.,"Gao J, Heintz J, Mack C, Glass L, Cross A, Sun J.",,Nature communications,2023,2023-05-29,Y,,,,"In this work, we aim to accurately predict the number of hospitalizations during the COVID-19 pandemic by developing a spatiotemporal prediction model. We propose HOIST, an Ising dynamics-based deep learning model for spatiotemporal COVID-19 hospitalization prediction. By drawing the analogy between locations and lattice sites in statistical mechanics, we use the Ising dynamics to guide the model to extract and utilize spatial relationships across locations and model the complex influence of granular information from real-world clinical evidence. By leveraging rich linked databases, including insurance claims, census information, and hospital resource usage data across the U.S., we evaluate the HOIST model on the large-scale spatiotemporal COVID-19 hospitalization prediction task for 2299 counties in the U.S. In the 4-week hospitalization prediction task, HOIST achieves 368.7 mean absolute error, 0.6 [Formula: see text] and 0.89 concordance correlation coefficient score on average. Our detailed number needed to treat (NNT) and cost analysis suggest that future COVID-19 vaccination efforts may be most impactful in rural areas. This model may serve as a resource for future county and state-level vaccination efforts.",,doi:https://doi.org/10.1038/s41467-023-38756-3; doi:https://doi.org/10.1038/s41467-023-38756-3; html:https://europepmc.org/articles/PMC10226446; pdf:https://europepmc.org/articles/PMC10226446?pdf=render +37927438,https://doi.org/10.1016/j.lanepe.2023.100741,Comparative effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised high-risk patients during Omicron waves: observational cohort study using the OpenSAFELY platform.,"Zheng B, Tazare J, Nab L, Green AC, Curtis HJ, Mahalingasivam V, Herrett EL, Costello RE, Eggo RM, Speed V, Bacon SC, Bates C, Parry J, Cockburn J, Hester F, Harper S, Schaffer AL, Hulme WJ, Mehrkar A, Evans SJ, MacKenna B, Goldacre B, Douglas IJ, Tomlinson LA, OpenSAFELY Collaborative.",,The Lancet regional health. Europe,2023,2023-10-08,Y,Comparative Effectiveness; Real-world Data; Covid-19; Sotrovimab; Paxlovid,,,"

Background

Timely evidence of the comparative effectiveness between COVID-19 therapies in real-world settings is needed to inform clinical care. This study aimed to compare the effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir in preventing severe COVID-19 outcomes in non-hospitalised high-risk COVID-19 adult patients during Omicron waves.

Methods

With the approval of NHS England, we conducted a real-world cohort study using the OpenSAFELY-TPP platform. Patient-level primary care data were obtained from 24 million people in England and were securely linked with data on COVID-19 infection and therapeutics, hospital admission, and death, covering a period where both nirmatrelvir/ritonavir and sotrovimab were first-line treatment options in community settings (February 10, 2022-November 27, 2022). Molnupiravir (third-line option) was used as an exploratory comparator to nirmatrelvir/ritonavir, both of which were antivirals. Cox proportional hazards model stratified by area was used to compare the risk of 28-day COVID-19 related hospitalisation/death across treatment groups.

Findings

A total of 9026 eligible patients treated with nirmatrelvir/ritonavir (n = 5704) and sotrovimab (n = 3322) were included in the main analysis. The mean age was 52.7 (SD = 14.9) years and 93% (8436/9026) had three or more COVID-19 vaccinations. Within 28 days after treatment initiation, 55/9026 (0.61%) COVID-19 related hospitalisations/deaths were observed (34/5704 [0.60%] treated with nirmatrelvir/ritonavir and 21/3322 [0.63%] with sotrovimab). After adjusting for demographics, high-risk cohort categories, vaccination status, calendar time, body mass index and other comorbidities, we observed no significant difference in outcome risk between nirmatrelvir/ritonavir and sotrovimab users (HR = 0.89, 95% CI: 0.48-1.63; P = 0.698). Results from propensity score weighted model also showed non-significant difference between treatment groups (HR = 0.82, 95% CI: 0.45-1.52; P = 0.535). The exploratory analysis comparing nirmatrelvir/ritonavir users with 1041 molnupiravir users (13/1041 [1.25%] COVID-19 related hospitalisations/deaths) showed an association in favour of nirmatrelvir/ritonavir (HR = 0.45, 95% CI: 0.22-0.94; P = 0.033).

Interpretation

In routine care of non-hospitalised high-risk adult patients with COVID-19 in England, no substantial difference in the risk of severe COVID-19 outcomes was observed between those who received nirmatrelvir/ritonavir and sotrovimab between February and November 2022, when Omicron subvariants BA.2, BA.5, or BQ.1 were dominant.

Funding

UK Research and Innovation, Wellcome Trust, UK Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.",,doi:https://doi.org/10.1016/j.lanepe.2023.100741; doi:https://doi.org/10.1016/j.lanepe.2023.100741; html:https://europepmc.org/articles/PMC10624988; pdf:https://europepmc.org/articles/PMC10624988?pdf=render 37311808,https://doi.org/10.1038/s41467-023-39193-y,"Natural history of long-COVID in a nationwide, population cohort study.","Hastie CE, Lowe DJ, McAuley A, Mills NL, Winter AJ, Black C, Scott JT, O'Donnell CA, Blane DN, Browne S, Ibbotson TR, Pell JP.",,Nature communications,2023,2023-06-13,Y,,,,"Previous studies on the natural history of long-COVID have been few and selective. Without comparison groups, disease progression cannot be differentiated from symptoms originating from other causes. The Long-COVID in Scotland Study (Long-CISS) is a Scotland-wide, general population cohort of adults who had laboratory-confirmed SARS-CoV-2 infection matched to PCR-negative adults. Serial, self-completed, online questionnaires collected information on pre-existing health conditions and current health six, 12 and 18 months after index test. Of those with previous symptomatic infection, 35% reported persistent incomplete/no recovery, 12% improvement and 12% deterioration. At six and 12 months, one or more symptom was reported by 71.5% and 70.7% respectively of those previously infected, compared with 53.5% and 56.5% of those never infected. Altered taste, smell and confusion improved over time compared to the never infected group and adjusted for confounders. Conversely, late onset dry and productive cough, and hearing problems were more likely following SARS-CoV-2 infection.",,pdf:https://www.nature.com/articles/s41467-023-39193-y.pdf; doi:https://doi.org/10.1038/s41467-023-39193-y; html:https://europepmc.org/articles/PMC10263377; pdf:https://europepmc.org/articles/PMC10263377?pdf=render 32877922,https://doi.org/10.1093/gerona/glaa216,Frailty Is Associated With Neutrophil Dysfunction Which Is Correctable With Phosphoinositol-3-Kinase Inhibitors.,"Wilson D, Drew W, Jasper A, Crisford H, Nightingale P, Newby P, Jackson T, Lord JM, Sapey E.",,"The journals of gerontology. Series A, Biological sciences and medical sciences",2020,2020-11-01,Y,Inflammation; Proteinases; innate immunity; Comorbidity,,,"Neutrophil dysfunction has been described with age, appears exaggerated in infection, with altered phosphoinositol signaling a potential mechanism. However, functional aging is heterogeneous. Frailty is a negative health status and is more common in older adults. We hypothesized that neutrophil migration may be compromised in frailty, associated with the degree of frailty experienced by the older person. We compared measures of frailty, neutrophil function, and systemic inflammation in 40 young and 77 older community-dwelling adults in the United Kingdom. Systemic neutrophils exhibited an age-associated reduction in the accuracy of migration (chemotaxis) which was further blunted with frailty. The degree of migratory inaccuracy correlated with physical (adjusted hand grip strength) and cognitive (Stroop test) markers of frailty. Regression analysis demonstrated that age, Charlson comorbidity index, and frailty index were able to predict neutrophil chemotaxis. Reduced chemotaxis of neutrophils from frail adults could be reversed using selective PI3K inhibitors. Exposure of neutrophils from young adults to plasma from chronically inflamed frail older adults could not recapitulate the migratory deficit in vitro, and there were no relationships with systemic inflammation and neutrophil dysfunction. Frailty exaggerated the neutrophil deficits seen with advanced age but aspects of the frailty-associated deficit in neutrophil function are rescuable and thus potentially form a therapeutic target to improve outcomes from infection in older adults.",,pdf:https://academic.oup.com/biomedgerontology/article-pdf/75/12/2320/34289886/glaa216.pdf; doi:https://doi.org/10.1093/gerona/glaa216; html:https://europepmc.org/articles/PMC7662170; pdf:https://europepmc.org/articles/PMC7662170?pdf=render 33611594,https://doi.org/10.1093/eurjpc/zwaa155,Excess deaths in people with cardiovascular diseases during the COVID-19 pandemic.,"Banerjee A, Chen S, Pasea L, Lai AG, Katsoulis M, Denaxas S, Nafilyan V, Williams B, Wong WK, Bakhai A, Khunti K, Pillay D, Noursadeghi M, Wu H, Pareek N, Bromage D, McDonagh TA, Byrne J, Teo JTH, Shah AM, Humberstone B, Tang LV, Shah ASV, Rubboli A, Guo Y, Hu Y, Sudlow CLM, Lip GYH, Hemingway H.",,European journal of preventive cardiology,2021,2021-12-01,Y,Cardiovascular disease; Public Health; Health Policy; Global Health; Coronavirus-2019,,,"

Aims

Cardiovascular diseases (CVDs) increase mortality risk from coronavirus infection (COVID-19). There are also concerns that the pandemic has affected supply and demand of acute cardiovascular care. We estimated excess mortality in specific CVDs, both 'direct', through infection, and 'indirect', through changes in healthcare.

Methods and results

We used (i) national mortality data for England and Wales to investigate trends in non-COVID-19 and CVD excess deaths; (ii) routine data from hospitals in England (n = 2), Italy (n = 1), and China (n = 5) to assess indirect pandemic effects on referral, diagnosis, and treatment services for CVD; and (iii) population-based electronic health records from 3 862 012 individuals in England to investigate pre- and post-COVID-19 mortality for people with incident and prevalent CVD. We incorporated pre-COVID-19 risk (by age, sex, and comorbidities), estimated population COVID-19 prevalence, and estimated relative risk (RR) of mortality in those with CVD and COVID-19 compared with CVD and non-infected (RR: 1.2, 1.5, 2.0, and 3.0).Mortality data suggest indirect effects on CVD will be delayed rather than contemporaneous (peak RR 1.14). CVD service activity decreased by 60-100% compared with pre-pandemic levels in eight hospitals across China, Italy, and England. In China, activity remained below pre-COVID-19 levels for 2-3 months even after easing lockdown and is still reduced in Italy and England. For total CVD (incident and prevalent), at 10% COVID-19 prevalence, we estimated direct impact of 31 205 and 62 410 excess deaths in England (RR 1.5 and 2.0, respectively), and indirect effect of 49 932 to 99 865 deaths.

Conclusion

Supply and demand for CVD services have dramatically reduced across countries with potential for substantial, but avoidable, excess mortality during and after the pandemic.",,pdf:https://academic.oup.com/eurjpc/article-pdf/28/14/1599/41827245/zwaa155.pdf; doi:https://doi.org/10.1093/eurjpc/zwaa155; html:https://europepmc.org/articles/PMC7928969; pdf:https://europepmc.org/articles/PMC7928969?pdf=render @@ -520,9 +520,9 @@ PMC10910267,https://doi.org/,Development and evaluation of a tool to optimise in 35677101,https://doi.org/10.23889/ijpds.v5i4.1715,"Impact of COVID-19 pandemic on community medication dispensing: a national cohort analysis in Wales, UK.","Torabi F, Akbari A, Bedston S, Davies G, Abbasizanjani H, Gravenor M, Griffiths R, Harris D, Jenkins N, Lyons J, Morris A, North L, Halcox J, Lyons RA.",,International journal of population data science,2020,2020-01-01,Y,Public Health; Covid-19; Dispensed Medication; Community Dispensing; Interactive Dispensing Dashboard,,,"

Background

Population-level information on dispensed medication provides insight on the distribution of treated morbidities, particularly if linked to other population-scale data at an individual-level.

Objective

To evaluate the impact of COVID-19 on dispensing patterns of medications.

Methods

Retrospective observational study using population-scale, individual-level dispensing records in Wales, UK. Total dispensed drug items for the population between 1 st January 2016 and 31 st December 2019 (3-years, pre-COVID-19) were compared to 2020 with follow up until 27 th July 2021 (COVID-19 period). We compared trends across all years and British National Formulary (BNF) chapters and highlighted the trends in three major chapters for 2019-21: 1-Cardiovascular system (CVD); 2-Central Nervous System (CNS); 3-Immunological & Vaccine. We developed an interactive dashboard to enable monitoring of changes as the pandemic evolves.

Result

Amongst all BNF chapters, 73,410,543 items were dispensed in 2020 compared to 74,121,180 items in 2019 demonstrating -0.96% relative decrease in 2020. Comparison of monthly patterns showed average difference (D) of -59,220 and average Relative Change (RC) of -0.74% between the number of dispensed items in 2020 and 2019. Maximum RC was observed in March 2020 (D = +1,224,909 and RC = +20.62), followed by second peak in June 2020 (D = +257,920, RC = +4.50%). A third peak was observed in September 2020 (D = +264,138, RC = +4.35%). Large increases in March 2020 were observed for CVD and CNS medications across all age groups. The Immunological and Vaccine products dropped to very low levels across all age groups and all months (including the March dispensing peak).

Conclusions

Reconfiguration of routine clinical services during COVID-19 led to substantial changes in community pharmacy drug dispensing. This change may contribute to a long-term burden of COVID-19, raising the importance of a comprehensive and timely monitoring of changes for evaluation of the potential impact on clinical care and outcomes.",,pdf:https://ijpds.org/article/download/1715/3382; doi:https://doi.org/10.23889/ijpds.v5i4.1715; html:https://europepmc.org/articles/PMC9135049; pdf:https://europepmc.org/articles/PMC9135049?pdf=render 37340508,https://doi.org/10.1186/s13059-023-02983-0,CNETML: maximum likelihood inference of phylogeny from copy number profiles of multiple samples.,"Lu B, Curtius K, Graham TA, Yang Z, Barnes CP.",,Genome biology,2023,2023-06-20,Y,Maximum likelihood; Copy Number Alteration; Phylogeny Inference; Low-coverage Sequencing; Model Of Evolution,,,"Phylogenetic trees based on copy number profiles from multiple samples of a patient are helpful to understand cancer evolution. Here, we develop a new maximum likelihood method, CNETML, to infer phylogenies from such data. CNETML is the first program to jointly infer the tree topology, node ages, and mutation rates from total copy numbers of longitudinal samples. Our extensive simulations suggest CNETML performs well on copy numbers relative to ploidy and under slight violation of model assumptions. The application of CNETML to real data generates results consistent with previous discoveries and provides novel early copy number events for further investigation.",,doi:https://doi.org/10.1186/s13059-023-02983-0; doi:https://doi.org/10.1186/s13059-023-02983-0; html:https://europepmc.org/articles/PMC10283241; pdf:https://europepmc.org/articles/PMC10283241?pdf=render 36573802,https://doi.org/10.1093/ije/dyac233,An empirical investigation into the impact of winner's curse on estimates from Mendelian randomization.,"Jiang T, Gill D, Butterworth AS, Burgess S.",,International journal of epidemiology,2023,2023-08-01,Y,Bias; Genome-wide Association Studies; Instrumental Variables; Mendelian Randomization; Winner’s Curse; Sample Overlap,,,"

Introduction

Genetic associations for variants identified through genome-wide association studies (GWASs) tend to be overestimated in the original discovery data set as, if the association was underestimated, the variant may not have been detected. This bias, known as winner's curse, can affect Mendelian randomization estimates, but its severity and potential impact are unclear.

Methods

We performed an empirical investigation to assess the potential bias from winner's curse in practice. We considered Mendelian randomization estimates for the effect of body mass index (BMI) on coronary artery disease risk. We randomly divided a UK Biobank data set 100 times into three equally sized subsets. The first subset was treated as the 'discovery GWAS'. We compared genetic associations estimated in the discovery GWAS to those estimated in the other subsets for each of the 100 iterations.

Results

For variants associated with BMI at P < 5 × 10-8 in at least one iteration, genetic associations with BMI were up to 5-fold greater in iterations in which the variant was associated with BMI at P < 5 × 10-8 compared with its mean association across all iterations. If the minimum P-value for association with BMI was P = 10-13 or lower, then this inflation was <25%. Mendelian randomization estimates were affected by winner's curse bias. However, bias did not materially affect results; all analyses indicated a deleterious effect of BMI on coronary artery disease risk.

Conclusions

Winner's curse can bias Mendelian randomization estimates, although its practical impact may not be substantial. If avoiding sample overlap is infeasible, analysts should consider performing a sensitivity analysis based on variants strongly associated with the exposure.",,pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac233/48422792/dyac233.pdf; doi:https://doi.org/10.1093/ije/dyac233; html:https://europepmc.org/articles/PMC10396423; pdf:https://europepmc.org/articles/PMC10396423?pdf=render -38569874,https://doi.org/10.1136/jnnp-2024-333530,"Trends in the prevalence and pharmacological management of migraine during pregnancy in the UK, 2000-2018.","Phillips K, Nirantharakumar K, Wakerley BR, Crowe FL.",,"Journal of neurology, neurosurgery, and psychiatry",2024,2024-04-03,N,Migraine,,,"

Background

Migraine is common in women of reproductive age. This study aimed to (1) describe the prevalence of migraine in pregnant women in the UK, (2) identify drugs commonly prescribed for migraine during pregnancy and (3) identify characteristics associated with being prescribed medication for migraine during pregnancy.

Methods

The Clinical Practice Research Datalink pregnancy register, a database of pregnancy episodes identified in anonymised primary care health records, was used.Crude and age-standardised prevalence of migraine during pregnancy and the proportion of women with migraine prescribed drugs used for migraine management were calculated for each year between 2000 and 2018.Logistic regression was used to describe the relationship between patient characteristics and being prescribed migraine medication during pregnancy.

Results

1 377 053 pregnancies were included, of which 187 328 were in women with a history of migraine. The age-adjusted prevalence increased from 11.4% in 2000 to 17.2% in 2018. There was an increase in the rates of prescription for numerous medications for the management of migraine.Older women (adjusted OR (aOR) 1.41 (1.20 to 1.66)), women of black (aOR 1.40 (1.32 to 1.48)) and South Asian ethnicity (aOR 1.48 (1.38 to 1.59)), those living in the most deprived areas (aOR 1.60 (1.54 to 1.66)), women who were obese (aOR 1.39 (1.35 to 1.43)), smokers (aOR 1.15 (1.12 to 1.18)) and those with comorbid conditions were more likely to receive a prescription during pregnancy.

Conclusions

Rates of recorded migraine have increased over the past two decades as well as rates of prescribing in women with migraine. Higher prescribing rates are seen in certain groups, which has the potential to exacerbate health inequalities.",,pdf:https://jnnp.bmj.com/content/jnnp/early/2024/04/03/jnnp-2024-333530.full.pdf; doi:https://doi.org/10.1136/jnnp-2024-333530 36716318,https://doi.org/10.1371/journal.pmed.1004174,Therapeutic potential of IL6R blockade for the treatment of sepsis and sepsis-related death: A Mendelian randomisation study.,"Hamilton FW, Thomas M, Arnold D, Palmer T, Moran E, Mentzer AJ, Maskell N, Baillie K, Summers C, Hingorani A, MacGowan A, Khandaker GM, Mitchell R, Davey Smith G, Ghazal P, Timpson NJ.",,PLoS medicine,2023,2023-01-30,Y,,,,"

Background

Sepsis is characterised by dysregulated, life-threatening immune responses, which are thought to be driven by cytokines such as interleukin 6 (IL-6). Genetic variants in IL6R known to down-regulate IL-6 signalling are associated with improved Coronavirus Disease 2019 (COVID-19) outcomes, a finding later confirmed in randomised trials of IL-6 receptor antagonists (IL6RAs). We hypothesised that blockade of IL6R could also improve outcomes in sepsis.

Methods and findings

We performed a Mendelian randomisation (MR) analysis using single nucleotide polymorphisms (SNPs) in and near IL6R to evaluate the likely causal effects of IL6R blockade on sepsis (primary outcome), sepsis severity, other infections, and COVID-19 (secondary outcomes). We weighted SNPs by their effect on CRP and combined results across them in inverse variance weighted meta-analysis, proxying the effect of IL6RA. Our outcomes were measured in UK Biobank, FinnGen, the COVID-19 Host Genetics Initiative (HGI), and the GenOSept and GainS consortium. We performed several sensitivity analyses to test assumptions of our methods, including utilising variants around CRP and gp130 in a similar analysis. In the UK Biobank cohort (N = 486,484, including 11,643 with sepsis), IL6R blockade was associated with a decreased risk of our primary outcome, sepsis (odds ratio (OR) = 0.80; 95% confidence interval (CI) 0.66 to 0.96, per unit of natural log-transformed CRP decrease). The size of this effect increased with severity, with larger effects on 28-day sepsis mortality (OR = 0.74; 95% CI 0.47 to 1.15); critical care admission with sepsis (OR = 0.48, 95% CI 0.30 to 0.78) and critical care death with sepsis (OR = 0.37, 95% CI 0.14 to 0.98). Similar associations were seen with severe respiratory infection: OR for pneumonia in critical care 0.69 (95% CI 0.49 to 0.97) and for sepsis survival in critical care (OR = 0.22; 95% CI 0.04 to 1.31) in the GainS and GenOSept consortium, although this result had a large degree of imprecision. We also confirm the previously reported protective effect of IL6R blockade on severe COVID-19 (OR = 0.69, 95% CI 0.57 to 0.84) in the COVID-19 HGI, which was of similar magnitude to that seen in sepsis. Sensitivity analyses did not alter our primary results. These results are subject to the limitations and assumptions of MR, which in this case reflects interpretation of these SNP effects as causally acting through blockade of IL6R, and reflect lifetime exposure to IL6R blockade, rather than the effect of therapeutic IL6R blockade.

Conclusions

IL6R blockade is causally associated with reduced incidence of sepsis. Similar but imprecisely estimated results supported a causal effect also on sepsis related mortality and critical care admission with sepsis. These effects are comparable in size to the effect seen in severe COVID-19, where IL-6 receptor antagonists were shown to improve survival. These data suggest that a randomised trial of IL-6 receptor antagonists in sepsis should be considered.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004174&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004174; html:https://europepmc.org/articles/PMC9925069; pdf:https://europepmc.org/articles/PMC9925069?pdf=render 38177344,https://doi.org/10.1038/s41588-023-01585-7,A compendium of genetic regulatory effects across pig tissues.,"Teng J, Gao Y, Yin H, Bai Z, Liu S, Zeng H, PigGTEx Consortium, Bai L, Cai Z, Zhao B, Li X, Xu Z, Lin Q, Pan Z, Yang W, Yu X, Guan D, Hou Y, Keel BN, Rohrer GA, Lindholm-Perry AK, Oliver WT, Ballester M, Crespo-Piazuelo D, Quintanilla R, Canela-Xandri O, Rawlik K, Xia C, Yao Y, Zhao Q, Yao W, Yang L, Li H, Zhang H, Liao W, Chen T, Karlskov-Mortensen P, Fredholm M, Amills M, Clop A, Giuffra E, Wu J, Cai X, Diao S, Pan X, Wei C, Li J, Cheng H, Wang S, Su G, Sahana G, Lund MS, Dekkers JCM, Kramer L, Tuggle CK, Corbett R, Groenen MAM, Madsen O, Gòdia M, Rocha D, Charles M, Li CJ, Pausch H, Hu X, Frantz L, Luo Y, Lin L, Zhou Z, Zhang Z, Chen Z, Cui L, Xiang R, Shen X, Li P, Huang R, Tang G, Li M, Zhao Y, Yi G, Tang Z, Jiang J, Zhao F, Yuan X, Liu X, Chen Y, Xu X, Zhao S, Zhao P, Haley C, Zhou H, Wang Q, Pan Y, Ding X, Ma L, Li J, Navarro P, Zhang Q, Li B, Tenesa A, Li K, Liu GE, Zhang Z, Fang L.",,Nature genetics,2024,2024-01-04,Y,,,,"The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.",,pdf:https://www.nature.com/articles/s41588-023-01585-7.pdf; doi:https://doi.org/10.1038/s41588-023-01585-7; html:https://europepmc.org/articles/PMC10786720; pdf:https://europepmc.org/articles/PMC10786720?pdf=render +38569874,https://doi.org/10.1136/jnnp-2024-333530,"Trends in the prevalence and pharmacological management of migraine during pregnancy in the UK, 2000-2018.","Phillips K, Nirantharakumar K, Wakerley BR, Crowe FL.",,"Journal of neurology, neurosurgery, and psychiatry",2024,2024-04-03,N,Migraine,,,"

Background

Migraine is common in women of reproductive age. This study aimed to (1) describe the prevalence of migraine in pregnant women in the UK, (2) identify drugs commonly prescribed for migraine during pregnancy and (3) identify characteristics associated with being prescribed medication for migraine during pregnancy.

Methods

The Clinical Practice Research Datalink pregnancy register, a database of pregnancy episodes identified in anonymised primary care health records, was used.Crude and age-standardised prevalence of migraine during pregnancy and the proportion of women with migraine prescribed drugs used for migraine management were calculated for each year between 2000 and 2018.Logistic regression was used to describe the relationship between patient characteristics and being prescribed migraine medication during pregnancy.

Results

1 377 053 pregnancies were included, of which 187 328 were in women with a history of migraine. The age-adjusted prevalence increased from 11.4% in 2000 to 17.2% in 2018. There was an increase in the rates of prescription for numerous medications for the management of migraine.Older women (adjusted OR (aOR) 1.41 (1.20 to 1.66)), women of black (aOR 1.40 (1.32 to 1.48)) and South Asian ethnicity (aOR 1.48 (1.38 to 1.59)), those living in the most deprived areas (aOR 1.60 (1.54 to 1.66)), women who were obese (aOR 1.39 (1.35 to 1.43)), smokers (aOR 1.15 (1.12 to 1.18)) and those with comorbid conditions were more likely to receive a prescription during pregnancy.

Conclusions

Rates of recorded migraine have increased over the past two decades as well as rates of prescribing in women with migraine. Higher prescribing rates are seen in certain groups, which has the potential to exacerbate health inequalities.",,pdf:https://jnnp.bmj.com/content/jnnp/early/2024/04/03/jnnp-2024-333530.full.pdf; doi:https://doi.org/10.1136/jnnp-2024-333530 37159441,https://doi.org/10.1371/journal.pdig.0000218,Hospital-wide natural language processing summarising the health data of 1 million patients.,"Bean DM, Kraljevic Z, Shek A, Teo J, Dobson RJB.",,PLOS digital health,2023,2023-05-09,Y,,,,"Electronic health records (EHRs) represent a major repository of real world clinical trajectories, interventions and outcomes. While modern enterprise EHR's try to capture data in structured standardised formats, a significant bulk of the available information captured in the EHR is still recorded only in unstructured text format and can only be transformed into structured codes by manual processes. Recently, Natural Language Processing (NLP) algorithms have reached a level of performance suitable for large scale and accurate information extraction from clinical text. Here we describe the application of open-source named-entity-recognition and linkage (NER+L) methods (CogStack, MedCAT) to the entire text content of a large UK hospital trust (King's College Hospital, London). The resulting dataset contains 157M SNOMED concepts generated from 9.5M documents for 1.07M patients over a period of 9 years. We present a summary of prevalence and disease onset as well as a patient embedding that captures major comorbidity patterns at scale. NLP has the potential to transform the health data lifecycle, through large-scale automation of a traditionally manual task.",,doi:https://doi.org/10.1371/journal.pdig.0000218; doi:https://doi.org/10.1371/journal.pdig.0000218; html:https://europepmc.org/articles/PMC10168555; pdf:https://europepmc.org/articles/PMC10168555?pdf=render 36841835,https://doi.org/10.1038/s41541-023-00614-0,Incidence determinants and serological correlates of reactive symptoms following SARS-CoV-2 vaccination.,"Holt H, Jolliffe DA, Talaei M, Faustini S, Vivaldi G, Greenig M, Richter AG, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Davies GA, Shaheen SO, Martineau AR.",,NPJ vaccines,2023,2023-02-25,Y,,,,"Prospective population-based studies investigating associations between reactive symptoms following SARS-CoV-2 vaccination and serologic responses to vaccination are lacking. We therefore conducted a study in 9003 adults from the UK general population receiving SARS-CoV-2 vaccines as part of the national vaccination programme. Titres of combined IgG/IgA/IgM responses to SARS-CoV-2 spike (S) glycoprotein were determined in eluates of dried blood spots collected from all participants before and after vaccination. 4262 (47.3%) participants experienced systemic reactive symptoms after a first vaccine dose. Factors associating with lower risk of such symptoms included older age (aOR per additional 10 years of age 0.85, 95% CI: 0.81-0.90), male vs. female sex (0.59, 0.53-0.65) and receipt of an mRNA vaccine vs. ChAdOx1 nCoV-19 (0.29, 0.26-0.32 for BNT162b2; 0.06, 0.01-0.26 for mRNA-1273). Higher risk of such symptoms was associated with SARS-CoV-2 seropositivity and COVID-19 symptoms prior to vaccination (2.23, 1.78-2.81), but not with SARS-CoV-2 seropositivity in the absence of COVID-19 symptoms (0.94, 0.81-1.09). Presence vs. absence of self-reported anxiety or depression at enrolment associated with higher risk of such symptoms (1.24, 1.12-1.39). Post-vaccination anti-S titres were higher among participants who experienced reactive symptoms after vaccination vs. those who did not (P < 0.001). We conclude that factors influencing risk of systemic symptoms after SARS-CoV-2 vaccination include demographic characteristics, pre-vaccination SARS-CoV-2 serostatus and vaccine type. Participants experiencing reactive symptoms following SARS-CoV-2 vaccination had higher post-vaccination titres of IgG/A/M anti-S antibodies. Improved public understanding of the frequency of reactogenic symptoms and their positive association with vaccine immunogenicity could potentially increase vaccine uptake.",,pdf:https://www.nature.com/articles/s41541-023-00614-0.pdf; doi:https://doi.org/10.1038/s41541-023-00614-0; html:https://europepmc.org/articles/PMC9959934; pdf:https://europepmc.org/articles/PMC9959934?pdf=render 36224173,https://doi.org/10.1038/s41467-022-33415-5,Outcomes among confirmed cases and a matched comparison group in the Long-COVID in Scotland study.,"Hastie CE, Lowe DJ, McAuley A, Winter AJ, Mills NL, Black C, Scott JT, O'Donnell CA, Blane DN, Browne S, Ibbotson TR, Pell JP.",,Nature communications,2022,2022-10-12,Y,,,,"With increasing numbers infected by SARS-CoV-2, understanding long-COVID is essential to inform health and social care support. A Scottish population cohort of 33,281 laboratory-confirmed SARS-CoV-2 infections and 62,957 never-infected individuals were followed-up via 6, 12 and 18-month questionnaires and linkage to hospitalization and death records. Of the 31,486 symptomatic infections,1,856 (6%) had not recovered and 13,350 (42%) only partially. No recovery was associated with hospitalized infection, age, female sex, deprivation, respiratory disease, depression and multimorbidity. Previous symptomatic infection was associated with poorer quality of life, impairment across all daily activities and 24 persistent symptoms including breathlessness (OR 3.43, 95% CI 3.29-3.58), palpitations (OR 2.51, OR 2.36-2.66), chest pain (OR 2.09, 95% CI 1.96-2.23), and confusion (OR 2.92, 95% CI 2.78-3.07). Asymptomatic infection was not associated with adverse outcomes. Vaccination was associated with reduced risk of seven symptoms. Here we describe the nature of long-COVID and the factors associated with it.",,pdf:https://researchonline.gcu.ac.uk/files/64233779/s41467_022_33415_5.pdf; doi:https://doi.org/10.1038/s41467-022-33415-5; html:https://europepmc.org/articles/PMC9556711; pdf:https://europepmc.org/articles/PMC9556711?pdf=render @@ -578,8 +578,8 @@ PMC10910267,https://doi.org/,Development and evaluation of a tool to optimise in 37236697,https://doi.org/10.1016/s2589-7500(23)00065-1,"Identifying subtypes of heart failure from three electronic health record sources with machine learning: an external, prognostic, and genetic validation study.","Banerjee A, Dashtban A, Chen S, Pasea L, Thygesen JH, Fatemifar G, Tyl B, Dyszynski T, Asselbergs FW, Lund LH, Lumbers T, Denaxas S, Hemingway H.",,The Lancet. Digital health,2023,2023-06-01,N,,,,"

Background

Machine learning has been used to analyse heart failure subtypes, but not across large, distinct, population-based datasets, across the whole spectrum of causes and presentations, or with clinical and non-clinical validation by different machine learning methods. Using our published framework, we aimed to discover heart failure subtypes and validate them upon population representative data.

Methods

In this external, prognostic, and genetic validation study we analysed individuals aged 30 years or older with incident heart failure from two population-based databases in the UK (Clinical Practice Research Datalink [CPRD] and The Health Improvement Network [THIN]) from 1998 to 2018. Pre-heart failure and post-heart failure factors (n=645) included demographic information, history, examination, blood laboratory values, and medications. We identified subtypes using four unsupervised machine learning methods (K-means, hierarchical, K-Medoids, and mixture model clustering) with 87 of 645 factors in each dataset. We evaluated subtypes for (1) external validity (across datasets); (2) prognostic validity (predictive accuracy for 1-year mortality); and (3) genetic validity (UK Biobank), association with polygenic risk score (PRS) for heart failure-related traits (n=11), and single nucleotide polymorphisms (n=12).

Findings

We included 188 800, 124 262, and 9573 individuals with incident heart failure from CPRD, THIN, and UK Biobank, respectively, between Jan 1, 1998, and Jan 1, 2018. After identifying five clusters, we labelled heart failure subtypes as (1) early onset, (2) late onset, (3) atrial fibrillation related, (4) metabolic, and (5) cardiometabolic. In the external validity analysis, subtypes were similar across datasets (c-statistics: THIN model in CPRD ranged from 0·79 [subtype 3] to 0·94 [subtype 1], and CPRD model in THIN ranged from 0·79 [subtype 1] to 0·92 [subtypes 2 and 5]). In the prognostic validity analysis, 1-year all-cause mortality after heart failure diagnosis (subtype 1 0·20 [95% CI 0·14-0·25], subtype 2 0·46 [0·43-0·49], subtype 3 0·61 [0·57-0·64], subtype 4 0·11 [0·07-0·16], and subtype 5 0·37 [0·32-0·41]) differed across subtypes in CPRD and THIN data, as did risk of non-fatal cardiovascular diseases and all-cause hospitalisation. In the genetic validity analysis the atrial fibrillation-related subtype showed associations with the related PRS. Late onset and cardiometabolic subtypes were the most similar and strongly associated with PRS for hypertension, myocardial infarction, and obesity (p<0·0009). We developed a prototype app for routine clinical use, which could enable evaluation of effectiveness and cost-effectiveness.

Interpretation

Across four methods and three datasets, including genetic data, in the largest study of incident heart failure to date, we identified five machine learning-informed subtypes, which might inform aetiological research, clinical risk prediction, and the design of heart failure trials.

Funding

European Union Innovative Medicines Initiative-2.",,pdf:http://www.thelancet.com/article/S2589750023000651/pdf; doi:https://doi.org/10.1016/S2589-7500(23)00065-1 35003715,https://doi.org/10.7189/jogh.11.05026,"Uptake, effectiveness and safety of COVID-19 vaccines in children and young people in Scotland: Protocol for early pandemic evaluation and enhanced surveillance of COVID-19 (EAVE II).","Adeloye D, Katikireddi SV, Woolford L, Simpson CR, Shah SA, Agrawal U, Richie LD, Swann OV, Stock SJ, Robertson C, Sheikh A, Rudan I.",,Journal of global health,2021,2021-12-25,Y,,,,"

Background

The dynamics of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and severity of disease among children and young people (CYP) across different settings are of considerable clinical, public health and societal interest. Severe COVID-19 cases, requiring hospitalisations, and deaths have been reported in some CYP suggesting a need to extend vaccinations to these age groups. As part of the ongoing Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) study, we aim to investigate the uptake, effectiveness and safety of COVID-19 vaccines in children and young people (CYP) aged 0 to 17 years in Scotland. Specifically, we will estimate: (i) uptake of vaccines against COVID-19, (ii) vaccine effectiveness (VE) against the outcomes of symptomatic SARS-CoV-2 infection, hospitalisation, intensive care unit (ICU) admissions, and death; (iii) VE for first/second dose timing among different age groups and risk groups; and (iv) the safety of vaccines.

Methods and analysis

We will conduct an open prospective cohort study classifying exposure as time-varying. We will compare outcomes amongst first dose vaccinated and second dose vaccinated CYP to those not yet vaccinated. A Test Negative Design (TND) case control study will be nested within this national cohort to investigate VE against symptomatic infection. The primary outcomes will be (i) uptake of vaccines against COVID-19, (ii) time to COVID-19 infection, hospitalisation, ICU admissions or death, and (iii) adverse events related to vaccines. Vaccination status (unvaccinated, one dose and two doses) will be defined as a time-varying exposure. Data from multiple sources will be linked using a unique identifier. We will conduct descriptive analyses to explore trends in vaccine uptake, and association between different exposure variables and vaccine uptake will be determined using multivariable logistic regression models. VE will be assessed from time-dependent Cox models or Poisson regression models, adjusted for relevant confounders, including age, sex, socioeconomic status, and comorbidities. We will employ self-controlled study designs to determine the risk of adverse events following COVID-19 vaccination.

Ethics and dissemination

Ethics approval was obtained from the National Research Ethics Committee, South East Scotland 02. We will present findings of this study at international conferences, in peer-reviewed journals and to policy-makers.",,doi:https://doi.org/10.7189/jogh.11.05026; doi:https://doi.org/10.7189/jogh.11.05026; html:https://europepmc.org/articles/PMC8709900; pdf:https://europepmc.org/articles/PMC8709900?pdf=render 33667930,https://doi.org/10.1016/j.ijmedinf.2021.104400,Real-time spatial health surveillance: Mapping the UK COVID-19 epidemic.,"Fry R, Hollinghurst J, Stagg HR, Thompson DA, Fronterre C, Orton C, Lyons RA, Ford DV, Sheikh A, Diggle PJ.",,International journal of medical informatics,2021,2021-01-28,Y,,,,"Introduction The COVID-19 pandemic has highlighted the need for robust data linkage systems and methods for identifying outbreaks of disease in near real-time. Objectives The primary objective of this study was to develop a real-time geospatial surveillance system to monitor the spread of COVID-19 across the UK. Methods Using self-reported app data and the Secure Anonymised Information Linkage (SAIL) Databank, we demonstrate the use of sophisticated spatial modelling for near-real-time prediction of COVID-19 prevalence at small-area resolution to inform strategic government policy areas. Results We demonstrate that using a combination of crowd-sourced app data and sophisticated geo-statistical techniques it is possible to predict hot spots of COVID-19 at fine geographic scales, nationally. We are also able to produce estimates of their precision, which is an important pre-requisite to an effective control strategy to guard against over-reaction to potentially spurious features of 'best guess' predictions. Conclusion In the UK, important emerging risk-factors such as social deprivation or ethnicity vary over small distances, hence risk needs to be modelled at fine spatial resolution to avoid aggregation bias. We demonstrate that existing geospatial statistical methods originally developed for global health applications are well-suited to this task and can be used in an anonymised databank environment, thus preserving the privacy of the individuals who contribute their data.",,doi:https://doi.org/10.1016/j.ijmedinf.2021.104400; doi:https://doi.org/10.1016/j.ijmedinf.2021.104400; html:https://europepmc.org/articles/PMC7843148 -37996473,https://doi.org/10.1038/s41598-023-47371-7,"Evidence for involvement of the alcohol consumption WDPCP gene in lipid metabolism, and liver cirrhosis.","O'Farrell F, Aleyakpo B, Mustafa R, Jiang X, Pinto RC, Elliott P, Tzoulaki I, Dehghan A, Loh SHY, Barclay JW, Martins LM, Pazoki R.",,Scientific reports,2023,2023-11-23,Y,,,,"Biological pathways between alcohol consumption and alcohol liver disease (ALD) are not fully understood. We selected genes with known effect on (1) alcohol consumption, (2) liver function, and (3) gene expression. Expression of the orthologs of these genes in Caenorhabditis elegans and Drosophila melanogaster was suppressed using mutations and/or RNA interference (RNAi). In humans, association analysis, pathway analysis, and Mendelian randomization analysis were performed to identify metabolic changes due to alcohol consumption. In C. elegans, we found a reduction in locomotion rate after exposure to ethanol for RNAi knockdown of ACTR1B and MAPT. In Drosophila, we observed (1) a change in sedative effect of ethanol for RNAi knockdown of WDPCP, TENM2, GPN1, ARPC1B, and SCN8A, (2) a reduction in ethanol consumption for RNAi knockdown of TENM2, (3) a reduction in triradylglycerols (TAG) levels for RNAi knockdown of WDPCP, TENM2, and GPN1. In human, we observed (1) a link between alcohol consumption and several metabolites including TAG, (2) an enrichment of the candidate (alcohol-associated) metabolites within the linoleic acid (LNA) and alpha-linolenic acid (ALA) metabolism pathways, (3) a causal link between gene expression of WDPCP to liver fibrosis and liver cirrhosis. Our results imply that WDPCP might be involved in ALD.",,pdf:https://www.nature.com/articles/s41598-023-47371-7.pdf; doi:https://doi.org/10.1038/s41598-023-47371-7; html:https://europepmc.org/articles/PMC10667215; pdf:https://europepmc.org/articles/PMC10667215?pdf=render 33965593,https://doi.org/10.1016/j.jaip.2021.04.055,Intolerance to Angiotensin Converting Enzyme Inhibitors in Asthma and the General Population: A UK Population-Based Cohort Study.,"Morales DR, Lipworth BJ, Donnan PT, Wang H.",,The journal of allergy and clinical immunology. In practice,2021,2021-05-06,Y,Hypertension; Angiotensin converting enzyme; Asthma; epidemiology; Cough,,,"

Background

Angiotensin converting enzyme inhibitor (ACEI) intolerance commonly occurs, requiring switching to an angiotensin-II receptor blocker (ARB). Angiotensin converting enzyme inhibitor intolerance may be mediated by bradykinin, potentially affecting airway hyperresponsiveness.

Objective

To assess the risk for switching to ARBs in asthma.

Methods

We conducted a new-user cohort study of ACEI initiators identified from electronic health records from the UK Clinical Practice Research Datalink. The risk for switching to ARBs in people with asthma or chronic obstructive pulmonary disease and the general population was compared. Adjusted hazard ratios (HRs) were calculated using Cox regression, stratified by British Thoracic Society (BTS) treatment step and ACEI type.

Results

Of 642,336 new users of ACEI, 6.4% had active asthma. The hazard of switching to ARB was greater in people with asthma (HR = 1.16; 95% confidence interval [CI], 1.14-1.18; P ≤ .001) and highest in those at BTS step 3 or greater (HR = 1.35, 95% CI, 1.32-1.39; and HR = 1.18, 95% CI, 1.15-1.22, P ≤ .001 for patients aged ≥60 and <60 years, respectively). Hazard was highest with enalapril (HR = 1.25, 95% CI, 1.18-1.34, P ≤ .001; HR = 1.44, 95% CI, 1.32-1.58, P ≤ .001 for BTS step 3 or greater asthma). No increased hazard was observed in chronic obstructive pulmonary disease or those younger than age 60 years at BTS step 1/2. The number needed to treat varied by age, sex, and body mass index (BMI), ranging between 21 and 4, and was lowest in older women with a BMI of 25 or greater.

Conclusions

People with active asthma are more likely to switch to ARBs after commencing ACEI therapy. The number needed to treat varies by age, sex, BMI, and BTS step. Angiotensin-II receptor blocker could potentially be considered first-line in people with asthma and in those with high-risk characteristics.",,pdf:https://europepmc.org/articles/pmc8443840?pdf=render; doi:https://doi.org/10.1016/j.jaip.2021.04.055; html:https://europepmc.org/articles/PMC8443840; pdf:https://europepmc.org/articles/PMC8443840?pdf=render +37996473,https://doi.org/10.1038/s41598-023-47371-7,"Evidence for involvement of the alcohol consumption WDPCP gene in lipid metabolism, and liver cirrhosis.","O'Farrell F, Aleyakpo B, Mustafa R, Jiang X, Pinto RC, Elliott P, Tzoulaki I, Dehghan A, Loh SHY, Barclay JW, Martins LM, Pazoki R.",,Scientific reports,2023,2023-11-23,Y,,,,"Biological pathways between alcohol consumption and alcohol liver disease (ALD) are not fully understood. We selected genes with known effect on (1) alcohol consumption, (2) liver function, and (3) gene expression. Expression of the orthologs of these genes in Caenorhabditis elegans and Drosophila melanogaster was suppressed using mutations and/or RNA interference (RNAi). In humans, association analysis, pathway analysis, and Mendelian randomization analysis were performed to identify metabolic changes due to alcohol consumption. In C. elegans, we found a reduction in locomotion rate after exposure to ethanol for RNAi knockdown of ACTR1B and MAPT. In Drosophila, we observed (1) a change in sedative effect of ethanol for RNAi knockdown of WDPCP, TENM2, GPN1, ARPC1B, and SCN8A, (2) a reduction in ethanol consumption for RNAi knockdown of TENM2, (3) a reduction in triradylglycerols (TAG) levels for RNAi knockdown of WDPCP, TENM2, and GPN1. In human, we observed (1) a link between alcohol consumption and several metabolites including TAG, (2) an enrichment of the candidate (alcohol-associated) metabolites within the linoleic acid (LNA) and alpha-linolenic acid (ALA) metabolism pathways, (3) a causal link between gene expression of WDPCP to liver fibrosis and liver cirrhosis. Our results imply that WDPCP might be involved in ALD.",,pdf:https://www.nature.com/articles/s41598-023-47371-7.pdf; doi:https://doi.org/10.1038/s41598-023-47371-7; html:https://europepmc.org/articles/PMC10667215; pdf:https://europepmc.org/articles/PMC10667215?pdf=render 31462651,https://doi.org/10.1038/s41598-019-48927-2,Hierarchical Template Matching for 3D Myocardial Tracking and Cardiac Strain Estimation.,"Bhalodiya JM, Palit A, Ferrante E, Tiwari MK, Bhudia SK, Arvanitis TN, Williams MA.",,Scientific reports,2019,2019-08-28,Y,,Applied Analytics,,"Myocardial tracking and strain estimation can non-invasively assess cardiac functioning using subject-specific MRI. As the left-ventricle does not have a uniform shape and functioning from base to apex, the development of 3D MRI has provided opportunities for simultaneous 3D tracking, and 3D strain estimation. We have extended a Local Weighted Mean (LWM) transformation function for 3D, and incorporated in a Hierarchical Template Matching model to solve 3D myocardial tracking and strain estimation problem. The LWM does not need to solve a large system of equations, provides smooth displacement of myocardial points, and adapt local geometric differences in images. Hence, 3D myocardial tracking can be performed with 1.49 mm median error, and without large error outliers. The maximum error of tracking is up to 24% reduced compared to benchmark methods. Moreover, the estimated strain can be insightful to improve 3D imaging protocols, and the computer code of LWM could also be useful for geo-spatial and manufacturing image analysis researchers.",,pdf:https://www.nature.com/articles/s41598-019-48927-2.pdf; doi:https://doi.org/10.1038/s41598-019-48927-2; html:https://europepmc.org/articles/PMC6713749; pdf:https://europepmc.org/articles/PMC6713749?pdf=render 32613083,https://doi.org/10.12688/wellcomeopenres.15922.2,"Black, Asian and Minority Ethnic groups in England are at increased risk of death from COVID-19: indirect standardisation of NHS mortality data.","Aldridge RW, Lewer D, Katikireddi SV, Mathur R, Pathak N, Burns R, Fragaszy EB, Johnson AM, Devakumar D, Abubakar I, Hayward A.",,Wellcome open research,2020,2020-06-24,Y,Mortality; Minority Ethnic Groups; Covid-19; Sars-cov-2,,,"Background: International and UK data suggest that Black, Asian and Minority Ethnic (BAME) groups are at increased risk of infection and death from COVID-19. We aimed to explore the risk of death in minority ethnic groups in England using data reported by NHS England. Methods: We used NHS data on patients with a positive COVID-19 test who died in hospitals in England published on 28th April, with deaths by ethnicity available from 1st March 2020 up to 5pm on 21 April 2020. We undertook indirect standardisation of these data (using the whole population of England as the reference) to produce ethnic specific standardised mortality ratios (SMRs) adjusted for age and geographical region. Results: The largest total number of deaths in minority ethnic groups were Indian (492 deaths) and Black Caribbean (460 deaths) groups. Adjusting for region we found a lower risk of death for White Irish (SMR 0.52; 95%CIs 0.45-0.60) and White British ethnic groups (0.88; 95%CIs 0.86-0.0.89), but increased risk of death for Black African (3.24; 95%CIs 2.90-3.62), Black Caribbean (2.21; 95%CIs 2.02-2.41), Pakistani (3.29; 95%CIs 2.96-3.64), Bangladeshi (2.41; 95%CIs 1.98-2.91) and Indian (1.70; 95%CIs 1.56-1.85) minority ethnic groups. Conclusion: Our analysis adds to the evidence that BAME people are at increased risk of death from COVID-19 even after adjusting for geographical region, but was limited by the lack of data on deaths outside of NHS settings and ethnicity denominator data being based on the 2011 census. Despite these limitations, we believe there is an urgent need to take action to reduce the risk of death for BAME groups and better understand why some ethnic groups experience greater risk. Actions that are likely to reduce these inequities include ensuring adequate income protection, reducing occupational risks, reducing barriers in accessing healthcare and providing culturally and linguistically appropriate public health communications.",,doi:https://doi.org/10.12688/wellcomeopenres.15922.2; html:https://europepmc.org/articles/PMC7317462; pdf:https://europepmc.org/articles/PMC7317462?pdf=render 36794597,https://doi.org/10.1111/trf.17277,Impact of a post-donation hemoglobin testing strategy on efficiency and safety of whole blood donation in England: A modeling study.,"Kim LG, Bolton T, Sweeting MJ, Bell S, Fahle S, McMahon A, Walker M, Ferguson E, Miflin G, Roberts DJ, Di Angelantonio E, Wood AM.",,Transfusion,2023,2023-02-16,Y,Blood Donation; Simulation Modeling; Post-donation Testing; Low Hemoglobin Deferral,,,"

Background

Deferrals due to low hemoglobin are time-consuming and costly for blood donors and donation services. Furthermore, accepting donations from those with low hemoglobin could represent a significant safety issue. One approach to reduce them is to use hemoglobin concentration alongside donor characteristics to inform personalized inter-donation intervals.

Study design and methods

We used data from 17,308 donors to inform a discrete event simulation model comparing personalized inter-donation intervals using ""post-donation"" testing (i.e., estimating current hemoglobin from that measured by a hematology analyzer at last donation) versus the current approach in England (i.e., pre-donation testing with fixed intervals of 12-weeks for men and 16-weeks for women). We reported the impact on total donations, low hemoglobin deferrals, inappropriate bleeds, and blood service costs. Personalized inter-donation intervals were defined using mixed-effects modeling to estimate hemoglobin trajectories and probability of crossing hemoglobin donation thresholds.

Results

The model had generally good internal validation, with predicted events similar to those observed. Over 1 year, a personalized strategy requiring ≥90% probability of being over the hemoglobin threshold, minimized adverse events (low hemoglobin deferrals and inappropriate bleeds) in both sexes and costs in women. Donations per adverse event improved from 3.4 (95% uncertainty interval 2.8, 3.7) under the current strategy to 14.8 (11.6, 19.2) in women, and from 7.1 (6.1, 8.5) to 26.9 (20.8, 42.6) in men. In comparison, a strategy incorporating early returns for those with high certainty of being over the threshold maximized total donations in both men and women, but was less favorable in terms of adverse events, with 8.4 donations per adverse event in women (7.0, 10,1) and 14.8 (12.1, 21.0) in men.

Discussion

Personalized inter-donation intervals using post-donation testing combined with modeling of hemoglobin trajectories can help reduce deferrals, inappropriate bleeds, and costs.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/trf.17277; doi:https://doi.org/10.1111/trf.17277; html:https://europepmc.org/articles/PMC10952564; pdf:https://europepmc.org/articles/PMC10952564?pdf=render @@ -595,8 +595,8 @@ PMC10910267,https://doi.org/,Development and evaluation of a tool to optimise in 34489241,https://doi.org/10.1136/bjsports-2021-104050,Reallocation of time between device-measured movement behaviours and risk of incident cardiovascular disease.,"Walmsley R, Chan S, Smith-Byrne K, Ramakrishnan R, Woodward M, Rahimi K, Dwyer T, Bennett D, Doherty A.",,British journal of sports medicine,2021,2021-09-06,Y,Cardiovascular diseases; Sleep; Methods; Physical Activity; Sedentary Behavior,,,"

Objective

To improve classification of movement behaviours in free-living accelerometer data using machine-learning methods, and to investigate the association between machine-learned movement behaviours and risk of incident cardiovascular disease (CVD) in adults.

Methods

Using free-living data from 152 participants, we developed a machine-learning model to classify movement behaviours (moderate-to-vigorous physical activity behaviours (MVPA), light physical activity behaviours, sedentary behaviour, sleep) in wrist-worn accelerometer data. Participants in UK Biobank, a prospective cohort, were asked to wear an accelerometer for 7 days, and we applied our machine-learning model to classify their movement behaviours. Using compositional data analysis Cox regression, we investigated how reallocating time between movement behaviours was associated with CVD incidence.

Results

In leave-one-participant-out analysis, our machine-learning method classified free-living movement behaviours with mean accuracy 88% (95% CI 87% to 89%) and Cohen's kappa 0.80 (95% CI 0.79 to 0.82). Among 87 498 UK Biobank participants, there were 4105 incident CVD events. Reallocating time from any behaviour to MVPA, or reallocating time from sedentary behaviour to any behaviour, was associated with lower CVD risk. For an average individual, reallocating 20 min/day to MVPA from all other behaviours proportionally was associated with 9% (95% CI 7% to 10%) lower risk, while reallocating 1 hour/day to sedentary behaviour from all other behaviours proportionally was associated with 5% (95% CI 3% to 7%) higher risk.

Conclusion

Machine-learning methods classified movement behaviours accurately in free-living accelerometer data. Reallocating time from other behaviours to MVPA, and from sedentary behaviour to other behaviours, was associated with lower risk of incident CVD, and should be promoted by interventions and guidelines.",,pdf:https://bjsm.bmj.com/content/bjsports/early/2022/02/15/bjsports-2021-104050.full.pdf; doi:https://doi.org/10.1136/bjsports-2021-104050; html:https://europepmc.org/articles/PMC9484395; pdf:https://europepmc.org/articles/PMC9484395?pdf=render 29992526,https://doi.org/10.1007/s11906-018-0877-8,An Overview of Metabolic Phenotyping in Blood Pressure Research.,"Tzoulaki I, Iliou A, Mikros E, Elliott P.",,Current hypertension reports,2018,2018-07-10,Y,Hypertension; Blood pressure; Metabolomics; Microbiome; Epidemiological Studies; Metabolic Phenotyping,,,"

Purpose of the review

This review presents the analytical techniques, processing and analytical steps used in metabolomics phenotyping studies, as well as the main results from epidemiological studies on the associations between metabolites and high blood pressure.

Recent findings

A variety of metabolomic approaches have been applied to a range of epidemiological studies to uncover the pathophysiology of high blood pressure. Several pathways have been suggested in relation to blood pressure including the possible role of the gut microflora, inflammatory, oxidative stress, and lipid pathways. Metabolic changes have also been identified associated with blood pressure lowering effects of diets high in fruits and vegetables and low in meat intake. However, the current body of literature on metabolic profiling and blood pressure is still in its infancy, not fully consistent and requires careful interpretation. Metabolic phenotyping is a promising approach to uncover metabolic pathways associated with high blood pressure and throw light into the complex pathophysiology of hypertension.",,pdf:https://link.springer.com/content/pdf/10.1007%2Fs11906-018-0877-8.pdf; doi:https://doi.org/10.1007/s11906-018-0877-8; html:https://europepmc.org/articles/PMC6061189; pdf:https://europepmc.org/articles/PMC6061189?pdf=render 33801002,https://doi.org/10.3390/s21062190,A Novel Coupled Reaction-Diffusion System for Explainable Gene Expression Profiling.,"Farouq MW, Boulila W, Hussain Z, Rashid A, Shah M, Hussain S, Ng N, Ng D, Hanif H, Shaikh MG, Sheikh A, Hussain A.",,"Sensors (Basel, Switzerland)",2021,2021-03-21,Y,Non-small cell lung cancer; Gene Expression; Diffusion Equation; Explainable Machine Learning; Coupled Reaction Pde,,,"Machine learning (ML)-based algorithms are playing an important role in cancer diagnosis and are increasingly being used to aid clinical decision-making. However, these commonly operate as 'black boxes' and it is unclear how decisions are derived. Recently, techniques have been applied to help us understand how specific ML models work and explain the rational for outputs. This study aims to determine why a given type of cancer has a certain phenotypic characteristic. Cancer results in cellular dysregulation and a thorough consideration of cancer regulators is required. This would increase our understanding of the nature of the disease and help discover more effective diagnostic, prognostic, and treatment methods for a variety of cancer types and stages. Our study proposes a novel explainable analysis of potential biomarkers denoting tumorigenesis in non-small cell lung cancer. A number of these biomarkers are known to appear following various treatment pathways. An enhanced analysis is enabled through a novel mathematical formulation for the regulators of mRNA, the regulators of ncRNA, and the coupled mRNA-ncRNA regulators. Temporal gene expression profiles are approximated in a two-dimensional spatial domain for the transition states before converging to the stationary state, using a system comprised of coupled-reaction partial differential equations. Simulation experiments demonstrate that the proposed mathematical gene-expression profile represents a best fit for the population abundance of these oncogenes. In future, our proposed solution can lead to the development of alternative interpretable approaches, through the application of ML models to discover unknown dynamics in gene regulatory systems.",,pdf:https://www.mdpi.com/1424-8220/21/6/2190/pdf?version=1616388230; doi:https://doi.org/10.3390/s21062190; html:https://europepmc.org/articles/PMC8003942; pdf:https://europepmc.org/articles/PMC8003942?pdf=render -37935836,https://doi.org/10.1093/eurheartj/ehad736,Mendelian randomization for cardiovascular diseases: principles and applications.,"Larsson SC, Butterworth AS, Burgess S.",,European heart journal,2023,2023-12-01,Y,Genetics; Cardiovascular disease; Single Nucleotide Polymorphisms; Mendelian Randomization,,,"Large-scale genome-wide association studies conducted over the last decade have uncovered numerous genetic variants associated with cardiometabolic traits and risk factors. These discoveries have enabled the Mendelian randomization (MR) design, which uses genetic variation as a natural experiment to improve causal inferences from observational data. By analogy with the random assignment of treatment in randomized controlled trials, the random segregation of genetic alleles when DNA is transmitted from parents to offspring at gamete formation is expected to reduce confounding in genetic associations. Mendelian randomization analyses make a set of assumptions that must hold for valid results. Provided that the assumptions are well justified for the genetic variants that are employed as instrumental variables, MR studies can inform on whether a putative risk factor likely has a causal effect on the disease or not. Mendelian randomization has been increasingly applied over recent years to predict the efficacy and safety of existing and novel drugs targeting cardiovascular risk factors and to explore the repurposing potential of available drugs. This review article describes the principles of the MR design and some applications in cardiovascular epidemiology.",,pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad736/52829421/ehad736.pdf; doi:https://doi.org/10.1093/eurheartj/ehad736; html:https://europepmc.org/articles/PMC10719501; pdf:https://europepmc.org/articles/PMC10719501?pdf=render 35997000,https://doi.org/10.1111/ene.15530,Longitudinal analysis of the relationship between motor and psychiatric symptoms in idiopathic dystonia.,"Bailey GA, Rawlings A, Torabi F, Pickrell WO, Peall KJ.",,European journal of neurology,2022,2022-09-11,Y,Psychiatric disorders; Movement Disorders; Dystonia; Neurological Disorders,,,"

Background and purpose

Although psychiatric diagnoses are recognized in idiopathic dystonia, no previous studies have examined the temporal relationship between idiopathic dystonia and psychiatric diagnoses at scale. Here, we determine rates of psychiatric diagnoses and psychiatric medication prescription in those diagnosed with idiopathic dystsuponia compared to matched controls.

Methods

A longitudinal population-based cohort study using anonymized electronic health care data in Wales (UK) was conducted to identify individuals with idiopathic dystonia and comorbid psychiatric diagnoses/prescriptions between 1 January 1994 and 31 December 2017. Psychiatric diagnoses/prescriptions were identified from primary and secondary health care records.

Results

Individuals with idiopathic dystonia (n = 52,589) had higher rates of psychiatric diagnosis and psychiatric medication prescription when compared to controls (n = 216,754, 43% vs. 31%, p < 0.001; 45% vs. 37.9%, p < 0.001, respectively), with depression and anxiety being most common (cases: 31% and 28%). Psychiatric diagnoses predominantly predated dystonia diagnosis, particularly in the 12 months prior to diagnosis (incidence rate ratio [IRR] = 1.98, 95% confidence interval [CI] = 1.9-2.1), with an IRR of 12.4 (95% CI = 11.8-13.1) for anxiety disorders. There was, however, an elevated rate of most psychiatric diagnoses throughout the study period, including the 12 months after dystonia diagnosis (IRR = 1.96, 95% CI = 1.85-2.07).

Conclusions

This study suggests a bidirectional relationship between psychiatric disorders and dystonia, particularly with mood disorders. Psychiatric and motor symptoms in dystonia may have common aetiological mechanisms, with psychiatric disorders potentially forming prodromal symptoms of idiopathic dystonia.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa62203/Download/62203__26254__0c88bfc9ff7e4fe2acaea5e2a2d74058.pdf; doi:https://doi.org/10.1111/ene.15530; html:https://europepmc.org/articles/PMC9826317; pdf:https://europepmc.org/articles/PMC9826317?pdf=render +37935836,https://doi.org/10.1093/eurheartj/ehad736,Mendelian randomization for cardiovascular diseases: principles and applications.,"Larsson SC, Butterworth AS, Burgess S.",,European heart journal,2023,2023-12-01,Y,Genetics; Cardiovascular disease; Single Nucleotide Polymorphisms; Mendelian Randomization,,,"Large-scale genome-wide association studies conducted over the last decade have uncovered numerous genetic variants associated with cardiometabolic traits and risk factors. These discoveries have enabled the Mendelian randomization (MR) design, which uses genetic variation as a natural experiment to improve causal inferences from observational data. By analogy with the random assignment of treatment in randomized controlled trials, the random segregation of genetic alleles when DNA is transmitted from parents to offspring at gamete formation is expected to reduce confounding in genetic associations. Mendelian randomization analyses make a set of assumptions that must hold for valid results. Provided that the assumptions are well justified for the genetic variants that are employed as instrumental variables, MR studies can inform on whether a putative risk factor likely has a causal effect on the disease or not. Mendelian randomization has been increasingly applied over recent years to predict the efficacy and safety of existing and novel drugs targeting cardiovascular risk factors and to explore the repurposing potential of available drugs. This review article describes the principles of the MR design and some applications in cardiovascular epidemiology.",,pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad736/52829421/ehad736.pdf; doi:https://doi.org/10.1093/eurheartj/ehad736; html:https://europepmc.org/articles/PMC10719501; pdf:https://europepmc.org/articles/PMC10719501?pdf=render 33495722,https://doi.org/10.1109/access.2021.3050524,Remote Assessment of Parkinson's Disease Symptom Severity Using the Simulated Cellular Mobile Telephone Network.,"Tsanas A, Little MA, Ramig LO.",,"IEEE access : practical innovations, open solutions",2021,2021-01-11,Y,Telemedicine; Parkinson’s Disease; Decision Support Tool; Nonlinear Speech Signal Processing,,,"Telemonitoring of Parkinson's Disease (PD) has attracted considerable research interest because of its potential to make a lasting, positive impact on the life of patients and their carers. Purpose-built devices have been developed that record various signals which can be associated with average PD symptom severity, as quantified on standard clinical metrics such as the Unified Parkinson's Disease Rating Scale (UPDRS). Speech signals are particularly promising in this regard, because they can be easily recorded without the use of expensive, dedicated hardware. Previous studies have demonstrated replication of UPDRS to within less than 2 points of a clinical raters' assessment of symptom severity, using high-quality speech signals collected using dedicated telemonitoring hardware. Here, we investigate the potential of using the standard voice-over-GSM (2G) or UMTS (3G) cellular mobile telephone networks for PD telemonitoring, networks that, together, have greater than 5 billion subscribers worldwide. We test the robustness of this approach using a simulated noisy mobile communication network over which speech signals are transmitted, and approximately 6000 recordings from 42 PD subjects. We show that UPDRS can be estimated to within less than 3.5 points difference from the clinical raters' assessment, which is clinically useful given that the inter-rater variability for UPDRS can be as high as 4-5 UPDRS points. This provides compelling evidence that the existing voice telephone network has potential towards facilitating inexpensive, mass-scale PD symptom telemonitoring applications.",,pdf:https://ieeexplore.ieee.org/ielx7/6287639/9312710/09319241.pdf; doi:https://doi.org/10.1109/ACCESS.2021.3050524; html:https://europepmc.org/articles/PMC7821632; pdf:https://europepmc.org/articles/PMC7821632?pdf=render 34389694,https://doi.org/10.1158/1535-7163.mct-20-1050,Clinical Positioning of the IAP Antagonist Tolinapant (ASTX660) in Colorectal Cancer.,"Crawford N, Stott KJ, Sessler T, McCann C, McDaid W, Lees A, Latimer C, Fox JP, Munck JM, Smyth T, Shah A, Martins V, Lawler M, Dunne PD, Kerr EM, McDade SS, Coyle VM, Longley DB.",,Molecular cancer therapeutics,2021,2021-08-13,Y,,,,"Inhibitors of apoptosis proteins (IAPs) are intracellular proteins, with important roles in regulating cell death, inflammation, and immunity. Here, we examined the clinical and therapeutic relevance of IAPs in colorectal cancer. We found that elevated expression of cIAP1 and cIAP2 (but not XIAP) significantly correlated with poor prognosis in patients with microsatellite stable (MSS) stage III colorectal cancer treated with 5-fluorouracil (5FU)-based adjuvant chemotherapy, suggesting their involvement in promoting chemoresistance. A novel IAP antagonist tolinapant (ASTX660) potently and rapidly downregulated cIAP1 in colorectal cancer models, demonstrating its robust on-target efficacy. In cells co-cultured with TNFα to mimic an inflammatory tumor microenvironment, tolinapant induced caspase-8-dependent apoptosis in colorectal cancer cell line models; however, the extent of apoptosis was limited because of inhibition by the caspase-8 paralogs FLIP and, unexpectedly, caspase-10. Importantly, tolinapant-induced apoptosis was augmented by FOLFOX in human colorectal cancer and murine organoid models in vitro and in vivo, due (at least in part) to FOLFOX-induced downregulation of class I histone deacetylases (HDAC), leading to acetylation of the FLIP-binding partner Ku70 and downregulation of FLIP. Moreover, the effects of FOLFOX could be phenocopied using the clinically relevant class I HDAC inhibitor, entinostat, which also induced acetylation of Ku70 and FLIP downregulation. Further analyses revealed that caspase-8 knockout RIPK3-positive colorectal cancer models were sensitive to tolinapant-induced necroptosis, an effect that could be exploited in caspase-8-proficient models using the clinically relevant caspase inhibitor emricasan. Our study provides evidence for immediate clinical exploration of tolinapant in combination with FOLFOX in poor prognosis MSS colorectal cancer with elevated cIAP1/2 expression.",,pdf:https://aacrjournals.org/mct/article-pdf/20/9/1627/3076208/1627.pdf; doi:https://doi.org/10.1158/1535-7163.MCT-20-1050; html:https://europepmc.org/articles/PMC7611622; pdf:https://europepmc.org/articles/PMC7611622?pdf=render 34164795,https://doi.org/10.1007/s40801-021-00256-5,Associations Between Anticholinergic Medication Exposure and Adverse Health Outcomes in Older People with Frailty: A Systematic Review and Meta-analysis.,"Mehdizadeh D, Hale M, Todd O, Zaman H, Marques I, Petty D, Alldred DP, Johnson O, Faisal M, Gardner P, Clegg A.",,Drugs - real world outcomes,2021,2021-06-23,Y,,,,"

Introduction

There are robust associations between use of anticholinergic medicines and adverse effects in older people. However, the nature of these associations for older people living with frailty is yet to be established.

Objectives

The aims were to identify and investigate associations between anticholinergics and adverse outcomes in older people living with frailty and to investigate whether exposure is associated with greater risks according to frailty status.

Methods

MEDLINE, CINAHL, EMBASE, Cochrane Database of Systematic Reviews, Web of Science and PsycINFO were searched to 1 August 2019. Observational studies reporting associations between anticholinergics and outcomes in older adults (average age ≥ 65 years) that reported frailty using validated measures were included. Primary outcomes were physical impairment, cognitive dysfunction, and change in frailty status. Risk of bias was evaluated using the Cochrane Risk of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. Meta-analysis was undertaken where appropriate.

Results

Thirteen studies (21,516 participants) were included (ten community, one residential aged-care facility and two hospital studies). Observed associations included reduced ability for chair standing, slower gait speeds, poorer physical performance, increased risk of falls and mortality. Conflicting results were reported for grip strength, timed up and go test, cognition and activities of daily living. No associations were observed for transitions between frailty states, psychological wellbeing or benzodiazepine-related adverse reactions. There was no clear evidence of differences in risks according to frailty status.

Conclusions

Anticholinergics are associated with adverse outcomes in older people living with frailty; however, the literature has significant methodological limitations. There is insufficient evidence to suggest greater risks based on frailty, and there is an urgent need to evaluate this further in well-designed studies stratifying by frailty.",,pdf:https://link.springer.com/content/pdf/10.1007/s40801-021-00256-5.pdf; doi:https://doi.org/10.1007/s40801-021-00256-5; html:https://europepmc.org/articles/PMC8605959; pdf:https://europepmc.org/articles/PMC8605959?pdf=render @@ -604,14 +604,14 @@ PMC10910267,https://doi.org/,Development and evaluation of a tool to optimise in PMC9644982,https://doi.org/,Assessing the impacts of COVID-19 on Care Homes in Wales.,"Fry R, Hollinghurst J, North L, Emmerson C, Long S, Akbari A, Gravenor M, Lyons R.",,International journal of population data science,,2022-11-21,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644982/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644982/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9644982; pdf:https://europepmc.org/articles/PMC9644982?pdf=render 36545688,https://doi.org/10.1192/bjb.2022.83,EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People): project outline.,"Hemmings A, Sharpe H, Allen K, Bartel H, Campbell IC, Desrivières S, Dobson RJB, Folarin AA, French T, Kelly J, Micali N, Raman S, Treasure J, Abbas R, Heslop B, Street T, Schmidt U.",,BJPsych bulletin,2023,2023-12-01,Y,Eating Disorders; Risk And Resilience; Prevention And Early Intervention; Youth Engagement; Interdisciplinary Working,,,"EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People) is an ambitious research project aiming to revolutionise how eating disorders are perceived, prevented and treated. Six integrated workstreams will address key questions, including: What are young people's experiences of eating disorders and recovery? What are the unique and shared risk factors in different groups? What helps or hinders recovery? How do the brain and behaviour change from early- to later-stage illness? How can we intervene earlier, quicker and in a more personalised way? This 4-year project, involving over 1000 participants, integrates arts, design and humanities with advanced neurobiological, psychosocial and bioinformatics approaches. Young people with lived experience of eating disorders are at the heart of EDIFY, serving as advisors and co-producers throughout. Ultimately, this work will expand public and professional perceptions of eating disorders, uplift under-represented voices and stimulate much-needed advances in policy and practice.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/C1E5FCC67F1D627908A5495EED02577B/S2056469422000833a.pdf/div-class-title-edify-eating-disorders-delineating-illness-and-recovery-trajectories-to-inform-personalised-prevention-and-early-intervention-in-young-people-project-outline-div.pdf; doi:https://doi.org/10.1192/bjb.2022.83; html:https://europepmc.org/articles/PMC10694679; pdf:https://europepmc.org/articles/PMC10694679?pdf=render 33939953,https://doi.org/10.1016/s0140-6736(21)00634-6,"Ethnic differences in SARS-CoV-2 infection and COVID-19-related hospitalisation, intensive care unit admission, and death in 17 million adults in England: an observational cohort study using the OpenSAFELY platform.","Mathur R, Rentsch CT, Morton CE, Hulme WJ, Schultze A, MacKenna B, Eggo RM, Bhaskaran K, Wong AYS, Williamson EJ, Forbes H, Wing K, McDonald HI, Bates C, Bacon S, Walker AJ, Evans D, Inglesby P, Mehrkar A, Curtis HJ, DeVito NJ, Croker R, Drysdale H, Cockburn J, Parry J, Hester F, Harper S, Douglas IJ, Tomlinson L, Evans SJW, Grieve R, Harrison D, Rowan K, Khunti K, Chaturvedi N, Smeeth L, Goldacre B, OpenSAFELY Collaborative.",,"Lancet (London, England)",2021,2021-04-30,Y,,,,"

Background

COVID-19 has disproportionately affected minority ethnic populations in the UK. Our aim was to quantify ethnic differences in SARS-CoV-2 infection and COVID-19 outcomes during the first and second waves of the COVID-19 pandemic in England.

Methods

We conducted an observational cohort study of adults (aged ≥18 years) registered with primary care practices in England for whom electronic health records were available through the OpenSAFELY platform, and who had at least 1 year of continuous registration at the start of each study period (Feb 1 to Aug 3, 2020 [wave 1], and Sept 1 to Dec 31, 2020 [wave 2]). Individual-level primary care data were linked to data from other sources on the outcomes of interest: SARS-CoV-2 testing and positive test results and COVID-19-related hospital admissions, intensive care unit (ICU) admissions, and death. The exposure was self-reported ethnicity as captured on the primary care record, grouped into five high-level census categories (White, South Asian, Black, other, and mixed) and 16 subcategories across these five categories, as well as an unknown ethnicity category. We used multivariable Cox regression to examine ethnic differences in the outcomes of interest. Models were adjusted for age, sex, deprivation, clinical factors and comorbidities, and household size, with stratification by geographical region.

Findings

Of 17 288 532 adults included in the study (excluding care home residents), 10 877 978 (62·9%) were White, 1 025 319 (5·9%) were South Asian, 340 912 (2·0%) were Black, 170 484 (1·0%) were of mixed ethnicity, 320 788 (1·9%) were of other ethnicity, and 4 553 051 (26·3%) were of unknown ethnicity. In wave 1, the likelihood of being tested for SARS-CoV-2 infection was slightly higher in the South Asian group (adjusted hazard ratio 1·08 [95% CI 1·07-1·09]), Black group (1·08 [1·06-1·09]), and mixed ethnicity group (1·04 [1·02-1·05]) and was decreased in the other ethnicity group (0·77 [0·76-0·78]) relative to the White group. The risk of testing positive for SARS-CoV-2 infection was higher in the South Asian group (1·99 [1·94-2·04]), Black group (1·69 [1·62-1·77]), mixed ethnicity group (1·49 [1·39-1·59]), and other ethnicity group (1·20 [1·14-1·28]). Compared with the White group, the four remaining high-level ethnic groups had an increased risk of COVID-19-related hospitalisation (South Asian group 1·48 [1·41-1·55], Black group 1·78 [1·67-1·90], mixed ethnicity group 1·63 [1·45-1·83], other ethnicity group 1·54 [1·41-1·69]), COVID-19-related ICU admission (2·18 [1·92-2·48], 3·12 [2·65-3·67], 2·96 [2·26-3·87], 3·18 [2·58-3·93]), and death (1·26 [1·15-1·37], 1·51 [1·31-1·71], 1·41 [1·11-1·81], 1·22 [1·00-1·48]). In wave 2, the risks of hospitalisation, ICU admission, and death relative to the White group were increased in the South Asian group but attenuated for the Black group compared with these risks in wave 1. Disaggregation into 16 ethnicity groups showed important heterogeneity within the five broader categories.

Interpretation

Some minority ethnic populations in England have excess risks of testing positive for SARS-CoV-2 and of adverse COVID-19 outcomes compared with the White population, even after accounting for differences in sociodemographic, clinical, and household characteristics. Causes are likely to be multifactorial, and delineating the exact mechanisms is crucial. Tackling ethnic inequalities will require action across many fronts, including reducing structural inequalities, addressing barriers to equitable care, and improving uptake of testing and vaccination.

Funding

Medical Research Council.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4659476/13/PIIS0140673621006346.pdf; doi:https://doi.org/10.1016/S0140-6736(21)00634-6; html:https://europepmc.org/articles/PMC8087292; pdf:https://europepmc.org/articles/PMC8087292?pdf=render -38662697,https://doi.org/10.1093/cid/ciae108,"Reducing the Antigen Prevalence Target Threshold for Stopping and Restarting Mass Drug Administration for Lymphatic Filariasis Elimination: A Model-Based Cost-effectiveness Simulation in Tanzania, India and Haiti.","Antony Oliver MC, Graham M, Gass KM, Medley GF, Clark J, Davis EL, Reimer LJ, King JD, Pouwels KB, Hollingsworth TD.",,Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,2024,2024-04-01,Y,Threshold; Modeling; Elimination; Health Economics; Lymphatic Filariasis,,,"

Background

The Global Programme to Eliminate Lymphatic Filariasis (GPELF) aims to reduce and maintain infection levels through mass drug administration (MDA), but there is evidence of ongoing transmission after MDA in areas where Culex mosquitoes are the main transmission vector, suggesting that a more stringent criterion is required for MDA decision making in these settings.

Methods

We use a transmission model to investigate how a lower prevalence threshold (<1% antigenemia [Ag] prevalence compared with <2% Ag prevalence) for MDA decision making would affect the probability of local elimination, health outcomes, the number of MDA rounds, including restarts, and program costs associated with MDA and surveys across different scenarios. To determine the cost-effectiveness of switching to a lower threshold, we simulated 65% and 80% MDA coverage of the total population for different willingness to pay per disability-adjusted life-year averted for India ($446.07), Tanzania ($389.83), and Haiti ($219.84).

Results

Our results suggest that with a lower Ag threshold, there is a small proportion of simulations where extra rounds are required to reach the target, but this also reduces the need to restart MDA later in the program. For 80% coverage, the lower threshold is cost-effective across all baseline prevalences for India, Tanzania, and Haiti. For 65% MDA coverage, the lower threshold is not cost-effective due to additional MDA rounds, although it increases the probability of local elimination. Valuing the benefits of elimination to align with the GPELF goals, we find that a willingness to pay per capita government expenditure of approximately $1000-$4000 for 1% increase in the probability of local elimination would be required to make a lower threshold cost-effective.

Conclusions

Lower Ag thresholds for stopping MDAs generally mean a higher probability of local elimination, reducing long-term costs and health impacts. However, they may also lead to an increased number of MDA rounds required to reach the lower threshold and, therefore, increased short-term costs. Collectively, our analyses highlight that lower target Ag thresholds have the potential to assist programs in achieving lymphatic filariasis goals.",,doi:https://doi.org/10.1093/cid/ciae108; html:https://europepmc.org/articles/PMC11045020; pdf:https://europepmc.org/articles/PMC11045020?pdf=render 37158960,https://doi.org/10.1186/s40168-023-01518-w,Pathobionts in the tumour microbiota predict survival following resection for colorectal cancer.,"Alexander JL, Posma JM, Scott A, Poynter L, Mason SE, Doria ML, Herendi L, Roberts L, McDonald JAK, Cameron S, Hughes DJ, Liska V, Susova S, Soucek P, der Sluis VH, Gomez-Romero M, Lewis MR, Hoyles L, Woolston A, Cunningham D, Darzi A, Gerlinger M, Goldin R, Takats Z, Marchesi JR, Teare J, Kinross J.",,Microbiome,2023,2023-05-08,Y,metabolome; Colorectal Cancer; Gut Microbiota; Metataxonomics,,,"

Background and aims

The gut microbiota is implicated in the pathogenesis of colorectal cancer (CRC). We aimed to map the CRC mucosal microbiota and metabolome and define the influence of the tumoral microbiota on oncological outcomes.

Methods

A multicentre, prospective observational study was conducted of CRC patients undergoing primary surgical resection in the UK (n = 74) and Czech Republic (n = 61). Analysis was performed using metataxonomics, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS), targeted bacterial qPCR and tumour exome sequencing. Hierarchical clustering accounting for clinical and oncological covariates was performed to identify clusters of bacteria and metabolites linked to CRC. Cox proportional hazards regression was used to ascertain clusters associated with disease-free survival over median follow-up of 50 months.

Results

Thirteen mucosal microbiota clusters were identified, of which five were significantly different between tumour and paired normal mucosa. Cluster 7, containing the pathobionts Fusobacterium nucleatum and Granulicatella adiacens, was strongly associated with CRC (PFDR = 0.0002). Additionally, tumoral dominance of cluster 7 independently predicted favourable disease-free survival (adjusted p = 0.031). Cluster 1, containing Faecalibacterium prausnitzii and Ruminococcus gnavus, was negatively associated with cancer (PFDR = 0.0009), and abundance was independently predictive of worse disease-free survival (adjusted p = 0.0009). UPLC-MS analysis revealed two major metabolic (Met) clusters. Met 1, composed of medium chain (MCFA), long-chain (LCFA) and very long-chain (VLCFA) fatty acid species, ceramides and lysophospholipids, was negatively associated with CRC (PFDR = 2.61 × 10-11); Met 2, composed of phosphatidylcholine species, nucleosides and amino acids, was strongly associated with CRC (PFDR = 1.30 × 10-12), but metabolite clusters were not associated with disease-free survival (p = 0.358). An association was identified between Met 1 and DNA mismatch-repair deficiency (p = 0.005). FBXW7 mutations were only found in cancers predominant in microbiota cluster 7.

Conclusions

Networks of pathobionts in the tumour mucosal niche are associated with tumour mutation and metabolic subtypes and predict favourable outcome following CRC resection. Video Abstract.",,pdf:https://microbiomejournal.biomedcentral.com/counter/pdf/10.1186/s40168-023-01518-w; doi:https://doi.org/10.1186/s40168-023-01518-w; html:https://europepmc.org/articles/PMC10165813; pdf:https://europepmc.org/articles/PMC10165813?pdf=render +38662697,https://doi.org/10.1093/cid/ciae108,"Reducing the Antigen Prevalence Target Threshold for Stopping and Restarting Mass Drug Administration for Lymphatic Filariasis Elimination: A Model-Based Cost-effectiveness Simulation in Tanzania, India and Haiti.","Antony Oliver MC, Graham M, Gass KM, Medley GF, Clark J, Davis EL, Reimer LJ, King JD, Pouwels KB, Hollingsworth TD.",,Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,2024,2024-04-01,Y,Threshold; Modeling; Elimination; Health Economics; Lymphatic Filariasis,,,"

Background

The Global Programme to Eliminate Lymphatic Filariasis (GPELF) aims to reduce and maintain infection levels through mass drug administration (MDA), but there is evidence of ongoing transmission after MDA in areas where Culex mosquitoes are the main transmission vector, suggesting that a more stringent criterion is required for MDA decision making in these settings.

Methods

We use a transmission model to investigate how a lower prevalence threshold (<1% antigenemia [Ag] prevalence compared with <2% Ag prevalence) for MDA decision making would affect the probability of local elimination, health outcomes, the number of MDA rounds, including restarts, and program costs associated with MDA and surveys across different scenarios. To determine the cost-effectiveness of switching to a lower threshold, we simulated 65% and 80% MDA coverage of the total population for different willingness to pay per disability-adjusted life-year averted for India ($446.07), Tanzania ($389.83), and Haiti ($219.84).

Results

Our results suggest that with a lower Ag threshold, there is a small proportion of simulations where extra rounds are required to reach the target, but this also reduces the need to restart MDA later in the program. For 80% coverage, the lower threshold is cost-effective across all baseline prevalences for India, Tanzania, and Haiti. For 65% MDA coverage, the lower threshold is not cost-effective due to additional MDA rounds, although it increases the probability of local elimination. Valuing the benefits of elimination to align with the GPELF goals, we find that a willingness to pay per capita government expenditure of approximately $1000-$4000 for 1% increase in the probability of local elimination would be required to make a lower threshold cost-effective.

Conclusions

Lower Ag thresholds for stopping MDAs generally mean a higher probability of local elimination, reducing long-term costs and health impacts. However, they may also lead to an increased number of MDA rounds required to reach the lower threshold and, therefore, increased short-term costs. Collectively, our analyses highlight that lower target Ag thresholds have the potential to assist programs in achieving lymphatic filariasis goals.",,doi:https://doi.org/10.1093/cid/ciae108; html:https://europepmc.org/articles/PMC11045020; pdf:https://europepmc.org/articles/PMC11045020?pdf=render 33623985,https://doi.org/10.1093/cid/ciab159,Shorter and Longer Courses of Antibiotics for Common Infections and the Association With Reductions of Infection-Related Complications Including Hospital Admissions.,"Palin V, Welfare W, Ashcroft DM, van Staa TP.",,Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,2021,2021-11-01,Y,Antibiotics; Antimicrobial resistance; Antibiotic Duration; Infection Complication,,,"

Background

Antimicrobial resistance is a serious global health concern that emphasizes completing treatment course. Recently, the effectiveness of short versus longer antibiotic courses has been questioned. This study investigated the duration of prescribed antibiotics, their effectiveness, and associated risk of infection-related complications.

Methods

Clinical Practice Research Datalink identified 4 million acute infection episodes prescribed an antibiotic in primary care between January 2014-June 2014, England. Prescriptions were categorized by duration. Risk of infection-related hospitalizations within 30 days was modelled overall and by infection type. Risk was assessed immediately after or within 30 days follow-up to measure confounders given similar and varying exposure, respectively. An interaction term with follow-up time assessed whether hazard ratios (HRs) remained parallel with different antibiotic durations.

Results

The duration of antibiotic courses increased over the study period (5.2-19.1%); 6-7 days were most common (66.9%). Most infection-related hospitalizations occurred with prescriptions of 8-15 days (0.21%), accompanied by greater risk of infection-related complications compared to patients who received a short prescription (HR: 1.75 [95% CI: 1.54-2.00]). Comparing HRs in the first 5 days versus remaining follow-up showed longer antibiotic courses were no more effective than shorter courses (1.02 [95% CI: 0.90-1.16] and 0.92 [95% CI: 0.75-1.12]). No variation by infection-type was observed.

Conclusions

Equal effectiveness was found between shorter and longer antibiotic courses and the reduction of infection-related hospitalizations. Stewardship programs should recommend shorter courses of antibiotics for acute infections. Further research is required for treating patients with a complex medical history.SummaryPrescribing of longer courses increased over the study period. The majority of hospitalizations occurred for patients receiving longer courses. Risk of developing a complication (immediate vs remaining follow-up) found longer courses were no more effective than shorter courses.",,pdf:https://academic.oup.com/cid/advance-article-pdf/doi/10.1093/cid/ciab159/37414330/ciab159.pdf; doi:https://doi.org/10.1093/cid/ciab159; html:https://europepmc.org/articles/PMC8599204; pdf:https://europepmc.org/articles/PMC8599204?pdf=render 37800588,https://doi.org/10.1097/js9.0000000000000781,Safety outcomes of bariatric surgery in patients with advanced organ disease: the ONWARD study: a prospective cohort study.,"Singhal R, Cardoso VR, Wiggins T, Rajeev Y, Ludwig C, Gkoutos GV, Hanif W, Mahawar K, ONWARD & GENEVA collaborators.",,"International journal of surgery (London, England)",2024,2024-01-01,Y,,,,"

Introduction

Increasing numbers of patients with advanced organ disease are being considered for bariatric and metabolic surgery (BMS). There is no prospective study on the safety of BMS in these patients. This study aimed to capture outcomes for patients with advanced cardiac, renal, or liver disease undergoing BMS.

Materials and methods

This was a multinational, prospective cohort study on the safety of elective BMS in adults (≥18 years) with advanced disease of the heart, liver, or kidney.

Results

Data on 177 patients with advanced diseases of heart, liver, or kidney were submitted by 75 centres in 33 countries. Mean age and BMI was 48.56±11.23 years and 45.55±7.35 kg/m 2 , respectively. Laparoscopic sleeve gastrectomy was performed in 124 patients (70%). The 30-day morbidity and mortality were 15.9% ( n =28) and 1.1% ( n =2), respectively. Thirty-day morbidity was 16.4%, 11.7%, 20.5%, and 50.0% in patients with advanced heart ( n =11/61), liver ( n =8/68), kidney ( n =9/44), and multi-organ disease ( n =2/4), respectively. Cardiac patients with left ventricular ejection fraction less than or equal to 35% and New York Heart Association classification 3 or 4, liver patients with model for end-stage liver disease score greater than or equal to 12, and patients with advanced renal disease not on dialysis were at increased risk of complications. Comparison with a propensity score-matched cohort found advanced disease of the heart, liver, or kidney to be significantly associated with higher 30-day morbidity.

Conclusion

Patients with advanced organ disease are at increased risk of 30-day morbidity following BMS. This prospective study quantifies that risk and identifies patients at the highest risk.",,html:https://journals.lww.com/international-journal-of-surgery/abstract/9900/safety_outcomes_of_bariatric_surgery_in_patients.696.aspx; doi:https://doi.org/10.1097/JS9.0000000000000781; html:https://europepmc.org/articles/PMC10793784; pdf:https://europepmc.org/articles/PMC10793784?pdf=render 36992264,https://doi.org/10.3390/vaccines11030680,"Determinants of Equity in Coverage of Measles-Containing Vaccines in Wales, UK, during the Elimination Era.","Perry M, Cottrell S, Gravenor MB, Griffiths L.",,Vaccines,2023,2023-03-17,Y,"Vaccination; Measles; Socioeconomic Factors; Immunisation; Mmr; Measles, Mumps And Rubella Vaccine",,,"In the context of the WHO's measles and rubella elimination targets and European Immunization Agenda 2030, this large cross-sectional study aimed to identify inequalities in measles vaccination coverage in Wales, UK. The vaccination status of individuals aged 2 to 25 years of age, alive and resident in Wales as of 31 August 2021, was ascertained through linkage of the National Community Child Health Database and primary care data. A series of predictor variables were derived from five national datasets and all analysis was carried out in the Secure Anonymised Information Linkage Databank at Swansea University. In these 648,895 individuals, coverage of the first dose of measles-containing vaccine (due at 12-13 months of age) was 97.1%, and coverage of the second dose (due at 3 years and 4 months) in 4 to 25-year-olds was 93.8%. In multivariable analysis, excluding 0.7% with known refusal, the strongest association with being unvaccinated was birth order (families with six or more children) and being born outside of the UK. Living in a deprived area, being eligible for free school meals, a lower level of maternal education, and having a recorded language other than English or Welsh were also associated with lower coverage. Some of these factors may also be associated with refusal. This knowledge can be used to target future interventions and prioritise areas for catch up in a time of limited resource.",,pdf:https://www.mdpi.com/2076-393X/11/3/680/pdf?version=1679031223; doi:https://doi.org/10.3390/vaccines11030680; html:https://europepmc.org/articles/PMC10057771; pdf:https://europepmc.org/articles/PMC10057771?pdf=render 34847950,https://doi.org/10.1186/s12916-021-02190-3,Models of COVID-19 vaccine prioritisation: a systematic literature search and narrative review.,"Saadi N, Chi YL, Ghosh S, Eggo RM, McCarthy CV, Quaife M, Dawa J, Jit M, Vassall A.",,BMC medicine,2021,2021-12-01,Y,"Covid-19, Vaccination, Mathematical Modelling",,,"

Background

How best to prioritise COVID-19 vaccination within and between countries has been a public health and an ethical challenge for decision-makers globally. We reviewed epidemiological and economic modelling evidence on population priority groups to minimise COVID-19 mortality, transmission, and morbidity outcomes.

Methods

We searched the National Institute of Health iSearch COVID-19 Portfolio (a database of peer-reviewed and pre-print articles), Econlit, the Centre for Economic Policy Research, and the National Bureau of Economic Research for mathematical modelling studies evaluating the impact of prioritising COVID-19 vaccination to population target groups. The first search was conducted on March 3, 2021, and an updated search on the LMIC literature was conducted from March 3, 2021, to September 24, 2021. We narratively synthesised the main study conclusions on prioritisation and the conditions under which the conclusions changed.

Results

The initial search identified 1820 studies and 36 studies met the inclusion criteria. The updated search on LMIC literature identified 7 more studies. 43 studies in total were narratively synthesised. 74% of studies described outcomes in high-income countries (single and multi-country). We found that for countries seeking to minimise deaths, prioritising vaccination of senior adults was the optimal strategy and for countries seeking to minimise cases the young were prioritised. There were several exceptions to the main conclusion, notably that reductions in deaths could be increased if groups at high risk of both transmission and death could be further identified. Findings were also sensitive to the level of vaccine coverage.

Conclusion

The evidence supports WHO SAGE recommendations on COVID-19 vaccine prioritisation. There is, however, an evidence gap on optimal prioritisation for low- and middle-income countries, studies that included an economic evaluation, and studies that explore prioritisation strategies if the aim is to reduce overall health burden including morbidity.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02190-3; doi:https://doi.org/10.1186/s12916-021-02190-3; html:https://europepmc.org/articles/PMC8632563; pdf:https://europepmc.org/articles/PMC8632563?pdf=render -37185641,https://doi.org/10.1136/bmjopen-2022-070022,EXAcerbations of COPD and their OutcomeS on CardioVascular diseases (EXACOS-CV) Programme: protocol of multicountry observational cohort studies.,"Nordon C, Rhodes K, Quint JK, Vogelmeier CF, Simons SO, Hawkins NM, Marshall J, Ouwens M, Garbe E, Müllerová H.",,BMJ open,2023,2023-04-26,Y,epidemiology; Cardiology; Vascular Medicine; Chronic Airways Disease,,,"

Introduction

In patients with chronic obstructive pulmonary disease (COPD), the risk of certain cardiovascular (CV) events is increased by threefold to fivefold in the year following acute exacerbation of COPD (AECOPD), compared with a non-exacerbation period. While the effect of severe AECOPD is well established, the relationship of moderate exacerbation or prior exacerbation to elevated risk of CV events is less clear. We will conduct cohort studies in multiple countries to further characterise the association between AECOPD and CV events.

Methods and analysis

Retrospective longitudinal cohort studies will be conducted within routinely collected electronic healthcare records or claims databases. The study cohorts will include patients meeting inclusion criteria for COPD between 1 January 2014 and 31 December 2018. Moderate exacerbation is defined as an outpatient visit and/or medication dispensation/prescription for exacerbation; severe exacerbation is defined as hospitalisation for COPD. The primary outcomes of interest are the time to (1) first hospitalisation for a CV event (including acute coronary syndrome, heart failure, arrhythmias or cerebral ischaemia) since cohort entry or (2) death. Time-dependent Cox proportional hazards models will compare the hazard of a CV event between exposed periods following exacerbation (split into these periods: 1-7, 8-14, 15-30, 31-180 and 181-365 days) and the unexposed reference time period, adjusted on time-fixed and time-varying confounders.

Ethics and dissemination

Studies have been approved in Canada, Japan, the Netherlands, Spain and the UK, where an institutional review board is mandated. For each study, the results will be published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e070022.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-070022; html:https://europepmc.org/articles/PMC10151875; pdf:https://europepmc.org/articles/PMC10151875?pdf=render 30928998,https://doi.org/10.4193/rhin18.237,Risk of mortality and cardiovascular events following macrolide prescription in chronic rhinosinusitis patients: a cohort study using linked primary care electronic health records.,"Williamson E, Denaxas S, Morris S, Clarke CS, Thomas M, Evans H, Direk K, Gonzalez-Izquierdo A, Little P, Lund V, Blackshaw H, Schilder A, Philpott C, Hopkins C, Carpenter J, Programme Team OBOTM.",,Rhinology,2019,2019-08-01,N,,,,"

Background

Macrolide antibiotics have demonstrated important anti-inflammatory and immunomodulatory properties in chronic rhinosinusitis (CRS) patients. However, reports of increased risks of cardiovascular events have led to safety concerns. We investigated the risk of all-cause and cardiac death, and cardiovascular outcomes, associated with macrolide use.

Methodology

Observational cohort (1997-2016) using linked data from the Clinical Practice Research Datalink, Hospital Episodes Statistics, and the Office for National Statistics. Patients aged 16-80 years with CRS prescribed a macrolide antibiotic or penicillin were included, comparing prescriptions for macrolide antibiotics to penicillin. Outcomes were all-cause mortality, cardiac death, myocardial infarction, stroke, diagnosis of peripheral vascular disease, and cardiac arrhythmia.

Results

Analysis included 320,798 prescriptions received by 66,331 patients. There were 3,251 deaths, 815 due to cardiovascular causes, 925 incident myocardial infarctions, 859 strokes, 637 diagnoses of peripheral vascular disease, and 1,436 cardiac arrhythmias. A non-statistically significant trend towards increased risk of myocardial infarction during the first 30 days following macrolide prescription was observed. No statistically significant short- or long-term risks were observed for macrolide prescription. No significant risks were identified for clarithromycin in particular.

Conclusions

Although not statistically significant, our best estimates suggest an increased short-term risk of myocardial infarction in patients with CRS following macrolide prescription, supporting previous observational evidence. However, confounding by indication remains a possible explanation for this apparent increased risk. We found no evidence of longer term increased risks.",,pdf:https://www.rhinologyjournal.com/download.php?id=1882; doi:https://doi.org/10.4193/Rhin18.237 +37185641,https://doi.org/10.1136/bmjopen-2022-070022,EXAcerbations of COPD and their OutcomeS on CardioVascular diseases (EXACOS-CV) Programme: protocol of multicountry observational cohort studies.,"Nordon C, Rhodes K, Quint JK, Vogelmeier CF, Simons SO, Hawkins NM, Marshall J, Ouwens M, Garbe E, Müllerová H.",,BMJ open,2023,2023-04-26,Y,epidemiology; Cardiology; Vascular Medicine; Chronic Airways Disease,,,"

Introduction

In patients with chronic obstructive pulmonary disease (COPD), the risk of certain cardiovascular (CV) events is increased by threefold to fivefold in the year following acute exacerbation of COPD (AECOPD), compared with a non-exacerbation period. While the effect of severe AECOPD is well established, the relationship of moderate exacerbation or prior exacerbation to elevated risk of CV events is less clear. We will conduct cohort studies in multiple countries to further characterise the association between AECOPD and CV events.

Methods and analysis

Retrospective longitudinal cohort studies will be conducted within routinely collected electronic healthcare records or claims databases. The study cohorts will include patients meeting inclusion criteria for COPD between 1 January 2014 and 31 December 2018. Moderate exacerbation is defined as an outpatient visit and/or medication dispensation/prescription for exacerbation; severe exacerbation is defined as hospitalisation for COPD. The primary outcomes of interest are the time to (1) first hospitalisation for a CV event (including acute coronary syndrome, heart failure, arrhythmias or cerebral ischaemia) since cohort entry or (2) death. Time-dependent Cox proportional hazards models will compare the hazard of a CV event between exposed periods following exacerbation (split into these periods: 1-7, 8-14, 15-30, 31-180 and 181-365 days) and the unexposed reference time period, adjusted on time-fixed and time-varying confounders.

Ethics and dissemination

Studies have been approved in Canada, Japan, the Netherlands, Spain and the UK, where an institutional review board is mandated. For each study, the results will be published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e070022.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-070022; html:https://europepmc.org/articles/PMC10151875; pdf:https://europepmc.org/articles/PMC10151875?pdf=render 35151397,https://doi.org/10.1016/s0140-6736(22)00163-5,"Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2022,2022-02-01,Y,,,,"

Background

Casirivimab and imdevimab are non-competing monoclonal antibodies that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike glycoprotein, blocking viral entry into host cells. We aimed to evaluate the efficacy and safety of casirivimab and imdevimab administered in combination in patients admitted to hospital with COVID-19.

Methods

RECOVERY is a randomised, controlled, open-label platform trial comparing several possible treatments with usual care in patients admitted to hospital with COVID-19. 127 UK hospitals took part in the evaluation of casirivimab and imdevimab. Eligible participants were any patients aged at least 12 years admitted to hospital with clinically suspected or laboratory-confirmed SARS-CoV-2 infection. Participants were randomly assigned (1:1) to either usual standard of care alone or usual care plus casirivimab 4 g and imdevimab 4 g administered together in a single intravenous infusion. Investigators and data assessors were masked to analyses of the outcome data during the trial. The primary outcome was 28-day all-cause mortality assessed by intention to treat, first only in patients without detectable antibodies to SARS-CoV-2 infection at randomisation (ie, those who were seronegative) and then in the overall population. Safety was assessed in all participants who received casirivimab and imdevimab. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between Sept 18, 2020, and May 22, 2021, 9785 patients enrolled in RECOVERY were eligible for casirivimab and imdevimab, of which 4839 were randomly assigned to casirivimab and imdevimab plus usual care and 4946 to usual care alone. 3153 (32%) of 9785 patients were seronegative, 5272 (54%) were seropositive, and 1360 (14%) had unknown baseline antibody status. 812 (8%) patients were known to have received at least one dose of a SARS-CoV-2 vaccine. In the primary efficacy population of seronegative patients, 396 (24%) of 1633 patients allocated to casirivimab and imdevimab versus 452 (30%) of 1520 patients allocated to usual care died within 28 days (rate ratio [RR] 0·79, 95% CI 0·69-0·91; p=0·0009). In an analysis of all randomly assigned patients (regardless of baseline antibody status), 943 (19%) of 4839 patients allocated to casirivimab and imdevimab versus 1029 (21%) of 4946 patients allocated to usual care died within 28 days (RR 0·94, 95% CI 0·86-1·02; p=0·14). The proportional effect of casirivimab and imdevimab on mortality differed significantly between seropositive and seronegative patients (p value for heterogeneity=0·002). There were no deaths attributed to the treatment, or meaningful between-group differences in the pre-specified safety outcomes of cause-specific mortality, cardiac arrhythmia, thrombosis, or major bleeding events. Serious adverse reactions reported in seven (<1%) participants were believed by the local investigator to be related to treatment with casirivimab and imdevimab.

Interpretation

In patients admitted to hospital with COVID-19, the monoclonal antibody combination of casirivimab and imdevimab reduced 28-day mortality in patients who were seronegative (and therefore had not mounted their own humoral immune response) at baseline but not in those who were seropositive at baseline.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/95149/5/1-s2.0-S0140673622001635-main.pdf; doi:https://doi.org/10.1016/S0140-6736(22)00163-5; html:https://europepmc.org/articles/PMC8830904 34518162,https://doi.org/10.1136/bjophthalmol-2021-319383,Predicting the immediate impact of national lockdown on neovascular age-related macular degeneration and associated visual morbidity: an INSIGHT Health Data Research Hub for Eye Health report.,"Mollan SP, Fu DJ, Chuo CY, Gannon JG, Lee WH, Hopkins JJ, Hughes C, Denniston AK, Keane PA, Cantrell R.",,The British journal of ophthalmology,2023,2021-09-13,Y,Clinical Trial; Neovascularisation; Covid-19,,,"

Objective

Predicting the impact of neovascular age-related macular degeneration (nAMD) service disruption on visual outcomes following national lockdown in the UK to contain SARS-CoV-2.

Methods and analysis

This retrospective cohort study includes deidentified data from 2229 UK patients from the INSIGHT Health Data Research digital hub. We forecasted the number of treatment-naïve nAMD patients requiring anti-vascular endothelial growth factor (anti-VEGF) initiation during UK lockdown (16 March 2020 through 31 July 2020) at Moorfields Eye Hospital (MEH) and University Hospitals Birmingham (UHB). Best-measured visual acuity (VA) changes without anti-VEGF therapy were predicted using post hoc analysis of Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD trial sham-control arm data (n=238).

Results

At our centres, 376 patients were predicted to require anti-VEGF initiation during lockdown (MEH: 325; UHB: 51). Without treatment, mean VA was projected to decline after 12 months. The proportion of eyes in the MEH cohort predicted to maintain the key positive visual outcome of ≥70 ETDRS letters (Snellen equivalent 6/12) fell from 25.5% at baseline to 5.8% at 12 months (UHB: 9.8%-7.8%). Similarly, eyes with VA <25 ETDRS letters (6/96) were predicted to increase from 4.3% to 14.2% at MEH (UHB: 5.9%-7.8%) after 12 months without treatment.

Conclusions

Here, we demonstrate how combining data from a recently founded national digital health data repository with historical industry-funded clinical trial data can enhance predictive modelling in nAMD. The demonstrated detrimental effects of prolonged treatment delay should incentivise healthcare providers to support nAMD patients accessing care in safe environments.

Trial registration number

NCT00056836.",,pdf:https://discovery.ucl.ac.uk/10164981/1/267.full.pdf; doi:https://doi.org/10.1136/bjophthalmol-2021-319383; html:https://europepmc.org/articles/PMC9887382; pdf:https://europepmc.org/articles/PMC9887382?pdf=render 38053867,https://doi.org/10.1016/j.heliyon.2023.e21734,Wastewater-based surveillance models for COVID-19: A focused review on spatio-temporal models.,"Torabi F, Li G, Mole C, Nicholson G, Rowlingson B, Smith CR, Jersakova R, Diggle PJ, Blangiardo M.",,Heliyon,2023,2023-11-08,Y,Wastewater-based Epidemiology; Covid-19; Wastewater-Based Surveillance; Spatio-Temporal Statistical Modelling,,,"The evident shedding of the SARS-CoV-2 RNA particles from infected individuals into the wastewater opened up a tantalizing array of possibilities for prediction of COVID-19 prevalence prior to symptomatic case identification through community testing. Many countries have therefore explored the use of wastewater metrics as a surveillance tool, replacing traditional direct measurement of prevalence with cost-effective approaches based on SARS-CoV-2 RNA concentrations in wastewater samples. Two important aspects in building prediction models are: time over which the prediction occurs and space for which the predicted case numbers is shown. In this review, our main focus was on finding mathematical models which take into the account both the time-varying and spatial nature of wastewater-based metrics into account. We used six main characteristics as our assessment criteria: i) modelling approach; ii) temporal coverage; iii) spatial coverage; iv) sample size; v) wastewater sampling method; and vi) covariates included in the modelling. The majority of studies in the early phases of the pandemic recognized the temporal association of SARS-CoV-2 RNA concentration level in wastewater with the number of COVID-19 cases, ignoring their spatial context. We examined 15 studies up to April 2023, focusing on models considering both temporal and spatial aspects of wastewater metrics. Most early studies correlated temporal SARS-CoV-2 RNA levels with COVID-19 cases but overlooked spatial factors. Linear regression and SEIR models were commonly used (n = 10, 66.6 % of studies), along with machine learning (n = 1, 6.6 %) and Bayesian approaches (n = 1, 6.6 %) in some cases. Three studies employed spatio-temporal modelling approach (n = 3, 20.0 %). We conclude that the development, validation and calibration of further spatio-temporally explicit models should be done in parallel with the advancement of wastewater metrics before the potential of wastewater as a surveillance tool can be fully realised.",,doi:https://doi.org/10.1016/j.heliyon.2023.e21734; html:https://europepmc.org/articles/PMC10694161; pdf:https://europepmc.org/articles/PMC10694161?pdf=render @@ -634,8 +634,8 @@ PMC9644860,https://doi.org/,Maternal mental health and children’s development: 38383380,https://doi.org/10.1186/s12939-024-02114-6,Rapid systematic review on risks and outcomes of sepsis: the influence of risk factors associated with health inequalities.,"Bladon S, Ashiru-Oredope D, Cunningham N, Pate A, Martin GP, Zhong X, Gilham EL, Brown CS, Mirfenderesky M, Palin V, van Staa TP.",,International journal for equity in health,2024,2024-02-21,Y,Sepsis; Antimicrobial resistance; communities; Socioeconomic status; Ethnicity; Deprivation; Health Inequalities; Maternal,,,"

Background and aims

Sepsis is a serious and life-threatening condition caused by a dysregulated immune response to an infection. Recent guidance issued in the UK gave recommendations around recognition and antibiotic treatment of sepsis, but did not consider factors relating to health inequalities. The aim of this study was to summarise the literature investigating associations between health inequalities and sepsis.

Methods

Searches were conducted in Embase for peer-reviewed articles published since 2010 that included sepsis in combination with one of the following five areas: socioeconomic status, race/ethnicity, community factors, medical needs and pregnancy/maternity.

Results

Five searches identified 1,402 studies, with 50 unique studies included in the review after screening (13 sociodemographic, 14 race/ethnicity, 3 community, 3 care/medical needs and 20 pregnancy/maternity; 3 papers examined multiple health inequalities). Most of the studies were conducted in the USA (31/50), with only four studies using UK data (all pregnancy related). Socioeconomic factors associated with increased sepsis incidence included lower socioeconomic status, unemployment and lower education level, although findings were not consistent across studies. For ethnicity, mixed results were reported. Living in a medically underserved area or being resident in a nursing home increased risk of sepsis. Mortality rates after sepsis were found to be higher in people living in rural areas or in those discharged to skilled nursing facilities while associations with ethnicity were mixed. Complications during delivery, caesarean-section delivery, increased deprivation and black and other ethnic minority race were associated with post-partum sepsis.

Conclusion

There are clear correlations between sepsis morbidity and mortality and the presence of factors associated with health inequalities. To inform local guidance and drive public health measures, there is a need for studies conducted across more diverse setting and countries.",,doi:https://doi.org/10.1186/s12939-024-02114-6; html:https://europepmc.org/articles/PMC10882893; pdf:https://europepmc.org/articles/PMC10882893?pdf=render 37663407,https://doi.org/10.1093/jamiaopen/ooad072,Identifying factors associated with user retention and outcomes of a digital intervention for substance use disorder: a retrospective analysis of real-world data.,"Günther F, Wong D, Elison-Davies S, Yau C.",,JAMIA open,2023,2023-09-02,Y,Substance Use Disorder; Secondary Use; Digital Health Intervention; Real-World Data Exploration; Real-World Uptake,,,"

Objectives

Successful delivery of digital health interventions is affected by multiple real-world factors. These factors may be identified in routinely collected, ecologically valid data from these interventions. We propose ideas for exploring these data, focusing on interventions targeting complex, comorbid conditions.

Materials and methods

This study retrospectively explores pre-post data collected between 2016 and 2019 from users of digital cognitive behavioral therapy (CBT)-containing psychoeducation and practical exercises-for substance use disorder (SUD) at UK addiction services. To identify factors associated with heterogenous user responses to the technology, we employed multivariable and multivariate regressions and random forest models of user-reported questionnaire data.

Results

The dataset contained information from 14 078 individuals of which 12 529 reported complete data at baseline and 2925 did so again after engagement with the CBT. Ninety-three percent screened positive for dependence on 1 of 43 substances at baseline, and 73% screened positive for anxiety or depression. Despite pre-post improvements independent of user sociodemographics, women reported more frequent and persistent symptoms of SUD, anxiety, and depression. Retention-minimum 2 use events recorded-was associated more with deployment environment than user characteristics. Prediction accuracy of post-engagement outcomes was acceptable (Area Under Curve [AUC]: 0.74-0.79), depending non-trivially on user characteristics.

Discussion

Traditionally, performance of digital health interventions is determined in controlled trials. Our analysis showcases multivariate models with which real-world data from these interventions can be explored and sources of user heterogeneity in retention and symptom reduction uncovered.

Conclusion

Real-world data from digital health interventions contain information on natural user-technology interactions which could enrich results from controlled trials.",,pdf:https://academic.oup.com/jamiaopen/article-pdf/6/3/ooad072/51335405/ooad072.pdf; doi:https://doi.org/10.1093/jamiaopen/ooad072; html:https://europepmc.org/articles/PMC10474970; pdf:https://europepmc.org/articles/PMC10474970?pdf=render 36434299,https://doi.org/10.1007/s00127-022-02393-w,Adverse outcomes associated with recorded victimization in mental health electronic records during the first UK COVID-19 lockdown.,"Kadra-Scalzo G, Kornblum D, Stewart R, Howard LM.",,Social psychiatry and psychiatric epidemiology,2023,2022-11-24,Y,Mental health; Domestic Violence; Victimisation; Adverse Outcomes; Covid-19,,,"

Purpose

The impact of COVID-19 pandemic policies on vulnerable groups such as people with mental health problems who experience violence remains unknown. This study aimed to investigate the prevalence of victimization recorded in mental healthcare records during the first UK lockdown, and associations with subsequent adverse outcomes.

Methods

Using a large mental healthcare database, we identified all adult patients receiving services between 16.12.2019 and 15.06.2020 and extracted records of victimisation between 16.03.2020 and 15.06.2020 (first UK COVID-19 lockdown). We investigated adverse outcomes including acute care, emergency department referrals and all-cause mortality in the year following the lockdown (16.06.2020- 01.11.2021). Multivariable Cox regressions models were constructed, adjusting for socio-demographic, socioeconomic, clinical, and service use factors.

Results

Of 21,037 adults receiving mental healthcare over the observation period, 3,610 (17.2%) had victimisation mentioned between 16.03.2020 and 15.06.2020 (first UK COVID-19 lockdown). Service users with mentions of victimisation in their records had an elevated risk for all outcomes: acute care (adjusted HR: 2.1; 95%CI 1.9-2.3, p < 0.001), emergency department referrals (aHR: 2.0; 95%CI 1.8-2.2; p < 0.001), and all-cause mortality (aHR: 1.5; 95%CI 1.1-1.9; p = 0.003), when compared to service users with no recorded victimisation. We did not observe a statistically significant interaction with gender; however, after adjusting for possible confounders, men had slightly higher hazard ratios for all-cause mortality and emergency department referrals than women.

Conclusion

Patients with documented victimisation during the first UK lockdown were at increased risk for acute care, emergency department referrals and all-cause mortality. Further research is needed into mediating mechanisms.",,pdf:https://link.springer.com/content/pdf/10.1007/s00127-022-02393-w.pdf; doi:https://doi.org/10.1007/s00127-022-02393-w; html:https://europepmc.org/articles/PMC9702612; pdf:https://europepmc.org/articles/PMC9702612?pdf=render -35836669,https://doi.org/10.1097/txd.0000000000001188,HLA Alleles Cw12 and DQ4 in Kidney Transplant Recipients Are Independent Risk Factors for the Development of Posttransplantation Diabetes.,"Phagura N, Hussain A, Culliford A, Hodson J, Evison F, Gallier S, Borrows R, Lane HA, Briggs D, Sharif A.",,Transplantation direct,2021,2021-07-23,Y,,,,"The association between specific HLA alleles and risk for posttransplantation diabetes (PTDM) in a contemporary and multiethnic kidney transplant recipient cohort is not clear.

Methods

In this single-center analysis, data were retrospectively analyzed for 1560 nondiabetic kidney transplant recipients at a single center between 2007 and 2018, with median follow-up of 33 mo (interquartile range 8-73). HLA typing methodology was by DNA analysis and reported at the resolution required for the national allocation scheme. Diagnosis of PTDM was aligned with International Consensus recommendations.

Results

PTDM developed in 231 kidney transplant recipients. Exploring 99 HLA alleles, the presence of Cw12, B52, B38, B58, DQ4, A80, and DR13 and the absence of DQ3 and DR04 were associated with significant increases in PTDM risk. In a multivariable Cox regression model, adjusting for other clinical risk factors for PTDM, the presence of Cw12 (hazard ratio [HR], 1.57; 95% CI, 1.08-2.27; P = 0.017) and DQ4 (HR, 1.78; 95% CI, 1.07-2.96; P = 0.026) were found to be independent risk factors for PTDM. There was also evidence that the presence of B58 increases PTDM risk within the subgroup of recipients of White ethnicity (HR, 5.01; 95% CI, 2.20-11.42; P < 0.001).

Conclusion

Our data suggest that specific HLA alleles can be associated with PTDM risk, which can be used pretransplantation for PTDM risk stratification. However, association is not causality, and this work requires replication and further investigation to understand underlying biological mechanisms.",,doi:https://doi.org/10.1097/txd.0000000000001188; doi:https://doi.org/10.1097/TXD.0000000000001188; html:https://europepmc.org/articles/PMC9276282; pdf:https://europepmc.org/articles/PMC9276282?pdf=render 31818272,https://doi.org/10.1186/s12889-019-8015-3,"Drinking beer, wine or spirits - does it matter for inequalities in alcohol-related hospital admission? A record-linked longitudinal study in Wales.","Gartner A, Trefan L, Moore S, Akbari A, Paranjothy S, Farewell D.",,BMC public health,2019,2019-12-09,Y,Alcohol; Inequalities; Deprivation; Hospital Admission; Beverage Type; Record Linked,Improving Public Health,,"

Background

Alcohol-related harm has been found to be higher in disadvantaged groups, despite similar alcohol consumption to advantaged groups. This is known as the alcohol harm paradox. Beverage type is reportedly socioeconomically patterned but has not been included in longitudinal studies investigating record-linked alcohol consumption and harm. We aimed to investigate whether and to what extent consumption by beverage type, BMI, smoking and other factors explain inequalities in alcohol-related harm.

Methods

11,038 respondents to the Welsh Health Survey answered questions on their health and lifestyle. Responses were record-linked to wholly attributable alcohol-related hospital admissions (ARHA) eight years before the survey month and until the end of 2016 within the Secure Anonymised Information Linkage (SAIL) Databank. We used survival analysis, specifically multi-level and multi-failure Cox mixed effects models, to calculate the hazard ratios of ARHA. In adjusted models we included the number of units consumed by beverage type and other factors, censoring for death or moving out of Wales.

Results

People living in more deprived areas had a higher risk of admission (HR 1.75; 95% CI 1.23-2.48) compared to less deprived. Adjustment for the number of units by type of alcohol consumed only reduced the risk of ARHA for more deprived areas by 4% (HR 1.72; 95% CI 1.21-2.44), whilst adding smoking and BMI reduced these inequalities by 35.7% (HR 1.48; 95% CI 1.01-2.17). These social patterns were similar for individual-level social class, employment, housing tenure and highest qualification. Inequalities were further reduced by including either health status (16.6%) or mental health condition (5%). Unit increases of spirits drunk were positively associated with increasing risk of ARHA (HR 1.06; 95% CI 1.01-1.12), higher than for other drink types.

Conclusions

Although consumption by beverage type was socioeconomically patterned, it did not help explain inequalities in alcohol-related harm. Smoking and BMI explained around a third of inequalities, but lower socioeconomic groups had a persistently higher risk of (multiple) ARHA. Comorbidities also explained a further proportion of inequalities and need further investigation, including the contribution of specific conditions. The increased harms from consumption of stronger alcoholic beverages may inform public health policy.","This longitudinal study investigated whether and to what extent consumption by beverage type, BMI, smoking and other factors explained inequalities in alcohol-related hospital admission (ARHA). Using statistical analysis methods, it was found that people living in more deprived areas had a higher risk of ARHA compared to less deprived. Smokers and people currently being treated for mental illness had higher risk of ARHA, while BMI appeared to be slightly protective. ",pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-019-8015-3; doi:https://doi.org/10.1186/s12889-019-8015-3; html:https://europepmc.org/articles/PMC6902530; pdf:https://europepmc.org/articles/PMC6902530?pdf=render +35836669,https://doi.org/10.1097/txd.0000000000001188,HLA Alleles Cw12 and DQ4 in Kidney Transplant Recipients Are Independent Risk Factors for the Development of Posttransplantation Diabetes.,"Phagura N, Hussain A, Culliford A, Hodson J, Evison F, Gallier S, Borrows R, Lane HA, Briggs D, Sharif A.",,Transplantation direct,2021,2021-07-23,Y,,,,"The association between specific HLA alleles and risk for posttransplantation diabetes (PTDM) in a contemporary and multiethnic kidney transplant recipient cohort is not clear.

Methods

In this single-center analysis, data were retrospectively analyzed for 1560 nondiabetic kidney transplant recipients at a single center between 2007 and 2018, with median follow-up of 33 mo (interquartile range 8-73). HLA typing methodology was by DNA analysis and reported at the resolution required for the national allocation scheme. Diagnosis of PTDM was aligned with International Consensus recommendations.

Results

PTDM developed in 231 kidney transplant recipients. Exploring 99 HLA alleles, the presence of Cw12, B52, B38, B58, DQ4, A80, and DR13 and the absence of DQ3 and DR04 were associated with significant increases in PTDM risk. In a multivariable Cox regression model, adjusting for other clinical risk factors for PTDM, the presence of Cw12 (hazard ratio [HR], 1.57; 95% CI, 1.08-2.27; P = 0.017) and DQ4 (HR, 1.78; 95% CI, 1.07-2.96; P = 0.026) were found to be independent risk factors for PTDM. There was also evidence that the presence of B58 increases PTDM risk within the subgroup of recipients of White ethnicity (HR, 5.01; 95% CI, 2.20-11.42; P < 0.001).

Conclusion

Our data suggest that specific HLA alleles can be associated with PTDM risk, which can be used pretransplantation for PTDM risk stratification. However, association is not causality, and this work requires replication and further investigation to understand underlying biological mechanisms.",,doi:https://doi.org/10.1097/txd.0000000000001188; doi:https://doi.org/10.1097/TXD.0000000000001188; html:https://europepmc.org/articles/PMC9276282; pdf:https://europepmc.org/articles/PMC9276282?pdf=render 31612961,https://doi.org/10.1093/nar/gkz895,GWAS Central: a comprehensive resource for the discovery and comparison of genotype and phenotype data from genome-wide association studies.,"Beck T, Shorter T, Brookes AJ.",,Nucleic acids research,2020,2020-01-01,Y,,,,"The GWAS Central resource provides a toolkit for integrative access and visualization of a uniquely extensive collection of genome-wide association study data, while ensuring safe open access to prevent research participant identification. GWAS Central is the world's most comprehensive openly accessible repository of summary-level GWAS association information, providing over 70 million P-values for over 3800 studies investigating over 1400 unique phenotypes. The database content comprises direct submissions received from GWAS authors and consortia, in addition to actively gathered data sets from various public sources. GWAS data are discoverable from the perspective of genetic markers, genes, genome regions or phenotypes, via graphical visualizations and detailed downloadable data reports. Tested genetic markers and relevant genomic features can be visually interrogated across up to sixteen multiple association data sets in a single view using the integrated genome browser. The semantic standardization of phenotype descriptions with Medical Subject Headings and the Human Phenotype Ontology allows the precise identification of genetic variants associated with diseases, phenotypes and traits of interest. Harmonization of the phenotype descriptions used across several GWAS-related resources has extended the phenotype search capabilities to enable cross-database study discovery using a range of ontologies. GWAS Central is updated regularly and available at https://www.gwascentral.org.",,pdf:https://academic.oup.com/nar/article-pdf/48/D1/D933/31697824/gkz895.pdf; doi:https://doi.org/10.1093/nar/gkz895; html:https://europepmc.org/articles/PMC7145571; pdf:https://europepmc.org/articles/PMC7145571?pdf=render 35845286,https://doi.org/10.1002/jha2.182,"An open-source, expert-designed decision tree application to support accurate diagnosis of myeloid malignancies.","Coats T, Bean D, Vatopoulou T, Vijayavalli D, El-Bashir R, Panopoulou A, Wood H, Wimalachandra M, Coppell J, Medd P, Furtado M, Tucker D, Kulasakeraraj A, Pawade J, Dobson R, Ireland R.",,EJHaem,2021,2021-03-26,Y,Myeloid Leukaemia; Classifications; Diagnostic Haematology; Clinical Haematology,,,"Accurate, reproducible diagnoses can be difficult to make in haemato-oncology due to multi-parameter clinical data, complex diagnostic criteria and time-pressured environments. We have designed a decision tree application (DTA) that reflects WHO diagnostic criteria to support accurate diagnoses of myeloid malignancies. The DTA returned the correct diagnoses in 94% of clinical cases tested. The DTA maintained a high level of accuracy in a second validation using artificially generated clinical cases. Optimisations have been made to the DTA based on the validations, and the revised version is now publicly available for use at http://bit.do/ADAtool.",,pdf:https://discovery.ucl.ac.uk/10145154/1/Bean_An%20open%20source%2C%20expert%20designed%20decision%20tree%20application%20to%20support%20accurate%20diagnosis%20of%20myeloid%20malignancies_VoR.pdf; doi:https://doi.org/10.1002/jha2.182; html:https://europepmc.org/articles/PMC9175663; pdf:https://europepmc.org/articles/PMC9175663?pdf=render 33020224,https://doi.org/10.1136/heartjnl-2020-317870,Monitoring indirect impact of COVID-19 pandemic on services for cardiovascular diseases in the UK.,"Ball S, Banerjee A, Berry C, Boyle JR, Bray B, Bradlow W, Chaudhry A, Crawley R, Danesh J, Denniston A, Falter F, Figueroa JD, Hall C, Hemingway H, Jefferson E, Johnson T, King G, Lee KK, McKean P, Mason S, Mills NL, Pearson E, Pirmohamed M, Poon MTC, Priedon R, Shah A, Sofat R, Sterne JAC, Strachan FE, Sudlow CLM, Szarka Z, Whiteley W, Wyatt M, CVD-COVID-UK Consortium.",,Heart (British Cardiac Society),2020,2020-10-05,Y,epidemiology; Heart Disease; Health Care Delivery; Global Health Care Delivery; Aortic And Arterial Disease,,,"

Objective

To monitor hospital activity for presentation, diagnosis and treatment of cardiovascular diseases during the COVID-19) pandemic to inform on indirect effects.

Methods

Retrospective serial cross-sectional study in nine UK hospitals using hospital activity data from 28 October 2019 (pre-COVID-19) to 10 May 2020 (pre-easing of lockdown) and for the same weeks during 2018-2019. We analysed aggregate data for selected cardiovascular diseases before and during the epidemic. We produced an online visualisation tool to enable near real-time monitoring of trends.

Results

Across nine hospitals, total admissions and emergency department (ED) attendances decreased after lockdown (23 March 2020) by 57.9% (57.1%-58.6%) and 52.9% (52.2%-53.5%), respectively, compared with the previous year. Activity for cardiac, cerebrovascular and other vascular conditions started to decline 1-2 weeks before lockdown and fell by 31%-88% after lockdown, with the greatest reductions observed for coronary artery bypass grafts, carotid endarterectomy, aortic aneurysm repair and peripheral arterial disease procedures. Compared with before the first UK COVID-19 (31 January 2020), activity declined across diseases and specialties between the first case and lockdown (total ED attendances relative reduction (RR) 0.94, 0.93-0.95; total hospital admissions RR 0.96, 0.95-0.97) and after lockdown (attendances RR 0.63, 0.62-0.64; admissions RR 0.59, 0.57-0.60). There was limited recovery towards usual levels of some activities from mid-April 2020.

Conclusions

Substantial reductions in total and cardiovascular activities are likely to contribute to a major burden of indirect effects of the pandemic, suggesting they should be monitored and mitigated urgently.",,pdf:https://heart.bmj.com/content/heartjnl/106/24/1890.full.pdf; doi:https://doi.org/10.1136/heartjnl-2020-317870; html:https://europepmc.org/articles/PMC7536637; pdf:https://europepmc.org/articles/PMC7536637?pdf=render @@ -652,8 +652,8 @@ PMC9644860,https://doi.org/,Maternal mental health and children’s development: 37889180,https://doi.org/10.1161/jaha.123.030661,Genome-Wide Association Study of Pericardial Fat Area in 28 161 UK Biobank Participants.,"Salih A, Ardissino M, Wagen AZ, Bard A, Szabo L, Ryten M, Petersen SE, Altmann A, Raisi-Estabragh Z.",,Journal of the American Heart Association,2023,2023-10-27,Y,Cardiovascular disease; Pericardial Adipose Tissue; Genome‐wide Association Study,,,"BACKGROUND Pericardial adipose tissue (PAT) is the visceral adipose tissue compartment surrounding the heart. Experimental and observational research has suggested that greater PAT deposition might mediate cardiovascular disease, independent of general or subcutaneous adiposity. We characterize the genetic architecture of adiposity-adjusted PAT and identify causal associations between PAT and adverse cardiac magnetic resonance imaging measures of cardiac structure and function in 28 161 UK Biobank participants. METHODS AND RESULTS The PAT phenotype was extracted from cardiac magnetic resonance images using an automated image analysis tool previously developed and validated in this cohort. A genome-wide association study was performed with PAT area set as the phenotype, adjusting for age, sex, and other measures of obesity. Functional mapping and Bayesian colocalization were used to understand the biologic role of identified variants. Mendelian randomization analysis was used to examine potential causal links between genetically determined PAT and cardiac magnetic resonance-derived measures of left ventricular structure and function. We discovered 12 genome-wide significant variants, with 2 independent sentinel variants (rs6428792, P=4.20×10-9 and rs11992444, P=1.30×10-12) at 2 distinct genomic loci, that were mapped to 3 potentially causal genes: T-box transcription factor 15 (TBX15), tryptophanyl tRNA synthetase 2, mitochondrial (WARS2) and early B-cell factor-2 (EBF2) through functional annotation. Bayesian colocalization additionally suggested a role of RP4-712E4.1. Genetically predicted differences in adiposity-adjusted PAT were causally associated with adverse left ventricular remodeling. CONCLUSIONS This study provides insights into the genetic architecture determining differential PAT deposition, identifies causal links with left structural and functional parameters, and provides novel data about the pathophysiological importance of adiposity distribution.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.030661; doi:https://doi.org/10.1161/JAHA.123.030661; html:https://europepmc.org/articles/PMC10727393; pdf:https://europepmc.org/articles/PMC10727393?pdf=render 32614817,https://doi.org/10.1371/journal.pcbi.1008031,Estimation of country-level basic reproductive ratios for novel Coronavirus (SARS-CoV-2/COVID-19) using synthetic contact matrices.,"Hilton J, Keeling MJ.",,PLoS computational biology,2020,2020-07-02,Y,,,,"The 2019-2020 pandemic of atypical pneumonia (COVID-19) caused by the virus SARS-CoV-2 has spread globally and has the potential to infect large numbers of people in every country. Estimating the country-specific basic reproductive ratio is a vital first step in public-health planning. The basic reproductive ratio (R0) is determined by both the nature of pathogen and the network of human contacts through which the disease can spread, which is itself dependent on population age structure and household composition. Here we introduce a transmission model combining age-stratified contact frequencies with age-dependent susceptibility, probability of clinical symptoms, and transmission from asymptomatic (or mild) cases, which we use to estimate the country-specific basic reproductive ratio of COVID-19 for 152 countries. Using early outbreak data from China and a synthetic contact matrix, we estimate an age-stratified transmission structure which can then be extrapolated to 151 other countries for which synthetic contact matrices also exist. This defines a set of country-specific transmission structures from which we can calculate the basic reproductive ratio for each country. Our predicted R0 is critically sensitive to the intensity of transmission from asymptomatic cases; with low asymptomatic transmission the highest values are predicted across Eastern Europe and Japan and the lowest across Africa, Central America and South-Western Asia. This pattern is largely driven by the ratio of children to older adults in each country and the observed propensity of clinical cases in the elderly. If asymptomatic cases have comparable transmission to detected cases, the pattern is reversed. Our results demonstrate the importance of age-specific heterogeneities going beyond contact structure to the spread of COVID-19. These heterogeneities give COVID-19 the capacity to spread particularly quickly in countries with older populations, and that intensive control measures are likely to be necessary to impede its progress in these countries.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008031&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1008031; html:https://europepmc.org/articles/PMC7363110; pdf:https://europepmc.org/articles/PMC7363110?pdf=render 33152012,https://doi.org/10.1371/journal.pone.0241800,Effect of long-chain polyunsaturated fatty acids in infant formula on long-term cognitive function in childhood: A systematic review and meta-analysis of randomised controlled trials.,"Verfuerden ML, Dib S, Jerrim J, Fewtrell M, Gilbert RE.",,PloS one,2020,2020-11-05,Y,,,,

Study registration

PROSPERO registration numbers CRD42018105196 and CRD42018088868.,,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0241800&type=printable; doi:https://doi.org/10.1371/journal.pone.0241800; html:https://europepmc.org/articles/PMC7644261; pdf:https://europepmc.org/articles/PMC7644261?pdf=render -36713473,https://doi.org/10.1093/ofid/ofac694,Clinical Effectiveness of SARS-CoV-2 Booster Vaccine Against Omicron Infection in Residents and Staff of Long-term Care Facilities: A Prospective Cohort Study (VIVALDI).,"Stirrup O, Shrotri M, Adams NL, Krutikov M, Nacer-Laidi H, Azmi B, Palmer T, Fuller C, Irwin-Singer A, Baynton V, Tut G, Moss P, Hayward A, Copas A, Shallcross L.",,Open forum infectious diseases,2023,2022-12-29,Y,Vaccine Effectiveness; Long-term Care Facilities; Covid-19; Sars-cov-2; Omicron,,,"

Background

Successive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have caused severe disease in long-term care facility (LTCF) residents. Primary vaccination provides strong short-term protection, but data are limited on duration of protection following booster vaccines, particularly against the Omicron variant. We investigated the effectiveness of booster vaccination against infections, hospitalizations, and deaths among LTCF residents and staff in England.

Methods

We included residents and staff of LTCFs within the VIVALDI study (ISRCTN 14447421) who underwent routine, asymptomatic testing (December 12, 2021-March 31, 2022). Cox regression was used to estimate relative hazards of SARS-CoV-2 infection, and associated hospitalization and death at 0-13, 14-48, 49-83, 84-111, 112-139, and 140+ days after dose 3 of SARS-CoV-2 vaccination compared with 2 doses (after 84+ days), stratified by previous SARS-CoV-2 infection and adjusting for age, sex, LTCF capacity, and local SARS-CoV-2 incidence.

Results

A total of 14 175 residents and 19 793 staff were included. In residents without prior SARS-CoV-2 infection, infection risk was reduced 0-111 days after the first booster, but no protection was apparent after 112 days. Additional protection following booster vaccination waned but was still present at 140+ days for COVID-associated hospitalization (adjusted hazard ratio [aHR], 0.20; 95% CI, 0.06-0.63) and death (aHR, 0.50; 95% CI, 0.20-1.27). Most residents (64.4%) had received primary course vaccine of AstraZeneca, but this did not impact pre- or postbooster risk. Staff showed a similar pattern of waning booster effectiveness against infection, with few hospitalizations and no deaths.

Conclusions

Our findings suggest that booster vaccination provided sustained protection against severe outcomes following infection with the Omicron variant, but no protection against infection from 4 months onwards. Ongoing surveillance for SARS-CoV-2 in LTCFs is crucial.",,pdf:https://academic.oup.com/ofid/article-pdf/10/1/ofac694/48846221/ofac694.pdf; doi:https://doi.org/10.1093/ofid/ofac694; html:https://europepmc.org/articles/PMC9874026; pdf:https://europepmc.org/articles/PMC9874026?pdf=render 33185672,https://doi.org/10.1093/jamia/ocaa295,Ensemble learning for poor prognosis predictions: A case study on SARS-CoV-2.,"Wu H, Zhang H, Karwath A, Ibrahim Z, Shi T, Zhang X, Wang K, Sun J, Dhaliwal K, Bean D, Cardoso VR, Li K, Teo JT, Banerjee A, Gao-Smith F, Whitehouse T, Veenith T, Gkoutos GV, Wu X, Dobson R, Guthrie B.",,Journal of the American Medical Informatics Association : JAMIA,2021,2021-03-01,Y,Decision Support; Risk Prediction; Ensemble Learning; Covid-19; Model Synergy,,,"

Objective

Risk prediction models are widely used to inform evidence-based clinical decision making. However, few models developed from single cohorts can perform consistently well at population level where diverse prognoses exist (such as the SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2] pandemic). This study aims at tackling this challenge by synergizing prediction models from the literature using ensemble learning.

Materials and methods

In this study, we selected and reimplemented 7 prediction models for COVID-19 (coronavirus disease 2019) that were derived from diverse cohorts and used different implementation techniques. A novel ensemble learning framework was proposed to synergize them for realizing personalized predictions for individual patients. Four diverse international cohorts (2 from the United Kingdom and 2 from China; N = 5394) were used to validate all 8 models on discrimination, calibration, and clinical usefulness.

Results

Results showed that individual prediction models could perform well on some cohorts while poorly on others. Conversely, the ensemble model achieved the best performances consistently on all metrics quantifying discrimination, calibration, and clinical usefulness. Performance disparities were observed in cohorts from the 2 countries: all models achieved better performances on the China cohorts.

Discussion

When individual models were learned from complementary cohorts, the synergized model had the potential to achieve better performances than any individual model. Results indicate that blood parameters and physiological measurements might have better predictive powers when collected early, which remains to be confirmed by further studies.

Conclusions

Combining a diverse set of individual prediction models, the ensemble method can synergize a robust and well-performing model by choosing the most competent ones for individual patients.",,pdf:https://academic.oup.com/jamia/article-pdf/28/4/791/41182395/ocaa295.pdf; doi:https://doi.org/10.1093/jamia/ocaa295; html:https://europepmc.org/articles/PMC7717299; pdf:https://europepmc.org/articles/PMC7717299?pdf=render +36713473,https://doi.org/10.1093/ofid/ofac694,Clinical Effectiveness of SARS-CoV-2 Booster Vaccine Against Omicron Infection in Residents and Staff of Long-term Care Facilities: A Prospective Cohort Study (VIVALDI).,"Stirrup O, Shrotri M, Adams NL, Krutikov M, Nacer-Laidi H, Azmi B, Palmer T, Fuller C, Irwin-Singer A, Baynton V, Tut G, Moss P, Hayward A, Copas A, Shallcross L.",,Open forum infectious diseases,2023,2022-12-29,Y,Vaccine Effectiveness; Long-term Care Facilities; Covid-19; Sars-cov-2; Omicron,,,"

Background

Successive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have caused severe disease in long-term care facility (LTCF) residents. Primary vaccination provides strong short-term protection, but data are limited on duration of protection following booster vaccines, particularly against the Omicron variant. We investigated the effectiveness of booster vaccination against infections, hospitalizations, and deaths among LTCF residents and staff in England.

Methods

We included residents and staff of LTCFs within the VIVALDI study (ISRCTN 14447421) who underwent routine, asymptomatic testing (December 12, 2021-March 31, 2022). Cox regression was used to estimate relative hazards of SARS-CoV-2 infection, and associated hospitalization and death at 0-13, 14-48, 49-83, 84-111, 112-139, and 140+ days after dose 3 of SARS-CoV-2 vaccination compared with 2 doses (after 84+ days), stratified by previous SARS-CoV-2 infection and adjusting for age, sex, LTCF capacity, and local SARS-CoV-2 incidence.

Results

A total of 14 175 residents and 19 793 staff were included. In residents without prior SARS-CoV-2 infection, infection risk was reduced 0-111 days after the first booster, but no protection was apparent after 112 days. Additional protection following booster vaccination waned but was still present at 140+ days for COVID-associated hospitalization (adjusted hazard ratio [aHR], 0.20; 95% CI, 0.06-0.63) and death (aHR, 0.50; 95% CI, 0.20-1.27). Most residents (64.4%) had received primary course vaccine of AstraZeneca, but this did not impact pre- or postbooster risk. Staff showed a similar pattern of waning booster effectiveness against infection, with few hospitalizations and no deaths.

Conclusions

Our findings suggest that booster vaccination provided sustained protection against severe outcomes following infection with the Omicron variant, but no protection against infection from 4 months onwards. Ongoing surveillance for SARS-CoV-2 in LTCFs is crucial.",,pdf:https://academic.oup.com/ofid/article-pdf/10/1/ofac694/48846221/ofac694.pdf; doi:https://doi.org/10.1093/ofid/ofac694; html:https://europepmc.org/articles/PMC9874026; pdf:https://europepmc.org/articles/PMC9874026?pdf=render 33728401,https://doi.org/10.1038/s42254-020-0178-4,Modelling COVID-19.,"Vespignani A, Tian H, Dye C, Lloyd-Smith JO, Eggo RM, Shrestha M, Scarpino SV, Gutierrez B, Kraemer MUG, Wu J, Leung K, Leung GM.",,Nature reviews. Physics,2020,2020-05-06,Y,Applied Mathematics; Complex Networks,,,"As the COVID-19 pandemic continues, mathematical epidemiologists share their views on what models reveal about how the disease has spread, the current state of play and what work still needs to be done.",Vespignani et al. used mathematical models to model the epidemic of covid-19 and to predict future scenarios for possible interventions and inform policy and practice.,pdf:https://www.nature.com/articles/s42254-020-0178-4.pdf; doi:https://doi.org/10.1038/s42254-020-0178-4; html:https://europepmc.org/articles/PMC7201389; pdf:https://europepmc.org/articles/PMC7201389?pdf=render 35501711,https://doi.org/10.1186/s12864-022-08562-0,Single-cell transcriptomic and chromatin accessibility analyses of dairy cattle peripheral blood mononuclear cells and their responses to lipopolysaccharide.,"Gao Y, Li J, Cai G, Wang Y, Yang W, Li Y, Zhao X, Li R, Gao Y, Tuo W, Baldwin RL, Li CJ, Fang L, Liu GE.",,BMC genomics,2022,2022-04-30,Y,Cattle; Lipopolysaccharide; Peripheral blood mononuclear cell; Single-cell Rna-seq; Single-cell Atac-seq,,,"

Background

Gram-negative bacteria are important pathogens in cattle, causing severe infectious diseases, including mastitis. Lipopolysaccharides (LPS) are components of the outer membrane of Gram-negative bacteria and crucial mediators of chronic inflammation in cattle. LPS modulations of bovine immune responses have been studied before. However, the single-cell transcriptomic and chromatin accessibility analyses of bovine peripheral blood mononuclear cells (PBMCs) and their responses to LPS stimulation were never reported.

Results

We performed single-cell RNA sequencing (scRNA-seq) and single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) in bovine PBMCs before and after LPS treatment and demonstrated that seven major cell types, which included CD4 T cells, CD8 T cells, and B cells, monocytes, natural killer cells, innate lymphoid cells, and dendritic cells. Bioinformatic analyses indicated that LPS could increase PBMC cell cycle progression, cellular differentiation, and chromatin accessibility. Gene analyses further showed significant changes in differential expression, transcription factor binding site, gene ontology, and regulatory interactions during the PBMC responses to LPS. Consistent with the findings of previous studies, LPS induced activation of monocytes and dendritic cells, likely through their upregulated TLR4 receptor. NF-κB was observed to be activated by LPS and an increased transcription of an array of pro-inflammatory cytokines, in agreement that NF-κB is an LPS-responsive regulator of innate immune responses. In addition, by integrating LPS-induced differentially expressed genes (DEGs) with large-scale GWAS of 45 complex traits in Holstein, we detected trait-relevant cell types. We found that selected DEGs were significantly associated with immune-relevant health, milk production, and body conformation traits.

Conclusion

This study provided the first scRNAseq and scATAC-seq data for cattle PBMCs and their responses to the LPS stimulation to the best of our knowledge. These results should also serve as valuable resources for the future study of the bovine immune system and open the door for discoveries about immune cell roles in complex traits like mastitis at single-cell resolution.",,pdf:https://bmcgenomics.biomedcentral.com/counter/pdf/10.1186/s12864-022-08562-0; doi:https://doi.org/10.1186/s12864-022-08562-0; html:https://europepmc.org/articles/PMC9063233; pdf:https://europepmc.org/articles/PMC9063233?pdf=render 35954935,https://doi.org/10.3390/ijerph19159578,Comparing Peak Burn Injury Times and Characteristics in Australia and New Zealand.,"Hong R, Perkins M, Gabbe BJ, Tracy LM.",,International journal of environmental research and public health,2022,2022-08-04,Y,Burns; Cooking; Registry; scald; Flame,,,"Burns are a leading cause of morbidity and mortality worldwide. Understanding when and how burns occur, as well as the differences between countries, would aid prevention efforts. A review of burn injuries occurring between July 2009 and June 2021 was undertaken using data from the Burns Registry of Australia and New Zealand. Peak injury times were identified on a country-by-country basis. Variations in demographic and injury event profiles between countries were compared using descriptive statistics. There were 26,925 admissions recorded across the two countries (23,323 for Australia; 3602 for New Zealand). The greatest number of injuries occurred between 6 PM to 7 PM in Australia (1871, 8.0%) and between 5 PM to 6 PM in New Zealand (280, 7.8%). In both countries, scalds accounted for the greatest proportion of injuries during peak times (988, 45.8%), but a greater proportion of young children (under three years) sustained burns during New Zealand's peak times. The number of burn injuries associated with the preparation and/or consumption of food offers an opportunity for a targeted prevention program that may yield benefits across the two countries. Age- and mechanism-related differences in the profile of burn-injured patients need to be considered when developing and implementing such a program.",,pdf:https://www.mdpi.com/1660-4601/19/15/9578/pdf?version=1659598966; doi:https://doi.org/10.3390/ijerph19159578; html:https://europepmc.org/articles/PMC9368485; pdf:https://europepmc.org/articles/PMC9368485?pdf=render @@ -677,8 +677,8 @@ PMC9644860,https://doi.org/,Maternal mental health and children’s development: 33371011,https://doi.org/10.1136/bmjresp-2020-000770,Physiological tests of small airways function in diagnosing asthma: a systematic review.,"Almeshari MA, Alobaidi NY, Edgar RG, Stockley J, Sapey E.",,BMJ open respiratory research,2020,2020-12-01,Y,Asthma; Lung Physiology,,,"

Background

Asthma is a common, heterogeneous disease that is characterised by chronic airway inflammation and variable expiratory airflow limitation. Current guidelines use spirometric measures for asthma assessment. This systematic review aimed to assess whether the most commonly reported tests of small airways function could contribute to the diagnosis of asthma.

Methods

Standard systematic review methodology was used, and a range of electronic databases was searched (Embase, MEDLINE, CINAHL, CENTRAL, Web of Science, DARE). Studies that included physiological tests of small airways function to diagnose asthma in adults were included, with no restrictions on language or date. The risk of bias and quality assessment tools used were Agency for Healthcare Research and Quality tool for cross-sectional studies and Quality Assessment of Diagnostic Accuracy Studies 2 for diagnostic test accuracy (DTA) studies.

Results

7072 studies were identified and 10 studies met review criteria. 7 included oscillation techniques and 5 included maximal mid-expiratory flow (MMEF). Studies were small and of variable quality. In oscillometry, total resistance (R5) and reactance at 5 Hz (X5) was altered in asthma compared with healthy controls. The percentage predicted of MMEF was lower in patients with asthma compared with controls in all studies and lower than the % predicted forced expiratory volume in 1 s. In DTA of oscillometry, R5 showed a sensitivity between 69% and 72% and specificity between 61% and 86%.

Conclusion

There were differences in the results of physiological tests of small airway function in patients with asthma compared with controls. However, studies are small and heterogeneous. Further studies are needed to assess the effectiveness of these tests on a larger scale, including studies to determine which test methodology is the most useful in asthma.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/7/1/e000770.full.pdf; doi:https://doi.org/10.1136/bmjresp-2020-000770; html:https://europepmc.org/articles/PMC7754643; pdf:https://europepmc.org/articles/PMC7754643?pdf=render 37550086,https://doi.org/10.1136/bmjment-2023-300762,Associations between air pollution and mental health service use in dementia: a retrospective cohort study.,"Ronaldson A, Stewart R, Mueller C, Das-Munshi J, Newbury JB, Mudway IS, Broadbent M, Fisher HL, Beevers S, Dajnak D, Hotopf M, Hatch SL, Bakolis I.",,BMJ mental health,2023,2023-07-01,Y,Psychiatry; Adult Psychiatry; Delirium & Cognitive Disorders,,,"

Background

Little is known about the role of air pollution in how people with dementia use mental health services.

Objective

We examined longitudinal associations between air pollution exposure and mental health service use in people with dementia.

Methods

In 5024 people aged 65 years or older with dementia in South London, high resolution estimates of nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10) levels in ambient air were linked to residential addresses. Associations between air pollution and Community Mental Health Team (CMHT) events (recorded over 9 years) were examined using negative binomial regression models. Cognitive function was measured using the Mini Mental State Examination (MMSE) and health and social functioning was measured using the Health of the Nation Outcomes Scale (HoNOS65+). Associations between air pollution and both MMSE and HoNOS65+ scores were assessed using linear regression models.

Findings

In the first year of follow-up, increased exposure to all air pollutants was associated with an increase in the use of CMHTs in a dose-response manner. These associations were strongest when we compared the highest air pollution quartile (quartile 4: Q4) with the lowest quartile (Q1) (eg, NO2: adjusted incidence rate ratio (aIRR) 1.27, 95% CI 1.11 to 1.45, p<0.001). Dose-response patterns between PM2.5 and CMHT events remained at 5 and 9 years. Associations were strongest for patients with vascular dementia. NO2 levels were linked with poor functional status, but not cognitive function.

Conclusions

Residential air pollution exposure is associated with increased CMHT usage among people with dementia.

Clinical implications

Efforts to reduce pollutant exposures in urban settings might reduce the use of mental health services in people with dementia, freeing up resources in already considerably stretched psychiatric services.",,doi:https://doi.org/10.1136/bmjment-2023-300762; html:https://europepmc.org/articles/PMC10577765; pdf:https://europepmc.org/articles/PMC10577765?pdf=render 36929232,https://doi.org/10.1002/jmri.28675,Image-Based Biological Heart Age Estimation Reveals Differential Aging Patterns Across Cardiac Chambers.,"Salih AM, Pujadas ER, Campello VM, McCracken C, Harvey NC, Neubauer S, Lekadir K, Nichols TE, Petersen SE, Raisi-Estabragh Z.",,Journal of magnetic resonance imaging : JMRI,2023,2023-03-16,Y,Aging; Cardiac Imaging; Cardiac Health; Radiomics,,,"

Background

Biological heart age estimation can provide insights into cardiac aging. However, existing studies do not consider differential aging across cardiac regions.

Purpose

To estimate biological age of the left ventricle (LV), right ventricle (RV), myocardium, left atrium, and right atrium using magnetic resonance imaging radiomics phenotypes and to investigate determinants of aging by cardiac region.

Study type

Cross-sectional.

Population

A total of 18,117 healthy UK Biobank participants including 8338 men (mean age = 64.2 ± 7.5) and 9779 women (mean age = 63.0 ± 7.4).

Field strength/sequence

A 1.5 T/balanced steady-state free precession.

Assessment

An automated algorithm was used to segment the five cardiac regions, from which radiomic features were extracted. Bayesian ridge regression was used to estimate biological age of each cardiac region with radiomics features as predictors and chronological age as the output. The ""age gap"" was the difference between biological and chronological age. Linear regression was used to calculate associations of age gap from each cardiac region with socioeconomic, lifestyle, body composition, blood pressure and arterial stiffness, blood biomarkers, mental well-being, multiorgan health, and sex hormone exposures (n = 49).

Statistical test

Multiple testing correction with false discovery method (threshold = 5%).

Results

The largest model error was with RV and the smallest with LV age (mean absolute error in men: 5.26 vs. 4.96 years). There were 172 statistically significant age gap associations. Greater visceral adiposity was the strongest correlate of larger age gaps, for example, myocardial age gap in women (Beta = 0.85, P = 1.69 × 10-26 ). Poor mental health associated with large age gaps, for example, ""disinterested"" episodes and myocardial age gap in men (Beta = 0.25, P = 0.001), as did a history of dental problems (eg LV in men Beta = 0.19, P = 0.02). Higher bone mineral density was the strongest associate of smaller age gaps, for example, myocardial age gap in men (Beta = -1.52, P = 7.44 × 10-6 ).

Data conclusion

This work demonstrates image-based heart age estimation as a novel method for understanding cardiac aging.

Evidence level

1.

Technical efficacy

Stage 1.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jmri.28675; doi:https://doi.org/10.1002/jmri.28675; html:https://europepmc.org/articles/PMC10947470; pdf:https://europepmc.org/articles/PMC10947470?pdf=render -38849195,https://doi.org/10.1136/archdischild-2023-326756,Utility and acceptability of remote 6-lead electrocardiographic monitoring in children with inherited cardiac conditions.,"Lawley CM, Luczak-Wozniak K, Chung SC, Field E, Barnes A, Starling L, Cervi E, Kaski JP.",,Archives of disease in childhood,2024,2024-06-07,N,Cardiology; Paediatrics,,,"

Objective

This pilot study sought to investigate the utility and acceptability of the KardiaMobile 6-lead ECG (KM6LECG) as a tool for remote monitoring in children with inherited cardiac conditions.

Design

A single-centre prospective cohort study. Children underwent standard clinical evaluation including a 12-lead ECG and a KM6LECG in the clinic. Participants recorded KM6LECGs monthly at home for 3 months. Families completed a questionnaire on their experience.

Setting

Great Ormond Street Hospital Centre for Inherited Cardiovascular Diseases.

Participants

64 children: 22 with hypertrophic cardiomyopathy (HCM); 22 with long QT syndrome and 20 unaffected siblings (controls).

Main outcome measures

Comparison of data extracted from the clinic 12-lead ECG and supervised KM6LECG, and the supervised and unsupervised KM6LECG recording.

Results

Of 64 children (35% female, mean age 12 years), 58 had a baseline 12-lead ECG and appropriate baseline KM6LECG. In children with HCM, abnormalities in ventricular depolarisation/repolarisation in the limb leads of the 12-lead ECG were reliably reproduced. From the whole cohort, there was a strong positive correlation between the corrected QT interval from the 12-lead ECG and baseline KM6LECG (intraclass correlation coefficient=0.839) and baseline KM6LECG with an unsupervised KM6LECG (intraclass correlation coefficient=0.736). Suspected 'lead' misplacement impacted 18% of unsupervised recordings. Overall, the acceptability of the KM6LECG to families was good.

Conclusions

The KM6LECG provides an accurate tool for assessing some ECG abnormalities associated with paediatric inherited cardiovascular disease and may provide a useful at-home adjunct to face-to-face clinical care of children requiring ECG assessment.",,doi:https://doi.org/10.1136/archdischild-2023-326756 37650026,https://doi.org/10.23889/ijpds.v7i1.1727,An overview of synthetic administrative data for research.,"Kokosi T, De Stavola B, Mitra R, Frayling L, Doherty A, Dove I, Sonnenberg P, Harron K.",,International journal of population data science,2022,2022-05-23,Y,Data Linkage; Statistical Disclosure Control; Data Utility; Synthetic Data; Data Confidentiality; Administrative Datasets,,,"Use of administrative data for research and for planning services has increased over recent decades due to the value of the large, rich information available. However, concerns about the release of sensitive or personal data and the associated disclosure risk can lead to lengthy approval processes and restricted data access. This can delay or prevent the production of timely evidence. A promising solution to facilitate more efficient data access is to create synthetic versions of the original datasets which are less likely to hold confidential information and can minimise disclosure risk. Such data may be used as an interim solution, allowing researchers to develop their analysis plans on non-disclosive data, whilst waiting for access to the real data. We aim to provide an overview of the background and uses of synthetic data and describe common methods used to generate synthetic data in the context of UK administrative research. We propose a simplified terminology for categories of synthetic data (univariate, multivariate, and complex modality synthetic data) as well as a more comprehensive description of the terminology used in the existing literature and illustrate challenges and future directions for research.",,pdf:https://ijpds.org/article/download/1727/3395; doi:https://doi.org/10.23889/ijpds.v7i1.1727; html:https://europepmc.org/articles/PMC10464868; pdf:https://europepmc.org/articles/PMC10464868?pdf=render +38849195,https://doi.org/10.1136/archdischild-2023-326756,Utility and acceptability of remote 6-lead electrocardiographic monitoring in children with inherited cardiac conditions.,"Lawley CM, Luczak-Wozniak K, Chung SC, Field E, Barnes A, Starling L, Cervi E, Kaski JP.",,Archives of disease in childhood,2024,2024-06-07,N,Cardiology; Paediatrics,,,"

Objective

This pilot study sought to investigate the utility and acceptability of the KardiaMobile 6-lead ECG (KM6LECG) as a tool for remote monitoring in children with inherited cardiac conditions.

Design

A single-centre prospective cohort study. Children underwent standard clinical evaluation including a 12-lead ECG and a KM6LECG in the clinic. Participants recorded KM6LECGs monthly at home for 3 months. Families completed a questionnaire on their experience.

Setting

Great Ormond Street Hospital Centre for Inherited Cardiovascular Diseases.

Participants

64 children: 22 with hypertrophic cardiomyopathy (HCM); 22 with long QT syndrome and 20 unaffected siblings (controls).

Main outcome measures

Comparison of data extracted from the clinic 12-lead ECG and supervised KM6LECG, and the supervised and unsupervised KM6LECG recording.

Results

Of 64 children (35% female, mean age 12 years), 58 had a baseline 12-lead ECG and appropriate baseline KM6LECG. In children with HCM, abnormalities in ventricular depolarisation/repolarisation in the limb leads of the 12-lead ECG were reliably reproduced. From the whole cohort, there was a strong positive correlation between the corrected QT interval from the 12-lead ECG and baseline KM6LECG (intraclass correlation coefficient=0.839) and baseline KM6LECG with an unsupervised KM6LECG (intraclass correlation coefficient=0.736). Suspected 'lead' misplacement impacted 18% of unsupervised recordings. Overall, the acceptability of the KM6LECG to families was good.

Conclusions

The KM6LECG provides an accurate tool for assessing some ECG abnormalities associated with paediatric inherited cardiovascular disease and may provide a useful at-home adjunct to face-to-face clinical care of children requiring ECG assessment.",,doi:https://doi.org/10.1136/archdischild-2023-326756 33632765,https://doi.org/10.1136/thoraxjnl-2020-215986,"Neutrophils in asthma: the good, the bad and the bacteria.","Crisford H, Sapey E, Rogers GB, Taylor S, Nagakumar P, Lokwani R, Simpson JL.",,Thorax,2021,2021-02-25,Y,Asthma; Bacterial Infection; Paediatric Asthma; Asthma Mechanisms; Neutrophil Biology,,,"Airway inflammation plays a key role in asthma pathogenesis but is heterogeneous in nature. There has been significant scientific discovery with regard to type 2-driven, eosinophil-dominated asthma, with effective therapies ranging from inhaled corticosteroids to novel biologics. However, studies suggest that approximately 1 in 5 adults with asthma have an increased proportion of neutrophils in their airways. These patients tend to be older, have potentially pathogenic airway bacteria and do not respond well to classical therapies. Currently, there are no specific therapeutic options for these patients, such as neutrophil-targeting biologics.Neutrophils comprise 70% of the total circulatory white cells and play a critical defence role during inflammatory and infective challenges. This makes them a problematic target for therapeutics. Furthermore, neutrophil functions change with age, with reduced microbial killing, increased reactive oxygen species release and reduced production of extracellular traps with advancing age. Therefore, different therapeutic strategies may be required for different age groups of patients.The pathogenesis of neutrophil-dominated airway inflammation in adults with asthma may reflect a counterproductive response to the defective neutrophil microbial killing seen with age, resulting in bystander damage to host airway cells and subsequent mucus hypersecretion and airway remodelling. However, in children with asthma, neutrophils are less associated with adverse features of disease, and it is possible that in children, neutrophils are less pathogenic.In this review, we explore the mechanisms of neutrophil recruitment, changes in cellular function across the life course and the implications this may have for asthma management now and in the future. We also describe the prevalence of neutrophilic asthma globally, with a focus on First Nations people of Australia, New Zealand and North America.",,pdf:https://thorax.bmj.com/content/thoraxjnl/76/8/835.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2020-215986; html:https://europepmc.org/articles/PMC8311087; pdf:https://europepmc.org/articles/PMC8311087?pdf=render 35531432,https://doi.org/10.1016/s2666-7568(22)00093-9,"Outcomes of SARS-CoV-2 omicron infection in residents of long-term care facilities in England (VIVALDI): a prospective, cohort study.","Krutikov M, Stirrup O, Nacer-Laidi H, Azmi B, Fuller C, Tut G, Palmer T, Shrotri M, Irwin-Singer A, Baynton V, Hayward A, Moss P, Copas A, Shallcross L, COVID-19 Genomics UK consortium.",,The lancet. Healthy longevity,2022,2022-05-04,Y,,,,"

Background

The SARS-CoV-2 omicron variant (B.1.1.529) is highly transmissible, but disease severity appears to be reduced compared with previous variants such as alpha and delta. We investigated the risk of severe outcomes following infection in residents of long-term care facilities.

Methods

We did a prospective cohort study in residents of long-term care facilities in England who were tested regularly for SARS-CoV-2 between Sept 1, 2021, and Feb 1, 2022, and who were participants of the VIVALDI study. Residents were eligible for inclusion if they had a positive PCR or lateral flow device test during the study period, which could be linked to a National Health Service (NHS) number, enabling linkage to hospital admissions and mortality datasets. PCR or lateral flow device test results were linked to national hospital admission and mortality records using the NHS-number-based pseudo-identifier. We compared the risk of hospital admission (within 14 days following a positive SARS-CoV-2 test) or death (within 28 days) in residents who had tested positive for SARS-CoV-2 in the period shortly before omicron emerged (delta-dominant) and in the omicron-dominant period, adjusting for age, sex, primary vaccine course, past infection, and booster vaccination. Variants were confirmed by sequencing or spike-gene status in a subset of samples.

Results

795 233 tests were done in 333 long-term care facilities, of which 159 084 (20·0%) could not be linked to a pseudo-identifier and 138 012 (17·4%) were done in residents. Eight residents had two episodes of infection (>28 days apart) and in these cases the second episode was excluded from the analysis. 2264 residents in 259 long-term care facilities (median age 84·5 years, IQR 77·9-90·0) were diagnosed with SARS-CoV-2, of whom 253 (11·2%) had a previous infection and 1468 (64·8%) had received a booster vaccination. About a third of participants were male. Risk of hospital admissions was markedly lower in the 1864 residents infected in the omicron-period (4·51%, 95% CI 3·65-5·55) than in the 400 residents infected in the pre-omicron period (10·50%, 7·87-13·94), as was risk of death (5·48% [4·52-6·64] vs 10·75% [8·09-14·22]). Adjusted hazard ratios (aHR) also indicated a reduction in hospital admissions (0·64, 95% CI 0·41-1·00; p=0·051) and mortality (aHR 0·68, 0·44-1·04; p=0·076) in the omicron versus the pre-omicron period. Findings were similar in residents with a confirmed variant.

Interpretation

Observed reduced severity of the omicron variant compared with previous variants suggests that the wave of omicron infections is unlikely to lead to a major surge in severe disease in long-term care facility populations with high levels of vaccine coverage or natural immunity. Continued surveillance in this vulnerable population is important to protect residents from infection and monitor the public health effect of emerging variants.

Funding

UK Department of Health and Social Care.",,pdf:http://www.thelancet.com/article/S2666756822000939/pdf; doi:https://doi.org/10.1016/S2666-7568(22)00093-9; html:https://europepmc.org/articles/PMC9067940; pdf:https://europepmc.org/articles/PMC9067940?pdf=render 31774502,https://doi.org/10.1093/ehjcvp/pvz071,An observational study of international normalized ratio control according to NICE criteria in patients with non-valvular atrial fibrillation: the SAIL Warfarin Out of Range Descriptors Study (SWORDS).,"Harris DE, Thayer D, Wang T, Brooks C, Murley G, Gravenor M, Hill NR, Lister S, Halcox J.",,European heart journal. Cardiovascular pharmacotherapy,2021,2021-01-01,Y,Atrial fibrillation; Warfarin; Pharmacoepidemiology,Improving Public Health,,"

Aims

In patients with non-valvular atrial fibrillation prescribed warfarin, the UK National Institute of Health and Care Excellence (NICE) defines poor anticoagulation as a time in therapeutic range (TTR) of <65%, any two international normalized ratios (INRs) within a 6-month period of ≤1.5 ('low'), two INRs ≥5 within 6 months, or any INR ≥8 ('high'). Our objectives were to (i) quantify the number of patients with poor INR control and (ii) describe the demographic and clinical characteristics associated with poor INR control.

Method and results

Linked anonymized health record data for Wales, UK (2006-2017) was used to evaluate patients prescribed warfarin who had at least 6 months of INR data. 32 380 patients were included. In total, 13 913 (43.0%) patients had at least one of the NICE markers of poor INR control. Importantly, in the 24 123 (74.6%) of the cohort with an acceptable TTR (≥65%), 5676 (23.5%) had either low or high INR readings at some point in their history. In a multivariable regression female gender, age (≥75 years), excess alcohol, diabetes heart failure, ischaemic heart disease, and respiratory disease were independently associated with all markers of poor INR control.

Conclusion

Acceptable INR control according to NICE standards is poor. Of those with an acceptable TTR (>65%), one-quarter still had unacceptably low or high INR levels according to NICE criteria. Thus, only using TTR to assess effectiveness with warfarin has the potential to miss a large number of patients with non-therapeutic INRs who are likely to be at increased risk.","This retrospective observational cohort study aimed to quanitfy the number of patients with non-valvular atrial fibrillation (NVAF) prescribed warfarin who exhibit NICE-defined poor international normalised ratio (INR) control. Another objective was to describe the relationship between demographic and clinical characteristics of these patients and poor INR control. The results from statistical analyses in this study suggest a considerable opportunity to improve both embloc and bleeding risk, eben though the relationship between poor INR control and these clinical outcomes remains to be determined.",pdf:https://academic.oup.com/ehjcvp/advance-article-pdf/doi/10.1093/ehjcvp/pvz071/31700014/pvz071.pdf; doi:https://doi.org/10.1093/ehjcvp/pvz071; html:https://europepmc.org/articles/PMC7811400; pdf:https://europepmc.org/articles/PMC7811400?pdf=render @@ -691,11 +691,11 @@ PMC9644860,https://doi.org/,Maternal mental health and children’s development: 38102763,https://doi.org/10.1177/15353702231214253,Explainable hierarchical clustering for patient subtyping and risk prediction.,"Werner E, Clark JN, Hepburn A, Bhamber RS, Ambler M, Bourdeaux CP, McWilliams CJ, Santos-Rodriguez R.",,"Experimental biology and medicine (Maywood, N.J.)",2023,2023-12-15,Y,Clinical evaluation; hierarchical clustering; Mortality Prediction; Early Warning Score; Explainability; Patient Subtypes,,,"We present a pipeline in which machine learning techniques are used to automatically identify and evaluate subtypes of hospital patients admitted between 2017 and 2021 in a large UK teaching hospital. Patient clusters are determined using routinely collected hospital data, such as those used in the UK's National Early Warning Score 2 (NEWS2). An iterative, hierarchical clustering process was used to identify the minimum set of relevant features for cluster separation. With the use of state-of-the-art explainability techniques, the identified subtypes are interpreted and assigned clinical meaning, illustrating their robustness. In parallel, clinicians assessed intracluster similarities and intercluster differences of the identified patient subtypes within the context of their clinical knowledge. For each cluster, outcome prediction models were trained and their forecasting ability was illustrated against the NEWS2 of the unclustered patient cohort. These preliminary results suggest that subtype models can outperform the established NEWS2 method, providing improved prediction of patient deterioration. By considering both the computational outputs and clinician-based explanations in patient subtyping, we aim to highlight the mutual benefit of combining machine learning techniques with clinical expertise.",,doi:https://doi.org/10.1177/15353702231214253; html:https://europepmc.org/articles/PMC10854470; pdf:https://europepmc.org/articles/PMC10854470?pdf=render 36329425,https://doi.org/10.1186/s12890-022-02189-3,Derivation of asthma severity from electronic prescription records using British thoracic society treatment steps.,"Tibble H, Sheikh A, Tsanas A.",,BMC pulmonary medicine,2022,2022-11-03,Y,Asthma; Pharmacotherapy; Severity; Pharmacoepidemiology; Electronic Health Records; Treatment Guidelines,,,"

Background

Asthma severity is typically assessed through a retrospective assessment of the treatment required to control symptoms and to prevent exacerbations. The joint British Thoracic Society and Scottish Intercollegiate Guidelines Network (BTS/SIGN) guidelines encourage a stepwise approach to pharmacotherapy, and as such, current treatment step can be considered as a severity categorisation proxy. Briefly, the steps for adults can be summarised as: no controller therapy (Step 0), low-strength Inhaled Corticosteroids (ICS; Step 1), ICS plus Long-Acting Beta-2 Agonist (LABA; Step 2), medium-dose ICS + LABA (Step 3), and finally either an increase in strength or additional therapies (Step 4). This study aimed to investigate how BTS/SIGN Steps can be estimated from across a large cohort using electronic prescription records, and to describe the incidence of each BTS/SIGN Step in a general population.

Methods

There were 41,433,707 prescriptions, for 671,304 individuals, in the Asthma Learning Health System Scottish cohort, between 1/2009 and 3/2017. Days on which an individual had a prescription for at least one asthma controller (preventer) medication were labelled prescription events. A rule-based algorithm was developed for extracting the strength and volume of medication instructed to be taken daily from free-text data fields. Asthma treatment regimens were categorised by the combination of medications prescribed in the 120 days preceding any prescription event and categorised into BTS/SIGN treatment steps.

Results

Almost 4.5 million ALHS prescriptions were for asthma controllers. 26% of prescription events had no inhaled corticosteroid prescriptions in the preceding 120 days (Step 0), 16% were assigned to BTS/SIGN Step 1, 7% to Step 2, 21% to Step 3, and 30% to Step 4. The median days spent on a treatment step before a step-down in treatment was 297 days, whereas a step-up only took a median of 134 days.

Conclusion

We developed a reproducible methodology enabling researchers to estimate BTS/SIGN asthma treatment steps in population health studies, providing valuable insights into population and patient-specific trajectories, towards improving the management of asthma.",,pdf:https://bmcpulmmed.biomedcentral.com/counter/pdf/10.1186/s12890-022-02189-3; doi:https://doi.org/10.1186/s12890-022-02189-3; html:https://europepmc.org/articles/PMC9635147; pdf:https://europepmc.org/articles/PMC9635147?pdf=render 38772405,https://doi.org/10.1016/s0140-6736(24)00537-3,Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91).,"Adler AI, Coleman RL, Leal J, Whiteley WN, Clarke P, Holman RR.",,"Lancet (London, England)",2024,2024-05-17,N,,,,"

Background

The 20-year UK Prospective Diabetes Study showed major clinical benefits for people with newly diagnosed type 2 diabetes randomly allocated to intensive glycaemic control with sulfonylurea or insulin therapy or metformin therapy, compared with conventional glycaemic control. 10-year post-trial follow-up identified enduring and emerging glycaemic and metformin legacy treatment effects. We aimed to determine whether these effects would wane by extending follow-up for another 14 years.

Methods

5102 patients enrolled between 1977 and 1991, of whom 4209 (82·5%) participants were originally randomly allocated to receive either intensive glycaemic control (sulfonylurea or insulin, or if overweight, metformin) or conventional glycaemic control (primarily diet). At the end of the 20-year interventional trial, 3277 surviving participants entered a 10-year post-trial monitoring period, which ran until Sept 30, 2007. Eligible participants for this study were all surviving participants at the end of the 10-year post-trial monitoring period. An extended follow-up of these participants was done by linking them to their routinely collected National Health Service (NHS) data for another 14 years. Clinical outcomes were derived from records of deaths, hospital admissions, outpatient visits, and accident and emergency unit attendances. We examined seven prespecified aggregate clinical outcomes (ie, any diabetes-related endpoint, diabetes-related death, death from any cause, myocardial infarction, stroke, peripheral vascular disease, and microvascular disease) by the randomised glycaemic control strategy on an intention-to-treat basis using Kaplan-Meier time-to-event and log-rank analyses. This study is registered with the ISRCTN registry, number ISRCTN75451837.

Findings

Between Oct 1, 2007, and Sept 30, 2021, 1489 (97·6%) of 1525 participants could be linked to routinely collected NHS administrative data. Their mean age at baseline was 50·2 years (SD 8·0), and 41·3% were female. The mean age of those still alive as of Sept 30, 2021, was 79·9 years (SD 8·0). Individual follow-up from baseline ranged from 0 to 42 years, median 17·5 years (IQR 12·3-26·8). Overall follow-up increased by 21%, from 66 972 to 80 724 person-years. For up to 24 years after trial end, the glycaemic and metformin legacy effects showed no sign of waning. Early intensive glycaemic control with sulfonylurea or insulin therapy, compared with conventional glycaemic control, showed overall relative risk reductions of 10% (95% CI 2-17; p=0·015) for death from any cause, 17% (6-26; p=0·002) for myocardial infarction, and 26% (14-36; p<0·0001) for microvascular disease. Corresponding absolute risk reductions were 2·7%, 3·3%, and 3·5%, respectively. Early intensive glycaemic control with metformin therapy, compared with conventional glycaemic control, showed overall relative risk reductions of 20% (95% CI 5-32; p=0·010) for death from any cause and 31% (12-46; p=0·003) for myocardial infarction. Corresponding absolute risk reductions were 4·9% and 6·2%, respectively. No significant risk reductions during or after the trial for stroke or peripheral vascular disease were observed for both intensive glycaemic control groups, and no significant risk reduction for microvascular disease was observed for metformin therapy.

Interpretation

Early intensive glycaemic control with sulfonylurea or insulin, or with metformin, compared with conventional glycaemic control, appears to confer a near-lifelong reduced risk of death and myocardial infarction. Achieving near normoglycaemia immediately following diagnosis might be essential to minimise the lifetime risk of diabetes-related complications to the greatest extent possible.

Funding

University of Oxford Nuffield Department of Population Health Pump Priming.",,doi:https://doi.org/10.1016/S0140-6736(24)00537-3 -37678576,https://doi.org/10.1016/j.jaci.2023.08.025,E-cigarette vapor renders neutrophils dysfunctional due to filamentous actin accumulation.,"Jasper AE, Faniyi AA, Davis LC, Grudzinska FS, Halston R, Hazeldine J, Parekh D, Sapey E, Thickett DR, Scott A.",,The Journal of allergy and clinical immunology,2024,2023-09-05,N,Neutrophils; Phagocytosis; Oxidative burst; Nicotine; Netosis; E-cigarettes,,,"

Background

Electronic cigarette (e-cigarette) use continues to rise despite concerns of long-term effects, especially the risk of developing lung diseases such as chronic obstructive pulmonary disease. Neutrophils are central to the pathogenesis of chronic obstructive pulmonary disease, with changes in phenotype and function implicated in tissue damage.

Objective

We sought to measure the impact of direct exposure to nicotine-containing and nicotine-free e-cigarette vapor on human neutrophil function and phenotype.

Methods

Neutrophils were isolated from the whole blood of self-reported nonsmoking, nonvaping healthy volunteers. Neutrophils were exposed to 40 puffs of e-cigarette vapor generated from e-cigarette devices using flavorless e-cigarette liquids with and without nicotine before functions, deformability, and phenotype were assessed.

Results

Neutrophil surface marker expression was altered, with CD62L and CXCR2 expression significantly reduced in neutrophils treated with e-cigarette vapor containing nicotine. Neutrophil migration to IL-8, phagocytosis of Escherichia coli and Staphylococcus aureus pHrodo bioparticles, oxidative burst response, and phorbol 12-myristate 13-acetate-stimulated neutrophil extracellular trap formation were all significantly reduced by e-cigarette vapor treatments, independent of nicotine content. E-cigarette vapor induced increased levels of baseline polymerized filamentous actin levels in the cytoplasm, compared with untreated controls.

Conclusions

The significant reduction in effector neutrophil functions after exposure to high-power e-cigarette devices, even in the absence of nicotine, is associated with excessive filamentous actin polymerization. This highlights the potentially damaging impact of vaping on respiratory health and reinforces the urgency of research to uncover the long-term health implications of e-cigarettes.",,doi:https://doi.org/10.1016/j.jaci.2023.08.025 35443953,https://doi.org/10.1136/bmjopen-2021-056523,Can we accurately forecast non-elective bed occupancy and admissions in the NHS? A time-series MSARIMA analysis of longitudinal data from an NHS Trust.,"Eyles E, Redaniel MT, Jones T, Prat M, Keen T.",,BMJ open,2022,2022-04-20,Y,epidemiology; Statistics & Research Methods; Health Services Administration & Management; Accident & Emergency Medicine,,,"

Objectives

The main objective of the study was to develop more accurate and precise short-term forecasting models for admissions and bed occupancy for an NHS Trust located in Bristol, England. Subforecasts for the medical and surgical specialties, and for different lengths of stay were realised DESIGN: Autoregressive integrated moving average models were specified on a training dataset of daily count data, then tested on a 6-week forecast horizon. Explanatory variables were included in the models: day of the week, holiday days, lagged temperature and precipitation.

Setting

A secondary care hospital in an NHS Trust in South West England.

Participants

Hospital admissions between September 2016 and March 2020, comprising 1291 days.

Primary and secondary outcome measures

The accuracy of the forecasts was assessed through standard measures, as well as compared with the actual data using accuracy thresholds of 10% and 20% of the mean number of admissions or occupied beds.

Results

The overall Autoregressive Integrated Moving Average (ARIMA) admissions forecast was compared with the Trust's forecast, and found to be more accurate, namely, being closer to the actual value 95.6% of the time. Furthermore, it was more precise than the Trust's. The subforecasts, as well as those for bed occupancy, tended to be less accurate compared with the overall forecasts. All of the explanatory variables improved the forecasts.

Conclusions

ARIMA models can forecast non-elective admissions in an NHS Trust accurately on a 6-week horizon, which is an improvement on the current predictive modelling in the Trust. These models can be readily applied to other contexts, improving patient flow.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e056523.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-056523; html:https://europepmc.org/articles/PMC9021768; pdf:https://europepmc.org/articles/PMC9021768?pdf=render +37678576,https://doi.org/10.1016/j.jaci.2023.08.025,E-cigarette vapor renders neutrophils dysfunctional due to filamentous actin accumulation.,"Jasper AE, Faniyi AA, Davis LC, Grudzinska FS, Halston R, Hazeldine J, Parekh D, Sapey E, Thickett DR, Scott A.",,The Journal of allergy and clinical immunology,2024,2023-09-05,N,Neutrophils; Phagocytosis; Oxidative burst; Nicotine; Netosis; E-cigarettes,,,"

Background

Electronic cigarette (e-cigarette) use continues to rise despite concerns of long-term effects, especially the risk of developing lung diseases such as chronic obstructive pulmonary disease. Neutrophils are central to the pathogenesis of chronic obstructive pulmonary disease, with changes in phenotype and function implicated in tissue damage.

Objective

We sought to measure the impact of direct exposure to nicotine-containing and nicotine-free e-cigarette vapor on human neutrophil function and phenotype.

Methods

Neutrophils were isolated from the whole blood of self-reported nonsmoking, nonvaping healthy volunteers. Neutrophils were exposed to 40 puffs of e-cigarette vapor generated from e-cigarette devices using flavorless e-cigarette liquids with and without nicotine before functions, deformability, and phenotype were assessed.

Results

Neutrophil surface marker expression was altered, with CD62L and CXCR2 expression significantly reduced in neutrophils treated with e-cigarette vapor containing nicotine. Neutrophil migration to IL-8, phagocytosis of Escherichia coli and Staphylococcus aureus pHrodo bioparticles, oxidative burst response, and phorbol 12-myristate 13-acetate-stimulated neutrophil extracellular trap formation were all significantly reduced by e-cigarette vapor treatments, independent of nicotine content. E-cigarette vapor induced increased levels of baseline polymerized filamentous actin levels in the cytoplasm, compared with untreated controls.

Conclusions

The significant reduction in effector neutrophil functions after exposure to high-power e-cigarette devices, even in the absence of nicotine, is associated with excessive filamentous actin polymerization. This highlights the potentially damaging impact of vaping on respiratory health and reinforces the urgency of research to uncover the long-term health implications of e-cigarettes.",,doi:https://doi.org/10.1016/j.jaci.2023.08.025 35383067,https://doi.org/10.1136/bmjopen-2021-055447,Potentially avoidable causes of hospitalisation in people with dementia: contemporaneous associations by stage of dementia in a South London clinical cohort.,"Gungabissoon U, Perera G, Galwey NW, Stewart R.",,BMJ open,2022,2022-04-05,Y,Dementia; epidemiology; Old Age Psychiatry,,,"

Objectives

To estimate the frequency of all-cause and ambulatory care sensitive condition (ACSCs)-related hospitalisations among individuals with dementia. In addition, to investigate differences by stage of dementia based on recorded cognitive function.

Setting

Data from a large London dementia care clinical case register, linked to a national hospitalisation database.

Participants

Individuals aged ≥65 years with a confirmed dementia diagnosis with recorded cognitive function.

Outcome measures

Acute general hospital admissions were evaluated within 6 months of a randomly selected cognitive function score in patients with a clinical diagnosis of dementia. To evaluate associations between ACSC-related hospital admissions (overall and individual ACSCs) and stage of dementia, an ordinal regression was performed, modelling stage of dementia as the dependant variable (to facilitate efficient model selection, with no implication concerning the direction of causality).

Results

Of the 5294 people with dementia, 2993 (56.5%) had at least one hospitalisation during a 12-month period of evaluation, and 1192 (22.5%) had an ACSC-related admission. Proportions with an all-cause or ACSC-related hospitalisation were greater in the groups with more advanced dementia (all-cause 53.9%, 57.1% and 60.9%, p 0.002; ACSC-related 19.5%, 24.0% and 25.3%, p<0.0001 in the mild, moderate and severe groups, respectively). An ACSC-related admission was associated with 1.3-fold (95% CI 1.1 to 1.5) increased odds of more severe dementia after adjusting for demographic factors. Concerning admissions for individual ACSCs, the most common ACSC was urinary tract infection /pyelonephritis (9.8% of hospitalised patients) followed by pneumonia (7.1%); in an adjusted model, these were each associated with 1.4-fold increased odds of more severe dementia (95% CI 1.2 to 1.7 and 1.1 to 1.7, respectively).

Conclusions

Potentially avoidable hospitalisations were common in people with dementia, particularly in those with greater cognitive impairment. Our results call for greater attention to the extent of cognitive status impairment, and not just dementia diagnosis, when evaluating measures to reduce the risk of potentially avoidable hospitalisations.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e055447.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055447; html:https://europepmc.org/articles/PMC8984034; pdf:https://europepmc.org/articles/PMC8984034?pdf=render -38689316,https://doi.org/10.1186/s13643-024-02540-1,Correction: Patient‑reported outcome (PRO) instruments used in patients undergoing adoptive cell therapy (ACT) for the treatment of cancer: a systematic review.,"Taylor S, Law K, Coomber-Moore J, Davies M, Thistlethwaite F, Calvert M, Aiyegbusi O, Yorke J.",,Systematic reviews,2024,2024-04-30,Y,,,,,,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-024-02540-1; doi:https://doi.org/10.1186/s13643-024-02540-1; html:https://europepmc.org/articles/PMC11059719; pdf:https://europepmc.org/articles/PMC11059719?pdf=render 37398988,https://doi.org/10.1007/s40258-023-00821-9,Correction to: The False Economy of Seeking to Eliminate Delayed Transfers of Care: Some Lessons from Queueing Theory.,"Wood RM, Harper AL, Onen-Dumlu Z, Forte PG, Pitt M, Vasilakis C.",,Applied health economics and health policy,2023,2023-09-01,Y,,,,,,pdf:https://link.springer.com/content/pdf/10.1007/s40258-023-00821-9.pdf; doi:https://doi.org/10.1007/s40258-023-00821-9; html:https://europepmc.org/articles/PMC10403424; pdf:https://europepmc.org/articles/PMC10403424?pdf=render +38689316,https://doi.org/10.1186/s13643-024-02540-1,Correction: Patient‑reported outcome (PRO) instruments used in patients undergoing adoptive cell therapy (ACT) for the treatment of cancer: a systematic review.,"Taylor S, Law K, Coomber-Moore J, Davies M, Thistlethwaite F, Calvert M, Aiyegbusi O, Yorke J.",,Systematic reviews,2024,2024-04-30,Y,,,,,,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-024-02540-1; doi:https://doi.org/10.1186/s13643-024-02540-1; html:https://europepmc.org/articles/PMC11059719; pdf:https://europepmc.org/articles/PMC11059719?pdf=render PMC9645061,https://doi.org/,Using population-scale medication data to evaluate the impact of the COVID-19 pandemic on the usage of analgesics by cancer patients.,"Han J, Akbari A, Torabi F, Griffiths R, Lyons J, Rolles M, Arnold C, Huws D, Lawler M, Lyons R.",,International journal of population data science,,2022-11-25,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645061/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645061/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9645061; pdf:https://europepmc.org/articles/PMC9645061?pdf=render 36680646,https://doi.org/10.1007/s10654-022-00962-6,Characterising patterns of COVID-19 and long COVID symptoms: evidence from nine UK longitudinal studies.,"Bowyer RCE, Huggins C, Toms R, Shaw RJ, Hou B, Thompson EJ, Kwong ASF, Williams DM, Kibble M, Ploubidis GB, Timpson NJ, Sterne JAC, Chaturvedi N, Steves CJ, Tilling K, Silverwood RJ, CONVALESCENCE Study.",,European journal of epidemiology,2023,2023-01-21,Y,Clustering; Longitudinal Studies; Symptom Patterns; Covid-19; Long Covid,,,"Multiple studies across global populations have established the primary symptoms characterising Coronavirus Disease 2019 (COVID-19) and long COVID. However, as symptoms may also occur in the absence of COVID-19, a lack of appropriate controls has often meant that specificity of symptoms to acute COVID-19 or long COVID, and the extent and length of time for which they are elevated after COVID-19, could not be examined. We analysed individual symptom prevalences and characterised patterns of COVID-19 and long COVID symptoms across nine UK longitudinal studies, totalling over 42,000 participants. Conducting latent class analyses separately in three groups ('no COVID-19', 'COVID-19 in last 12 weeks', 'COVID-19 > 12 weeks ago'), the data did not support the presence of more than two distinct symptom patterns, representing high and low symptom burden, in each group. Comparing the high symptom burden classes between the 'COVID-19 in last 12 weeks' and 'no COVID-19' groups we identified symptoms characteristic of acute COVID-19, including loss of taste and smell, fatigue, cough, shortness of breath and muscle pains or aches. Comparing the high symptom burden classes between the 'COVID-19 > 12 weeks ago' and 'no COVID-19' groups we identified symptoms characteristic of long COVID, including fatigue, shortness of breath, muscle pain or aches, difficulty concentrating and chest tightness. The identified symptom patterns among individuals with COVID-19 > 12 weeks ago were strongly associated with self-reported length of time unable to function as normal due to COVID-19 symptoms, suggesting that the symptom pattern identified corresponds to long COVID. Building the evidence base regarding typical long COVID symptoms will improve diagnosis of this condition and the ability to elicit underlying biological mechanisms, leading to better patient access to treatment and services.",,pdf:https://link.springer.com/content/pdf/10.1007/s10654-022-00962-6.pdf; doi:https://doi.org/10.1007/s10654-022-00962-6; html:https://europepmc.org/articles/PMC9860244; pdf:https://europepmc.org/articles/PMC9860244?pdf=render 34240125,https://doi.org/10.1093/clinchem/hvab109,Sex Differences in Cardiac Troponin I and T and the Prediction of Cardiovascular Events in the General Population.,"Kimenai DM, Shah ASV, McAllister DA, Lee KK, Tsanas A, Meex SJR, Porteous DJ, Hayward C, Campbell A, Sattar N, Mills NL, Welsh P.",,Clinical chemistry,2021,2021-10-01,Y,Sex; cardiac troponin; Cardiovascular events; risk factors,,,"

Background

Cardiac troponin concentrations differ in women and men, but how this influences risk prediction and whether a sex-specific approach is required is unclear. We evaluated whether sex influences the predictive ability of cardiac troponin I and T for cardiovascular events in the general population.

Methods

High-sensitivity cardiac troponin (hs-cTn) I and T were measured in the Generation Scotland Scottish Family Health Study of randomly selected volunteers drawn from the general population between 2006 and 2011. Cox-regression models evaluated associations between hs-cTnI and hs-cTnT and the primary outcome of cardiovascular death, myocardial infarction, or stroke.

Results

In 19 501 (58% women, mean age 47 years) participants, the primary outcome occurred in 2.7% (306/11 375) of women and 5.1% (411/8126) of men during the median follow-up period of 7.9 (IQR, 7.1-9.2) years. Cardiac troponin I and T concentrations were lower in women than men (P < 0.001 for both), and both were more strongly associated with cardiovascular events in women than men. For example, at a hs-cTnI concentration of 10 ng/L, the hazard ratio relative to the limit of blank was 9.7 (95% CI 7.6-12.4) and 5.6 (95% CI 4.7-6.6) for women and men, respectively. The hazard ratio for hs-cTnT at a concentration of 10 ng/L relative to the limit of blank was 3.7 (95% CI 3.1-4.3) and 2.2 (95% CI 2.0-2.5) for women and men, respectively.

Conclusions

Cardiac troponin concentrations differ in women and men and are stronger predictors of cardiovascular events in women. Sex-specific approaches are required to provide equivalent risk prediction.",,pdf:https://academic.oup.com/clinchem/article-pdf/67/10/1351/40494927/hvab109.pdf; doi:https://doi.org/10.1093/clinchem/hvab109; html:https://europepmc.org/articles/PMC8486023; pdf:https://europepmc.org/articles/PMC8486023?pdf=render @@ -707,8 +707,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 38022395,https://doi.org/10.1088/2515-7620/acf81b,How to estimate carbon footprint when training deep learning models? A guide and review.,"Bouza L, Bugeau A, Lannelongue L.",,Environmental research communications,2023,2023-11-21,Y,Ai Carbon Footprint; Environmental Impacts Of Deep Learning; Measuring Electrical Consumption Of Ai,,,"Machine learning and deep learning models have become essential in the recent fast development of artificial intelligence in many sectors of the society. It is now widely acknowledge that the development of these models has an environmental cost that has been analyzed in many studies. Several online and software tools have been developed to track energy consumption while training machine learning models. In this paper, we propose a comprehensive introduction and comparison of these tools for AI practitioners wishing to start estimating the environmental impact of their work. We review the specific vocabulary, the technical requirements for each tool. We compare the energy consumption estimated by each tool on two deep neural networks for image processing and on different types of servers. From these experiments, we provide some advice for better choosing the right tool and infrastructure.",,doi:https://doi.org/10.1088/2515-7620/acf81b; html:https://europepmc.org/articles/PMC10661046; pdf:https://europepmc.org/articles/PMC10661046?pdf=render 31594227,https://doi.org/10.3233/jad-190571,Partner Bereavement and Detection of Dementia: A UK-Based Cohort Study Using Routine Health Data.,"Forbes HJ, Wong AYS, Morton C, Bhaskaran K, Smeeth L, Richards M, Schmidt SAJ, Langan SM, Warren-Gash C.",,Journal of Alzheimer's disease : JAD,2019,2019-01-01,Y,Diagnosis; Dementia; epidemiology; Bereavement; Clinical Practice Research Datalink,"Improving Public Health, Understanding the Causes of Disease",,"

Background

In the UK, an estimated one third of people with dementia have not received a diagnosis. Good evidence suggests that dementia risk is increased among widowed individuals; however, it is not clear if they are being diagnosed in routine primary care.

Objective

This study aimed to investigate if bereavement influenced the probability of having received a dementia diagnosis.

Methods

A population-based cohort study using UK electronic health records, between 1997 and 2017, among 247,586 opposite-sex partners. Those experiencing partner bereavement were matched (age, sex, and date of bereavement) to a non-bereaved person living in a partnership. Multivariate cox regression was performed.

Results

Partner bereavement was associated with an increased risk of receiving a diagnosis of dementia in the first three months (hazard ratio (HR) 1.43, 95% CI 1.20-1.71) and first six months (HR 1.24, 95% CI 1.09-1.41), while there was a small reduced risk of getting a dementia diagnosis over all follow-up (HR 0.94, 95% CI 0.89-0.98).

Conclusions

Partner bereavement appears to lead to a short-term increased risk of the surviving partner receiving a diagnosis of dementia, suggesting that bereavement unmasks existing undiagnosed dementia. Over the longer term, however, bereaved individuals are less likely to have a diagnosis of dementia in their health records than non-bereaved individuals.",,pdf:https://europepmc.org/articles/pmc6918907?pdf=render; doi:https://doi.org/10.3233/JAD-190571; html:https://europepmc.org/articles/PMC6918907; pdf:https://europepmc.org/articles/PMC6918907?pdf=render 34842128,https://doi.org/10.1192/j.eurpsy.2021.2255,Investigating the association between physical health comorbidities and disability in individuals with severe mental illness.,"Mirza L, Das-Munshi J, Chaturvedi J, Wu H, Kraljevic Z, Searle T, Shaari S, Mascio A, Skiada N, Roberts A, Bean D, Stewart R, Dobson R, Bendayan R.",,European psychiatry : the journal of the Association of European Psychiatrists,2021,2021-11-29,Y,Schizophrenia; Bipolar disorder; Electronic Health Records; Multimorbidity; Health Of Nations Outcome Scale,,,"

Background

Research suggests that an increased risk of physical comorbidities might have a key role in the association between severe mental illness (SMI) and disability. We examined the association between physical multimorbidity and disability in individuals with SMI.

Methods

Data were extracted from the clinical record interactive search system at South London and Maudsley Biomedical Research Centre. Our sample (n = 13,933) consisted of individuals who had received a primary or secondary SMI diagnosis between 2007 and 2018 and had available data for Health of Nations Outcome Scale (HoNOS) as disability measure. Physical comorbidities were defined using Chapters II-XIV of the International Classification of Diagnoses (ICD-10).

Results

More than 60 % of the sample had complex multimorbidity. The most common organ system affected were neurological (34.7%), dermatological (15.4%), and circulatory (14.8%). All specific comorbidities (ICD-10 Chapters) were associated with higher levels of disability, HoNOS total scores. Individuals with musculoskeletal, skin/dermatological, respiratory, endocrine, neurological, hematological, or circulatory disorders were found to be associated with significant difficulties associated with more than five HoNOS domains while others had a lower number of domains affected.

Conclusions

Individuals with SMI and musculoskeletal, skin/dermatological, respiratory, endocrine, neurological, hematological, or circulatory disorders are at higher risk of disability compared to those who do not have those comorbidities. Individuals with SMI and physical comorbidities are at greater risk of reporting difficulties associated with activities of daily living, hallucinations, and cognitive functioning. Therefore, these should be targeted for prevention and intervention programs.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/F22DF5FD826B1626B9873013DBAFF82B/S0924933821022550a.pdf/div-class-title-investigating-the-association-between-physical-health-comorbidities-and-disability-in-individuals-with-severe-mental-illness-div.pdf; doi:https://doi.org/10.1192/j.eurpsy.2021.2255; html:https://europepmc.org/articles/PMC8727716; pdf:https://europepmc.org/articles/PMC8727716?pdf=render -38216198,https://doi.org/10.1136/bmjopen-2023-080410,"Rationale and design of the THIRST Alert feasibility study: a pragmatic, single-centre, parallel-group randomised controlled trial of an interruptive alert for oral fluid restriction in patients treated with intravenous furosemide.","Chen Y, Shah A, Jani Y, Higgins D, Saleem N, Chafer K, Sydes MR, Asselbergs FW, Lumbers RT.",,BMJ open,2024,2024-01-11,Y,Randomized controlled trial; Heart Failure; Electronic Health Records; Feasibility Studies,,,"

Introduction

Acute heart failure (HF) is a major cause of unplanned hospitalisation characterised by excess body water. A restriction in oral fluid intake is commonly imposed on patients as an adjunct to pharmacological therapy with loop diuretics, but there is a lack of evidence from traditional randomised controlled trials (RCTs) to support the safety and effectiveness of this intervention in the acute setting.This study aims to explore the feasibility of using computer alerts within the electronic health record (EHR) system to invite clinical care teams to enrol patients into a pragmatic RCT at the time of clinical decision-making. It will additionally assess the effectiveness of using an alert to help address the clinical research question of whether oral fluid restriction is a safe and effective adjunct to pharmacological therapy for patients admitted with fluid overload.

Methods and analysis

THIRST (Randomised Controlled Trial within the electronic Health record of an Interruptive alert displaying a fluid Restriction Suggestion in patients with the treatable Trait of congestion) Alert is a single-centre, parallel-group, open-label pragmatic RCT embedded in the EHR system that will be conducted as a feasibility study at an National Health Service (NHS) hospital in London. The clinical care team will be invited to enrol suitable patients in the study using a point-of-care alert with a target sample size of 50 patients. Enrolled patients will then be randomised to either restricted or unrestricted oral fluid intake. Two primary outcomes will be explored (1) the proportion of eligible patients enrolled in the study and (2) the mean difference in oral fluid intake between randomised groups. A series of secondary outcomes are specified to evaluate the effectiveness of the alert, adherence to the randomised treatment allocation and the quality of data generated from routine care, relevant to the outcomes of interest.

Ethics and dissemination

This study was approved by Riverside Research Ethics Committee (Ref: 22/LO/0889) and will be published on completion.

Trial registration number

NCT05869656.",,pdf:https://bmjopen.bmj.com/content/bmjopen/14/1/e080410.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-080410; html:https://europepmc.org/articles/PMC10806795; pdf:https://europepmc.org/articles/PMC10806795?pdf=render 37667866,https://doi.org/10.1111/cen.14966,Genetically predicted plasma cortisol and common chronic diseases: A Mendelian randomization study.,"Lee WH, Larsson SC, Wood A, Di Angelantonio E, Butterworth AS, Burgess S, Allara E.",,Clinical endocrinology,2024,2023-09-05,Y,Hypertension; Cortisol; Osteoporosis; Type 2 diabetes; chronic diseases; Mendelian Randomization; Major Mental Illness,,,"

Objective

Cushing's syndrome is characterized by hypercortisolaemia and is frequently accompanied by comorbidities such as type 2 diabetes, hypertension, osteoporosis, depression and schizophrenia. It is unclear whether moderate but lifelong hypercortisolaemia is causally associated with these diseases in the general population. We aimed to address this research gap using a Mendelian randomization approach.

Methods

We used three cortisol-associated genetic variants in the SERPINA6/SERPINA1 region as genetic instruments in a two-sample, inverse-variance-weighted Mendelian randomization analysis. We obtained summary-level statistics for cortisol and disease outcomes from publicly available genetic consortia, and meta-analysed them as appropriate. We conducted a multivariable Mendelian randomization analysis to assess potential mediating effects.

Results

A 1 standard deviation higher genetically predicted plasma cortisol was associated with greater odds of hypertension (odds ratio: 1.12; 95% confidence interval [CI]: 1.05-1.18) as well as higher systolic blood pressure (mean difference [MD]: 0.03 SD change; 95% CI: 0.01-0.05) and diastolic blood pressure (MD: 0.03 SD change; 95% CI: 0.01-0.04). There was no evidence of association with type 2 diabetes, osteoporosis, depression and schizophrenia. The association with hypertension was attenuated upon adjustment for waist circumference, suggesting potential mediation through central obesity.

Conclusion

There is strong evidence for a causal association between plasma cortisol and greater risk for hypertension, potentially mediated by obesity.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cen.14966; doi:https://doi.org/10.1111/cen.14966; html:https://europepmc.org/articles/PMC7615603; pdf:https://europepmc.org/articles/PMC7615603?pdf=render +38216198,https://doi.org/10.1136/bmjopen-2023-080410,"Rationale and design of the THIRST Alert feasibility study: a pragmatic, single-centre, parallel-group randomised controlled trial of an interruptive alert for oral fluid restriction in patients treated with intravenous furosemide.","Chen Y, Shah A, Jani Y, Higgins D, Saleem N, Chafer K, Sydes MR, Asselbergs FW, Lumbers RT.",,BMJ open,2024,2024-01-11,Y,Randomized controlled trial; Heart Failure; Electronic Health Records; Feasibility Studies,,,"

Introduction

Acute heart failure (HF) is a major cause of unplanned hospitalisation characterised by excess body water. A restriction in oral fluid intake is commonly imposed on patients as an adjunct to pharmacological therapy with loop diuretics, but there is a lack of evidence from traditional randomised controlled trials (RCTs) to support the safety and effectiveness of this intervention in the acute setting.This study aims to explore the feasibility of using computer alerts within the electronic health record (EHR) system to invite clinical care teams to enrol patients into a pragmatic RCT at the time of clinical decision-making. It will additionally assess the effectiveness of using an alert to help address the clinical research question of whether oral fluid restriction is a safe and effective adjunct to pharmacological therapy for patients admitted with fluid overload.

Methods and analysis

THIRST (Randomised Controlled Trial within the electronic Health record of an Interruptive alert displaying a fluid Restriction Suggestion in patients with the treatable Trait of congestion) Alert is a single-centre, parallel-group, open-label pragmatic RCT embedded in the EHR system that will be conducted as a feasibility study at an National Health Service (NHS) hospital in London. The clinical care team will be invited to enrol suitable patients in the study using a point-of-care alert with a target sample size of 50 patients. Enrolled patients will then be randomised to either restricted or unrestricted oral fluid intake. Two primary outcomes will be explored (1) the proportion of eligible patients enrolled in the study and (2) the mean difference in oral fluid intake between randomised groups. A series of secondary outcomes are specified to evaluate the effectiveness of the alert, adherence to the randomised treatment allocation and the quality of data generated from routine care, relevant to the outcomes of interest.

Ethics and dissemination

This study was approved by Riverside Research Ethics Committee (Ref: 22/LO/0889) and will be published on completion.

Trial registration number

NCT05869656.",,pdf:https://bmjopen.bmj.com/content/bmjopen/14/1/e080410.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-080410; html:https://europepmc.org/articles/PMC10806795; pdf:https://europepmc.org/articles/PMC10806795?pdf=render 38434152,https://doi.org/10.5334/gh.1298,Characterization of Non-Ischemic Dilated Cardiomyopathy in a Native Tanzanian Cohort: MOYO Study.,"Fundikira LS, Chillo P, Alimohamed MZ, Mayala H, Kifai E, Aloyce GM, Kamuhabwa A, Kwesigabo G, van Laake LW, Asselbergs FW.",,Global heart,2024,2024-02-29,Y,Echocardiography; Heart Failure; Non-ischemic Dilated Cardiomyopathy,,,"

Background

Non-ischemic dilated cardiomyopathy (NIDCM) is a common cause of heart failure with progressive tendency. The disease occurs in one in every 2,500 individuals in the developed world, with high morbidity and mortality. However, detailed data on the role of NIDCM in heart failure in Tanzania is lacking.

Aim

To characterize NIDCM in a Tanzanian cohort with respect to demographics, clinical profile, imaging findings and management.

Methods

Characterization of non-ischemic dilated cardioMyOpathY in a native Tanzanian cOhort (MOYO) is a prospective cohort study of NIDCM patients seen at the Jakaya Kikwete Cardiac Institute. Patients aged ≥18 years with a clinical diagnosis of heart failure, an ejection fraction of ≤45% on echocardiography and no evidence of ischemia were enrolled. Clinical data, echocardiography, electrocardiography (ECG), coronary angiography and stress ECG information were collected from February 2020 to March 2022.

Results

Of 402 patients, n = 220 (54.7%) were males with a median (IQR) age of 55.0 (41.0, 66.0) years. Causes of NIDCM were presumably hypertensive n = 218 (54.2%), idiopathic n = 116 (28.9%), PPCM n = 45 (11.2%), alcoholic n = 10 (2.5%) and other causes n = 13 (3.2%). The most common presenting symptoms were dyspnea n = 342 (85.1%), with the majority of patients presenting with New York Heart Association (NYHA) Class III n = 195 (48.5%). The mean (SD) left ventricular ejection fraction (LVEF) was 29.4% (±7.7), and severe systolic dysfunction (LVEF <30%) was common n = 208 (51.7%). Compared with other forms of DCM, idiopathic DCM patients were significantly younger, had more advanced NYHA class (p < 0.001) and presented more often with left bundle branch block on ECG (p = 0.0042). There was suboptimal use of novel guidelines recommended medications ARNI n = 10 (2.5%) and SGLT2 2-inhibitors n = 2 (0.5%).

Conclusions

In our Tanzanian cohort, the majority of patients with NIDCM have an identified underlying cause, and they present at late stages of the disease. Patients with idiopathic DCM are younger with more severe disease compared to other forms of NIDCM.",,doi:https://doi.org/10.5334/gh.1298; html:https://europepmc.org/articles/PMC10906337; pdf:https://europepmc.org/articles/PMC10906337?pdf=render 35814295,https://doi.org/10.1038/s43856-022-00146-z,Machine learning to support visual auditing of home-based lateral flow immunoassay self-test results for SARS-CoV-2 antibodies.,"Wong NCK, Meshkinfamfard S, Turbé V, Whitaker M, Moshe M, Bardanzellu A, Dai T, Pignatelli E, Barclay W, Darzi A, Elliott P, Ward H, Tanaka RJ, Cooke GS, McKendry RA, Atchison CJ, Bharath AA.",,Communications medicine,2022,2022-07-06,Y,Databases; Public Health,,,"

Background

Lateral flow immunoassays (LFIAs) are being used worldwide for COVID-19 mass testing and antibody prevalence studies. Relatively simple to use and low cost, these tests can be self-administered at home, but rely on subjective interpretation of a test line by eye, risking false positives and false negatives. Here, we report on the development of ALFA (Automated Lateral Flow Analysis) to improve reported sensitivity and specificity.

Methods

Our computational pipeline uses machine learning, computer vision techniques and signal processing algorithms to analyse images of the Fortress LFIA SARS-CoV-2 antibody self-test, and subsequently classify results as invalid, IgG negative and IgG positive. A large image library of 595,339 participant-submitted test photographs was created as part of the REACT-2 community SARS-CoV-2 antibody prevalence study in England, UK. Alongside ALFA, we developed an analysis toolkit which could also detect device blood leakage issues.

Results

Automated analysis showed substantial agreement with human experts (Cohen's kappa 0.90-0.97) and performed consistently better than study participants, particularly for weak positive IgG results. Specificity (98.7-99.4%) and sensitivity (90.1-97.1%) were high compared with visual interpretation by human experts (ranges due to the varying prevalence of weak positive IgG tests in datasets).

Conclusions

Given the potential for LFIAs to be used at scale in the COVID-19 response (for both antibody and antigen testing), even a small improvement in the accuracy of the algorithms could impact the lives of millions of people by reducing the risk of false-positive and false-negative result read-outs by members of the public. Our findings support the use of machine learning-enabled automated reading of at-home antibody lateral flow tests as a tool for improved accuracy for population-level community surveillance.",,pdf:https://www.nature.com/articles/s43856-022-00146-z.pdf; doi:https://doi.org/10.1038/s43856-022-00146-z; html:https://europepmc.org/articles/PMC9259560; pdf:https://europepmc.org/articles/PMC9259560?pdf=render 33933206,https://doi.org/10.1016/s0140-6736(21)00676-0,"Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2021,2021-05-01,Y,,,,"

Background

In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation.

Methods

This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg-800 mg (depending on weight) given intravenously. A second dose could be given 12-24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76-0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12-1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77-0·92; p<0·0001).

Interpretation

In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,pdf:https://aura.abdn.ac.uk/bitstream/2164/16630/1/Recovery_etal_TL_Tocilizumab_In_Patients_VoR.pdf; doi:https://doi.org/10.1016/S0140-6736(21)00676-0; html:https://europepmc.org/articles/PMC8084355 @@ -720,20 +720,20 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 33952557,https://doi.org/10.1136/bmjopen-2021-049964,Study protocol of the Edinburgh and Lothian Virus Intervention Study in Kids: a randomised controlled trial of hypertonic saline nose drops in children with upper respiratory tract infections (ELVIS Kids).,"Ramalingam S, Graham C, Oatey K, Rayson P, Stoddart A, Sheikh A, Cunningham S, ELVIS Kids Trial Investigators.",,BMJ open,2021,2021-05-05,Y,Virology; Community Child Health; Neonatology; Primary Care; Paediatric Infectious Disease & Immunisation,,,"

Introduction

Edinburgh and Lothians' Viral Intervention Study Kids is a parallel, open-label, randomised controlled trial of hypertonic saline (HS) nose drops (~2.6% sodium chloride) vs standard care in children <7 years of age with symptoms of an upper respiratory tract infection (URTI).

Methods and analysis

Children are recruited prior to URTI or within 48 hours of developing URTI symptoms by advertising in areas such as local schools/nurseries, health centres/hospitals, recreational facilities, public events, workplaces, local/social media. Willing parents/guardians, of children <7 years of age will be asked to contact the research team at their local site. Children will be randomised to either a control arm (standard symptomatic care), or intervention arm (three drops/nostril of HS, at least four times a day, until 24 hours after asymptomatic or a maximum of 28 days). All participants are requested to provide a nasal swab at the start of the study (intervention arm: before HS drops) and then daily for four more days. Parent/guardian complete a validated daily diary, an end of illness diary, a satisfaction questionnaire and a wheeze questionnaire (day 28). The parent/guardian of a child in the intervention arm is taught to prepare HS nose drops. Parent/guardian of children asymptomatic at recruitment are requested to inform the research team within 48 hours of their child developing an URTI and follow the instructions already provided. The day 28 questionnaire determines if the child experienced a wheeze following illness. Participation in the study ends on day 28.

Ethics and dissemination

The study has been approved by the West of Scotland Research Ethics Service (18/WS/0080). It is cosponsored by Academic and Clinical Central Office for Research and Development-a partnership between the University of Edinburgh and National Health Service Lothian Health Board. The findings will be disseminated through peer-reviewed publications, conference presentations and via the study website.

Trial registration number

NCT03463694.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/5/e049964.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049964; html:https://europepmc.org/articles/PMC8103393; pdf:https://europepmc.org/articles/PMC8103393?pdf=render 35835543,https://doi.org/10.1136/heartjnl-2022-321196,Eligibility for early rhythm control in patients with atrial fibrillation in the UK Biobank.,"Kany S, Cardoso VR, Bravo L, Williams JA, Schnabel R, Fabritz L, Gkoutos GV, Kirchhof P.",,Heart (British Cardiac Society),2022,2022-11-10,Y,Atrial fibrillation; Stroke; Catheter ablation,,,"

Objective

The Early Treatment of Atrial Fibrillation for Stroke Prevention (EAST-AFNET4) trial showed a clinical benefit of early rhythm-control therapy in patients with recently diagnosed atrial fibrillation (AF). The generalisability of the results in the general population is not known.

Methods

Participants in the population-based UK Biobank were assessed for eligibility based on the EAST-AFNET4 inclusion/exclusion criteria. Treatment of all eligible participants was classified as early rhythm-control (antiarrhythmic drug therapy or AF ablation) or usual care. To assess treatment effects, primary care data and Hospital Episode Statistics were merged with UK Biobank data.Efficacy and safety outcomes were compared between groups in the entire cohort and in a propensity-matched data set.

Results

AF was present in 35 526/502 493 (7.1%) participants, including 8340 (988 with AF <1 year) with AF at enrolment and 27 186 with incident AF during follow-up. Most participants (22 003/27 186; 80.9%) with incident AF were eligible for early rhythm-control.Eligible participants were older (70 years vs 63 years) and more likely to be female (42% vs 21%) compared with ineligible patients. Of 9004 participants with full primary care data, 874 (9.02%) received early rhythm-control. Safety outcomes were not different between patients receiving early rhythm-control and controls. The primary outcome of EAST-AFNET 4, a composite of cardiovascular death, stroke/transient ischaemic attack and hospitalisation for heart failure or acute coronary syndrome occurred less often in participants receiving early rhythm-control compared with controls in the entire cohort (HR 0.82, 95% CI 0.71 to 0.94, p=0.005). In the propensity-score matched analysis, early rhythm-control did not significantly decrease of the primary outcome compared with usual care (HR 0.87, 95% CI 0.72 to 1.04, p=0.124).

Conclusion

Around 80% of participants diagnosed with AF in the UK population are eligible for early rhythm-control. Early rhythm-control therapy was safe in routine care.",,pdf:https://heart.bmj.com/content/heartjnl/early/2022/07/13/heartjnl-2022-321196.full.pdf; doi:https://doi.org/10.1136/heartjnl-2022-321196; html:https://europepmc.org/articles/PMC9664114; pdf:https://europepmc.org/articles/PMC9664114?pdf=render 34430954,https://doi.org/10.1016/s2666-7568(21)00168-9,Profile of humoral and cellular immune responses to single doses of BNT162b2 or ChAdOx1 nCoV-19 vaccines in residents and staff within residential care homes (VIVALDI): an observational study.,"Tut G, Lancaster T, Krutikov M, Sylla P, Bone D, Kaur N, Spalkova E, Bentley C, Amin U, Jadir AT, Hulme S, Butler MS, Ayodele M, Bruton R, Shrotri M, Azmi B, Fuller C, Irwin-Singer A, Hayward A, Copas A, Shallcross L, Moss P.",,The lancet. Healthy longevity,2021,2021-08-19,Y,,,,"

Background

Residents of long-term care facilities (LTCFs) have been prioritised for COVID-19 vaccination because of the high COVID-19 mortality in this population. Several countries have implemented an extended interval of up to 12 weeks between the first and second vaccine doses to increase population coverage of single-dose vaccination. We aimed to assess the magnitude and quality of adaptive immune responses following a single dose of COVID-19 vaccine in LTCF residents and staff.

Methods

From the LTCFs participating in the ongoing VIVALDI study (ISRCTN14447421), staff and residents who had received a first dose of COVID-19 vaccine (BNT162b2 [tozinameran] or ChAdOx1 nCoV-19), had pre-vaccination and post-vaccination blood samples (collected between Dec 11, 2020, and Feb 16, 2021), and could be linked to a pseudoidentifier in the COVID-19 Data Store were included in our cohort. Past infection with SARS-CoV-2 was defined on the basis of nucleocapsid-specific IgG antibodies being detected through a semiquantitative immunoassay, and participants who tested positive on this assay after but not before vaccination were excluded from the study. Processed blood samples were assessed for spike-specific immune responses, including spike-specific IgG antibody titres, T-cell responses to spike protein peptide mixes, and inhibition of ACE2 binding by spike protein from four variants of SARS-CoV-2 (the original strain as well as the B.1.1.7, B.1.351, and P.1 variants). Responses before and after vaccination were compared on the basis of age, previous infection status, role (staff or resident), and time since vaccination.

Findings

Our cohort comprised 124 participants from 14 LTCFs: 89 (72%) staff (median age 48 years [IQR 35·5-56]) and 35 (28%) residents (87 years [77-90]). Blood samples were collected a median 40 days (IQR 25-47; range 6-52) after vaccination. 30 (24%) participants (18 [20%] staff and 12 [34%] residents) had serological evidence of previous SARS-CoV-2 infection. All participants with previous infection had high antibody titres following vaccination that were independent of age (r s=0·076, p=0·70). In participants without evidence of previous infection, titres were negatively correlated with age (r s=-0·434, p<0·0001) and were 8·2-times lower in residents than in staff. This effect appeared to result from a kinetic delay antibody generation in older infection-naive participants, with the negative age correlation disappearing only in samples taken more than 42 days post-vaccination (r s=-0·207, p=0·20; n=40), in contrast to samples taken after 0-21 days (r s=-0·774, p=0·0043; n=12) or 22-42 days (r s=-0·437, p=0·0034; n=43). Spike-specific cellular responses were similar between older and younger participants. In infection-naive participants, antibody inhibition of ACE2 binding by spike protein from the original SARS-CoV-2 strain was negatively correlated with age (r s=-0·439, p<0·0001), and was significantly lower against spike protein from the B.1.351 variant (median inhibition 31% [14-100], p=0·010) and the P.1 variant (23% [14-97], p<0·0001) than against the original strain (58% [27-100]). By contrast, a single dose of vaccine resulted in around 100% inhibition of the spike-ACE2 interaction against all variants in people with a history of infection.

Interpretation

History of SARS-CoV-2 infection impacts the magnitude and quality of antibody response after a single dose of COVID-19 vaccine in LTCF residents. Residents who are infection-naive have delayed antibody responses to the first dose of vaccine and should be considered for an early second dose where possible.

Funding

UK Government Department of Health and Social Care.",,pdf:https://discovery.ucl.ac.uk/10133388/1/1-s2.0-S2666756821001689-main.pdf; doi:https://doi.org/10.1016/S2666-7568(21)00168-9; html:https://europepmc.org/articles/PMC8376213 -36994768,https://doi.org/10.1002/cphy.c210037,Autonomic Cardiovascular Control in Health and Disease.,"Karim S, Chahal A, Khanji MY, Petersen SE, Somers VK.",,Comprehensive Physiology,2023,2023-03-30,N,,,,"Autonomic neural control of the cardiovascular system is formed of complex and dynamic processes able to adjust rapidly to mitigate perturbations in hemodynamics and maintain homeostasis. Alterations in autonomic control feature in the development or progression of a multitude of diseases with wide-ranging physiological implications given the neural system's responsibility for controlling inotropy, chronotropy, lusitropy, and dromotropy. Imbalances in sympathetic and parasympathetic neural control are also implicated in the development of arrhythmia in several cardiovascular conditions sparking interest in autonomic modulation as a form of treatment. A number of measures of autonomic function have shown prognostic significance in health and in pathological states and have undergone varying degrees of refinement, yet adoption into clinical practice remains extremely limited. The focus of this contemporary narrative review is to summarize the anatomy, physiology, and pathophysiology of the cardiovascular autonomic nervous system and describe the merits and shortfalls of testing modalities available. © 2023 American Physiological Society. Compr Physiol 13:4493-4511, 2023.",,doi:https://doi.org/10.1002/cphy.c210037; html:https://europepmc.org/articles/PMC10406398; pdf:https://europepmc.org/articles/PMC10406398?pdf=render; doi:https://doi.org/10.1002/cphy.c210037 34556677,https://doi.org/10.1038/s41598-021-96189-8,Combining multi-site magnetic resonance imaging with machine learning predicts survival in pediatric brain tumors.,"Grist JT, Withey S, Bennett C, Rose HEL, MacPherson L, Oates A, Powell S, Novak J, Abernethy L, Pizer B, Bailey S, Clifford SC, Mitra D, Arvanitis TN, Auer DP, Avula S, Grundy R, Peet AC.",,Scientific reports,2021,2021-09-23,Y,,,,"Brain tumors represent the highest cause of mortality in the pediatric oncological population. Diagnosis is commonly performed with magnetic resonance imaging. Survival biomarkers are challenging to identify due to the relatively low numbers of individual tumor types. 69 children with biopsy-confirmed brain tumors were recruited into this study. All participants had perfusion and diffusion weighted imaging performed at diagnosis. Imaging data were processed using conventional methods, and a Bayesian survival analysis performed. Unsupervised and supervised machine learning were performed with the survival features, to determine novel sub-groups related to survival. Sub-group analysis was undertaken to understand differences in imaging features. Survival analysis showed that a combination of diffusion and perfusion imaging were able to determine two novel sub-groups of brain tumors with different survival characteristics (p < 0.01), which were subsequently classified with high accuracy (98%) by a neural network. Analysis of high-grade tumors showed a marked difference in survival (p = 0.029) between the two clusters with high risk and low risk imaging features. This study has developed a novel model of survival for pediatric brain tumors. Tumor perfusion plays a key role in determining survival and should be considered as a high priority for future imaging protocols.",,pdf:https://www.nature.com/articles/s41598-021-96189-8.pdf; doi:https://doi.org/10.1038/s41598-021-96189-8; html:https://europepmc.org/articles/PMC8460620; pdf:https://europepmc.org/articles/PMC8460620?pdf=render +36994768,https://doi.org/10.1002/cphy.c210037,Autonomic Cardiovascular Control in Health and Disease.,"Karim S, Chahal A, Khanji MY, Petersen SE, Somers VK.",,Comprehensive Physiology,2023,2023-03-30,N,,,,"Autonomic neural control of the cardiovascular system is formed of complex and dynamic processes able to adjust rapidly to mitigate perturbations in hemodynamics and maintain homeostasis. Alterations in autonomic control feature in the development or progression of a multitude of diseases with wide-ranging physiological implications given the neural system's responsibility for controlling inotropy, chronotropy, lusitropy, and dromotropy. Imbalances in sympathetic and parasympathetic neural control are also implicated in the development of arrhythmia in several cardiovascular conditions sparking interest in autonomic modulation as a form of treatment. A number of measures of autonomic function have shown prognostic significance in health and in pathological states and have undergone varying degrees of refinement, yet adoption into clinical practice remains extremely limited. The focus of this contemporary narrative review is to summarize the anatomy, physiology, and pathophysiology of the cardiovascular autonomic nervous system and describe the merits and shortfalls of testing modalities available. © 2023 American Physiological Society. Compr Physiol 13:4493-4511, 2023.",,doi:https://doi.org/10.1002/cphy.c210037; html:https://europepmc.org/articles/PMC10406398; pdf:https://europepmc.org/articles/PMC10406398?pdf=render; doi:https://doi.org/10.1002/cphy.c210037 34894331,https://doi.org/10.1007/s10461-021-03551-y,Influence of Material Deprivation on Clinical Outcomes Among People Living with HIV in High-Income Countries: A Systematic Review and Meta-analysis.,"Papageorgiou V, Davies B, Cooper E, Singer A, Ward H.",,AIDS and behavior,2022,2021-12-11,Y,HIV; Meta-analysis; Systematic review; Antiretroviral therapy; Socioeconomic Factors; Viral Suppression; Social Determinants Of Health,,,"Despite developments in HIV treatment and care, disparities persist with some not fully benefiting from improvements in the HIV care continuum. We conducted a systematic review to explore associations between social determinants and HIV treatment outcomes (viral suppression and treatment adherence) in high-income countries. A random effects meta-analysis was performed where there were consistent measurements of exposures. We identified 83 observational studies eligible for inclusion. Social determinants linked to material deprivation were identified as education, employment, food security, housing, income, poverty/deprivation, socioeconomic status/position, and social class; however, their measurement and definition varied across studies. Our review suggests a social gradient of health persists in the HIV care continuum; people living with HIV who reported material deprivation were less likely to be virologically suppressed or adherent to antiretrovirals. Future research should use an ecosocial approach to explore these interactions across the lifecourse to help propose a causal pathway.",,pdf:https://link.springer.com/content/pdf/10.1007/s10461-021-03551-y.pdf; doi:https://doi.org/10.1007/s10461-021-03551-y; html:https://europepmc.org/articles/PMC9046343; pdf:https://europepmc.org/articles/PMC9046343?pdf=render 34141852,https://doi.org/10.1016/j.ssmph.2021.100828,Media representations of opposition to the 'junk food advertising ban' on the Transport for London (TfL) network: A thematic content analysis of UK news and trade press.,"Thompson C, Clary C, Er V, Adams J, Boyland E, Burgoine T, Cornelsen L, de Vocht F, Egan M, Lake AA, Lock K, Mytton O, Petticrew M, White M, Yau A, Cummins S.",,SSM - population health,2021,2021-05-27,Y,Regulation; Media; Advertising; Childhood Obesity,,,"

Background

Advertising of less healthy foods and drinks is hypothesised to be associated with obesity in adults and children. In February 2019, Transport for London implemented restrictions on advertisements for foods and beverages high in fat, salt or sugar across its network as part of a city-wide strategy to tackle childhood obesity. The policy was extensively debated in the press. This paper identifies arguments for and against the restrictions. Focusing on arguments against the restrictions, it then goes on to deconstruct the discursive strategies underpinning them.

Methods

A qualitative thematic content analysis of media coverage of the restrictions (the 'ban') in UK newspapers and trade press was followed by a document analysis of arguments against the ban. A search period of March 1, 2018 to May 31, 2019 covered: (i) the launch of the public consultation on the ban in May 2018; (ii) the announcement of the ban in November 2018; and (iii) its implementation in February 2019. A systematic search of printed and online publications in English distributed in the UK or published on UK-specific websites identified 152 articles.

Results

Arguments in favour of the ban focused on inequalities and childhood obesity. Arguments against the ban centred on two claims: that childhood obesity was not the 'right' priority; and that an advertising ban was not an effective way to address childhood obesity. These claims were justified via three discursive approaches: (i) claiming more 'important' priorities for action; (ii) disputing the science behind the ban; (iii) emphasising potential financial costs of the ban.

Conclusion

The discursive tactics used in media sources to argue against the ban draw on frames widely used by unhealthy commodities industries in response to structural public health interventions. Our analyses highlight the need for interventions to be framed in ways that can pre-emptively counter common criticisms.",,doi:https://doi.org/10.1016/j.ssmph.2021.100828; doi:https://doi.org/10.1016/j.ssmph.2021.100828; html:https://europepmc.org/articles/PMC8184652; pdf:https://europepmc.org/articles/PMC8184652?pdf=render 34527726,https://doi.org/10.1183/23120541.00167-2021,Identifying COPD in routinely collected electronic health records: a systematic scoping review.,"Sivakumaran S, Alsallakh MA, Lyons RA, Quint JK, Davies GA.",,ERJ open research,2021,2021-07-01,Y,,,,"Although routinely collected electronic health records (EHRs) are widely used to examine outcomes related to COPD, consensus regarding the identification of cases from electronic healthcare databases is lacking. We systematically examine and summarise approaches from the recent literature. MEDLINE via EBSCOhost was searched for COPD-related studies using EHRs published from January 1, 2018 to November 30, 2019. Data were extracted relating to the case definition of COPD and determination of COPD severity and phenotypes. From 185 eligible studies, we found widespread variation in the definitions used to identify people with COPD in terms of code sets used (with 20 different code sets in use based on the ICD-10 classification alone) and requirement of additional criteria (relating to age (n=139), medication (n=31), multiplicity of events (n=21), spirometry (n=19) and smoking status (n=9)). Only seven studies used a case definition which had been validated against a reference standard in the same dataset. Various proxies of disease severity were used since spirometry results and patient-reported outcomes were not often available. To enable the research community to draw reliable insights from EHRs and aid comparability between studies, clear reporting and greater consistency of the definitions used to identify COPD and related outcome measures is key.",,pdf:https://openres.ersjournals.com/content/erjor/7/3/00167-2021.full.pdf; doi:https://doi.org/10.1183/23120541.00167-2021; html:https://europepmc.org/articles/PMC8435805; pdf:https://europepmc.org/articles/PMC8435805?pdf=render 36446790,https://doi.org/10.1038/s41467-022-35017-7,Genetically personalised organ-specific metabolic models in health and disease.,"Foguet C, Xu Y, Ritchie SC, Lambert SA, Persyn E, Nath AP, Davenport EE, Roberts DJ, Paul DS, Di Angelantonio E, Danesh J, Butterworth AS, Yau C, Inouye M.",,Nature communications,2022,2022-11-29,Y,,,,"Understanding how genetic variants influence disease risk and complex traits (variant-to-function) is one of the major challenges in human genetics. Here we present a model-driven framework to leverage human genome-scale metabolic networks to define how genetic variants affect biochemical reaction fluxes across major human tissues, including skeletal muscle, adipose, liver, brain and heart. As proof of concept, we build personalised organ-specific metabolic flux models for 524,615 individuals of the INTERVAL and UK Biobank cohorts and perform a fluxome-wide association study (FWAS) to identify 4312 associations between personalised flux values and the concentration of metabolites in blood. Furthermore, we apply FWAS to identify 92 metabolic fluxes associated with the risk of developing coronary artery disease, many of which are linked to processes previously described to play in role in the disease. Our work demonstrates that genetically personalised metabolic models can elucidate the downstream effects of genetic variants on biochemical reactions involved in common human diseases.",,pdf:https://www.nature.com/articles/s41467-022-35017-7.pdf; doi:https://doi.org/10.1038/s41467-022-35017-7; html:https://europepmc.org/articles/PMC9708841; pdf:https://europepmc.org/articles/PMC9708841?pdf=render -37080566,https://doi.org/10.1183/13993003.01720-2022,Collaboration between explainable artificial intelligence and pulmonologists improves the accuracy of pulmonary function test interpretation.,"Das N, Happaerts S, Gyselinck I, Staes M, Derom E, Brusselle G, Burgos F, Contoli M, Dinh-Xuan AT, Franssen FME, Gonem S, Greening N, Haenebalcke C, Man WD, Moisés J, Peché R, Poberezhets V, Quint JK, Steiner MC, Vanderhelst E, Abdo M, Topalovic M, Janssens W.",,The European respiratory journal,2023,2023-05-18,Y,,,,"

Background

Few studies have investigated the collaborative potential between artificial intelligence (AI) and pulmonologists for diagnosing pulmonary disease. We hypothesised that the collaboration between a pulmonologist and AI with explanations (explainable AI (XAI)) is superior in diagnostic interpretation of pulmonary function tests (PFTs) than the pulmonologist without support.

Methods

The study was conducted in two phases, a monocentre study (phase 1) and a multicentre intervention study (phase 2). Each phase utilised two different sets of 24 PFT reports of patients with a clinically validated gold standard diagnosis. Each PFT was interpreted without (control) and with XAI's suggestions (intervention). Pulmonologists provided a differential diagnosis consisting of a preferential diagnosis and optionally up to three additional diagnoses. The primary end-point compared accuracy of preferential and additional diagnoses between control and intervention. Secondary end-points were the number of diagnoses in differential diagnosis, diagnostic confidence and inter-rater agreement. We also analysed how XAI influenced pulmonologists' decisions.

Results

In phase 1 (n=16 pulmonologists), mean preferential and differential diagnostic accuracy significantly increased by 10.4% and 9.4%, respectively, between control and intervention (p<0.001). Improvements were somewhat lower but highly significant (p<0.0001) in phase 2 (5.4% and 8.7%, respectively; n=62 pulmonologists). In both phases, the number of diagnoses in the differential diagnosis did not reduce, but diagnostic confidence and inter-rater agreement significantly increased during intervention. Pulmonologists updated their decisions with XAI's feedback and consistently improved their baseline performance if AI provided correct predictions.

Conclusion

A collaboration between a pulmonologist and XAI is better at interpreting PFTs than individual pulmonologists reading without XAI support or XAI alone.",,pdf:https://erj.ersjournals.com/content/erj/early/2023/03/15/13993003.01720-2022.full.pdf; doi:https://doi.org/10.1183/13993003.01720-2022; html:https://europepmc.org/articles/PMC10196345; pdf:https://europepmc.org/articles/PMC10196345?pdf=render 35176022,https://doi.org/10.1371/journal.pmed.1003915,"Changes in household food and drink purchases following restrictions on the advertisement of high fat, salt, and sugar products across the Transport for London network: A controlled interrupted time series analysis.","Yau A, Berger N, Law C, Cornelsen L, Greener R, Adams J, Boyland EJ, Burgoine T, de Vocht F, Egan M, Er V, Lake AA, Lock K, Mytton O, Petticrew M, Thompson C, White M, Cummins S.",,PLoS medicine,2022,2022-02-17,Y,,,,"

Background

Restricting the advertisement of products with high fat, salt, and sugar (HFSS) content has been recommended as a policy tool to improve diet and tackle obesity, but the impact on HFSS purchasing is unknown. This study aimed to evaluate the impact of HFSS advertising restrictions, implemented across the London (UK) transport network in February 2019, on HFSS purchases.

Methods and findings

Over 5 million take-home food and drink purchases were recorded by 1,970 households (London [intervention], n = 977; North of England [control], n = 993) randomly selected from the Kantar Fast Moving Consumer Goods panel. The intervention and control samples were similar in household characteristics but had small differences in main food shopper sex, socioeconomic position, and body mass index. Using a controlled interrupted time series design, we estimated average weekly household purchases of energy and nutrients from HFSS products in the post-intervention period (44 weeks) compared to a counterfactual constructed from the control and pre-intervention (36 weeks) series. Energy purchased from HFSS products was 6.7% (1,001.0 kcal, 95% CI 456.0 to 1,546.0) lower among intervention households compared to the counterfactual. Relative reductions in purchases of fat (57.9 g, 95% CI 22.1 to 93.7), saturated fat (26.4 g, 95% CI 12.4 to 40.4), and sugar (80.7 g, 95% CI 41.4 to 120.1) from HFSS products were also observed. Energy from chocolate and confectionery purchases was 19.4% (317.9 kcal, 95% CI 200.0 to 435.8) lower among intervention households than for the counterfactual, with corresponding relative reductions in fat (13.1 g, 95% CI 7.5 to 18.8), saturated fat (8.7 g, 95% CI 5.7 to 11.7), sugar (41.4 g, 95% CI 27.4 to 55.4), and salt (0.2 g, 95% CI 0.1 to 0.2) purchased from chocolate and confectionery. Relative reductions are in the context of secular increases in HFSS purchases in both the intervention and control areas, so the policy was associated with attenuated growth of HFSS purchases rather than absolute reduction in HFSS purchases. Study limitations include the lack of out-of-home purchases in our analyses and not being able to assess the sustainability of observed changes beyond 44 weeks.

Conclusions

This study finds an association between the implementation of restrictions on outdoor HFSS advertising and relative reductions in energy, sugar, and fat purchased from HFSS products. These findings provide support for policies that restrict HFSS advertising as a tool to reduce purchases of HFSS products.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003915&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003915; html:https://europepmc.org/articles/PMC8853584; pdf:https://europepmc.org/articles/PMC8853584?pdf=render -35879616,https://doi.org/10.1038/s41591-022-01909-w,Symptoms and risk factors for long COVID in non-hospitalized adults.,"Subramanian A, Nirantharakumar K, Hughes S, Myles P, Williams T, Gokhale KM, Taverner T, Chandan JS, Brown K, Simms-Williams N, Shah AD, Singh M, Kidy F, Okoth K, Hotham R, Bashir N, Cockburn N, Lee SI, Turner GM, Gkoutos GV, Aiyegbusi OL, McMullan C, Denniston AK, Sapey E, Lord JM, Wraith DC, Leggett E, Iles C, Marshall T, Price MJ, Marwaha S, Davies EH, Jackson LJ, Matthews KL, Camaradou J, Calvert M, Haroon S.",,Nature medicine,2022,2022-07-25,Y,,,,"Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02-8.39), hair loss (3.99, 3.63-4.39), sneezing (2.77, 1.40-5.50), ejaculation difficulty (2.63, 1.61-4.28) and reduced libido (2.36, 1.61-3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.",,pdf:https://www.nature.com/articles/s41591-022-01909-w.pdf; doi:https://doi.org/10.1038/s41591-022-01909-w; html:https://europepmc.org/articles/PMC9388369; pdf:https://europepmc.org/articles/PMC9388369?pdf=render +37080566,https://doi.org/10.1183/13993003.01720-2022,Collaboration between explainable artificial intelligence and pulmonologists improves the accuracy of pulmonary function test interpretation.,"Das N, Happaerts S, Gyselinck I, Staes M, Derom E, Brusselle G, Burgos F, Contoli M, Dinh-Xuan AT, Franssen FME, Gonem S, Greening N, Haenebalcke C, Man WD, Moisés J, Peché R, Poberezhets V, Quint JK, Steiner MC, Vanderhelst E, Abdo M, Topalovic M, Janssens W.",,The European respiratory journal,2023,2023-05-18,Y,,,,"

Background

Few studies have investigated the collaborative potential between artificial intelligence (AI) and pulmonologists for diagnosing pulmonary disease. We hypothesised that the collaboration between a pulmonologist and AI with explanations (explainable AI (XAI)) is superior in diagnostic interpretation of pulmonary function tests (PFTs) than the pulmonologist without support.

Methods

The study was conducted in two phases, a monocentre study (phase 1) and a multicentre intervention study (phase 2). Each phase utilised two different sets of 24 PFT reports of patients with a clinically validated gold standard diagnosis. Each PFT was interpreted without (control) and with XAI's suggestions (intervention). Pulmonologists provided a differential diagnosis consisting of a preferential diagnosis and optionally up to three additional diagnoses. The primary end-point compared accuracy of preferential and additional diagnoses between control and intervention. Secondary end-points were the number of diagnoses in differential diagnosis, diagnostic confidence and inter-rater agreement. We also analysed how XAI influenced pulmonologists' decisions.

Results

In phase 1 (n=16 pulmonologists), mean preferential and differential diagnostic accuracy significantly increased by 10.4% and 9.4%, respectively, between control and intervention (p<0.001). Improvements were somewhat lower but highly significant (p<0.0001) in phase 2 (5.4% and 8.7%, respectively; n=62 pulmonologists). In both phases, the number of diagnoses in the differential diagnosis did not reduce, but diagnostic confidence and inter-rater agreement significantly increased during intervention. Pulmonologists updated their decisions with XAI's feedback and consistently improved their baseline performance if AI provided correct predictions.

Conclusion

A collaboration between a pulmonologist and XAI is better at interpreting PFTs than individual pulmonologists reading without XAI support or XAI alone.",,pdf:https://erj.ersjournals.com/content/erj/early/2023/03/15/13993003.01720-2022.full.pdf; doi:https://doi.org/10.1183/13993003.01720-2022; html:https://europepmc.org/articles/PMC10196345; pdf:https://europepmc.org/articles/PMC10196345?pdf=render 33971933,https://doi.org/10.1186/s13063-021-05295-5,Accessing routinely collected health data to improve clinical trials: recent experience of access.,"Macnair A, Love SB, Murray ML, Gilbert DC, Parmar MKB, Denwood T, Carpenter J, Sydes MR, Langley RE, Cafferty FH.",,Trials,2021,2021-05-10,Y,Clinical Trials; Electronic Health Records; Data Accessibility; Routinely Collected Data,,,"

Background

Routinely collected electronic health records (EHRs) have the potential to enhance randomised controlled trials (RCTs) by facilitating recruitment and follow-up. Despite this, current EHR use is minimal in UK RCTs, in part due to ongoing concerns about the utility (reliability, completeness, accuracy) and accessibility of the data. The aim of this manuscript is to document the process, timelines and challenges of the application process to help improve the service both for the applicants and data holders.

Methods

This is a qualitative paper providing a descriptive narrative from one UK clinical trials unit (MRC CTU at UCL) on the experience of two trial teams' application process to access data from three large English national datasets: National Cancer Registration and Analysis Service (NCRAS), National Institute for Cardiovascular Outcomes Research (NICOR) and NHS Digital to establish themes for discussion. The underpinning reason for applying for the data was to compare EHRs with data collected through case report forms in two RCTs, Add-Aspirin (ISRCTN 74358648) and PATCH (ISRCTN 70406718).

Results

The Add-Aspirin trial, which had a pre-planned embedded sub-study to assess EHR, received data from NCRAS 13 months after the first application. In the PATCH trial, the decision to request data was made whilst the trial was recruiting. The study received data after 8 months from NICOR and 15 months for NHS Digital following final application submission. This concluded in May 2020. Prior to application submission, significant time and effort was needed particularly in relation to the PATCH trial where negotiations over consent and data linkage took many years.

Conclusions

Our experience demonstrates that data access can be a prolonged and complex process. This is compounded if multiple data sources are required for the same project. This needs to be factored in when planning to use EHR within RCTs and is best considered prior to conception of the trial. Data holders and researchers are endeavouring to simplify and streamline the application process so that the potential of EHR can be realised for clinical trials.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-021-05295-5; doi:https://doi.org/10.1186/s13063-021-05295-5; html:https://europepmc.org/articles/PMC8108438; pdf:https://europepmc.org/articles/PMC8108438?pdf=render +35879616,https://doi.org/10.1038/s41591-022-01909-w,Symptoms and risk factors for long COVID in non-hospitalized adults.,"Subramanian A, Nirantharakumar K, Hughes S, Myles P, Williams T, Gokhale KM, Taverner T, Chandan JS, Brown K, Simms-Williams N, Shah AD, Singh M, Kidy F, Okoth K, Hotham R, Bashir N, Cockburn N, Lee SI, Turner GM, Gkoutos GV, Aiyegbusi OL, McMullan C, Denniston AK, Sapey E, Lord JM, Wraith DC, Leggett E, Iles C, Marshall T, Price MJ, Marwaha S, Davies EH, Jackson LJ, Matthews KL, Camaradou J, Calvert M, Haroon S.",,Nature medicine,2022,2022-07-25,Y,,,,"Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02-8.39), hair loss (3.99, 3.63-4.39), sneezing (2.77, 1.40-5.50), ejaculation difficulty (2.63, 1.61-4.28) and reduced libido (2.36, 1.61-3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.",,pdf:https://www.nature.com/articles/s41591-022-01909-w.pdf; doi:https://doi.org/10.1038/s41591-022-01909-w; html:https://europepmc.org/articles/PMC9388369; pdf:https://europepmc.org/articles/PMC9388369?pdf=render 36384749,https://doi.org/10.1136/heartjnl-2022-321733,Lower birth weight is linked to poorer cardiovascular health in middle-aged population-based adults.,"Raisi-Estabragh Z, Cooper J, Bethell MS, McCracken C, Lewandowski AJ, Leeson P, Neubauer S, Harvey NC, Petersen SE.",,Heart (British Cardiac Society),2023,2023-03-10,Y,epidemiology; Magnetic Resonance Imaging; risk factors,,,"

Objective

To examine associations of birth weight with clinical and imaging indicators of cardiovascular health and evaluate mechanistic pathways in the UK Biobank.

Methods

Competing risk regression was used to estimate associations of birth weight with incident myocardial infarction (MI) and mortality (all-cause, cardiovascular disease, ischaemic heart disease, MI), over 7-12 years of longitudinal follow-up, adjusting for age, sex, deprivation, maternal smoking/hypertension and maternal/paternal diabetes. Mediation analysis was used to evaluate the role of childhood growth, adulthood obesity, cardiometabolic diseases and blood biomarkers in mediating the birth weight-MI relationship. Linear regression was used to estimate associations of birth weight with left ventricular (LV) mass-to-volume ratio, LV stroke volume, global longitudinal strain, LV global function index and left atrial ejection fraction.

Results

258 787 participants from white ethnicities (61% women, median age 56 (49, 62) years) were studied. Birth weight had a non-linear relationship with incident MI, with a significant inverse association below an optimal threshold of 3.2 kg (subdistribution HR: 1.15 (1.08 to 1.22), p=6.0×10-5) and attenuation to the null above this threshold. The birth weight-MI effect was mediated through hypertension (8.4%), glycated haemoglobin (7.0%), C reactive protein (6.4%), high-density lipoprotein (5.2%) and high cholesterol (4.1%). Birth weight-mortality associations were statistically non-significant after Bonferroni correction. In participants with cardiovascular magnetic resonance (n=19 314), lower birth weight was associated with adverse LV remodelling (greater concentricity, poorer function).

Conclusions

Lower birth weight was associated with greater risk of incident MI and unhealthy LV phenotypes; effects were partially mediated through cardiometabolic disease and systemic inflammation. These findings support consideration of birth weight in risk prediction and highlight actionable areas for disease prevention.",,pdf:https://heart.bmj.com/content/heartjnl/early/2022/11/15/heartjnl-2022-321733.full.pdf; doi:https://doi.org/10.1136/heartjnl-2022-321733; html:https://europepmc.org/articles/PMC10086465; pdf:https://europepmc.org/articles/PMC10086465?pdf=render 32856160,https://doi.org/10.1007/s10654-020-00677-6,Data extraction for epidemiological research (DExtER): a novel tool for automated clinical epidemiology studies.,"Gokhale KM, Chandan JS, Toulis K, Gkoutos G, Tino P, Nirantharakumar K.",,European journal of epidemiology,2021,2020-08-27,Y,Extract; Research methods; epidemiology; Transform; Observational Study; Computer Science; Load,,,"The use of primary care electronic health records for research is abundant. The benefits gained from utilising such records lies in their size, longitudinal data collection and data quality. However, the use of such data to undertake high quality epidemiological studies, can lead to significant challenges particularly in dealing with misclassification, variation in coding and the significant effort required to pre-process the data in a meaningful format for statistical analysis. In this paper, we describe a methodology to aid with the extraction and processing of such databases, delivered by a novel software programme; the ""Data extraction for epidemiological research"" (DExtER). The basis of DExtER relies on principles of extract, transform and load processes. The tool initially provides the ability for the healthcare dataset to be extracted, then transformed in a format whereby data is normalised, converted and reformatted. DExtER has a user interface designed to obtain data extracts specific to each research question and observational study design. There are facilities to input the requirements for; eligible study period, definition of exposed and unexposed groups, outcome measures and important baseline covariates. To date the tool has been utilised and validated in a multitude of settings. There have been over 35 peer-reviewed publications using the tool, and DExtER has been implemented as a validated public health surveillance tool for obtaining accurate statistics on epidemiology of key morbidities. Future direction of this work will be the application of the framework to linked as well as international datasets and the development of standardised methods for conducting electronic pre-processing and extraction from datasets for research purposes.",,pdf:https://link.springer.com/content/pdf/10.1007/s10654-020-00677-6.pdf; doi:https://doi.org/10.1007/s10654-020-00677-6; html:https://europepmc.org/articles/PMC7987616; pdf:https://europepmc.org/articles/PMC7987616?pdf=render -36541282,https://doi.org/10.14814/phy2.15546,Reduced oxygen saturation entropy is associated with poor prognosis in critically ill patients with sepsis.,"Gheorghita M, Wikner M, Cawthorn A, Oyelade T, Nemeth K, Rockenschaub P, Gonzalez Hernandez F, Swanepoel N, Lilaonitkul W, Mani AR.",,Physiological reports,2022,2022-12-01,Y,Variability; Survival; Sepsis; Entropy; Oxygen saturation; Spo2,,,"Recent studies have found that oxygen saturation (SpO2 ) variability analysis has potential for noninvasive assessment of the functional connectivity of cardiorespiratory control systems during hypoxia. Patients with sepsis have suboptimal tissue oxygenation and impaired organ system connectivity. Our objective with this report was to highlight the potential use for SpO2 variability analysis in predicting intensive care survival in patients with sepsis. MIMIC-III clinical data of 164 adults meeting Sepsis-3 criteria and with 30 min of SpO2 and respiratory rate data were analyzed. The complexity of SpO2 signals was measured through various entropy calculations such as sample entropy and multiscale entropy analysis. The sequential organ failure assessment (SOFA) score was calculated to assess the severity of sepsis and multiorgan failure. While the standard deviation of SpO2 signals was comparable in the non-survivor and survivor groups, non-survivors had significantly lower SpO2 entropy than those who survived their ICU stay (0.107 ± 0.084 vs. 0.070 ± 0.083, p < 0.05). According to Cox regression analysis, higher SpO2 entropy was a predictor of survival in patients with sepsis. Multivariate analysis also showed that the prognostic value of SpO2 entropy was independent of other covariates such as age, SOFA score, mean SpO2 , and ventilation status. When SpO2 entropy was combined with mean SpO2 , the composite had a significantly higher performance in prediction of survival. Analysis of SpO2 entropy can predict patient outcome, and when combined with SpO2 mean, can provide improved prognostic information. The prognostic power is on par with the SOFA score. This analysis can easily be incorporated into current ICU practice and has potential for noninvasive assessment of critically ill patients.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.14814/phy2.15546; doi:https://doi.org/10.14814/phy2.15546; html:https://europepmc.org/articles/PMC9768724; pdf:https://europepmc.org/articles/PMC9768724?pdf=render 34007896,https://doi.org/10.23889/ijpds.v6i1.1387,"A retrospective epidemiological study of type 1 diabetes mellitus in wales, UK between 2008 and 2018.","Rafferty J, Stephens JW, Atkinson MD, Luzio SD, Akbari A, Gregory JW, Bain S, Owens DR, Thomas RL.",,International journal of population data science,2021,2021-04-15,Y,Diabetes mellitus; epidemiology; Electronic Health Records,,,"

Introduction

Studies of prevalence and the demographic profile of type 1 diabetes are challenging because of the relative rarity of the condition, however, these outcomes can be determined using routine healthcare data repositories. Understanding the epidemiology of type 1 diabetes allows for targeted interventions and care of this life-affecting condition.

Objectives

To describe the prevalence, incidence and demographics of persons with type 1 diabetes diagnosed in Wales, UK, using the Secure Anonymised Information Linkage (SAIL) Databank.

Methods

Data derived from primary and secondary care throughout Wales available in the SAIL Databank were used to identify people with type 1 diabetes to determine the prevalence and incidence of type 1 diabetes over a 10 year period (2008-18) and describe the demographic and clinical characteristics of this population by age, socioeconomic deprivation and settlement type. The seasonal variation in incidence rates was also examined.

Results

The prevalence of type 1 diabetes in 2018 was 0.32% in the whole population, being greater in men compared to women (0.35% vs 0.28% respectively); highest in those aged 15-29 years (0.52%) and living in the most socioeconomically deprived areas (0.38%). The incidence of type 1 diabetes over 10 years was 14.0 cases/100,000 people/year for the whole population of Wales. It was highest in children aged 0-14 years (33.6 cases/100,000 people/year) and areas of high socioeconomic deprivation (16.8 cases/100,000 people/year) and least in those aged 45-60 years (6.5 cases/100,000 people/year) and in areas of low socioeconomic deprivation (11.63 cases/100,000 people/year). A seasonal trend in the diagnoses of type 1 diabetes was observed with higher incidence in winter months.

Conclusion

This nation-wide retrospective epidemiological study using routine data revealed that the incidence of type 1 diabetes in Wales was greatest in those aged 0-14 years with a higher incidence and prevalence in the most deprived areas. These findings illustrate the need for health-related policies targeted at high deprivation areas to include type 1 diabetes in their remit.",,pdf:https://ijpds.org/article/download/1387/3155; doi:https://doi.org/10.23889/ijpds.v6i1.1387; html:https://europepmc.org/articles/PMC8103995; pdf:https://europepmc.org/articles/PMC8103995?pdf=render +36541282,https://doi.org/10.14814/phy2.15546,Reduced oxygen saturation entropy is associated with poor prognosis in critically ill patients with sepsis.,"Gheorghita M, Wikner M, Cawthorn A, Oyelade T, Nemeth K, Rockenschaub P, Gonzalez Hernandez F, Swanepoel N, Lilaonitkul W, Mani AR.",,Physiological reports,2022,2022-12-01,Y,Variability; Survival; Sepsis; Entropy; Oxygen saturation; Spo2,,,"Recent studies have found that oxygen saturation (SpO2 ) variability analysis has potential for noninvasive assessment of the functional connectivity of cardiorespiratory control systems during hypoxia. Patients with sepsis have suboptimal tissue oxygenation and impaired organ system connectivity. Our objective with this report was to highlight the potential use for SpO2 variability analysis in predicting intensive care survival in patients with sepsis. MIMIC-III clinical data of 164 adults meeting Sepsis-3 criteria and with 30 min of SpO2 and respiratory rate data were analyzed. The complexity of SpO2 signals was measured through various entropy calculations such as sample entropy and multiscale entropy analysis. The sequential organ failure assessment (SOFA) score was calculated to assess the severity of sepsis and multiorgan failure. While the standard deviation of SpO2 signals was comparable in the non-survivor and survivor groups, non-survivors had significantly lower SpO2 entropy than those who survived their ICU stay (0.107 ± 0.084 vs. 0.070 ± 0.083, p < 0.05). According to Cox regression analysis, higher SpO2 entropy was a predictor of survival in patients with sepsis. Multivariate analysis also showed that the prognostic value of SpO2 entropy was independent of other covariates such as age, SOFA score, mean SpO2 , and ventilation status. When SpO2 entropy was combined with mean SpO2 , the composite had a significantly higher performance in prediction of survival. Analysis of SpO2 entropy can predict patient outcome, and when combined with SpO2 mean, can provide improved prognostic information. The prognostic power is on par with the SOFA score. This analysis can easily be incorporated into current ICU practice and has potential for noninvasive assessment of critically ill patients.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.14814/phy2.15546; doi:https://doi.org/10.14814/phy2.15546; html:https://europepmc.org/articles/PMC9768724; pdf:https://europepmc.org/articles/PMC9768724?pdf=render 33875444,https://doi.org/10.1136/bmjopen-2020-045077,COVID-19 in patients with hepatobiliary and pancreatic diseases: a single-centre cross-sectional study in East London.,"Dayem Ullah AZM, Sivapalan L, Kocher HM, Chelala C.",,BMJ open,2021,2021-04-19,Y,Pancreatic Disease; Hepatobiliary Disease; Covid-19,,,"

Objective

To explore risk factors associated with COVID-19 susceptibility and survival in patients with pre-existing hepato-pancreato-biliary (HPB) conditions.

Design

Cross-sectional study.

Setting

East London Pancreatic Cancer Epidemiology (EL-PaC-Epidem) Study at Barts Health National Health Service Trust, UK. Linked electronic health records were interrogated on a cohort of participants (age ≥18 years), reported with HPB conditions between 1 April 2008 and 6 March 2020.

Participants

EL-PaC-Epidem Study participants, alive on 12 February 2020, and living in East London within the previous 6 months (n=15 440). The cohort represents a multi-ethnic population with 51.7% belonging to the non-White background.

Main outcome measure

COVID-19 incidence and mortality.

Results

Some 226 (1.5%) participants had confirmed COVID-19 diagnosis between 12 February and 12 June 2020, with increased odds for men (OR 1.56; 95% CI 1.2 to 2.04) and Black ethnicity (2.04; 1.39 to 2.95) as well as patients with moderate to severe liver disease (2.2; 1.35 to 3.59). Each additional comorbidity increased the odds of infection by 62%. Substance misusers were at more risk of infection, so were patients on vitamin D treatment. The higher ORs in patients with chronic pancreatic or mild liver conditions, age >70, and a history of smoking or obesity were due to coexisting comorbidities. Increased odds of death were observed for men (3.54; 1.68 to 7.85) and Black ethnicity (3.77; 1.38 to 10.7). Patients having respiratory complications from COVID-19 without a history of chronic respiratory disease also had higher odds of death (5.77; 1.75 to 19).

Conclusions

In this large population-based study of patients with HPB conditions, men, Black ethnicity, pre-existing moderate to severe liver conditions, six common medical multimorbidities, substance misuse and a history of vitamin D treatment independently posed higher odds of acquiring COVID-19 compared with their respective counterparts. The odds of death were significantly high for men and Black people.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/4/e045077.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-045077; html:https://europepmc.org/articles/PMC8057071; pdf:https://europepmc.org/articles/PMC8057071?pdf=render 37118449,https://doi.org/10.1038/s43587-022-00224-w,Robust SARS-CoV-2-specific and heterologous immune responses in vaccine-naïve residents of long-term care facilities who survive natural infection.,"Tut G, Lancaster T, Butler MS, Sylla P, Spalkova E, Bone D, Kaur N, Bentley C, Amin U, Jadir AT, Hulme S, Ayodel M, Dowell AC, Pearce H, Zuo J, Margielewska-Davies S, Verma K, Nicol S, Begum J, Jinks E, Tut E, Bruton R, Krutikov M, Shrotri M, Giddings R, Azmi B, Fuller C, Irwin-Singer A, Hayward A, Copas A, Shallcross L, Moss P.",,Nature aging,2022,2022-05-30,Y,,,,"We studied humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 152 long-term care facility staff and 124 residents over a prospective 4-month period shortly after the first wave of infection in England. We show that residents of long-term care facilities developed high and stable levels of antibodies against spike protein and receptor-binding domain. Nucleocapsid-specific responses were also elevated but waned over time. Antibodies showed stable and equivalent levels of functional inhibition against spike-angiotensin-converting enzyme 2 binding in all age groups with comparable activity against viral variants of concern. SARS-CoV-2 seropositive donors showed high levels of antibodies to other beta-coronaviruses but serostatus did not impact humoral immunity to influenza or other respiratory syncytial viruses. SARS-CoV-2-specific cellular responses were similar across all ages but virus-specific populations showed elevated levels of activation in older donors. Thus, survivors of SARS-CoV-2 infection show a robust and stable immunity against the virus that does not negatively impact responses to other seasonal viruses.",,pdf:https://www.nature.com/articles/s43587-022-00224-w.pdf; doi:https://doi.org/10.1038/s43587-022-00224-w; html:https://europepmc.org/articles/PMC10154219; pdf:https://europepmc.org/articles/PMC10154219?pdf=render 35923560,https://doi.org/10.1016/j.lanepe.2022.100475,Equity of access to NHS-funded hip replacements in England and Wales: Trends from 2006 to 2016.,"Wyatt S, Bailey R, Moore P, Revell M.",,The Lancet regional health. Europe,2022,2022-07-29,Y,trends; Equity; Hip Replacements; Socio-economic Deprivation,,,"

Background

Elective hip replacement is a cost-effective means of improving hip function. Previous research has suggested that the supply of hip replacements in the NHS is governed by the inverse care law. We examine whether inequities in supply improved in England and Wales between 2006 and 2016.

Methods

We compare levels of need and supply of NHS funded hip replacements to adults aged 50+ years, across quintiles of deprivation in England and Wales between 2006 and 2016. We use data from routine health records and a large longitudinal study and adjust for age and sex using general additive negative-binomial regression.

Findings

The number of NHS-funded hip replacements per 100,000 population rose substantially from 272.6 and 266.7 in 2002, to 539.7 and 466.3 in 2018 in England and Wales respectively. Having adjusted for age and sex, people living in the most deprived quintile were 2.36 (95% CI, 1.69 to 3.29) times more likely to need a hip replacement in 2006 than those living in quintile 3, whereas those living in the least deprived quintile were 0.45 (95% CI, 0.39 to 0.69) as likely. Despite this, people living in the most deprived quintile were 0.81 (95% CI, 0.78 to 0.83) times as likely in England and 0.93 (95% CI, 0.84 to 1.04) as likely in Wales to receive an NHS-funded hip replacement in 2006 than those living in quintile 3. We found no evidence that these substantial inequities had reduced between 2006 and 2016.

Interpretation

With respect to hip-replacement surgery in England and Wales, policy ambitions to reduce healthcare inequities have not been realised.

Funding

This work was supported by Health Data Research UK.",,doi:https://doi.org/10.1016/j.lanepe.2022.100475; doi:https://doi.org/10.1016/j.lanepe.2022.100475; html:https://europepmc.org/articles/PMC9340533; pdf:https://europepmc.org/articles/PMC9340533?pdf=render @@ -742,16 +742,16 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 35256633,https://doi.org/10.1038/s41598-022-07291-4,Shared genetic loci for body fat storage and adipocyte lipolysis in humans.,"Kulyté A, Lundbäck V, Arner P, Strawbridge RJ, Dahlman I.",,Scientific reports,2022,2022-03-07,Y,,,,"Total body fat and central fat distribution are heritable traits and well-established predictors of adverse metabolic outcomes. Lipolysis is the process responsible for the hydrolysis of triacylglycerols stored in adipocytes. To increase our understanding of the genetic regulation of body fat distribution and total body fat, we set out to determine if genetic variants associated with body mass index (BMI) or waist-hip-ratio adjusted for BMI (WHRadjBMI) in genome-wide association studies (GWAS) mediate their effect by influencing adipocyte lipolysis. We utilized data from the recent GWAS of spontaneous and isoprenaline-stimulated lipolysis in the unique GENetics of Adipocyte Lipolysis (GENiAL) cohort. GENiAL consists of 939 participants who have undergone abdominal subcutaneous adipose biopsy for the determination of spontaneous and isoprenaline-stimulated lipolysis in adipocytes. We report 11 BMI and 15 WHRadjBMI loci with SNPs displaying nominal association with lipolysis and allele-dependent gene expression in adipose tissue according to in silico analysis. Functional evaluation of candidate genes in these loci by small interfering RNAs (siRNA)-mediated knock-down in adipose-derived stem cells identified ZNF436 and NUP85 as intrinsic regulators of lipolysis consistent with the associations observed in the clinical cohorts. Furthermore, candidate genes in another BMI-locus (STX17) and two more WHRadjBMI loci (NID2, GGA3, GRB2) control lipolysis alone, or in conjunction with lipid storage, and may hereby be involved in genetic control of body fat. The findings expand our understanding of how genetic variants mediate their impact on the complex traits of fat storage and distribution.",,pdf:https://www.nature.com/articles/s41598-022-07291-4.pdf; doi:https://doi.org/10.1038/s41598-022-07291-4; html:https://europepmc.org/articles/PMC8901764; pdf:https://europepmc.org/articles/PMC8901764?pdf=render 38286672,https://doi.org/10.1136/bmjopen-2023-073582,Improving our understanding of the social determinants of mental health: a data linkage study of mental health records and the 2011 UK census.,"Cybulski L, Chilman N, Jewell A, Dewey M, Hildersley R, Morgan C, Huck R, Hotopf M, Stewart R, Pritchard M, Wuerth M, Das-Munshi J.",,BMJ open,2024,2024-01-29,Y,Psychiatry; Mental health; Schizophrenia & Psychotic Disorders,,,"

Objectives

To address the lack of individual-level socioeconomic information in electronic healthcare records, we linked the 2011 census of England and Wales to patient records from a large mental healthcare provider. This paper describes the linkage process and methods for mitigating bias due to non-matching.

Setting

South London and Maudsley NHS Foundation Trust (SLaM), a mental healthcare provider in Southeast London.

Design

Clinical records from SLaM were supplied to the Office of National Statistics for linkage to the census through a deterministic matching algorithm. We examined clinical (International Classification of Disease-10 diagnosis, history of hospitalisation, frequency of service contact) and socio-demographic (age, gender, ethnicity, deprivation) information recorded in Clinical Record Interactive Search (CRIS) as predictors of linkage success with the 2011 census. To assess and adjust for potential biases caused by non-matching, we evaluated inverse probability weighting for mortality associations.

Participants

Individuals of all ages in contact with SLaM up until December 2019 (N=459 374).

Outcome measures

Likelihood of mental health records' linkage to census.

Results

220 864 (50.4%) records from CRIS linked to the 2011 census. Young adults (prevalence ratio (PR) 0.80, 95% CI 0.80 to 0.81), individuals living in more deprived areas (PR 0.78, 95% CI 0.78 to 0.79) and minority ethnic groups (eg, Black African, PR 0.67, 0.66 to 0.68) were less likely to match to census. After implementing inverse probability weighting, we observed little change in the strength of association between clinical/demographic characteristics and mortality (eg, presence of any psychiatric disorder: unweighted PR 2.66, 95% CI 2.52 to 2.80; weighted PR 2.70, 95% CI 2.56 to 2.84).

Conclusions

Lower response rates to the 2011 census among people with psychiatric disorders may have contributed to lower match rates, a potential concern as the census informs service planning and allocation of resources. Due to its size and unique characteristics, the linked data set will enable novel investigations into the relationship between socioeconomic factors and psychiatric disorders.",,doi:https://doi.org/10.1136/bmjopen-2023-073582; html:https://europepmc.org/articles/PMC10826590; pdf:https://europepmc.org/articles/PMC10826590?pdf=render 33716109,https://doi.org/10.1016/j.jinf.2021.03.002,Short durations of corticosteroids for hospitalised COVID-19 patients are associated with a high readmission rate.,"Chaudhry Z, Shawe-Taylor M, Rampling T, Cutfield T, Bidwell G, Chan XHS, Last A, Williams B, Logan S, Marks M, Esmail H.",,The Journal of infection,2021,2021-03-11,Y,Dexamethasone; Corticosteroids; Hospital; Readmissions; Covid-19,,,"

Objective

Our objective was to describe the characteristics of patients admitted, discharged and readmitted, due to COVID-19, to a central London acute-care hospital during the second peak, in particular in relation to corticosteroids use.

Methods

We reviewed patients admitted from the community to University College Hospital (UCH) with COVID-19 as their primary diagnosis between 1st-31st December 2020. Re-attendance and readmission data were collected for patients who re-presented within 10 days following discharge. Data were retrospectively collected.

Results

196 patients were admitted from the community with a diagnosis of COVID-19 and discharged alive in December 2020. Corticosteroids were prescribed in hospital for a median of 5 days (IQR 3-8). 20 patients (10.2%) were readmitted within 10 days. 11/20 received corticosteroids in the first admission of which 10 had received 1-3 days of corticosteroids. Readmission rate in those receiving 1-3 days of corticosteroids was 25%.

Conclusions

Most international guidelines have recommended providing up to 10 days of corticosteroids for severe COVID-19 but stopping on discharge. Our findings show shorter courses of corticosteroids during admission are associated with an increased risk of being readmitted and support continuing the course of corticosteroids after hospital discharge monitored in the virtual ward setting.",,pdf:http://www.journalofinfection.com/article/S0163445321001158/pdf; doi:https://doi.org/10.1016/j.jinf.2021.03.002; html:https://europepmc.org/articles/PMC7948670; pdf:https://europepmc.org/articles/PMC7948670?pdf=render -36350656,https://doi.org/10.1093/nar/gkac1010,The NHGRI-EBI GWAS Catalog: knowledgebase and deposition resource.,"Sollis E, Mosaku A, Abid A, Buniello A, Cerezo M, Gil L, Groza T, Güneş O, Hall P, Hayhurst J, Ibrahim A, Ji Y, John S, Lewis E, MacArthur JAL, McMahon A, Osumi-Sutherland D, Panoutsopoulou K, Pendlington Z, Ramachandran S, Stefancsik R, Stewart J, Whetzel P, Wilson R, Hindorff L, Cunningham F, Lambert SA, Inouye M, Parkinson H, Harris LW.",,Nucleic acids research,2023,2023-01-01,Y,,,,"The NHGRI-EBI GWAS Catalog (www.ebi.ac.uk/gwas) is a FAIR knowledgebase providing detailed, structured, standardised and interoperable genome-wide association study (GWAS) data to >200 000 users per year from academic research, healthcare and industry. The Catalog contains variant-trait associations and supporting metadata for >45 000 published GWAS across >5000 human traits, and >40 000 full P-value summary statistics datasets. Content is curated from publications or acquired via author submission of prepublication summary statistics through a new submission portal and validation tool. GWAS data volume has vastly increased in recent years. We have updated our software to meet this scaling challenge and to enable rapid release of submitted summary statistics. The scope of the repository has expanded to include additional data types of high interest to the community, including sequencing-based GWAS, gene-based analyses and copy number variation analyses. Community outreach has increased the number of shared datasets from under-represented traits, e.g. cancer, and we continue to contribute to awareness of the lack of population diversity in GWAS. Interoperability of the Catalog has been enhanced through links to other resources including the Polygenic Score Catalog and the International Mouse Phenotyping Consortium, refinements to GWAS trait annotation, and the development of a standard format for GWAS data.",,pdf:https://academic.oup.com/nar/article-pdf/51/D1/D977/48440802/gkac1010.pdf; doi:https://doi.org/10.1093/nar/gkac1010; html:https://europepmc.org/articles/PMC9825413; pdf:https://europepmc.org/articles/PMC9825413?pdf=render 34265229,https://doi.org/10.1177/01410768211032850,"Symptoms, complications and management of long COVID: a review.","Aiyegbusi OL, Hughes SE, Turner G, Rivera SC, McMullan C, Chandan JS, Haroon S, Price G, Davies EH, Nirantharakumar K, Sapey E, Calvert MJ, TLC Study Group.",,Journal of the Royal Society of Medicine,2021,2021-07-15,Y,Infectious diseases; epidemiology; Public Health; Respiratory Medicine; Health Service Research; Covid-19; Long Covid; Post-Covid-19 Syndrome; Persistent Covid-19 Symptoms,,,"Globally, there are now over 160 million confirmed cases of COVID-19 and more than 3 million deaths. While the majority of infected individuals recover, a significant proportion continue to experience symptoms and complications after their acute illness. Patients with 'long COVID' experience a wide range of physical and mental/psychological symptoms. Pooled prevalence data showed the 10 most prevalent reported symptoms were fatigue, shortness of breath, muscle pain, joint pain, headache, cough, chest pain, altered smell, altered taste and diarrhoea. Other common symptoms were cognitive impairment, memory loss, anxiety and sleep disorders. Beyond symptoms and complications, people with long COVID often reported impaired quality of life, mental health and employment issues. These individuals may require multidisciplinary care involving the long-term monitoring of symptoms, to identify potential complications, physical rehabilitation, mental health and social services support. Resilient healthcare systems are needed to ensure efficient and effective responses to future health challenges.",,doi:https://doi.org/10.1177/01410768211032850; doi:https://doi.org/10.1177/01410768211032850; html:https://europepmc.org/articles/PMC8450986; pdf:https://europepmc.org/articles/PMC8450986?pdf=render +36350656,https://doi.org/10.1093/nar/gkac1010,The NHGRI-EBI GWAS Catalog: knowledgebase and deposition resource.,"Sollis E, Mosaku A, Abid A, Buniello A, Cerezo M, Gil L, Groza T, Güneş O, Hall P, Hayhurst J, Ibrahim A, Ji Y, John S, Lewis E, MacArthur JAL, McMahon A, Osumi-Sutherland D, Panoutsopoulou K, Pendlington Z, Ramachandran S, Stefancsik R, Stewart J, Whetzel P, Wilson R, Hindorff L, Cunningham F, Lambert SA, Inouye M, Parkinson H, Harris LW.",,Nucleic acids research,2023,2023-01-01,Y,,,,"The NHGRI-EBI GWAS Catalog (www.ebi.ac.uk/gwas) is a FAIR knowledgebase providing detailed, structured, standardised and interoperable genome-wide association study (GWAS) data to >200 000 users per year from academic research, healthcare and industry. The Catalog contains variant-trait associations and supporting metadata for >45 000 published GWAS across >5000 human traits, and >40 000 full P-value summary statistics datasets. Content is curated from publications or acquired via author submission of prepublication summary statistics through a new submission portal and validation tool. GWAS data volume has vastly increased in recent years. We have updated our software to meet this scaling challenge and to enable rapid release of submitted summary statistics. The scope of the repository has expanded to include additional data types of high interest to the community, including sequencing-based GWAS, gene-based analyses and copy number variation analyses. Community outreach has increased the number of shared datasets from under-represented traits, e.g. cancer, and we continue to contribute to awareness of the lack of population diversity in GWAS. Interoperability of the Catalog has been enhanced through links to other resources including the Polygenic Score Catalog and the International Mouse Phenotyping Consortium, refinements to GWAS trait annotation, and the development of a standard format for GWAS data.",,pdf:https://academic.oup.com/nar/article-pdf/51/D1/D977/48440802/gkac1010.pdf; doi:https://doi.org/10.1093/nar/gkac1010; html:https://europepmc.org/articles/PMC9825413; pdf:https://europepmc.org/articles/PMC9825413?pdf=render 31315158,https://doi.org/10.1002/cnm.3235,Non-invasive coronary CT angiography-derived fractional flow reserve: A benchmark study comparing the diagnostic performance of four different computational methodologies.,"Carson JM, Pant S, Roobottom C, Alcock R, Javier Blanco P, Alberto Bulant C, Vassilevski Y, Simakov S, Gamilov T, Pryamonosov R, Liang F, Ge X, Liu Y, Nithiarasu P.",,International journal for numerical methods in biomedical engineering,2019,2019-08-16,Y,Fractional Flow Reserve; Benchmark; Haemodynamic Models,,,"Non-invasive coronary computed tomography (CT) angiography-derived fractional flow reserve (cFFR) is an emergent approach to determine the functional relevance of obstructive coronary lesions. Its feasibility and diagnostic performance has been reported in several studies. It is unclear if differences in sensitivity and specificity between these studies are due to study design, population, or ""computational methodology."" We evaluate the diagnostic performance of four different computational workflows for the prediction of cFFR using a limited data set of 10 patients, three based on reduced-order modelling and one based on a 3D rigid-wall model. The results for three of these methodologies yield similar accuracy of 6.5% to 10.5% mean absolute difference between computed and measured FFR. The main aspects of modelling which affected cFFR estimation were choice of inlet and outlet boundary conditions and estimation of flow distribution in the coronary network. One of the reduced-order models showed the lowest overall deviation from the clinical FFR measurements, indicating that reduced-order models are capable of a similar level of accuracy to a 3D model. In addition, this reduced-order model did not include a lumped pressure-drop model for a stenosis, which implies that the additional effort of isolating a stenosis and inserting a pressure-drop element in the spatial mesh may not be required for FFR estimation. The present benchmark study is the first of this kind, in which we attempt to homogenize the data required to compute FFR using mathematical models. The clinical data utilised in the cFFR workflows are made publicly available online.","Retrospective case series of 10 patients having coronary angiogram and invasive fractional flow reserve measurement. The authors used 4 different techniques to estimate coronary vessel flow rate and compared their measurement agreement with clinical FFA measurements and with each other. They found that all 4 methods gave different results, but one approach was more similar with the clinical gold standard. They propose this method with most worthy of further investigaiton.",pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cnm.3235; doi:https://doi.org/10.1002/cnm.3235; html:https://europepmc.org/articles/PMC6851543; pdf:https://europepmc.org/articles/PMC6851543?pdf=render 34148732,https://doi.org/10.1016/j.bja.2021.05.001,Surgical activity in England and Wales during the COVID-19 pandemic: a nationwide observational cohort study.,"Dobbs TD, Gibson JAG, Fowler AJ, Abbott TE, Shahid T, Torabi F, Griffiths R, Lyons RA, Pearse RM, Whitaker IS.",,British journal of anaesthesia,2021,2021-06-18,Y,Surgery; Anaesthesia; Public Policy; Waiting List; Surgical Activity; Covid-19,,,"

Background

A significant proportion of healthcare resource has been diverted to the care of those with COVID-19. This study reports the volume of surgical activity and the number of cancelled surgical procedures during the COVID-19 pandemic.

Methods

We used hospital episode statistics for all adult patients undergoing surgery between January 1, 2020 and December 31, 2020 in England and Wales. We identified surgical procedures using a previously published list of procedure codes. Procedures were stratified by urgency of surgery as defined by NHS England. We calculated the deficit of surgical activity by comparing the expected number of procedures from 2016 to 2019 with the actual number of procedures in 2020. Using a linear regression model, we calculated the expected cumulative number of cancelled procedures by December 31, 2021.

Results

The total number of surgical procedures carried out in England and Wales in 2020 was 3 102 674 compared with the predicted number of 4 671 338 (95% confidence interval [CI]: 4 218 740-5 123 932). This represents a 33.6% reduction in the national volume of surgical activity. There were 763 730 emergency surgical procedures (13.4% reduction) compared with 2 338 944 elective surgical procedures (38.6% reduction). The cumulative number of cancelled or postponed procedures was 1 568 664 (95% CI: 1 116 066-2 021 258). We estimate that this will increase to 2 358 420 (95% CI: 1 667 587-3 100 808) up to December 31, 2021.

Conclusions

The volume of surgical activity in England and Wales was reduced by 33.6% in 2020, resulting in more than 1.5 million cancelled operations. This deficit will continue to grow in 2021.",,pdf:http://www.bjanaesthesia.org/article/S0007091221002737/pdf; doi:https://doi.org/10.1016/j.bja.2021.05.001; html:https://europepmc.org/articles/PMC8277602; pdf:https://europepmc.org/articles/PMC8277602?pdf=render 30950797,https://doi.org/10.2196/12286,Applications of Machine Learning in Real-Life Digital Health Interventions: Review of the Literature.,"Triantafyllidis AK, Tsanas A.",,Journal of medical Internet research,2019,2019-04-05,Y,Artificial intelligence; Review; data mining; Telemedicine; Machine Learning; Digital Health,Applied Analytics,,"

Background

Machine learning has attracted considerable research interest toward developing smart digital health interventions. These interventions have the potential to revolutionize health care and lead to substantial outcomes for patients and medical professionals.

Objective

Our objective was to review the literature on applications of machine learning in real-life digital health interventions, aiming to improve the understanding of researchers, clinicians, engineers, and policy makers in developing robust and impactful data-driven interventions in the health care domain.

Methods

We searched the PubMed and Scopus bibliographic databases with terms related to machine learning, to identify real-life studies of digital health interventions incorporating machine learning algorithms. We grouped those interventions according to their target (ie, target condition), study design, number of enrolled participants, follow-up duration, primary outcome and whether this had been statistically significant, machine learning algorithms used in the intervention, and outcome of the algorithms (eg, prediction).

Results

Our literature search identified 8 interventions incorporating machine learning in a real-life research setting, of which 3 (37%) were evaluated in a randomized controlled trial and 5 (63%) in a pilot or experimental single-group study. The interventions targeted depression prediction and management, speech recognition for people with speech disabilities, self-efficacy for weight loss, detection of changes in biopsychosocial condition of patients with multiple morbidity, stress management, treatment of phantom limb pain, smoking cessation, and personalized nutrition based on glycemic response. The average number of enrolled participants in the studies was 71 (range 8-214), and the average follow-up study duration was 69 days (range 3-180). Of the 8 interventions, 6 (75%) showed statistical significance (at the P=.05 level) in health outcomes.

Conclusions

This review found that digital health interventions incorporating machine learning algorithms in real-life studies can be useful and effective. Given the low number of studies identified in this review and that they did not follow a rigorous machine learning evaluation methodology, we urge the research community to conduct further studies in intervention settings following evaluation principles and demonstrating the potential of machine learning in clinical practice.",,pdf:https://www.jmir.org/2019/4/e12286/PDF; doi:https://doi.org/10.2196/12286; html:https://europepmc.org/articles/PMC6473205 33212507,https://doi.org/10.1093/molbev/msaa279,Genomic Analysis Revealed a Convergent Evolution of LINE-1 in Coat Color: A Case Study in Water Buffaloes (Bubalus bubalis).,"Liang D, Zhao P, Si J, Fang L, Pairo-Castineira E, Hu X, Xu Q, Hou Y, Gong Y, Liang Z, Tian B, Mao H, Yindee M, Faruque MO, Kongvongxay S, Khamphoumee S, Liu GE, Wu DD, Barker JSF, Han J, Zhang Y.",,Molecular biology and evolution,2021,2021-03-01,Y,Transposon; Water buffalo; Convergent Evolution; Line-1; Asip Gene; White Coat Color,,,"Visible pigmentation phenotypes can be used to explore the regulation of gene expression and the evolution of coat color patterns in animals. Here, we performed whole-genome and RNA sequencing and applied genome-wide association study, comparative population genomics and biological experiments to show that the 2,809-bp-long LINE-1 insertion in the ASIP (agouti signaling protein) gene is the causative mutation for the white coat phenotype in swamp buffalo (Bubalus bubalis). This LINE-1 insertion (3' truncated and containing only 5' UTR) functions as a strong proximal promoter that leads to a 10-fold increase in the transcription of ASIP in white buffalo skin. The 165 bp of 5' UTR transcribed from the LINE-1 is spliced into the first coding exon of ASIP, resulting in a chimeric transcript. The increased expression of ASIP prevents melanocyte maturation, leading to the absence of pigment in white buffalo skin and hairs. Phylogenetic analyses indicate that the white buffalo-specific ASIP allele originated from a recent genetic transposition event in swamp buffalo. Interestingly, as a similar LINE-1 insertion has been identified in the cattle ASIP gene, we discuss the convergent mechanism of coat color evolution in the Bovini tribe.",,pdf:https://academic.oup.com/mbe/article-pdf/38/3/1122/36533820/msaa279.pdf; doi:https://doi.org/10.1093/molbev/msaa279; html:https://europepmc.org/articles/PMC7947781; pdf:https://europepmc.org/articles/PMC7947781?pdf=render -38837310,https://doi.org/10.1002/ejhf.3306,"A nationwide, population-based study on specialized care for acute heart failure throughout the COVID-19 pandemic.","Cannata A, Mizani MA, Bromage DI, Piper SE, Hardman SMC, Sudlow C, de Belder M, Deanfield J, Gardner RS, Clark AL, Cleland JGF, McDonagh TA,  on behalf of the CVD‐COVID‐UK/COVID‐IMPACT Consortium.",,European journal of heart failure,2024,2024-06-04,N,Heart Failure; Specialist Care; Covid‐19; National Heart Failure Audit,,,"

Aims

The COVID-19 pandemic disrupted the delivery of care for patients with heart failure (HF), leading to fewer HF hospitalizations and increased mortality. However, nationwide data on quality of care and long-term outcomes across the pandemic are scarce.

Methods and results

We used data from the National Heart Failure Audit (NHFA) linked to national records for hospitalization and deaths. We compared pre-COVID (2018-2019), COVID (2020), and late/post-COVID (2021-2022) periods. Data for 227 250 patients admitted to hospital with HF were analysed and grouped according to the admission year and the presence of HF with (HFrEF) or without reduced ejection fraction (non-HFrEF). The median age at admission was 81 years (interquartile range 72-88), 55% were men (n = 125 975), 87% were of white ethnicity (n = 102 805), and 51% had HFrEF (n = 116 990). In-hospital management and specialized cardiology care were maintained throughout the pandemic with an increasing percentage of patients discharged on disease-modifying medications over time (p < 0.001). Long-term outcomes improved over time (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.90-0.95, p < 0.001), mainly driven by a reduction in cardiovascular death. Receiving specialized cardiology care was associated with better long-term outcomes both for those who had HFrEF (HR 0.79, 95% CI 0.77-0.82, p < 0.001) and for those who had non-HFrEF (HR 0.87, 95% CI 0.85-0.90, p < 0.001).

Conclusions

Despite the disruption of healthcare systems, the clinical characteristics of patients admitted with HF were similar and the overall standard of care was maintained throughout the pandemic. Long-term survival of patients hospitalized with HF continued to improve after COVID-19, especially for HFrEF.",,doi:https://doi.org/10.1002/ejhf.3306; doi:https://doi.org/10.1002/ejhf.3306 34534697,https://doi.org/10.1016/j.jbi.2021.103916,Ranking sets of morbidities using hypergraph centrality.,"Rafferty J, Watkins A, Lyons J, Lyons RA, Akbari A, Peek N, Jalali-Najafabadi F, Ba Dhafari T, Pate A, Martin GP, Bailey R.",,Journal of biomedical informatics,2021,2021-09-15,Y,Network Analysis; Hypergraph; Multi-morbidity,,,"Multi-morbidity, the health state of having two or more concurrent chronic conditions, is becoming more common as populations age, but is poorly understood. Identifying and understanding commonly occurring sets of diseases is important to inform clinical decisions to improve patient services and outcomes. Network analysis has been previously used to investigate multi-morbidity, but a classic application only allows for information on binary sets of diseases to contribute to the graph. We propose the use of hypergraphs, which allows for the incorporation of data on people with any number of conditions, and also allows us to obtain a quantitative understanding of the centrality, a measure of how well connected items in the network are to each other, of both single diseases and sets of conditions. Using this framework we illustrate its application with the set of conditions described in the Charlson morbidity index using data extracted from routinely collected population-scale, patient level electronic health records (EHR) for a cohort of adults in Wales, UK. Stroke and diabetes were found to be the most central single conditions. Sets of diseases featuring diabetes; diabetes with Chronic Pulmonary Disease, Renal Disease, Congestive Heart Failure and Cancer were the most central pairs of diseases. We investigated the differences between results obtained from the hypergraph and a classic binary graph and found that the centrality of diseases such as paraplegia, which are connected strongly to a single other disease is exaggerated in binary graphs compared to hypergraphs. The measure of centrality is derived from the weighting metrics calculated for disease sets and further investigation is needed to better understand the effect of the metric used in identifying the clinical significance and ranked centrality of grouped diseases. These initial results indicate that hypergraphs can be used as a valuable tool for analysing previously poorly understood relationships and information available in EHR data.",,doi:https://doi.org/10.1016/j.jbi.2021.103916; doi:https://doi.org/10.1016/j.jbi.2021.103916; html:https://europepmc.org/articles/PMC8524321 -38833617,https://doi.org/10.1093/cvr/cvae123,Sex inequalities in cardiovascular risk prediction.,"Elliott J, Bodinier B, Whitaker M, Wada R, Cooke G, Ward H, Tzoulaki I, Elliott P, Chadeau-Hyam M.",,Cardiovascular research,2024,2024-06-04,N,Biomarkers; Cvd Risk Prediction; Pooled Cohort Equations; Qrisk3; Sparse Variable Selection,,,"

Aims

Evaluate sex differences in cardiovascular disease (CVD) risk prediction, including use of i) optimal sex-specific risk predictors and ii) sex-specific risk thresholds.

Methods and results

Prospective cohort study using UK Biobank, including 121,724 and 182,632 healthy men and women, respectively, aged 38-73 years at baseline. There were 11,899 (men) and 9,110 (women) incident CVD cases (hospitalization or mortality) with median 12.1 years follow-up. We used recalibrated Pooled Cohort Equations (PCE, 7.5% 10-year risk threshold as per US guidelines), QRISK3 (10% 10-year risk threshold as per UK guidelines) and Cox survival models using sparse sex-specific variable sets (via LASSO stability selection) to predict CVD risk separately in men and women. LASSO stability selection included 12 variables in common between men and women, with three additional variables selected for men and one for women. C-statistics were slightly lower for PCE than QRISK3 and models using stably-selected variables, but were similar between men and women: 0.67 [0.66-0.68], 0.70 [0.69-0.71], and 0.71 [0.70-0.72] in men and 0.69 [0.68-0.70], 0.72 [0.71-0.73], and 0.72 [0.71-0.73] in women for PCE, QRISK3 and models using stably-selected variables, respectively. At current clinically implemented risk thresholds, test sensitivity was markedly lower in women than men for all models: at 7.5% 10-year risk, sensitivity was 65.1% and 68.2% in men and 24.0% and 33.4% in women for PCE and models using stably-selected variables, respectively; at 10% 10-year risk, sensitivity was 53.7% and 52.3% in men and 16.8% and 20.2% in women for QRISK3 and models using stably-selected variables, respectively. Specificity was correspondingly higher in women than men. However, the sensitivity in women at 5% 10-year risk threshold increased to 50.1%, 58.5% and 55.7% for PCE, QRISK3 and models using stably-selected variables, respectively.

Conclusions

Use of sparse sex-specific variables improved CVD risk prediction compared with PCE but not QRISK3. At current risk thresholds, PCE and QRISK3 work less well for women than men but sensitivity was improved in women using a 5% 10-year risk threshold. Use of sex-specific risk thresholds should be considered in any re-evaluation of CVD risk calculators.

Translational perspective

Cardiovascular disease (CVD) risk prediction is an important component of clinical risk management and disease prevention. We find that at risk prediction thresholds used by currently applied risk prediction algorithms (PCE 7.5% 10-year risk threshold in the US and QRISK3 10% risk threshold in the UK), sensitivity of these risk prediction tools is markedly lower in women than in men. This sex inequality implies that women are proportionately less likely to receive appropriate clinical management including lipid-lowering therapy. If the risk prediction threshold is lowered to 5% 10-year risk in women, then sensitivity in women is substantially increased.",,doi:https://doi.org/10.1093/cvr/cvae123 +38837310,https://doi.org/10.1002/ejhf.3306,"A nationwide, population-based study on specialized care for acute heart failure throughout the COVID-19 pandemic.","Cannata A, Mizani MA, Bromage DI, Piper SE, Hardman SMC, Sudlow C, de Belder M, Deanfield J, Gardner RS, Clark AL, Cleland JGF, McDonagh TA,  on behalf of the CVD‐COVID‐UK/COVID‐IMPACT Consortium.",,European journal of heart failure,2024,2024-06-04,N,Heart Failure; Specialist Care; Covid‐19; National Heart Failure Audit,,,"

Aims

The COVID-19 pandemic disrupted the delivery of care for patients with heart failure (HF), leading to fewer HF hospitalizations and increased mortality. However, nationwide data on quality of care and long-term outcomes across the pandemic are scarce.

Methods and results

We used data from the National Heart Failure Audit (NHFA) linked to national records for hospitalization and deaths. We compared pre-COVID (2018-2019), COVID (2020), and late/post-COVID (2021-2022) periods. Data for 227 250 patients admitted to hospital with HF were analysed and grouped according to the admission year and the presence of HF with (HFrEF) or without reduced ejection fraction (non-HFrEF). The median age at admission was 81 years (interquartile range 72-88), 55% were men (n = 125 975), 87% were of white ethnicity (n = 102 805), and 51% had HFrEF (n = 116 990). In-hospital management and specialized cardiology care were maintained throughout the pandemic with an increasing percentage of patients discharged on disease-modifying medications over time (p < 0.001). Long-term outcomes improved over time (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.90-0.95, p < 0.001), mainly driven by a reduction in cardiovascular death. Receiving specialized cardiology care was associated with better long-term outcomes both for those who had HFrEF (HR 0.79, 95% CI 0.77-0.82, p < 0.001) and for those who had non-HFrEF (HR 0.87, 95% CI 0.85-0.90, p < 0.001).

Conclusions

Despite the disruption of healthcare systems, the clinical characteristics of patients admitted with HF were similar and the overall standard of care was maintained throughout the pandemic. Long-term survival of patients hospitalized with HF continued to improve after COVID-19, especially for HFrEF.",,doi:https://doi.org/10.1002/ejhf.3306; doi:https://doi.org/10.1002/ejhf.3306 37272361,https://doi.org/10.2340/actadv.v103.5268,Relationship between Eczema and Self-reported Difficulties Keeping up with School Education: A Cross-sectional Study.,"Beckman L, Hagquist C, Svensson Å, Langan SM, Von Kobyletzki L.",,Acta dermato-venereologica,2023,2023-06-05,Y,,,,"Eczema is a common chronic disease that affects both children and adults, and may have an adverse impact on school performance, as it is characteristically pruritic, and hence may lead to poor concentration and inadequate sleep. The aim of this study was to elucidate the relationship between eczema and self-reported difficulties keeping up with school education. The study was based on cross-sectional questionnaire data collected in schools among all 9th graders (15-16 years old) within a Swedish county. Logistic regression analyses were used to assess the association between having eczema and self-reported difficulties keeping up with school education. A total of 2,620 pupils participated (50.1% female). An increased odds ratio (OR) of self-reported difficulties keeping up with school education was found in adolescents with eczema compared with those without eczema after adjustment for sex and  family residence (OR 2.13, 95% confidence interval (95% CI) 1.32-3.44), and with additional adjustment for sleeping problems, attention-deficit hyperactivity disorder, allergy, rhinitis, asthma, and alcohol consumption (adjusted OR 1.78, CI 1.05-3.00). Eczema may be a relevant risk factor for difficulty keeping up with school education in adolescents. However, studies that can assess temporality, based in different settings with objective reports of both eczema and self-reported difficulties at school, are needed to confirm these findings.",,doi:https://doi.org/10.2340/actadv.v103.5268; html:https://europepmc.org/articles/PMC10259463; pdf:https://europepmc.org/articles/PMC10259463?pdf=render +38833617,https://doi.org/10.1093/cvr/cvae123,Sex inequalities in cardiovascular risk prediction.,"Elliott J, Bodinier B, Whitaker M, Wada R, Cooke G, Ward H, Tzoulaki I, Elliott P, Chadeau-Hyam M.",,Cardiovascular research,2024,2024-06-04,N,Biomarkers; Cvd Risk Prediction; Pooled Cohort Equations; Qrisk3; Sparse Variable Selection,,,"

Aims

Evaluate sex differences in cardiovascular disease (CVD) risk prediction, including use of i) optimal sex-specific risk predictors and ii) sex-specific risk thresholds.

Methods and results

Prospective cohort study using UK Biobank, including 121,724 and 182,632 healthy men and women, respectively, aged 38-73 years at baseline. There were 11,899 (men) and 9,110 (women) incident CVD cases (hospitalization or mortality) with median 12.1 years follow-up. We used recalibrated Pooled Cohort Equations (PCE, 7.5% 10-year risk threshold as per US guidelines), QRISK3 (10% 10-year risk threshold as per UK guidelines) and Cox survival models using sparse sex-specific variable sets (via LASSO stability selection) to predict CVD risk separately in men and women. LASSO stability selection included 12 variables in common between men and women, with three additional variables selected for men and one for women. C-statistics were slightly lower for PCE than QRISK3 and models using stably-selected variables, but were similar between men and women: 0.67 [0.66-0.68], 0.70 [0.69-0.71], and 0.71 [0.70-0.72] in men and 0.69 [0.68-0.70], 0.72 [0.71-0.73], and 0.72 [0.71-0.73] in women for PCE, QRISK3 and models using stably-selected variables, respectively. At current clinically implemented risk thresholds, test sensitivity was markedly lower in women than men for all models: at 7.5% 10-year risk, sensitivity was 65.1% and 68.2% in men and 24.0% and 33.4% in women for PCE and models using stably-selected variables, respectively; at 10% 10-year risk, sensitivity was 53.7% and 52.3% in men and 16.8% and 20.2% in women for QRISK3 and models using stably-selected variables, respectively. Specificity was correspondingly higher in women than men. However, the sensitivity in women at 5% 10-year risk threshold increased to 50.1%, 58.5% and 55.7% for PCE, QRISK3 and models using stably-selected variables, respectively.

Conclusions

Use of sparse sex-specific variables improved CVD risk prediction compared with PCE but not QRISK3. At current risk thresholds, PCE and QRISK3 work less well for women than men but sensitivity was improved in women using a 5% 10-year risk threshold. Use of sex-specific risk thresholds should be considered in any re-evaluation of CVD risk calculators.

Translational perspective

Cardiovascular disease (CVD) risk prediction is an important component of clinical risk management and disease prevention. We find that at risk prediction thresholds used by currently applied risk prediction algorithms (PCE 7.5% 10-year risk threshold in the US and QRISK3 10% risk threshold in the UK), sensitivity of these risk prediction tools is markedly lower in women than in men. This sex inequality implies that women are proportionately less likely to receive appropriate clinical management including lipid-lowering therapy. If the risk prediction threshold is lowered to 5% 10-year risk in women, then sensitivity in women is substantially increased.",,doi:https://doi.org/10.1093/cvr/cvae123 36921925,https://doi.org/10.1136/bmj-2022-072808,Comparative effectiveness of BNT162b2 versus mRNA-1273 covid-19 vaccine boosting in England: matched cohort study in OpenSAFELY-TPP.,"Hulme WJ, Horne EMF, Parker EPK, Keogh RH, Williamson EJ, Walker V, Palmer TM, Curtis HJ, Walker AJ, Andrews CD, Mehrkar A, Morley J, MacKenna B, Bacon SCJ, Goldacre B, Hernán MA, Sterne JAC.",,BMJ (Clinical research ed.),2023,2023-03-15,Y,,,,"

Objective

To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and mRNA-1273 (Moderna) covid-19 vaccines during the booster programme in England.

Design

Matched cohort study, emulating a comparative effectiveness trial.

Setting

Linked primary care, hospital, and covid-19 surveillance records available within the OpenSAFELY-TPP research platform, covering a period when the SARS-CoV-2 delta and omicron variants were dominant.

Participants

3 237 918 adults who received a booster dose of either vaccine between 29 October 2021 and 25 February 2022 as part of the national booster programme in England and who received a primary course of BNT162b2 or ChAdOx1.

Intervention

Vaccination with either BNT162b2 or mRNA-1273 as a booster vaccine dose.

Main outcome measures

Recorded SARS-CoV-2 positive test, covid-19 related hospital admission, covid-19 related death, and non-covid-19 related death at 20 weeks after receipt of the booster dose.

Results

1 618 959 people were matched in each vaccine group, contributing a total 64 546 391 person weeks of follow-up. The 20 week risks per 1000 for a positive SARS-CoV-2 test were 164.2 (95% confidence interval 163.3 to 165.1) for BNT162b2 and 159.9 (159.0 to 160.8) for mRNA-1273; the hazard ratio comparing mRNA-1273 with BNT162b2 was 0.95 (95% confidence interval 0.95 to 0.96). The 20 week risks per 1000 for hospital admission with covid-19 were 0.75 (0.71 to 0.79) for BNT162b2 and 0.65 (0.61 to 0.69) for mRNA-1273; the hazard ratio was 0.89 (0.82 to 0.95). Covid-19 related deaths were rare: the 20 week risks per 1000 were 0.028 (0.021 to 0.037) for BNT162b2 and 0.024 (0.018 to 0.033) for mRNA-1273; hazard ratio 0.83 (0.58 to 1.19). Comparative effectiveness was generally similar within subgroups defined by the primary course vaccine brand, age, previous SARS-CoV-2 infection, and clinical vulnerability. Relative benefit was similar when vaccines were compared separately in the delta and omicron variant eras.

Conclusions

This matched observational study of adults estimated a modest benefit of booster vaccination with mRNA-1273 compared with BNT162b2 in preventing positive SARS-CoV-2 tests and hospital admission with covid-19 20 weeks after vaccination, during a period of delta followed by omicron variant dominance.",,pdf:https://www.bmj.com/content/bmj/380/bmj-2022-072808.full.pdf; doi:https://doi.org/10.1136/bmj-2022-072808; html:https://europepmc.org/articles/PMC10014664; pdf:https://europepmc.org/articles/PMC10014664?pdf=render 36374585,https://doi.org/10.1177/01410768221131897,Using national electronic health records for pandemic preparedness: validation of a parsimonious model for predicting excess deaths among those with COVID-19-a data-driven retrospective cohort study.,"Mizani MA, Dashtban A, Pasea L, Lai AG, Thygesen J, Tomlinson C, Handy A, Mamza JB, Morris T, Khalid S, Zaccardi F, Macleod MJ, Torabi F, Canoy D, Akbari A, Berry C, Bolton T, Nolan J, Khunti K, Denaxas S, Hemingway H, Sudlow C, Banerjee A, CVD-COVID-UK Consortium.",,Journal of the Royal Society of Medicine,2023,2022-11-14,N,Infectious diseases; Clinical; epidemiology; Public Health; Health Informatics,,,"

Objectives

To use national, pre- and post-pandemic electronic health records (EHR) to develop and validate a scenario-based model incorporating baseline mortality risk, infection rate (IR) and relative risk (RR) of death for prediction of excess deaths.

Design

An EHR-based, retrospective cohort study.

Setting

Linked EHR in Clinical Practice Research Datalink (CPRD); and linked EHR and COVID-19 data in England provided in NHS Digital Trusted Research Environment (TRE).

Participants

In the development (CPRD) and validation (TRE) cohorts, we included 3.8 million and 35.1 million individuals aged ≥30 years, respectively.

Main outcome measures

One-year all-cause excess deaths related to COVID-19 from March 2020 to March 2021.

Results

From 1 March 2020 to 1 March 2021, there were 127,020 observed excess deaths. Observed RR was 4.34% (95% CI, 4.31-4.38) and IR was 6.27% (95% CI, 6.26-6.28). In the validation cohort, predicted one-year excess deaths were 100,338 compared with the observed 127,020 deaths with a ratio of predicted to observed excess deaths of 0.79.

Conclusions

We show that a simple, parsimonious model incorporating baseline mortality risk, one-year IR and RR of the pandemic can be used for scenario-based prediction of excess deaths in the early stages of a pandemic. Our analyses show that EHR could inform pandemic planning and surveillance, despite limited use in emergency preparedness to date. Although infection dynamics are important in the prediction of mortality, future models should take greater account of underlying conditions.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/01410768221131897; doi:https://doi.org/10.1177/01410768221131897; html:https://europepmc.org/articles/PMC9909113; pdf:https://europepmc.org/articles/PMC9909113?pdf=render; doi:https://doi.org/10.1177/01410768221131897 35172999,https://doi.org/10.1136/bmjopen-2021-052911,Can natural language processing models extract and classify instances of interpersonal violence in mental healthcare electronic records: an applied evaluative study.,"Botelle R, Bhavsar V, Kadra-Scalzo G, Mascio A, Williams MV, Roberts A, Velupillai S, Stewart R.",,BMJ open,2022,2022-02-16,Y,Psychiatry; Mental health; Public Health; Health Informatics,,,"

Objective

This paper evaluates the application of a natural language processing (NLP) model for extracting clinical text referring to interpersonal violence using electronic health records (EHRs) from a large mental healthcare provider.

Design

A multidisciplinary team iteratively developed guidelines for annotating clinical text referring to violence. Keywords were used to generate a dataset which was annotated (ie, classified as affirmed, negated or irrelevant) for: presence of violence, patient status (ie, as perpetrator, witness and/or victim of violence) and violence type (domestic, physical and/or sexual). An NLP approach using a pretrained transformer model, BioBERT (Bidirectional Encoder Representations from Transformers for Biomedical Text Mining) was fine-tuned on the annotated dataset and evaluated using 10-fold cross-validation.

Setting

We used the Clinical Records Interactive Search (CRIS) database, comprising over 500 000 de-identified EHRs of patients within the South London and Maudsley NHS Foundation Trust, a specialist mental healthcare provider serving an urban catchment area.

Participants

Searches of CRIS were carried out based on 17 predefined keywords. Randomly selected text fragments were taken from the results for each keyword, amounting to 3771 text fragments from the records of 2832 patients.

Outcome measures

We estimated precision, recall and F1 score for each NLP model. We examined sociodemographic and clinical variables in patients giving rise to the text data, and frequencies for each annotated violence characteristic.

Results

Binary classification models were developed for six labels (violence presence, perpetrator, victim, domestic, physical and sexual). Among annotations affirmed for the presence of any violence, 78% (1724) referred to physical violence, 61% (1350) referred to patients as perpetrator and 33% (731) to domestic violence. NLP models' precision ranged from 89% (perpetrator) to 98% (sexual); recall ranged from 89% (victim, perpetrator) to 97% (sexual).

Conclusions

State of the art NLP models can extract and classify clinical text on violence from EHRs at acceptable levels of scale, efficiency and accuracy.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e052911.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-052911; html:https://europepmc.org/articles/PMC8852656; pdf:https://europepmc.org/articles/PMC8852656?pdf=render @@ -759,8 +759,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 37954687,https://doi.org/10.1177/20552076231211551,"Moving from development to implementation of digital innovations within the NHS: myHealthE, a remote monitoring system for tracking patient outcomes in child and adolescent mental health services.","Morris AC, Ibrahim Z, Moghraby OS, Stringaris A, Grant IM, Zalewski L, McClellan S, Moriarty G, Simonoff E, Dobson RJ, Downs J.",,Digital health,2023,2023-01-01,Y,Health; Medicine; Psychology; Mental health; general; Studies; Paediatrics; Outcomes; Wellbeing; Mixed Methods; Online; Personalised Medicine; Mhealth; Electronic; Digital Health,,,"

Objective

This paper aims to report our experience of developing, implementing, and evaluating myHealthE (MHE), a digital innovation for Child and Adolescents Mental Health Services (CAMHS), which automates the remote collection and reporting of Patient-Reported Outcome Measures (PROMs) into National Health Services (NHS) electronic healthcare records.

Methods

We describe the logistical and governance issues encountered in developing the MHE interface with patient-identifiable information, and the steps taken to overcome these development barriers. We describe the application's architecture and hosting environment to enable its operability within the NHS, as well as the capabilities needed within the technical team to bridge the gap between academic development and NHS operational teams.

Results

We present evidence on the feasibility and acceptability of this system within clinical services and the process of iterative development, highlighting additional functions that were incorporated to increase system utility.

Conclusion

This article provides a framework with which to plan, develop, and implement automated PROM collection from remote devices back to NHS infrastructure. The challenges and solutions described in this paper will be pertinent to other digital health innovation researchers aspiring to deploy interoperable systems within NHS clinical systems.",,doi:https://doi.org/10.1177/20552076231211551; html:https://europepmc.org/articles/PMC10638880; pdf:https://europepmc.org/articles/PMC10638880?pdf=render 37156754,https://doi.org/10.1111/1471-0528.17531,Risk factors for a serious adverse outcome in neonates: a retrospective cohort study of vaginal births.,"Jindal S, Steer PJ, Savvidou M, Draycott T, Dixon-Woods M, Wood A, Kim LG.",,BJOG : an international journal of obstetrics and gynaecology,2023,2023-05-08,Y,risk factors; Meconium; Pyrexia; Intrapartum Fetal Monitoring; Labour Outcome; Fetal Deterioration,,,"

Objective

To investigate the hypothesis that risk factors in addition to an abnormal fetal heart rate pattern (aFHRp) are independently associated with adverse neonatal outcomes of labour.

Design

Observational prospective cohort study.

Setting

17 UK maternity units.

Sample

585 291 pregnancies between 1988 and 2000 inclusive.

Methods

Adjusted odds ratios (OR) with 95% confidence intervals (95% CI) were estimated from multivariable logistic regression.

Main outcome measures

Adverse neonatal outcome at term (5-minute Apgar score <7, and a composite measure comprising 5-minute Apgar score <7, resuscitation by intubation and/or perinatal death).

Results

Analysis was based on 302 137 vaginal births at 37-42 weeks inclusive. We found a higher odds of Apgar score at 5 minutes <7 with suspected fetal growth restriction (OR 1.34, 95% CI 1.16-1.53), induction of labour (OR 1.41, 95% CI 1.25-1.58), nulliparity (OR 1.48, 95% CI 1.34-1.63), booking body mass index ≥30 (OR 1.18, 95% CI 1.02-1.37), maternal age <25 (OR 1.23, 95% CI 1.10-1.39), black ethnicity (OR 1.21, 95% CI 1.03-1.43), early-term birth at 37-38 weeks (OR 1.13, 95% CI 1.02-1.25), late-term birth at 41-42 weeks (OR 1.14, 95% CI 1.01-1.28), use of oxytocin (OR 1.27, 95% CI 1.14-1.41), maternal pyrexia (OR 1.87, 95% CI 1.46-2.40), aFHRp and presence of meconium (aFHRp without meconium: OR 2.40, 95% CI 2.15-2.69; meconium without aFHRp: OR 2.20, 195% CI.94-2.49; both aFHRp and meconium: OR 4.26, 95% CI 3.74-4.87). The results were similar when the composite adverse outcome was considered.

Conclusions

A range of risk factors, including suspicion of fetal growth restriction, maternal pyrexia and presence of meconium, are implicated in poor birth outcomes in addition to aFHRp. Interpretation of the fetal heart rate pattern alone is insufficient as a basis for decisions about escalation and intervention.",,doi:https://doi.org/10.1111/1471-0528.17531; doi:https://doi.org/10.1111/1471-0528.17531; html:https://europepmc.org/articles/PMC10952606; pdf:https://europepmc.org/articles/PMC10952606?pdf=render 35780515,https://doi.org/10.1016/j.epidem.2022.100604,Appropriately smoothing prevalence data to inform estimates of growth rate and reproduction number.,"Eales O, Ainslie KEC, Walters CE, Wang H, Atchison C, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P, Riley S.",,Epidemics,2022,2022-06-22,Y,Cross-sectional study; Reproduction Number; Covid-19; Sars-cov-2; Bayesian P-Spline,,,"The time-varying reproduction number (Rt) can change rapidly over the course of a pandemic due to changing restrictions, behaviours, and levels of population immunity. Many methods exist that allow the estimation of Rt from case data. However, these are not easily adapted to point prevalence data nor can they infer Rt across periods of missing data. We developed a Bayesian P-spline model suitable for fitting to a wide range of epidemic time-series, including point-prevalence data. We demonstrate the utility of the model by fitting to periodic daily SARS-CoV-2 swab-positivity data in England from the first 7 rounds (May 2020-December 2020) of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Estimates of Rt over the period of two subsequent rounds (6-8 weeks) and single rounds (2-3 weeks) inferred using the Bayesian P-spline model were broadly consistent with estimates from a simple exponential model, with overlapping credible intervals. However, there were sometimes substantial differences in point estimates. The Bayesian P-spline model was further able to infer changes in Rt over shorter periods tracking a temporary increase above one during late-May 2020, a gradual increase in Rt over the summer of 2020 as restrictions were eased, and a reduction in Rt during England's second national lockdown followed by an increase as the Alpha variant surged. The model is robust against both under-fitting and over-fitting and is able to interpolate between periods of available data; it is a particularly versatile model when growth rate can change over small timescales, as in the current SARS-CoV-2 pandemic. This work highlights the importance of pairing robust methods with representative samples to track pandemics.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220254; doi:https://doi.org/10.1016/j.epidem.2022.100604; html:https://europepmc.org/articles/PMC9220254; pdf:https://europepmc.org/articles/PMC9220254?pdf=render -33634312,https://doi.org/10.1093/bib/bbab006,Benchmarking network-based gene prioritization methods for cerebral small vessel disease.,"Zhang H, Ferguson A, Robertson G, Jiang M, Zhang T, Sudlow C, Smith K, Rannikmae K, Wu H.",,Briefings in bioinformatics,2021,2021-09-01,Y,Cerebral Small Vessel Disease; Protein–protein Interaction; Benchmarking; Disease Gene Association; Network-based Gene Prioritization,,,"Network-based gene prioritization algorithms are designed to prioritize disease-associated genes based on known ones using biological networks of protein interactions, gene-disease associations (GDAs) and other relationships between biological entities. Various algorithms have been developed based on different mechanisms, but it is not obvious which algorithm is optimal for a specific disease. To address this issue, we benchmarked multiple algorithms for their application in cerebral small vessel disease (cSVD). We curated protein-gene interactions (PGIs) and GDAs from databases and assembled PGI networks and disease-gene heterogeneous networks. A screening of algorithms resulted in seven representative algorithms to be benchmarked. Performance of algorithms was assessed using both leave-one-out cross-validation (LOOCV) and external validation with MEGASTROKE genome-wide association study (GWAS). We found that random walk with restart on the heterogeneous network (RWRH) showed best LOOCV performance, with median LOOCV rediscovery rank of 185.5 (out of 19 463 genes). The GenePanda algorithm had most GWAS-confirmable genes in top 200 predictions, while RWRH had best ranks for small vessel stroke-associated genes confirmed in GWAS. In conclusion, RWRH has overall better performance for application in cSVD despite its susceptibility to bias caused by degree centrality. Choice of algorithms should be determined before applying to specific disease. Current pure network-based gene prioritization algorithms are unlikely to find novel disease-associated genes that are not associated with known ones. The tools for implementing and benchmarking algorithms have been made available and can be generalized for other diseases.",,pdf:https://www.pure.ed.ac.uk/ws/files/198917679/bbab006.pdf; doi:https://doi.org/10.1093/bib/bbab006; html:https://europepmc.org/articles/PMC8425308; pdf:https://europepmc.org/articles/PMC8425308?pdf=render 35611160,https://doi.org/10.1016/j.eclinm.2022.101462,Impact of first UK COVID-19 lockdown on hospital admissions: Interrupted time series study of 32 million people.,"Shah SA, Brophy S, Kennedy J, Fisher L, Walker A, Mackenna B, Curtis H, Inglesby P, Davy S, Bacon S, Goldacre B, Agrawal U, Moore E, Simpson CR, Macleod J, Cooksey R, Sheikh A, Katikireddi SV.",,EClinicalMedicine,2022,2022-05-20,Y,Pandemic; Healthcare Inequalities; Healthcare Disruption; Interrupted Time Series Analysis; Covid-19; Sars-cov-2,,,"

Background

Uncontrolled infection and lockdown measures introduced in response have resulted in an unprecedented challenge for health systems internationally. Whether such unprecedented impact was due to lockdown itself and recedes when such measures are lifted is unclear. We assessed the short- and medium-term impacts of the first lockdown measures on hospital care for tracer non-COVID-19 conditions in England, Scotland and Wales across diseases, sexes, and socioeconomic and ethnic groups.

Methods

We used OpenSAFELY (for England), EAVEII (Scotland), and SAIL Databank (Wales) to extract weekly hospital admission rates for cancer, cardiovascular and respiratory conditions (excluding COVID-19) from the pre-pandemic period until 25/10/2020 and conducted a controlled interrupted time series analysis. We undertook stratified analyses and assessed admission rates over seven months during which lockdown restrictions were gradually lifted.

Findings

Our combined dataset included 32 million people who contributed over 74 million person-years. Admission rates for all three conditions fell by 34.2% (Confidence Interval (CI): -43.0, -25.3) in England, 20.9% (CI: -27.8, -14.1) in Scotland, and 24.7% (CI: -36.7, -12.7) in Wales, with falls across every stratum considered. In all three nations, cancer-related admissions fell the most while respiratory-related admissions fell the least (e.g., rates fell by 40.5% (CI: -47.4, -33.6), 21.9% (CI: -35.4, -8.4), and 19.0% (CI: -30.6, -7.4) in England for cancer, cardiovascular-related, and respiratory-related admissions respectively). Unscheduled admissions rates fell more in the most than the least deprived quintile across all three nations. Some ethnic minority groups experienced greater falls in admissions (e.g., in England, unscheduled admissions fell by 9.5% (CI: -20.2, 1.2) for Whites, but 44.3% (CI: -71.0, -17.6), 34.6% (CI: -63.8, -5.3), and 25.6% (CI: -45.0, -6.3) for Mixed, Other and Black ethnic groups respectively). Despite easing of restrictions, the overall admission rates remained lower in England, Scotland, and Wales by 20.8%, 21.6%, and 22.0%, respectively when compared to the same period (August-September) during the pre-pandemic years. This corresponds to a reduction of 26.2, 23.8 and 30.2 admissions per 100,000 people in England, Scotland, and Wales respectively.

Interpretation

Hospital care for non-COVID diseases fell substantially across England, Scotland, and Wales during the first lockdown, with reductions persisting for at least six months. The most deprived and minority ethnic groups were impacted more severely.

Funding

This work was funded by the Medical Research Council as part of the Lifelong Health and Wellbeing study as part of National Core Studies (MC_PC_20030). SVK acknowledges funding from the Medical Research Council (MC_UU_00022/2), and the Scottish Government Chief Scientist Office (SPHSU17). EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE - The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. BG has received research funding from the NHS National Institute for Health Research (NIHR), the Wellcome Trust, Health Data Research UK, Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme.",,pdf:http://www.thelancet.com/article/S2589537022001924/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101462; html:https://europepmc.org/articles/PMC9121886; pdf:https://europepmc.org/articles/PMC9121886?pdf=render +33634312,https://doi.org/10.1093/bib/bbab006,Benchmarking network-based gene prioritization methods for cerebral small vessel disease.,"Zhang H, Ferguson A, Robertson G, Jiang M, Zhang T, Sudlow C, Smith K, Rannikmae K, Wu H.",,Briefings in bioinformatics,2021,2021-09-01,Y,Cerebral Small Vessel Disease; Protein–protein Interaction; Benchmarking; Disease Gene Association; Network-based Gene Prioritization,,,"Network-based gene prioritization algorithms are designed to prioritize disease-associated genes based on known ones using biological networks of protein interactions, gene-disease associations (GDAs) and other relationships between biological entities. Various algorithms have been developed based on different mechanisms, but it is not obvious which algorithm is optimal for a specific disease. To address this issue, we benchmarked multiple algorithms for their application in cerebral small vessel disease (cSVD). We curated protein-gene interactions (PGIs) and GDAs from databases and assembled PGI networks and disease-gene heterogeneous networks. A screening of algorithms resulted in seven representative algorithms to be benchmarked. Performance of algorithms was assessed using both leave-one-out cross-validation (LOOCV) and external validation with MEGASTROKE genome-wide association study (GWAS). We found that random walk with restart on the heterogeneous network (RWRH) showed best LOOCV performance, with median LOOCV rediscovery rank of 185.5 (out of 19 463 genes). The GenePanda algorithm had most GWAS-confirmable genes in top 200 predictions, while RWRH had best ranks for small vessel stroke-associated genes confirmed in GWAS. In conclusion, RWRH has overall better performance for application in cSVD despite its susceptibility to bias caused by degree centrality. Choice of algorithms should be determined before applying to specific disease. Current pure network-based gene prioritization algorithms are unlikely to find novel disease-associated genes that are not associated with known ones. The tools for implementing and benchmarking algorithms have been made available and can be generalized for other diseases.",,pdf:https://www.pure.ed.ac.uk/ws/files/198917679/bbab006.pdf; doi:https://doi.org/10.1093/bib/bbab006; html:https://europepmc.org/articles/PMC8425308; pdf:https://europepmc.org/articles/PMC8425308?pdf=render 33587202,https://doi.org/10.1007/s10654-021-00722-y,COVID-19 mortality in the UK Biobank cohort: revisiting and evaluating risk factors.,"Elliott J, Bodinier B, Whitaker M, Delpierre C, Vermeulen R, Tzoulaki I, Elliott P, Chadeau-Hyam M.",,European journal of epidemiology,2021,2021-02-15,Y,Risk factor; Prospective Cohort; Uk Biobank; Sars-cov-2; Covid-19 Mortality,,,"Most studies of severe/fatal COVID-19 risk have used routine/hospitalisation data without detailed pre-morbid characterisation. Using the community-based UK Biobank cohort, we investigate risk factors for COVID-19 mortality in comparison with non-COVID-19 mortality. We investigated demographic, social (education, income, housing, employment), lifestyle (smoking, drinking, body mass index), biological (lipids, cystatin C, vitamin D), medical (comorbidities, medications) and environmental (air pollution) data from UK Biobank (N = 473,550) in relation to 459 COVID-19 and 2626 non-COVID-19 deaths to 21 September 2020. We used univariate, multivariable and penalised regression models. Age (OR = 2.76 [2.18-3.49] per S.D. [8.1 years], p = 2.6 × 10-17), male sex (OR = 1.47 [1.26-1.73], p = 1.3 × 10-6) and Black versus White ethnicity (OR = 1.21 [1.12-1.29], p = 3.0 × 10-7) were independently associated with and jointly explanatory of (area under receiver operating characteristic curve, AUC = 0.79) increased risk of COVID-19 mortality. In multivariable regression, alongside demographic covariates, being a healthcare worker, current smoker, having cardiovascular disease, hypertension, diabetes, autoimmune disease, and oral steroid use at enrolment were independently associated with COVID-19 mortality. Penalised regression models selected income, cardiovascular disease, hypertension, diabetes, cystatin C, and oral steroid use as jointly contributing to COVID-19 mortality risk; Black ethnicity, hypertension and oral steroid use contributed to COVID-19 but not non-COVID-19 mortality. Age, male sex and Black ethnicity, as well as comorbidities and oral steroid use at enrolment were associated with increased risk of COVID-19 death. Our results suggest that previously reported associations of COVID-19 mortality with body mass index, low vitamin D, air pollutants, renin-angiotensin-aldosterone system inhibitors may be explained by the aforementioned factors.",,pdf:https://link.springer.com/content/pdf/10.1007/s10654-021-00722-y.pdf; doi:https://doi.org/10.1007/s10654-021-00722-y; html:https://europepmc.org/articles/PMC7882869; pdf:https://europepmc.org/articles/PMC7882869?pdf=render 35440469,https://doi.org/10.3399/bjgp.2022.0083,"Colchicine for COVID-19 in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial.","Dorward J, Yu LM, Hayward G, Saville BR, Gbinigie O, Van Hecke O, Ogburn E, Evans PH, Thomas NP, Patel MG, Richards D, Berry N, Detry MA, Saunders C, Fitzgerald M, Harris V, Shanyinde M, de Lusignan S, Andersson MI, Butler CC, Hobbs FR, PRINCIPLE Trial Collaborative Group.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2022,2022-06-30,Y,Colchicine; Community; Primary Health Care; Randomised Controlled Trial; Covid-19,,,"

Background

Colchicine has been proposed as a COVID-19 treatment.

Aim

To determine whether colchicine reduces time to recovery and COVID-19-related admissions to hospital and/or deaths among people in the community.

Design and setting

Prospective, multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial (PRINCIPLE).

Method

Adults aged ≥65 years or ≥18 years with comorbidities or shortness of breath, and unwell for ≤14 days with suspected COVID-19 in the community, were randomised to usual care, usual care plus colchicine (500 µg daily for 14 days), or usual care plus other interventions. The co-primary endpoints were time to first self-reported recovery and admission to hospital/death related to COVID-19, within 28 days, analysed using Bayesian models.

Results

The trial opened on 2 April 2020. Randomisation to colchicine started on 4 March 2021 and stopped on 26 May 2021 because the prespecified time to recovery futility criterion was met. The primary analysis model included 2755 participants who were SARS-CoV-2 positive, randomised to colchicine (n = 156), usual care (n = 1145), and other treatments (n = 1454). Time to first self-reported recovery was similar in the colchicine group compared with usual care with an estimated hazard ratio of 0.92 (95% credible interval (CrI) = 0.72 to 1.16) and an estimated increase of 1.4 days in median time to self-reported recovery for colchicine versus usual care. The probability of meaningful benefit in time to recovery was very low at 1.8%. COVID-19-related admissions to hospital/deaths were similar in the colchicine group versus usual care, with an estimated odds ratio of 0.76 (95% CrI = 0.28 to 1.89) and an estimated difference of -0.4% (95% CrI = -2.7 to 2.4).

Conclusion

Colchicine did not improve time to recovery in people at higher risk of complications with COVID-19 in the community.",,pdf:https://bjgp.org/content/bjgp/72/720/e446.full.pdf; doi:https://doi.org/10.3399/BJGP.2022.0083; html:https://europepmc.org/articles/PMC9037186; pdf:https://europepmc.org/articles/PMC9037186?pdf=render 37781298,https://doi.org/10.3389/fcvm.2023.1141026,Radiomics analysis enhances the diagnostic performance of CMR stress perfusion: a proof-of-concept study using the Dan-NICAD dataset.,"Raisi-Estabragh Z, Martin-Isla C, Nissen L, Szabo L, Campello VM, Escalera S, Winther S, Bøttcher M, Lekadir K, Petersen SE.",,Frontiers in cardiovascular medicine,2023,2023-09-15,Y,Machine Learning (Ml); Radiomics; Cmr (Cardiovascular Magnetic Resonance); Stress Perfusion Cardiac Mri; Dan-nicad,,,"

Objectives

To assess the feasibility of extracting radiomics signal intensity based features from the myocardium using cardiovascular magnetic resonance (CMR) imaging stress perfusion sequences. Furthermore, to compare the diagnostic performance of radiomics models against standard-of-care qualitative visual assessment of stress perfusion images, with the ground truth stenosis label being defined by invasive Fractional Flow Reserve (FFR) and quantitative coronary angiography.

Methods

We used the Dan-NICAD 1 dataset, a multi-centre study with coronary computed tomography angiography, 1,5 T CMR stress perfusion, and invasive FFR available for a subset of 148 patients with suspected coronary artery disease. Image segmentation was performed by two independent readers. We used the Pyradiomics platform to extract radiomics first-order (n = 14) and texture (n = 75) features from the LV myocardium (basal, mid, apical) in rest and stress perfusion images.

Results

Overall, 92 patients (mean age 62 years, 56 men) were included in the study, 39 with positive FFR. We double-cross validated the model and, in each inner fold, we trained and validated a per territory model. The conventional analysis results reported sensitivity of 41% and specificity of 84%. Our final radiomics model demonstrated an improvement on these results with an average sensitivity of 53% and specificity of 86%.

Conclusion

In this proof-of-concept study from the Dan-NICAD dataset, we demonstrate the feasibility of radiomics analysis applied to CMR perfusion images with a suggestion of superior diagnostic performance of radiomics models over conventional visual analysis of perfusion images in picking up perfusion defects defined by invasive coronary angiography.",,doi:https://doi.org/10.3389/fcvm.2023.1141026; html:https://europepmc.org/articles/PMC10541220; pdf:https://europepmc.org/articles/PMC10541220?pdf=render @@ -778,8 +778,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 34249083,https://doi.org/10.3389/fgene.2021.652878,Polymorphism in INSR Locus Modifies Risk of Atrial Fibrillation in Patients on Thyroid Hormone Replacement Therapy.,"Soto-Pedre E, Siddiqui MK, Maroteau C, Dawed AY, Doney AS, Palmer CNA, Pearson ER, Leese GP.",,Frontiers in genetics,2021,2021-06-23,Y,Genetics; Insulin receptor; Hypothyroidism; Atrial fibrillation; Thyroid Hormone Replacement Therapy,,,"

Aims

Atrial fibrillation (AF) is a risk for patients receiving thyroid hormone replacement therapy. No published work has focused on pharmacogenetics relevant to thyroid dysfunction and AF risk. We aimed to assess the effect of L-thyroxine on AF risk stratified by a variation in a candidate gene.

Methods and results

A retrospective follow-up study was done among European Caucasian patients from the Genetics of Diabetes Audit and Research in Tayside Scotland cohort (Scotland, United Kingdom). Linked data on biochemistry, prescribing, hospital admissions, demographics, and genetic biobank were used to ascertain patients on L-thyroxine and diagnosis of AF. A GWAS-identified insulin receptor-INSR locus (rs4804416) was the candidate gene. Cox survival models and sensitivity analyses by taking competing risk of death into account were used. Replication was performed in additional sample (The Genetics of Scottish Health Research register, GoSHARE), and meta-analyses across the results of the study and replication cohorts were done. We analyzed 962 exposed to L-thyroxine and 5,840 unexposed patients who were rs4804416 genotyped. The rarer G/G genotype was present in 18% of the study population. The total follow-up was up to 20 years, and there was a significant increased AF risk for patients homozygous carriers of the G allele exposed to L-thyroxine (RHR = 2.35, P = 1.6e-02). The adjusted increased risk was highest within the first 3 years of exposure (RHR = 9.10, P = 8.5e-04). Sensitivity analysis yielded similar results. Effects were replicated in GoSHARE (n = 3,190).

Conclusion

Homozygous G/G genotype at the INSR locus (rs4804416) is associated with an increased risk of AF in patients on L-thyroxine, independent of serum of free thyroxine and thyroid-stimulating hormone serum concentrations.",,pdf:https://www.frontiersin.org/articles/10.3389/fgene.2021.652878/pdf; doi:https://doi.org/10.3389/fgene.2021.652878; html:https://europepmc.org/articles/PMC8260687; pdf:https://europepmc.org/articles/PMC8260687?pdf=render 36933612,https://doi.org/10.1016/j.cct.2023.107162,Healthcare systems data in the context of clinical trials - A comparison of cardiovascular data from a clinical trial dataset with routinely collected data.,"Macnair A, Nankivell M, Murray ML, Rosen SD, Appleyard S, Sydes MR, Forcat S, Welland A, Clarke NW, Mangar S, Kynaston H, Kockelbergh R, Al-Hasso A, Deighan J, Marshall J, Parmar M, Langley RE, Gilbert DC.",,Contemporary clinical trials,2023,2023-03-16,N,Cardiovascular disease; prostate cancer; Clinical Trials; Healthcare Systems Data,,,"

Background

Routinely-collected healthcare systems data (HSD) are proposed to improve the efficiency of clinical trials. A comparison was undertaken between cardiovascular (CVS) data from a clinical trial database with two HSD resources.

Methods

Protocol-defined and clinically reviewed CVS events (heart failure (HF), acute coronary syndrome (ACS), thromboembolic stroke, venous and arterial thromboembolism) were identified within the trial data. Data (using pre-specified codes) was obtained from NHS Hospital Episode Statistics (HES) and National Institute for Cardiovascular Outcomes Research (NICOR) HF and myocardial ischaemia audits for trial participants recruited in England between 2010 and 2018 who had provided consent. The primary comparison was trial data versus HES inpatient (APC) main diagnosis (Box-1). Correlations are presented with descriptive statistics and Venn diagrams. Reasons for non-correlation were explored.

Results

From 1200 eligible participants, 71 protocol-defined clinically reviewed CVS events were recorded in the trial database. 45 resulted in a hospital admission and therefore could have been recorded by either HES APC/ NICOR. Of these, 27/45 (60%) were recorded by HES inpatient (Box-1) with an additional 30 potential events also identified. HF and ACS were potentially recorded in all 3 datasets; trial data recorded 18, HES APC 29 and NICOR 24 events respectively. 12/18 (67%) of the HF/ACS events in the trial dataset were recorded by NICOR.

Conclusion

Concordance between datasets was lower than anticipated and the HSD used could not straightforwardly replace current trial practices, nor directly identify protocol-defined CVS events. Further work is required to improve the quality of HSD and consider event definitions when designing clinical trials incorporating HSD.",,doi:https://doi.org/10.1016/j.cct.2023.107162; doi:https://doi.org/10.1016/j.cct.2023.107162 35932242,https://doi.org/10.1093/ageing/afac176,"Annual risk of falls resulting in emergency department and hospital attendances for older people: an observational study of 781,081 individuals living in Wales (United Kingdom) including deprivation, frailty and dementia diagnoses between 2010 and 2020.","Hollinghurst R, Williams N, Pedrick-Case R, North L, Long S, Fry R, Hollinghurst J.",,Age and ageing,2022,2022-08-01,Y,Frailty; Dementia; Falls; Older People; Covid-19,,,"

Background

falls are common in older people, but associations between falls, dementia and frailty are relatively unknown. The impact of the COVID-19 pandemic on falls admissions has not been studied.

Aim

to investigate the impact of dementia, frailty, deprivation, previous falls and the differences between years for falls resulting in an emergency department (ED) or hospital admission.

Study design

longitudinal cross-sectional observational study.

Setting

older people (aged 65+) resident in Wales between 1 January 2010 and 31 December 2020.

Methods

we created a binary (yes/no) indicator for a fall resulting in an attendance to an ED, hospital or both, per person, per year. We analysed the outcomes using multilevel logistic and multinomial models.

Results

we analysed a total of 5,141,244 person years of data from 781,081 individuals. Fall admission rates were highest in 2012 (4.27%) and lowest in 2020 (4.27%). We found an increased odds ratio (OR [95% confidence interval]) of a fall admission for age (1.05 [1.05, 1.05] per year of age), people with dementia (2.03 [2.00, 2.06]) and people who had a previous fall (2.55 [2.51, 2.60]). Compared with fit individuals, those with frailty had ORs of 1.60 [1.58, 1.62], 2.24 [2.21, 2.28] and 2.94 [2.89, 3.00] for mild, moderate and severe frailty respectively. Reduced odds were observed for males (0.73 [0.73, 0.74]) and less deprived areas; most deprived compared with least OR 0.75 [0.74, 0.76].

Conclusions

falls prevention should be targeted to those at highest risk, and investigations into the reduction in admissions in 2020 is warranted.",,doi:https://doi.org/10.1093/ageing/afac176; doi:https://doi.org/10.1093/ageing/afac176; html:https://europepmc.org/articles/PMC9356534; pdf:https://europepmc.org/articles/PMC9356534?pdf=render -38528230,https://doi.org/10.1038/s43587-024-00590-7,Integration of polygenic and gut metagenomic risk prediction for common diseases.,"Liu Y, Ritchie SC, Teo SM, Ruuskanen MO, Kambur O, Zhu Q, Sanders J, Vázquez-Baeza Y, Verspoor K, Jousilahti P, Lahti L, Niiranen T, Salomaa V, Havulinna AS, Knight R, Méric G, Inouye M.",,Nature aging,2024,2024-03-25,Y,,,,"Multiomics has shown promise in noninvasive risk profiling and early detection of various common diseases. In the present study, in a prospective population-based cohort with ~18 years of e-health record follow-up, we investigated the incremental and combined value of genomic and gut metagenomic risk assessment compared with conventional risk factors for predicting incident coronary artery disease (CAD), type 2 diabetes (T2D), Alzheimer disease and prostate cancer. We found that polygenic risk scores (PRSs) improved prediction over conventional risk factors for all diseases. Gut microbiome scores improved predictive capacity over baseline age for CAD, T2D and prostate cancer. Integrated risk models of PRSs, gut microbiome scores and conventional risk factors achieved the highest predictive performance for all diseases studied compared with models based on conventional risk factors alone. The present study demonstrates that integrated PRSs and gut metagenomic risk models improve the predictive value over conventional risk factors for common chronic diseases.",,pdf:https://www.nature.com/articles/s43587-024-00590-7.pdf; doi:https://doi.org/10.1038/s43587-024-00590-7; html:https://europepmc.org/articles/PMC11031402; pdf:https://europepmc.org/articles/PMC11031402?pdf=render 35802764,https://doi.org/10.7189/jogh.12.05025,COVID-19 vaccine effectiveness against symptomatic SARS-CoV-2 infection and severe COVID-19 outcomes from Delta AY.4.2: Cohort and test-negative study of 5.4 million individuals in Scotland.,"Kerr S, Vasileiou E, Robertson C, Sheikh A.",,Journal of global health,2022,2022-07-09,Y,,,,"

Background

In July 2021, a new variant of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in the Delta lineage was detected in the United Kingdom (UK), named AY.4.2 or ""Delta plus"". By October 2021, the AY.4.2 variant accounted for approximately 10-11% of cases in the UK. AY.4.2 was designated as a variant under investigation by the UK Health and Security Agency on 20 October 2021. This study aimed to investigate vaccine effectiveness (VE) against symptomatic COVID-19 (Coronavirus disease 2019) infection and COVID-19 hospitalisation/death for the AY.4.2 variant.

Methods

We used the Scotland-wide Early Pandemic Evaluation and Enhanced Surveillance (EAVE-II) platform to estimate the VE of the ChAdOx1, BNT162b2, and mRNA-1273 vaccines against symptomatic infection and severe COVID-19 outcomes in adults. The study was conducted from June 8 to October 25, 2021. We used a test-negative design (TND) to estimate VE against reverse transcriptase polymerase chain reaction (RT-PCR) confirmed symptomatic SARS-CoV-2 infection while adjusting for sex, socioeconomic status, number of coexisting conditions, and splines in time and age. We also performed a cohort study using a Cox proportional hazards model to estimate VE against a composite outcome of COVID-19 hospital admission or death, with the same adjustments.

Results

We found an overall VE against symptomatic SARS-CoV-2 infection due to AY.4.2 of 73% (95% confidence interval (CI) = 62-81) for >14 days post-second vaccine dose. Good protection against AY.4.2 symptomatic infection was observed for BNT162b2, ChAdOx1, and mRNA-1273. In unvaccinated individuals, the hazard ratio (HR) for COVID-19 hospital admission or death from AY.4.2 among community detected cases was 1.77 (95% CI = 1.02-3.07) relative to unvaccinated individuals who were infected with Delta, after adjusting for multiple potential confounders. VE against AY.4.2 COVID-19 admissions or deaths was 87% (95% CI = 74-93) >28 days post-second vaccination relative to unvaccinated.

Conclusions

We found that AY.4.2 was associated with an increased risk of COVID-19 hospitalisations or deaths in unvaccinated individuals compared with Delta and that vaccination provided substantial protection against symptomatic SARS-CoV-2 and severe COVID-19 outcomes following Delta AY.4.2 infection. High levels of vaccine uptake and protection offered by existing vaccines, as well as the rapid emergence of the Omicron variant may have contributed to the AY.4.2 variant never progressing to a variant of concern.",,pdf:https://jogh.org/wp-content/uploads/2022/07/jogh-12-05025.pdf; doi:https://doi.org/10.7189/jogh.12.05025; html:https://europepmc.org/articles/PMC9269984; pdf:https://europepmc.org/articles/PMC9269984?pdf=render +38528230,https://doi.org/10.1038/s43587-024-00590-7,Integration of polygenic and gut metagenomic risk prediction for common diseases.,"Liu Y, Ritchie SC, Teo SM, Ruuskanen MO, Kambur O, Zhu Q, Sanders J, Vázquez-Baeza Y, Verspoor K, Jousilahti P, Lahti L, Niiranen T, Salomaa V, Havulinna AS, Knight R, Méric G, Inouye M.",,Nature aging,2024,2024-03-25,Y,,,,"Multiomics has shown promise in noninvasive risk profiling and early detection of various common diseases. In the present study, in a prospective population-based cohort with ~18 years of e-health record follow-up, we investigated the incremental and combined value of genomic and gut metagenomic risk assessment compared with conventional risk factors for predicting incident coronary artery disease (CAD), type 2 diabetes (T2D), Alzheimer disease and prostate cancer. We found that polygenic risk scores (PRSs) improved prediction over conventional risk factors for all diseases. Gut microbiome scores improved predictive capacity over baseline age for CAD, T2D and prostate cancer. Integrated risk models of PRSs, gut microbiome scores and conventional risk factors achieved the highest predictive performance for all diseases studied compared with models based on conventional risk factors alone. The present study demonstrates that integrated PRSs and gut metagenomic risk models improve the predictive value over conventional risk factors for common chronic diseases.",,pdf:https://www.nature.com/articles/s43587-024-00590-7.pdf; doi:https://doi.org/10.1038/s43587-024-00590-7; html:https://europepmc.org/articles/PMC11031402; pdf:https://europepmc.org/articles/PMC11031402?pdf=render 35105585,https://doi.org/10.1136/bmjopen-2021-054376,Development of an algorithm to classify primary care electronic health records of alcohol consumption: experience using data linkage from UK Biobank and primary care electronic health data sources.,"Fraile-Navarro D, Azcoaga-Lorenzo A, Agrawal U, Jani B, Fagbamigbe A, Currie D, Baldacchino A, Sullivan F.",,BMJ open,2022,2022-02-01,Y,Public Health; Primary Care; Health Informatics,,,"

Objectives

Develop a novel algorithm to categorise alcohol consumption using primary care electronic health records (EHRs) and asses its reliability by comparing this classification with self-reported alcohol consumption data obtained from the UK Biobank (UKB) cohort.

Design

Cross-sectional study.

Setting

The UKB, a population-based cohort with participants aged between 40 and 69 years recruited across the UK between 2006 and 2010.

Participants

UKB participants from Scotland with linked primary care data.

Primary and secondary outcome measures

Create a rule-based multiclass algorithm to classify alcohol consumption reported by Scottish UKB participants and compare it with their classification using data present in primary care EHRs based on Read Codes. We evaluated agreement metrics (simple agreement and kappa statistic).

Results

Among the Scottish UKB participants, 18 838 (69%) had at least one Read Code related to alcohol consumption and were used in the classification. The agreement of alcohol consumption categories between UKB and primary care data, including assessments within 5 years was 59.6%, and kappa was 0.23 (95% CI 0.21 to 0.24). Differences in classification between the two sources were statistically significant (p<0.001); More individuals were classified as 'sensible drinkers' and in lower alcohol consumption levels in primary care records compared with the UKB. Agreement improved slightly when using only numerical values (k=0.29; 95% CI 0.27 to 0.31) and decreased when using qualitative descriptors only (k=0.18;95% CI 0.16 to 0.20).

Conclusion

Our algorithm classifies alcohol consumption recorded in Primary Care EHRs into discrete meaningful categories. These results suggest that alcohol consumption may be underestimated in primary care EHRs. Using numerical values (alcohol units) may improve classification when compared with qualitative descriptors.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e054376.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054376; html:https://europepmc.org/articles/PMC8808438; pdf:https://europepmc.org/articles/PMC8808438?pdf=render 32206896,https://doi.org/10.1007/s00394-020-02220-5,Alcohol consumption in relation to carotid subclinical atherosclerosis and its progression: results from a European longitudinal multicentre study.,"Laguzzi F, Baldassarre D, Veglia F, Strawbridge RJ, Humphries SE, Rauramaa R, Smit AJ, Giral P, Silveira A, Tremoli E, Hamsten A, de Faire U, Frumento P, Leander K, IMPROVE Study group.",,European journal of nutrition,2021,2020-03-24,Y,Atherosclerosis; epidemiology; Carotid intima-media thickness; Alcohol drinking; Progression,,,"

Background/aim

The association between alcohol consumption and subclinical atherosclerosis is still unclear. Using data from a European multicentre study, we assess subclinical atherosclerosis and its 30-month progression by carotid intima-media thickness (C-IMT) measurements, and correlate this information with self-reported data on alcohol consumption.

Methods

Between 2002-2004, 1772 men and 1931 women aged 54-79 years with at least three risk factors for cardiovascular disease (CVD) were recruited in Italy, France, Netherlands, Sweden, and Finland. Self-reported alcohol consumption, assessed at baseline, was categorized as follows: none (0 g/d), very-low (0 - 5 g/d), low (> 5 to  ≤ 10 g/d), moderate (> 10 to ≤ 20 g/d for women,  > 10 to ≤ 30 g/d for men) and high (> 20 g/d for women, > 30 g/d for men). C-IMT was measured in millimeters at baseline and after 30 months. Measurements consisted of the mean and maximum values of the common carotids (CC), internal carotid artery (ICA), and bifurcations (Bif) and whole carotid tree. We used quantile regression to describe the associations between C-IMT measures and alcohol consumption categories, adjusting for sex, age, physical activity, education, smoking, diet, and latitude.

Results

Adjusted differences between median C-IMT values in different levels of alcohol consumption (vs. very-low) showed that moderate alcohol consumption was associated with lower C-IMTmax[- 0.17(95%CI - 0.32; - 0.02)], and Bif-IMTmean[- 0.07(95%CI - 0.13; - 0.01)] at baseline and decreasing C-IMTmean[- 0.006 (95%CI - 0.011; - 0.000)], Bif-IMTmean[- 0.016(95%CI - 0.027; - 0.005)], ICA-IMTmean[- 0.009(95% - 0.016; - 0.002)] and ICA-IMTmax[- 0.016(95%: - 0.032; - 0.000)] after 30 months. There was no evidence of departure from linearity in the association between alcohol consumption and C-IMT.

Conclusion

In this European population at high risk of CVD, findings show an inverse relation between moderate alcohol consumption and carotid subclinical atherosclerosis and its 30-month progression, independently of several potential confounders.",,pdf:https://link.springer.com/content/pdf/10.1007/s00394-020-02220-5.pdf; doi:https://doi.org/10.1007/s00394-020-02220-5; html:https://europepmc.org/articles/PMC7867553; pdf:https://europepmc.org/articles/PMC7867553?pdf=render 38589621,https://doi.org/10.1038/s41590-024-01778-0,Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease.,"Liew F, Efstathiou C, Fontanella S, Richardson M, Saunders R, Swieboda D, Sidhu JK, Ascough S, Moore SC, Mohamed N, Nunag J, King C, Leavy OC, Elneima O, McAuley HJC, Shikotra A, Singapuri A, Sereno M, Harris VC, Houchen-Wolloff L, Greening NJ, Lone NI, Thorpe M, Thompson AAR, Rowland-Jones SL, Docherty AB, Chalmers JD, Ho LP, Horsley A, Raman B, Poinasamy K, Marks M, Kon OM, Howard LS, Wootton DG, Quint JK, de Silva TI, Ho A, Chiu C, Harrison EM, Greenhalf W, Baillie JK, Semple MG, Turtle L, Evans RA, Wain LV, Brightling C, Thwaites RS, Openshaw PJM, PHOSP-COVID collaborative group, ISARIC investigators.",,Nature immunology,2024,2024-04-08,Y,,,,"One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.",,doi:https://doi.org/10.1038/s41590-024-01778-0; html:https://europepmc.org/articles/PMC11003868; pdf:https://europepmc.org/articles/PMC11003868?pdf=render @@ -793,17 +793,17 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 37000839,https://doi.org/10.1371/journal.pone.0279076,Predicting a diagnosis of ankylosing spondylitis using primary care health records-A machine learning approach.,"Kennedy J, Kennedy N, Cooksey R, Choy E, Siebert S, Rahman M, Brophy S.",,PloS one,2023,2023-03-31,Y,,,,"Ankylosing spondylitis is the second most common cause of inflammatory arthritis. However, a successful diagnosis can take a decade to confirm from symptom onset (via x-rays). The aim of this study was to use machine learning methods to develop a profile of the characteristics of people who are likely to be given a diagnosis of AS in future. The Secure Anonymised Information Linkage databank was used. Patients with ankylosing spondylitis were identified using their routine data and matched with controls who had no record of a diagnosis of ankylosing spondylitis or axial spondyloarthritis. Data was analysed separately for men and women. The model was developed using feature/variable selection and principal component analysis to develop decision trees. The decision tree with the highest average F value was selected and validated with a test dataset. The model for men indicated that lower back pain, uveitis, and NSAID use under age 20 is associated with AS development. The model for women showed an older age of symptom presentation compared to men with back pain and multiple pain relief medications. The models showed good prediction (positive predictive value 70%-80%) in test data but in the general population where prevalence is very low (0.09% of the population in this dataset) the positive predictive value would be very low (0.33%-0.25%). Machine learning can be used to help profile and understand the characteristics of people who will develop AS, and in test datasets with artificially high prevalence, will perform well. However, when applied to a general population with low prevalence rates, such as that in primary care, the positive predictive value for even the best model would be 1.4%. Multiple models may be needed to narrow down the population over time to improve the predictive value and therefore reduce the time to diagnosis of ankylosing spondylitis.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279076&type=printable; doi:https://doi.org/10.1371/journal.pone.0279076; html:https://europepmc.org/articles/PMC10065228; pdf:https://europepmc.org/articles/PMC10065228?pdf=render 34353320,https://doi.org/10.1186/s12916-021-02045-x,Adverse childhood experiences and child mental health: an electronic birth cohort study.,"Lowthian E, Anthony R, Evans A, Daniel R, Long S, Bandyopadhyay A, John A, Bellis MA, Paranjothy S.",,BMC medicine,2021,2021-08-06,Y,Survival analysis; Cohort; Mental health; Wales; Administrative Data; Adverse Childhood Experiences,,,"

Background

Adverse childhood experiences (ACEs) are negatively associated with a range of child health outcomes. In this study, we explored associations between five individual ACEs and child mental health diagnoses or symptoms. ACEs included living with someone who had an alcohol-related problem, common mental health disorder or serious mental illness, or experienced victimisation or death of a household member.

Methods

We analysed data from a population-level electronic cohort of children in Wales, UK, (N = 191,035) between the years of 1998 and 2012. We used Cox regression with discrete time-varying exposure variables to model time to child mental health diagnosis during the first 15 years of life. Child mental health diagnoses include five categories: (i) externalising symptoms (anti-social behaviour), (ii) internalising symptoms (stress, anxiety, depression), (iii) developmental delay (e.g. learning disability), (iv) other (e.g. eating disorder, personality disorders), and (v) any mental health diagnosis, which was created by combining externalising symptoms, internalising symptoms and other. Our analyses were adjusted for social deprivation and perinatal risk factors.

Results

There were strong univariable associations between the five individual ACEs, sociodemographic and perinatal factors (e.g. gestational weight at birth) and an increased risk of child mental health diagnoses. After adjusting for sociodemographic and perinatal aspects, there was a remaining conditional increased risk of any child mental health diagnosis, associated with victimisation (conditional hazard ratio (cHR) 1.90, CI 95% 1.34-2.69), and living with an adult with a common mental health diagnosis (cHR 1.63, CI 95% 1.52-1.75). Coefficients of product terms between ACEs and deprivation were not statistically significant.

Conclusion

The increased risk of child mental health diagnosis associated with victimisation, or exposure to common mental health diagnoses, and alcohol problems in the household supports the need for policy measures and intervention strategies for children and their families.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-021-02045-x; doi:https://doi.org/10.1186/s12916-021-02045-x; html:https://europepmc.org/articles/PMC8344166; pdf:https://europepmc.org/articles/PMC8344166?pdf=render 33446033,https://doi.org/10.1177/1460458220977579,Identifying strategies to overcome roadblocks to utilising near real-time healthcare and administrative data to create a Scotland-wide learning health system.,"Mukherjee M, Cresswell K, Sheikh A.",,Health informatics journal,2021,2021-01-01,N,Qualitative Research; Governance; Electronic Health Records; Health Data; Learning Health System,,,"Creating a learning health system could help reduce variations in quality of care. Success is dependent on timely access to health data. To explore the barriers and facilitators to timely access to patients' data, we conducted in-depth semi-structured interviews with 37 purposively sampled participants from government, the NHS and academia across Scotland. Interviews were analysed using the framework approach. Participants were of the view that Scotland could play a leading role in the exploitation of routine data to drive forward service improvements, but highlighted major impediments: (i) persistence of paper-based records and a variety of information systems; (ii) the need for a proportionate approach to managing information governance; and (iii) the need for support structures to facilitate accrual, processing, linking, analysis and timely use and reuse of data for patient benefit. There is a pressing need to digitise and integrate existing health information infrastructures, guided by a nationwide proportionate information governance approach and the need to enhance technological and human capabilities to support these efforts.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/1460458220977579; doi:https://doi.org/10.1177/1460458220977579 -38304287,https://doi.org/10.3389/fpsyt.2024.1347358,How will AI make sense of our messy lives and improve our mental health?,"Speechley J, McTernan M.",,Frontiers in psychiatry,2024,2024-01-18,Y,Artificial intelligence; Data; Mental health; TRUST; Patient And Public Engagement,,,,,doi:https://doi.org/10.3389/fpsyt.2024.1347358; html:https://europepmc.org/articles/PMC10832992; pdf:https://europepmc.org/articles/PMC10832992?pdf=render 33469151,https://doi.org/10.1038/s42003-020-01613-w,LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes.,"Herdenberg C, Mutie PM, Billing O, Abdullah A, Strawbridge RJ, Dahlman I, Tuck S, Holmlund C, Arner P, Henriksson R, Franks PW, Hedman H.",,Communications biology,2021,2021-01-19,Y,,,,"Leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins have been implicated as regulators of growth factor signaling; however, the possible redundancy among mammalian LRIG1, LRIG2, and LRIG3 has hindered detailed elucidation of their physiological functions. Here, we show that Lrig-null mouse embryonic fibroblasts (MEFs) are deficient in adipogenesis and bone morphogenetic protein (BMP) signaling. In contrast, transforming growth factor-beta (TGF-β) and receptor tyrosine kinase (RTK) signaling appeared unaltered in Lrig-null cells. The BMP signaling defect was rescued by ectopic expression of LRIG1 or LRIG3 but not by expression of LRIG2. Caenorhabditis elegans with mutant LRIG/sma-10 variants also exhibited a lipid storage defect. Human LRIG1 variants were strongly associated with increased body mass index (BMI) yet protected against type 2 diabetes; these effects were likely mediated by altered adipocyte morphology. These results demonstrate that LRIG proteins function as evolutionarily conserved regulators of lipid metabolism and BMP signaling and have implications for human disease.",,pdf:https://www.nature.com/articles/s42003-020-01613-w.pdf; doi:https://doi.org/10.1038/s42003-020-01613-w; html:https://europepmc.org/articles/PMC7815736; pdf:https://europepmc.org/articles/PMC7815736?pdf=render +38304287,https://doi.org/10.3389/fpsyt.2024.1347358,How will AI make sense of our messy lives and improve our mental health?,"Speechley J, McTernan M.",,Frontiers in psychiatry,2024,2024-01-18,Y,Artificial intelligence; Data; Mental health; TRUST; Patient And Public Engagement,,,,,doi:https://doi.org/10.3389/fpsyt.2024.1347358; html:https://europepmc.org/articles/PMC10832992; pdf:https://europepmc.org/articles/PMC10832992?pdf=render 36377225,https://doi.org/10.1177/18333583221135710,Concordance between coding sources of burn size and depth across Australian and New Zealand specialist burn services.,"Perkins M, Cleland H, Gabbe BJ, Tracy LM.",,Health information management : journal of the Health Information Management Association of Australia,2024,2022-11-14,N,Burns; Australia; New Zealand; Registries; Health Information Management; International Classification Of Diseases; Clinical Coding,,,"

Background

The percentage of total body surface area (%TBSA) burned and burn depth provide valuable information on burn injury severity.

Objective

This study investigated the concordance between The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) codes and expert burn clinicians in assessing burn injury severity.

Method

We conducted a retrospective population-based review of all patients who sustained a burn injury between July 1, 2009, and June 30, 2019, requiring admission into a specialist burn service across Australia and New Zealand. The %TBSA burned (including the percentage of full thickness burns) recorded by expert burn clinicians within the Burns Registry of Australia and New Zealand (BRANZ) were compared to ICD-10-AM coding.

Results

20,642 cases (71.5%) with ICD-10-AM code data were recorded. Overall, kappa scores (95% confidence interval [CI]) for burn size ranged from 0.64 (95% CI 0.63-0.66) to 0.86 (95% CI 0.78-0.94) indicating substantial to almost perfect agreement across all %TBSA groups. When stratified by depth, the lowest agreement was observed for < 10% TBSA and < 10% full thickness (kappa 0.03; 95% CI 0.02-0.04) and the highest agreement was observed for burns of ≥ 90% TBSA and ≥ 90% full thickness (kappa 0.72; 95% CI 0.58-0.85).

Conclusion

Overall, there was substantial agreement between the BRANZ and ICD-10-AM coded data for %TBSA classification. When %TBSA classification was stratified by burn depth, greater agreement was observed for larger and deeper burns compared with smaller and superficial burns.

Implications

Greater consistency in the classification of burns is needed.",,doi:https://doi.org/10.1177/18333583221135710 30727941,https://doi.org/10.1186/s12859-019-2633-8,DeepPVP: phenotype-based prioritization of causative variants using deep learning.,"Boudellioua I, Kulmanov M, Schofield PN, Gkoutos GV, Hoehndorf R.",,BMC bioinformatics,2019,2019-02-06,Y,Phenotype; Ontology; Machine Learning; Variant Prioritization,Applied Analytics,,"

Background

Prioritization of variants in personal genomic data is a major challenge. Recently, computational methods that rely on comparing phenotype similarity have shown to be useful to identify causative variants. In these methods, pathogenicity prediction is combined with a semantic similarity measure to prioritize not only variants that are likely to be dysfunctional but those that are likely involved in the pathogenesis of a patient's phenotype.

Results

We have developed DeepPVP, a variant prioritization method that combined automated inference with deep neural networks to identify the likely causative variants in whole exome or whole genome sequence data. We demonstrate that DeepPVP performs significantly better than existing methods, including phenotype-based methods that use similar features. DeepPVP is freely available at https://github.com/bio-ontology-research-group/phenomenet-vp .

Conclusions

DeepPVP further improves on existing variant prioritization methods both in terms of speed as well as accuracy.",,pdf:https://bmcbioinformatics.biomedcentral.com/track/pdf/10.1186/s12859-019-2633-8; doi:https://doi.org/10.1186/s12859-019-2633-8; html:https://europepmc.org/articles/PMC6364462; pdf:https://europepmc.org/articles/PMC6364462?pdf=render 35079022,https://doi.org/10.1038/s41467-022-28157-3,Regional excess mortality during the 2020 COVID-19 pandemic in five European countries.,"Konstantinoudis G, Cameletti M, Gómez-Rubio V, Gómez IL, Pirani M, Baio G, Larrauri A, Riou J, Egger M, Vineis P, Blangiardo M.",,Nature communications,2022,2022-01-25,Y,,,,"The impact of the COVID-19 pandemic on excess mortality from all causes in 2020 varied across and within European countries. Using data for 2015-2019, we applied Bayesian spatio-temporal models to quantify the expected weekly deaths at the regional level had the pandemic not occurred in England, Greece, Italy, Spain, and Switzerland. With around 30%, Madrid, Castile-La Mancha, Castile-Leon (Spain) and Lombardia (Italy) were the regions with the highest excess mortality. In England, Greece and Switzerland, the regions most affected were Outer London and the West Midlands (England), Eastern, Western and Central Macedonia (Greece), and Ticino (Switzerland), with 15-20% excess mortality in 2020. Our study highlights the importance of the large transportation hubs for establishing community transmission in the first stages of the pandemic. Here, we show that acting promptly to limit transmission around these hubs is essential to prevent spread to other regions and countries.",,pdf:https://www.nature.com/articles/s41467-022-28157-3.pdf; doi:https://doi.org/10.1038/s41467-022-28157-3; html:https://europepmc.org/articles/PMC8789777; pdf:https://europepmc.org/articles/PMC8789777?pdf=render 35074819,https://doi.org/10.1136/bmjopen-2021-054414,Mapping multimorbidity in individuals with schizophrenia and bipolar disorders: evidence from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLAM BRC) case register.,"Bendayan R, Kraljevic Z, Shaari S, Das-Munshi J, Leipold L, Chaturvedi J, Mirza L, Aldelemi S, Searle T, Chance N, Mascio A, Skiada N, Wang T, Roberts A, Stewart R, Bean D, Dobson R.",,BMJ open,2022,2022-01-24,Y,Psychiatry; Mental health; epidemiology; Public Health; Health Informatics,,,"

Objectives

The first aim of this study was to design and develop a valid and replicable strategy to extract physical health conditions from clinical notes which are common in mental health services. Then, we examined the prevalence of these conditions in individuals with severe mental illness (SMI) and compared their individual and combined prevalence in individuals with bipolar (BD) and schizophrenia spectrum disorders (SSD).

Design

Observational study.

Setting

Secondary mental healthcare services from South London PARTICIPANTS: Our maximal sample comprised 17 500 individuals aged 15 years or older who had received a primary or secondary SMI diagnosis (International Classification of Diseases, 10th edition, F20-31) between 2007 and 2018.

Measures

We designed and implemented a data extraction strategy for 21 common physical comorbidities using a natural language processing pipeline, MedCAT. Associations were investigated with sex, age at SMI diagnosis, ethnicity and social deprivation for the whole cohort and the BD and SSD subgroups. Linear regression models were used to examine associations with disability measured by the Health of Nations Outcome Scale.

Results

Physical health data were extracted, achieving precision rates (F1) above 0.90 for all conditions. The 10 most prevalent conditions were diabetes, hypertension, asthma, arthritis, epilepsy, cerebrovascular accident, eczema, migraine, ischaemic heart disease and chronic obstructive pulmonary disease. The most prevalent combination in this population included diabetes, hypertension and asthma, regardless of their SMI diagnoses.

Conclusions

Our data extraction strategy was found to be adequate to extract physical health data from clinical notes, which is essential for future multimorbidity research using text records. We found that around 40% of our cohort had multimorbidity from which 20% had complex multimorbidity (two or more physical conditions besides SMI). Sex, age, ethnicity and social deprivation were found to be key to understand their heterogeneity and their differential contribution to disability levels in this population. These outputs have direct implications for researchers and clinicians.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/1/e054414.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054414; html:https://europepmc.org/articles/PMC8788233; pdf:https://europepmc.org/articles/PMC8788233?pdf=render -37432340,https://doi.org/10.1093/rheumatology/kead346,Trends for opioid prescribing and the impact of the COVID-19 pandemic in patients with rheumatic and musculoskeletal diseases between 2006 and 2021.,"Huang YT, Jenkins DA, Yimer BB, Benitez-Aurioles J, Peek N, Lunt M, Dixon WG, Jani M.",,"Rheumatology (Oxford, England)",2024,2024-04-01,Y,RA; SLE; Trend; PSA; Opioids; Oa; Axial Spondyloarthritis; Fm; Covid-19,,,"

Objective

To investigate opioid prescribing trends and assess the impact of the COVID-19 pandemic on opioid prescribing in rheumatic and musculoskeletal diseases (RMDs).

Methods

Adult patients with RA, PsA, axial spondyloarthritis (AxSpA), SLE, OA and FM with opioid prescriptions between 1 January 2006 and 31 August 2021 without cancer in UK primary care were included. Age- and gender-standardized yearly rates of new and prevalent opioid users were calculated between 2006 and 2021. For prevalent users, monthly measures of mean morphine milligram equivalents (MME)/day were calculated between 2006 and 2021. To assess the impact of the pandemic, we fitted regression models to the monthly number of prevalent opioid users between January 2015 and August 2021. The time coefficient reflects the trend pre-pandemic and the interaction term coefficient represents the change in the trend during the pandemic.

Results

The study included 1 313 519 RMD patients. New opioid users for RA, PsA and FM increased from 2.6, 1.0 and 3.4/10 000 persons in 2006 to 4.5, 1.8 and 8.7, respectively, in 2018 or 2019. This was followed by a fall to 2.4, 1.2 and 5.9, respectively, in 2021. Prevalent opioid users for all RMDs increased from 2006 but plateaued or dropped beyond 2018, with a 4.5-fold increase in FM between 2006 and 2021. In this period, MME/day increased for all RMDs, with the highest for FM (≥35). During COVID-19 lockdowns, RA, PsA and FM showed significant changes in the trend of prevalent opioid users. The trend for FM increased pre-pandemic and started decreasing during the pandemic.

Conclusion

The plateauing or decreasing trend of opioid users for RMDs after 2018 may reflect the efforts to tackle rising opioid prescribing in the UK. The pandemic led to fewer people on opioids for most RMDs, providing reassurance that there was no sudden increase in opioid prescribing during the pandemic.",,pdf:https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/kead346/50930066/kead346.pdf; doi:https://doi.org/10.1093/rheumatology/kead346; html:https://europepmc.org/articles/PMC10986805; pdf:https://europepmc.org/articles/PMC10986805?pdf=render -38578666,https://doi.org/10.2196/49548,Implementation of an Electronic Clinical Decision Support System for the Early Recognition and Management of Dysglycemia in an Inpatient Mental Health Setting Using CogStack: Protocol for a Pilot Hybrid Type 3 Effectiveness-Implementation Randomized Controlled Cluster Trial.,"Patel D, Msosa YJ, Wang T, Williams J, Mustafa OG, Gee S, Arroyo B, Larkin D, Tiedt T, Roberts A, Dobson RJB, Gaughran F.",,JMIR research protocols,2024,2024-04-05,Y,Blood sugar; Diabetes; Diabetic; Implementation; Mental health; Randomized controlled trial; hyperglycemia; Hypoglycemia; Mental Illness; Clinical Decision Support System; Decision Support; Medical Informatics; Rct; Cdss; Metabolic Health; Mental Healthcare; Electronic Clinical Decision Support; Dysglycemia,,,"

Background

Severe mental illnesses (SMIs), including schizophrenia, bipolar affective disorder, and major depressive disorder, are associated with an increased risk of physical health comorbidities and premature mortality from conditions including cardiovascular disease and diabetes. Digital technologies such as electronic clinical decision support systems (eCDSSs) could play a crucial role in improving the clinician-led management of conditions such as dysglycemia (deranged blood sugar levels) and associated conditions such as diabetes in people with a diagnosis of SMI in mental health settings.

Objective

We have developed a real-time eCDSS using CogStack, an information retrieval and extraction platform, to automatically alert clinicians with National Health Service Trust-approved, guideline-based recommendations for dysglycemia monitoring and management in secondary mental health care. This novel system aims to improve the management of dysglycemia and associated conditions, such as diabetes, in SMI. This protocol describes a pilot study to explore the acceptability, feasibility, and evaluation of its implementation in a mental health inpatient setting.

Methods

This will be a pilot hybrid type 3 effectiveness-implementation randomized controlled cluster trial in inpatient mental health wards. A ward will be the unit of recruitment, where it will be randomly allocated to receive either access to the eCDSS plus usual care or usual care alone over a 4-month period. We will measure implementation outcomes, including the feasibility and acceptability of the eCDSS to clinicians, as primary outcomes, alongside secondary outcomes relating to the process of care measures such as dysglycemia screening rates. An evaluation of other implementation outcomes relating to the eCDSS will be conducted, identifying facilitators and barriers based on established implementation science frameworks.

Results

Enrollment of wards began in April 2022, after which clinical staff were recruited to take part in surveys and interviews. The intervention period of the trial began in February 2023, and subsequent data collection was completed in August 2023. Data are currently being analyzed, and results are expected to be available in June 2024.

Conclusions

An eCDSS can have the potential to improve clinician-led management of dysglycemia in inpatient mental health settings. If found to be feasible and acceptable, then, in combination with the results of the implementation evaluation, the system can be refined and improved to support future successful implementation. A larger and more definitive effectiveness trial should then be conducted to assess its impact on clinical outcomes and to inform scalability and application to other conditions in wider mental health care settings.

Trial registration

ClinicalTrials.gov NCT04792268; https://clinicaltrials.gov/study/NCT04792268.

International registered report identifier (irrid)

DERR1-10.2196/49548.",,pdf:https://www.researchprotocols.org/2024/1/e49548/PDF; doi:https://doi.org/10.2196/49548; html:https://europepmc.org/articles/PMC11031689 31971603,https://doi.org/10.2340/00015555-3384,Psoriasis and Genetics.,"Dand N, Mahil SK, Capon F, Smith CH, Simpson MA, Barker JN.",,Acta dermato-venereologica,2020,2020-01-30,Y,Genetics; Psoriasis; Treatment outcome; Disease Progression; Precision Medicine,,,"Psoriasis is a common inflammatory skin disease caused by the interplay between multiple genetic and environmental risk factors. This review summarises recent progress in elucidating the genetic basis of psoriasis, particularly through large genome-wide association studies. We illustrate the power of genetic analyses for disease stratification. Psoriasis can be stratified by phenotype (common plaque versus rare pustular variants), or by outcome (prognosis, comorbidities, response to treatment); recent progress has been made in delineating the genetic contribution in each of these areas. We also highlight how genetic data can directly inform the development of effective psoriasis treatments.",,doi:https://doi.org/10.2340/00015555-3384; doi:https://doi.org/10.2340/00015555-3384; html:https://europepmc.org/articles/PMC9128944; pdf:https://europepmc.org/articles/PMC9128944?pdf=render 32641105,https://doi.org/10.1186/s12874-020-01025-8,Multivariate network meta-analysis incorporating class effects.,"Owen RK, Bujkiewicz S, Tincello DG, Abrams KR.",,BMC medical research methodology,2020,2020-07-08,Y,Meta-analysis; Multivariate; Class Effect; Network Meta-analysis; Mixed Treatment Comparisons,,,"

Background

Network meta-analysis synthesises data from a number of clinical trials in order to assess the comparative efficacy of multiple healthcare interventions in similar patient populations. In situations where clinical trial data are heterogeneously reported i.e. data are missing for one or more outcomes of interest, synthesising such data can lead to disconnected networks of evidence, increased uncertainty, and potentially biased estimates which can have severe implications for decision-making. To overcome this issue, strength can be borrowed between outcomes of interest in multivariate network meta-analyses. Furthermore, in situations where there are relatively few trials informing each treatment comparison, there is a potential issue with the sparsity of data in the treatment networks, which can lead to substantial parameter uncertainty. A multivariate network meta-analysis approach can be further extended to borrow strength between interventions of the same class using hierarchical models.

Methods

We extend the trivariate network meta-analysis model to incorporate the exchangeability between treatment effects belonging to the same class of intervention to increase precision in treatment effect estimates. We further incorporate a missing data framework to estimate uncertainty in trials that did not report measures of variability in order to maximise the use of all available information for healthcare decision-making. The methods are applied to a motivating dataset in overactive bladder syndrome. The outcomes of interest were mean change from baseline in incontinence, voiding and urgency episodes. All models were fitted using Bayesian Markov Chain Monte Carlo (MCMC) methods in WinBUGS.

Results

All models (univariate, multivariate, and multivariate models incorporating class effects) produced similar point estimates for all treatment effects. Incorporating class effects in multivariate models often increased precision in treatment effect estimates.

Conclusions

Multivariate network meta-analysis incorporating class effects allowed for the comparison of all interventions across all outcome measures to ameliorate the potential impact of outcome reporting bias, and further borrowed strength between interventions belonging to the same class of treatment to increase the precision in treatment effect estimates for healthcare policy and decision-making.",,pdf:https://bmcmedresmethodol.biomedcentral.com/track/pdf/10.1186/s12874-020-01025-8; doi:https://doi.org/10.1186/s12874-020-01025-8; html:https://europepmc.org/articles/PMC7341581; pdf:https://europepmc.org/articles/PMC7341581?pdf=render +37432340,https://doi.org/10.1093/rheumatology/kead346,Trends for opioid prescribing and the impact of the COVID-19 pandemic in patients with rheumatic and musculoskeletal diseases between 2006 and 2021.,"Huang YT, Jenkins DA, Yimer BB, Benitez-Aurioles J, Peek N, Lunt M, Dixon WG, Jani M.",,"Rheumatology (Oxford, England)",2024,2024-04-01,Y,RA; SLE; Trend; PSA; Opioids; Oa; Axial Spondyloarthritis; Fm; Covid-19,,,"

Objective

To investigate opioid prescribing trends and assess the impact of the COVID-19 pandemic on opioid prescribing in rheumatic and musculoskeletal diseases (RMDs).

Methods

Adult patients with RA, PsA, axial spondyloarthritis (AxSpA), SLE, OA and FM with opioid prescriptions between 1 January 2006 and 31 August 2021 without cancer in UK primary care were included. Age- and gender-standardized yearly rates of new and prevalent opioid users were calculated between 2006 and 2021. For prevalent users, monthly measures of mean morphine milligram equivalents (MME)/day were calculated between 2006 and 2021. To assess the impact of the pandemic, we fitted regression models to the monthly number of prevalent opioid users between January 2015 and August 2021. The time coefficient reflects the trend pre-pandemic and the interaction term coefficient represents the change in the trend during the pandemic.

Results

The study included 1 313 519 RMD patients. New opioid users for RA, PsA and FM increased from 2.6, 1.0 and 3.4/10 000 persons in 2006 to 4.5, 1.8 and 8.7, respectively, in 2018 or 2019. This was followed by a fall to 2.4, 1.2 and 5.9, respectively, in 2021. Prevalent opioid users for all RMDs increased from 2006 but plateaued or dropped beyond 2018, with a 4.5-fold increase in FM between 2006 and 2021. In this period, MME/day increased for all RMDs, with the highest for FM (≥35). During COVID-19 lockdowns, RA, PsA and FM showed significant changes in the trend of prevalent opioid users. The trend for FM increased pre-pandemic and started decreasing during the pandemic.

Conclusion

The plateauing or decreasing trend of opioid users for RMDs after 2018 may reflect the efforts to tackle rising opioid prescribing in the UK. The pandemic led to fewer people on opioids for most RMDs, providing reassurance that there was no sudden increase in opioid prescribing during the pandemic.",,pdf:https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/kead346/50930066/kead346.pdf; doi:https://doi.org/10.1093/rheumatology/kead346; html:https://europepmc.org/articles/PMC10986805; pdf:https://europepmc.org/articles/PMC10986805?pdf=render 35216844,https://doi.org/10.1016/j.vaccine.2022.02.056,Localising vaccination services: Qualitative insights on public health and minority group collaborations to co-deliver coronavirus vaccines.,"Kasstan B, Mounier-Jack S, Letley L, Gaskell KM, Roberts CH, Stone NRH, Lal S, Eggo RM, Marks M, Chantler T.",,Vaccine,2022,2022-02-17,Y,Qualitative Research; Ethnic Minorities; Coronavirus Vaccine; Localising Services; Public Health Collaboration,,,"Ethnic and religious minorities have been disproportionately affected by the SARS-CoV-2 pandemic and are less likely to accept coronavirus vaccinations. Orthodox (Haredi) Jewish neighbourhoods in England experienced high incidences of SARS-CoV-2 in 2020-21 and measles outbreaks (2018-19) due to suboptimal childhood vaccination coverage. The objective of our study was to explore how the coronavirus vaccination programme (CVP) was co-delivered between public health services and an Orthodox Jewish health organisation. Methods included 28 semi-structured interviews conducted virtually with public health professionals, community welfare and religious representatives, and household members. We examined CVP delivery from the perspectives of those involved in organising services and vaccine beneficiaries. Interview data was contextualised within debates of the CVP in Orthodox (Haredi) Jewish print and social media. Thematic analysis generated five considerations: i) Prior immunisation-related collaboration with public health services carved a role for Jewish health organisations to host and promote coronavirus vaccination sessions, distribute appointments, and administer vaccines ii) Public health services maintained responsibility for training, logistics, and maintaining vaccination records; iii) The localised approach to service delivery promoted vaccination in a minority with historically suboptimal levels of coverage; iv) Co-delivery promoted trust in the CVP, though a minority of participants maintained concerns around safety; v) Provision of CVP information and stakeholders' response to situated (context-specific) challenges and concerns. Drawing on this example of CVP co-delivery, we propose that a localised approach to delivering immunisation programmes could address service provision gaps in ways that involve trusted community organisations. Localisation of vaccination services can include communication or implementation strategies, but both approaches involve consideration of investment, engagement and coordination, which are not cost-neutral. Localising vaccination services in collaboration with welfare groups raises opportunities for the on-going CVP and other immunisation programmes, and constitutes an opportunity for ethnic and religious minorities to collaborate in safeguarding community health.",,doi:https://doi.org/10.1016/j.vaccine.2022.02.056; doi:https://doi.org/10.1016/j.vaccine.2022.02.056; html:https://europepmc.org/articles/PMC8849863 +38578666,https://doi.org/10.2196/49548,Implementation of an Electronic Clinical Decision Support System for the Early Recognition and Management of Dysglycemia in an Inpatient Mental Health Setting Using CogStack: Protocol for a Pilot Hybrid Type 3 Effectiveness-Implementation Randomized Controlled Cluster Trial.,"Patel D, Msosa YJ, Wang T, Williams J, Mustafa OG, Gee S, Arroyo B, Larkin D, Tiedt T, Roberts A, Dobson RJB, Gaughran F.",,JMIR research protocols,2024,2024-04-05,Y,Blood sugar; Diabetes; Diabetic; Implementation; Mental health; Randomized controlled trial; hyperglycemia; Hypoglycemia; Mental Illness; Clinical Decision Support System; Decision Support; Medical Informatics; Rct; Cdss; Metabolic Health; Mental Healthcare; Electronic Clinical Decision Support; Dysglycemia,,,"

Background

Severe mental illnesses (SMIs), including schizophrenia, bipolar affective disorder, and major depressive disorder, are associated with an increased risk of physical health comorbidities and premature mortality from conditions including cardiovascular disease and diabetes. Digital technologies such as electronic clinical decision support systems (eCDSSs) could play a crucial role in improving the clinician-led management of conditions such as dysglycemia (deranged blood sugar levels) and associated conditions such as diabetes in people with a diagnosis of SMI in mental health settings.

Objective

We have developed a real-time eCDSS using CogStack, an information retrieval and extraction platform, to automatically alert clinicians with National Health Service Trust-approved, guideline-based recommendations for dysglycemia monitoring and management in secondary mental health care. This novel system aims to improve the management of dysglycemia and associated conditions, such as diabetes, in SMI. This protocol describes a pilot study to explore the acceptability, feasibility, and evaluation of its implementation in a mental health inpatient setting.

Methods

This will be a pilot hybrid type 3 effectiveness-implementation randomized controlled cluster trial in inpatient mental health wards. A ward will be the unit of recruitment, where it will be randomly allocated to receive either access to the eCDSS plus usual care or usual care alone over a 4-month period. We will measure implementation outcomes, including the feasibility and acceptability of the eCDSS to clinicians, as primary outcomes, alongside secondary outcomes relating to the process of care measures such as dysglycemia screening rates. An evaluation of other implementation outcomes relating to the eCDSS will be conducted, identifying facilitators and barriers based on established implementation science frameworks.

Results

Enrollment of wards began in April 2022, after which clinical staff were recruited to take part in surveys and interviews. The intervention period of the trial began in February 2023, and subsequent data collection was completed in August 2023. Data are currently being analyzed, and results are expected to be available in June 2024.

Conclusions

An eCDSS can have the potential to improve clinician-led management of dysglycemia in inpatient mental health settings. If found to be feasible and acceptable, then, in combination with the results of the implementation evaluation, the system can be refined and improved to support future successful implementation. A larger and more definitive effectiveness trial should then be conducted to assess its impact on clinical outcomes and to inform scalability and application to other conditions in wider mental health care settings.

Trial registration

ClinicalTrials.gov NCT04792268; https://clinicaltrials.gov/study/NCT04792268.

International registered report identifier (irrid)

DERR1-10.2196/49548.",,pdf:https://www.researchprotocols.org/2024/1/e49548/PDF; doi:https://doi.org/10.2196/49548; html:https://europepmc.org/articles/PMC11031689 37139857,https://doi.org/10.1111/dom.15102,Impact of severe hypoglycaemia requiring hospitalization on mortality in people with type 1 diabetes: A national retrospective observational cohort study.,"Moser O, Rafferty J, Eckstein ML, Aziz F, Bain SC, Bergenstal R, Sourij H, Thomas RL.",,"Diabetes, obesity & metabolism",2023,2023-05-04,N,Mortality; type 1 diabetes; Risk Prediction; Severe Hypoglycaemia,,,"

Aims

To assess if the risk of all-cause mortality increases in people with type 1 diabetes (T1D) with increasing number of severe hypoglycaemia episodes requiring hospitalization.

Materials and methods

We conducted a national retrospective observational cohort study in people with T1D (diagnosed between 2000 and 2018). Clinical, comorbidity and demographic variables were assessed for impact on mortality for people with no, one, two and three or more episodes of severe hypoglycaemia requiring hospitalization. The time to death (all-cause mortality) from the timepoint of the last episode of severe hypoglycaemia was modelled using a parametric survival model.

Results

A total of 8224 people had a T1D diagnosis in Wales during the study period. The mortality rate (95% confidence interval [CI]) was 6.9 (6.1-7.8) deaths/ 1000 person-years (crude) and 15.31 (13.3-17.63) deaths/ 1000 person-years (age-adjusted) for those with no occurrence of severe hypoglycaemia requiring hospitalization. For those with one episode of severe hypoglycaemia requiring hospitalization the mortality rate (95% CI) was 24.9 (21.0-29.6; crude) and 53.8 (44.6-64.7) deaths/ 1000 person-years (age-adjusted), for those with two episodes of severe hypoglycaemia requiring hospitalization it was 28.0 (23.1-34.0; crude) and 72.8 (59.2-89.5) deaths/ 1000 person-years (age-adjusted), and for those with three or more episodes of severe hypoglycaemia requiring hospitalization it was 33.5 (30.0-37.3; crude) and 86.3 (71.7-103.9) deaths/ 1000 person years (age-adjusted; P < 0.001). A parametric survival model showed that having two episodes of severe hypoglycaemia requiring hospitalization was the strongest predictor for time to death (accelerated failure time coefficient 0.073 [95% CI 0.009-0.565]), followed by having one episode of severe hypoglycaemia requiring hospitalization (0.126 [0.036-0.438]) and age at most recent episode of severe hypoglycaemia requiring hospitalization (0.917 [0.885-0.951]).

Conclusions

The strongest predictor for time to death was having two or more episodes of severe hypoglycaemia requiring hospitalization.",,doi:https://doi.org/10.1111/dom.15102 33711543,https://doi.org/10.1016/j.jbi.2021.103728,Explainable automated coding of clinical notes using hierarchical label-wise attention networks and label embedding initialisation.,"Dong H, Suárez-Paniagua V, Whiteley W, Wu H.",,Journal of biomedical informatics,2021,2021-03-09,N,Natural Language Processing; Multi-label Classification; Deep Learning; Attention Mechanisms; Automated Medical Coding; Explainability; Label Correlation,,,"

Background

Diagnostic or procedural coding of clinical notes aims to derive a coded summary of disease-related information about patients. Such coding is usually done manually in hospitals but could potentially be automated to improve the efficiency and accuracy of medical coding. Recent studies on deep learning for automated medical coding achieved promising performances. However, the explainability of these models is usually poor, preventing them to be used confidently in supporting clinical practice. Another limitation is that these models mostly assume independence among labels, ignoring the complex correlations among medical codes which can potentially be exploited to improve the performance.

Methods

To address the issues of model explainability and label correlations, we propose a Hierarchical Label-wise Attention Network (HLAN), which aimed to interpret the model by quantifying importance (as attention weights) of words and sentences related to each of the labels. Secondly, we propose to enhance the major deep learning models with a label embedding (LE) initialisation approach, which learns a dense, continuous vector representation and then injects the representation into the final layers and the label-wise attention layers in the models. We evaluated the methods using three settings on the MIMIC-III discharge summaries: full codes, top-50 codes, and the UK NHS (National Health Service) COVID-19 (Coronavirus disease 2019) shielding codes. Experiments were conducted to compare the HLAN model and label embedding initialisation to the state-of-the-art neural network based methods, including variants of Convolutional Neural Networks (CNNs) and Recurrent Neural Networks (RNNs).

Results

HLAN achieved the best Micro-level AUC and F1 on the top-50 code prediction, 91.9% and 64.1%, respectively; and comparable results on the NHS COVID-19 shielding code prediction to other models: around 97% Micro-level AUC. More importantly, in the analysis of model explanations, by highlighting the most salient words and sentences for each label, HLAN showed more meaningful and comprehensive model interpretation compared to the CNN-based models and its downgraded baselines, HAN and HA-GRU. Label embedding (LE) initialisation significantly boosted the previous state-of-the-art model, CNN with attention mechanisms, on the full code prediction to 52.5% Micro-level F1. The analysis of the layers initialised with label embeddings further explains the effect of this initialisation approach. The source code of the implementation and the results are openly available at https://github.com/acadTags/Explainable-Automated-Medical-Coding.

Conclusion

We draw the conclusion from the evaluation results and analyses. First, with hierarchical label-wise attention mechanisms, HLAN can provide better or comparable results for automated coding to the state-of-the-art, CNN-based models. Second, HLAN can provide more comprehensive explanations for each label by highlighting key words and sentences in the discharge summaries, compared to the n-grams in the CNN-based models and the downgraded baselines, HAN and HA-GRU. Third, the performance of deep learning based multi-label classification for automated coding can be consistently boosted by initialising label embeddings that captures the correlations among labels. We further discuss the advantages and drawbacks of the overall method regarding its potential to be deployed to a hospital and suggest areas for future studies.",,doi:https://doi.org/10.1016/j.jbi.2021.103728; doi:https://doi.org/10.1016/j.jbi.2021.103728 31532828,https://doi.org/10.1210/clinem/dgz006,Increased Infection Risk in Addison's Disease and Congenital Adrenal Hyperplasia.,"Tresoldi AS, Sumilo D, Perrins M, Toulis KA, Prete A, Reddy N, Wass JAH, Arlt W, Nirantharakumar K.",,The Journal of clinical endocrinology and metabolism,2020,2020-02-01,Y,,,,"

Context

Mortality and infection-related hospital admissions are increased in patients with primary adrenal insufficiency (PAI). However, the risk of primary care-managed infections in patients with PAI is unknown.

Objective

To estimate infection risk in PAI due to Addison's disease (AD) and congenital adrenal hyperplasia (CAH) in a primary care setting.

Design

Retrospective cohort study using UK data collected from 1995 to 2018.

Main outcome measures

Incidence of lower respiratory tract infections (LRTIs), urinary tract infections (UTIs), gastrointestinal infections (GIIs), and prescription counts of antimicrobials in adult PAI patients compared to unexposed controls.

Results

A diagnosis of PAI was established in 1580 AD patients (mean age 51.7 years) and 602 CAH patients (mean age 35.4 years). All AD patients and 42% of CAH patients were prescribed glucocorticoids, most frequently hydrocortisone in AD (82%) and prednisolone in CAH (50%). AD and CAH patients exposed to glucocorticoids, but not CAH patients without glucocorticoid treatment, had a significantly increased risk of LRTIs (adjusted incidence rate ratio AD 2.11 [95% confidence interval (CI) 1.64-2.69], CAH 3.23 [95% CI 1.21-8.61]), UTIs (AD 1.51 [95% CI 1.29-1.77], CAH 2.20 [95% CI 1.43-3.34]), and GIIs (AD 3.80 [95% CI 2.99-4.84], CAH 1.93 [95% CI 1.06-3.52]). This was mirrored by increased prescription of antibiotics (AD 1.73 [95% CI 1.69-1.77], CAH 1.77 [95% CI 1.66-1.89]) and antifungals (AD 1.89 [95% CI 1.74-2.05], CAH 1.91 [95% CI 1.50-2.43]).

Conclusions

There is an increased risk of infections and antimicrobial use in PAI in the primary care setting at least partially linked to glucocorticoid treatment. Future studies will need to address whether more physiological glucocorticoid replacement modes could reduce this risk.",People who suffer with primary adrenal insufficiency are more likely to be admitted to hospital. But the risk to patients catching infections whilst being treated in hospital is unknown. This study found that people with PAI being treated in hospital have a higher risk of catching an infection. Some of this risk is linked with how PAI is treated.,pdf:https://academic.oup.com/jcem/article-pdf/105/2/418/33574680/dgz006.pdf; doi:https://doi.org/10.1210/clinem/dgz006; html:https://europepmc.org/articles/PMC7046014 @@ -813,20 +813,20 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 36567336,https://doi.org/10.1186/s12872-022-03005-w,Diagnostic signature for heart failure with preserved ejection fraction (HFpEF): a machine learning approach using multi-modality electronic health record data.,"Farajidavar N, O'Gallagher K, Bean D, Nabeebaccus A, Zakeri R, Bromage D, Kraljevic Z, Teo JTH, Dobson RJ, Shah AM.",,BMC cardiovascular disorders,2022,2022-12-26,Y,Dyspnea; Machine Learning; Hfpef,,,"

Background

Heart failure with preserved ejection fraction (HFpEF) is thought to be highly prevalent yet remains underdiagnosed. Evidence-based treatments are available that increase quality of life and decrease hospitalization. We sought to develop a data-driven diagnostic model to predict from electronic health records (EHR) the likelihood of HFpEF among patients with unexplained dyspnea and preserved left ventricular EF.

Methods and results

The derivation cohort comprised patients with dyspnea and echocardiography results. Structured and unstructured data were extracted using an automated informatics pipeline. Patients were retrospectively diagnosed as HFpEF (cases), non-HF (control cohort I), or HF with reduced EF (HFrEF; control cohort II). The ability of clinical parameters and investigations to discriminate cases from controls was evaluated by extreme gradient boosting. A likelihood scoring system was developed and validated in a separate test cohort. The derivation cohort included 1585 consecutive patients: 133 cases of HFpEF (9%), 194 non-HF cases (Control cohort I) and 1258 HFrEF cases (Control cohort II). Two HFpEF diagnostic signatures were derived, comprising symptoms, diagnoses and investigation results. A final prediction model was generated based on the averaged likelihood scores from these two models. In a validation cohort consisting of 269 consecutive patients [with 66 HFpEF cases (24.5%)], the diagnostic power of detecting HFpEF had an AUROC of 90% (P < 0.001) and average precision of 74%.

Conclusion

This diagnostic signature enables discrimination of HFpEF from non-cardiac dyspnea or HFrEF from EHR and can assist in the diagnostic evaluation in patients with unexplained dyspnea. This approach will enable identification of HFpEF patients who may then benefit from new evidence-based therapies.",,pdf:https://bmccardiovascdisord.biomedcentral.com/counter/pdf/10.1186/s12872-022-03005-w; doi:https://doi.org/10.1186/s12872-022-03005-w; html:https://europepmc.org/articles/PMC9791783; pdf:https://europepmc.org/articles/PMC9791783?pdf=render 36001371,https://doi.org/10.2196/38122,Deployment of a Free-Text Analytics Platform at a UK National Health Service Research Hospital: CogStack at University College London Hospitals.,"Noor K, Roguski L, Bai X, Handy A, Klapaukh R, Folarin A, Romao L, Matteson J, Lea N, Zhu L, Asselbergs FW, Wong WK, Shah A, Dobson RJ.",,JMIR medical informatics,2022,2022-08-24,Y,Information Retrieval; Natural Language Processing; Text Mining; Electronic Health Record System; Clinical Support,,,"

Background

As more health care organizations transition to using electronic health record (EHR) systems, it is important for these organizations to maximize the secondary use of their data to support service improvement and clinical research. These organizations will find it challenging to have systems capable of harnessing the unstructured data fields in the record (clinical notes, letters, etc) and more practically have such systems interact with all of the hospital data systems (legacy and current).

Objective

We describe the deployment of the EHR interfacing information extraction and retrieval platform CogStack at University College London Hospitals (UCLH).

Methods

At UCLH, we have deployed the CogStack platform, an information retrieval platform with natural language processing capabilities. The platform addresses the problem of data ingestion and harmonization from multiple data sources using the Apache NiFi module for managing complex data flows. The platform also facilitates the extraction of structured data from free-text records through use of the MedCAT natural language processing library. Finally, data science tools are made available to support data scientists and the development of downstream applications dependent upon data ingested and analyzed by CogStack.

Results

The platform has been deployed at the hospital, and in particular, it has facilitated a number of research and service evaluation projects. To date, we have processed over 30 million records, and the insights produced from CogStack have informed a number of clinical research use cases at the hospital.

Conclusions

The CogStack platform can be configured to handle the data ingestion and harmonization challenges faced by a hospital. More importantly, the platform enables the hospital to unlock important clinical information from the unstructured portion of the record using natural language processing technology.",,pdf:https://medinform.jmir.org/2022/8/e38122/PDF; doi:https://doi.org/10.2196/38122; html:https://europepmc.org/articles/PMC9453582 36808078,https://doi.org/10.1136/pn-2021-003286,Outpatient neurology diagnostic coding: a proposed scheme for standardised implementation.,"Biggin F, Knight J, Dayanandan R, Marson A, Wilson M, Nitkunan A, Rog D, Kipps C, Mummery C, Williams A, Emsley HCA.",,Practical neurology,2023,2023-02-20,Y,Clinical Neurology,,,"Clinical coding uses a classification system to assign standard codes to clinical terms and so facilitates good clinical practice through audit, service design and research. However, despite clinical coding being mandatory for inpatient activity, this is often not so for outpatient services, where most neurological care is delivered. Recent reports by the UK National Neurosciences Advisory Group and NHS England's 'Getting It Right First Time' initiative recommend implementing outpatient coding. The UK currently has no standardised system for outpatient neurology diagnostic coding. However, most new attendances at general neurology clinics appear to be classifiable with a limited number of diagnostic terms. We present the rationale for diagnostic coding and its benefits, and the need for clinical engagement to develop a system that is pragmatic, quick and easy to use. We outline a scheme developed in the UK that could be used elsewhere.",,pdf:https://pn.bmj.com/content/practneurol/early/2023/02/19/pn-2021-003286.full.pdf; doi:https://doi.org/10.1136/pn-2021-003286; html:https://europepmc.org/articles/PMC10423506; pdf:https://europepmc.org/articles/PMC10423506?pdf=render -36895179,https://doi.org/10.1093/eurjpc/zwad055,Determining cardiovascular risk in patients with unattributed chest pain in UK primary care: an electronic health record study.,"Jordan KP, Rathod-Mistry T, van der Windt DA, Bailey J, Chen Y, Clarson L, Denaxas S, Hayward RA, Hemingway H, Kyriacou T, Mamas MA.",,European journal of preventive cardiology,2023,2023-08-01,Y,Cardiovascular disease; Chest pain; epidemiology; Primary Health Care; risk; Electronic Health Records,,,"

Aims

Most adults presenting in primary care with chest pain symptoms will not receive a diagnosis ('unattributed' chest pain) but are at increased risk of cardiovascular events. To assess within patients with unattributed chest pain, risk factors for cardiovascular events and whether those at greatest risk of cardiovascular disease can be ascertained by an existing general population risk prediction model or by development of a new model.

Methods and results

The study used UK primary care electronic health records from the Clinical Practice Research Datalink linked to admitted hospitalizations. Study population was patients aged 18 plus with recorded unattributed chest pain 2002-2018. Cardiovascular risk prediction models were developed with external validation and comparison of performance to QRISK3, a general population risk prediction model. There were 374 917 patients with unattributed chest pain in the development data set. The strongest risk factors for cardiovascular disease included diabetes, atrial fibrillation, and hypertension. Risk was increased in males, patients of Asian ethnicity, those in more deprived areas, obese patients, and smokers. The final developed model had good predictive performance (external validation c-statistic 0.81, calibration slope 1.02). A model using a subset of key risk factors for cardiovascular disease gave nearly identical performance. QRISK3 underestimated cardiovascular risk.

Conclusion

Patients presenting with unattributed chest pain are at increased risk of cardiovascular events. It is feasible to accurately estimate individual risk using routinely recorded information in the primary care record, focusing on a small number of risk factors. Patients at highest risk could be targeted for preventative measures.",,pdf:https://academic.oup.com/eurjpc/advance-article-pdf/doi/10.1093/eurjpc/zwad055/49604587/zwad055.pdf; doi:https://doi.org/10.1093/eurjpc/zwad055; html:https://europepmc.org/articles/PMC10442054; pdf:https://europepmc.org/articles/PMC10442054?pdf=render 34649997,https://doi.org/10.2337/dc21-0437,"Polycystic Ovary Syndrome, Combined Oral Contraceptives, and the Risk of Dysglycemia: A Population-Based Cohort Study With a Nested Pharmacoepidemiological Case-Control Study.","Kumarendran B, O'Reilly MW, Subramanian A, Šumilo D, Toulis K, Gokhale KM, Wijeratne CN, Coomarasamy A, Tahrani AA, Azoulay L, Arlt W, Nirantharakumar K.",,Diabetes care,2021,2021-10-14,Y,,,,"

Objective

Irregular menstrual cycles are associated with increased cardiovascular mortality. Polycystic ovary syndrome (PCOS) is characterized by androgen excess and irregular menses; androgens are drivers of increased metabolic risk in women with PCOS. Combined oral contraceptive pills (COCPs) are used in PCOS both for cycle regulation and to reduce the biologically active androgen fraction. We examined COCP use and risk of dysglycemia (prediabetes and type 2 diabetes) in women with PCOS.

Research design and methods

Using a large U.K. primary care database (The Health Improvement Network [THIN]; 3.7 million patients from 787 practices), we carried out a retrospective population-based cohort study to determine dysglycemia risk (64,051 women with PCOS and 123,545 matched control subjects), as well as a nested pharmacoepidemiological case-control study to investigate COCP use in relation to dysglycemia risk (2,407 women with PCOS with [case subjects] and without [control subjects] a diagnosis of dysglycemia during follow-up). Cox models were used to estimate the unadjusted and adjusted hazard ratio, and conditional logistic regression was used to obtain adjusted odds ratios (aORs).

Results

The adjusted hazard ratio for dysglycemia in women with PCOS was 1.87 (95% CI 1.78-1.97, P < 0.001; adjustment for age, social deprivation, BMI, ethnicity, and smoking), with increased rates of dysglycemia in all BMI subgroups. Women with PCOS and COCP use had a reduced dysglycemia risk (aOR 0.72, 95% CI 0.59-0.87).

Conclusions

In this study, limited by its retrospective nature and the use of routinely collected electronic general practice record data, which does not allow for exclusion of the impact of prescription-by-indication bias, women with PCOS exposed to COCPs had a reduced risk of dysglycemia across all BMI subgroups. Future prospective studies should be considered for further understanding of these observations and potential causality.",,pdf:https://diabetesjournals.org/care/article-pdf/44/12/2758/631597/dc210437.pdf; doi:https://doi.org/10.2337/dc21-0437; html:https://europepmc.org/articles/PMC8669537; pdf:https://europepmc.org/articles/PMC8669537?pdf=render +36895179,https://doi.org/10.1093/eurjpc/zwad055,Determining cardiovascular risk in patients with unattributed chest pain in UK primary care: an electronic health record study.,"Jordan KP, Rathod-Mistry T, van der Windt DA, Bailey J, Chen Y, Clarson L, Denaxas S, Hayward RA, Hemingway H, Kyriacou T, Mamas MA.",,European journal of preventive cardiology,2023,2023-08-01,Y,Cardiovascular disease; Chest pain; epidemiology; Primary Health Care; risk; Electronic Health Records,,,"

Aims

Most adults presenting in primary care with chest pain symptoms will not receive a diagnosis ('unattributed' chest pain) but are at increased risk of cardiovascular events. To assess within patients with unattributed chest pain, risk factors for cardiovascular events and whether those at greatest risk of cardiovascular disease can be ascertained by an existing general population risk prediction model or by development of a new model.

Methods and results

The study used UK primary care electronic health records from the Clinical Practice Research Datalink linked to admitted hospitalizations. Study population was patients aged 18 plus with recorded unattributed chest pain 2002-2018. Cardiovascular risk prediction models were developed with external validation and comparison of performance to QRISK3, a general population risk prediction model. There were 374 917 patients with unattributed chest pain in the development data set. The strongest risk factors for cardiovascular disease included diabetes, atrial fibrillation, and hypertension. Risk was increased in males, patients of Asian ethnicity, those in more deprived areas, obese patients, and smokers. The final developed model had good predictive performance (external validation c-statistic 0.81, calibration slope 1.02). A model using a subset of key risk factors for cardiovascular disease gave nearly identical performance. QRISK3 underestimated cardiovascular risk.

Conclusion

Patients presenting with unattributed chest pain are at increased risk of cardiovascular events. It is feasible to accurately estimate individual risk using routinely recorded information in the primary care record, focusing on a small number of risk factors. Patients at highest risk could be targeted for preventative measures.",,pdf:https://academic.oup.com/eurjpc/advance-article-pdf/doi/10.1093/eurjpc/zwad055/49604587/zwad055.pdf; doi:https://doi.org/10.1093/eurjpc/zwad055; html:https://europepmc.org/articles/PMC10442054; pdf:https://europepmc.org/articles/PMC10442054?pdf=render 36447757,https://doi.org/10.1136/gpsych-2022-100819,Body mass index and mortality in patients with schizophrenia spectrum disorders: a cohort study in a South London catchment area.,"Chen J, Perera G, Shetty H, Broadbent M, Xu Y, Stewart R.",,General psychiatry,2022,2022-11-04,Y,Schizophrenia; Life style; Mental Health Services,,,"

Background

People with schizophrenia have a high premature mortality risk. Obesity is a key potential underlying risk factor that is relatively unevaluated to date.

Aims

In this study, we investigated the associations of routinely recorded body size with all-cause mortality and deaths from common causes in a large cohort of people with schizophrenia spectrum disorders.

Methods

We assembled a retrospective observational cohort using data from a large mental health service in South London. We followed all patients over the age of 18 years with a clinical diagnosis of schizophrenia spectrum disorders from the date of their first recorded body mass index (BMI) between 1 January 2007 and 31 March 2018.

Results

Of 11 900 patients with a BMI recording, 1566 died. The Cox proportional hazards regression models, after adjusting for sociodemographic, socioeconomic variables and comorbidities, indicated that all-cause mortality was only associated with underweight status compared with healthy weight status (hazard ratio (HR): 1.33, 95% confidence interval (CI): 1.01 to 1.76). Obesity (HR: 1.24, 95% CI: 1.01 to 1.52) and morbid obesity (HR: 1.54, 95% CI: 1.03 to 2.42) were associated with all-cause mortality in the 18-45 years age range, and obesity was associated with lower risk (HR: 0.66, 95% CI: 0.50 to 0.87) in those aged 65+ years. Cancer mortality was raised in underweight individuals (HR: 1.93, 95% CI: 1.03 to 4.10) and respiratory disease mortality raised in those with morbid obesity (HR: 2.17, 95% CI: 1.02 to 5.22).

Conclusions

Overall, being underweight was associated with higher mortality in this disorder group; however, this was potentially accounted for by frailty in older age groups, and obesity was a risk factor for premature mortality in younger ages. The impact of obesity on life expectancy for people with schizophrenia spectrum disorders is clear from our findings. A deeper biological understanding of the relationship between these diseases and schizophrenia will help improve clinical practice.",,pdf:https://gpsych.bmj.com/content/gpsych/35/5/e100819.full.pdf; doi:https://doi.org/10.1136/gpsych-2022-100819; html:https://europepmc.org/articles/PMC9639123; pdf:https://europepmc.org/articles/PMC9639123?pdf=render -38036971,https://doi.org/10.1186/s12859-023-05576-7,Completing a genomic characterisation of microscopic tumour samples with copy number.,"Nulsen J, Hussain N, Al-Deka A, Yap J, Uddin K, Yau C, Ahmed AA.",,BMC bioinformatics,2023,2023-11-30,Y,Copy number; Microscopic Samples; Cancer Genomics,,,"

Background

Genomic insights in settings where tumour sample sizes are limited to just hundreds or even tens of cells hold great clinical potential, but also present significant technical challenges. We previously developed the DigiPico sequencing platform to accurately identify somatic mutations from such samples.

Results

Here, we complete this genomic characterisation with copy number. We present a novel protocol, PicoCNV, to call allele-specific somatic copy number alterations from picogram quantities of tumour DNA. We find that PicoCNV provides exactly accurate copy number in 84% of the genome for even the smallest samples, and demonstrate its clinical potential in maintenance therapy.

Conclusions

PicoCNV complements our existing platform, allowing for accurate and comprehensive genomic characterisations of cancers in settings where only microscopic samples are available.",,pdf:https://bmcbioinformatics.biomedcentral.com/counter/pdf/10.1186/s12859-023-05576-7; doi:https://doi.org/10.1186/s12859-023-05576-7; html:https://europepmc.org/articles/PMC10688092; pdf:https://europepmc.org/articles/PMC10688092?pdf=render 33123364,https://doi.org/10.1093/ckj/sfaa192,Temporal changes in complement activation in haemodialysis patients with COVID-19 as a predictor of disease progression.,"Prendecki M, Clarke C, Medjeral-Thomas N, McAdoo SP, Sandhu E, Peters JE, Thomas DC, Willicombe M, Botto M, Pickering MC.",,Clinical kidney journal,2020,2020-10-02,Y,Complement; Haemodialysis; Covid-19,,,"

Background

Complement activation may play a pathogenic role in patients with severe coronavirus disease 2019 (COVID-19) by contributing to tissue inflammation and microvascular thrombosis.

Methods

Serial samples were collected from patients receiving maintenance haemodialysis (HD). Thirty-nine patients had confirmed COVID-19 and 10 patients had no evidence of COVID-19. Plasma C5a and C3a levels were measured using enzyme-linked immunosorbent assay.

Results

We identified elevated levels of plasma C3a and C5a in HD patients with severe COVID-19 compared with controls. Serial sampling identified that C5a levels were elevated prior to clinical deterioration in patients who developed severe disease. C3a more closely mirrored both clinical and biochemical disease severity.

Conclusions

Our findings suggest that activation of complement plays a role in the pathogenesis of COVID-19, leading to endothelial injury and lung damage. C5a may be an earlier biomarker of disease severity than conventional parameters such as C-reactive protein and this warrants further investigation in dedicated biomarker studies. Our data support the testing of complement inhibition as a therapeutic strategy for patients with severe COVID-19.",,pdf:https://academic.oup.com/ckj/article-pdf/13/5/889/33980535/sfaa192.pdf; doi:https://doi.org/10.1093/ckj/sfaa192; html:https://europepmc.org/articles/PMC7577776; pdf:https://europepmc.org/articles/PMC7577776?pdf=render +38036971,https://doi.org/10.1186/s12859-023-05576-7,Completing a genomic characterisation of microscopic tumour samples with copy number.,"Nulsen J, Hussain N, Al-Deka A, Yap J, Uddin K, Yau C, Ahmed AA.",,BMC bioinformatics,2023,2023-11-30,Y,Copy number; Microscopic Samples; Cancer Genomics,,,"

Background

Genomic insights in settings where tumour sample sizes are limited to just hundreds or even tens of cells hold great clinical potential, but also present significant technical challenges. We previously developed the DigiPico sequencing platform to accurately identify somatic mutations from such samples.

Results

Here, we complete this genomic characterisation with copy number. We present a novel protocol, PicoCNV, to call allele-specific somatic copy number alterations from picogram quantities of tumour DNA. We find that PicoCNV provides exactly accurate copy number in 84% of the genome for even the smallest samples, and demonstrate its clinical potential in maintenance therapy.

Conclusions

PicoCNV complements our existing platform, allowing for accurate and comprehensive genomic characterisations of cancers in settings where only microscopic samples are available.",,pdf:https://bmcbioinformatics.biomedcentral.com/counter/pdf/10.1186/s12859-023-05576-7; doi:https://doi.org/10.1186/s12859-023-05576-7; html:https://europepmc.org/articles/PMC10688092; pdf:https://europepmc.org/articles/PMC10688092?pdf=render 38018286,https://doi.org/10.1111/vox.13564,"The value of genetic data from 665,460 individuals in managing iron deficiency anaemia and suitability to donate blood.","Toivonen J, Allara E, FinnGen, Castrén J, di Angelantonio E, Arvas M.",,Vox sanguinis,2024,2023-11-28,N,statistical inference; Gwas; Iron Deficiency Anaemia; Genetic Risk; Prs; Hb-deferral,,,"

Background and objectives

Although the genetic determinants of haemoglobin and ferritin have been widely studied, those of the clinically and globally relevant iron deficiency anaemia (IDA) and deferral due to hypohaemoglobinemia (Hb-deferral) are unclear. In this investigation, we aimed to quantify the value of genetic information in predicting IDA and Hb-deferral.

Materials and methods

We analysed genetic data from up to 665,460 participants of the FinnGen, Blood Service Biobank and UK Biobank, and used INTERVAL (N = 39,979) for validation. We performed genome-wide association studies (GWASs) of IDA and Hb-deferral and utilized publicly available genetic associations to compute polygenic scores for IDA, ferritin and Hb. We fitted models to estimate the effect sizes of these polygenic risk scores (PRSs) on IDA and Hb-deferral risk while accounting for the individual's age, sex, weight, height, smoking status and blood donation history.

Results

Significant variants in GWASs of IDA and Hb-deferral appear to be a small subset of variants associated with ferritin and Hb. Effect sizes of genetic predictors of IDA and Hb-deferral are similar to those of age and weight which are typically used in blood donor management. A total genetic score for Hb-deferral was estimated for each individual. The odds ratio estimate between first decile against that at ninth decile of total genetic score distribution ranged from 1.4 to 2.2.

Conclusion

The value of genetic data in predicting IDA or suitability to donate blood appears to be on a practically useful level.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/vox.13564; doi:https://doi.org/10.1111/vox.13564 -36280346,https://doi.org/10.1136/heartjnl-2022-321492,Cardiovascular disease and mortality sequelae of COVID-19 in the UK Biobank.,"Raisi-Estabragh Z, Cooper J, Salih A, Raman B, Lee AM, Neubauer S, Harvey NC, Petersen SE.",,Heart (British Cardiac Society),2022,2022-12-22,Y,epidemiology; Covid-19,,,"

Objective

To examine association of COVID-19 with incident cardiovascular events in 17 871 UK Biobank cases between March 2020 and 2021.

Methods

COVID-19 cases were defined using health record linkage. Each case was propensity score-matched to two uninfected controls on age, sex, deprivation, body mass index, ethnicity, diabetes, prevalent ischaemic heart disease (IHD), smoking, hypertension and high cholesterol. We included the following incident outcomes: myocardial infarction, stroke, heart failure, atrial fibrillation, venous thromboembolism (VTE), pericarditis, all-cause death, cardiovascular death, IHD death. Cox proportional hazards regression was used to estimate associations of COVID-19 with each outcome over an average of 141 days (range 32-395) of prospective follow-up.

Results

Non-hospitalised cases (n=14 304) had increased risk of incident VTE (HR 2.74 (95% CI 1.38 to 5.45), p=0.004) and death (HR 10.23 (95% CI 7.63 to 13.70), p<0.0001). Individuals with primary COVID-19 hospitalisation (n=2701) had increased risk of all outcomes considered. The largest effect sizes were with VTE (HR 27.6 (95% CI 14.5 to 52.3); p<0.0001), heart failure (HR 21.6 (95% CI 10.9 to 42.9); p<0.0001) and stroke (HR 17.5 (95% CI 5.26 to 57.9); p<0.0001). Those hospitalised with COVID-19 as a secondary diagnosis (n=866) had similarly increased cardiovascular risk. The associated risks were greatest in the first 30 days after infection but remained higher than controls even after this period.

Conclusions

Individuals hospitalised with COVID-19 have increased risk of incident cardiovascular events across a range of disease and mortality outcomes. The risk of most events is highest in the early postinfection period. Individuals not requiring hospitalisation have increased risk of VTE, but not of other cardiovascular-specific outcomes.",,pdf:https://heart.bmj.com/content/heartjnl/109/2/119.full.pdf; doi:https://doi.org/10.1136/heartjnl-2022-321492; html:https://europepmc.org/articles/PMC9811071; pdf:https://europepmc.org/articles/PMC9811071?pdf=render 33436761,https://doi.org/10.1038/s41598-020-79964-x,The overlap of genetic susceptibility to schizophrenia and cardiometabolic disease can be used to identify metabolically different groups of individuals.,"Strawbridge RJ, Johnston KJA, Bailey MES, Baldassarre D, Cullen B, Eriksson P, deFaire U, Ferguson A, Gigante B, Giral P, Graham N, Hamsten A, Humphries SE, Kurl S, Lyall DM, Lyall LM, Pell JP, Pirro M, Savonen K, Smit AJ, Tremoli E, Tomainen TP, Veglia F, Ward J, Sennblad B, Smith DJ.",,Scientific reports,2021,2021-01-12,Y,,,,"Understanding why individuals with severe mental illness (Schizophrenia, Bipolar Disorder and Major Depressive Disorder) have increased risk of cardiometabolic disease (including obesity, type 2 diabetes and cardiovascular disease), and identifying those at highest risk of cardiometabolic disease are important priority areas for researchers. For individuals with European ancestry we explored whether genetic variation could identify sub-groups with different metabolic profiles. Loci associated with schizophrenia, bipolar disorder and major depressive disorder from previous genome-wide association studies and loci that were also implicated in cardiometabolic processes and diseases were selected. In the IMPROVE study (a high cardiovascular risk sample) and UK Biobank (general population sample) multidimensional scaling was applied to genetic variants implicated in both psychiatric and cardiometabolic disorders. Visual inspection of the resulting plots used to identify distinct clusters. Differences between these clusters were assessed using chi-squared and Kruskall-Wallis tests. In IMPROVE, genetic loci associated with both schizophrenia and cardiometabolic disease (but not bipolar disorder or major depressive disorder) identified three groups of individuals with distinct metabolic profiles. This grouping was replicated within UK Biobank, with somewhat less distinction between metabolic profiles. This work focused on individuals of European ancestry and is unlikely to apply to more genetically diverse populations. Overall, this study provides proof of concept that common biology underlying mental and physical illness may help to stratify subsets of individuals with different cardiometabolic profiles.",,pdf:https://www.nature.com/articles/s41598-020-79964-x.pdf; doi:https://doi.org/10.1038/s41598-020-79964-x; html:https://europepmc.org/articles/PMC7804422; pdf:https://europepmc.org/articles/PMC7804422?pdf=render +36280346,https://doi.org/10.1136/heartjnl-2022-321492,Cardiovascular disease and mortality sequelae of COVID-19 in the UK Biobank.,"Raisi-Estabragh Z, Cooper J, Salih A, Raman B, Lee AM, Neubauer S, Harvey NC, Petersen SE.",,Heart (British Cardiac Society),2022,2022-12-22,Y,epidemiology; Covid-19,,,"

Objective

To examine association of COVID-19 with incident cardiovascular events in 17 871 UK Biobank cases between March 2020 and 2021.

Methods

COVID-19 cases were defined using health record linkage. Each case was propensity score-matched to two uninfected controls on age, sex, deprivation, body mass index, ethnicity, diabetes, prevalent ischaemic heart disease (IHD), smoking, hypertension and high cholesterol. We included the following incident outcomes: myocardial infarction, stroke, heart failure, atrial fibrillation, venous thromboembolism (VTE), pericarditis, all-cause death, cardiovascular death, IHD death. Cox proportional hazards regression was used to estimate associations of COVID-19 with each outcome over an average of 141 days (range 32-395) of prospective follow-up.

Results

Non-hospitalised cases (n=14 304) had increased risk of incident VTE (HR 2.74 (95% CI 1.38 to 5.45), p=0.004) and death (HR 10.23 (95% CI 7.63 to 13.70), p<0.0001). Individuals with primary COVID-19 hospitalisation (n=2701) had increased risk of all outcomes considered. The largest effect sizes were with VTE (HR 27.6 (95% CI 14.5 to 52.3); p<0.0001), heart failure (HR 21.6 (95% CI 10.9 to 42.9); p<0.0001) and stroke (HR 17.5 (95% CI 5.26 to 57.9); p<0.0001). Those hospitalised with COVID-19 as a secondary diagnosis (n=866) had similarly increased cardiovascular risk. The associated risks were greatest in the first 30 days after infection but remained higher than controls even after this period.

Conclusions

Individuals hospitalised with COVID-19 have increased risk of incident cardiovascular events across a range of disease and mortality outcomes. The risk of most events is highest in the early postinfection period. Individuals not requiring hospitalisation have increased risk of VTE, but not of other cardiovascular-specific outcomes.",,pdf:https://heart.bmj.com/content/heartjnl/109/2/119.full.pdf; doi:https://doi.org/10.1136/heartjnl-2022-321492; html:https://europepmc.org/articles/PMC9811071; pdf:https://europepmc.org/articles/PMC9811071?pdf=render 35301875,https://doi.org/10.1161/jaha.121.023146,Long-Term Cardiovascular Risk and Management of Patients Recorded in Primary Care With Unattributed Chest Pain: An Electronic Health Record Study.,"Jordan KP, Rathod-Mistry T, Bailey J, Chen Y, Clarson L, Denaxas S, Hayward RA, Hemingway H, van der Windt DA, Mamas MA.",,Journal of the American Heart Association,2022,2022-03-18,Y,Cardiovascular disease; Chest pain; Primary Care; Electronic Health Records,,,"Background Most adults presenting with chest pain will not receive a diagnosis and be recorded with unattributed chest pain. The objective was to assess if they have increased risk of cardiovascular disease compared with those with noncoronary chest pain and determine whether investigations and interventions are targeted at those at highest risk. Methods and Results We used records from general practices in England linked to hospitalization and mortality information. The study population included patients aged 18 years or over with a new record of chest pain with a noncoronary cause or unattributed between 2002 and 2018, and no cardiovascular disease recorded up to 6 months (diagnostic window) afterward. We compared risk of a future cardiovascular event by type of chest pain, adjusting for cardiovascular risk factors and alternative explanations for chest pain. We determined prevalence of cardiac diagnostic investigations and preventative medication during the diagnostic window in patients with estimated cardiovascular risk ≥10%. There were 375 240 patients with unattributed chest pain (245 329 noncoronary chest pain). There was an increased risk of cardiovascular events for patients with unattributed chest pain, highest in the first year (hazard ratio, 1.25 [95% CI, 1.21-1.29]), persistent up to 10 years. Patients with unattributed chest pain had consistently increased risk of myocardial infarction over time but no increased risk of stroke. Thirty percent of patients at higher risk were prescribed lipid-lowering medication. Conclusions Patients presenting to primary care with unattributed chest pain are at increased risk of cardiovascular events. Primary prevention to reduce cardiovascular events appears suboptimal in those at higher risk.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.023146; doi:https://doi.org/10.1161/JAHA.121.023146; html:https://europepmc.org/articles/PMC9075433; pdf:https://europepmc.org/articles/PMC9075433?pdf=render 38045436,https://doi.org/10.1093/ehjdh/ztad062,Monitoring left ventricular assist device parameters to detect flow- and power-impacting complications: a proof of concept.,"Moazeni M, Numan L, Szymanski MK, Van der Kaaij NP, Asselbergs FW, van Laake LW, Aarts E.",,European heart journal. Digital health,2023,2023-10-27,Y,Lvad; Intensive Longitudinal Data; Remote Patient Monitoring; Patient-Specific Monitoring,,,"

Aims

The number of patients on left ventricular assist device (LVAD) support increases due to the growing number of patients with end-stage heart failure and the limited number of donor hearts. Despite improving survival rates, patients frequently suffer from adverse events such as cardiac arrhythmia and major bleeding. Telemonitoring is a potentially powerful tool to early detect deteriorations and may further improve outcome after LVAD implantation. Hence, we developed a personalized algorithm to remotely monitor HeartMate3 (HM3) pump parameters aiming to early detect unscheduled admissions due to cardiac arrhythmia or major bleeding.

Methods and results

The source code of the algorithm is published in an open repository. The algorithm was optimized and tested retrospectively using HeartMate 3 (HM3) power and flow data of 120 patients, including 29 admissions due to cardiac arrhythmia and 14 admissions due to major bleeding. Using a true alarm window of 14 days prior to the admission date, the algorithm detected 59 and 79% of unscheduled admissions due to cardiac arrhythmia and major bleeding, respectively, with a false alarm rate of 2%.

Conclusion

The proposed algorithm showed that the personalized algorithm is a viable approach to early identify cardiac arrhythmia and major bleeding by monitoring HM3 pump parameters. External validation is needed and integration with other clinical parameters could potentially improve the predictive value. In addition, the algorithm can be further enhanced using continuous data.",,doi:https://doi.org/10.1093/ehjdh/ztad062; html:https://europepmc.org/articles/PMC10689906; pdf:https://europepmc.org/articles/PMC10689906?pdf=render 34765951,https://doi.org/10.1016/j.eclinm.2021.101163,Net effects of sodium-glucose co-transporter-2 inhibition in different patient groups: a meta-analysis of large placebo-controlled randomized trials.,"Staplin N, Roddick AJ, Emberson J, Reith C, Riding A, Wonnacott A, Kuverji A, Bhandari S, Baigent C, Haynes R, Herrington WG.",,EClinicalMedicine,2021,2021-10-26,Y,Safety; Heart Failure; Randomized Trials; Ckd; Sodium-glucose Co-transporter 2 Inhibitors,,,"

Background

The net absolute effects of sodium-glucose co-transporter-2 (SGLT-2) inhibitors across different patient groups have not been quantified.

Methods

We performed a meta-analysis of published large (>500 participants/arm) placebo-controlled SGLT-2 inhibitor trials after systematically searching MEDLINE and Embase databases from inception to 28th August 2021 (PROSPERO 2021 CRD42021240468).

Findings

Four heart failure trials (n=15,684 participants), four trials in type 2 diabetes mellitus at high atherosclerotic cardiovascular risk (n=42,568), and three trials in chronic kidney disease (n=19,289) were included. Relative risks (RRs) for all cardiovascular, renal and safety outcomes were broadly similar across these three patient groups, and between people with or without diabetes. Overall, compared to placebo, allocation to SGLT-2 inhibition reduced risk of hospitalization for heart failure or cardiovascular death by 23% (RR=0.77, 95%CI 0.73-0.80; n=6658), cardiovascular death by 14% (0.86, 0.81-0.92; n=3962), major adverse cardiovascular events by 11% (0.89, 0.84-0.94; n=5703), kidney disease progression by 36% (0.64, 0.59-0.70; n=2275), acute kidney injury by 30% (0.70, 0.62-0.79; n=1013 events) and severe hypoglycaemia by 13% (0.87, 0.79-0.97; n=1484). There was no effect of SGLT-2 inhibition on risk of non-cardiovascular death (0.93, 0.86-1.01; n=2226), but a net 12% reduction in all-cause mortality remained evident (0.88, 0.84-0.93; n=6188). However, the risk of ketoacidosis was 2-times higher among those allocated SGLT-2 inhibitors compared to placebo (2.03, 1.41-2.93; n=159; absolute excess in people with diabetes ∼0.3/1000 patient years). A small increased risk of urinary tract infection was evident (1.07, 1.02-1.13; n=5384) alongside a known increased risk of mycotic genital infections. Overall, risk of lower limb amputations was increased by 16% (1.16, 1.02-1.31; n=1074), but this risk was largely driven by a single outlying trial (CANVAS).

Interpretations

The relative effects of SGLT-2 inhibition on key safety and efficacy outcomes are consistent across the different studied groups of patient. Consequently, absolute benefits and harms are determined by the absolute baseline risk of particular outcomes, with absolute benefits on mortality and on non-fatal serious cardiac/renal outcomes substantially exceeding the risks of amputation and ketoacidosis in the main patient groups studied to date.

Funding

MRC-UK & KRUK.",,doi:https://doi.org/10.1016/j.eclinm.2021.101163; doi:https://doi.org/10.1016/j.eclinm.2021.101163; html:https://europepmc.org/articles/PMC8571171; pdf:https://europepmc.org/articles/PMC8571171?pdf=render +34298561,https://doi.org/10.1177/2047487320914115,Achievement of European guideline-recommended lipid levels post-percutaneous coronary intervention: A population-level observational cohort study.,"Harris DE, Lacey A, Akbari A, Torabi F, Smith D, Jenkins G, Obaid D, Chase A, Gravenor M, Halcox J.",,European journal of preventive cardiology,2021,2021-07-01,N,Lipids; Cholesterol; Percutaneous coronary intervention; Secondary Prevention; Pharmacoepidemiology; statins,,,"

Aims

European Society of Cardiology/European Atherosclerosis Society 2019 guidelines recommend more aggressive lipid targets in high- and very high-risk patients and the addition of adjuvant treatments to statins in uncontrolled patients. We aimed to assess (a) achievement of prior and new European Society of Cardiology/European Atherosclerosis Society lipid targets and (b) lipid-lowering therapy prescribing in a nationwide cohort of very high-risk patients.

Methods

We conducted a retrospective observational population study using linked health data in patients undergoing percutaneous coronary intervention (2012-2017). Follow-up was for one-year post-discharge.

Results

Altogether, 10,071 patients had a documented LDL-C level, of whom 48% had low-density lipoprotein cholesterol (LDL-C)<1.8 mmol/l (2016 target) and (23%) <1.4 mmol/l (2019 target). Five thousand three hundred and forty patients had non-high-density lipoprotein cholesterol (non-HDL-C) documented with 57% <2.6 mmol/l (2016) and 37% <2.2 mmol/l (2019). In patients with recurrent vascular events, fewer than 6% of the patients achieved the 2019 LDL-C target of <1.0 mmol/l. A total of 10,592 patients had triglyceride (TG) levels documented, of whom 14% were ≥2.3 mmol/l and 41% ≥1.5 mmol/l (2019). High-intensity statins were prescribed in 56.4% of the cohort, only 3% were prescribed ezetimibe, fibrates or prescription-grade N-3 fatty acids. Prescribing of these agents was lower amongst patients above target LDL-C, non-HDL-C and triglyceride levels. Females were more likely to have LDL-C, non-HDL-C and triglyceride levels above target.

Conclusion

There was a low rate of achievement of the new European Society of Cardiology/European Atherosclerosis Society lipid targets in this large post-percutaneous coronary intervention population and relatively low rates of intensive lipid-lowering therapy prescribing in those with uncontrolled lipids. There is considerable potential to optimise lipid-lowering therapy further through statin intensification and appropriate use of novel lipid-lowering therapy, especially in women.",,pdf:https://academic.oup.com/eurjpc/article-pdf/28/8/854/39301721/zwaa298.pdf; doi:https://doi.org/10.1177/2047487320914115 PMC10686417,https://doi.org/,The impact of restricted provision of publicly funded elective hip and knee joints replacement during the COVID-19 pandemic in England,"Penfold C, Blom A, Redaniel M, Jones T, Eyles E, Keen T, Elliott A, Judge A.",,PloS one,2023,2023-01-01,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686417/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686417/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC10686417; pdf:https://europepmc.org/articles/PMC10686417?pdf=render 37022975,https://doi.org/10.1210/clinem/dgad201,Stable Incidence and Increasing Prevalence of Primary Hyperparathyroidism in a Population-based Study in Scotland.,"Soto-Pedre E, Newey PJ, Leese GP.",,The Journal of clinical endocrinology and metabolism,2023,2023-09-01,Y,Parathyroid gland; Prevalence; epidemiology; incidence; Primary Hyperparathyroidism,,,"

Context

Previous studies, including our own, have demonstrated a highly variable incidence of primary hyperparathyroidism (PHPT) from year to year.

Objective

We planned to provide a current estimate of the incidence and prevalence of PHPT in a community-based study.

Methods

A population-based retrospective follow-up study was conducted in Tayside (Scotland) from 2007 to 2018. Record-linkage technology (demography, biochemistry, prescribing, hospital admissions, radiology, and mortality data) was used to identify all patients. Cases of PHPT were defined as those with at least 2 raised serum corrected calcium concentration CCA (> 2.55 mmol/L) and/or hospital admissions with PHPT diagnoses and/or surgery records with parathyroidectomy during the follow-up period. The number of prevalent and incident cases of PHPT per calendar year by age and sex were estimated.

Results

A total of 2118 people (72.3% female, mean age 65 years) were identified with an incident case of PHPT. The overall prevalence of PHPT over the 12 years of the study was 0.84% (95% CI, 0.68%-1.02%), steadily increasing from 0.71% in 2007 to 1.02% in 2018. From 2008, the incidence of PHPT was relatively stable from 4 to 6 cases per 10 000 person-years, declining from 11.5 per 10 000 person-years in 2007. The incidence varied from 0.59 per 10 000 person-years (95% CI, 0.40%-0.77%) for those aged 20 to 29 years, to 12.4 per 10 000 person-years (95% CI, 11.2%-13.3%) in those aged 70 to 79 years. Incidence of PHPT was 2.5 times higher in women than in men.

Conclusion

This study is the first showing a relatively steady annual incidence of PHPT at 4 to 6 per 10 000 person-years. This population-based study reports a PHPT prevalence of 0.84%.",,pdf:https://academic.oup.com/jcem/advance-article-pdf/doi/10.1210/clinem/dgad201/50034331/dgad201.pdf; doi:https://doi.org/10.1210/clinem/dgad201; html:https://europepmc.org/articles/PMC10505547 -34298561,https://doi.org/10.1177/2047487320914115,Achievement of European guideline-recommended lipid levels post-percutaneous coronary intervention: A population-level observational cohort study.,"Harris DE, Lacey A, Akbari A, Torabi F, Smith D, Jenkins G, Obaid D, Chase A, Gravenor M, Halcox J.",,European journal of preventive cardiology,2021,2021-07-01,N,Lipids; Cholesterol; Percutaneous coronary intervention; Secondary Prevention; Pharmacoepidemiology; statins,,,"

Aims

European Society of Cardiology/European Atherosclerosis Society 2019 guidelines recommend more aggressive lipid targets in high- and very high-risk patients and the addition of adjuvant treatments to statins in uncontrolled patients. We aimed to assess (a) achievement of prior and new European Society of Cardiology/European Atherosclerosis Society lipid targets and (b) lipid-lowering therapy prescribing in a nationwide cohort of very high-risk patients.

Methods

We conducted a retrospective observational population study using linked health data in patients undergoing percutaneous coronary intervention (2012-2017). Follow-up was for one-year post-discharge.

Results

Altogether, 10,071 patients had a documented LDL-C level, of whom 48% had low-density lipoprotein cholesterol (LDL-C)<1.8 mmol/l (2016 target) and (23%) <1.4 mmol/l (2019 target). Five thousand three hundred and forty patients had non-high-density lipoprotein cholesterol (non-HDL-C) documented with 57% <2.6 mmol/l (2016) and 37% <2.2 mmol/l (2019). In patients with recurrent vascular events, fewer than 6% of the patients achieved the 2019 LDL-C target of <1.0 mmol/l. A total of 10,592 patients had triglyceride (TG) levels documented, of whom 14% were ≥2.3 mmol/l and 41% ≥1.5 mmol/l (2019). High-intensity statins were prescribed in 56.4% of the cohort, only 3% were prescribed ezetimibe, fibrates or prescription-grade N-3 fatty acids. Prescribing of these agents was lower amongst patients above target LDL-C, non-HDL-C and triglyceride levels. Females were more likely to have LDL-C, non-HDL-C and triglyceride levels above target.

Conclusion

There was a low rate of achievement of the new European Society of Cardiology/European Atherosclerosis Society lipid targets in this large post-percutaneous coronary intervention population and relatively low rates of intensive lipid-lowering therapy prescribing in those with uncontrolled lipids. There is considerable potential to optimise lipid-lowering therapy further through statin intensification and appropriate use of novel lipid-lowering therapy, especially in women.",,pdf:https://academic.oup.com/eurjpc/article-pdf/28/8/854/39301721/zwaa298.pdf; doi:https://doi.org/10.1177/2047487320914115 35365351,https://doi.org/10.1016/j.injury.2022.03.039,Injury severity and increased socioeconomic differences: A population-based cohort study.,"Madsen C, Gabbe BJ, Holvik K, Alver K, Grøholt EK, Lund J, Lyons J, Lyons RA, Ohm E.",,Injury,2022,2022-03-24,N,Injury; Socioeconomic status; Hospitalization; Iciss; Injury-vibes; Risk-adjusted Severity,,,"

Background

Several studies have documented an inverse gradient between socioeconomic status (SES) and injury mortality, but the evidence is less consistent for injury morbidity. The aim of this study was to investigate the association between SES and injury severity for acute hospitalizations in a nationwide population-based cohort.

Methods

We conducted a registry-based cohort study of all individuals aged 25-64 years residing in Norway by 1st of January 2008. This cohort was followed from 2008 through 2014 using inpatient registrations for acute hospitalizations due to all-cause injuries. We derived two measures of severity: threat-to-life using the International Classification of Disease-based Injury Severity Score (ICISS), and threat of disability using long-term disability weights from the Injury-VIBES project. Robust Poisson regression models, with adjustment for age, sex, marital status, immigrant status, municipality population size and healthcare region of residence, were used to calculate incidence rate ratios (IRRs) by SES measured as an index of education, income, and occupation.

Results

We identified 177,663 individuals (7% of the population) hospitalized with at least one acute injury in the observation period. Two percent (n = 4,186) had injuries categorized with high threat-to-life, while one quarter (n = 43,530) had injuries with high threat of disability. The overall adjusted IRR of hospitalization among people with low compared to high SES was 1.57 (95% CI 1.55, 1.60). Comparing low to high SES, injuries with low threat-to-life were associated with an IRR of 1.56 (95% CI 1.54, 1.59), while injuries with high threat-to-life had an IRR of 2.25 (95% CI 2.03, 2.51). Comparing low to high SES, injuries with low, medium, and high threat of disability were associated with IRRs of respectively, 1.15 (95% CI 1.11, 1.19), 1.70 (95% CI 1.66, 1.73) and 1.99 (95% CI 1.92, 2.07).

Discussion

We observed an inverse gradient between SES and injury morbidity, with the steepest gradient for the most severe injuries. This suggests a need for targeted preventive measures to reduce the magnitude and burden of severe injuries for patients with low socioeconomic status.",,pdf:http://www.injuryjournal.com/article/S0020138322002327/pdf; doi:https://doi.org/10.1016/j.injury.2022.03.039 36150783,https://doi.org/10.1016/s2589-7500(22)00147-9,Data capture and sharing in the COVID-19 pandemic: a cause for concern.,"Dron L, Kalatharan V, Gupta A, Haggstrom J, Zariffa N, Morris AD, Arora P, Park J.",,The Lancet. Digital health,2022,2022-10-01,Y,,,,"Routine health care and research have been profoundly influenced by digital-health technologies. These technologies range from primary data collection in electronic health records (EHRs) and administrative claims to web-based artificial-intelligence-driven analyses. There has been increased use of such health technologies during the COVID-19 pandemic, driven in part by the availability of these data. In some cases, this has resulted in profound and potentially long-lasting positive effects on medical research and routine health-care delivery. In other cases, high profile shortcomings have been evident, potentially attenuating the effect of-or representing a decreased appetite for-digital-health transformation. In this Series paper, we provide an overview of how facets of health technologies in routinely collected medical data (including EHRs and digital data sharing) have been used for COVID-19 research and tracking, and how these technologies might influence future pandemics and health-care research. We explore the strengths and weaknesses of digital-health research during the COVID-19 pandemic and discuss how learnings from COVID-19 might translate into new approaches in a post-pandemic era.",,doi:https://doi.org/10.1016/s2589-7500(22)00147-9; doi:https://doi.org/10.1016/S2589-7500(22)00147-9; html:https://europepmc.org/articles/PMC9489064; pdf:https://europepmc.org/articles/PMC9489064?pdf=render 36102151,https://doi.org/10.1210/clinem/dgac527,Identification of 4 New Loci Associated With Primary Hyperparathyroidism (PHPT) and a Polygenic Risk Score for PHPT.,"Soto-Pedre E, Newey PJ, Srinivasan S, Siddiqui MK, Palmer CNA, Leese GP.",,The Journal of clinical endocrinology and metabolism,2022,2022-11-01,Y,Genetics; Genome-wide Association Study; Primary Hyperparathyroidism; Polygenic Risk Score,,,"

Context

A hypothesis-free genetic association analysis has not been reported for patients with primary hyperparathyroidism (PHPT).

Objective

We aimed to investigate genetic associations with PHPT using both genome-wide association study (GWAS) and candidate gene approaches.

Methods

A cross-sectional study was conducted among patients of European White ethnicity recruited in Tayside (Scotland, UK). Electronic medical records were used to identify PHPT cases and controls, and linked to genetic biobank data. Genetic associations were performed by logistic regression models and odds ratios (ORs). The combined effect of the genotypes was researched by genetic risk score (GRS) analysis.

Results

We identified 15 622 individuals for the GWAS that yielded 34 top single-nucleotide variations (formerly single-nucleotide polymorphisms), and LPAR3-rs147672681 reached genome-wide statistical significance (P = 1.2e-08). Using a more restricted PHPT definition, 8722 individuals with data on the GWAS-identified loci were found. Age- and sex-adjusted ORs for the effect alleles of SOX9-rs11656269, SLITRK5-rs185436526, and BCDIN3D-AS1-rs2045094 showed statistically significant increased risks (P < 1.5e-03). GRS analysis of 5482 individuals showed an OR of 2.51 (P = 1.6e-04), 3.78 (P = 4.0e-08), and 7.71 (P = 5.3e-17) for the second, third, and fourth quartiles, respectively, compared to the first, and there was a statistically significant linear trend across quartiles (P < 1.0e-04). Results were similar when stratifying by sex.

Conclusion

Using genetic loci discovered in a GWAS of PHPT carried out in a Scottish population, this study suggests new evidence for the involvement of genetic variants at SOX9, SLITRK5, LPAR3, and BCDIN3D-AS1. It also suggests that male and female carriers of greater numbers of PHPT-risk alleles both have a statistically significant increased risk of PHPT.",,pdf:https://academic.oup.com/jcem/article-pdf/107/12/3302/47260242/dgac527.pdf; doi:https://doi.org/10.1210/clinem/dgac527; html:https://europepmc.org/articles/PMC9693767 @@ -845,11 +845,11 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 35945198,https://doi.org/10.1038/s41467-022-32095-5,Transferability of genetic loci and polygenic scores for cardiometabolic traits in British Pakistani and Bangladeshi individuals.,"Huang QQ, Sallah N, Dunca D, Trivedi B, Hunt KA, Hodgson S, Lambert SA, Arciero E, Wright J, Griffiths C, Trembath RC, Hemingway H, Inouye M, Finer S, van Heel DA, Lumbers RT, Martin HC, Kuchenbaecker K.",,Nature communications,2022,2022-08-09,Y,,,,"Individuals with South Asian ancestry have a higher risk of heart disease than other groups but have been largely excluded from genetic research. Using data from 22,000 British Pakistani and Bangladeshi individuals with linked electronic health records from the Genes & Health cohort, we conducted genome-wide association studies of coronary artery disease and its key risk factors. Using power-adjusted transferability ratios, we found evidence for transferability for the majority of cardiometabolic loci powered to replicate. The performance of polygenic scores was high for lipids and blood pressure, but lower for BMI and coronary artery disease. Adding a polygenic score for coronary artery disease to clinical risk factors showed significant improvement in reclassification. In Mendelian randomisation using transferable loci as instruments, our findings were consistent with results in European-ancestry individuals. Taken together, trait-specific transferability of trait loci between populations is an important consideration with implications for risk prediction and causal inference.",,pdf:https://www.nature.com/articles/s41467-022-32095-5.pdf; doi:https://doi.org/10.1038/s41467-022-32095-5; html:https://europepmc.org/articles/PMC9363492; pdf:https://europepmc.org/articles/PMC9363492?pdf=render 37526977,https://doi.org/10.5830/cvja-2023-037,Yield of family screening in dilated cardiomyopathy within low-income setting: Tanzanian experience.,"Fundikira LS, Julius J, Chillo P, Mayala H, Kifai E, van Laake LW, Kamuhabwa A, Kwesigabo G, Asselbergs FW.",,Cardiovascular journal of Africa,2023,2023-07-25,N,Screening; Dilated cardiomyopathy; First‐degree Relatives,,,"

Background

Dilated cardiomyopathy (DCM) is often familial and screening of relatives is recommended. However, studies on the yield of screening are scarce in developing countries.

Aim

The aim of the study was to identify and characterise First-degree relatives of patients with DCM in Tanzania.

Methods

We recruited first-degree relatives of 57 DCM patients. DCM in the relatives was diagnosed using the 2016 revised definition by the European Society of Cardiology working group on myocardial and pericardial diseases.

Results

We screened 120 first-degree relatives. All were asymptomatic (100%) with a median age of 39.0 years (29.5-49.0), slightly over a half (53.3%) were females and 17 (14.1%) were found to have previously unknown DCM. The mean (± SD) indexed left ventricular end-diastolic volume was significantly higher in relatives with DCM (71 ± 11.5 ml) compared to relatives without DCM (50 ± 11.5) (p = 0.001).

Conclusion

First-degree relatives of patients with DCM are at risk of developing asymptomatic DCM at a young age.",,doi:https://doi.org/10.5830/CVJA-2023-037 36805366,https://doi.org/10.2196/43419,Prediction of Suicidal Behaviors in the Middle-aged Population: Machine Learning Analyses of UK Biobank.,"Wang J, Qiu J, Zhu T, Zeng Y, Yang H, Shang Y, Yin J, Sun Y, Qu Y, Valdimarsdóttir UA, Song H.",,JMIR public health and surveillance,2023,2023-02-20,Y,Sex; Model; Behavior; Genetic susceptibility; Data; Suicide; risk; Machine Learning; Risk Prediction; Cost-effective; Machine Learning Approach; Suicidal Behaviors,,,"

Background

Suicidal behaviors, including suicide deaths and attempts, are major public health concerns. However, previous suicide models required a huge amount of input features, resulting in limited applicability in clinical practice.

Objective

We aimed to construct applicable models (ie, with limited features) for short- and long-term suicidal behavior prediction. We further validated these models among individuals with different genetic risks of suicide.

Methods

Based on the prospective cohort of UK Biobank, we included 223 (0.06%) eligible cases of suicide attempts or deaths, according to hospital inpatient or death register data within 1 year from baseline and randomly selected 4460 (1.18%) controls (1:20) without such records. We similarly identified 833 (0.22%) cases of suicidal behaviors 1 to 6 years from baseline and 16,660 (4.42%) corresponding controls. Based on 143 input features, mainly including sociodemographic, environmental, and psychosocial factors; medical history; and polygenic risk scores (PRS) for suicidality, we applied a bagged balanced light gradient-boosting machine (LightGBM) with stratified 10-fold cross-validation and grid-search to construct the full prediction models for suicide attempts or deaths within 1 year or between 1 and 6 years. The Shapley Additive Explanations (SHAP) approach was used to quantify the importance of input features, and the top 20 features with the highest SHAP values were selected to train the applicable models. The external validity of the established models was assessed among 50,310 individuals who participated in UK Biobank repeated assessments both overall and by the level of PRS for suicidality.

Results

Individuals with suicidal behaviors were on average 56 years old, with equal sex distribution. The application of these full models in the external validation data set demonstrated good model performance, with the area under the receiver operating characteristic (AUROC) curves of 0.919 and 0.892 within 1 year and between 1 and 6 years, respectively. Importantly, the applicable models with the top 20 most important features showed comparable external-validated performance (AUROC curves of 0.901 and 0.885) as the full models, based on which we found that individuals in the top quintile of predicted risk accounted for 91.7% (n=11) and 80.7% (n=25) of all suicidality cases within 1 year and during 1 to 6 years, respectively. We further obtained comparable prediction accuracy when applying these models to subpopulations with different genetic susceptibilities to suicidality. For example, for the 1-year risk prediction, the AUROC curves were 0.907 and 0.885 for the high (>2nd tertile of PRS) and low (<1st) genetic susceptibilities groups, respectively.

Conclusions

We established applicable machine learning-based models for predicting both the short- and long-term risk of suicidality with high accuracy across populations of varying genetic risk for suicide, highlighting a cost-effective method of identifying individuals with a high risk of suicidality.",,pdf:https://publichealth.jmir.org/2023/1/e43419/PDF; doi:https://doi.org/10.2196/43419; html:https://europepmc.org/articles/PMC9989910 -36773891,https://doi.org/10.1016/j.jinf.2023.02.012,"Real-world effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab on preventing hospital admission among higher-risk patients with COVID-19 in Wales: A retrospective cohort study.","Evans A, Qi C, Adebayo JO, Underwood J, Coulson J, Bailey R, Lyons R, Edwards A, Cooper A, John G, Akbari A.",,The Journal of infection,2023,2023-02-10,Y,Health protection; Public Health; Covid-19,,,"

Objective

To compare the effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab with no treatment in preventing hospital admission or death in higher-risk patients infected with SARS-CoV-2 in the community.

Design

Retrospective cohort study of non-hospitalized adult patients with COVID-19 using the Secure Anonymised Information Linkage (SAIL) Databank.

Setting

A real-world cohort study was conducted within the SAIL Databank (a secure trusted research environment containing anonymised, individual, population-scale electronic health record (EHR) data) for the population of Wales, UK.

Participants

Adult patients with COVID-19 in the community, at higher risk of hospitalization and death, testing positive for SARS-CoV-2 between 16th December 2021 and 22nd April 2022.

Interventions

Molnupiravir, nirmatrelvir-ritonavir, and sotrovimab given in the community by local health boards and the National Antiviral Service in Wales.

Main outcome measures

All-cause admission to hospital or death within 28 days of a positive test for SARS-CoV-2.

Statistical analysis

Cox proportional hazard model with treatment status (treated/untreated) as a time-dependent covariate and adjusted for age, sex, number of comorbidities, Welsh Index of Multiple Deprivation, and vaccination status. Secondary subgroup analyses were by treatment type, number of comorbidities, and before and on or after 20th February 2022, when omicron BA.1 and omicron BA.2 were the dominant subvariants in Wales.

Results

Between 16th December 2021 and 22nd April 2022, 7013 higher-risk patients were eligible for inclusion in the study. Of these, 2040 received treatment with molnupiravir (359, 17.6%), nirmatrelvir-ritonavir (602, 29.5%), or sotrovimab (1079, 52.9%). Patients in the treatment group were younger (mean age 53 vs 57 years), had fewer comorbidities, and a higher proportion had received four or more doses of the COVID-19 vaccine (36.3% vs 17.6%). Within 28 days of a positive test, 628 (9.0%) patients were admitted to hospital or died (84 treated and 544 untreated). The primary analysis indicated a lower risk of hospitalization or death at any point within 28 days in treated participants compared to those not receiving treatment. The adjusted hazard rate was 35% (95% CI: 18-49%) lower in treated than untreated participants. There was no indication of the superiority of one treatment over another and no evidence of a reduction in risk of hospitalization or death within 28 days for patients with no or only one comorbidity. In patients treated with sotrovimab, the event rates before and on or after 20th February 2022 were similar (5.0% vs 4.9%) with no significant difference in the hazard ratios for sotrovimab between the time periods.

Conclusions

In higher-risk adult patients in the community with COVID-19, those who received treatment with molnupiravir, nirmatrelvir-ritonavir, or sotrovimab were at lower risk of hospitalization or death than those not receiving treatment.",,pdf:http://www.journalofinfection.com/article/S0163445323000828/pdf; doi:https://doi.org/10.1016/j.jinf.2023.02.012; html:https://europepmc.org/articles/PMC9911979; pdf:https://europepmc.org/articles/PMC9911979?pdf=render 29938349,https://doi.org/10.1007/s11892-018-1021-5,Shared Genetic Contribution of Type 2 Diabetes and Cardiovascular Disease: Implications for Prognosis and Treatment.,"Strawbridge RJ, van Zuydam NR.",,Current diabetes reports,2018,2018-06-25,Y,Type 2 diabetes; Ischemic stroke; coronary artery disease; risk factors; Peripheral Artery Disease; Genetics; Mendelian Randomisation,,,"

Purpose of review

The increased cardiovascular disease (CVD) risk in subjects with type 2 diabetes (T2D) is well established. This review collates the available evidence and assesses the shared genetic background between T2D and CVD: the causal contribution of common risk factors to T2D and CVD and how genetics can be used to improve drug development and clinical outcomes.

Recent findings

Large-scale genome-wide association studies (GWAS) of T2D and CVD support a shared genetic background but minimal individual locus overlap. Mendelian randomisation (MR) analyses show that T2D is causal for CVD, but GWAS of CVD, T2D and their common risk factors provided limited evidence for individual locus overlap. Distinct but functionally related pathways were enriched for CVD and T2D genetic associations reflecting the lack of locus overlap and providing some explanation for the variable associations of common risk factors with CVD and T2D from MR analyses.",,pdf:https://link.springer.com/content/pdf/10.1007/s11892-018-1021-5.pdf; doi:https://doi.org/10.1007/s11892-018-1021-5; html:https://europepmc.org/articles/PMC6015804; pdf:https://europepmc.org/articles/PMC6015804?pdf=render +36773891,https://doi.org/10.1016/j.jinf.2023.02.012,"Real-world effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab on preventing hospital admission among higher-risk patients with COVID-19 in Wales: A retrospective cohort study.","Evans A, Qi C, Adebayo JO, Underwood J, Coulson J, Bailey R, Lyons R, Edwards A, Cooper A, John G, Akbari A.",,The Journal of infection,2023,2023-02-10,Y,Health protection; Public Health; Covid-19,,,"

Objective

To compare the effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab with no treatment in preventing hospital admission or death in higher-risk patients infected with SARS-CoV-2 in the community.

Design

Retrospective cohort study of non-hospitalized adult patients with COVID-19 using the Secure Anonymised Information Linkage (SAIL) Databank.

Setting

A real-world cohort study was conducted within the SAIL Databank (a secure trusted research environment containing anonymised, individual, population-scale electronic health record (EHR) data) for the population of Wales, UK.

Participants

Adult patients with COVID-19 in the community, at higher risk of hospitalization and death, testing positive for SARS-CoV-2 between 16th December 2021 and 22nd April 2022.

Interventions

Molnupiravir, nirmatrelvir-ritonavir, and sotrovimab given in the community by local health boards and the National Antiviral Service in Wales.

Main outcome measures

All-cause admission to hospital or death within 28 days of a positive test for SARS-CoV-2.

Statistical analysis

Cox proportional hazard model with treatment status (treated/untreated) as a time-dependent covariate and adjusted for age, sex, number of comorbidities, Welsh Index of Multiple Deprivation, and vaccination status. Secondary subgroup analyses were by treatment type, number of comorbidities, and before and on or after 20th February 2022, when omicron BA.1 and omicron BA.2 were the dominant subvariants in Wales.

Results

Between 16th December 2021 and 22nd April 2022, 7013 higher-risk patients were eligible for inclusion in the study. Of these, 2040 received treatment with molnupiravir (359, 17.6%), nirmatrelvir-ritonavir (602, 29.5%), or sotrovimab (1079, 52.9%). Patients in the treatment group were younger (mean age 53 vs 57 years), had fewer comorbidities, and a higher proportion had received four or more doses of the COVID-19 vaccine (36.3% vs 17.6%). Within 28 days of a positive test, 628 (9.0%) patients were admitted to hospital or died (84 treated and 544 untreated). The primary analysis indicated a lower risk of hospitalization or death at any point within 28 days in treated participants compared to those not receiving treatment. The adjusted hazard rate was 35% (95% CI: 18-49%) lower in treated than untreated participants. There was no indication of the superiority of one treatment over another and no evidence of a reduction in risk of hospitalization or death within 28 days for patients with no or only one comorbidity. In patients treated with sotrovimab, the event rates before and on or after 20th February 2022 were similar (5.0% vs 4.9%) with no significant difference in the hazard ratios for sotrovimab between the time periods.

Conclusions

In higher-risk adult patients in the community with COVID-19, those who received treatment with molnupiravir, nirmatrelvir-ritonavir, or sotrovimab were at lower risk of hospitalization or death than those not receiving treatment.",,pdf:http://www.journalofinfection.com/article/S0163445323000828/pdf; doi:https://doi.org/10.1016/j.jinf.2023.02.012; html:https://europepmc.org/articles/PMC9911979; pdf:https://europepmc.org/articles/PMC9911979?pdf=render 36112916,https://doi.org/10.1177/09622802211055853,Inferring risks of coronavirus transmission from community household data.,"House T, Riley H, Pellis L, Pouwels KB, Bacon S, Eidukas A, Jahanshahi K, Eggo RM, Sarah Walker A.",,Statistical methods in medical research,2022,2022-09-01,Y,Infection; Model; epidemic; risk factors; Covid-19,,,"The response of many governments to the COVID-19 pandemic has involved measures to control within- and between-household transmission, providing motivation to improve understanding of the absolute and relative risks in these contexts. Here, we perform exploratory, residual-based, and transmission-dynamic household analysis of the Office for National Statistics COVID-19 Infection Survey data from 26 April 2020 to 15 July 2021 in England. This provides evidence for: (i) temporally varying rates of introduction of infection into households broadly following the trajectory of the overall epidemic and vaccination programme; (ii) susceptible-Infectious transmission probabilities of within-household transmission in the 15-35% range; (iii) the emergence of the Alpha and Delta variants, with the former being around 50% more infectious than wildtype and 35% less infectious than Delta within households; (iv) significantly (in the range of 25-300%) more risk of bringing infection into the household for workers in patient-facing roles pre-vaccine; (v) increased risk for secondary school-age children of bringing the infection into the household when schools are open; (vi) increased risk for primary school-age children of bringing the infection into the household when schools were open since the emergence of new variants.",,doi:https://doi.org/10.1177/09622802211055853; doi:https://doi.org/10.1177/09622802211055853; html:https://europepmc.org/articles/PMC9465559; pdf:https://europepmc.org/articles/PMC9465559?pdf=render -38765656,https://doi.org/10.1016/j.jacasi.2024.01.005,The Prognostic Value of Left Ventricular Entropy From T1 Mapping in Patients With Hypertrophic Cardiomyopathy.,"Wang J, Zhang J, Pu L, Qi W, Xu Y, Wan K, Zhu Y, Gkoutos GV, Han Y, Chen Y.",,JACC. Asia,2024,2024-03-26,Y,Entropy; hypertrophic cardiomyopathy; Sudden Cardiac Death; Cardiac Magnetic Resonance; T1 Mapping,,,"

Background

The prognostic value of left ventricular (LV) entropy in hypertrophic cardiomyopathy (HCM) is unclear.

Objectives

This study aimed to assess the prognostic value of LV entropy from T1 mapping in HCM.

Methods

A total of 748 participants with HCM, who underwent cardiovascular magnetic resonance (CMR), were consecutively enrolled. LV entropy was quantified by native T1 mapping. A competing risk analysis and a Cox proportional hazards regression analysis were performed to identify potential associations of LV entropy with sudden cardiac death (SCD) and cardiovascular death (CVD), respectively.

Results

A total of 40 patients with HCM experienced SCD, and 65 experienced CVD during a median follow-up of 43 months. Participants with increased LV entropy (≥4.06) were more likely to experience SCD and CVD (all P < 0.05) in the entire study cohort or the subgroup with low late gadolinium enhancement (LGE) extent (<15%). After adjustment for the European Society of Cardiology predictors and the presence of high LGE extent (≥15%), LV mean entropy was an independent predictor for SCD (HR: 1.03; all P < 0.05) by the multivariable competing risk analysis and CVD (HR: 1.06; 95% CI: 1.03-1.09; P < 0.001) by multivariable Cox regression analysis.

Conclusions

LV mean entropy derived from native T1 mapping, reflecting myocardial tissue heterogeneity, was an independent predictor of SCD and CVD in participants with HCM. (Cardiac Magnetic Resonance Imaging Clinical Application Registration Study; ChiCTR1900024094).",,doi:https://doi.org/10.1016/j.jacasi.2024.01.005; html:https://europepmc.org/articles/PMC11099820; pdf:https://europepmc.org/articles/PMC11099820?pdf=render 33521768,https://doi.org/10.1016/s2666-7568(20)30011-8,Tackling immunosenescence to improve COVID-19 outcomes and vaccine response in older adults.,"Cox LS, Bellantuono I, Lord JM, Sapey E, Mannick JB, Partridge L, Gordon AL, Steves CJ, Witham MD.",,The lancet. Healthy longevity,2020,2020-11-09,Y,,,,,,pdf:http://www.thelancet.com/article/S2666756820300118/pdf; doi:https://doi.org/10.1016/S2666-7568(20)30011-8; html:https://europepmc.org/articles/PMC7834195; pdf:https://europepmc.org/articles/PMC7834195?pdf=render +38765656,https://doi.org/10.1016/j.jacasi.2024.01.005,The Prognostic Value of Left Ventricular Entropy From T1 Mapping in Patients With Hypertrophic Cardiomyopathy.,"Wang J, Zhang J, Pu L, Qi W, Xu Y, Wan K, Zhu Y, Gkoutos GV, Han Y, Chen Y.",,JACC. Asia,2024,2024-03-26,Y,Entropy; hypertrophic cardiomyopathy; Sudden Cardiac Death; Cardiac Magnetic Resonance; T1 Mapping,,,"

Background

The prognostic value of left ventricular (LV) entropy in hypertrophic cardiomyopathy (HCM) is unclear.

Objectives

This study aimed to assess the prognostic value of LV entropy from T1 mapping in HCM.

Methods

A total of 748 participants with HCM, who underwent cardiovascular magnetic resonance (CMR), were consecutively enrolled. LV entropy was quantified by native T1 mapping. A competing risk analysis and a Cox proportional hazards regression analysis were performed to identify potential associations of LV entropy with sudden cardiac death (SCD) and cardiovascular death (CVD), respectively.

Results

A total of 40 patients with HCM experienced SCD, and 65 experienced CVD during a median follow-up of 43 months. Participants with increased LV entropy (≥4.06) were more likely to experience SCD and CVD (all P < 0.05) in the entire study cohort or the subgroup with low late gadolinium enhancement (LGE) extent (<15%). After adjustment for the European Society of Cardiology predictors and the presence of high LGE extent (≥15%), LV mean entropy was an independent predictor for SCD (HR: 1.03; all P < 0.05) by the multivariable competing risk analysis and CVD (HR: 1.06; 95% CI: 1.03-1.09; P < 0.001) by multivariable Cox regression analysis.

Conclusions

LV mean entropy derived from native T1 mapping, reflecting myocardial tissue heterogeneity, was an independent predictor of SCD and CVD in participants with HCM. (Cardiac Magnetic Resonance Imaging Clinical Application Registration Study; ChiCTR1900024094).",,doi:https://doi.org/10.1016/j.jacasi.2024.01.005; html:https://europepmc.org/articles/PMC11099820; pdf:https://europepmc.org/articles/PMC11099820?pdf=render 36806317,https://doi.org/10.1038/s41746-023-00749-3,Long-term participant retention and engagement patterns in an app and wearable-based multinational remote digital depression study.,"Zhang Y, Pratap A, Folarin AA, Sun S, Cummins N, Matcham F, Vairavan S, Dineley J, Ranjan Y, Rashid Z, Conde P, Stewart C, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Rambla CH, Simblett S, Nica R, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BWJH, Annas P, Narayan VA, Hotopf M, Dobson RJB, RADAR-CNS consortium.",,NPJ digital medicine,2023,2023-02-17,Y,,,,"Recent growth in digital technologies has enabled the recruitment and monitoring of large and diverse populations in remote health studies. However, the generalizability of inference drawn from remotely collected health data could be severely impacted by uneven participant engagement and attrition over the course of the study. We report findings on long-term participant retention and engagement patterns in a large multinational observational digital study for depression containing active (surveys) and passive sensor data collected via Android smartphones, and Fitbit devices from 614 participants for up to 2 years. Majority of participants (67.6%) continued to remain engaged in the study after 43 weeks. Unsupervised clustering of participants' study apps and Fitbit usage data showed 3 distinct engagement subgroups for each data stream. We found: (i) the least engaged group had the highest depression severity (4 PHQ8 points higher) across all data streams; (ii) the least engaged group (completed 4 bi-weekly surveys) took significantly longer to respond to survey notifications (3.8 h more) and were 5 years younger compared to the most engaged group (completed 20 bi-weekly surveys); and (iii) a considerable proportion (44.6%) of the participants who stopped completing surveys after 8 weeks continued to share passive Fitbit data for significantly longer (average 42 weeks). Additionally, multivariate survival models showed participants' age, ownership and brand of smartphones, and recruitment sites to be associated with retention in the study. Together these findings could inform the design of future digital health studies to enable equitable and balanced data collection from diverse populations.",,pdf:https://www.nature.com/articles/s41746-023-00749-3.pdf; doi:https://doi.org/10.1038/s41746-023-00749-3; html:https://europepmc.org/articles/PMC9938183; pdf:https://europepmc.org/articles/PMC9938183?pdf=render 35976089,https://doi.org/10.1515/cclm-2022-0135,"Reference ranges for GDF-15, and risk factors associated with GDF-15, in a large general population cohort.","Welsh P, Kimenai DM, Marioni RE, Hayward C, Campbell A, Porteous D, Mills NL, O'Rahilly S, Sattar N.",,Clinical chemistry and laboratory medicine,2022,2022-08-18,N,Biochemical markers; Guidelines; Reference Ranges,,,"

Objectives

Growth differentiation factor (GDF)-15 is attracting interest as a biomarker in several areas of medicine. We aimed to evaluate the reference range for GDF-15 in a general population, and to explore demographics, classical cardiovascular disease risk factors, and other cardiac biomarkers associated with GDF-15.

Methods

GDF-15 was measured in serum from 19,462 individuals in the Generation Scotland Scottish Family Health Study. Associations of cardiometabolic risk factors with GDF-15 were tested using adjusted linear regression. Among 18,507 participants with no heart disease, heart failure, or stroke, and not pregnant, reference ranges (median and 97.5th centiles) were derived by decade age bands and sex.

Results

Among males in the reference range population, median (97.5th centile) GDF-15 concentration at age <30 years was 537 (1,135) pg/mL, rising to 931 (2,492) pg/mL at 50-59 years, and 2,152 (5,972) pg/mL at ≥80 years. In females, median GDF-15 at age <30 years was 628 (2,195) pg/mL, 881 (2,323) pg/mL at 50-59 years, and 1847 (6,830) pg/mL at ≥80 years. Among those known to be pregnant, median GDF-15 was 19,311 pg/mL. After adjustment, GDF-15 was higher in participants with adverse cardiovascular risk factors, including current smoking (+26.1%), those with previous heart disease (+12.7%), stroke (+17.1%), heart failure (+25.3%), and particularly diabetes (+60.2%). GDF-15 had positive associations with cardiac biomarkers cardiac troponin I, cardiac troponin T, and N-terminal pro B-type natriuretic peptide (NT-proBNP).

Conclusions

These data define reference ranges for GDF-15 for comparison in future studies, and identify potentially confounding risk factors and mediators to be considered in interpreting GDF-15 concentrations.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9524804; doi:https://doi.org/10.1515/cclm-2022-0135; html:https://europepmc.org/articles/PMC9524804; pdf:https://europepmc.org/articles/PMC9524804?pdf=render; doi:https://doi.org/10.1515/cclm-2022-0135 37468148,https://doi.org/10.1136/bmj-2023-075133,Associations between self-reported healthcare disruption due to covid-19 and avoidable hospital admission: evidence from seven linked longitudinal studies for England.,"Green MA, McKee M, Hamilton OK, Shaw RJ, Macleod J, Boyd A, Katikireddi SV, LH&W NCS Collaborative.",,BMJ (Clinical research ed.),2023,2023-07-19,Y,,,,"

Objectives

To examine whether there is an association between people who experienced disrupted access to healthcare during the covid-19 pandemic and risk of an avoidable hospital admission.

Design

Observational analysis using evidence from seven linked longitudinal cohort studies for England.

Setting

Studies linked to electronic health records from NHS Digital from 1 March 2020 to 25 August 2022. Data were accessed using the UK Longitudinal Linkage Collaboration trusted research environment.

Participants

Individual level records for 29 276 people.

Main outcome measures

Avoidable hospital admissions defined as emergency hospital admissions for ambulatory care sensitive and emergency urgent care sensitive conditions.

Results

9742 participants (weighted percentage 35%, adjusted for sample structure of longitudinal cohorts) self-reported some form of disrupted access to healthcare during the covid-19 pandemic. People with disrupted access were at increased risk of any (odds ratio 1.80, 95% confidence interval 1.39 to 2.34), acute (2.01, 1.39 to 2.92), and chronic (1.80, 1.31 to 2.48) ambulatory care sensitive hospital admissions. For people who experienced disrupted access to appointments (eg, visiting their doctor or an outpatient department) and procedures (eg, surgery, cancer treatment), positive associations were found with measures of avoidable hospital admissions.

Conclusions

Evidence from linked individual level data shows that people whose access to healthcare was disrupted were more likely to have a potentially preventable hospital admission. The findings highlight the need to increase healthcare investment to tackle the short and long term implications of the pandemic, and to protect treatments and procedures during future pandemics.",,doi:https://doi.org/10.1136/bmj-2023-075133; html:https://europepmc.org/articles/PMC10354595; pdf:https://europepmc.org/articles/PMC10354595?pdf=render @@ -861,19 +861,19 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 32737300,https://doi.org/10.1038/s41467-020-17696-2,Distinct genetic architectures and environmental factors associate with host response to the γ2-herpesvirus infections.,"Sallah N, Miley W, Labo N, Carstensen T, Fatumo S, Gurdasani D, Pollard MO, Dilthey AT, Mentzer AJ, Marshall V, Cornejo Castro EM, Pomilla C, Young EH, Asiki G, Hibberd ML, Sandhu M, Kellam P, Newton R, Whitby D, Barroso I.",,Nature communications,2020,2020-07-31,Y,,,,"Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr Virus (EBV) establish life-long infections and are associated with malignancies. Striking geographic variation in incidence and the fact that virus alone is insufficient to cause disease, suggests other co-factors are involved. Here we present epidemiological analysis and genome-wide association study (GWAS) in 4365 individuals from an African population cohort, to assess the influence of host genetic and non-genetic factors on virus antibody responses. EBV/KSHV co-infection (OR = 5.71(1.58-7.12)), HIV positivity (OR = 2.22(1.32-3.73)) and living in a more rural area (OR = 1.38(1.01-1.89)) are strongly associated with immunogenicity. GWAS reveals associations with KSHV antibody response in the HLA-B/C region (p = 6.64 × 10-09). For EBV, associations are identified for VCA (rs71542439, p = 1.15 × 10-12). Human leucocyte antigen (HLA) and trans-ancestry fine-mapping substantiate that distinct variants in HLA-DQA1 (p = 5.24 × 10-44) are driving associations for EBNA-1 in Africa. This study highlights complex interactions between KSHV and EBV, in addition to distinct genetic architectures resulting in important differences in pathogenesis and transmission.",,pdf:https://www.nature.com/articles/s41467-020-17696-2.pdf; doi:https://doi.org/10.1038/s41467-020-17696-2; html:https://europepmc.org/articles/PMC7395761; pdf:https://europepmc.org/articles/PMC7395761?pdf=render 34785588,https://doi.org/10.1136/openhrt-2021-001784,OpenSAFELY: impact of national guidance on switching anticoagulant therapy during COVID-19 pandemic.,"OpenSAFELY Collaborative, Curtis HJ, MacKenna B, Walker AJ, Croker R, Mehrkar A, Morton C, Bacon S, Hickman G, Inglesby P, Bates C, Evans D, Ward T, Cockburn J, Davy S, Bhaskaran K, Schultze A, Rentsch CT, Williamson E, Hulme W, Tomlinson L, Mathur R, Drysdale H, Eggo RM, Wong AY, Forbes H, Parry J, Hester F, Harper S, Douglas I, Smeeth L, Goldacre B.",,Open heart,2021,2021-11-01,Y,Stroke; Medication Adherence; Healthcare Economics And Organisations; Covid-19,,,"

Background

Early in the COVID-19 pandemic, the National Health Service (NHS) recommended that appropriate patients anticoagulated with warfarin should be switched to direct-acting oral anticoagulants (DOACs), requiring less frequent blood testing. Subsequently, a national safety alert was issued regarding patients being inappropriately coprescribed two anticoagulants following a medication change and associated monitoring.

Objective

To describe which people were switched from warfarin to DOACs; identify potentially unsafe coprescribing of anticoagulants; and assess whether abnormal clotting results have become more frequent during the pandemic.

Methods

With the approval of NHS England, we conducted a cohort study using routine clinical data from 24 million NHS patients in England.

Results

20 000 of 164 000 warfarin patients (12.2%) switched to DOACs between March and May 2020, most commonly to edoxaban and apixaban. Factors associated with switching included: older age, recent renal function test, higher number of recent INR tests recorded, atrial fibrillation diagnosis and care home residency. There was a sharp rise in coprescribing of warfarin and DOACs from typically 50-100 per month to 246 in April 2020, 0.06% of all people receiving a DOAC or warfarin. International normalised ratio (INR) testing fell by 14% to 506.8 patients tested per 1000 warfarin patients each month. We observed a very small increase in elevated INRs (n=470) during April compared with January (n=420).

Conclusions

Increased switching of anticoagulants from warfarin to DOACs was observed at the outset of the COVID-19 pandemic in England following national guidance. There was a small but substantial number of people coprescribed warfarin and DOACs during this period. Despite a national safety alert on the issue, a widespread rise in elevated INR test results was not found. Primary care has responded rapidly to changes in patient care during the COVID-19 pandemic.",,pdf:https://openheart.bmj.com/content/openhrt/8/2/e001784.full.pdf; doi:https://doi.org/10.1136/openhrt-2021-001784; html:https://europepmc.org/articles/PMC8595296; pdf:https://europepmc.org/articles/PMC8595296?pdf=render 33472631,https://doi.org/10.1186/s12916-020-01893-3,Evaluation and improvement of the National Early Warning Score (NEWS2) for COVID-19: a multi-hospital study.,"Carr E, Bendayan R, Bean D, Stammers M, Wang W, Zhang H, Searle T, Kraljevic Z, Shek A, Phan HTT, Muruet W, Gupta RK, Shinton AJ, Wyatt M, Shi T, Zhang X, Pickles A, Stahl D, Zakeri R, Noursadeghi M, O'Gallagher K, Rogers M, Folarin A, Karwath A, Wickstrøm KE, Köhn-Luque A, Slater L, Cardoso VR, Bourdeaux C, Holten AR, Ball S, McWilliams C, Roguski L, Borca F, Batchelor J, Amundsen EK, Wu X, Gkoutos GV, Sun J, Pinto A, Guthrie B, Breen C, Douiri A, Wu H, Curcin V, Teo JT, Shah AM, Dobson RJB.",,BMC medicine,2021,2021-01-21,Y,Prediction model; Blood parameters; Covid-19; News2 Score,,,"

Background

The National Early Warning Score (NEWS2) is currently recommended in the UK for the risk stratification of COVID-19 patients, but little is known about its ability to detect severe cases. We aimed to evaluate NEWS2 for the prediction of severe COVID-19 outcome and identify and validate a set of blood and physiological parameters routinely collected at hospital admission to improve upon the use of NEWS2 alone for medium-term risk stratification.

Methods

Training cohorts comprised 1276 patients admitted to King's College Hospital National Health Service (NHS) Foundation Trust with COVID-19 disease from 1 March to 30 April 2020. External validation cohorts included 6237 patients from five UK NHS Trusts (Guy's and St Thomas' Hospitals, University Hospitals Southampton, University Hospitals Bristol and Weston NHS Foundation Trust, University College London Hospitals, University Hospitals Birmingham), one hospital in Norway (Oslo University Hospital), and two hospitals in Wuhan, China (Wuhan Sixth Hospital and Taikang Tongji Hospital). The outcome was severe COVID-19 disease (transfer to intensive care unit (ICU) or death) at 14 days after hospital admission. Age, physiological measures, blood biomarkers, sex, ethnicity, and comorbidities (hypertension, diabetes, cardiovascular, respiratory and kidney diseases) measured at hospital admission were considered in the models.

Results

A baseline model of 'NEWS2 + age' had poor-to-moderate discrimination for severe COVID-19 infection at 14 days (area under receiver operating characteristic curve (AUC) in training cohort = 0.700, 95% confidence interval (CI) 0.680, 0.722; Brier score = 0.192, 95% CI 0.186, 0.197). A supplemented model adding eight routinely collected blood and physiological parameters (supplemental oxygen flow rate, urea, age, oxygen saturation, C-reactive protein, estimated glomerular filtration rate, neutrophil count, neutrophil/lymphocyte ratio) improved discrimination (AUC = 0.735; 95% CI 0.715, 0.757), and these improvements were replicated across seven UK and non-UK sites. However, there was evidence of miscalibration with the model tending to underestimate risks in most sites.

Conclusions

NEWS2 score had poor-to-moderate discrimination for medium-term COVID-19 outcome which raises questions about its use as a screening tool at hospital admission. Risk stratification was improved by including readily available blood and physiological parameters measured at hospital admission, but there was evidence of miscalibration in external sites. This highlights the need for a better understanding of the use of early warning scores for COVID.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01893-3; doi:https://doi.org/10.1186/s12916-020-01893-3; html:https://europepmc.org/articles/PMC7817348; pdf:https://europepmc.org/articles/PMC7817348?pdf=render -36543561,https://doi.org/10.3399/bjgp.2022.0156,Anticoagulation in older people with atrial fibrillation moving to care homes: a data linkage study.,"Ritchie LA, Harrison SL, Penson PE, Akbari A, Torabi F, Hollinghurst J, Harris D, Oke OB, Akpan A, Halcox JP, Rodgers SE, Lip GY, Lane DA.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2023,2022-12-21,Y,"Anticoagulants; Atrial fibrillation; Primary Health Care; Nursing Homes; Long-term Care; Practice Patterns, Physicians’",,,"

Background

Treatment decisions about oral anticoagulants (OACs) for atrial fibrillation (AF) are complex in older care home residents.

Aim

To explore factors associated with OAC prescription.

Design and setting

Retrospective cohort study set in care homes in Wales, UK, listed in the Care Inspectorate Wales Registry 2017/18.

Method

Analysis of anonymised individual-level electronic health and administrative data was carried out on people aged ≥65 years entering a care home between 1 January 2003 and 31 December 2018, provisioned from the Secure Anonymised Information Linkage Databank.

Results

Between 2003 and 2018, 14 493 people with AF aged ≥65 years became new residents in care homes in Wales and 7057 (48.7%) were prescribed OACs (32.7% in 2003 compared with 72.7% in 2018) within 6 months before care home entry. Increasing age and prescription of antiplatelet therapy were associated with lower odds of OAC prescription (adjusted odds ratio [aOR] 0.96 per 1-year age increase, 95% confidence interval [CI] = 0.95 to 0.96 and aOR 0.91, 95% CI = 0.84 to 0.98, respectively). Conversely, prior venous thromboembolism (aOR 4.06, 95% CI = 3.17 to 5.20), advancing frailty (mild: aOR 4.61, 95% CI = 3.95 to 5.38; moderate: aOR 6.69, 95% CI = 5.74 to 7.80; and severe: aOR 8.42, 95% CI = 7.16 to 9.90), and year of care home entry from 2011 onwards (aOR 1.91, 95% CI = 1.76 to 2.06) were associated with higher odds of an OAC prescription.

Conclusion

There has been an increase in OAC prescribing in older people newly admitted to care homes with AF. This study provides an insight into the factors influencing OAC prescribing in this population.",,pdf:https://bjgp.org/content/bjgp/73/726/e43.full.pdf; doi:https://doi.org/10.3399/BJGP.2022.0156; html:https://europepmc.org/articles/PMC9799341; pdf:https://europepmc.org/articles/PMC9799341?pdf=render 32855306,https://doi.org/10.1136/gutjnl-2020-321650,Prioritisation by FIT to mitigate the impact of delays in the 2-week wait colorectal cancer referral pathway during the COVID-19 pandemic: a UK modelling study.,"Loveday C, Sud A, Jones ME, Broggio J, Scott S, Gronthound F, Torr B, Garrett A, Nicol DL, Jhanji S, Boyce SA, Williams M, Barry C, Riboli E, Kipps E, McFerran E, Muller DC, Lyratzopoulos G, Lawler M, Abulafi M, Houlston RS, Turnbull C.",,Gut,2021,2020-08-27,Y,Colonoscopy; Colorectal Cancer; Colorectal Cancer Screening,,,"

Objective

To evaluate the impact of faecal immunochemical testing (FIT) prioritisation to mitigate the impact of delays in the colorectal cancer (CRC) urgent diagnostic (2-week-wait (2WW)) pathway consequent from the COVID-19 pandemic.

Design

We modelled the reduction in CRC survival and life years lost resultant from per-patient delays of 2-6 months in the 2WW pathway. We stratified by age group, individual-level benefit in CRC survival versus age-specific nosocomial COVID-19-related fatality per referred patient undergoing colonoscopy. We modelled mitigation strategies using thresholds of FIT triage of 2, 10 and 150 µg Hb/g to prioritise 2WW referrals for colonoscopy. To construct the underlying models, we employed 10-year net CRC survival for England 2008-2017, 2WW pathway CRC case and referral volumes and per-day-delay HRs generated from observational studies of diagnosis-to-treatment interval.

Results

Delay of 2/4/6 months across all 11 266 patients with CRC diagnosed per typical year via the 2WW pathway were estimated to result in 653/1419/2250 attributable deaths and loss of 9214/20 315/32 799 life years. Risk-benefit from urgent investigatory referral is particularly sensitive to nosocomial COVID-19 rates for patients aged >60. Prioritisation out of delay for the 18% of symptomatic referrals with FIT >10 µg Hb/g would avoid 89% of these deaths attributable to presentational/diagnostic delay while reducing immediate requirement for colonoscopy by >80%.

Conclusions

Delays in the pathway to CRC diagnosis and treatment have potential to cause significant mortality and loss of life years. FIT triage of symptomatic patients in primary care could streamline access to colonoscopy, reduce delays for true-positive CRC cases and reduce nosocomial COVID-19 mortality in older true-negative 2WW referrals. However, this strategy offers benefit only in short-term rationalisation of limited endoscopy services: the appreciable false-negative rate of FIT in symptomatic patients means most colonoscopies will still be required.",,pdf:https://gut.bmj.com/content/gutjnl/70/6/1053.full.pdf; doi:https://doi.org/10.1136/gutjnl-2020-321650; html:https://europepmc.org/articles/PMC7447105; pdf:https://europepmc.org/articles/PMC7447105?pdf=render -38509467,https://doi.org/10.1186/s12874-024-02175-9,Implementation and external validation of the Cambridge Multimorbidity Score in the UK Biobank cohort.,"Harrison H, Ip S, Renzi C, Li Y, Barclay M, Usher-Smith J, Lyratzopoulos G, Wood A, Antoniou AC.",,BMC medical research methodology,2024,2024-03-20,Y,Electronic Health Records; Multimorbidity; Uk Biobank; External Validation; Primary Care Records,,,"

Background

Patients with multiple conditions present a growing challenge for healthcare provision. Measures of multimorbidity may support clinical management, healthcare resource allocation and accounting for the health of participants in purpose-designed cohorts. The recently developed Cambridge Multimorbidity scores (CMS) have the potential to achieve these aims using primary care records, however, they have not yet been validated outside of their development cohort.

Methods

The CMS, developed in the Clinical Research Practice Dataset (CPRD), were validated in UK Biobank participants whose data is not available in CPRD (the cohort used for CMS development) with available primary care records (n = 111,898). This required mapping of the 37 pre-existing conditions used in the CMS to the coding frameworks used by UK Biobank data providers. We used calibration plots and measures of discrimination to validate the CMS for two of the three outcomes used in the development study (death and primary care consultation rate) and explored variation by age and sex. We also examined the predictive ability of the CMS for the outcome of cancer diagnosis. The results were compared to an unweighted count score of the 37 pre-existing conditions.

Results

For all three outcomes considered, the CMS were poorly calibrated in UK Biobank. We observed a similar discriminative ability for the outcome of primary care consultation rate to that reported in the development study (C-index: 0.67 (95%CI:0.66-0.68) for both, 5-year follow-up); however, we report lower discrimination for the outcome of death than the development study (0.69 (0.68-0.70) and 0.89 (0.88-0.90) respectively). Discrimination for cancer diagnosis was adequate (0.64 (0.63-0.65)). The CMS performs favourably to the unweighted count score for death, but not for the outcomes of primary care consultation rate or cancer diagnosis.

Conclusions

In the UK Biobank, CMS discriminates reasonably for the outcomes of death, primary care consultation rate and cancer diagnosis and may be a valuable resource for clinicians, public health professionals and data scientists. However, recalibration will be required to make accurate predictions when cohort composition and risk levels differ substantially from the development cohort. The generated resources (including codelists for the conditions and code for CMS implementation in UK Biobank) are available online.",,pdf:https://bmcmedresmethodol.biomedcentral.com/counter/pdf/10.1186/s12874-024-02175-9; doi:https://doi.org/10.1186/s12874-024-02175-9; html:https://europepmc.org/articles/PMC10953059; pdf:https://europepmc.org/articles/PMC10953059?pdf=render +36543561,https://doi.org/10.3399/bjgp.2022.0156,Anticoagulation in older people with atrial fibrillation moving to care homes: a data linkage study.,"Ritchie LA, Harrison SL, Penson PE, Akbari A, Torabi F, Hollinghurst J, Harris D, Oke OB, Akpan A, Halcox JP, Rodgers SE, Lip GY, Lane DA.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2023,2022-12-21,Y,"Anticoagulants; Atrial fibrillation; Primary Health Care; Nursing Homes; Long-term Care; Practice Patterns, Physicians’",,,"

Background

Treatment decisions about oral anticoagulants (OACs) for atrial fibrillation (AF) are complex in older care home residents.

Aim

To explore factors associated with OAC prescription.

Design and setting

Retrospective cohort study set in care homes in Wales, UK, listed in the Care Inspectorate Wales Registry 2017/18.

Method

Analysis of anonymised individual-level electronic health and administrative data was carried out on people aged ≥65 years entering a care home between 1 January 2003 and 31 December 2018, provisioned from the Secure Anonymised Information Linkage Databank.

Results

Between 2003 and 2018, 14 493 people with AF aged ≥65 years became new residents in care homes in Wales and 7057 (48.7%) were prescribed OACs (32.7% in 2003 compared with 72.7% in 2018) within 6 months before care home entry. Increasing age and prescription of antiplatelet therapy were associated with lower odds of OAC prescription (adjusted odds ratio [aOR] 0.96 per 1-year age increase, 95% confidence interval [CI] = 0.95 to 0.96 and aOR 0.91, 95% CI = 0.84 to 0.98, respectively). Conversely, prior venous thromboembolism (aOR 4.06, 95% CI = 3.17 to 5.20), advancing frailty (mild: aOR 4.61, 95% CI = 3.95 to 5.38; moderate: aOR 6.69, 95% CI = 5.74 to 7.80; and severe: aOR 8.42, 95% CI = 7.16 to 9.90), and year of care home entry from 2011 onwards (aOR 1.91, 95% CI = 1.76 to 2.06) were associated with higher odds of an OAC prescription.

Conclusion

There has been an increase in OAC prescribing in older people newly admitted to care homes with AF. This study provides an insight into the factors influencing OAC prescribing in this population.",,pdf:https://bjgp.org/content/bjgp/73/726/e43.full.pdf; doi:https://doi.org/10.3399/BJGP.2022.0156; html:https://europepmc.org/articles/PMC9799341; pdf:https://europepmc.org/articles/PMC9799341?pdf=render 34044910,https://doi.org/10.1016/bs.acc.2020.08.002,Translational biomarkers in the era of precision medicine.,"Bravo-Merodio L, Acharjee A, Russ D, Bisht V, Williams JA, Tsaprouni LG, Gkoutos GV.",,Advances in clinical chemistry,2021,2020-10-03,N,Artificial intelligence; Clinical Trials; Omics; Big Data; Translational Biomarkers,,,"In this chapter we discuss the past, present and future of clinical biomarker development. We explore the advent of new technologies, paving the way in which health, medicine and disease is understood. This review includes the identification of physicochemical assays, current regulations, the development and reproducibility of clinical trials, as well as, the revolution of omics technologies and state-of-the-art integration and analysis approaches.",,doi:https://doi.org/10.1016/bs.acc.2020.08.002 +38509467,https://doi.org/10.1186/s12874-024-02175-9,Implementation and external validation of the Cambridge Multimorbidity Score in the UK Biobank cohort.,"Harrison H, Ip S, Renzi C, Li Y, Barclay M, Usher-Smith J, Lyratzopoulos G, Wood A, Antoniou AC.",,BMC medical research methodology,2024,2024-03-20,Y,Electronic Health Records; Multimorbidity; Uk Biobank; External Validation; Primary Care Records,,,"

Background

Patients with multiple conditions present a growing challenge for healthcare provision. Measures of multimorbidity may support clinical management, healthcare resource allocation and accounting for the health of participants in purpose-designed cohorts. The recently developed Cambridge Multimorbidity scores (CMS) have the potential to achieve these aims using primary care records, however, they have not yet been validated outside of their development cohort.

Methods

The CMS, developed in the Clinical Research Practice Dataset (CPRD), were validated in UK Biobank participants whose data is not available in CPRD (the cohort used for CMS development) with available primary care records (n = 111,898). This required mapping of the 37 pre-existing conditions used in the CMS to the coding frameworks used by UK Biobank data providers. We used calibration plots and measures of discrimination to validate the CMS for two of the three outcomes used in the development study (death and primary care consultation rate) and explored variation by age and sex. We also examined the predictive ability of the CMS for the outcome of cancer diagnosis. The results were compared to an unweighted count score of the 37 pre-existing conditions.

Results

For all three outcomes considered, the CMS were poorly calibrated in UK Biobank. We observed a similar discriminative ability for the outcome of primary care consultation rate to that reported in the development study (C-index: 0.67 (95%CI:0.66-0.68) for both, 5-year follow-up); however, we report lower discrimination for the outcome of death than the development study (0.69 (0.68-0.70) and 0.89 (0.88-0.90) respectively). Discrimination for cancer diagnosis was adequate (0.64 (0.63-0.65)). The CMS performs favourably to the unweighted count score for death, but not for the outcomes of primary care consultation rate or cancer diagnosis.

Conclusions

In the UK Biobank, CMS discriminates reasonably for the outcomes of death, primary care consultation rate and cancer diagnosis and may be a valuable resource for clinicians, public health professionals and data scientists. However, recalibration will be required to make accurate predictions when cohort composition and risk levels differ substantially from the development cohort. The generated resources (including codelists for the conditions and code for CMS implementation in UK Biobank) are available online.",,pdf:https://bmcmedresmethodol.biomedcentral.com/counter/pdf/10.1186/s12874-024-02175-9; doi:https://doi.org/10.1186/s12874-024-02175-9; html:https://europepmc.org/articles/PMC10953059; pdf:https://europepmc.org/articles/PMC10953059?pdf=render 36764720,https://doi.org/10.1136/bmjopen-2022-063836,"Weighting of risk factors for low birth weight: a linked routine data cohort study in Wales, UK.","Bandyopadhyay A, Jones H, Parker M, Marchant E, Evans J, Todd C, Rahman MA, Healy J, Win TL, Rowe B, Moore S, Jones A, Brophy S.",,BMJ open,2023,2023-02-10,Y,epidemiology; Public Health; Statistics & Research Methods,,,"

Objective

Globally, 20 million children are born with a birth weight below 2500 g every year, which is considered as a low birthweight (LBW) baby. This study investigates the contribution of modifiable risk factors in a nationally representative Welsh e-cohort of children and their mothers to inform opportunities to reduce LBW prevalence.

Design

A longitudinal cohort study based on anonymously linked, routinely collected multiple administrative data sets.

Participants

The cohort, (N=693 377) comprising of children born between 1 January 1998 and 31 December 2018 in Wales, was selected from the National Community Child Health Database.

Outcome measures

The risk factors associated with a binary LBW (outcome) variable were investigated with multivariable logistic regression (MLR) and decision tree (DT) models.

Results

The MLR model showed that non-singleton children had the highest risk of LBW (adjusted OR 21.74 (95% CI 21.09 to 22.40)), followed by pregnancy interval less than 1 year (2.92 (95% CI 2.70 to 3.15)), maternal physical and mental health conditions including diabetes (2.03 (1.81 to 2.28)), anaemia (1.26 (95% CI 1.16 to 1.36)), depression (1.58 (95% CI 1.43 to 1.75)), serious mental illness (1.46 (95% CI 1.04 to 2.05)), anxiety (1.22 (95% CI 1.08 to 1.38)) and use of antidepressant medication during pregnancy (1.92 (95% CI 1.20 to 3.07)). Additional maternal risk factors include smoking (1.80 (95% CI 1.76 to 1.84)), alcohol-related hospital admission (1.60 (95% CI 1.30 to 1.97)), substance misuse (1.35 (95% CI 1.29 to 1.41)) and evidence of domestic abuse (1.98 (95% CI 1.39 to 2.81)). Living in less deprived area has lower risk of LBW (0.70 (95% CI 0.67 to 0.72)). The most important risk factors from the DT models include maternal factors such as smoking, maternal weight, substance misuse record, maternal age along with deprivation-Welsh Index of Multiple Deprivation score, pregnancy interval and birth order of the child.

Conclusion

Resources to reduce the prevalence of LBW should focus on improving maternal health, reducing preterm births, increasing awareness of what is a sufficient pregnancy interval, and to provide adequate support for mothers' mental health and well-being.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/2/e063836.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-063836; html:https://europepmc.org/articles/PMC9923297; pdf:https://europepmc.org/articles/PMC9923297?pdf=render 38035863,https://doi.org/10.1016/j.injury.2023.111200,A scoping review of models of care for the management of older trauma patients.,"Ferrah N, Kennedy B, Beck B, Ibrahim J, Gabbe B, Cameron P.",,Injury,2024,2023-11-14,N,Trauma; co-management; Older Adult; Model Of Care; Geriatric Consultation,,,"

Introduction

The number of older people hospitalised with major trauma is rapidly increasing. New models of care have emerged, such as co-management, and trauma centres dedicated to delivering geriatric trauma care. The aim of this scoping review was to explore in-hospital models of care for older adults who experience physical trauma.

Patients and methods

The search was conducted in accordance with the PRISMA- SC (preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews) reporting guidelines. The National Heart Lung, and Blood Institute (NIH) study quality assessment tool was used to evaluate risk of bias in before and after non-randomised experimental studies.

Results

Of 2127 records returned from the database search, 43 papers were included. We identified five types of care models investigated in the reviewed studies: centralised trauma management, consultation services, co-management, patient care protocols, and alert and triage systems. The majority of patients were admitted under a specialised trauma service, intervention teams were for the most part multidisciplinary, and follow-up of patients post-discharge was seldom reported. Consultation services more often had advanced care and discharge planning as treatment objectives. In contrast, patient care protocol and alert systems commonly had management of anticoagulation as a treatment objective. Overall, the impact of the five models of care on patient outcomes was mixed.

Discussion

Given the variability in patient characteristics and capabilities of health services, models of care need to be matched to the local profile of older trauma patients. However, some standards should be incorporated into a care model, including identifying goals of care, medication review and follow up post-discharge.",,doi:https://doi.org/10.1016/j.injury.2023.111200 33619467,https://doi.org/10.1093/jamiaopen/ooaa047,A semi-supervised approach for rapidly creating clinical biomarker phenotypes in the UK Biobank using different primary care EHR and clinical terminology systems.,"Denaxas S, Shah AD, Mateen BA, Kuan V, Quint JK, Fitzpatrick N, Torralbo A, Fatemifar G, Hemingway H.",,JAMIA open,2020,2020-12-05,Y,Phenotyping; Medical Informatics; Electronic Health Records; Uk Biobank,,,"

Objectives

The UK Biobank (UKB) is making primary care electronic health records (EHRs) for 500 000 participants available for COVID-19-related research. Data are extracted from four sources, recorded using five clinical terminologies and stored in different schemas. The aims of our research were to: (a) develop a semi-supervised approach for bootstrapping EHR phenotyping algorithms in UKB EHR, and (b) to evaluate our approach by implementing and evaluating phenotypes for 31 common biomarkers.

Materials and methods

We describe an algorithmic approach to phenotyping biomarkers in primary care EHR involving (a) bootstrapping definitions using existing phenotypes, (b) excluding generic, rare, or semantically distant terms, (c) forward-mapping terminology terms, (d) expert review, and (e) data extraction. We evaluated the phenotypes by assessing the ability to reproduce known epidemiological associations with all-cause mortality using Cox proportional hazards models.

Results

We created and evaluated phenotyping algorithms for 31 biomarkers many of which are directly related to COVID-19 complications, for example diabetes, cardiovascular disease, respiratory disease. Our algorithm identified 1651 Read v2 and Clinical Terms Version 3 terms and automatically excluded 1228 terms. Clinical review excluded 103 terms and included 44 terms, resulting in 364 terms for data extraction (sensitivity 0.89, specificity 0.92). We extracted 38 190 682 events and identified 220 978 participants with at least one biomarker measured.

Discussion and conclusion

Bootstrapping phenotyping algorithms from similar EHR can potentially address pre-existing methodological concerns that undermine the outputs of biomarker discovery pipelines and provide research-quality phenotyping algorithms.",,pdf:https://academic.oup.com/jamiaopen/article-pdf/3/4/545/36625793/ooaa047.pdf; doi:https://doi.org/10.1093/jamiaopen/ooaa047; html:https://europepmc.org/articles/PMC7717266; pdf:https://europepmc.org/articles/PMC7717266?pdf=render -37907891,https://doi.org/10.1186/s12888-023-05217-6,"Association between 5-min Apgar score and attention deficit hyperactivity disorder: a Scotland-wide record linkage study of 758,423 school children.","Bala JJ, Bala JD, Pell JP, Fleming M.",,BMC psychiatry,2023,2023-10-31,Y,attention deficit disorder with hyperactivity; Cohort studies; Education; Medical Record Linkage; Apgar Score,,,"

Background

Attention-deficit hyperactivity disorder (ADHD) affects around 1 in 20 children and is associated with life-long sequelae. Previous studies of the association between Apgar score and ADHD have reported inconsistent findings.

Methods

Record linkage of maternity, prescribing and school pupil census databases was used to conduct a population e-cohort study of singleton children born in Scotland and attending school in Scotland at any point between 2009 and 2013. Binary logistic regression analysis was used to investigate the association between 5-min Apgar score and treated ADHD adjusting for sociodemographic and maternity confounders.

Results

Of the 758,423 children, 7,292 (0.96%) received ADHD medication. The results suggested a potential dose-response relationship between Apgar score and treated ADHD independent of confounders. Referent to an Apgar score of 10, risk of treated ADHD was higher for scores of 0-3 (adjusted OR 1.76, 95% CI 1.32-2.34), 4-6 (adjusted OR 1.50, 95% CI 1.21-1.86) and even 7-9 (adjusted OR 1.26, 95% CI 1.18-1.36) which are traditionally considered within the normal range.

Conclusions

In addition to reinforcing the need to maximise Apgar score through good obstetric practice, the findings suggest that Apgar score may be useful in predicting future risk of ADHD and therefore facilitating early diagnosis and treatment.",,doi:https://doi.org/10.1186/s12888-023-05217-6; html:https://europepmc.org/articles/PMC10619264; pdf:https://europepmc.org/articles/PMC10619264?pdf=render 33262478,https://doi.org/10.1038/s41433-020-01326-8,Risk factors for having diabetic retinopathy at first screening in persons with type 1 diabetes diagnosed under 18 years of age.,"Rafferty J, Owens DR, Luzio SD, Watts P, Akbari A, Thomas RL.",,"Eye (London, England)",2021,2020-12-01,N,,,,"

Objective

To determine the risk factors for having diabetic retinopathy (DR) in children and young people (CYP) with type 1 diabetes (T1DM) at first screening.

Methods

Records from the Diabetes Eye Screening Wales (DESW) service for people in Wales, UK, with T1DM diagnosed under age 18 years were combined with other electronic health record (EHR) data in the Secure Anonymised Information Linkage (SAIL) Databank. Data close to the screening date were collected, and risk factors derived from multivariate, multinomial logistic regression modelling.

Results

Data from 4172 persons, with median (lower quartile, upper quartile) age 16.3 (13.0, 22.3) years and duration of diabetes 6.6 (2.3, 12.3) years were analysed. 62.6% (n = 2613) had no DR, 26.7% (n = 1112) background DR, and 10.7% (n = 447) had referable DR (RDR). No RDR was observed under 19 years of age. Factors associated with an increased risk of DR were diabetes duration, elevated HbA1c, and diastolic blood pressure. People diagnosed with T1DM at 12 years or older had an additional risk for each year they had diabetes compared to those diagnosed before age 12 controlling for the diabetes duration (odds ratios 1.23 and 1.34, respectively).

Conclusions

This study found that 37.4% of the study cohort had DR at first screening, the risk being greater the longer the duration of diabetes or higher the HbA1c and diastolic blood pressure. In addition, people diagnosed at 12 years of age or over were more likely to have DR with each additional year with diabetes.",,pdf:https://www.nature.com/articles/s41433-020-01326-8.pdf; doi:https://doi.org/10.1038/s41433-020-01326-8; html:https://europepmc.org/articles/PMC8452782; pdf:https://europepmc.org/articles/PMC8452782?pdf=render; doi:https://doi.org/10.1038/s41433-020-01326-8 -37657941,https://doi.org/10.1212/wnl.0000000000207777,Exploring the Role of Plasma Lipids and Statin Interventions on Multiple Sclerosis Risk and Severity: A Mendelian Randomization Study.,"Almramhi MM, Finan C, Storm CS, Schmidt AF, Kia DA, Coneys R, Chopade S, Hingorani AD, Wood NW.",,Neurology,2023,2023-09-01,Y,,,,"

Background and objectives

There has been considerable interest in statins because of their pleiotropic effects beyond their lipid-lowering properties. Many of these pleiotropic effects are predominantly ascribed to Rho small guanosine triphosphatases (Rho GTPases) proteins. We aimed to genetically investigate the role of lipids and statin interventions on multiple sclerosis (MS) risk and severity.

Method

We used two-sample Mendelian randomization (MR) to investigate (1) the causal role of genetically mimic both cholesterol-dependent (through low-density lipoprotein cholesterol (LDL-C) and cholesterol biosynthesis pathway) and cholesterol-independent (through Rho GTPases) effects of statins on MS risk and MS severity, (2) the causal link between lipids (high-density lipoprotein cholesterol [HDL-C] and triglycerides [TG]) levels and MS risk and severity, and (3) the reverse causation between lipid fractions and MS risk. We used summary statistics from the Global Lipids Genetics Consortium (GLGC), eQTLGen Consortium, and the International MS Genetics Consortium (IMSGC) for lipids, expression quantitative trait loci, and MS, respectively (GLGC: n = 188,577; eQTLGen: n = 31,684; IMSGC (MS risk): n = 41,505; IMSGC (MS severity): n = 7,069).

Results

The results of MR using the inverse-variance weighted method show that genetically predicted RAC2, a member of cholesterol-independent pathway (OR 0.86 [95% CI 0.78-0.95], p-value 3.80E-03), is implicated causally in reducing MS risk. We found no evidence for the causal role of LDL-C and the member of cholesterol biosynthesis pathway on MS risk. The MR results also show that lifelong higher HDL-C (OR 1.14 [95% CI 1.04-1.26], p-value 7.94E-03) increases MS risk but TG was not. Furthermore, we found no evidence for the causal role of lipids and genetically mimicked statins on MS severity. There is no evidence of reverse causation between MS risk and lipids.

Discussion

Evidence from this study suggests that RAC2 is a genetic modifier of MS risk. Because RAC2 has been reported to mediate some of the pleiotropic effects of statins, we suggest that statins may reduce MS risk through a cholesterol-independent pathway (that is, RAC2-related mechanism(s)). MR analyses also support a causal effect of HDL-C on MS risk.",,pdf:https://n.neurology.org/content/neurology/early/2023/09/01/WNL.0000000000207777.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000207777; html:https://europepmc.org/articles/PMC10624499; pdf:https://europepmc.org/articles/PMC10624499?pdf=render -37042240,https://doi.org/10.1161/circimaging.122.014519,Explainable Artificial Intelligence and Cardiac Imaging: Toward More Interpretable Models.,"Salih A, Boscolo Galazzo I, Gkontra P, Lee AM, Lekadir K, Raisi-Estabragh Z, Petersen SE.",,Circulation. Cardiovascular imaging,2023,2023-04-12,N,Artificial intelligence; Diagnostic Imaging; Machine Learning; Cardiac Imaging Techniques,,,"Artificial intelligence applications have shown success in different medical and health care domains, and cardiac imaging is no exception. However, some machine learning models, especially deep learning, are considered black box as they do not provide an explanation or rationale for model outcomes. Complexity and vagueness in these models necessitate a transition to explainable artificial intelligence (XAI) methods to ensure that model results are both transparent and understandable to end users. In cardiac imaging studies, there are a limited number of papers that use XAI methodologies. This article provides a comprehensive literature review of state-of-the-art works using XAI methods for cardiac imaging. Moreover, it provides simple and comprehensive guidelines on XAI. Finally, open issues and directions for XAI in cardiac imaging are discussed.",,doi:https://doi.org/10.1161/CIRCIMAGING.122.014519 +37907891,https://doi.org/10.1186/s12888-023-05217-6,"Association between 5-min Apgar score and attention deficit hyperactivity disorder: a Scotland-wide record linkage study of 758,423 school children.","Bala JJ, Bala JD, Pell JP, Fleming M.",,BMC psychiatry,2023,2023-10-31,Y,attention deficit disorder with hyperactivity; Cohort studies; Education; Medical Record Linkage; Apgar Score,,,"

Background

Attention-deficit hyperactivity disorder (ADHD) affects around 1 in 20 children and is associated with life-long sequelae. Previous studies of the association between Apgar score and ADHD have reported inconsistent findings.

Methods

Record linkage of maternity, prescribing and school pupil census databases was used to conduct a population e-cohort study of singleton children born in Scotland and attending school in Scotland at any point between 2009 and 2013. Binary logistic regression analysis was used to investigate the association between 5-min Apgar score and treated ADHD adjusting for sociodemographic and maternity confounders.

Results

Of the 758,423 children, 7,292 (0.96%) received ADHD medication. The results suggested a potential dose-response relationship between Apgar score and treated ADHD independent of confounders. Referent to an Apgar score of 10, risk of treated ADHD was higher for scores of 0-3 (adjusted OR 1.76, 95% CI 1.32-2.34), 4-6 (adjusted OR 1.50, 95% CI 1.21-1.86) and even 7-9 (adjusted OR 1.26, 95% CI 1.18-1.36) which are traditionally considered within the normal range.

Conclusions

In addition to reinforcing the need to maximise Apgar score through good obstetric practice, the findings suggest that Apgar score may be useful in predicting future risk of ADHD and therefore facilitating early diagnosis and treatment.",,doi:https://doi.org/10.1186/s12888-023-05217-6; html:https://europepmc.org/articles/PMC10619264; pdf:https://europepmc.org/articles/PMC10619264?pdf=render 30423068,https://doi.org/10.1093/bioinformatics/bty605,Ontology-based validation and identification of regulatory phenotypes.,"Kulmanov M, Schofield PN, Gkoutos GV, Hoehndorf R.",,"Bioinformatics (Oxford, England)",2018,2018-09-01,Y,,"Applied Analytics, The Human Phenome",,"

Motivation

Function annotations of gene products, and phenotype annotations of genotypes, provide valuable information about molecular mechanisms that can be utilized by computational methods to identify functional and phenotypic relatedness, improve our understanding of disease and pathobiology, and lead to discovery of drug targets. Identifying functions and phenotypes commonly requires experiments which are time-consuming and expensive to carry out; creating the annotations additionally requires a curator to make an assertion based on reported evidence. Support to validate the mutual consistency of functional and phenotype annotations as well as a computational method to predict phenotypes from function annotations, would greatly improve the utility of function annotations.

Results

We developed a novel ontology-based method to validate the mutual consistency of function and phenotype annotations. We apply our method to mouse and human annotations, and identify several inconsistencies that can be resolved to improve overall annotation quality. We also apply our method to the rule-based prediction of regulatory phenotypes from functions and demonstrate that we can predict these phenotypes with Fmax of up to 0.647.

Availability and implementation

https://github.com/bio-ontology-research-group/phenogocon.",,pdf:https://academic.oup.com/bioinformatics/article-pdf/34/17/i857/25702307/bty605.pdf; doi:https://doi.org/10.1093/bioinformatics/bty605; html:https://europepmc.org/articles/PMC6129279; pdf:https://europepmc.org/articles/PMC6129279?pdf=render 34135032,https://doi.org/10.1136/bmjopen-2020-043906,Realising the full potential of data-enabled trials in the UK: a call for action.,"Sydes MR, Barbachano Y, Bowman L, Denwood T, Farmer A, Garfield-Birkbeck S, Gibson M, Gulliford MC, Harrison DA, Hewitt C, Logue J, Navaie W, Norrie J, O'Kane M, Quint JK, Rycroft-Malone J, Sheffield J, Smeeth L, Sullivan F, Tizzard J, Walker P, Wilding J, Williamson PR, Landray M, Morris A, Walker RR, Williams HC, Valentine J, Data Enabled Trials Group Workshop Group members.",,BMJ open,2021,2021-06-16,Y,Clinical Trials; Health Informatics; Statistics & Research Methods,,,"

Rationale

Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHRs). Opportunities exist to use these in innovative ways to decrease duplication of effort and speed trial recruitment, conduct and follow-up.

Approach

The National Institute of Health Research (NIHR), Health Data Research UK and Clinical Practice Research Datalink co-organised a national workshop to accelerate the agenda for 'data-enabled clinical trials'. Showcasing successful examples and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility; recruitment; conduct/follow-up; collecting benefits/harms; and analysis/interpretation.

Reflection

Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected; others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a 'route map' to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution.

Discussion

EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial's specific challenges. The short-term emphasis should be on facilitating patient recruitment and for postmarketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR's funding call for ambitious data-enabled trials at scale. There is the opportunity for the UK to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e043906.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-043906; html:https://europepmc.org/articles/PMC8211043; pdf:https://europepmc.org/articles/PMC8211043?pdf=render +37657941,https://doi.org/10.1212/wnl.0000000000207777,Exploring the Role of Plasma Lipids and Statin Interventions on Multiple Sclerosis Risk and Severity: A Mendelian Randomization Study.,"Almramhi MM, Finan C, Storm CS, Schmidt AF, Kia DA, Coneys R, Chopade S, Hingorani AD, Wood NW.",,Neurology,2023,2023-09-01,Y,,,,"

Background and objectives

There has been considerable interest in statins because of their pleiotropic effects beyond their lipid-lowering properties. Many of these pleiotropic effects are predominantly ascribed to Rho small guanosine triphosphatases (Rho GTPases) proteins. We aimed to genetically investigate the role of lipids and statin interventions on multiple sclerosis (MS) risk and severity.

Method

We used two-sample Mendelian randomization (MR) to investigate (1) the causal role of genetically mimic both cholesterol-dependent (through low-density lipoprotein cholesterol (LDL-C) and cholesterol biosynthesis pathway) and cholesterol-independent (through Rho GTPases) effects of statins on MS risk and MS severity, (2) the causal link between lipids (high-density lipoprotein cholesterol [HDL-C] and triglycerides [TG]) levels and MS risk and severity, and (3) the reverse causation between lipid fractions and MS risk. We used summary statistics from the Global Lipids Genetics Consortium (GLGC), eQTLGen Consortium, and the International MS Genetics Consortium (IMSGC) for lipids, expression quantitative trait loci, and MS, respectively (GLGC: n = 188,577; eQTLGen: n = 31,684; IMSGC (MS risk): n = 41,505; IMSGC (MS severity): n = 7,069).

Results

The results of MR using the inverse-variance weighted method show that genetically predicted RAC2, a member of cholesterol-independent pathway (OR 0.86 [95% CI 0.78-0.95], p-value 3.80E-03), is implicated causally in reducing MS risk. We found no evidence for the causal role of LDL-C and the member of cholesterol biosynthesis pathway on MS risk. The MR results also show that lifelong higher HDL-C (OR 1.14 [95% CI 1.04-1.26], p-value 7.94E-03) increases MS risk but TG was not. Furthermore, we found no evidence for the causal role of lipids and genetically mimicked statins on MS severity. There is no evidence of reverse causation between MS risk and lipids.

Discussion

Evidence from this study suggests that RAC2 is a genetic modifier of MS risk. Because RAC2 has been reported to mediate some of the pleiotropic effects of statins, we suggest that statins may reduce MS risk through a cholesterol-independent pathway (that is, RAC2-related mechanism(s)). MR analyses also support a causal effect of HDL-C on MS risk.",,pdf:https://n.neurology.org/content/neurology/early/2023/09/01/WNL.0000000000207777.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000207777; html:https://europepmc.org/articles/PMC10624499; pdf:https://europepmc.org/articles/PMC10624499?pdf=render +37042240,https://doi.org/10.1161/circimaging.122.014519,Explainable Artificial Intelligence and Cardiac Imaging: Toward More Interpretable Models.,"Salih A, Boscolo Galazzo I, Gkontra P, Lee AM, Lekadir K, Raisi-Estabragh Z, Petersen SE.",,Circulation. Cardiovascular imaging,2023,2023-04-12,N,Artificial intelligence; Diagnostic Imaging; Machine Learning; Cardiac Imaging Techniques,,,"Artificial intelligence applications have shown success in different medical and health care domains, and cardiac imaging is no exception. However, some machine learning models, especially deep learning, are considered black box as they do not provide an explanation or rationale for model outcomes. Complexity and vagueness in these models necessitate a transition to explainable artificial intelligence (XAI) methods to ensure that model results are both transparent and understandable to end users. In cardiac imaging studies, there are a limited number of papers that use XAI methodologies. This article provides a comprehensive literature review of state-of-the-art works using XAI methods for cardiac imaging. Moreover, it provides simple and comprehensive guidelines on XAI. Finally, open issues and directions for XAI in cardiac imaging are discussed.",,doi:https://doi.org/10.1161/CIRCIMAGING.122.014519 29925668,https://doi.org/10.1136/jech-2017-210370,Emergency hospital admissions associated with a non-randomised housing intervention meeting national housing quality standards: a longitudinal data linkage study.,"Rodgers SE, Bailey R, Johnson R, Berridge D, Poortinga W, Lannon S, Smith R, Lyons RA.",,Journal of epidemiology and community health,2018,2018-06-20,Y,Morbidity; Health Services; Public Health; Housing; Longitudinal Studies,Improving Public Health,,"

Background

We investigated tenant healthcare utilisation associated with upgrading 8558 council houses to a national quality standard. Homes received multiple internal and external improvements and were analysed using repeated measures of healthcare utilisation.

Methods

The primary outcome was emergency hospital admissions for cardiorespiratory conditions and injuries for residents aged 60 years and over. Secondary outcomes included each of the separate conditions, for tenants aged 60 and over, and for all ages. Council home address and intervention records for eight housing cointerventions were anonymously linked to demographic data, hospital admissions and deaths for individuals in a dynamic cohort. Counts of health events were analysed using multilevel regression models to investigate associations between receipt of each housing improvement, adjusting for potential confounding factors and regional trends.

Results

Residents aged 60 years and over living in homes when improvements were made were associated with up to 39% fewer admissions compared with those living in homes that were not upgraded (incidence rate ratio=0.61, 95% CI 0.53 to 0.72). Reduced admissions were associated with electrical systems, windows and doors, wall insulation, and garden paths. There were small non-significant reductions for the primary outcome associated with upgrading heating, adequate loft insulation, new kitchens and new bathrooms.

Conclusion

Results suggest that hospital admissions can be avoided through improving whole home quality standards. This is the first large-scale longitudinal evaluation of a whole home intervention that has evaluated multiple improvement elements using individual-level objective routine health data.",,pdf:https://jech.bmj.com/content/jech/72/10/896.full.pdf; doi:https://doi.org/10.1136/jech-2017-210370; html:https://europepmc.org/articles/PMC6161658; pdf:https://europepmc.org/articles/PMC6161658?pdf=render 36620207,https://doi.org/10.3389/fphys.2022.1089343,Incorporating structural abnormalities in equivalent dipole layer based ECG simulations.,"Boonstra MJ, Oostendorp TF, Roudijk RW, Kloosterman M, Asselbergs FW, Loh P, Van Dam PM.",,Frontiers in physiology,2022,2022-12-22,Y,Simulation; Myocardial Disease; Electrocardiogram (Ecg); Cardiac Activation; Ecgsim; Equivalent Dipole Layer,,,"Introduction: Electrical activity of the myocardium is recorded with the 12-lead ECG. ECG simulations can improve our understanding of the relation between abnormal ventricular activation in diseased myocardium and body surface potentials (BSP). However, in equivalent dipole layer (EDL)-based ECG simulations, the presence of diseased myocardium breaks the equivalence of the dipole layer. To simulate diseased myocardium, patches with altered electrophysiological characteristics were incorporated within the model. The relation between diseased myocardium and corresponding BSP was investigated in a simulation study. Methods: Activation sequences in normal and diseased myocardium were simulated and corresponding 64-lead BSP were computed in four models with distinct patch locations. QRS-complexes were compared using correlation coefficient (CC). The effect of different types of patch activation was assessed. Of one patient, simulated electrograms were compared to electrograms recorded during invasive electro-anatomical mapping. Results: Hundred-fifty-three abnormal activation sequences were simulated. Median QRS-CC of delayed versus dyssynchronous were significantly different (1.00 vs. 0.97, p < 0.001). Depending on the location of the patch, BSP leads were affected differently. Within diseased regions, fragmentation, low bipolar voltages and late potentials were observed in both recorded and simulated electrograms. Discussion: A novel method to simulate cardiomyopathy in EDL-based ECG simulations was established and evaluated. The new patch-based approach created a realistic relation between ECG waveforms and underlying activation sequences. Findings in the simulated cases were in agreement with clinical observations. With this method, our understanding of disease progression in cardiomyopathies may be further improved and used in advanced inverse ECG procedures.",,pdf:https://www.frontiersin.org/articles/10.3389/fphys.2022.1089343/pdf; doi:https://doi.org/10.3389/fphys.2022.1089343; html:https://europepmc.org/articles/PMC9814485; pdf:https://europepmc.org/articles/PMC9814485?pdf=render 36475361,https://doi.org/10.1302/2633-1462.312.bjo-2022-0130.r1,Variation in timely surgery for severe open tibial fractures by time and place of presentation in England from 2012 to 2019 : a cohort study using data collected nationally by the Trauma Audit and Research Network.,"Shah A, Judge A, Griffin XL.",,Bone & joint open,2022,2022-12-01,Y,Trauma; Sensitivity analysis; Debridement; Logistic regression; Cohort study; Orthopaedics; Injury Severity Score; Health Care Quality; Soft-tissue; Open Fracture; Tarn; Regression Analyses; Open Fractures Of The Tibia,,,"

Aims

Several studies have reported that patients presenting during the evening or weekend have poorer quality healthcare. Our objective was to examine how timely surgery for patients with severe open tibial fracture varies by day and time of presentation and by type of hospital. This cohort study included patients with severe open tibial fractures from the Trauma Audit and Research Network (TARN).

Methods

Provision of prompt surgery (debridement within 12 hours and soft-tissue coverage in 72 hours) was examined, using multivariate logistic regression to derive adjusted risk ratios (RRs). Time was categorized into three eight-hour intervals for each day of the week. The models were adjusted for treatment in a major trauma centre (MTC), sex, age, year of presentation, injury severity score, injury mechanism, and number of operations each patient received.

Results

We studied 8,258 patients from 175 hospitals. Patients presenting during the day (08:00 to 15:59; risk ratio (RR) 1.11, 95% confidence interval (CI) 1.02 to 1.20) were more likely to receive debridement within 12 hours, and patients presenting at night (16:00 to 23:59; RR 0.56, 95% CI 0.51 to 0.62) were less likely to achieve the target; triage to a MTC had no effect. Day of presentation was associated with soft-tissue coverage within 72 hours; patients presenting on a Thursday or Friday being less likely to receive this surgery within 72 hours (Thursday RR 0.88, 95% CI 0.81 to 0.97; Friday RR 0.89, 95% CI 0.81 to 0.98), and the standard less likely to be achieved for those treated in 'non-MTC' hospitals (RR 0.76, 95% CI 0.70 to 0.82).

Conclusion

Variations in care were observed for timely surgery for severe open tibial fractures with debridement surgery affected by time of presentation and soft-tissue coverage affected by day of presentation and type of hospital. The variation is unwarranted and highlights that there are opportunities to substantially improve the delivery and quality of care for patients with severe open tibial fracture.Cite this article: Bone Jt Open 2022;3(12):941-952.",,pdf:https://boneandjoint.org.uk/article/10.1302/2633-1462.312.BJO-2022-0130.R1/pdf; doi:https://doi.org/10.1302/2633-1462.312.BJO-2022-0130.R1; html:https://europepmc.org/articles/PMC9783273; pdf:https://europepmc.org/articles/PMC9783273?pdf=render @@ -885,12 +885,12 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 35032176,https://doi.org/10.1007/s00125-021-05640-y,Cardiovascular risk prediction in type 2 diabetes: a comparison of 22 risk scores in primary care settings.,"Dziopa K, Asselbergs FW, Gratton J, Chaturvedi N, Schmidt AF.",,Diabetologia,2022,2022-01-15,Y,Prediction; Diabetes; Cardiovascular disease; Risk Score,,,"

Aims/hypothesis

We aimed to compare the performance of risk prediction scores for CVD (i.e., coronary heart disease and stroke), and a broader definition of CVD including atrial fibrillation and heart failure (CVD+), in individuals with type 2 diabetes.

Methods

Scores were identified through a literature review and were included irrespective of the type of predicted cardiovascular outcome or the inclusion of individuals with type 2 diabetes. Performance was assessed in a contemporary, representative sample of 168,871 UK-based individuals with type 2 diabetes (age ≥18 years without pre-existing CVD+). Missing observations were addressed using multiple imputation.

Results

We evaluated 22 scores: 13 derived in the general population and nine in individuals with type 2 diabetes. The Systemic Coronary Risk Evaluation (SCORE) CVD rule derived in the general population performed best for both CVD (C statistic 0.67 [95% CI 0.67, 0.67]) and CVD+ (C statistic 0.69 [95% CI 0.69, 0.70]). The C statistic of the remaining scores ranged from 0.62 to 0.67 for CVD, and from 0.64 to 0.69 for CVD+. Calibration slopes (1 indicates perfect calibration) ranged from 0.38 (95% CI 0.37, 0.39) to 0.74 (95% CI 0.72, 0.76) for CVD, and from 0.41 (95% CI 0.40, 0.42) to 0.88 (95% CI 0.86, 0.90) for CVD+. A simple recalibration process considerably improved the performance of the scores, with calibration slopes now ranging between 0.96 and 1.04 for CVD. Scores with more predictors did not outperform scores with fewer predictors: for CVD+, QRISK3 (19 variables) had a C statistic of 0.68 (95% CI 0.68, 0.69), compared with SCORE CVD (six variables) which had a C statistic of 0.69 (95% CI 0.69, 0.70). Scores specific to individuals with diabetes did not discriminate better than scores derived in the general population: the UK Prospective Diabetes Study (UKPDS) scores performed significantly worse than SCORE CVD (p value <0.001).

Conclusions/interpretation

CVD risk prediction scores could not accurately identify individuals with type 2 diabetes who experienced a CVD event in the 10 years of follow-up. All 22 evaluated models had a comparable and modest discriminative ability.",,pdf:https://link.springer.com/content/pdf/10.1007/s00125-021-05640-y.pdf; doi:https://doi.org/10.1007/s00125-021-05640-y; html:https://europepmc.org/articles/PMC8894164; pdf:https://europepmc.org/articles/PMC8894164?pdf=render 34641870,https://doi.org/10.1186/s12911-021-01638-z,An informatics consult approach for generating clinical evidence for treatment decisions.,"Lai AG, Chang WH, Parisinos CA, Katsoulis M, Blackburn RM, Shah AD, Nguyen V, Denaxas S, Davey Smith G, Gaunt TR, Nirantharakumar K, Cox MP, Forde D, Asselbergs FW, Harris S, Richardson S, Sofat R, Dobson RJB, Hingorani A, Patel R, Sterne J, Banerjee A, Denniston AK, Ball S, Sebire NJ, Shah NH, Foster GR, Williams B, Hemingway H.",,BMC medical informatics and decision making,2021,2021-10-12,Y,,,,"

Background

An Informatics Consult has been proposed in which clinicians request novel evidence from large scale health data resources, tailored to the treatment of a specific patient. However, the availability of such consultations is lacking. We seek to provide an Informatics Consult for a situation where a treatment indication and contraindication coexist in the same patient, i.e., anti-coagulation use for stroke prevention in a patient with both atrial fibrillation (AF) and liver cirrhosis.

Methods

We examined four sources of evidence for the effect of warfarin on stroke risk or all-cause mortality from: (1) randomised controlled trials (RCTs), (2) meta-analysis of prior observational studies, (3) trial emulation (using population electronic health records (N = 3,854,710) and (4) genetic evidence (Mendelian randomisation). We developed prototype forms to request an Informatics Consult and return of results in electronic health record systems.

Results

We found 0 RCT reports and 0 trials recruiting for patients with AF and cirrhosis. We found broad concordance across the three new sources of evidence we generated. Meta-analysis of prior observational studies showed that warfarin use was associated with lower stroke risk (hazard ratio [HR] = 0.71, CI 0.39-1.29). In a target trial emulation, warfarin was associated with lower all-cause mortality (HR = 0.61, CI 0.49-0.76) and ischaemic stroke (HR = 0.27, CI 0.08-0.91). Mendelian randomisation served as a drug target validation where we found that lower levels of vitamin K1 (warfarin is a vitamin K1 antagonist) are associated with lower stroke risk. A pilot survey with an independent sample of 34 clinicians revealed that 85% of clinicians found information on prognosis useful and that 79% thought that they should have access to the Informatics Consult as a service within their healthcare systems. We identified candidate steps for automation to scale evidence generation and to accelerate the return of results.

Conclusion

We performed a proof-of-concept Informatics Consult for evidence generation, which may inform treatment decisions in situations where there is dearth of randomised trials. Patients are surprised to know that their clinicians are currently not able to learn in clinic from data on 'patients like me'. We identify the key challenges in offering such an Informatics Consult as a service.",,doi:https://doi.org/10.1186/s12911-021-01638-z; doi:https://doi.org/10.1186/s12911-021-01638-z; html:https://europepmc.org/articles/PMC8506488; pdf:https://europepmc.org/articles/PMC8506488?pdf=render 33320878,https://doi.org/10.1371/journal.pone.0243843,Developing a national birth cohort for child health research using a hospital admissions database in England: The impact of changes to data collection practices.,"Zylbersztejn A, Gilbert R, Hardelid P.",,PloS one,2020,2020-12-15,Y,,,,"

Background

National birth cohorts derived from administrative health databases constitute unique resources for child health research due to whole country coverage, ongoing follow-up and linkage to other data sources. In England, a national birth cohort can be developed using Hospital Episode Statistics (HES), an administrative database covering details of all publicly funded hospital activity, including 97% of births, with longitudinal follow-up via linkage to hospital and mortality records. We present methods for developing a national birth cohort using HES and assess the impact of changes to data collection over time on coverage and completeness of linked follow-up records for children.

Methods

We developed a national cohort of singleton live births in 1998-2015, with information on key risk factors at birth (birth weight, gestational age, maternal age, ethnicity, area-level deprivation). We identified three changes to data collection, which could affect linkage of births to follow-up records: (1) the introduction of the ""NHS Numbers for Babies (NN4B)"", an on-line system which enabled maternity staff to request a unique healthcare patient identifier (NHS number) immediately at birth rather than at civil registration, in Q4 2002; (2) the introduction of additional data quality checks at civil registration in Q3 2009; and (3) correcting a postcode extraction error for births by the data provider in Q2 2013. We evaluated the impact of these changes on trends in two outcomes in infancy: hospital readmissions after birth (using interrupted time series analyses) and mortality rates (compared to published national statistics).

Results

The cohort covered 10,653,998 babies, accounting for 96% of singleton live births in England in 1998-2015. Overall, 2,077,929 infants (19.5%) had at least one hospital readmission after birth. Readmission rates declined by 0.2% percentage points per annual quarter in Q1 1998 to Q3 2002, shifted up by 6.1% percentage points (compared to the expected value based on the trend before Q4 2002) to 17.7% in Q4 2002 when NN4B was introduced, and increased by 0.1% percentage points per annual quarter thereafter. Infant mortality rates were under-reported by 16% for births in 1998-2002 and similar to published national mortality statistics for births in 2003-2015. The trends in infant readmission were not affected by changes to data collection practices in Q3 2009 and Q2 2013, but the proportion of unlinked mortality records in HES and in ONS further declined after 2009.

Discussion

HES can be used to develop a national birth cohort for child health research with follow-up via linkage to hospital and mortality records for children born from 2003 onwards. Re-linking births before 2003 to their follow-up records would maximise potential benefits of this rich resource, enabling studies of outcomes in adolescents with over 20 years of follow-up.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0243843&type=printable; doi:https://doi.org/10.1371/journal.pone.0243843; html:https://europepmc.org/articles/PMC7737962; pdf:https://europepmc.org/articles/PMC7737962?pdf=render -38740716,https://doi.org/10.1007/s40266-024-01116-x,Associations Between Midlife Anticholinergic Medication Use and Subsequent Cognitive Decline: A British Birth Cohort Study.,"Rawle MJ, Lau WCY, Gonzalez-Izquierdo A, Patalay P, Richards M, Davis D.",,Drugs & aging,2024,2024-05-13,N,,,,"

Background

Anticholinergic medication use is associated with cognitive decline and incident dementia. Our study, a prospective birth cohort analysis, aimed to determine if repeated exposure to anticholinergic medications was associated with greater decline, and whether decline was reversed with medication reduction.

Methods

From the Medical Research Council (MRC) National Survey of Health and Development, a British birth cohort with all participants born in a single week of March 1946, we quantified anticholinergic exposure between ages 53 and 69 years using the Anticholinergic Cognitive Burden Scale (ACBS). We used multinomial regression to estimate associations with global cognition, quantified by the Addenbrooke's Cognitive Examination, 3rd Edition (ACE-III). Longitudinal associations between ACBS and cognitive test results (Verbal memory quantified by the Word Learning Test [WLT], and processing speed quantified by the Timed Letter Search Task [TLST]) at three time points (age 53, 60-64 and 69) were assessed using mixed and fixed effects linear regression models. Analyses were adjusted for sex, childhood cognition, education, chronic disease count and severity, and mental health symptoms.

Results

Anticholinergic exposure was associated cross-sectionally with lower ACE-III scores at age 69, with the greatest effects in those with high exposure at ages 60-64 (mean difference - 2.34, 95% confidence interval [CI] - 3.51 to - 1.17). Longitudinally, both mild-moderate and high ACBS scores were linked to lower WLT scores, again with high exposure showing larger effects (mean difference with contemporaneous exposure - 0.90, 95% CI - 1.63 to - 0.17; mean difference with lagged exposure - 1.53, 95% CI - 2.43 to - 0.64). Associations remained in fixed effects models (mean difference with contemporaneous exposure -1.78, 95% CI -2.85 to - 0.71; mean difference with lagged exposure - 2.23, 95% CI - 3.33 to - 1.13). Associations with TLST were noted only in isolated contemporaneous exposure (mean difference - 13.14, 95% CI - 19.04 to - 7.23; p < 0.01).

Conclusions

Anticholinergic exposure throughout mid and later life was associated with lower cognitive function. Reduced processing speed was associated only with contemporaneous anticholinergic medication use, and not historical use. Associations with lower verbal recall were evident with both historical and contemporaneous use of anticholinergic medication, and associations with historical use persisted in individuals even when their anticholinergic medication use decreased over the course of the study.",,doi:https://doi.org/10.1007/s40266-024-01116-x 35429382,https://doi.org/10.1093/infdis/jiac146,Severe Acute Respiratory Syndrome Coronavirus 2 Anti-Spike Antibody Levels Following Second Dose of ChAdOx1 nCov-19 or BNT162b2 Vaccine in Residents of Long-term Care Facilities in England (VIVALDI).,"Stirrup O, Krutikov M, Tut G, Palmer T, Bone D, Bruton R, Fuller C, Azmi B, Lancaster T, Sylla P, Kaur N, Spalkova E, Bentley C, Amin U, Jadir A, Hulme S, Giddings R, Nacer-Laidi H, Baynton V, Irwin-Singer A, Hayward A, Moss P, Copas A, Shallcross L.",,The Journal of infectious diseases,2022,2022-11-01,Y,Antibodies; Vaccination; Waning; Long-term Care Facilities; Covid-19,,,"General population studies have shown strong humoral response following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination with subsequent waning of anti-spike antibody levels. Vaccine-induced immune responses are often attenuated in frail and older populations, but published data are scarce. We measured SARS-CoV-2 anti-spike antibody levels in long-term care facility residents and staff following a second vaccination dose with Oxford-AstraZeneca or Pfizer-BioNTech. Vaccination elicited robust antibody responses in older residents, suggesting comparable levels of vaccine-induced immunity to that in the general population. Antibody levels are higher after Pfizer-BioNTech vaccination but fall more rapidly compared to Oxford-AstraZeneca recipients and are enhanced by prior infection in both groups.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047242; doi:https://doi.org/10.1093/infdis/jiac146; html:https://europepmc.org/articles/PMC9047242; pdf:https://europepmc.org/articles/PMC9047242?pdf=render 34174193,https://doi.org/10.1016/s1473-3099(21)00289-9,Vaccine effectiveness of the first dose of ChAdOx1 nCoV-19 and BNT162b2 against SARS-CoV-2 infection in residents of long-term care facilities in England (VIVALDI): a prospective cohort study.,"Shrotri M, Krutikov M, Palmer T, Giddings R, Azmi B, Subbarao S, Fuller C, Irwin-Singer A, Davies D, Tut G, Lopez Bernal J, Moss P, Hayward A, Copas A, Shallcross L.",,The Lancet. Infectious diseases,2021,2021-06-23,Y,,,,"

Background

The effectiveness of SARS-CoV-2 vaccines in older adults living in long-term care facilities is uncertain. We investigated the protective effect of the first dose of the Oxford-AstraZeneca non-replicating viral-vectored vaccine (ChAdOx1 nCoV-19; AZD1222) and the Pfizer-BioNTech mRNA-based vaccine (BNT162b2) in residents of long-term care facilities in terms of PCR-confirmed SARS-CoV-2 infection over time since vaccination.

Methods

The VIVALDI study is a prospective cohort study that commenced recruitment on June 11, 2020, to investigate SARS-CoV-2 transmission, infection outcomes, and immunity in residents and staff in long-term care facilities in England that provide residential or nursing care for adults aged 65 years and older. In this cohort study, we included long-term care facility residents undergoing routine asymptomatic SARS-CoV-2 testing between Dec 8, 2020 (the date the vaccine was first deployed in a long-term care facility), and March 15, 2021, using national testing data linked within the COVID-19 Datastore. Using Cox proportional hazards regression, we estimated the relative hazard of PCR-positive infection at 0-6 days, 7-13 days, 14-20 days, 21-27 days, 28-34 days, 35-48 days, and 49 days and beyond after vaccination, comparing unvaccinated and vaccinated person-time from the same cohort of residents, adjusting for age, sex, previous infection, local SARS-CoV-2 incidence, long-term care facility bed capacity, and clustering by long-term care facility. We also compared mean PCR cycle threshold (Ct) values for positive swabs obtained before and after vaccination. The study is registered with ISRCTN, number 14447421.

Findings

10 412 care home residents aged 65 years and older from 310 LTCFs were included in this analysis. The median participant age was 86 years (IQR 80-91), 7247 (69·6%) of 10 412 residents were female, and 1155 residents (11·1%) had evidence of previous SARS-CoV-2 infection. 9160 (88·0%) residents received at least one vaccine dose, of whom 6138 (67·0%) received ChAdOx1 and 3022 (33·0%) received BNT162b2. Between Dec 8, 2020, and March 15, 2021, there were 36 352 PCR results in 670 628 person-days, and 1335 PCR-positive infections (713 in unvaccinated residents and 612 in vaccinated residents) were included. Adjusted hazard ratios (HRs) for PCR-positive infection relative to unvaccinated residents declined from 28 days after the first vaccine dose to 0·44 (95% CI 0·24-0·81) at 28-34 days and 0·38 (0·19-0·77) at 35-48 days. Similar effect sizes were seen for ChAdOx1 (adjusted HR 0·32, 95% CI 0·15-0·66) and BNT162b2 (0·35, 0·17-0·71) vaccines at 35-48 days. Mean PCR Ct values were higher for infections that occurred at least 28 days after vaccination than for those occurring before vaccination (31·3 [SD 8·7] in 107 PCR-positive tests vs 26·6 [6·6] in 552 PCR-positive tests; p<0·0001).

Interpretation

Single-dose vaccination with BNT162b2 and ChAdOx1 vaccines provides substantial protection against infection in older adults from 4-7 weeks after vaccination and might reduce SARS-CoV-2 transmission. However, the risk of infection is not eliminated, highlighting the ongoing need for non-pharmaceutical interventions to prevent transmission in long-term care facilities.

Funding

UK Government Department of Health and Social Care.",,pdf:http://www.thelancet.com/article/S1473309921002899/pdf; doi:https://doi.org/10.1016/S1473-3099(21)00289-9; html:https://europepmc.org/articles/PMC8221738 +38740716,https://doi.org/10.1007/s40266-024-01116-x,Associations Between Midlife Anticholinergic Medication Use and Subsequent Cognitive Decline: A British Birth Cohort Study.,"Rawle MJ, Lau WCY, Gonzalez-Izquierdo A, Patalay P, Richards M, Davis D.",,Drugs & aging,2024,2024-05-13,N,,,,"

Background

Anticholinergic medication use is associated with cognitive decline and incident dementia. Our study, a prospective birth cohort analysis, aimed to determine if repeated exposure to anticholinergic medications was associated with greater decline, and whether decline was reversed with medication reduction.

Methods

From the Medical Research Council (MRC) National Survey of Health and Development, a British birth cohort with all participants born in a single week of March 1946, we quantified anticholinergic exposure between ages 53 and 69 years using the Anticholinergic Cognitive Burden Scale (ACBS). We used multinomial regression to estimate associations with global cognition, quantified by the Addenbrooke's Cognitive Examination, 3rd Edition (ACE-III). Longitudinal associations between ACBS and cognitive test results (Verbal memory quantified by the Word Learning Test [WLT], and processing speed quantified by the Timed Letter Search Task [TLST]) at three time points (age 53, 60-64 and 69) were assessed using mixed and fixed effects linear regression models. Analyses were adjusted for sex, childhood cognition, education, chronic disease count and severity, and mental health symptoms.

Results

Anticholinergic exposure was associated cross-sectionally with lower ACE-III scores at age 69, with the greatest effects in those with high exposure at ages 60-64 (mean difference - 2.34, 95% confidence interval [CI] - 3.51 to - 1.17). Longitudinally, both mild-moderate and high ACBS scores were linked to lower WLT scores, again with high exposure showing larger effects (mean difference with contemporaneous exposure - 0.90, 95% CI - 1.63 to - 0.17; mean difference with lagged exposure - 1.53, 95% CI - 2.43 to - 0.64). Associations remained in fixed effects models (mean difference with contemporaneous exposure -1.78, 95% CI -2.85 to - 0.71; mean difference with lagged exposure - 2.23, 95% CI - 3.33 to - 1.13). Associations with TLST were noted only in isolated contemporaneous exposure (mean difference - 13.14, 95% CI - 19.04 to - 7.23; p < 0.01).

Conclusions

Anticholinergic exposure throughout mid and later life was associated with lower cognitive function. Reduced processing speed was associated only with contemporaneous anticholinergic medication use, and not historical use. Associations with lower verbal recall were evident with both historical and contemporaneous use of anticholinergic medication, and associations with historical use persisted in individuals even when their anticholinergic medication use decreased over the course of the study.",,doi:https://doi.org/10.1007/s40266-024-01116-x 36763324,https://doi.org/10.1007/s12687-023-00635-1,What makes a good life: using theatrical performance to enhance communication about polygenic risk scores research in patient and public involvement.,"Mason AM, Obi I, Ayodele O, Lambert SA, Fahle S.",,Journal of community genetics,2023,2023-02-10,Y,,,,"The aim of this patient and public involvement and engagement (PPIE) work was to explore improvised theatre as a tool for facilitating bi-directional dialogue between researchers and patients/members of the public on the topic of polygenic risk scores (PRS) use within primary or secondary care. PRS are a tool to quantify genetic risk for a heritable disease or trait and may be used to predict future health outcomes. In the United Kingdom (UK), they are often cited as a next-in-line public health tool to be implemented, and their use in consumer genetic testing as well as patient-facing settings is increasing. Despite their potential clinical utility, broader themes about how they might influence an individual's perception of disease risk and decision-making are an active area of research; however, this has mostly been in the setting of return of results to patients. We worked with a youth theatre group and patients involved in a PPIE group to develop two short plays about public perceptions of genetic risk information that could be captured by PRS. These plays were shared in a workshop with patients/members of the public to facilitate discussions about PRS and their perceived benefits, concerns and emotional reactions. Discussions with both performers and patients/public raised three key questions: (1) can the data be trusted?; (2) does knowing genetic risk actually help the patient?; and (3) what makes a life worthwhile? Creating and watching fictional narratives helped all participants explore the potential use of PRS in a clinical setting, informing future research considerations and improving communication between the researchers and lay members of the PPIE group.",,pdf:https://link.springer.com/content/pdf/10.1007/s12687-023-00635-1.pdf; doi:https://doi.org/10.1007/s12687-023-00635-1; html:https://europepmc.org/articles/PMC10576689; pdf:https://europepmc.org/articles/PMC10576689?pdf=render -36382153,https://doi.org/10.5334/gh.1166,Risk Factors and Prevalence of Dilated Cardiomyopathy in Sub-Saharan Africa: A Systematic Review.,"Fundikira LS, Chillo P, Mutagaywa R, Kamuhabwa A, Kwesigabo G, Asselbergs FW, van Laake LW.",,Global heart,2022,2022-10-21,Y,Dilated cardiomyopathy; Sub-Saharan Africa; Cardiovascular risk factors,,,Highlights  Prevalence of DCM varies widely in SSA.Cardiovascular risk factors are important in patients with DCM.The role of genetics in idiopathic DCM is not studied in major part of SSA.,,pdf:http://globalheartjournal.com/articles/10.5334/gh.1166/galley/1329/download/; doi:https://doi.org/10.5334/gh.1166; html:https://europepmc.org/articles/PMC9585983; pdf:https://europepmc.org/articles/PMC9585983?pdf=render 34716166,https://doi.org/10.1136/bmjopen-2021-053268,Electronic reminders and rewards to improve adherence to inhaled asthma treatment in adolescents: a non-randomised feasibility study in tertiary care.,"De Simoni A, Fleming L, Holliday L, Horne R, Priebe S, Bush A, Sheikh A, Griffiths C.",,BMJ open,2021,2021-10-29,Y,Asthma; Respiratory Medicine (See Thoracic Medicine); Paediatric Thoracic Medicine,,,"

Objective

To test the feasibility and acceptability of a short-term reminder and incentives intervention in adolescents with low adherence to asthma medications.

Methods

Mixed-methods feasibility study in a tertiary care clinic. Adolescents recruited to a 24-week programme with three 8-weekly visits, receiving electronic reminders to prompt inhaled corticosteroid (ICS) inhalation through a mobile app coupled with electronic monitoring devices (EMD). From the second visit, monetary incentives based on adherence of ICS inhalation: £1 per dose, maximum £2 /day, up to £112/study, collected as gift cards at the third visit. End of study interviews and questionnaires assessing perceptions of asthma and ICS, analysed using the Perceptions and Practicalities Framework.

Participants

Adolescents (11-18 years) with documented low ICS adherence (<80% by EMD), and poor asthma control at the first clinic visit.

Results

10 out of 12 adolescents approached were recruited (7 males, 3 females, 12-16 years). Eight participants provided adherence measures up to the fourth visits and received rewards. Mean study duration was 281 days, with 7/10 participants unable to attend their fourth visit due to COVID-19 lockdown. Only 3/10 participants managed to pair the app/EMD up to the fourth visit, which was associated with improved ICS adherence (from 0.51, SD 0.07 to 0.86, SD 0.05). Adherence did not change in adolescents unable to pair the app/EMD. The intervention was acceptable to participants and parents/guardians. Exit interviews showed that participants welcomed reminders and incentives, though expressed frustration with app/EMD technological difficulties. Participants stated the intervention helped through reminding ICS doses, promoting self-monitoring and increasing motivation to take inhalers.

Conclusions

An intervention using electronic reminders and incentives through an app coupled with an EMD was feasible and acceptable to adolescents with asthma. A pilot randomised controlled trial is warranted to better estimate the effect size on adherence, with improved technical support for the EMD.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/10/e053268.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-053268; html:https://europepmc.org/articles/PMC8559117; pdf:https://europepmc.org/articles/PMC8559117?pdf=render +36382153,https://doi.org/10.5334/gh.1166,Risk Factors and Prevalence of Dilated Cardiomyopathy in Sub-Saharan Africa: A Systematic Review.,"Fundikira LS, Chillo P, Mutagaywa R, Kamuhabwa A, Kwesigabo G, Asselbergs FW, van Laake LW.",,Global heart,2022,2022-10-21,Y,Dilated cardiomyopathy; Sub-Saharan Africa; Cardiovascular risk factors,,,Highlights  Prevalence of DCM varies widely in SSA.Cardiovascular risk factors are important in patients with DCM.The role of genetics in idiopathic DCM is not studied in major part of SSA.,,pdf:http://globalheartjournal.com/articles/10.5334/gh.1166/galley/1329/download/; doi:https://doi.org/10.5334/gh.1166; html:https://europepmc.org/articles/PMC9585983; pdf:https://europepmc.org/articles/PMC9585983?pdf=render 36038914,https://doi.org/10.1186/s12916-022-02473-3,Polycystic ovary syndrome and risk of adverse obstetric outcomes: a retrospective population-based matched cohort study in England.,"Subramanian A, Lee SI, Phillips K, Toulis KA, Kempegowda P, O'Reilly MW, Adderley NJ, Thangaratinam S, Arlt W, Nirantharakumar K.",,BMC medicine,2022,2022-08-30,Y,Delivery; Preterm; PCOS; Polycystic ovary syndrome; Stillbirth; Birthweight,,,"

Background

Polycystic ovary syndrome (PCOS) affects up to one in five women of childbearing age. Observational studies assessing the association between maternal PCOS and adverse obstetric outcomes have reported varying results, depending on patient population, diagnostic criteria for PCOS and covariates accounted for in their analyses. We aimed to assess the risk of obstetric outcomes among a population-based representative cohort of women with PCOS compared to an age-matched cohort of women without PCOS.

Methods

A retrospective cohort study was conducted of pregnancies of women in England aged 15-49 years identified from the Clinical Practice Research Datalink (CPRD) GOLD pregnancy register and linked Hospital Episodes Statistic (HES) data between March 1997 and March 2020. Pregnancies from the register that had a linked HES delivery record were included. Linked CPRD primary care data was used to ascertain maternal PCOS exposure prior to pregnancy. To improve detection of PCOS, in addition to PCOS diagnostic codes, codes for (1) polycystic ovaries or (2) hyperandrogenism and anovulation together were also considered. Sensitivity analysis was limited to only pregnant women with a diagnostic code for PCOS. Primary outcomes ascertained from linked HES data were (1) preterm delivery (gestation < 37 weeks), (2) mode of delivery, (3) high (> 4000 g) or low birthweight (< 2500 g) and (4) stillbirth. Secondary outcomes were (1) very preterm delivery (< 32 weeks), (2) extremely preterm delivery (< 28 weeks), (3) small and (4) large for gestational age. Conditional logistic regression models were performed adjusting for age, ethnicity, deprivation, dysglycaemia, hypertension, thyroid disorders, number of babies born at index pregnancy, and pre-gravid BMI. Multiple imputation was performed for missing outcome data.

Results

27,586 deliveries with maternal PCOS were matched for age (± 1 year) to 110,344 deliveries without PCOS. In the fully adjusted models, maternal PCOS was associated with an increased risk of (1) preterm birth [aOR: 1.11 (95% CI 1.06-1.17)], and (2) emergency caesarean, elective caesarean and instrumental vaginal compared to spontaneous delivery [aOR: 1.10 (1.05-1.15), 1.07 (1.03-1.12) and 1.04 (1.00-1.09), respectively]. There was absence of association with low birthweight, high birthweight and stillbirth. In the sensitivity analysis, the association with preterm birth [aOR: 1.31 (95% CI 1.13-1.52)], emergency caesarean [aOR: 1.15 (95% CI 1.02-1.30)], and elective caesarean [aOR: 1.03 (95% CI 1.02-1.03)] remained. While there was no significant association with any of the secondary outcomes in the primary analysis, in the sensitivity analysis maternal PCOS was associated with increased risk of extremely preterm delivery [aOR: 1.86 (95% CI 1.31-2.65)], and lower risk of small for gestational age babies [aOR: 0.74 (95% CI 0.59-0.94)].

Conclusions

Maternal PCOS was associated with increased risk of preterm and caesarean delivery. Association with low birthweight may be largely mediated by lower gestational age at birth.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02473-3; doi:https://doi.org/10.1186/s12916-022-02473-3; html:https://europepmc.org/articles/PMC9425992; pdf:https://europepmc.org/articles/PMC9425992?pdf=render 31616478,https://doi.org/10.3389/fgene.2019.00922,Machine Learning Predicts Accurately Mycobacterium tuberculosis Drug Resistance From Whole Genome Sequencing Data.,"Deelder W, Christakoudi S, Phelan J, Benavente ED, Campino S, McNerney R, Palla L, Clark TG.",,Frontiers in genetics,2019,2019-09-26,Y,Mycobacterium tuberculosis; Drug resistance; Mdr-tb; Xdr-tb; Machine Learning,Applied Analytics,,"Background: Tuberculosis disease, caused by Mycobacterium tuberculosis, is a major public health problem. The emergence of M. tuberculosis strains resistant to existing treatments threatens to derail control efforts. Resistance is mainly conferred by mutations in genes coding for drug targets or converting enzymes, but our knowledge of these mutations is incomplete. Whole genome sequencing (WGS) is an increasingly common approach to rapidly characterize isolates and identify mutations predicting antimicrobial resistance and thereby providing a diagnostic tool to assist clinical decision making. Methods: We applied machine learning approaches to 16,688 M. tuberculosis isolates that have undergone WGS and laboratory drug-susceptibility testing (DST) across 14 antituberculosis drugs, with 22.5% of samples being multidrug resistant and 2.1% being extensively drug resistant. We used non-parametric classification-tree and gradient-boosted-tree models to predict drug resistance and uncover any associated novel putative mutations. We fitted separate models for each drug, with and without ""co-occurrent resistance"" markers known to be causing resistance to drugs other than the one of interest. Predictive performance was measured using sensitivity, specificity, and the area under the receiver operating characteristic curve, assuming DST results as the gold standard. Results: The predictive performance was highest for resistance to first-line drugs, amikacin, kanamycin, ciprofloxacin, moxifloxacin, and multidrug-resistant tuberculosis (area under the receiver operating characteristic curve above 96%), and lowest for third-line drugs such as D-cycloserine and Para-aminosalisylic acid (area under the curve below 85%). The inclusion of co-occurrent resistance markers led to improved performance for some drugs and superior results when compared to similar models in other large-scale studies, which had smaller sample sizes. Overall, the gradient-boosted-tree models performed better than the classification-tree models. The mutation-rank analysis detected no new single nucleotide polymorphisms linked to drug resistance. Discordance between DST and genotypically inferred resistance may be explained by DST errors, novel rare mutations, hetero-resistance, and nongenomic drivers such as efflux-pump upregulation. Conclusion: Our work demonstrates the utility of machine learning as a flexible approach to drug resistance prediction that is able to accommodate a much larger number of predictors and to summarize their predictive ability, thus assisting clinical decision making and single nucleotide polymorphism detection in an era of increasing WGS data generation.",,pdf:https://www.frontiersin.org/articles/10.3389/fgene.2019.00922/pdf; doi:https://doi.org/10.3389/fgene.2019.00922; html:https://europepmc.org/articles/PMC6775242; pdf:https://europepmc.org/articles/PMC6775242?pdf=render 35786634,https://doi.org/10.2196/37821,Methodological Issues in Using a Common Data Model of COVID-19 Vaccine Uptake and Important Adverse Events of Interest: Feasibility Study of Data and Connectivity COVID-19 Vaccines Pharmacovigilance in the United Kingdom.,"Delanerolle G, Williams R, Stipancic A, Byford R, Forbes A, Tsang RSM, Anand SN, Bradley D, Murphy S, Akbari A, Bedston S, Lyons RA, Owen R, Torabi F, Beggs J, Chuter A, Balharry D, Joy M, Sheikh A, Hobbs FDR, de Lusignan S.",,JMIR formative research,2022,2022-08-22,Y,Clinical outcome; Sinus Thrombosis; Health Information; Pharmacovigilance; anaphylaxis; Systematized Nomenclature Of Medicine; Medical Outcome; Covid-19; Data Model; Covid-19 Vaccines; Clinical Coding System; Vaccine Uptake; Health Database; Vaccine Effect,,,"

Background

The Data and Connectivity COVID-19 Vaccines Pharmacovigilance (DaC-VaP) UK-wide collaboration was created to monitor vaccine uptake and effectiveness and provide pharmacovigilance using routine clinical and administrative data. To monitor these, pooled analyses may be needed. However, variation in terminologies present a barrier as England uses the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT), while the rest of the United Kingdom uses the Read v2 terminology in primary care. The availability of data sources is not uniform across the United Kingdom.

Objective

This study aims to use the concept mappings in the Observational Medical Outcomes Partnership (OMOP) common data model (CDM) to identify common concepts recorded and to report these in a repeated cross-sectional study. We planned to do this for vaccine coverage and 2 adverse events of interest (AEIs), cerebral venous sinus thrombosis (CVST) and anaphylaxis. We identified concept mappings to SNOMED CT, Read v2, the World Health Organization's International Classification of Disease Tenth Revision (ICD-10) terminology, and the UK Dictionary of Medicines and Devices (dm+d).

Methods

Exposures and outcomes of interest to DaC-VaP for pharmacovigilance studies were selected. Mappings of these variables to different terminologies used across the United Kingdom's devolved nations' health services were identified from the Observational Health Data Sciences and Informatics (OHDSI) Automated Terminology Harmonization, Extraction, and Normalization for Analytics (ATHENA) online browser. Lead analysts from each nation then confirmed or added to the mappings identified. These mappings were then used to report AEIs in a common format. We reported rates for windows of 0-2 and 3-28 days postvaccine every 28 days.

Results

We listed the mappings between Read v2, SNOMED CT, ICD-10, and dm+d. For vaccine exposure, we found clear mapping from OMOP to our clinical terminologies, though dm+d had codes not listed by OMOP at the time of searching. We found a list of CVST and anaphylaxis codes. For CVST, we had to use a broader cerebral venous thrombosis conceptual approach to include Read v2. We identified 56 SNOMED CT codes, of which we selected 47 (84%), and 15 Read v2 codes. For anaphylaxis, our refined search identified 60 SNOMED CT codes and 9 Read v2 codes, of which we selected 10 (17%) and 4 (44%), respectively, to include in our repeated cross-sectional studies.

Conclusions

This approach enables the use of mappings to different terminologies within the OMOP CDM without the need to catalogue an entire database. However, Read v2 has less granular concepts than some terminologies, such as SNOMED CT. Additionally, the OMOP CDM cannot compensate for limitations in the clinical coding system. Neither Read v2 nor ICD-10 is sufficiently granular to enable CVST to be specifically flagged. Hence, any pooled analysis will have to be at the less specific level of cerebrovascular venous thrombosis. Overall, the mappings within this CDM are useful, and our method could be used for rapid collaborations where there are only a limited number of concepts to pool.",,pdf:https://formative.jmir.org/2022/8/e37821/PDF; doi:https://doi.org/10.2196/37821; html:https://europepmc.org/articles/PMC9400842; pdf:https://europepmc.org/articles/PMC9400842?pdf=render @@ -901,8 +901,8 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 38176879,https://doi.org/10.1136/bmjopen-2023-078021,"RELEASE-HF study: a protocol for an observational, registry-based study on the effectiveness of telemedicine in heart failure in the Netherlands.","van Eijk J, Luijken K, Jaarsma T, Reitsma JB, Schuit E, Frederix GWJ, Derks L, Schaap J, Rutten FH, Brugts J, de Boer RA, Asselbergs FW, Trappenburg JCA, RELEASE-HF Investigators.",,BMJ open,2024,2024-01-04,Y,Heart Failure; Health Economics; Registries; Telemedicine; Clinical Decision-making; Protocols & Guidelines,,,"

Introduction

Meta-analyses show postive effects of telemedicine in heart failure (HF) management on hospitalisation, mortality and costs. However, these effects are heterogeneous due to variation in the included HF population, the telemedicine components and the quality of the comparator usual care. Still, telemedicine is gaining acceptance in HF management. The current nationwide study aims to identify (1) in which subgroup(s) of patients with HF telemedicine is (cost-)effective and (2) which components of telemedicine are most (cost-)effective.

Methods and analysis

The RELEASE-HF ('REsponsible roLl-out of E-heAlth through Systematic Evaluation - Heart Failure') study is a multicentre, observational, registry-based cohort study that plans to enrol 6480 patients with HF using data from the HF registry facilitated by the Netherlands Heart Registration. Collected data include patient characteristics, treatment information and clinical outcomes, and are measured at HF diagnosis and at 6 and 12 months afterwards. The components of telemedicine are described at the hospital level based on closed-ended interviews with clinicians and at the patient level based on additional data extracted from electronic health records and telemedicine-generated data. The costs of telemedicine are calculated using registration data and interviews with clinicians and finance department staff. To overcome missing data, additional national databases will be linked to the HF registry if feasible. Heterogeneity of the effects of offering telemedicine compared with not offering on days alive without unplanned hospitalisations in 1 year is assessed across predefined patient characteristics using exploratory stratified analyses. The effects of telemedicine components are assessed by fitting separate models for component contrasts.

Ethics and dissemination

The study has been approved by the Medical Ethics Committee 2021 of the University Medical Center Utrecht (the Netherlands). Results will be published in peer-reviewed journals and presented at (inter)national conferences. Effective telemedicine scenarios will be proposed among hospitals throughout the country and abroad, if applicable and feasible.

Trial registration number

NCT05654961.",,pdf:https://bmjopen.bmj.com/content/bmjopen/14/1/e078021.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-078021; html:https://europepmc.org/articles/PMC10773380; pdf:https://europepmc.org/articles/PMC10773380?pdf=render 36098502,https://doi.org/10.7554/elife.78427,"Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection: Multicentre, prospective study.","Stirrup O, Blackstone J, Mapp F, MacNeil A, Panca M, Holmes A, Machin N, Shin GY, Mahungu T, Saeed K, Saluja T, Taha Y, Mahida N, Pope C, Chawla A, Cutino-Moguel MT, Tamuri A, Williams R, Darby A, Robertson DL, Flaviani F, Nastouli E, Robson S, Smith D, Loose M, Laing K, Monahan I, Kele B, Haldenby S, George R, Bashton M, Witney AA, Byott M, Coll F, Chapman M, Peacock SJ, COG-UK HOCI Investigators, COVID-19 Genomics UK (COG-UK) consortium, Hughes J, Nebbia G, Partridge DG, Parker M, Price JR, Peters C, Roy S, Snell LB, de Silva TI, Thomson E, Flowers P, Copas A, Breuer J.",,eLife,2022,2022-09-13,Y,Human; Microbiology; Infectious disease; Molecular epidemiology; Infection control; epidemiology; Global Health; Hospital-acquired Infection; Infection Prevention; Viral Genomics; Healthcare-associated Infection; Covid-19,,,"

Background

Viral sequencing of SARS-CoV-2 has been used for outbreak investigation, but there is limited evidence supporting routine use for infection prevention and control (IPC) within hospital settings.

Methods

We conducted a prospective non-randomised trial of sequencing at 14 acute UK hospital trusts. Sites each had a 4-week baseline data collection period, followed by intervention periods comprising 8 weeks of 'rapid' (<48 hr) and 4 weeks of 'longer-turnaround' (5-10 days) sequencing using a sequence reporting tool (SRT). Data were collected on all hospital-onset COVID-19 infections (HOCIs; detected ≥48 hr from admission). The impact of the sequencing intervention on IPC knowledge and actions, and on the incidence of probable/definite hospital-acquired infections (HAIs), was evaluated.

Results

A total of 2170 HOCI cases were recorded from October 2020 to April 2021, corresponding to a period of extreme strain on the health service, with sequence reports returned for 650/1320 (49.2%) during intervention phases. We did not detect a statistically significant change in weekly incidence of HAIs in longer-turnaround (incidence rate ratio 1.60, 95% CI 0.85-3.01; p=0.14) or rapid (0.85, 0.48-1.50; p=0.54) intervention phases compared to baseline phase. However, IPC practice was changed in 7.8 and 7.4% of all HOCI cases in rapid and longer-turnaround phases, respectively, and 17.2 and 11.6% of cases where the report was returned. In a 'per-protocol' sensitivity analysis, there was an impact on IPC actions in 20.7% of HOCI cases when the SRT report was returned within 5 days. Capacity to respond effectively to insights from sequencing was breached in most sites by the volume of cases and limited resources.

Conclusions

While we did not demonstrate a direct impact of sequencing on the incidence of nosocomial transmission, our results suggest that sequencing can inform IPC response to HOCIs, particularly when returned within 5 days.

Funding

COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) (grant code: MC_PC_19027), and Genome Research Limited, operating as the Wellcome Sanger Institute.

Clinical trial number

NCT04405934.",,doi:https://doi.org/10.7554/elife.78427; doi:https://doi.org/10.7554/eLife.78427; html:https://europepmc.org/articles/PMC9596156; pdf:https://europepmc.org/articles/PMC9596156?pdf=render 38563665,https://doi.org/10.1148/radiol.232455,Left Ventricular Trabeculations at Cardiac MRI: Reference Ranges and Association with Cardiovascular Risk Factors in UK Biobank.,"Aung N, Bartoli A, Rauseo E, Cortaredona S, Sanghvi MM, Fournel J, Ghattas B, Khanji MY, Petersen SE, Jacquier A.",,Radiology,2024,2024-04-01,N,,,,"Background The extent of left ventricular (LV) trabeculation and its relationship with cardiovascular (CV) risk factors is unclear. Purpose To apply automated segmentation to UK Biobank cardiac MRI scans to (a) assess the association between individual characteristics and CV risk factors and trabeculated LV mass (LVM) and (b) establish normal reference ranges in a selected group of healthy UK Biobank participants. Materials and Methods In this cross-sectional secondary analysis, prospectively collected data from the UK Biobank (2006 to 2010) were retrospectively analyzed. Automated segmentation of trabeculations was performed using a deep learning algorithm. After excluding individuals with known CV diseases, White adults without CV risk factors (reference group) and those with preexisting CV risk factors (hypertension, hyperlipidemia, diabetes mellitus, or smoking) (exposed group) were compared. Multivariable regression models, adjusted for potential confounders (age, sex, and height), were fitted to evaluate the associations between individual characteristics and CV risk factors and trabeculated LVM. Results Of 43 038 participants (mean age, 64 years ± 8 [SD]; 22 360 women), 28 672 individuals (mean age, 66 years ± 7; 14 918 men) were included in the exposed group, and 7384 individuals (mean age, 60 years ± 7; 4729 women) were included in the reference group. Higher body mass index (BMI) (β = 0.66 [95% CI: 0.63, 0.68]; P < .001), hypertension (β = 0.42 [95% CI: 0.36, 0.48]; P < .001), and higher physical activity level (β = 0.15 [95% CI: 0.12, 0.17]; P < .001) were associated with higher trabeculated LVM. In the reference group, the median trabeculated LVM was 6.3 g (IQR, 4.7-8.5 g) for men and 4.6 g (IQR, 3.4-6.0 g) for women. Median trabeculated LVM decreased with age for men from 6.5 g (IQR, 4.8-8.7 g) at age 45-50 years to 5.9 g (IQR, 4.3-7.8 g) at age 71-80 years (P = .03). Conclusion Higher trabeculated LVM was observed with hypertension, higher BMI, and higher physical activity level. Age- and sex-specific reference ranges of trabeculated LVM in a healthy middle-aged White population were established. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Kawel-Boehm in this issue.",,doi:https://doi.org/10.1148/radiol.232455 -37777816,https://doi.org/10.1186/s13643-023-02337-8,Patient-reported outcome (PRO) instruments used in patients undergoing adoptive cell therapy (ACT) for the treatment of cancer: a systematic review.,"Taylor S, Law K, Coomber-Moore J, Davies M, Thistlethwaite F, Calvert M, Aiyegbusi O, Yorke J.",,Systematic reviews,2023,2023-09-30,Y,Cancer; Systematic; Review; Quality of life; Patient-reported Outcomes (Pros); Adoptive Cell Therapy (Act),,,"

Introduction

Adoptive cell therapy (ACT) is a rapidly evolving field. Patient-reported outcomes (PROs) allow patients to report the impact of treatment on their quality of life during and after treatment. The systematic review aims to characterise the breadth of PROs utilised in ACT cancer care and provide guidance for the use of PROs in this patient population in the future.

Methods

A systematic search was conducted (MEDLINE, PsycINFO, Embase and CINAHL) in August 2021 by two reviewers. Search terms covered the following: ""adoptive cell therapy"", ""patient-reported outcomes"" and ""cancer"". Studies were included if they used a PRO measure to report the impact of ACT. The methodological quality of PROs was assessed. Forward and backward reference searching was conducted of any relevant papers. A quality grading scale was applied based on Cochrane and Revenson criteria for classification of high-quality studies. Key data from the studies and the included PROs was extracted by two researchers and tabulated.

Results

One-hundred nine papers were identified; 11 papers were included. The majority of studies were single-arm trials or observational studies. Twenty-two different PROs were identified; none was ACT specific. The PROMIS-29 and EQ-5D were most commonly used. Few studies collected PRO data in the first 1-2 weeks. Four studies followed patients up for over a year, and a further four studies followed patients for approximately 3 months.

Discussion

None of the PROs identified have been designed specifically for ACT. Appropriateness of existing instruments should be considered. It should be considered whether it is appropriate to collect data more frequently in the acute stage and then less frequently during follow-up. It should be considered if one tool is suitable at all time points or if the tool should be adapted depending on time since treatment. More research is needed to identify the exact timings of PRO assessments, and qualitative work with patients is needed to determine the most important issues for them throughout the treatment and follow-up.",,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02337-8; doi:https://doi.org/10.1186/s13643-023-02337-8; html:https://europepmc.org/articles/PMC10541698; pdf:https://europepmc.org/articles/PMC10541698?pdf=render 35776101,https://doi.org/10.1093/ije/dyac140,Incremental value of risk factor variability for cardiovascular risk prediction in individuals with type 2 diabetes: results from UK primary care electronic health records.,"Xu Z, Arnold M, Sun L, Stevens D, Chung R, Ip S, Barrett J, Kaptoge S, Pennells L, Di Angelantonio E, Wood AM.",,International journal of epidemiology,2022,2022-12-01,Y,Variability; Cardiovascular disease; Type 2 diabetes; Risk Prediction; Repeated Measurements; Electronic Health Records,,,"

Background

Cardiovascular disease (CVD) risk prediction models for individuals with type 2 diabetes are important tools to guide intensification of interventions for CVD prevention. We aimed to assess the added value of incorporating risk factors variability in CVD risk prediction for people with type 2 diabetes.

Methods

We used electronic health records (EHRs) data from 83 910 adults with type 2 diabetes but without pre-existing CVD from the UK Clinical Practice Research Datalink for 2004-2017. Using a landmark-modelling approach, we developed and validated sex-specific Cox models, incorporating conventional predictors and trajectories plus variability of systolic blood pressure (SBP), total and high-density lipoprotein (HDL) cholesterol, and glycated haemoglobin (HbA1c). Such models were compared against simpler models using single last observed values or means.

Results

The standard deviations (SDs) of SBP, HDL cholesterol and HbA1c were associated with higher CVD risk (P < 0.05). Models incorporating trajectories and variability of continuous predictors demonstrated improvement in risk discrimination (C-index = 0.659, 95% CI: 0.654-0.663) as compared with using last observed values (C-index = 0.651, 95% CI: 0.646-0.656) or means (C-index = 0.650, 95% CI: 0.645-0.655). Inclusion of SDs of SBP yielded the greatest improvement in discrimination (C-index increase = 0.005, 95% CI: 0.004-0.007) in comparison to incorporating SDs of total cholesterol (C-index increase = 0.002, 95% CI: 0.000-0.003), HbA1c (C-index increase = 0.002, 95% CI: 0.000-0.003) or HDL cholesterol (C-index increase= 0.003, 95% CI: 0.002-0.005).

Conclusion

Incorporating variability of predictors from EHRs provides a modest improvement in CVD risk discrimination for individuals with type 2 diabetes. Given that repeat measures are readily available in EHRs especially for regularly monitored patients with diabetes, this improvement could easily be achieved.",,pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac140/45030523/dyac140.pdf; doi:https://doi.org/10.1093/ije/dyac140; html:https://europepmc.org/articles/PMC9749723; pdf:https://europepmc.org/articles/PMC9749723?pdf=render +37777816,https://doi.org/10.1186/s13643-023-02337-8,Patient-reported outcome (PRO) instruments used in patients undergoing adoptive cell therapy (ACT) for the treatment of cancer: a systematic review.,"Taylor S, Law K, Coomber-Moore J, Davies M, Thistlethwaite F, Calvert M, Aiyegbusi O, Yorke J.",,Systematic reviews,2023,2023-09-30,Y,Cancer; Systematic; Review; Quality of life; Patient-reported Outcomes (Pros); Adoptive Cell Therapy (Act),,,"

Introduction

Adoptive cell therapy (ACT) is a rapidly evolving field. Patient-reported outcomes (PROs) allow patients to report the impact of treatment on their quality of life during and after treatment. The systematic review aims to characterise the breadth of PROs utilised in ACT cancer care and provide guidance for the use of PROs in this patient population in the future.

Methods

A systematic search was conducted (MEDLINE, PsycINFO, Embase and CINAHL) in August 2021 by two reviewers. Search terms covered the following: ""adoptive cell therapy"", ""patient-reported outcomes"" and ""cancer"". Studies were included if they used a PRO measure to report the impact of ACT. The methodological quality of PROs was assessed. Forward and backward reference searching was conducted of any relevant papers. A quality grading scale was applied based on Cochrane and Revenson criteria for classification of high-quality studies. Key data from the studies and the included PROs was extracted by two researchers and tabulated.

Results

One-hundred nine papers were identified; 11 papers were included. The majority of studies were single-arm trials or observational studies. Twenty-two different PROs were identified; none was ACT specific. The PROMIS-29 and EQ-5D were most commonly used. Few studies collected PRO data in the first 1-2 weeks. Four studies followed patients up for over a year, and a further four studies followed patients for approximately 3 months.

Discussion

None of the PROs identified have been designed specifically for ACT. Appropriateness of existing instruments should be considered. It should be considered whether it is appropriate to collect data more frequently in the acute stage and then less frequently during follow-up. It should be considered if one tool is suitable at all time points or if the tool should be adapted depending on time since treatment. More research is needed to identify the exact timings of PRO assessments, and qualitative work with patients is needed to determine the most important issues for them throughout the treatment and follow-up.",,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02337-8; doi:https://doi.org/10.1186/s13643-023-02337-8; html:https://europepmc.org/articles/PMC10541698; pdf:https://europepmc.org/articles/PMC10541698?pdf=render 36715329,https://doi.org/10.1093/bjd/ljac090,"The epidemiology, healthcare and societal burden of basal cell carcinoma in Wales 2000-2018: a retrospective nationwide analysis.","Ibrahim N, Jovic M, Ali S, Williams N, Gibson JAG, Griffiths R, Dobbs TD, Akbari A, Lyons RA, Hutchings HA, Whitaker IS.",,The British journal of dermatology,2023,2023-02-01,N,,,,"

Background

Basal cell carcinoma (BCC) represents the most commonly occurring cancer worldwide within the white population. Reports predict 298 308 cases of BCC in the UK by 2025, at a cost of £265-366 million to the National Health Service (NHS). Despite the morbidity, societal and healthcare pressures brought about by BCC, routinely collected healthcare data and global registration remain limited.

Objectives

To calculate the incidence of BCC in Wales between 2000 and 2018 and to establish the related healthcare utilization and estimated cost of care.

Methods

The Secure Anonymised Information Linkage (SAIL) databank is one of the largest and most robust health and social care data repositories in the UK. Cancer registry data were linked to routinely collected healthcare databases between 2000 and 2018. Pathological data from Swansea Bay University Health Board (SBUHB) were used for internal validation.

Results

A total of 61 404 histologically proven BCCs were identified within the SAIL Databank during the study period. The European age-standardized incidence for BCC in 2018 was 224.6 per 100 000 person-years. Based on validated regional data, a 45% greater incidence was noted within SBUHB pathology vs. matched regions within SAIL between 2016 and 2018. A negative association between deprivation and incidence was noted with a higher incidence in the least socially deprived and rural dwellers. Approximately 2% travelled 25-50 miles for dermatological services compared with 37% for plastic surgery. Estimated NHS costs of surgically managed lesions for 2002-2019 equated to £119.2-164.4 million.

Conclusions

Robust epidemiological data that are internationally comparable and representative are scarce for nonmelanoma skin cancer. The rising global incidence coupled with struggling healthcare systems in the post-COVID-19 recovery period serve to intensify the societal and healthcare impact. This study is the first to demonstrate the incidence of BCC in Wales and is one of a small number in the UK using internally validated large cohort datasets. Furthermore, our findings demonstrate one of the highest published incidences within the UK and Europe.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa62055/Download/62055__26915__ae11794993454389b6ceddbb7f50caaa.pdf; doi:https://doi.org/10.1093/bjd/ljac090 34161326,https://doi.org/10.1371/journal.pcbi.1009121,Contrasting factors associated with COVID-19-related ICU admission and death outcomes in hospitalised patients by means of Shapley values.,"Cavallaro M, Moiz H, Keeling MJ, McCarthy ND.",,PLoS computational biology,2021,2021-06-23,Y,,,,"Identification of those at greatest risk of death due to the substantial threat of COVID-19 can benefit from novel approaches to epidemiology that leverage large datasets and complex machine-learning models, provide data-driven intelligence, and guide decisions such as intensive-care unit admission (ICUA). The objective of this study is two-fold, one substantive and one methodological: substantively to evaluate the association of demographic and health records with two related, yet different, outcomes of severe COVID-19 (viz., death and ICUA); methodologically to compare interpretations based on logistic regression and on gradient-boosted decision tree (GBDT) predictions interpreted by means of the Shapley impacts of covariates. Very different association of some factors, e.g., obesity and chronic respiratory diseases, with death and ICUA may guide review of practice. Shapley explanation of GBDTs identified varying effects of some factors among patients, thus emphasising the importance of individual patient assessment. The results of this study are also relevant for the evaluation of complex automated clinical decision systems, which should optimise prediction scores whilst remaining interpretable to clinicians and mitigating potential biases.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009121&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1009121; html:https://europepmc.org/articles/PMC8259985; pdf:https://europepmc.org/articles/PMC8259985?pdf=render 35039282,https://doi.org/10.1136/bmjopen-2021-049506,Development and external validation of prognostic models for COVID-19 to support risk stratification in secondary care.,"Adderley NJ, Taverner T, Price MJ, Sainsbury C, Greenwood D, Chandan JS, Takwoingi Y, Haniffa R, Hosier I, Welch C, Parekh D, Gallier S, Gokhale K, Denniston AK, Sapey E, Nirantharakumar K.",,BMJ open,2022,2022-01-17,Y,Public Health; Covid-19,,,"

Objectives

Existing UK prognostic models for patients admitted to the hospital with COVID-19 are limited by reliance on comorbidities, which are under-recorded in secondary care, and lack of imaging data among the candidate predictors. Our aims were to develop and externally validate novel prognostic models for adverse outcomes (death and intensive therapy unit (ITU) admission) in UK secondary care and externally validate the existing 4C score.

Design

Candidate predictors included demographic variables, symptoms, physiological measures, imaging and laboratory tests. Final models used logistic regression with stepwise selection.

Setting

Model development was performed in data from University Hospitals Birmingham (UHB). External validation was performed in the CovidCollab dataset.

Participants

Patients with COVID-19 admitted to UHB January-August 2020 were included.

Main outcome measures

Death and ITU admission within 28 days of admission.

Results

1040 patients with COVID-19 were included in the derivation cohort; 288 (28%) died and 183 (18%) were admitted to ITU within 28 days of admission. Area under the receiver operating characteristic curve (AUROC) for mortality was 0.791 (95% CI 0.761 to 0.822) in UHB and 0.767 (95% CI 0.754 to 0.780) in CovidCollab; AUROC for ITU admission was 0.906 (95% CI 0.883 to 0.929) in UHB and 0.811 (95% CI 0.795 to 0.828) in CovidCollab. Models showed good calibration. Addition of comorbidities to candidate predictors did not improve model performance. AUROC for the International Severe Acute Respiratory and Emerging Infection Consortium 4C score in the UHB dataset was 0.753 (95% CI 0.720 to 0.785).

Conclusions

The novel prognostic models showed good discrimination and calibration in derivation and external validation datasets, and performed at least as well as the existing 4C score using only routinely collected patient information. The models can be integrated into electronic medical records systems to calculate each individual patient's probability of death or ITU admission at the time of hospital admission. Implementation of the models and clinical utility should be evaluated.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/1/e049506.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049506; html:https://europepmc.org/articles/PMC8764710; pdf:https://europepmc.org/articles/PMC8764710?pdf=render @@ -912,13 +912,13 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 34626176,https://doi.org/10.1093/brain/awab253,Whole-exome sequencing reveals a role of HTRA1 and EGFL8 in brain white matter hyperintensities.,"Malik R, Beaufort N, Frerich S, Gesierich B, Georgakis MK, Rannikmäe K, Ferguson AC, Haffner C, Traylor M, Ehrmann M, Sudlow CLM, Dichgans M.",,Brain : a journal of neurology,2021,2021-10-01,N,Whole-exome Sequencing; White Matter Hyperintensities; Uk Biobank; Htra1; Burden Test,,,"White matter hyperintensities (WMH) are among the most common radiological abnormalities in the ageing population and an established risk factor for stroke and dementia. While common variant association studies have revealed multiple genetic loci with an influence on their volume, the contribution of rare variants to the WMH burden in the general population remains largely unexplored. We conducted a comprehensive analysis of this burden in the UK Biobank using publicly available whole-exome sequencing data (n up to 17 830) and found a splice-site variant in GBE1, encoding 1,4-alpha-glucan branching enzyme 1, to be associated with lower white matter burden on an exome-wide level [c.691+2T>C, β = -0.74, standard error (SE) = 0.13, P = 9.7 × 10-9]. Applying whole-exome gene-based burden tests, we found damaging missense and loss-of-function variants in HTRA1 (frequency of 1 in 275 in the UK Biobank population) to associate with an increased WMH volume (P = 5.5 × 10-6, false discovery rate = 0.04). HTRA1 encodes a secreted serine protease implicated in familial forms of small vessel disease. Domain-specific burden tests revealed that the association with WMH volume was restricted to rare variants in the protease domain (amino acids 204-364; β = 0.79, SE = 0.14, P = 9.4 × 10-8). The frequency of such variants in the UK Biobank population was 1 in 450. The WMH volume was brought forward by ∼11 years in carriers of a rare protease domain variant. A comparison with the effect size of established risk factors for WMH burden revealed that the presence of a rare variant in the HTRA1 protease domain corresponded to a larger effect than meeting the criteria for hypertension (β = 0.26, SE = 0.02, P = 2.9 × 10-59) or being in the upper 99.8% percentile of the distribution of a polygenic risk score based on common genetic variants (β = 0.44, SE = 0.14, P = 0.002). In biochemical experiments, most (6/9) of the identified protease domain variants resulted in markedly reduced protease activity. We further found EGFL8, which showed suggestive evidence for association with WMH volume (P = 1.5 × 10-4, false discovery rate = 0.22) in gene burden tests, to be a direct substrate of HTRA1 and to be preferentially expressed in cerebral arterioles and arteries. In a phenome-wide association study mapping ICD-10 diagnoses to 741 standardized Phecodes, rare variants in the HTRA1 protease domain were associated with multiple neurological and non-neurological conditions including migraine with aura (odds ratio = 12.24, 95%CI: 2.54-35.25; P = 8.3 × 10-5]. Collectively, these findings highlight an important role of rare genetic variation and the HTRA1 protease in determining WMH burden in the general population.",,pdf:https://academic.oup.com/brain/article-pdf/144/9/2670/40880367/awab253.pdf; doi:https://doi.org/10.1093/brain/awab253; html:https://europepmc.org/articles/PMC8557338; pdf:https://europepmc.org/articles/PMC8557338?pdf=render; doi:https://doi.org/10.1093/brain/awab253 36881701,https://doi.org/10.1097/jtn.0000000000000708,Perceptions of an Interactive Trauma Recovery Information Booklet.,"Reeder SC, Ekegren CL, Mather AM, Kimmel LA, Webb MJ, Pellegrini M, Cameron PA, Cameron PA, Gabbe BJ.",,Journal of trauma nursing : the official journal of the Society of Trauma Nurses,2023,2023-03-01,N,,,,"

Background

Previous research has shown that people with traumatic injuries have unmet information needs with respect to their injuries, management, and recovery. An interactive trauma recovery information booklet was developed and implemented to address these information needs at a major trauma center in Victoria, Australia.

Objective

The aim of this quality improvement project was to explore patient and clinician perceptions of a recovery information booklet introduced into a trauma ward.

Methods

Semistructured interviews with trauma patients, family members, and health professionals were undertaken and thematically analyzed using a framework approach. In total, 34 patients, 10 family members, and 26 health professionals were interviewed.

Results

Overall, the booklet was well accepted by most participants and was perceived to contain useful information. The design, content, pictures, and readability were all positively appraised. Many participants used the booklet to record personalized information and to ask health professionals questions about their injuries and management.

Conclusion

Our findings highlight the usefulness and acceptability of a low-cost interactive booklet intervention to facilitate the provision of quality of information and patient-health professional interactions on a trauma ward.",,doi:https://doi.org/10.1097/JTN.0000000000000708 37350492,https://doi.org/10.1093/eurheartj/ehad376,Troponin in early presenters to rule out myocardial infarction.,"Lowry MTH, Doudesis D, Boeddinghaus J, Kimenai DM, Bularga A, Taggart C, Wereski R, Ferry AV, Stewart SD, Tuck C, Koechlin L, Nestelberger T, Lopez-Ayala P, Huré G, Lee KK, Chapman AR, Newby DE, Anand A, Collinson PO, Mueller C, Mills NL, High-STEACS Investigators.",,European heart journal,2023,2023-08-01,Y,Myocardial infarction; cardiac troponin; Symptoms,,,"

Aims

Whether a single cardiac troponin measurement can safely rule out myocardial infarction in patients presenting within a few hours of symptom onset is uncertain. The study aim was to assess the performance of troponin in early presenters.

Methods and results

In patients with possible myocardial infarction, the diagnostic performance of a single measurement of high-sensitivity cardiac troponin I at presentation was evaluated and externally validated in those tested ≤3, 4-12, and >12 h from symptom onset. The limit-of-detection (2 ng/L), rule-out (5 ng/L), and sex-specific 99th centile (16 ng/L in women; 34 ng/L in men) thresholds were compared. In 41 103 consecutive patients [60 (17) years, 46% women], 12 595 (31%) presented within 3 h, and 3728 (9%) had myocardial infarction. In those presenting ≤3 h, a threshold of 2 ng/L had greater sensitivity and negative predictive value [99.4% (95% confidence interval 99.2%-99.5%) and 99.7% (99.6%-99.8%)] compared with 5 ng/L [96.5% (96.2%-96.8%) and 99.3% (99.1%-99.4%)]. In those presenting ≥3 h, the sensitivity and negative predictive value were similar for both thresholds. The sensitivity of the 99th centile was low in early and late presenters at 71.4% (70.6%-72.2%) and 92.5% (92.0%-93.0%), respectively. Findings were consistent in an external validation cohort of 7088 patients.

Conclusion

In early presenters, a single measurement of high-sensitivity cardiac troponin I below the limit of detection may facilitate the safe rule out of myocardial infarction. The 99th centile should not be used to rule out myocardial infarction at presentation even in those presenting later following symptom onset.",,pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad376/50684614/ehad376.pdf; doi:https://doi.org/10.1093/eurheartj/ehad376; html:https://europepmc.org/articles/PMC10406338; pdf:https://europepmc.org/articles/PMC10406338?pdf=render -37294923,https://doi.org/10.1093/eurjpc/zwad192,Incidence of 12 common cardiovascular diseases and subsequent mortality risk in the general population.,"Prugger C, Perier MC, Gonzalez-Izquierdo A, Hemingway H, Denaxas S, Empana JP.",,European journal of preventive cardiology,2023,2023-10-01,N,Prevention; Survival analysis; Stroke; epidemiology; Coronary Heart Disease; incidence,,,"

Background

Incident events of cardiovascular diseases (CVDs) are heterogenous and may result in different mortality risks. Such evidence may help inform patient and physician decisions in CVD prevention and risk factor management.

Aims

This study aimed to determine the extent to which incident events of common CVD show heterogeneous associations with subsequent mortality risk in the general population.

Methods and results

Based on England-wide linked electronic health records, we established a cohort of 1 310 518 people ≥30 years of age initially free of CVD and followed up for non-fatal events of 12 common CVD and cause-specific mortality. The 12 CVDs were considered as time-varying exposures in Cox's proportional hazards models to estimate hazard rate ratios (HRRs) with 95% confidence intervals (CIs). Over the median follow-up of 4.2 years (2010-16), 81 516 non-fatal CVD, 10 906 cardiovascular deaths, and 40 843 non-cardiovascular deaths occurred. All 12 CVDs were associated with increased risk of cardiovascular mortality, with HRR (95% CI) ranging from 1.67 (1.47-1.89) for stable angina to 7.85 (6.62-9.31) for haemorrhagic stroke. All 12 CVDs were also associated with increased non-cardiovascular and all-cause mortality risk but to a lesser extent: HRR (95% CI) ranged from 1.10 (1.00-1.22) to 4.55 (4.03-5.13) and from 1.24 (1.13-1.35) to 4.92 (4.44-5.46) for transient ischaemic attack and sudden cardiac arrest, respectively.

Conclusion

Incident events of 12 common CVD show significant adverse and markedly differential associations with subsequent cardiovascular, non-cardiovascular, and all-cause mortality risk in the general population.",,doi:https://doi.org/10.1093/eurjpc/zwad192 33413610,https://doi.org/10.1186/s13073-020-00822-6,An integrated in silico immuno-genetic analytical platform provides insights into COVID-19 serological and vaccine targets.,"Ward D, Higgins M, Phelan JE, Hibberd ML, Campino S, Clark TG.",,Genome medicine,2021,2021-01-07,Y,Mutation; Epitopes; Surveillance; cross-reactivity; Immuno-informatics; Sars-cov-2; Covid; Human-coronavirus,,,"During COVID-19, diagnostic serological tools and vaccines have been developed. To inform control activities in a post-vaccine surveillance setting, we have developed an online ""immuno-analytics"" resource that combines epitope, sequence, protein and SARS-CoV-2 mutation analysis. SARS-CoV-2 spike and nucleocapsid proteins are both vaccine and serological diagnostic targets. Using the tool, the nucleocapsid protein appears to be a sub-optimal target for use in serological platforms. Spike D614G (and nsp12 L314P) mutations were most frequent (> 86%), whilst spike A222V/L18F have recently increased. Also, Orf3a proteins may be a suitable target for serology. The tool can accessed from: http://genomics.lshtm.ac.uk/immuno (online); https://github.com/dan-ward-bio/COVID-immunoanalytics (source code).",,pdf:https://genomemedicine.biomedcentral.com/counter/pdf/10.1186/s13073-020-00822-6; doi:https://doi.org/10.1186/s13073-020-00822-6; html:https://europepmc.org/articles/PMC7790334; pdf:https://europepmc.org/articles/PMC7790334?pdf=render +37294923,https://doi.org/10.1093/eurjpc/zwad192,Incidence of 12 common cardiovascular diseases and subsequent mortality risk in the general population.,"Prugger C, Perier MC, Gonzalez-Izquierdo A, Hemingway H, Denaxas S, Empana JP.",,European journal of preventive cardiology,2023,2023-10-01,N,Prevention; Survival analysis; Stroke; epidemiology; Coronary Heart Disease; incidence,,,"

Background

Incident events of cardiovascular diseases (CVDs) are heterogenous and may result in different mortality risks. Such evidence may help inform patient and physician decisions in CVD prevention and risk factor management.

Aims

This study aimed to determine the extent to which incident events of common CVD show heterogeneous associations with subsequent mortality risk in the general population.

Methods and results

Based on England-wide linked electronic health records, we established a cohort of 1 310 518 people ≥30 years of age initially free of CVD and followed up for non-fatal events of 12 common CVD and cause-specific mortality. The 12 CVDs were considered as time-varying exposures in Cox's proportional hazards models to estimate hazard rate ratios (HRRs) with 95% confidence intervals (CIs). Over the median follow-up of 4.2 years (2010-16), 81 516 non-fatal CVD, 10 906 cardiovascular deaths, and 40 843 non-cardiovascular deaths occurred. All 12 CVDs were associated with increased risk of cardiovascular mortality, with HRR (95% CI) ranging from 1.67 (1.47-1.89) for stable angina to 7.85 (6.62-9.31) for haemorrhagic stroke. All 12 CVDs were also associated with increased non-cardiovascular and all-cause mortality risk but to a lesser extent: HRR (95% CI) ranged from 1.10 (1.00-1.22) to 4.55 (4.03-5.13) and from 1.24 (1.13-1.35) to 4.92 (4.44-5.46) for transient ischaemic attack and sudden cardiac arrest, respectively.

Conclusion

Incident events of 12 common CVD show significant adverse and markedly differential associations with subsequent cardiovascular, non-cardiovascular, and all-cause mortality risk in the general population.",,doi:https://doi.org/10.1093/eurjpc/zwad192 37156273,https://doi.org/10.1016/j.jad.2023.04.138,Subjective and objective sleep and circadian parameters as predictors of depression-related outcomes: A machine learning approach in UK Biobank.,"Lyall LM, Sangha N, Zhu X, Lyall DM, Ward J, Strawbridge RJ, Cullen B, Smith DJ.",,Journal of affective disorders,2023,2023-05-06,N,Sleep; Depression; Circadian rhythms; Postnatal Depression; Inactivity; Rest-activity,,,"

Background

Sleep and circadian disruption are associated with depression onset and severity, but it is unclear which features (e.g., sleep duration, chronotype) are important and whether they can identify individuals showing poorer outcomes.

Methods

Within a subset of the UK Biobank with actigraphy and mental health data (n = 64,353), penalised regression identified the most useful of 51 sleep/rest-activity predictors of depression-related outcomes; including case-control (Major Depression (MD) vs. controls; postnatal depression vs. controls) and within-case comparisons (severe vs. moderate MD; early vs. later onset, atypical vs. typical symptoms; comorbid anxiety; suicidality). Best models (of lasso, ridge, and elastic net) were selected based on Area Under the Curve (AUC).

Results

For MD vs. controls (n(MD) = 24,229; n(control) = 40,124), lasso AUC was 0.68, 95 % confidence interval (CI) 0.67-0.69. Discrimination was reasonable for atypical vs. typical symptoms (n(atypical) = 958; n(typical) = 18,722; ridge: AUC 0.74, 95 % CI 0.71-0.77) but poor for remaining models (AUCs 0.59-0.67). Key predictors across most models included: difficulty getting up, insomnia symptoms, snoring, actigraphy-measured daytime inactivity and lower morning activity (~8 am). In a distinct subset (n = 310,718), the number of these factors shown was associated with all depression outcomes.

Limitations

Analyses were cross-sectional and in middle-/older aged adults: comparison with longitudinal investigations and younger cohorts is necessary.

Discussion

Sleep and circadian measures alone provided poor to moderate discrimination of depression outcomes, but several characteristics were identified that may be clinically useful. Future work should assess these features alongside broader sociodemographic, lifestyle and genetic features.",,doi:https://doi.org/10.1016/j.jad.2023.04.138; doi:https://doi.org/10.1016/j.jad.2023.04.138 36654802,https://doi.org/10.1002/lrh2.10315,"A framework for understanding, designing, developing and evaluating learning health systems.","Foley T, Vale L.",,Learning health systems,2023,2022-05-20,Y,Quality improvement; Informatics; Implementation Science; Learning Health Systems; Learning Healthcare Systems,,,"

Introduction

A Learning Health System is not a technical project. It is the evolution of an existing health system into one capable of learning from every patient. This paper outlines a recently published framework intended to aid the understanding, design, development and evaluation of Learning Health Systems.

Methods

This work extended an existing repository of Learning Health System evidence, adding five more workshops. The total was subjected to thematic analysis, yielding a framework of elements important to understanding, designing, developing and evaluating Learning Health Systems. Purposeful literature reviews were conducted on each element. The findings were revised following a review by a group of international experts.

Results

The resulting framework was arranged around four questions:What is our rationale for developing a Learning Health System?There can be many reasons for developing a Learning Health System. Understanding these will guide its development.What sources of complexity exist at the system and the intervention level?An understanding of complexity is central to making Learning Health Systems work. The non-adoption, abandonment, scale-up, spread and sustainability framework was utilised to help understand and manage it.What strategic approaches to change do we need to consider?A range of strategic issues must be addressed to enable successful change in a Learning Health System. These include, strategy, organisational structure, culture, workforce, implementation science, behaviour change, co-design and evaluation.What technical building blocks will we need?A Learning Health System must capture data from practice, turn it into knowledge and apply it back into practice. There are many methods to achieve this and a range of platforms to help.

Discussion

The results form a framework for understanding, designing, developing and evaluating Learning Health Systems at any scale.

Conclusion

It is hoped that this framework will evolve with use and feedback.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9835047; doi:https://doi.org/10.1002/lrh2.10315; html:https://europepmc.org/articles/PMC9835047; pdf:https://europepmc.org/articles/PMC9835047?pdf=render 33112263,https://doi.org/10.1530/eje-20-0296,Pubertal timing in boys and girls born to mothers with gestational diabetes mellitus: a systematic review.,"Subramanian A, Idkowiak J, Toulis KA, Thangaratinam S, Arlt W, Nirantharakumar K.",,European journal of endocrinology,2021,2021-01-01,Y,,,,"

Context

The incidence of gestational diabetes mellitus (GDM) has been on the rise, driven by maternal obesity. In parallel, pubertal tempo has increased in the general population, driven by childhood obesity.

Objective

To evaluate the available evidence on pubertal timing of boys and girls born to mothers with GDM.

Data sources

We searched MEDLINE, EMBASE, CINAHL Plus, Cochrane library and grey literature for observational studies up to October 2019.

Study selection and extraction

Two reviewers independently selected studies, collected data and appraised the studies for risk of bias. Results were tabulated and narratively described as reported in the primary studies.

Results

Seven articles (six for girls and four for boys) were included. Study quality score was mostly moderate (ranging from 4 to 10 out of 11). In girls born to mothers with GDM, estimates suggest earlier timing of pubarche, thelarche and menarche although for each of these outcomes only one study each showed a statistically significant association. In boys, there was some association between maternal GDM and earlier pubarche, but inconsistency in the direction of shift of age at onset of genital and testicular development and first ejaculation. Only a single study analysed growth patterns in children of mothers with GDM, describing a 3-month advancement in the age of attainment of peak height velocity and a slight increase in pubertal tempo.

Conclusions

Pubertal timing may be influenced by the presence of maternal GDM, though current evidence is sparse and of limited quality. Prospective cohort studies should be conducted, ideally coupled with objective biochemical tests.",,pdf:https://eje.bioscientifica.com/downloadpdf/journals/eje/184/1/EJE-20-0296.pdf; doi:https://doi.org/10.1530/EJE-20-0296; html:https://europepmc.org/articles/PMC7707806; pdf:https://europepmc.org/articles/PMC7707806?pdf=render -33856367,https://doi.org/10.1097/sla.0000000000004904,Optimizing Trauma Systems: A Geospatial Analysis of the Victorian State Trauma System.,"Beck B, Tack G, Cameron P, Smith K, Gabbe B.",,Annals of surgery,2023,2023-01-10,N,,,,"

Objective

The aim of this study was to develop a data-driven approach to assessing the influence of trauma system parameters and optimizing the configuration of the Victorian State Trauma System (VSTS).

Summary background data

Regionalized trauma systems have been shown to reduce the risk of mortality and improve patient function and health-related quality of life. However, major trauma case numbers are rapidly increasing and there is a need to evolve the configuration of trauma systems.

Methods

A retrospective review of major trauma patients from 2016 to 2018 in Victoria, Australia. Drive times and flight times were calculated for transport to each of 138 trauma receiving hospitals. Changes to the configuration of the VSTS were modeled using a Mixed Integer Linear Programming algorithm across 156 simulations.

Results

There were 8327 patients included in the study, of which 58% were transported directly to a major trauma service (MTS). For adult patients, the proportion of patients transported directly to an MTS increased with higher transport time limit, greater probability of helicopter emergency medical service utilization, and lower hospital patient threshold numbers. The proportion of adult patients transported directly to an MTS varied from 66% to 90% across simulations. Across all simulations for pediatric patients, only 1 pediatric MTS was assigned.

Conclusions

We have developed a robust and data-driven approach to optimizing trauma systems. Through the use of geospatial and mathematical models, we have modeled how potential future changes to trauma system characteristics may impact on the optimal configuration of the system, which will enable policy makers to make informed decisions about health service planning into the future.",,doi:https://doi.org/10.1097/SLA.0000000000004904 32226230,https://doi.org/10.1016/j.neucom.2018.04.087,Covariate shift estimation based adaptive ensemble learning for handling non-stationarity in motor imagery related EEG-based brain-computer interface.,"Raza H, Rathee D, Zhou SM, Cecotti H, Prasad G.",,Neurocomputing,2019,2019-05-01,Y,"Electroencephalogram (Eeg); Pca, Principal Component Analysis; Brain-computer Interface (Bci); Ensemble Learning; Lda, Linear Discriminant Analysis; Eeg, Electroencephalography; Ssl, Semi-supervised Learning; Mi, Motor Imagery; Covariate Shift; Non-stationary Learning; Bci, Brain-computer-interface; Cs, Covariate Shift; Csa, Covariate Shift Adaptation; Cse, Covariate Shift Estimation; Cse-uael, Cse-based Unsupervised Adaptive Ensemble Learning; Csp, Common Spatial Pattern; Csv, Covariate Shift Validation; Csw, Covariate Shift Warning; Dwec, Dynamically Weighted Ensemble Classification; Erd, Synchronization; Ers, Desynchronization; Ewma, Exponential Weighted Moving Average; Fb, Frequency Band; Fbcsp, Filter Bank Common Spatial Pattern; Knn, K-nearest-neighbors; Nsl, Non-stationary Learning; Pwknn, Probabilistic Weighted K-nearest Neighbour; Rsm, Random Subspace Method",Applied Analytics,neurological,"The non-stationary nature of electroencephalography (EEG) signals makes an EEG-based brain-computer interface (BCI) a dynamic system, thus improving its performance is a challenging task. In addition, it is well-known that due to non-stationarity based covariate shifts, the input data distributions of EEG-based BCI systems change during inter- and intra-session transitions, which poses great difficulty for developments of online adaptive data-driven systems. Ensemble learning approaches have been used previously to tackle this challenge. However, passive scheme based implementation leads to poor efficiency while increasing high computational cost. This paper presents a novel integration of covariate shift estimation and unsupervised adaptive ensemble learning (CSE-UAEL) to tackle non-stationarity in motor-imagery (MI) related EEG classification. The proposed method first employs an exponentially weighted moving average model to detect the covariate shifts in the common spatial pattern features extracted from MI related brain responses. Then, a classifier ensemble was created and updated over time to account for changes in streaming input data distribution wherein new classifiers are added to the ensemble in accordance with estimated shifts. Furthermore, using two publicly available BCI-related EEG datasets, the proposed method was extensively compared with the state-of-the-art single-classifier based passive scheme, single-classifier based active scheme and ensemble based passive schemes. The experimental results show that the proposed active scheme based ensemble learning algorithm significantly enhances the BCI performance in MI classifications.",,doi:https://doi.org/10.1016/j.neucom.2018.04.087; doi:https://doi.org/10.1016/j.neucom.2018.04.087; html:https://europepmc.org/articles/PMC7086459 +33856367,https://doi.org/10.1097/sla.0000000000004904,Optimizing Trauma Systems: A Geospatial Analysis of the Victorian State Trauma System.,"Beck B, Tack G, Cameron P, Smith K, Gabbe B.",,Annals of surgery,2023,2023-01-10,N,,,,"

Objective

The aim of this study was to develop a data-driven approach to assessing the influence of trauma system parameters and optimizing the configuration of the Victorian State Trauma System (VSTS).

Summary background data

Regionalized trauma systems have been shown to reduce the risk of mortality and improve patient function and health-related quality of life. However, major trauma case numbers are rapidly increasing and there is a need to evolve the configuration of trauma systems.

Methods

A retrospective review of major trauma patients from 2016 to 2018 in Victoria, Australia. Drive times and flight times were calculated for transport to each of 138 trauma receiving hospitals. Changes to the configuration of the VSTS were modeled using a Mixed Integer Linear Programming algorithm across 156 simulations.

Results

There were 8327 patients included in the study, of which 58% were transported directly to a major trauma service (MTS). For adult patients, the proportion of patients transported directly to an MTS increased with higher transport time limit, greater probability of helicopter emergency medical service utilization, and lower hospital patient threshold numbers. The proportion of adult patients transported directly to an MTS varied from 66% to 90% across simulations. Across all simulations for pediatric patients, only 1 pediatric MTS was assigned.

Conclusions

We have developed a robust and data-driven approach to optimizing trauma systems. Through the use of geospatial and mathematical models, we have modeled how potential future changes to trauma system characteristics may impact on the optimal configuration of the system, which will enable policy makers to make informed decisions about health service planning into the future.",,doi:https://doi.org/10.1097/SLA.0000000000004904 33052324,https://doi.org/10.1016/j.eclinm.2020.100574,A case-control and cohort study to determine the relationship between ethnic background and severe COVID-19.,"Zakeri R, Bendayan R, Ashworth M, Bean DM, Dodhia H, Durbaba S, O'Gallagher K, Palmer C, Curcin V, Aitken E, Bernal W, Barker RD, Norton S, Gulliford M, Teo JTH, Galloway J, Dobson RJB, Shah AM.",,EClinicalMedicine,2020,2020-10-09,Y,Case-control study; Ethnicity; Deprivation; Comorbidities; Covid-19,,,"

Background

People of minority ethnic backgrounds may be disproportionately affected by severe COVID-19. Whether this relates to increased infection risk, more severe disease progression, or worse in-hospital survival is unknown. The contribution of comorbidities or socioeconomic deprivation to ethnic patterning of outcomes is also unclear.

Methods

We conducted a case-control and a cohort study in an inner city primary and secondary care setting to examine whether ethnic background affects the risk of hospital admission with severe COVID-19 and/or in-hospital mortality. Inner city adult residents admitted to hospital with confirmed COVID-19 (n = 872 cases) were compared with 3,488 matched controls randomly sampled from a primary healthcare database comprising 344,083 people residing in the same region. For the cohort study, we studied 1827 adults consecutively admitted with COVID-19. The primary exposure variable was self-defined ethnicity. Analyses were adjusted for socio-demographic and clinical variables.

Findings

The 872 cases comprised 48.1% Black, 33.7% White, 12.6% Mixed/Other and 5.6% Asian patients. In conditional logistic regression analyses, Black and Mixed/Other ethnicity were associated with higher admission risk than white (OR 3.12 [95% CI 2.63-3.71] and 2.97 [2.30-3.85] respectively). Adjustment for comorbidities and deprivation modestly attenuated the association (OR 2.24 [1.83-2.74] for Black, 2.70 [2.03-3.59] for Mixed/Other). Asian ethnicity was not associated with higher admission risk (adjusted OR 1.01 [0.70-1.46]). In the cohort study of 1827 patients, 455 (28.9%) died over a median (IQR) of 8 (4-16) days. Age and male sex, but not Black (adjusted HR 1.06 [0.82-1.37]) or Mixed/Other ethnicity (adjusted HR 0.72 [0.47-1.10]), were associated with in-hospital mortality. Asian ethnicity was associated with higher in-hospital mortality but with a large confidence interval (adjusted HR 1.71 [1.15-2.56]).

Interpretation

Black and Mixed ethnicity are independently associated with greater admission risk with COVID-19 and may be risk factors for development of severe disease, but do not affect in-hospital mortality risk. Comorbidities and socioeconomic factors only partly account for this and additional ethnicity-related factors may play a large role. The impact of COVID-19 may be different in Asians.

Funding

British Heart Foundation; the National Institute for Health Research; Health Data Research UK.",,pdf:http://www.thelancet.com/article/S2589537020303187/pdf; doi:https://doi.org/10.1016/j.eclinm.2020.100574; html:https://europepmc.org/articles/PMC7545271; pdf:https://europepmc.org/articles/PMC7545271?pdf=render 33402395,https://doi.org/10.1136/jech-2020-215204,Hospital readmission among people experiencing homelessness in England: a cohort study of 2772 matched homeless and housed inpatients.,"Lewer D, Menezes D, Cornes M, Blackburn RM, Byng R, Clark M, Denaxas S, Evans H, Fuller J, Hewett N, Kilmister A, Luchenski SA, Manthorpe J, McKee M, Neale J, Story A, Tinelli M, Whiteford M, Wurie F, Yavlinsky A, Hayward A, Aldridge R.",,Journal of epidemiology and community health,2021,2021-01-05,Y,Homelessness; Health Inequalities; Record Linkage; Access To Hlth Care,,,"

Background

Inpatients experiencing homelessness are often discharged to unstable accommodation or the street, which may increase the risk of readmission.

Methods

We conducted a cohort study of 2772 homeless patients discharged after an emergency admission at 78 hospitals across England between November 2013 and November 2016. For each individual, we selected a housed patient who lived in a socioeconomically deprived area, matched on age, sex, hospital, and year of discharge. Counts of emergency readmissions, planned readmissions, and Accident and Emergency (A&E) visits post-discharge were derived from national hospital databases, with a median of 2.8 years of follow-up. We estimated the cumulative incidence of readmission over 12 months, and used negative binomial regression to estimate rate ratios.

Results

After adjusting for health measured at the index admission, homeless patients had 2.49 (95% CI 2.29 to 2.70) times the rate of emergency readmission, 0.60 (95% CI 0.53 to 0.68) times the rate of planned readmission and 2.57 (95% CI 2.41 to 2.73) times the rate of A&E visits compared with housed patients. The 12-month risk of emergency readmission was higher for homeless patients (61%, 95% CI 59% to 64%) than housed patients (33%, 95% CI 30% to 36%); and the risk of planned readmission was lower for homeless patients (17%, 95% CI 14% to 19%) than for housed patients (30%, 95% CI 28% to 32%). While the risk of emergency readmission varied with the reason for admission for housed patients, for example being higher for admissions due to cancers than for those due to accidents, the risk was high across all causes for homeless patients.

Conclusions

Hospital patients experiencing homelessness have high rates of emergency readmission that are not explained by health. This highlights the need for discharge arrangements that address their health, housing and social care needs.",,pdf:https://jech.bmj.com/content/jech/75/7/681.full.pdf; doi:https://doi.org/10.1136/jech-2020-215204; html:https://europepmc.org/articles/PMC8223662; pdf:https://europepmc.org/articles/PMC8223662?pdf=render 33710281,https://doi.org/10.1093/ageing/afab060,COVID-19 infection and attributable mortality in UK care homes: cohort study using active surveillance and electronic records (March-June 2020).,"Dutey-Magni PF, Williams H, Jhass A, Rait G, Lorencatto F, Hemingway H, Hayward A, Shallcross L.",,Age and ageing,2021,2021-06-01,Y,Mortality; Morbidity; Older People; Long-term Care; Covid-19; Sars-cov-2,,,"

Background

epidemiological data on COVID-19 infection in care homes are scarce. We analysed data from a large provider of long-term care for older people to investigate infection and mortality during the first wave of the pandemic.

Methods

cohort study of 179 UK care homes with 9,339 residents and 11,604 staff. We used manager-reported daily tallies to estimate the incidence of suspected and confirmed infection and mortality in staff and residents. Individual-level electronic health records from 8,713 residents were used to model risk factors for confirmed infection, mortality and estimate attributable mortality.

Results

2,075/9,339 residents developed COVID-19 symptoms (22.2% [95% confidence interval: 21.4%; 23.1%]), while 951 residents (10.2% [9.6%; 10.8%]) and 585 staff (5.0% [4.7%; 5.5%]) had laboratory-confirmed infections. The incidence of confirmed infection was 152.6 [143.1; 162.6] and 62.3 [57.3; 67.5] per 100,000 person-days in residents and staff, respectively. Sixty-eight percent (121/179) of care homes had at least one COVID-19 infection or COVID-19-related death. Lower staffing ratios and higher occupancy rates were independent risk factors for infection.Out of 607 residents with confirmed infection, 217 died (case fatality rate: 35.7% [31.9%; 39.7%]). Mortality in residents with no direct evidence of infection was twofold higher in care homes with outbreaks versus those without (adjusted hazard ratio: 2.2 [1.8; 2.6]).

Conclusions

findings suggest many deaths occurred in people who were infected with COVID-19, but not tested. Higher occupancy and lower staffing levels were independently associated with risks of infection. Protecting staff and residents from infection requires regular testing for COVID-19 and fundamental changes to staffing and care home occupancy.",,pdf:https://academic.oup.com/ageing/article-pdf/50/4/1019/40971734/afab060.pdf; doi:https://doi.org/10.1093/ageing/afab060; html:https://europepmc.org/articles/PMC7989651; pdf:https://europepmc.org/articles/PMC7989651?pdf=render @@ -929,8 +929,8 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 38327760,https://doi.org/10.1016/j.jmh.2024.100214,Sexual and reproductive health and rights of migrant women attending primary care in England: A population-based cohort study of 1.2 million individuals of reproductive age (2009-2018).,"Pathak N, Zhang CX, Boukari Y, Burns R, Menezes D, Hugenholtz G, French RS, Gonzalez-Izquierdo A, Mathur R, Denaxas S, Hayward A, Sonnenberg P, Aldridge RW.",,Journal of migration and health,2024,2024-01-17,Y,Migration; Migrant; Reproductive Health; Sexual Health; Primary Care; Electronic Health Records; Sexual And Reproductive Health And Rights; Migration Health; Srhr,,,"

Background

Evidence on the sexual and reproductive health and rights (SRHR) of migrants is lacking globally. We describe SRHR healthcare resource use and long-acting reversible contraceptives (LARCs) prescriptions for migrant versus non-migrant women attending primary care in England (2009-2018).

Methods

This population-based observational cohort study, using Clinical Practice Research Datalink (CPRD) GOLD, included females living in England aged 15 to 49. Migration was defined using a validated codelist. Rates per 100 person years at risk (pyar) and adjusted rate ratios (RRs) were measured in migrants versus non-migrants for consultations related to all-causes, six exemplar SRHR outcomes, and LARC prescriptions. Proportions of migrants and non-migrants ever prescribed LARC were calculated.

Findings

There were 25,112,116 consultations across 1,246,353 eligible individuals. 98,214 (7.9 %) individuals were migrants. All-cause consultation rates were lower in migrants versus non-migrants (509 vs 583/100pyar;RR 0.9;95 %CI 0.9-0.9), as were consultations rates for emergency contraception (RR 0.7;95 %CI 0.7-0.7) and cervical screening (RR 0.96;95 %CI 0.95-0.97). Higher rates of consultations were found in migrants for abortion (RR 1.2;95 %CI 1.1-1.2) and management of fertility problems (RR 1.39;95 %CI 1.08-1.79). No significant difference was observed for chlamydia testing and domestic violence. Of 1,205,258 individuals eligible for contraception, the proportion of non-migrants ever prescribed LARC (12.2 %;135,047/1,107,894) was almost double that of migrants (6.91 %;6,728/97,364). Higher copper intrauterine devices prescription rates were found in migrants (RR 1.53;95 %CI 1.45-1.61), whilst hormonal LARC rates were lower for migrants: levonorgestrel intrauterine device (RR 0.63;95 %CI 0.60-0.66), subdermal implant (RR 0.72;95 %CI 0.69-0.75), and progesterone-only injection (RR 0.35;95 %CI 0.34-0.36).

Interpretation

Healthcare resource use differs between migrant and non-migrant women of reproductive age. Opportunities identified for tailored interventions include access to primary care, LARCs, emergency contraception and cervical screening. An inclusive approach to examining health needs is essential to actualise sexual and reproductive health as a human right.",,doi:https://doi.org/10.1016/j.jmh.2024.100214; doi:https://doi.org/10.1016/j.jmh.2024.100214; html:https://europepmc.org/articles/PMC10847991; pdf:https://europepmc.org/articles/PMC10847991?pdf=render 35896970,https://doi.org/10.1186/s12879-022-07628-4,SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2.,"Eales O, Page AJ, de Oliveira Martins L, Wang H, Bodinier B, Haw D, Jonnerby J, Atchison C, COVID-19 Genomics UK (COG-UK) Consortium, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S, Chadeau-Hyam M, Donnelly CA, Elliott P.",,BMC infectious diseases,2022,2022-07-27,Y,Mutation; Genetic diversity; Transmission Advantage; Covid-19; Sars-cov-2; Delta Variant,,,"

Background

Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Genomic surveillance in regions of high immunity is crucial in detecting emerging variants that can more successfully navigate the immune landscape.

Methods

We present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. During round 14 (9 September-27 September 2021) and 15 (19 October-5 November 2021) lineages were determined for 1322 positive individuals, with 27.1% of those which reported their symptom status reporting no symptoms in the previous month.

Results

We identified 44 unique lineages, all of which were Delta or Delta sub-lineages, and found a reduction in their mutation rate over the study period. The proportion of the Delta sub-lineage AY.4.2 was increasing, with a reproduction number 15% (95% CI 8-23%) greater than the most prevalent lineage, AY.4. Further, AY.4.2 was less associated with the most predictive COVID-19 symptoms (p = 0.029) and had a reduced mutation rate (p = 0.050). Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England.

Conclusions

As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals.",,pdf:https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-022-07628-4; doi:https://doi.org/10.1186/s12879-022-07628-4; html:https://europepmc.org/articles/PMC9326417; pdf:https://europepmc.org/articles/PMC9326417?pdf=render 34266851,https://doi.org/10.1136/bmjhci-2021-100356,Development of a core competency framework for clinical informatics.,"Davies A, Mueller J, Hassey A, Moulton G.",,BMJ health & care informatics,2021,2021-07-01,Y,Medical Informatics; Bmj Health Informatics,,,"

Objectives

Until this point there was no national core competency framework for clinical informatics in the UK. We report on the final two iterations of work carried out in the formation of a national core competency framework. This follows an initial systematic literature review of existing skills and competencies and a job listing analysis.MethodsAn iterative approach was applied to framework development. Using a mixed-methods design we carried out semi-structured interviews with participants involved in informatics (n=15). The framework was updated based on the interview findings and was subsequently distributed as part of a bespoke online digital survey for wider participation (n=87). The final version of the framework is based on the findings of the survey.

Results

Over 102 people reviewed the framework as part of the interview or survey process. This led to a final core competency framework containing 6 primary domains with 36 subdomains containing 111 individual competencies.

Conclusions

An iterative mixed-methods approach for competency development involving the target community was appropriate for development of the competency framework. There is some contention around the depth of technical competencies required. Care is also needed to avoid professional burnout, as clinicians and healthcare practitioners already have clinical competencies to maintain. Therefore, how the framework is applied in practice and how practitioners meet the competencies requires careful consideration.",,pdf:https://informatics.bmj.com/content/bmjhci/28/1/e100356.full.pdf; doi:https://doi.org/10.1136/bmjhci-2021-100356; html:https://europepmc.org/articles/PMC8286765; pdf:https://europepmc.org/articles/PMC8286765?pdf=render -38655112,https://doi.org/10.1089/neur.2023.0127,The Australian Traumatic Brain Injury Initiative: Review and Recommendations for Outcome Measures for Use With Adults and Children After Moderate-to-Severe Traumatic Brain Injury.,"Ponsford JL, Hicks AJ, Bagg MK, Phyland R, Carrier S, James AC, Lannin NA, Rushworth N, O'Brien TJ, Cameron PA, Cooper DJ, Hill R, Gabbe BJ, Fitzgerald M.",,Neurotrauma reports,2024,2024-04-11,Y,Review; Traumatic brain injury; Outcome Measures; Common Data Elements,,,"The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to select a set of measures to comprehensively predict and assess outcomes following moderate-to-severe traumatic brain injury (TBI) across Australia. The aim of this article was to report on the implementation and findings of an evidence-based consensus approach to develop AUS-TBI recommendations for outcome measures following adult and pediatric moderate-to-severe TBI. Following consultation with a panel of expert clinicians, Aboriginal and Torres Strait Islander representatives and a Living Experience group, and preliminary literature searches with a broader focus, a decision was made to focus on measures of mortality, everyday functional outcomes, and quality of life. Standardized searches of bibliographic databases were conducted through March 2022. Characteristics of 75 outcome measures were extracted from 1485 primary studies. Consensus meetings among the AUS-TBI Steering Committee, an expert panel of clinicians and researchers and a group of individuals with lived experience of TBI resulted in the production of a final list of 11 core outcome measures: the Functional Independence Measure (FIM); Glasgow Outcome Scale-Extended (GOS-E); Satisfaction With Life Scale (SWLS) (adult); mortality; EuroQol-5 Dimensions (EQ5D); Mayo-Portland Adaptability Inventory (MPAI); Return to Work /Study (adult and pediatric); Functional Independence Measure for Children (WEEFIM); Glasgow Outcome Scale Modified for Children (GOS-E PEDS); Paediatric Quality of Life Scale (PEDS-QL); and Strengths and Difficulties Questionnaire (pediatric). These 11 outcome measures will be included as common data elements in the AUS-TBI data dictionary. Review Registration PROSPERO (CRD42022290954).",,doi:https://doi.org/10.1089/neur.2023.0127; html:https://europepmc.org/articles/PMC11035854; pdf:https://europepmc.org/articles/PMC11035854?pdf=render 34190735,https://doi.org/,The changing characteristics of COVID-19 presentations. A regional comparison of SARS-CoV-2 hospitalised patients during the first and second wave.,"Atkin C, Kamwa V, Reddy-Kolanu V, Parekh D, Evison F, Nightingale P, Gallier S, Ball S, Sapey E.",,Acute medicine,2021,2021-01-01,N,,,,"

Background

This study assesses COVID-19 hospitalised patient demography and outcomes during wave 1 and wave 2, prior to new variants of the virus.

Methods

All patients with a positive SARS-CoV-2 swab between 10th March 2020 and 5th July 2020 (wave 1) and 1st September 2020 and 16th November 2020 (wave 2) admitted to University Hospitals Birmingham NHS Foundation Trust were included (n=4856), followed for 28 days.

Results

Wave 2 patients were younger, more ethnically diverse, had less co-morbidities and disease presentation was milder on presentation. After matching for these factors, mortality was reduced, but without differences in intensive care admissions.

Conclusion

Prior to new SARS-CoV-2 variants, outcomes for hospitalised patients with COVID-19 were improving but with similar intensive care needs.",, +38655112,https://doi.org/10.1089/neur.2023.0127,The Australian Traumatic Brain Injury Initiative: Review and Recommendations for Outcome Measures for Use With Adults and Children After Moderate-to-Severe Traumatic Brain Injury.,"Ponsford JL, Hicks AJ, Bagg MK, Phyland R, Carrier S, James AC, Lannin NA, Rushworth N, O'Brien TJ, Cameron PA, Cooper DJ, Hill R, Gabbe BJ, Fitzgerald M.",,Neurotrauma reports,2024,2024-04-11,Y,Review; Traumatic brain injury; Outcome Measures; Common Data Elements,,,"The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to select a set of measures to comprehensively predict and assess outcomes following moderate-to-severe traumatic brain injury (TBI) across Australia. The aim of this article was to report on the implementation and findings of an evidence-based consensus approach to develop AUS-TBI recommendations for outcome measures following adult and pediatric moderate-to-severe TBI. Following consultation with a panel of expert clinicians, Aboriginal and Torres Strait Islander representatives and a Living Experience group, and preliminary literature searches with a broader focus, a decision was made to focus on measures of mortality, everyday functional outcomes, and quality of life. Standardized searches of bibliographic databases were conducted through March 2022. Characteristics of 75 outcome measures were extracted from 1485 primary studies. Consensus meetings among the AUS-TBI Steering Committee, an expert panel of clinicians and researchers and a group of individuals with lived experience of TBI resulted in the production of a final list of 11 core outcome measures: the Functional Independence Measure (FIM); Glasgow Outcome Scale-Extended (GOS-E); Satisfaction With Life Scale (SWLS) (adult); mortality; EuroQol-5 Dimensions (EQ5D); Mayo-Portland Adaptability Inventory (MPAI); Return to Work /Study (adult and pediatric); Functional Independence Measure for Children (WEEFIM); Glasgow Outcome Scale Modified for Children (GOS-E PEDS); Paediatric Quality of Life Scale (PEDS-QL); and Strengths and Difficulties Questionnaire (pediatric). These 11 outcome measures will be included as common data elements in the AUS-TBI data dictionary. Review Registration PROSPERO (CRD42022290954).",,doi:https://doi.org/10.1089/neur.2023.0127; html:https://europepmc.org/articles/PMC11035854; pdf:https://europepmc.org/articles/PMC11035854?pdf=render 35444210,https://doi.org/10.1038/s41698-022-00269-5,Pan-cancer prognostic genetic mutations and clinicopathological factors associated with survival outcomes: a systematic review.,"Gammall J, Lai AG.",,NPJ precision oncology,2022,2022-04-20,Y,,,,"Cancer is a leading cause of death, accounting for almost 10 million deaths annually worldwide. Personalised therapies harnessing genetic and clinical information may improve survival outcomes and reduce the side effects of treatments. The aim of this study is to appraise published evidence on clinicopathological factors and genetic mutations (single nucleotide polymorphisms [SNPs]) associated with prognosis across 11 cancer types: lung, colorectal, breast, prostate, melanoma, renal, glioma, bladder, leukaemia, endometrial, ovarian. A systematic literature search of PubMed/MEDLINE and Europe PMC was conducted from database inception to July 1, 2021. 2497 publications from PubMed/MEDLINE and 288 preprints from Europe PMC were included. Subsequent reference and citation search was conducted and a further 39 articles added. 2824 articles were reviewed by title/abstract and 247 articles were selected for systematic review. Majority of the articles were retrospective cohort studies focusing on one cancer type, 8 articles were on pan-cancer level and 6 articles were reviews. Studies analysing clinicopathological factors included 908,567 patients and identified 238 factors, including age, gender, stage, grade, size, site, subtype, invasion, lymph nodes. Genetic studies included 210,802 patients and identified 440 gene mutations associated with cancer survival, including genes TP53, BRCA1, BRCA2, BRAF, KRAS, BIRC5. We generated a comprehensive knowledge base of biomarkers that can be used to tailor treatment according to patients' unique genetic and clinical characteristics. Our pan-cancer investigation uncovers the biomarker landscape and their combined influence that may help guide health practitioners and researchers across the continuum of cancer care from drug development to long-term survivorship.",,pdf:https://www.nature.com/articles/s41698-022-00269-5.pdf; doi:https://doi.org/10.1038/s41698-022-00269-5; html:https://europepmc.org/articles/PMC9021198; pdf:https://europepmc.org/articles/PMC9021198?pdf=render 30984881,https://doi.org/10.12688/wellcomeopenres.15151.1,Causes of death among homeless people: a population-based cross-sectional study of linked hospitalisation and mortality data in England.,"Aldridge RW, Menezes D, Lewer D, Cornes M, Evans H, Blackburn RM, Byng R, Clark M, Denaxas S, Fuller J, Hewett N, Kilmister A, Luchenski S, Manthorpe J, McKee M, Neale J, Story A, Tinelli M, Whiteford M, Wurie F, Hayward A.",,Wellcome open research,2019,2019-03-11,Y,Mortality; Data Linkage; Hospital Discharge; Amenable Mortality; Homeless Health; Homeless Healthcare,,,"Background: Homelessness has increased by 165% since 2010 in England, with evidence from many settings that those affected experience high levels of mortality. In this paper we examine the contribution of different causes of death to overall mortality in homeless people recently admitted to hospitals in England with specialist integrated homeless health and care (SIHHC) schemes.  Methods: We undertook an analysis of linked hospital admission records and mortality data for people attending any one of 17 SIHHC schemes between 1st November 2013 and 30th November 2016. Our primary outcome was death, which we analysed in subgroups of 10th version international classification of disease (ICD-10) specific deaths; and deaths from amenable causes. We compared our results to a sample of people living in areas of high social deprivation (IMD5 group). Results: We collected data on 3,882 individual homeless hospital admissions that were linked to 600 deaths. The median age of death was 51.6 years (interquartile range 42.7-60.2) for SIHHC and 71.5 for the IMD5 (60.67-79.0).  The top three underlying causes of death by ICD-10 chapter in the SIHHC group were external causes of death (21.7%; 130/600), cancer (19.0%; 114/600) and digestive disease (19.0%; 114/600).  The percentage of deaths due to an amenable cause after age and sex weighting was 30.2% in the homeless SIHHC group (181/600) compared to 23.0% in the IMD5 group (578/2,512). Conclusion: Nearly one in three homeless deaths were due to causes amenable to timely and effective health care. The high burden of amenable deaths highlights the extreme health harms of homelessness and the need for greater emphasis on prevention of homelessness and early healthcare interventions.",,doi:https://doi.org/10.12688/wellcomeopenres.15151.1; html:https://europepmc.org/articles/PMC6449792; pdf:https://europepmc.org/articles/PMC6449792?pdf=render 34158612,https://doi.org/10.1038/s41366-021-00846-x,Effects of increased body mass index on employment status: a Mendelian randomisation study.,"Campbell DD, Green M, Davies N, Demou E, Ward J, Howe LD, Harrison S, Johnston KJA, Strawbridge RJ, Popham F, Smith DJ, Munafò MR, Katikireddi SV.",,International journal of obesity (2005),2021,2021-06-22,Y,,,,"

Background

The obesity epidemic may have substantial implications for the global workforce, including causal effects on employment, but clear evidence is lacking. Obesity may prevent people from being in paid work through poor health or through social discrimination. We studied genetic variants robustly associated with body mass index (BMI) to investigate its causal effects on employment.

Dataset/methods

White UK ethnicity participants of working age (men 40-64 years, women 40-59 years), with suitable genetic data were selected in the UK Biobank study (N = 230,791). Employment status was categorised in two ways: first, contrasting being in paid employment with any other status; and second, contrasting being in paid employment with sickness/disability, unemployment, early retirement and caring for home/family. Socioeconomic indicators also investigated were hours worked, household income, educational attainment and Townsend deprivation index (TDI). We conducted observational and two-sample Mendelian randomisation (MR) analyses to investigate the effect of increased BMI on employment-related outcomes.

Results

Regressions showed BMI associated with all the employment-related outcomes investigated. MR analyses provided evidence for higher BMI causing increased risk of sickness/disability (OR 1.08, 95% CI 1.04, 1.11, per 1 Kg/m2 BMI increase) and decreased caring for home/family (OR 0.96, 95% CI 0.93, 0.99), higher TDI (Beta 0.038, 95% CI 0.018, 0.059), and lower household income (OR 0.98, 95% CI 0.96, 0.99). In contrast, MR provided evidence for no causal effect of BMI on unemployment, early retirement, non-employment, hours worked or educational attainment. There was little evidence for causal effects differing by sex or age. Robustness tests yielded consistent results.

Discussion

BMI appears to exert a causal effect on employment status, largely by affecting an individual's health rather than through increased unemployment arising from social discrimination. The obesity epidemic may be contributing to increased worklessness and therefore could impose a substantial societal burden.",,pdf:https://www.nature.com/articles/s41366-021-00846-x.pdf; doi:https://doi.org/10.1038/s41366-021-00846-x; html:https://europepmc.org/articles/PMC8310793; pdf:https://europepmc.org/articles/PMC8310793?pdf=render @@ -944,9 +944,9 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 37367415,https://doi.org/10.3390/jcdd10060250,Risk Factors of Secondary Cardiovascular Events in a Multi-Ethnic Asian Population with Acute Myocardial Infarction: A Retrospective Cohort Study from Malaysia.,"Ismail SR, Mohammad MSF, Butterworth AS, Chowdhury R, Danesh J, Di Angelantonio E, Griffin SJ, Pennells L, Wood AM, Md Noh MF, Shah SA.",,Journal of cardiovascular development and disease,2023,2023-06-09,Y,Myocardial infarction; risk factors; Asian; Cardiovascular Mortality; Major Adverse Cardiovascular Events,,,"This retrospective cohort study investigated the incidence and risk factors of major adverse cardiovascular events (MACE) after 1 year of first-documented myocardial infarctions (MIs) in a multi-ethnic Asian population. Secondary MACE were observed in 231 (14.3%) individuals, including 92 (5.7%) cardiovascular-related deaths. Both histories of hypertension and diabetes were associated with secondary MACE after adjustment for age, sex, and ethnicity (HR 1.60 [95%CI 1.22-2.12] and 1.46 [95%CI 1.09-1.97], respectively). With further adjustments for traditional risk factors, individuals with conduction disturbances demonstrated higher risks of MACE: new left-bundle branch block (HR 2.86 [95%CI 1.15-6.55]), right-bundle branch block (HR 2.09 [95%CI 1.02-4.29]), and second-degree heart block (HR 2.45 [95%CI 0.59-10.16]). These associations were broadly similar across different age, sex, and ethnicity groups, although somewhat greater for history of hypertension and BMI among women versus men, for HbA1c control in individuals aged >50 years, and for LVEF ≤ 40% in those with Indian versus Chinese or Bumiputera ethnicities. Several traditional and cardiac risk factors are associated with a higher risk of secondary major adverse cardiovascular events. In addition to hypertension and diabetes, the identification of conduction disturbances in individuals with first-onset MI may be useful for the risk stratification of high-risk individuals.",,pdf:https://www.mdpi.com/2308-3425/10/6/250/pdf?version=1686288586; doi:https://doi.org/10.3390/jcdd10060250; html:https://europepmc.org/articles/PMC10299045; pdf:https://europepmc.org/articles/PMC10299045?pdf=render 38274035,https://doi.org/10.1136/bmjmed-2023-000738,Availability of results of clinical trials registered on EU Clinical Trials Register: cross sectional audit study.,"DeVito NJ, Morley J, Smith JA, Drysdale H, Goldacre B, Heneghan C.",,BMJ medicine,2024,2024-01-12,Y,"Ethics, Medical; Clinical Governance; Clinical Trial; Health Policy",,,"

Objective

To identify the availability of results for trials registered on the European Union Clinical Trials Register (EUCTR) compared with other dissemination routes to understand its value as a results repository.

Design

Cross sectional audit study.

Setting

EUCTR protocols and results sections, data extracted 1-3 December 2020.

Population

Random sample of 500 trials registered on EUCTR with a completion date of more than two years from the beginning of searches (ie, 1 December 2018).

Main outcome measures

Proportion of trials with results across the examined dissemination routes (EUCTR, ClinicalTrials.gov, ISRCTN registry, and journal publications), and for each dissemination route individually. Prespecified secondary outcomes were number and proportion of unique results, and the timing of results, for each dissemination route.

Results

In the sample of 500 trials, availability of results on EUCTR (53.2%, 95% confidence interval 48.8% to 57.6%) was similar to the peer reviewed literature (58.6%, 54.3% to 62.9%) and exceeded the proportion of results available on other registries with matched records. Among the 383 trials with any results, 55 (14.4%, 10.9% to 17.9%) were only available on EUCTR. Also, after the launch of the EUCTR results database, median time to results was fastest on EUCTR (1142 days, 95% confidence interval 812 to 1492), comparable with journal publications (1226 days, 1074 to 1551), and exceeding ClinicalTrials.gov (3321 days, 1653 to undefined). For 117 trials (23.4%, 19.7% to 27.1%), however, results were published elsewhere but not submitted to the EUCTR registry, and no results were located in any dissemination route for 117 trials (23.4%, 19.7% to 27.1).

Conclusions

EUCTR should be considered in results searches for systematic reviews and can help researchers and the public to access the results of clinical trials, unavailable elsewhere, in a timely way. Reporting requirements, such as the EU's, can help in avoiding research waste by ensuring results are reported. The registry's true value, however, is unrealised because of inadequate compliance with EU guidelines, and problems with data quality that complicate the routine use of the registry. As the EU transitions to a new registry, continuing to emphasise the importance of EUCTR and the provision of timely and complete data is critical. For the future, EUCTR will still hold important information from the past two decades of clinical research in Europe. With increased efforts from sponsors and regulators, the registry can continue to grow as a source of results of clinical trials, many of which might be unavailable from other dissemination routes.",,doi:https://doi.org/10.1136/bmjmed-2023-000738; html:https://europepmc.org/articles/PMC10806997; pdf:https://europepmc.org/articles/PMC10806997?pdf=render 37679419,https://doi.org/10.1038/s41588-023-01462-3,"GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification.","Lagou V, Jiang L, Ulrich A, Zudina L, González KSG, Balkhiyarova Z, Faggian A, Maina JG, Chen S, Todorov PV, Sharapov S, David A, Marullo L, Mägi R, Rujan RM, Ahlqvist E, Thorleifsson G, Gao Η, Εvangelou Ε, Benyamin B, Scott RA, Isaacs A, Zhao JH, Willems SM, Johnson T, Gieger C, Grallert H, Meisinger C, Müller-Nurasyid M, Strawbridge RJ, Goel A, Rybin D, Albrecht E, Jackson AU, Stringham HM, Corrêa IR, Farber-Eger E, Steinthorsdottir V, Uitterlinden AG, Munroe PB, Brown MJ, Schmidberger J, Holmen O, Thorand B, Hveem K, Wilsgaard T, Mohlke KL, Wang Z, GWA-PA Consortium, Shmeliov A, den Hoed M, Loos RJF, Kratzer W, Haenle M, Koenig W, Boehm BO, Tan TM, Tomas A, Salem V, Barroso I, Tuomilehto J, Boehnke M, Florez JC, Hamsten A, Watkins H, Njølstad I, Wichmann HE, Caulfield MJ, Khaw KT, van Duijn CM, Hofman A, Wareham NJ, Langenberg C, Whitfield JB, Martin NG, Montgomery G, Scapoli C, Tzoulaki I, Elliott P, Thorsteinsdottir U, Stefansson K, Brittain EL, McCarthy MI, Froguel P, Sexton PM, Wootten D, Groop L, Dupuis J, Meigs JB, Deganutti G, Demirkan A, Pers TH, Reynolds CA, Aulchenko YS, Kaakinen MA, Jones B, Prokopenko I, Meta-Analysis of Glucose and Insulin-Related Traits Consortium (MAGIC).",,Nature genetics,2023,2023-09-07,Y,,,,"Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on 'around the clock' glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstandardized conditions (random glucose (RG)) in 476,326 individuals of diverse ancestries and without diabetes enables locus discovery and innovative pathophysiological observations. We discovered 120 RG loci represented by 150 distinct signals, including 13 with sex-dimorphic effects, two cross-ancestry and seven rare frequency signals. Of these, 44 loci are new for glycemic traits. Regulatory, glycosylation and metagenomic annotations highlight ileum and colon tissues, indicating an underappreciated role of the gastrointestinal tract in controlling blood glucose. Functional follow-up and molecular dynamics simulations of lower frequency coding variants in glucagon-like peptide-1 receptor (GLP1R), a type 2 diabetes treatment target, reveal that optimal selection of GLP-1R agonist therapy will benefit from tailored genetic stratification. We also provide evidence from Mendelian randomization that lung function is modulated by blood glucose and that pulmonary dysfunction is a diabetes complication. Our investigation yields new insights into the biology of glucose regulation, diabetes complications and pathways for treatment stratification.",,pdf:https://www.nature.com/articles/s41588-023-01462-3.pdf; doi:https://doi.org/10.1038/s41588-023-01462-3; html:https://europepmc.org/articles/PMC10484788; pdf:https://europepmc.org/articles/PMC10484788?pdf=render -38811438,https://doi.org/10.1007/s00586-024-08315-5,Early evaluation of a natural language processing tool to improve access to educational resources for surgical patients.,"Booker J, Penn J, Noor K, Dobson RJB, Funnell JP, Koh CH, Khan DZ, Newall N, Rowland D, Sinha S, Williams SC, Sayal P, Marcus HJ.",,"European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society",2024,2024-05-30,N,Spine; Education; Machine Learning; Natural Language Processing; automation,,,"

Purpose

Accessible patient information sources are vital in educating patients about the benefits and risks of spinal surgery, which is crucial for obtaining informed consent. We aim to assess the effectiveness of a natural language processing (NLP) pipeline in recognizing surgical procedures from clinic letters and linking this with educational resources.

Methods

Retrospective examination of letters from patients seeking surgery for degenerative spinal disease at a single neurosurgical center. We utilized MedCAT, a named entity recognition and linking NLP, integrated into the electronic health record (EHR), which extracts concepts and links them to systematized nomenclature of medicine-clinical terms (SNOMED-CT). Investigators reviewed clinic letters, identifying words or phrases that described or identified operations and recording the SNOMED-CT terms as ground truth. This was compared to SNOMED-CT terms identified by the model, untrained on our dataset. A pipeline linking clinic letters to patient-specific educational resources was established, and precision, recall, and F1 scores were calculated.

Results

Across 199 letters the model identified 582 surgical procedures, and the overall pipeline after adding rules a total of 784 procedures (precision = 0.94, recall = 0.86, F1 = 0.91). Across 187 letters with identified SNOMED-CT terms the integrated pipeline linking education resources directly to the EHR was successful in 157 (78%) patients (precision = 0.99, recall = 0.87, F1 = 0.92).

Conclusions

NLP accurately identifies surgical procedures in pre-operative clinic letters within an untrained subspecialty. Performance varies among letter authors and depends on the language used by clinicians. The identified procedures can be linked to patient education resources, potentially improving patients' understanding of surgical procedures.",,doi:https://doi.org/10.1007/s00586-024-08315-5; doi:https://doi.org/10.1007/s00586-024-08315-5 34481555,https://doi.org/10.1016/s2213-8587(21)00207-2,"Identifying adults at high-risk for change in weight and BMI in England: a longitudinal, large-scale, population-based cohort study using electronic health records.","Katsoulis M, Lai AG, Diaz-Ordaz K, Gomes M, Pasea L, Banerjee A, Denaxas S, Tsilidis K, Lagiou P, Misirli G, Bhaskaran K, Wannamethee G, Dobson R, Batterham RL, Kipourou DK, Lumbers RT, Wen L, Wareham N, Langenberg C, Hemingway H.",,The lancet. Diabetes & endocrinology,2021,2021-09-02,Y,,,,"

Background

Targeted obesity prevention policies would benefit from the identification of population groups with the highest risk of weight gain. The relative importance of adult age, sex, ethnicity, geographical region, and degree of social deprivation on weight gain is not known. We aimed to identify high-risk groups for changes in weight and BMI using electronic health records (EHR).

Methods

In this longitudinal, population-based cohort study we used linked EHR data from 400 primary care practices (via the Clinical Practice Research Datalink) in England, accessed via the CALIBER programme. Eligible participants were aged 18-74 years, were registered at a general practice clinic, and had BMI and weight measurements recorded between Jan 1, 1998, and June 30, 2016, during the period when they had eligible linked data with at least 1 year of follow-up time. We calculated longitudinal changes in BMI over 1, 5, and 10 years, and investigated the absolute risk and odds ratios (ORs) of transitioning between BMI categories (underweight, normal weight, overweight, obesity class 1 and 2, and severe obesity [class 3]), as defined by WHO. The associations of demographic factors with BMI transitions were estimated by use of logistic regression analysis, adjusting for baseline BMI, family history of cardiovascular disease, use of diuretics, and prevalent chronic conditions.

Findings

We included 2 092 260 eligible individuals with more than 9 million BMI measurements in our study. Young adult age was the strongest risk factor for weight gain at 1, 5, and 10 years of follow-up. Compared with the oldest age group (65-74 years), adults in the youngest age group (18-24 years) had the highest OR (4·22 [95% CI 3·86-4·62]) and greatest absolute risk (37% vs 24%) of transitioning from normal weight to overweight or obesity at 10 years. Likewise, adults in the youngest age group with overweight or obesity at baseline were also at highest risk to transition to a higher BMI category; OR 4·60 (4·06-5·22) and absolute risk (42% vs 18%) of transitioning from overweight to class 1 and 2 obesity, and OR 5·87 (5·23-6·59) and absolute risk (22% vs 5%) of transitioning from class 1 and 2 obesity to class 3 obesity. Other demographic factors were consistently less strongly associated with these transitions; for example, the OR of transitioning from normal weight to overweight or obesity in people living in the most socially deprived versus least deprived areas was 1·23 (1·18-1·27), for men versus women was 1·12 (1·08-1·16), and for Black individuals versus White individuals was 1·13 (1·04-1·24). We provide an open access online risk calculator, and present high-resolution obesity risk charts over a 1-year, 5-year, and 10-year follow-up period.

Interpretation

A radical shift in policy is required to focus on individuals at the highest risk of weight gain (ie, young adults aged 18-24 years) for individual-level and population-level prevention of obesity and its long-term consequences for health and health care.

Funding

The British Hearth Foundation, Health Data Research UK, the UK Medical Research Council, and the National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S2213858721002072/pdf; doi:https://doi.org/10.1016/S2213-8587(21)00207-2; html:https://europepmc.org/articles/PMC8440227; pdf:https://europepmc.org/articles/PMC8440227?pdf=render 32626822,https://doi.org/10.1007/s41109-020-00273-3,Normalised degree variance.,"Smith KM, Escudero J.",,Applied network science,2020,2020-06-22,Y,,,,"Finding graph indices which are unbiased to network size and density is of high importance both within a given field and across fields for enhancing comparability of modern network science studies. The degree variance is an important metric for characterising network degree heterogeneity. Here, we provide an analytically valid normalisation of degree variance to replace previous normalisations which are either invalid or not applicable to all networks. It is shown that this normalisation provides equal values for graphs and their complements; it is maximal in the star graph (and its complement); and its expected value is constant with respect to density for Erdös-Rényi (ER) random graphs of the same size. We strengthen these results with model observations in ER random graphs, random geometric graphs, scale-free networks, random hierarchy networks and resting-state brain networks, showing that the proposed normalisation is generally less affected by both network size and density than previous normalisation attempts. The closed form expression proposed also benefits from high computational efficiency and straightforward mathematical analysis. Analysis of 184 real-world binary networks across different disciplines shows that normalised degree variance is not correlated with average degree and is robust to node and edge subsampling. Comparisons across subdomains of biological networks reveals greater degree heterogeneity among brain connectomes and food webs than in protein interaction networks.",,pdf:https://appliednetsci.springeropen.com/track/pdf/10.1007/s41109-020-00273-3; doi:https://doi.org/10.1007/s41109-020-00273-3; html:https://europepmc.org/articles/PMC7319291; pdf:https://europepmc.org/articles/PMC7319291?pdf=render +38811438,https://doi.org/10.1007/s00586-024-08315-5,Early evaluation of a natural language processing tool to improve access to educational resources for surgical patients.,"Booker J, Penn J, Noor K, Dobson RJB, Funnell JP, Koh CH, Khan DZ, Newall N, Rowland D, Sinha S, Williams SC, Sayal P, Marcus HJ.",,"European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society",2024,2024-05-30,N,Spine; Education; Machine Learning; Natural Language Processing; automation,,,"

Purpose

Accessible patient information sources are vital in educating patients about the benefits and risks of spinal surgery, which is crucial for obtaining informed consent. We aim to assess the effectiveness of a natural language processing (NLP) pipeline in recognizing surgical procedures from clinic letters and linking this with educational resources.

Methods

Retrospective examination of letters from patients seeking surgery for degenerative spinal disease at a single neurosurgical center. We utilized MedCAT, a named entity recognition and linking NLP, integrated into the electronic health record (EHR), which extracts concepts and links them to systematized nomenclature of medicine-clinical terms (SNOMED-CT). Investigators reviewed clinic letters, identifying words or phrases that described or identified operations and recording the SNOMED-CT terms as ground truth. This was compared to SNOMED-CT terms identified by the model, untrained on our dataset. A pipeline linking clinic letters to patient-specific educational resources was established, and precision, recall, and F1 scores were calculated.

Results

Across 199 letters the model identified 582 surgical procedures, and the overall pipeline after adding rules a total of 784 procedures (precision = 0.94, recall = 0.86, F1 = 0.91). Across 187 letters with identified SNOMED-CT terms the integrated pipeline linking education resources directly to the EHR was successful in 157 (78%) patients (precision = 0.99, recall = 0.87, F1 = 0.92).

Conclusions

NLP accurately identifies surgical procedures in pre-operative clinic letters within an untrained subspecialty. Performance varies among letter authors and depends on the language used by clinicians. The identified procedures can be linked to patient education resources, potentially improving patients' understanding of surgical procedures.",,doi:https://doi.org/10.1007/s00586-024-08315-5; doi:https://doi.org/10.1007/s00586-024-08315-5 37578823,https://doi.org/10.2196/45233,Challenges in Using mHealth Data From Smartphones and Wearable Devices to Predict Depression Symptom Severity: Retrospective Analysis.,"Sun S, Folarin AA, Zhang Y, Cummins N, Garcia-Dias R, Stewart C, Ranjan Y, Rashid Z, Conde P, Laiou P, Sankesara H, Matcham F, Leightley D, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Simblett S, Nica R, Rintala A, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BWJH, Vairavan S, Narayan VA, Annas P, Hotopf M, Dobson RJB, RADAR-CNS Consortium.",,Journal of medical Internet research,2023,2023-08-14,Y,Depression; Mobile phone; Missing Data; Smartphones; Behavioral Patterns; Digital Phenotypes; Mobile Health; Wearable Devices,,,"

Background

Major depressive disorder (MDD) affects millions of people worldwide, but timely treatment is not often received owing in part to inaccurate subjective recall and variability in the symptom course. Objective and frequent MDD monitoring can improve subjective recall and help to guide treatment selection. Attempts have been made, with varying degrees of success, to explore the relationship between the measures of depression and passive digital phenotypes (features) extracted from smartphones and wearables devices to remotely and continuously monitor changes in symptomatology. However, a number of challenges exist for the analysis of these data. These include maintaining participant engagement over extended time periods and therefore understanding what constitutes an acceptable threshold of missing data; distinguishing between the cross-sectional and longitudinal relationships for different features to determine their utility in tracking within-individual longitudinal variation or screening individuals at high risk; and understanding the heterogeneity with which depression manifests itself in behavioral patterns quantified by the passive features.

Objective

We aimed to address these 3 challenges to inform future work in stratified analyses.

Methods

Using smartphone and wearable data collected from 479 participants with MDD, we extracted 21 features capturing mobility, sleep, and smartphone use. We investigated the impact of the number of days of available data on feature quality using the intraclass correlation coefficient and Bland-Altman analysis. We then examined the nature of the correlation between the 8-item Patient Health Questionnaire (PHQ-8) depression scale (measured every 14 days) and the features using the individual-mean correlation, repeated measures correlation, and linear mixed effects model. Furthermore, we stratified the participants based on their behavioral difference, quantified by the features, between periods of high (depression) and low (no depression) PHQ-8 scores using the Gaussian mixture model.

Results

We demonstrated that at least 8 (range 2-12) days were needed for reliable calculation of most of the features in the 14-day time window. We observed that features such as sleep onset time correlated better with PHQ-8 scores cross-sectionally than longitudinally, whereas features such as wakefulness after sleep onset correlated well with PHQ-8 longitudinally but worse cross-sectionally. Finally, we found that participants could be separated into 3 distinct clusters according to their behavioral difference between periods of depression and periods of no depression.

Conclusions

This work contributes to our understanding of how these mobile health-derived features are associated with depression symptom severity to inform future work in stratified analyses.",,pdf:https://www.jmir.org/2023/1/e45233/PDF; doi:https://doi.org/10.2196/45233; html:https://europepmc.org/articles/PMC10463088 34870259,https://doi.org/10.1016/j.xgen.2021.100005,Sequencing-based genome-wide association studies reporting standards.,"McMahon A, Lewis E, Buniello A, Cerezo M, Hall P, Sollis E, Parkinson H, Hindorff LA, Harris LW, MacArthur JAL.",,Cell genomics,2021,2021-10-01,Y,,,,"Genome sequencing has recently become a viable genotyping technology for use in genome-wide association studies (GWASs), offering the potential to analyze a broader range of genome-wide variation, including rare variants. To survey current standards, we assessed the content and quality of reporting of statistical methods, analyses, results, and datasets in 167 exome- or genome-wide-sequencing-based GWAS publications published from 2014 to 2020; 81% of publications included tests of aggregate association across multiple variants, with multiple test models frequently used. We observed a lack of standardized terms and incomplete reporting of datasets, particularly for variants analyzed in aggregate tests. We also find a lower frequency of sharing of summary statistics compared with array-based GWASs. Reporting standards and increased data sharing are required to ensure sequencing-based association study data are findable, interoperable, accessible, and reusable (FAIR). To support that, we recommend adopting the standard terminology of sequencing-based GWAS (seqGWAS). Further, we recommend that single-variant analyses be reported following the same standards and conventions as standard array-based GWASs and be shared in the GWAS Catalog. We also provide initial recommended standards for aggregate analyses metadata and summary statistics.",,doi:https://doi.org/10.1016/j.xgen.2021.100005; doi:https://doi.org/10.1016/j.xgen.2021.100005; html:https://europepmc.org/articles/PMC8637874; pdf:https://europepmc.org/articles/PMC8637874?pdf=render 33722197,https://doi.org/10.1186/s12879-021-05951-w,Renin-angiotensin system inhibitors and susceptibility to COVID-19 in patients with hypertension: a propensity score-matched cohort study in primary care.,"Haroon S, Subramanian A, Cooper J, Anand A, Gokhale K, Byne N, Dhalla S, Acosta-Mena D, Taverner T, Okoth K, Wang J, Chandan JS, Sainsbury C, Zemedikun DT, Thomas GN, Parekh D, Marshall T, Sapey E, Adderley NJ, Nirantharakumar K.",,BMC infectious diseases,2021,2021-03-15,Y,,,,"

Introduction

Renin-angiotensin system (RAS) inhibitors have been postulated to influence susceptibility to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This study investigated whether there is an association between their prescription and the incidence of COVID-19 and all-cause mortality.

Methods

We conducted a propensity-score matched cohort study comparing the incidence of COVID-19 among patients with hypertension prescribed angiotensin-converting enzyme I (ACE) inhibitors or angiotensin II type-1 receptor blockers (ARBs) to those treated with calcium channel blockers (CCBs) in a large UK-based primary care database (The Health Improvement Network). We estimated crude incidence rates for confirmed/suspected COVID-19 in each drug exposure group. We used Cox proportional hazards models to produce adjusted hazard ratios for COVID-19. We assessed all-cause mortality as a secondary outcome.

Results

The incidence rate of COVID-19 among users of ACE inhibitors and CCBs was 9.3 per 1000 person-years (83 of 18,895 users [0.44%]) and 9.5 per 1000 person-years (85 of 18,895 [0.45%]), respectively. The adjusted hazard ratio was 0.92 (95% CI 0.68 to 1.26). The incidence rate among users of ARBs was 15.8 per 1000 person-years (79 out of 10,623 users [0.74%]). The adjusted hazard ratio was 1.38 (95% CI 0.98 to 1.95). There were no significant associations between use of RAS inhibitors and all-cause mortality.

Conclusion

Use of ACE inhibitors was not associated with the risk of COVID-19 whereas use of ARBs was associated with a statistically non-significant increase compared to the use of CCBs. However, no significant associations were observed between prescription of either ACE inhibitors or ARBs and all-cause mortality.",,pdf:https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-021-05951-w; doi:https://doi.org/10.1186/s12879-021-05951-w; html:https://europepmc.org/articles/PMC7957446; pdf:https://europepmc.org/articles/PMC7957446?pdf=render @@ -955,22 +955,22 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 38193339,https://doi.org/10.1161/jaha.123.029827,Soluble Suppression of Tumorigenicity-2 Predicts Mortality and Right Heart Failure in Patients With a Left Ventricular Assist Device.,"Numan L, Aarts E, Ramjankhan F, Oerlemans MIF, van der Meer MG, de Jonge N, Oppelaar AM, Kemperman H, Asselbergs FW, Van Laake LW.",,Journal of the American Heart Association,2024,2024-01-09,Y,Right Heart Failure; Left Ventricular Assist Device; End‐stage Heart Failure; Soluble Suppression Of Tumorigenicity‐2,,,"

Background

Soluble suppression of tumorigenicity-2 (sST2) predicts mortality in patients with heart failure. The predictive value of sST2 in patients with a left ventricular assist device remains unknown. Therefore, we studied the relationship between sST2 and outcome after left ventricular assist device implantation.

Methods and results

sST2 levels of patients with a left ventricular assist device implanted between January 2015 and December 2022 were included in this observational study. The median follow-up was 25 months, during which 1573 postoperative sST2 levels were measured in 199 patients, with a median of 29 ng/mL. Survival of patients with normal and elevated preoperative levels was compared using Kaplan-Meier analysis, which did not differ significantly (P=0.22) between both groups. The relationship between postoperative sST2, survival, and right heart failure was evaluated using a joint model, which showed a significant relationship between the absolute sST2 level and mortality, with a hazard ratio (HR) of 1.20 (95% CI, 1.10-1.130; P<0.01) and an HR of 1.22 (95% CI, 1.07-1.39; P=0.01) for right heart failure, both per 10-unit sST2 increase. The sST2 instantaneous change was not predictive for survival or right heart failure (P=0.99 and P=0.94, respectively). Multivariate joint model analysis showed a significant relationship between sST2 with mortality adjusted for NT-proBNP (N-terminal pro-B-type natriuretic peptide), with an HR of 1.19 (95% CI, 1.00-1.42; P=0.05), whereas the HR of right heart failure was not significant (1.22 [95% CI, 0.94-1.59]; P=0.14), both per 10-unit sST2 increase.

Conclusions

Time-dependent postoperative sST2 predicts all-cause mortality after left ventricular assist device implantation after adjustment for NT-proBNP. Future research is warranted into possible target interventions and the optimal monitoring frequency.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.029827; doi:https://doi.org/10.1161/JAHA.123.029827; html:https://europepmc.org/articles/PMC10926819; pdf:https://europepmc.org/articles/PMC10926819?pdf=render 36813664,https://doi.org/10.1016/j.injury.2023.02.029,Friction burns in cyclists: An under-recognised problem.,"Tracy LM, Gabbe BJ, Beck B.",,Injury,2023,2023-02-15,N,Cycling; Australia; Burn; New Zealand; Registry; Friction,,,"

Introduction

Cycling-related friction burns, also known as abrasions or ""road rash"", can occur when cyclists are involved in a fall or a collision. However, less is known about this type of injury as they are often overshadowed by concurrent traumatic and/or orthopaedic injuries. The aims of this project were to describe the nature and severity of friction burns in cyclists admitted to hospitals with specialist burn services in Australia and New Zealand.

Methods

A review of cycling-related friction burns recorded by the Burns Registry of Australia and New Zealand was undertaken. Summary statistics described demographic, injury event and severity, and in-hospital management data for this cohort of patients.

Results

Between July 2009 and June 2021, 143 cycling-related friction burn admissions were identified (accounting for 0.4% of all burns admissions during the study period). Seventy-six percent of patients with a cycling-related friction burn were male, and the median (interquartile range) of patients was 14 (5-41) years. The greatest proportion of cycling-related friction burns were attributed to non-collision events, namely falls (44% of all cases) and body parts being caught or coming into contact with the bicycle (27% of all cases). Although 89% of patients had a burn affecting less than five percent of their body, 71% of patients underwent a burn wound management procedure in theatre such as debridement and/or skin grafting.

Conclusions

In summary, friction burns in cyclists admitted to participating services were rare. Despite this, there remains opportunities to better understand these events to inform the development of interventions to reduce burn injury in cyclists.",,doi:https://doi.org/10.1016/j.injury.2023.02.029 37828025,https://doi.org/10.1038/s41467-023-41876-5,ADRA2A and IRX1 are putative risk genes for Raynaud's phenomenon.,"Hartmann S, Yasmeen S, Jacobs BM, Denaxas S, Pirmohamed M, Gamazon ER, Caulfield MJ, Genes & Health Research Team, Hemingway H, Pietzner M, Langenberg C.",,Nature communications,2023,2023-10-12,Y,,,,"Raynaud's phenomenon (RP) is a common vasospastic disorder that causes severe pain and ulcers, but despite its high reported heritability, no causal genes have been robustly identified. We conducted a genome-wide association study including 5,147 RP cases and 439,294 controls, based on diagnoses from electronic health records, and identified three unreported genomic regions associated with the risk of RP (p < 5 × 10-8). We prioritized ADRA2A (rs7090046, odds ratio (OR) per allele: 1.26; 95%-CI: 1.20-1.31; p < 9.6 × 10-27) and IRX1 (rs12653958, OR: 1.17; 95%-CI: 1.12-1.22, p < 4.8 × 10-13) as candidate causal genes through integration of gene expression in disease relevant tissues. We further identified a likely causal detrimental effect of low fasting glucose levels on RP risk (rG = -0.21; p-value = 2.3 × 10-3), and systematically highlighted drug repurposing opportunities, like the antidepressant mirtazapine. Our results provide the first robust evidence for a strong genetic contribution to RP and highlight a so far underrated role of α2A-adrenoreceptor signalling, encoded at ADRA2A, as a possible mechanism for hypersensitivity to catecholamine-induced vasospasms.",,pdf:https://www.nature.com/articles/s41467-023-41876-5.pdf; doi:https://doi.org/10.1038/s41467-023-41876-5; html:https://europepmc.org/articles/PMC10570309; pdf:https://europepmc.org/articles/PMC10570309?pdf=render +33813844,https://doi.org/10.1161/hypertensionaha.120.16534,Relationship Between Blood Pressure and Incident Cardiovascular Disease: Linear and Nonlinear Mendelian Randomization Analyses.,"Malik R, Georgakis MK, Vujkovic M, Damrauer SM, Elliott P, Karhunen V, Giontella A, Fava C, Hellwege JN, Shuey MM, Edwards TL, Rogne T, Åsvold BO, Brumpton BM, Burgess S, Dichgans M, Gill D.",,"Hypertension (Dallas, Tex. : 1979)",2021,2021-04-05,Y,Hypertension; Blood pressure; Stroke; coronary artery disease; Primary Prevention,,,[Figure: see text].,,pdf:https://www.ahajournals.org/doi/pdf/10.1161/HYPERTENSIONAHA.120.16534; doi:https://doi.org/10.1161/HYPERTENSIONAHA.120.16534; html:https://europepmc.org/articles/PMC8115430; pdf:https://europepmc.org/articles/PMC8115430?pdf=render 37773956,https://doi.org/10.1371/journal.pone.0292240,Prioritising cardiovascular disease risk assessment to high risk individuals based on primary care records.,"Chung R, Xu Z, Arnold M, Stevens D, Keogh R, Barrett J, Harrison H, Pennells L, Kim LG, DiAngelantonio E, Paige E, Usher-Smith JA, Wood AM.",,PloS one,2023,2023-09-29,Y,,,,"

Objective

To provide quantitative evidence for systematically prioritising individuals for full formal cardiovascular disease (CVD) risk assessment using primary care records with a novel tool (eHEART) with age- and sex- specific risk thresholds.

Methods and analysis

eHEART was derived using landmark Cox models for incident CVD with repeated measures of conventional CVD risk predictors in 1,642,498 individuals from the Clinical Practice Research Datalink. Using 119,137 individuals from UK Biobank, we modelled the implications of initiating guideline-recommended statin therapy using eHEART with age- and sex-specific prioritisation thresholds corresponding to 5% false negative rates to prioritise adults aged 40-69 years in a population in England for invitation to a formal CVD risk assessment.

Results

Formal CVD risk assessment on all adults would identify 76% and 49% of future CVD events amongst men and women respectively, and 93 (95% CI: 90, 95) men and 279 (95% CI: 259, 297) women would need to be screened (NNS) to prevent one CVD event. In contrast, if eHEART was first used to prioritise individuals for formal CVD risk assessment, we would identify 73% and 47% of future events amongst men and women respectively, and a NNS of 75 (95% CI: 72, 77) men and 162 (95% CI: 150, 172) women. Replacing the age- and sex-specific prioritisation thresholds with a 10% threshold identify around 10% less events.

Conclusions

The use of prioritisation tools with age- and sex-specific thresholds could lead to more efficient CVD assessment programmes with only small reductions in effectiveness at preventing new CVD events.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0292240&type=printable; doi:https://doi.org/10.1371/journal.pone.0292240; html:https://europepmc.org/articles/PMC10540947; pdf:https://europepmc.org/articles/PMC10540947?pdf=render 36299367,https://doi.org/10.1183/23120541.00211-2022,Mortality associated with metabolic syndrome in people with COPD managed in primary care.,"Karsanji U, Evans RA, Quint JK, Khunti K, Lawson CA, Petherick E, Greening NJ, Singh SJ, Richardson M, Steiner MC.",,ERJ open research,2022,2022-10-24,Y,,,,"

Objective

The prevalence of metabolic syndrome (MetS) has been reported to be higher in selected populations of people with COPD. The impact of MetS on mortality in COPD is unknown. We used routinely collected healthcare data to estimate the prevalence of MetS in people with COPD managed in primary care and determine its impact on 5-year mortality.

Methods

Records from 103 955 patients with COPD from the Clinical Practice Research Datalink (CPRD-GOLD) between 2009 to 2017 were scrutinised. MetS was defined as the presence of three or more of: obesity, hypertension, lowered high-density lipoprotein cholesterol, elevated triglycerides or type 2 diabetes mellitus (T2DM). Univariate and multivariable Cox regression models were constructed to determine the prognostic impact of MetS on 5-year mortality. Similar univariate models were constructed for individual components of the definition of MetS.

Results

The prevalence of MetS in the COPD cohort was 10.1%. Univariate analyses showed the presence of MetS increased mortality (hazard ratio (HR) 1.19, 95% CI: 1.12-1.27, p<0.001), but this risk was substantially attenuated in the multivariable analysis (HR 1.06, 95% CI: 0.99-1.13, p=0.085). The presence of hypertension (HR 1.70, 95% CI: 1.63-1.77, p<0.001) and T2DM (HR 1.41, 95% CI: 1.34-1.48, p<0.001) increased and obesity (HR 0.74, 95% CI: 0.71-0.78, p<0.001) reduced mortality risk.

Conclusion

MetS in patients with COPD is associated with higher 5-year mortality, but this impact was minimal when adjusted for indices of COPD disease severity and other comorbidities. Individual components of the MetS definition exerted differential impacts on mortality suggesting limitation to the use of MetS as a multicomponent condition in predicting outcome in COPD.",,pdf:https://openres.ersjournals.com/content/erjor/8/4/00211-2022.full.pdf; doi:https://doi.org/10.1183/23120541.00211-2022; html:https://europepmc.org/articles/PMC9589337; pdf:https://europepmc.org/articles/PMC9589337?pdf=render -33813844,https://doi.org/10.1161/hypertensionaha.120.16534,Relationship Between Blood Pressure and Incident Cardiovascular Disease: Linear and Nonlinear Mendelian Randomization Analyses.,"Malik R, Georgakis MK, Vujkovic M, Damrauer SM, Elliott P, Karhunen V, Giontella A, Fava C, Hellwege JN, Shuey MM, Edwards TL, Rogne T, Åsvold BO, Brumpton BM, Burgess S, Dichgans M, Gill D.",,"Hypertension (Dallas, Tex. : 1979)",2021,2021-04-05,Y,Hypertension; Blood pressure; Stroke; coronary artery disease; Primary Prevention,,,[Figure: see text].,,pdf:https://www.ahajournals.org/doi/pdf/10.1161/HYPERTENSIONAHA.120.16534; doi:https://doi.org/10.1161/HYPERTENSIONAHA.120.16534; html:https://europepmc.org/articles/PMC8115430; pdf:https://europepmc.org/articles/PMC8115430?pdf=render 32997638,https://doi.org/10.1109/jbhi.2020.3027987,A Novel Intelligent Computational Approach to Model Epidemiological Trends and Assess the Impact of Non-Pharmacological Interventions for COVID-19.,"Ren J, Yan Y, Zhao H, Ma P, Zabalza J, Hussain Z, Luo S, Dai Q, Zhao S, Sheikh A, Hussain A, Li H.",,IEEE journal of biomedical and health informatics,2020,2020-12-04,Y,,,,"The novel coronavirus disease 2019 (COVID-19) pandemic has led to a worldwide crisis in public health. It is crucial we understand the epidemiological trends and impact of non-pharmacological interventions (NPIs), such as lockdowns for effective management of the disease and control of its spread. We develop and validate a novel intelligent computational model to predict epidemiological trends of COVID-19, with the model parameters enabling an evaluation of the impact of NPIs. By representing the number of daily confirmed cases (NDCC) as a time-series, we assume that, with or without NPIs, the pattern of the pandemic satisfies a series of Gaussian distributions according to the central limit theorem. The underlying pandemic trend is first extracted using a singular spectral analysis (SSA) technique, which decomposes the NDCC time series into the sum of a small number of independent and interpretable components such as a slow varying trend, oscillatory components and structureless noise. We then use a mixture of Gaussian fitting (GF) to derive a novel predictive model for the SSA extracted NDCC incidence trend, with the overall model termed SSA-GF. Our proposed model is shown to accurately predict the NDCC trend, peak daily cases, the length of the pandemic period, the total confirmed cases and the associated dates of the turning points on the cumulated NDCC curve. Further, the three key model parameters, specifically, the amplitude (alpha), mean (mu), and standard deviation (sigma) are linked to the underlying pandemic patterns, and enable a directly interpretable evaluation of the impact of NPIs, such as strict lockdowns and travel restrictions. The predictive model is validated using available data from China and South Korea, and new predictions are made, partially requiring future validation, for the cases of Italy, Spain, the UK and the USA. Comparative results demonstrate that the introduction of consistent control measures across countries can lead to development of similar parametric models, reflected in particular by relative variations in their underlying sigma, alpha and mu values. The paper concludes with a number of open questions and outlines future research directions.",,pdf:https://ieeexplore.ieee.org/ielx7/6221020/9281055/09210178.pdf; doi:https://doi.org/10.1109/JBHI.2020.3027987; html:https://europepmc.org/articles/PMC8545177; pdf:https://europepmc.org/articles/PMC8545177?pdf=render -37667806,https://doi.org/10.1177/17562848231193211,Planning to conceive within a year is associated with better pregnancy-specific disease-related patient knowledge and better medication adherence in women of childbearing age with inflammatory bowel disease.,"Selinger CP, Laube R, Steed H, Brookes M, BioResource N, Leong RWL.",,Therapeutic advances in gastroenterology,2023,2023-08-30,Y,Pregnancy; Inflammatory Bowel Disease; Patient Knowledge; Medication Adherence,,,"

Background

Adherence to inflammatory bowel disease (IBD) medication is crucial to maintain remission, especially during pregnancy.

Objective

To examine the influence of family planning and pregnancy-related patient knowledge regarding IBD and pregnancy on adherence.

Design

Cross-sectional survey study.

Methods

We surveyed female patients with IBD aged 18-35 years, who at recruitment to the UK IBD BioResource had not had children. We elicited disease and treatment history, demographics and family planning status via an online questionnaire. Patient knowledge as assessed by the validated Crohn's and Colitis Pregnancy Knowledge Score (CCPKnow) and adherence by visual analogue scale (VAS).

Results

In 326 responders (13.8% response rate), good adherence (VAS ⩾ 80) was found in only 38.35%. Disease- and treatment-related factors were not significantly associated with good adherence, except for methotrexate (70.0% adherent of 10 exposed patients versus 37.2% non-exposed; p = 0.036). Patients planning pregnancy for the next year were more often adherent (59.0% versus 35.5%; p = 0.019) and knowledgeable (median CCPKnow 8 versus 7; p = 0.035) compared to those in other family planning categories. Pregnancy-related patient knowledge was significantly associated with adherence (Pearson correlation 0.141; p = 0.015). Adherent patients had significantly higher CCPKnow scores than non-adherent patients (median 8 versus 6; p = 0.009). On binary regression analysis, only planning to conceive within 12 months was independently associated with better adherence (p = 0.016), but not methotrexate exposure (p = 0.076) and CCPKnow (p = 0.056).

Conclusions

In a cohort of women of childbearing age with IBD overall medication, adherence was low. Planning to conceive within the next year was associated with better adherence and greater patient knowledge.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/17562848231193211; doi:https://doi.org/10.1177/17562848231193211; html:https://europepmc.org/articles/PMC10475232; pdf:https://europepmc.org/articles/PMC10475232?pdf=render 31607513,https://doi.org/10.1016/j.cell.2019.08.051,"Genome-wide Association Studies in Ancestrally Diverse Populations: Opportunities, Methods, Pitfalls, and Recommendations.","Peterson RE, Kuchenbaecker K, Walters RK, Chen CY, Popejoy AB, Periyasamy S, Lam M, Iyegbe C, Strawbridge RJ, Brick L, Carey CE, Martin AR, Meyers JL, Su J, Chen J, Edwards AC, Kalungi A, Koen N, Majara L, Schwarz E, Smoller JW, Stahl EA, Sullivan PF, Vassos E, Mowry B, Prieto ML, Cuellar-Barboza A, Bigdeli TB, Edenberg HJ, Huang H, Duncan LE.",,Cell,2019,2019-10-10,N,Population genetics; Diversity; Psychiatry; complex disease; Gwas; Ancestry; Admixed Populations; Trans-ancestry; Cross-ancestry; Trans-ethnic,,,"Genome-wide association studies (GWASs) have focused primarily on populations of European descent, but it is essential that diverse populations become better represented. Increasing diversity among study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. To facilitate and promote research in multi-ancestry and admixed cohorts, we outline key methodological considerations and highlight opportunities, challenges, solutions, and areas in need of development. Despite the perception that analyzing genetic data from diverse populations is difficult, it is scientifically and ethically imperative, and there is an expanding analytical toolbox to do it well.",,pdf:http://www.cell.com/article/S0092867419310025/pdf; doi:https://doi.org/10.1016/j.cell.2019.08.051; html:https://europepmc.org/articles/PMC6939869; pdf:https://europepmc.org/articles/PMC6939869?pdf=render; doi:https://doi.org/10.1016/j.cell.2019.08.051 +37667806,https://doi.org/10.1177/17562848231193211,Planning to conceive within a year is associated with better pregnancy-specific disease-related patient knowledge and better medication adherence in women of childbearing age with inflammatory bowel disease.,"Selinger CP, Laube R, Steed H, Brookes M, BioResource N, Leong RWL.",,Therapeutic advances in gastroenterology,2023,2023-08-30,Y,Pregnancy; Inflammatory Bowel Disease; Patient Knowledge; Medication Adherence,,,"

Background

Adherence to inflammatory bowel disease (IBD) medication is crucial to maintain remission, especially during pregnancy.

Objective

To examine the influence of family planning and pregnancy-related patient knowledge regarding IBD and pregnancy on adherence.

Design

Cross-sectional survey study.

Methods

We surveyed female patients with IBD aged 18-35 years, who at recruitment to the UK IBD BioResource had not had children. We elicited disease and treatment history, demographics and family planning status via an online questionnaire. Patient knowledge as assessed by the validated Crohn's and Colitis Pregnancy Knowledge Score (CCPKnow) and adherence by visual analogue scale (VAS).

Results

In 326 responders (13.8% response rate), good adherence (VAS ⩾ 80) was found in only 38.35%. Disease- and treatment-related factors were not significantly associated with good adherence, except for methotrexate (70.0% adherent of 10 exposed patients versus 37.2% non-exposed; p = 0.036). Patients planning pregnancy for the next year were more often adherent (59.0% versus 35.5%; p = 0.019) and knowledgeable (median CCPKnow 8 versus 7; p = 0.035) compared to those in other family planning categories. Pregnancy-related patient knowledge was significantly associated with adherence (Pearson correlation 0.141; p = 0.015). Adherent patients had significantly higher CCPKnow scores than non-adherent patients (median 8 versus 6; p = 0.009). On binary regression analysis, only planning to conceive within 12 months was independently associated with better adherence (p = 0.016), but not methotrexate exposure (p = 0.076) and CCPKnow (p = 0.056).

Conclusions

In a cohort of women of childbearing age with IBD overall medication, adherence was low. Planning to conceive within the next year was associated with better adherence and greater patient knowledge.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/17562848231193211; doi:https://doi.org/10.1177/17562848231193211; html:https://europepmc.org/articles/PMC10475232; pdf:https://europepmc.org/articles/PMC10475232?pdf=render 37794871,https://doi.org/10.1093/ehjdh/ztad044,An artificial intelligence tool for automated analysis of large-scale unstructured clinical cine cardiac magnetic resonance databases.,"Mariscal-Harana J, Asher C, Vergani V, Rizvi M, Keehn L, Kim RJ, Judd RM, Petersen SE, Razavi R, King AP, Ruijsink B, Puyol-Antón E.",,European heart journal. Digital health,2023,2023-07-13,Y,Artificial intelligence; Quality control; Cardiac function; Cardiac Segmentation; Cardiac Magnetic Resonance,,,"

Aims

Artificial intelligence (AI) techniques have been proposed for automating analysis of short-axis (SAX) cine cardiac magnetic resonance (CMR), but no CMR analysis tool exists to automatically analyse large (unstructured) clinical CMR datasets. We develop and validate a robust AI tool for start-to-end automatic quantification of cardiac function from SAX cine CMR in large clinical databases.

Methods and results

Our pipeline for processing and analysing CMR databases includes automated steps to identify the correct data, robust image pre-processing, an AI algorithm for biventricular segmentation of SAX CMR and estimation of functional biomarkers, and automated post-analysis quality control to detect and correct errors. The segmentation algorithm was trained on 2793 CMR scans from two NHS hospitals and validated on additional cases from this dataset (n = 414) and five external datasets (n = 6888), including scans of patients with a range of diseases acquired at 12 different centres using CMR scanners from all major vendors. Median absolute errors in cardiac biomarkers were within the range of inter-observer variability: <8.4 mL (left ventricle volume), <9.2 mL (right ventricle volume), <13.3 g (left ventricular mass), and <5.9% (ejection fraction) across all datasets. Stratification of cases according to phenotypes of cardiac disease and scanner vendors showed good performance across all groups.

Conclusion

We show that our proposed tool, which combines image pre-processing steps, a domain-generalizable AI algorithm trained on a large-scale multi-domain CMR dataset and quality control steps, allows robust analysis of (clinical or research) databases from multiple centres, vendors, and cardiac diseases. This enables translation of our tool for use in fully automated processing of large multi-centre databases.",,pdf:https://academic.oup.com/ehjdh/advance-article-pdf/doi/10.1093/ehjdh/ztad044/50878931/ztad044.pdf; doi:https://doi.org/10.1093/ehjdh/ztad044; html:https://europepmc.org/articles/PMC10545512; pdf:https://europepmc.org/articles/PMC10545512?pdf=render 35277405,https://doi.org/10.1136/bmjopen-2021-055070,Predictors of falls and fractures leading to hospitalisation in 36 101 people with affective disorders: a large representative cohort study.,"Ma R, Perera G, Romano E, Vancampfort D, Koyanagi A, Stewart R, Mueller C, Stubbs B.",,BMJ open,2022,2022-03-11,Y,Mental health; Anxiety Disorders; Adult Psychiatry; Depression & Mood Disorders,,,"

Objectives

To investigate predictors of falls and fractures leading to hospitalisation in people with affective disorders.

Design

Cohort study.

Setting

The South London and Maudsley National Health Service (NHS) Foundation Trust (SLaM) Biomedical Research Centre (BRC) Case Register.

Participants

A large cohort of people with affective disorders (International Classification of Diseases- 10th version [ICD-10] codes F30-F34) diagnosed between January 2008 and March 2016 was assembled using data from the SLaM BRC Case Register.

Primary and secondary outcome measures

Falls and fractures leading to hospitalisation were ascertained from linked national hospitalisation data. Multivariable Cox proportional hazards analyses were administrated to identify predictors of first falls and fractures.

Results

Of 36 101 people with affective disorders (mean age 44.4 years, 60.2% female), 816 (incidence rate 9.91 per 1000 person-years) and 1117 (incidence rate 11.92 per 1000 person-years) experienced either a fall or fracture, respectively. In multivariable analyses, older age, analgesic use, increased physical illness burden, previous hospital admission due to certain comorbid physical illnesses and increase in attendances to accident and emergency services following diagnosis were significant risk factors for both falls and fractures. Having a history of falls was a strong risk factor for recurrent falls, and a previous fracture was also associated with future fractures.

Conclusions

Over a mean 5 years' follow-up, approximately 8% of people with affective disorders were hospitalised with a fall or fracture. Several similar factors were found to predict risk of falls and fracture, for example, older age, comorbid physical disorders and analgesic use. Routine screening for bone mineral density and fall prevention programmes should be considered for this clinical group.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/3/e055070.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055070; html:https://europepmc.org/articles/PMC8919445; pdf:https://europepmc.org/articles/PMC8919445?pdf=render 33280008,https://doi.org/10.1093/cercor/bhaa345,Hierarchical Complexity of the Macro-Scale Neonatal Brain.,"Blesa M, Galdi P, Cox SR, Sullivan G, Stoye DQ, Lamb GJ, Quigley AJ, Thrippleton MJ, Escudero J, Bastin ME, Smith KM, Boardman JP.",,"Cerebral cortex (New York, N.Y. : 1991)",2021,2021-03-01,Y,Newborn; Network Analysis; Developing Brain; Dmri; Structural Connectome; Hierarchical Complexity,,,"The human adult structural connectome has a rich nodal hierarchy, with highly diverse connectivity patterns aligned to the diverse range of functional specializations in the brain. The emergence of this hierarchical complexity in human development is unknown. Here, we substantiate the hierarchical tiers and hierarchical complexity of brain networks in the newborn period, assess correspondences with hierarchical complexity in adulthood, and investigate the effect of preterm birth, a leading cause of atypical brain development and later neurocognitive impairment, on hierarchical complexity. We report that neonatal and adult structural connectomes are both composed of distinct hierarchical tiers and that hierarchical complexity is greater in term born neonates than in preterms. This is due to diversity of connectivity patterns of regions within the intermediate tiers, which consist of regions that underlie sensorimotor processing and its integration with cognitive information. For neonates and adults, the highest tier (hub regions) is ordered, rather than complex, with more homogeneous connectivity patterns in structural hubs. This suggests that the brain develops first a more rigid structure in hub regions allowing for the development of greater and more diverse functional specialization in lower level regions, while connectivity underpinning this diversity is dysmature in infants born preterm.",,pdf:https://academic.oup.com/cercor/article-pdf/31/4/2071/36458400/bhaa345.pdf; doi:https://doi.org/10.1093/cercor/bhaa345; html:https://europepmc.org/articles/PMC7945030; pdf:https://europepmc.org/articles/PMC7945030?pdf=render -37562944,https://doi.org/10.1136/emermed-2023-213186,"Biases in the collection of blood alcohol data for adult major trauma patients in Victoria, Australia.","Lau G, Gabbe B, Mitra B, Dietze P, Reeder S, Cameron P, Read DJ, Symons E, Beck B.",,Emergency medicine journal : EMJ,2023,2023-08-10,N,epidemiology; wounds and injuries; toxicology; Alcohol Abuse,,,"

Background

In-hospital alcohol testing provides an opportunity to implement prevention strategies for patients with high risk of experiencing repeated alcohol-related injuries. However, barriers to alcohol testing in emergency settings can prevent patients from being tested. In this study, we aimed to understand potential biases in current data on the completion of blood alcohol tests for major trauma patients at hospitals in Victoria, Australia.

Methods

Victorian State Trauma Registry data on all adult major trauma patients from 1 January 2018 to 31 December 2021 were used. Characteristics associated with having a blood alcohol test recorded in the registry were assessed using logistic regression models.

Results

This study included 14 221 major trauma patients, of which 4563 (32.1%) had a blood alcohol test recorded. Having a blood alcohol test completed was significantly associated with age, socioeconomic disadvantage level, preferred language, having pre-existing mental health or substance use conditions, smoking status, presenting during times associated with heavy community alcohol consumption, injury cause and intent, and Glasgow Coma Scale scores (p<0.05). Restricting analyses to patients from a trauma centre where blood alcohol testing was part of routine clinical care mitigated most biases. However, relative to patients injured while driving a motor vehicle/motorcycle, lower odds of testing were still observed for patients with injuries from flames/scalds/contact burns (adjusted OR (aOR)=0.33, 95% CI 0.18 to 0.61) and low falls (aOR=0.17, 95% CI 0.12 to 0.25). Higher odds of testing were associated with pre-existing mental health (aOR=1.39, 95% CI 1.02 to 1.89) or substance use conditions (aOR=2.33, 95% CI to 1.47-3.70), and living in a more disadvantaged area (most disadvantaged quintile relative to least disadvantaged quintile: aOR=2.30, 95% CI 1.52 to 3.48).

Conclusion

Biases in the collection of blood alcohol data likely impact the surveillance of alcohol-related injuries. Routine alcohol testing after major trauma is needed to accurately inform epidemiology and the subsequent implementation of strategies for reducing alcohol-related injuries.",,doi:https://doi.org/10.1136/emermed-2023-213186 36564466,https://doi.org/10.1038/s41598-022-26141-x,Assessing and removing the effect of unwanted technical variations in microbiome data.,"Fachrul M, Méric G, Inouye M, Pamp SJ, Salim A.",,Scientific reports,2022,2022-12-23,Y,,,,"Varying technologies and experimental approaches used in microbiome studies often lead to irreproducible results due to unwanted technical variations. Such variations, often unaccounted for and of unknown source, may interfere with true biological signals, resulting in misleading biological conclusions. In this work, we aim to characterize the major sources of technical variations in microbiome data and demonstrate how in-silico approaches can minimize their impact. We analyzed 184 pig faecal metagenomes encompassing 21 specific combinations of deliberately introduced factors of technical and biological variations. Using the novel Removing Unwanted Variations-III-Negative Binomial (RUV-III-NB), we identified several known experimental factors, specifically storage conditions and freeze-thaw cycles, as likely major sources of unwanted variation in metagenomes. We also observed that these unwanted technical variations do not affect taxa uniformly, with freezing samples affecting taxa of class Bacteroidia the most, for example. Additionally, we benchmarked the performances of different correction methods, including ComBat, ComBat-seq, RUVg, RUVs, and RUV-III-NB. While RUV-III-NB performed consistently robust across our sensitivity and specificity metrics, most other methods did not remove unwanted variations optimally. Our analyses suggest that a careful consideration of possible technical confounders is critical during experimental design of microbiome studies, and that the inclusion of technical replicates is necessary to efficiently remove unwanted variations computationally.",,pdf:https://www.nature.com/articles/s41598-022-26141-x.pdf; doi:https://doi.org/10.1038/s41598-022-26141-x; html:https://europepmc.org/articles/PMC9789116; pdf:https://europepmc.org/articles/PMC9789116?pdf=render +37562944,https://doi.org/10.1136/emermed-2023-213186,"Biases in the collection of blood alcohol data for adult major trauma patients in Victoria, Australia.","Lau G, Gabbe B, Mitra B, Dietze P, Reeder S, Cameron P, Read DJ, Symons E, Beck B.",,Emergency medicine journal : EMJ,2023,2023-08-10,N,epidemiology; wounds and injuries; toxicology; Alcohol Abuse,,,"

Background

In-hospital alcohol testing provides an opportunity to implement prevention strategies for patients with high risk of experiencing repeated alcohol-related injuries. However, barriers to alcohol testing in emergency settings can prevent patients from being tested. In this study, we aimed to understand potential biases in current data on the completion of blood alcohol tests for major trauma patients at hospitals in Victoria, Australia.

Methods

Victorian State Trauma Registry data on all adult major trauma patients from 1 January 2018 to 31 December 2021 were used. Characteristics associated with having a blood alcohol test recorded in the registry were assessed using logistic regression models.

Results

This study included 14 221 major trauma patients, of which 4563 (32.1%) had a blood alcohol test recorded. Having a blood alcohol test completed was significantly associated with age, socioeconomic disadvantage level, preferred language, having pre-existing mental health or substance use conditions, smoking status, presenting during times associated with heavy community alcohol consumption, injury cause and intent, and Glasgow Coma Scale scores (p<0.05). Restricting analyses to patients from a trauma centre where blood alcohol testing was part of routine clinical care mitigated most biases. However, relative to patients injured while driving a motor vehicle/motorcycle, lower odds of testing were still observed for patients with injuries from flames/scalds/contact burns (adjusted OR (aOR)=0.33, 95% CI 0.18 to 0.61) and low falls (aOR=0.17, 95% CI 0.12 to 0.25). Higher odds of testing were associated with pre-existing mental health (aOR=1.39, 95% CI 1.02 to 1.89) or substance use conditions (aOR=2.33, 95% CI to 1.47-3.70), and living in a more disadvantaged area (most disadvantaged quintile relative to least disadvantaged quintile: aOR=2.30, 95% CI 1.52 to 3.48).

Conclusion

Biases in the collection of blood alcohol data likely impact the surveillance of alcohol-related injuries. Routine alcohol testing after major trauma is needed to accurately inform epidemiology and the subsequent implementation of strategies for reducing alcohol-related injuries.",,doi:https://doi.org/10.1136/emermed-2023-213186 36571960,https://doi.org/10.1016/j.bjps.2022.11.049,Artificial intelligence in the management and treatment of burns: A systematic review and meta-analyses.,"Taib BG, Karwath A, Wensley K, Minku L, Gkoutos GV, Moiemen N.",,"Journal of plastic, reconstructive & aesthetic surgery : JPRAS",2023,2022-11-23,N,Burns; Systematic review; Machine Learning (Ml); Artificial Intelligence (Ai); Diagnostic Test Meta Analyses,,,"

Introduction and aim

Artificial Intelligence (AI) is already being successfully employed to aid the interpretation of multiple facets of burns care. In the light of the growing influence of AI, this systematic review and diagnostic test accuracy meta-analyses aim to appraise and summarise the current direction of research in this field.

Method

A systematic literature review was conducted of relevant studies published between 1990 and 2021, yielding 35 studies. Twelve studies were suitable for a Diagnostic Test Meta-Analyses.

Results

The studies generally focussed on burn depth (Accuracy 68.9%-95.4%, Sensitivity 90.8% and Specificity 84.4%), burn segmentation (Accuracy 76.0%-99.4%, Sensitivity 97.9% and specificity 97.6%) and burn related mortality (Accuracy >90%-97.5% Sensitivity 92.9% and specificity 93.4%). Neural networks were the most common machine learning (ML) algorithm utilised in 69% of the studies. The QUADAS-2 tool identified significant heterogeneity between studies.

Discussion

The potential application of AI in the management of burns patients is promising, especially given its propitious results across a spectrum of dimensions, including burn depth, size, mortality, related sepsis and acute kidney injuries. The accuracy of the results analysed within this study is comparable to current practices in burns care.

Conclusion

The application of AI in the treatment and management of burns patients, as a series of point of care diagnostic adjuncts, is promising. Whilst AI is a potentially valuable tool, a full evaluation of its current utility and potential is limited by significant variations in research methodology and reporting.",,doi:https://doi.org/10.1016/j.bjps.2022.11.049 35055401,https://doi.org/10.3390/jpm12010086,Predicting Hospital Readmission for Campylobacteriosis from Electronic Health Records: A Machine Learning and Text Mining Perspective.,"Zhou SM, Lyons RA, Rahman MA, Holborow A, Brophy S.",,Journal of personalized medicine,2022,2022-01-10,Y,Hospitalisation; Feature Selection; Machine Learning; Readmission; Electronic Health Records; Text Mining; Campylobacter Infections,,,"(1) Background: This study investigates influential risk factors for predicting 30-day readmission to hospital for Campylobacter infections (CI). (2) Methods: We linked general practitioner and hospital admission records of 13,006 patients with CI in Wales (1990-2015). An approach called TF-zR (term frequency-zRelevance) technique was presented to evaluates how relevant a clinical term is to a patient in a cohort characterized by coded health records. The zR is a supervised term-weighting metric to assign weight to a term based on relative frequencies of the term across different classes. Cost-sensitive classifier with swarm optimization and weighted subset learning was integrated to identify influential clinical signals as predictors and optimal model for readmission prediction. (3) Results: From a pool of up to 17,506 variables, 33 most predictive factors were identified, including age, gender, Townsend deprivation quintiles, comorbidities, medications, and procedures. The predictive model predicted readmission with 73% sensitivity and 54% specificity. Variables associated with readmission included male gender, recurrent tonsillitis, non-healing open wounds, operation for in-gown toenails. Cystitis, paracetamol/codeine use, age (21-25), and heliclear triple pack use, were associated with a lower risk of readmission. (4) Conclusions: This study gives a profile of clustered variables that are predictive of readmission associated with campylobacteriosis.",,pdf:https://www.mdpi.com/2075-4426/12/1/86/pdf?version=1641832520; doi:https://doi.org/10.3390/jpm12010086; html:https://europepmc.org/articles/PMC8779953; pdf:https://europepmc.org/articles/PMC8779953?pdf=render 36525457,https://doi.org/10.1371/journal.pone.0279250,Undergoing radical treatment for prostate cancer and its impact on wellbeing: A qualitative study exploring men's experiences.,"Vyas N, Brunckhorst O, Fox L, Van Hemelrijck M, Muir G, Stewart R, Dasgupta P, Ahmed K.",,PloS one,2022,2022-12-16,Y,,,,"

Introduction

Quality of life in prostate cancer survivorship is becoming increasingly important, with mental and social wellbeing recognised as key components. However, limited global evaluation of psychosocial challenges experienced after treatment exists. Therefore, we aimed to explore the lived experiences of men who underwent radical treatment, and its psychosocial impact.

Material and methods

This qualitative study was conducted using 19 men who had undergone radical treatment (prostatectomy or radiotherapy) for their cancer. Semi-structured interviews were conducted exploring lived experiences of men after treatment. A Structured thematic analysis of collected data was undertaken, with an inductive co-construction of themes through the lens of the biopsychosocial model. Themes generated were considered within a psychological, social, and physical wellbeing framework.

Results

An initial knowledge gap meant mental wellbeing was strongly impacted initially leading to a 'Diagnostic Blow and the Search for Clarity'. Doubt over individuals' future resulted in 'An Uncertain Future' in many men. Once treatment was completed a 'Reflective journey' began, with men considering their outcomes and decisions made. Social wellbeing was also impacted with many identifying the 'Emotional Repercussions' on their relationships and the impact their diagnosis had on their partner and family. Many subsequently sought to increase their support through 'The Social Network and Advocacy', while physical changes led to an increased need for 'Social Planning'. Finally, physical wellbeing was highlighted by a continual acknowledgement of the 'Natural process of ageing' leading to a reluctancy to seek help, whilst simultaneously attempting to improve existing health via 'The Health Kick'.

Conclusions

Radical treatments have a considerable impact on mental and social wellbeing of individuals. Anxiety after diagnosis and significant uncertainty over individual futures exist, with physical complications of treatment leading to social repercussions. Future research should aim to identify forms of support to improve quality of life of these men.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279250&type=printable; doi:https://doi.org/10.1371/journal.pone.0279250; html:https://europepmc.org/articles/PMC9757548; pdf:https://europepmc.org/articles/PMC9757548?pdf=render -38660461,https://doi.org/10.1089/neur.2023.0116,The Australian Traumatic Brain Injury Initiative: Statement of Working Principles and Rapid Review of Methods to Define Data Dictionaries for Neurological Conditions.,"Bagg MK, Hicks AJ, Hellewell SC, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Gabbe BJ, Fitzgerald M.",,Neurotrauma reports,2024,2024-04-11,Y,Brain injuries; Traumatic; Neurology; Common Data Elements; Systematic Review [Publication Type],,,"The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to develop a health informatics approach to collect data predictive of outcomes for persons with moderate-severe TBI across Australia. Central to this approach is a data dictionary; however, no systematic reviews of methods to define and develop data dictionaries exist to-date. This rapid systematic review aimed to identify and characterize methods for designing data dictionaries to collect outcomes or variables in persons with neurological conditions. Database searches were conducted from inception through October 2021. Records were screened in two stages against set criteria to identify methods to define data dictionaries for neurological conditions (International Classification of Diseases, 11th Revision: 08, 22, and 23). Standardized data were extracted. Processes were checked at each stage by independent review of a random 25% of records. Consensus was reached through discussion where necessary. Thirty-nine initiatives were identified across 29 neurological conditions. No single established or recommended method for defining a data dictionary was identified. Nine initiatives conducted systematic reviews to collate information before implementing a consensus process. Thirty-seven initiatives consulted with end-users. Methods of consultation were ""roundtable"" discussion (n = 30); with facilitation (n = 16); that was iterative (n = 27); and frequently conducted in-person (n = 27). Researcher stakeholders were involved in all initiatives and clinicians in 25. Importantly, only six initiatives involved persons with lived experience of TBI and four involved carers. Methods for defining data dictionaries were variable and reporting is sparse. Our findings are instructive for AUS-TBI and can be used to further development of methods for defining data dictionaries.",,doi:https://doi.org/10.1089/neur.2023.0116; html:https://europepmc.org/articles/PMC11040195; pdf:https://europepmc.org/articles/PMC11040195?pdf=render 37953241,https://doi.org/10.1186/s12916-023-03153-6,Cardiovascular events and venous thromboembolism after primary malignant or non-malignant brain tumour diagnosis: a population matched cohort study in Wales (United Kingdom).,"Poon MTC, Brennan PM, Jin K, Sudlow CLM, Figueroa JD.",,BMC medicine,2023,2023-11-13,Y,Brain cancer; Cerebrovascular disease; Neuro-oncology; Population-based,,,"

Background

Elevated standardised mortality ratio of cardiovascular diseases (CVD) in patients with brain tumours may result from differences in the CVD incidences and cardiovascular risk factors. We compared the risk of CVD among patients with a primary malignant or non-malignant brain tumour to a matched general population cohort, accounting for other co-morbidities.

Methods

Using data from the Secured Anonymised Information Linkage (SAIL) Databank in Wales (United Kingdom), we identified all adults aged ≥ 18 years in the primary care database with first diagnosis of malignant or non-malignant brain tumour identified in the cancer registry in 2000-2014 and a matched cohort (case-to-control ratio 1:5) by age, sex and primary care provider from the general population without any cancer diagnosis. Outcomes included fatal and non-fatal major vascular events (stroke, ischaemic heart disease, aortic and peripheral vascular diseases) and venous thromboembolism (VTE). We used multivariable Cox models adjusted for clinical risk factors to compare risks, stratified by tumour behaviour (malignant or non-malignant) and follow-up period.

Results

There were 2869 and 3931 people diagnosed with malignant or non-malignant brain tumours, respectively, between 2000 and 2014 in Wales. They were matched to 33,785 controls. Within the first year of tumour diagnosis, malignant tumour was associated with a higher risk of VTE (hazard ratio [HR] 21.58, 95% confidence interval 16.12-28.88) and stroke (HR 3.32, 2.44-4.53). After the first year, the risks of VTE (HR 2.20, 1.52-3.18) and stroke (HR 1.45, 1.00-2.10) remained higher than controls. Patients with non-malignant tumours had higher risks of VTE (HR 3.72, 2.73-5.06), stroke (HR 4.06, 3.35-4.93) and aortic and peripheral arterial disease (HR 2.09, 1.26-3.48) within the first year of diagnosis compared with their controls.

Conclusions

The elevated CVD and VTE risks suggested risk reduction may be a strategy to improve life quality and survival in people with a brain tumour.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-03153-6; doi:https://doi.org/10.1186/s12916-023-03153-6; html:https://europepmc.org/articles/PMC10641987; pdf:https://europepmc.org/articles/PMC10641987?pdf=render +38660461,https://doi.org/10.1089/neur.2023.0116,The Australian Traumatic Brain Injury Initiative: Statement of Working Principles and Rapid Review of Methods to Define Data Dictionaries for Neurological Conditions.,"Bagg MK, Hicks AJ, Hellewell SC, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Gabbe BJ, Fitzgerald M.",,Neurotrauma reports,2024,2024-04-11,Y,Brain injuries; Traumatic; Neurology; Common Data Elements; Systematic Review [Publication Type],,,"The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to develop a health informatics approach to collect data predictive of outcomes for persons with moderate-severe TBI across Australia. Central to this approach is a data dictionary; however, no systematic reviews of methods to define and develop data dictionaries exist to-date. This rapid systematic review aimed to identify and characterize methods for designing data dictionaries to collect outcomes or variables in persons with neurological conditions. Database searches were conducted from inception through October 2021. Records were screened in two stages against set criteria to identify methods to define data dictionaries for neurological conditions (International Classification of Diseases, 11th Revision: 08, 22, and 23). Standardized data were extracted. Processes were checked at each stage by independent review of a random 25% of records. Consensus was reached through discussion where necessary. Thirty-nine initiatives were identified across 29 neurological conditions. No single established or recommended method for defining a data dictionary was identified. Nine initiatives conducted systematic reviews to collate information before implementing a consensus process. Thirty-seven initiatives consulted with end-users. Methods of consultation were ""roundtable"" discussion (n = 30); with facilitation (n = 16); that was iterative (n = 27); and frequently conducted in-person (n = 27). Researcher stakeholders were involved in all initiatives and clinicians in 25. Importantly, only six initiatives involved persons with lived experience of TBI and four involved carers. Methods for defining data dictionaries were variable and reporting is sparse. Our findings are instructive for AUS-TBI and can be used to further development of methods for defining data dictionaries.",,doi:https://doi.org/10.1089/neur.2023.0116; html:https://europepmc.org/articles/PMC11040195; pdf:https://europepmc.org/articles/PMC11040195?pdf=render 37812323,https://doi.org/10.1186/s41687-023-00634-3,Development and usability testing of an electronic patient-reported outcome (ePRO) solution for patients with inflammatory diseases in an Advanced Therapy Medicinal Product (ATMP) basket trial.,"McMullan C, Retzer A, Hughes SE, Aiyegbusi OL, Bathurst C, Boyd A, Coleman J, Davies EH, Denniston AK, Dunster H, Frost C, Harding R, Hunn A, Kyte D, Malpass R, McNamara G, Mitchell S, Mittal S, Newsome PN, Price G, Rowe A, van Reil W, Walker A, Wilson R, Calvert M.",,Journal of patient-reported outcomes,2023,2023-10-09,Y,Inflammatory Conditions; Usability Testing; Cognitive Interviews; Electronic Patient Reported Outcomes; Early Phase Advanced Therapy Trial,,,"

Background

Electronic patient-reported outcome (ePRO) systems are increasingly used in clinical trials to provide evidence of efficacy and tolerability of treatment from the patient perspective. The aim of this study is twofold: (1) to describe how we developed an electronic platform for patients to report their symptoms, and (2) to develop and undertake usability testing of an ePRO solution for use in a study of cell therapy seeking to provide early evidence of efficacy and tolerability of treatment and test the feasibility of the system for use in later phase studies.

Methods

An ePRO system was designed to be used in a single arm, multi-centre, phase II basket trial investigating the safety and activity of the use of ORBCEL-C™ in the treatment of patients with inflammatory conditions. ORBCEL-C™ is an enriched Mesenchymal Stromal Cells product isolated from human umbilical cord tissue using CD362+ cell selection. Usability testing sessions were conducted using cognitive interviews and the 'Think Aloud' method with patient advisory group members and Research Nurses to assess the usability of the system.

Results

Nine patient partners and seven research nurses took part in one usability testing session. Measures of fatigue and health-related quality of life, the PRO-CTCAE™ and FACT-GP5 global tolerability question were included in the ePRO system. Alert notifications to the clinical team were triggered by PRO-CTCAE™ and FACT-GP5 scores. Patient participants liked the simplicity and responsiveness of the patient-facing app. Two patients were unable to complete the testing session, due to technical issues. Research Nurses suggested minor modifications to improve functionality and the layout of the clinician dashboard and the training materials.

Conclusion

By testing the effectiveness, efficiency, and satisfaction of our novel ePRO system (PROmicsR), we learnt that most people with an inflammatory condition found it easy to report their symptoms using an app on their own device. Their experiences using the PROmicsR ePRO system within a trial environment will be further explored in our upcoming feasibility testing. Research nurses were also positive and found the clinical dashboard easy-to-use. Using ePROs in early phase trials is important in order to provide evidence of therapeutic responses and tolerability, increase the evidence based, and inform methodology development.

Trial registration

ISRCTN, ISRCTN80103507. Registered 01 April 2022, https://www.isrctn.com/ISRCTN80103507.",,pdf:https://jpro.springeropen.com/counter/pdf/10.1186/s41687-023-00634-3; doi:https://doi.org/10.1186/s41687-023-00634-3; html:https://europepmc.org/articles/PMC10562321; pdf:https://europepmc.org/articles/PMC10562321?pdf=render 35964473,https://doi.org/10.1016/j.socscimed.2022.115237,"""We've all got the virus inside us now"": Disaggregating public health relations and responsibilities for health protection in pandemic London.","Kasstan B, Mounier-Jack S, Gaskell KM, Eggo RM, Marks M, Chantler T.",,Social science & medicine (1982),2022,2022-08-07,Y,Pandemic; Public Health; Judaism; Responsibility; London; Covid-19,,,"The COVID-19 pandemic has disproportionately impacted ethnic minorities in the global north, evidenced by higher rates of transmission, morbidity, and mortality relative to population sizes. Orthodox Jewish neighbourhoods in London had extremely high SARS-CoV-2 seroprevalence rates, reflecting patterns in Israel and the US. The aim of this paper is to examine how responsibilities over health protection are conveyed, and to what extent responsibility is sought by, and shared between, state services, and 'community' stakeholders or representative groups, and families in public health emergencies. The study investigates how public health and statutory services stakeholders, Orthodox Jewish communal custodians and households sought to enact health protection in London during the first year of the pandemic (March 2020-March 2021). Twenty-eight semi-structured interviews were conducted across these cohorts. Findings demonstrate that institutional relations - both their formation and at times fragmentation - were directly shaped by issues surrounding COVID-19 control measures. Exchanges around protective interventions (whether control measures, contact tracing technologies, or vaccines) reveal diverse and diverging attributions of responsibility and authority. The paper develops a framework of public health relations to understand negotiations between statutory services and minority groups over responsiveness and accountability in health protection. Disaggregating public health relations can help social scientists to critique who and what characterises institutional relationships with minority groups, and what ideas of responsibility and responsiveness are projected by differently-positioned stakeholders in health protection.",,doi:https://doi.org/10.1016/j.socscimed.2022.115237; doi:https://doi.org/10.1016/j.socscimed.2022.115237; html:https://europepmc.org/articles/PMC9357441; pdf:https://europepmc.org/articles/PMC9357441?pdf=render 36745557,https://doi.org/10.1093/bjd/ljac132,"Factors associated with depression, anxiety and severe mental illness among adults with atopic eczema or psoriasis: a systematic review and meta-analysis.","Adesanya EI, Matthewman J, Schonmann Y, Hayes JF, Henderson A, Mathur R, Mulick AR, Smith CH, Langan SM, Mansfield KE.",,The British journal of dermatology,2023,2023-03-01,N,,,,"

Background

Evidence suggests an association between atopic eczema (AE) or psoriasis and mental illness; however, the factors associated with mental illness are unclear.

Objectives

To synthesize and evaluate all available evidence on factors associated with depression, anxiety and severe mental illness (SMI) among adults with AE or psoriasis.

Methods

We searched electronic databases, grey literature databases and clinical trial registries from inception to February 2022 for studies of adults with AE or psoriasis. Eligible studies included randomized controlled trials (RCTs), cohort, cross-sectional or case-control studies where effect estimates of factors associated with depression, anxiety or SMI were reported. We did not apply language or geographical restrictions. We assessed risk of bias using the Quality in Prognosis Studies tool. We synthesized results narratively, and if at least two studies were sufficiently homogeneous, we pooled effect estimates in a random effects meta-analysis.

Results

We included 21 studies (11 observational, 10 RCTs). No observational studies in AE fulfilled our eligibility criteria. Observational studies in people with psoriasis mostly investigated factors associated with depression or anxiety - one cross-sectional study investigated factors associated with schizophrenia. Pooled effect estimates suggest that female sex and psoriatic arthritis were associated with depression [female sex: odds ratio (OR) 1.62, 95% confidence interval (CI) 1.09-2.40, 95% prediction intervals (PIs) 0.62-4.23, I2 = 24.90%, τ2 = 0.05; psoriatic arthritis: OR 2.26, 95% CI 1.56-3.25, 95% PI 0.21-24.23, I2 = 0.00%, τ2 = 0.00] and anxiety (female sex: OR 2.59, 95% CI 1.32-5.07, 95% PI 0.00-3956.27, I2 = 61.90%, τ2 = 0.22; psoriatic arthritis: OR 1.98, 95% CI 1.33-2.94, I2 = 0.00%, τ2 = 0.00). Moderate/severe psoriasis was associated with anxiety (OR 1.14, 95% CI 1.05-1.25, I2 0.00%, τ2 = 0.00), but not depression. Evidence from RCTs suggested that adults with AE or psoriasis given placebo had higher depression and anxiety scores compared with comparators given targeted treatment (e.g. biologic agents).

Conclusions

Our review highlights limited existing research on factors associated with depression, anxiety and SMI in adults with AE or psoriasis. Observational evidence on factors associated with depression or anxiety in people with psoriasis was conflicting or from single studies, but some identified factors were consistent with those in the general population. Evidence on factors associated with SMIs in people with AE or psoriasis was particularly limited. Evidence from RCTs suggested that AE and psoriasis treated with placebo was associated with higher depression and anxiety scores compared with skin disease treated with targeted therapy; however, follow-up was limited. Therefore, long-term effects on mental health are unclear.",,pdf:https://academic.oup.com/bjd/article-pdf/188/4/460/51790111/ljac132.pdf; doi:https://doi.org/10.1093/bjd/ljac132 @@ -978,9 +978,9 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 30240446,https://doi.org/10.1371/journal.pone.0203896,Polygenic risk scores for major depressive disorder and neuroticism as predictors of antidepressant response: Meta-analysis of three treatment cohorts.,"Ward J, Graham N, Strawbridge RJ, Ferguson A, Jenkins G, Chen W, Hodgson K, Frye M, Weinshilboum R, Uher R, Lewis CM, Biernacka J, Smith DJ.",,PloS one,2018,2018-09-21,Y,,Better Care,,"There are currently no reliable approaches for correctly identifying which patients with major depressive disorder (MDD) will respond well to antidepressant therapy. However, recent genetic advances suggest that Polygenic Risk Scores (PRS) could allow MDD patients to be stratified for antidepressant response. We used PRS for MDD and PRS for neuroticism as putative predictors of antidepressant response within three treatment cohorts: The Genome-based Therapeutic Drugs for Depression (GENDEP) cohort, and 2 sub-cohorts from the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study PRGN-AMPS (total patient number = 760). Results across cohorts were combined via meta-analysis within a random effects model. Overall, PRS for MDD and neuroticism did not significantly predict antidepressant response but there was a consistent direction of effect, whereby greater genetic loading for both MDD (best MDD result, p < 5*10-5 MDD-PRS at 4 weeks, β = -0.019, S.E = 0.008, p = 0.01) and neuroticism (best neuroticism result, p < 0.1 neuroticism-PRS at 8 weeks, β = -0.017, S.E = 0.008, p = 0.03) were associated with less favourable response. We conclude that the PRS approach may offer some promise for treatment stratification in MDD and should now be assessed within larger clinical cohorts.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0203896&type=printable; doi:https://doi.org/10.1371/journal.pone.0203896; html:https://europepmc.org/articles/PMC6150505; pdf:https://europepmc.org/articles/PMC6150505?pdf=render 35781133,https://doi.org/10.3310/zyzc8514,Long-term impact of pre-incision antibiotics on children born by caesarean section: a longitudinal study based on UK electronic health records.,"Šumilo D, Nirantharakumar K, Willis BH, Rudge GM, Martin J, Gokhale K, Thayakaran R, Adderley NJ, Chandan JS, Okoth K, Harris IM, Hewston R, Skrybant M, Deeks JJ, Brocklehurst P.",,"Health technology assessment (Winchester, England)",2022,2022-06-01,N,Asthma; Caesarean section; Eczema; Child Health; Anti-bacterial Agents; Microbiome; Electronic Health Records; Interrupted Time Series Analysis,,,"

Background

Since changes in the national guidance in 2011, prophylactic antibiotics for women undergoing caesarean section are recommended prior to skin incision, rather than after the baby's umbilical cord has been clamped. Evidence from randomised controlled trials conducted outside the UK has shown that this reduces maternal infectious morbidity; however, the prophylactic antibiotics also cross the placenta, meaning that babies are exposed to them around the time of birth. Antibiotics are known to affect the gut microbiota of the babies, but the long-term effects of exposure to high-dose broad-spectrum antibiotics around the time of birth on allergy and immune-related diseases are unknown.

Objectives

We aimed to examine whether or not in-utero exposure to antibiotics immediately prior to birth compared with no pre-incisional antibiotic exposure increases the risk of (1) asthma and (2) eczema in children born by caesarean section.

Design

This was a controlled interrupted time series study.

Setting

The study took place in primary and secondary care.

Participants

Children born in the UK during 2006-18 delivered by caesarean section were compared with a control cohort delivered vaginally.

Interventions

In-utero exposure to antibiotics immediately prior to birth.

Main outcome measures

Asthma and eczema in children in the first 5 years of life. Additional secondary outcomes, including other allergy-related conditions, autoimmune diseases, infections, other immune system-related diseases and neurodevelopmental conditions, were also assessed.

Data sources

The Health Improvement Network (THIN) and the Clinical Practice Research Datalink (CPRD) primary care databases and the Hospital Episode Statistics (HES) database. Previously published linkage strategies were adapted to link anonymised data on mothers and babies in these databases. Duplicate practices contributing to both THIN and the CPRD databases were removed to create a THIN-CPRD data set.

Results

In the THIN-CPRD and HES data sets, records of 515,945 and 3,945,351 mother-baby pairs were analysed, respectively. The risk of asthma was not significantly higher in children born by caesarean section exposed to pre-incision antibiotics than in children whose mothers received post-cord clamping antibiotics, with an incidence rate ratio of 0.91 (95% confidence interval 0.78 to 1.05) for diagnosis of asthma in primary care and an incidence rate ratio of 1.05 (95% confidence interval 0.99 to 1.11) for asthma resulting in a hospital admission. We also did not find an increased risk of eczema, with an incidence rate ratio of 0.98 (95% confidence interval 0.94 to1.03) and an incidence rate ratio of 0.96 (95% confidence interval 0.71 to 1.29) for diagnosis in primary care and hospital admissions, respectively.

Limitations

It was not possible to ascertain the exposure to pre-incision antibiotics at an individual level. The maximum follow-up of children was 5 years.

Conclusions

There was no evidence that the policy change from post-cord clamping to pre-incision prophylactic antibiotics for caesarean sections during 2006-18 had an impact on the incidence of asthma and eczema in early childhood in the UK.

Future work

There is a need for further research to investigate if pre-incision antibiotics have any impact on developing asthma and other allergy and immune-related conditions in older children.

Study registration

This study is registered as researchregistry3736.

Funding

This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 30. See the NIHR Journals Library website for further project information.",,pdf:https://njl-admin.nihr.ac.uk/document/download/2039937; doi:https://doi.org/10.3310/ZYZC8514 36446449,https://doi.org/10.1136/bmjopen-2022-061849,Effect of lifting COVID-19 restrictions on utilisation of primary care services in Nepal: a difference-in-differences analysis.,"Kapoor NR, Aryal A, Mehata S, Dulal M, Kruk ME, Bauhoff S, Arsenault C.",,BMJ open,2022,2022-11-29,Y,Primary Care; Health Policy; Covid-19,,,"

Introduction

An increasing number of studies have reported disruptions in health service utilisation due to the COVID-19 pandemic and its associated restrictions. However, little is known about the effect of lifting COVID-19 restrictions on health service utilisation. The objective of this study was to estimate the effect of lifting COVID-19 restrictions on primary care service utilisation in Nepal.

Methods

Data on utilisation of 10 primary care services were extracted from the Health Management Information System across all health facilities in Nepal. We used a difference-in-differences design and linear fixed effects regressions to estimate the effect of lifting COVID-19 restrictions. The treatment group included palikas that had lifted restrictions in place from 17 August 2020 to 16 September 2020 (Bhadra 2077) and the control group included palikas that had maintained restrictions during that period. The pre-period included the 4 months of national lockdown from 24 March 2020 to 22 July 2020 (Chaitra 2076 to Ashar 2077). Models included month and palika fixed effects and controlled for COVID-19 incidence.

Results

We found that lifting COVID-19 restrictions was associated with an average increase per palika of 57.5 contraceptive users (95% CI 14.6 to 100.5), 15.6 antenatal care visits (95% CI 5.3 to 25.9) and 1.6 child pneumonia visits (95% CI 0.2 to 2.9). This corresponded to a 9.4% increase in contraceptive users, 34.2% increase in antenatal care visits and 15.6% increase in child pneumonia visits. Utilisation of most other primary care services also increased after lifting restrictions, but coefficients were not statistically significant.

Conclusions

Despite the ongoing pandemic, lifting restrictions can lead to an increase in some primary care services. Our results point to a causal link between restrictions and health service utilisation and call for policy makers in low- and middle-income countries to carefully consider the trade-offs of strict lockdowns during future COVID-19 waves or future pandemics.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e061849.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-061849; html:https://europepmc.org/articles/PMC9709811; pdf:https://europepmc.org/articles/PMC9709811?pdf=render +32398093,https://doi.org/10.1186/s13063-020-04329-8,Access to routinely collected health data for clinical trials - review of successful data requests to UK registries.,"Lensen S, Macnair A, Love SB, Yorke-Edwards V, Noor NM, Martyn M, Blenkinsop A, Diaz-Montana C, Powell G, Williamson E, Carpenter J, Sydes MR.",,Trials,2020,2020-05-12,Y,Systematic review; Rct; Registry; Routinely Collected Health Data,,,"

Background

Clinical trials generally each collect their own data despite routinely collected health data (RCHD) increasing in quality and breadth. Our aim is to quantify UK-based randomised controlled trials (RCTs) accessing RCHD for participant data, characterise how these data are used and thereby recommend how more trials could use RCHD.

Methods

We conducted a systematic review of RCTs accessing RCHD from at least one registry in the UK between 2013 and 2018 for the purposes of informing or supplementing participant data. A list of all registries holding RCHD in the UK was compiled. In cases where registries published release registers, these were searched for RCTs accessing RCHD. Where no release register was available, registries were contacted to request a list of RCTs. For each identified RCT, information was collected from all publicly available sources (release registers, websites, protocol etc.). The search and data extraction were undertaken between January and May 2019.

Results

We identified 160 RCTs accessing RCHD between 2013 and 2018 from a total of 22 registries; this corresponds to only a very small proportion of all UK RCTs (about 3%). RCTs accessing RCHD were generally large (median sample size 1590), commonly evaluating treatments for cancer or cardiovascular disease. Most of the included RCTs accessed RCHD from NHS Digital (68%), and the most frequently accessed datasets were mortality (76%) and hospital visits (55%). RCHD was used to inform the primary trial (82%) and long-term follow-up (57%). There was substantial variation in how RCTs used RCHD to inform participant outcome measures. A limitation was the lack of information and transparency from registries and RCTs with respect to which datasets have been accessed and for what purposes.

Conclusions

In the last five years, only a small minority of UK-based RCTs have accessed RCHD to inform participant data. We ask for improved accessibility, confirmed data quality and joined-up thinking between the registries and the regulatory authorities.

Trial registration

PROSPERO CRD42019123088.",,pdf:https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-020-04329-8; doi:https://doi.org/10.1186/s13063-020-04329-8; html:https://europepmc.org/articles/PMC7218527; pdf:https://europepmc.org/articles/PMC7218527?pdf=render 33262239,https://doi.org/10.1128/msystems.00677-20,Investigating the Role of Diet and Exercise in Gut Microbe-Host Cometabolism.,"Penney N, Barton W, Posma JM, Darzi A, Frost G, Cotter PD, Holmes E, Shanahan F, O'Sullivan O, Garcia-Perez I.",,mSystems,2020,2020-12-01,Y,Metabolism; Diet; Exercise; Microbiome,,,"We investigated the individual and combined effects of diet and physical exercise on metabolism and the gut microbiome to establish how these lifestyle factors influence host-microbiome cometabolism. Urinary and fecal samples were collected from athletes and less active controls. Individuals were further classified according to an objective dietary assessment score of adherence to healthy dietary habits according to WHO guidelines, calculated from their proton nuclear magnetic resonance (1H-NMR) urinary profiles. Subsequent models were generated comparing extremes of dietary habits, exercise, and the combined effect of both. Differences in metabolic phenotypes and gut microbiome profiles between the two groups were assessed. Each of the models pertaining to diet healthiness, physical exercise, or a combination of both displayed a metabolic and functional microbial signature, with a significant proportion of the metabolites identified as discriminating between the various pairwise comparisons resulting from gut microbe-host cometabolism. Microbial diversity was associated with a combination of high adherence to healthy dietary habits and exercise and was correlated with a distinct array of microbially derived metabolites, including markers of proteolytic activity. Improved control of dietary confounders, through the use of an objective dietary assessment score, has uncovered further insights into the complex, multifactorial relationship between diet, exercise, the gut microbiome, and metabolism. Furthermore, the observation of higher proteolytic activity associated with higher microbial diversity indicates that increased microbial diversity may confer deleterious as well as beneficial effects on the host.IMPORTANCE Improved control of dietary confounders, through the use of an objective dietary assessment score, has uncovered further insights into the complex, multifactorial relationship between diet, exercise, the gut microbiome, and metabolism. Each of the models pertaining to diet healthiness, physical exercise, or a combination of both, displayed a distinct metabolic and functional microbial signature. A significant proportion of the metabolites identified as discriminating between the various pairwise comparisons result from gut microbe-host cometabolism, and the identified interactions have expanded current knowledge in this area. Furthermore, although increased microbial diversity has previously been linked with health, our observation of higher microbial diversity being associated with increased proteolytic activity indicates that it may confer deleterious as well as beneficial effects on the host.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/85021/8/mSystems-2020-Penney-e00677-20.full.pdf; doi:https://doi.org/10.1128/mSystems.00677-20; html:https://europepmc.org/articles/PMC7716389; pdf:https://europepmc.org/articles/PMC7716389?pdf=render 37717234,https://doi.org/10.1111/1742-6723.14312,Prevalence of alcohol and other drug detections in non-transport injury events.,"Lau G, Mitra B, Gabbe BJ, Dietze PM, Reeder S, Cameron PA, Smit V, Schneider HG, Symons E, Koolstra C, Stewart C, Beck B.",,Emergency medicine Australasia : EMA,2024,2023-09-17,Y,Alcoholic Intoxication; Illicit Drug; Blood Alcohol Content; Wounds And Injury; Substance-related Disorder; Substance Use Detection,,,"

Objective

To measure the prevalence of alcohol and/or other drug (AOD) detections in suspected major trauma patients with non-transport injuries who presented to an adult major trauma centre.

Methods

This registry-based cohort study examined the prevalence of AOD detections in patients aged ≥18 years who: (i) sustained non-transport injuries; and (ii) met predefined trauma call-out criteria and were therefore managed by an interdisciplinary trauma team between 1 July 2021 and 31 December 2022. Prevalence was measured using routine in-hospital blood alcohol and urine drug screens.

Results

A total of 1469 cases met the inclusion criteria. Of cases with a valid blood test (n = 1248, 85.0%), alcohol was detected in 313 (25.1%) patients. Of the 733 (49.9%) cases with urine drug screen results, cannabinoids were most commonly detected (n = 103, 14.1%), followed by benzodiazepines (n = 98, 13.4%), amphetamine-type substances (n = 80, 10.9%), opioids (n = 28, 3.8%) and cocaine (n = 17, 2.3%). Alcohol and/or at least one other drug was detected in 37.4% (n = 472) of cases with either a blood alcohol or urine drug test completed (n = 1263, 86.0%). Multiple substances were detected in 16.6% (n = 119) of cases with both blood alcohol and urine drug screens (n = 718, 48.9%). Detections were prevalent in cases of interpersonal violence (n = 123/179, 68.7%) and intentional self-harm (n = 50/106, 47.2%), and in those occurring on Friday and Saturday nights (n = 118/191, 61.8%).

Conclusion

AOD detections were common in trauma patients with non-transport injury causes. Population-level surveillance is needed to inform prevention strategies that address AOD use as a significant risk factor for serious injury.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/1742-6723.14312; doi:https://doi.org/10.1111/1742-6723.14312; html:https://europepmc.org/articles/PMC10952644; pdf:https://europepmc.org/articles/PMC10952644?pdf=render -32398093,https://doi.org/10.1186/s13063-020-04329-8,Access to routinely collected health data for clinical trials - review of successful data requests to UK registries.,"Lensen S, Macnair A, Love SB, Yorke-Edwards V, Noor NM, Martyn M, Blenkinsop A, Diaz-Montana C, Powell G, Williamson E, Carpenter J, Sydes MR.",,Trials,2020,2020-05-12,Y,Systematic review; Rct; Registry; Routinely Collected Health Data,,,"

Background

Clinical trials generally each collect their own data despite routinely collected health data (RCHD) increasing in quality and breadth. Our aim is to quantify UK-based randomised controlled trials (RCTs) accessing RCHD for participant data, characterise how these data are used and thereby recommend how more trials could use RCHD.

Methods

We conducted a systematic review of RCTs accessing RCHD from at least one registry in the UK between 2013 and 2018 for the purposes of informing or supplementing participant data. A list of all registries holding RCHD in the UK was compiled. In cases where registries published release registers, these were searched for RCTs accessing RCHD. Where no release register was available, registries were contacted to request a list of RCTs. For each identified RCT, information was collected from all publicly available sources (release registers, websites, protocol etc.). The search and data extraction were undertaken between January and May 2019.

Results

We identified 160 RCTs accessing RCHD between 2013 and 2018 from a total of 22 registries; this corresponds to only a very small proportion of all UK RCTs (about 3%). RCTs accessing RCHD were generally large (median sample size 1590), commonly evaluating treatments for cancer or cardiovascular disease. Most of the included RCTs accessed RCHD from NHS Digital (68%), and the most frequently accessed datasets were mortality (76%) and hospital visits (55%). RCHD was used to inform the primary trial (82%) and long-term follow-up (57%). There was substantial variation in how RCTs used RCHD to inform participant outcome measures. A limitation was the lack of information and transparency from registries and RCTs with respect to which datasets have been accessed and for what purposes.

Conclusions

In the last five years, only a small minority of UK-based RCTs have accessed RCHD to inform participant data. We ask for improved accessibility, confirmed data quality and joined-up thinking between the registries and the regulatory authorities.

Trial registration

PROSPERO CRD42019123088.",,pdf:https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-020-04329-8; doi:https://doi.org/10.1186/s13063-020-04329-8; html:https://europepmc.org/articles/PMC7218527; pdf:https://europepmc.org/articles/PMC7218527?pdf=render 38581198,https://doi.org/10.1001/jama.2024.4011,Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality: A Secondary Analysis of the CAP Randomized Clinical Trial.,"Martin RM, Turner EL, Young GJ, Metcalfe C, Walsh EI, Lane JA, Sterne JAC, Noble S, Holding P, Ben-Shlomo Y, Williams NJ, Pashayan N, Bui MN, Albertsen PC, Seibert TM, Zietman AL, Oxley J, Adolfsson J, Mason MD, Davey Smith G, Neal DE, Hamdy FC, Donovan JL, CAP Trial Group.",,JAMA,2024,2024-05-01,N,,,,"

Importance

The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) reported no effect of prostate-specific antigen (PSA) screening on prostate cancer mortality at a median 10-year follow-up (primary outcome), but the long-term effects of PSA screening on prostate cancer mortality remain unclear.

Objective

To evaluate the effect of a single invitation for PSA screening on prostate cancer-specific mortality at a median 15-year follow-up compared with no invitation for screening.

Design, setting, and participants

This secondary analysis of the CAP randomized clinical trial included men aged 50 to 69 years identified at 573 primary care practices in England and Wales. Primary care practices were randomized between September 25, 2001, and August 24, 2007, and men were enrolled between January 8, 2002, and January 20, 2009. Follow-up was completed on March 31, 2021.

Intervention

Men received a single invitation for a PSA screening test with subsequent diagnostic tests if the PSA level was 3.0 ng/mL or higher. The control group received standard practice (no invitation).

Main outcomes and measures

The primary outcome was reported previously. Of 8 prespecified secondary outcomes, results of 4 were reported previously. The 4 remaining prespecified secondary outcomes at 15-year follow-up were prostate cancer-specific mortality, all-cause mortality, and prostate cancer stage and Gleason grade at diagnosis.

Results

Of 415 357 eligible men (mean [SD] age, 59.0 [5.6] years), 98% were included in these analyses. Overall, 12 013 and 12 958 men with a prostate cancer diagnosis were in the intervention and control groups, respectively (15-year cumulative risk, 7.08% [95% CI, 6.95%-7.21%] and 6.94% [95% CI, 6.82%-7.06%], respectively). At a median 15-year follow-up, 1199 men in the intervention group (0.69% [95% CI, 0.65%-0.73%]) and 1451 men in the control group (0.78% [95% CI, 0.73%-0.82%]) died of prostate cancer (rate ratio [RR], 0.92 [95% CI, 0.85-0.99]; P = .03). Compared with the control, the PSA screening intervention increased detection of low-grade (Gleason score [GS] ≤6: 2.2% vs 1.6%; P < .001) and localized (T1/T2: 3.6% vs 3.1%; P < .001) disease but not intermediate (GS of 7), high-grade (GS ≥8), locally advanced (T3), or distally advanced (T4/N1/M1) tumors. There were 45 084 all-cause deaths in the intervention group (23.2% [95% CI, 23.0%-23.4%]) and 50 336 deaths in the control group (23.3% [95% CI, 23.1%-23.5%]) (RR, 0.97 [95% CI, 0.94-1.01]; P = .11). Eight of the prostate cancer deaths in the intervention group (0.7%) and 7 deaths in the control group (0.5%) were related to a diagnostic biopsy or prostate cancer treatment.

Conclusions and relevance

In this secondary analysis of a randomized clinical trial, a single invitation for PSA screening compared with standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years. However, the absolute reduction in deaths was small.

Trial registration

isrctn.org Identifier: ISRCTN92187251.",,doi:https://doi.org/10.1001/jama.2024.4011 32460529,https://doi.org/10.1161/circimaging.119.010389,Novel Approach to Imaging Active Takayasu Arteritis Using Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging.,"Tarkin JM, Wall C, Gopalan D, Aloj L, Manavaki R, Fryer TD, Aboagye EO, Bennett MR, Peters JE, Rudd JHF, Mason JC.",,Circulation. Cardiovascular imaging,2020,2020-05-28,N,Positron emission tomography; Vasculitis; Aortic Diseases; Molecular Imaging; Takayasu Arteritis,,,,,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCIMAGING.119.010389; doi:https://doi.org/10.1161/CIRCIMAGING.119.010389; html:https://europepmc.org/articles/PMC7610536; pdf:https://europepmc.org/articles/PMC7610536?pdf=render; doi:https://doi.org/10.1161/circimaging.119.010389 36617894,https://doi.org/10.1080/1354750x.2022.2162966,Longitudinal profile of circulating endothelial cells in post-acute coronary syndrome patients.,"de Bakker M, Kraan J, Akkerhuis KM, Oemrawsingh R, Asselbergs FW, Hoefer I, Kardys I, Boersma E.",,"Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals",2023,2023-01-08,N,Atherosclerosis; Cardiovascular disease; Circulating endothelial cells; acute coronary syndrome; Vascular Injury; Repeated Measurements,,,"IntroductionPatients who have experienced an acute coronary syndrome (ACS) are at risk of a recurrent event, but their level of risk varies. Because of their close temporal relationship with vascular injury, longitudinal measurements of circulating endothelial cells (CECs) carry potential to improve individual risk assessment.MethodsWe conducted an explorative nested case-control study within our multicenter, prospective, observational biomarker study (BIOMArCS) of 844 ACS patients. Following an index ACS, high-frequency blood sampling was performed during 1-year follow-up. CECs were identified using flow cytometric analyses in 15 cases with recurrent event, and 30 matched controls.ResultsCases and controls had a median (25th-75thpercentile) age of 64.1 (58.1-75.1) years and 80% were men. During the months preceding the endpoint, the mean (95%CI) CEC concentration in cases was persistently higher than in controls (12.8 [8.2-20.0] versus 10.0 [7.0-14.4] cells/ml), although this difference was non-significant (P = 0.339). In controls, the mean cell concentration was significantly (P = 0.030) lower in post 30-day samples compared to samples collected within one day after index ACS: 10.1 (7.5-13.6) versus 17.0 (10.8-26.6) cells/ml. Similar results were observed for CEC subsets co-expressing CD133 and CD309 (VEGFR-2) or CD106 (VCAM-1).ConclusionDespite their close relation to vascular damage, no increase in cell concentrations were found prior to the occurrence of a secondary adverse cardiac event.",,doi:https://doi.org/10.1080/1354750x.2022.2162966; doi:https://doi.org/10.1080/1354750X.2022.2162966 @@ -991,23 +991,23 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund .",,The British journal of surgery,2021,2021-11-01,Y,,,,,,pdf:https://academic.oup.com/bjs/article-pdf/108/11/1274/47371055/znab183.pdf; doi:https://doi.org/10.1093/bjs/znab183; html:https://europepmc.org/articles/PMC8344569; pdf:https://europepmc.org/articles/PMC8344569?pdf=render 36529816,https://doi.org/10.1038/s41598-022-26357-x,Novel multimorbidity clusters in people with eczema and asthma: a population-based cluster analysis.,"Mulick AR, Henderson AD, Prieto-Merino D, Mansfield KE, Matthewman J, Quint JK, Lyons RA, Sheikh A, McAllister DA, Nitsch D, Langan SM.",,Scientific reports,2022,2022-12-18,Y,,,,"Eczema and asthma are allergic diseases and two of the commonest chronic conditions in high-income countries. Their co-existence with other allergic conditions is common, but little research exists on wider multimorbidity with these conditions. We set out to identify and compare clusters of multimorbidity in people with eczema or asthma and people without. Using routinely-collected primary care data from the U.K. Clinical Research Practice Datalink GOLD, we identified adults ever having eczema (or asthma), and comparison groups never having eczema (or asthma). We derived clusters of multimorbidity from hierarchical cluster analysis of Jaccard distances between pairs of diagnostic categories estimated from mixed-effects logistic regressions. We analysed 434,422 individuals with eczema (58% female, median age 47 years) and 1,333,281 individuals without (55% female, 47 years), and 517,712 individuals with asthma (53% female, 44 years) and 1,601,210 individuals without (53% female, 45 years). Age at first morbidity, sex and having eczema/asthma affected the scope of multimorbidity, with women, older age and eczema/asthma being associated with larger morbidity clusters. Injuries, digestive, nervous system and mental health disorders were more commonly seen in eczema and asthma than control clusters. People with eczema and asthma of all ages and both sexes may experience greater multimorbidity than people without eczema and asthma, including conditions not previously recognised as contributing to their disease burden. This work highlights areas where there is a critical need for research addressing the burden and drivers of multimorbidity in order to inform strategies to reduce poor health outcomes.",,pdf:https://www.nature.com/articles/s41598-022-26357-x.pdf; doi:https://doi.org/10.1038/s41598-022-26357-x; html:https://europepmc.org/articles/PMC9760185; pdf:https://europepmc.org/articles/PMC9760185?pdf=render 34605164,https://doi.org/10.1002/mnfr.202100316,Odd Chain Fatty Acids Are Not Robust Biomarkers for Dietary Intake of Fiber.,"Wu Y, Posma JM, Holmes E, Frost G, Chambers ES, Garcia-Perez I.",,Molecular nutrition & food research,2021,2021-10-22,N,dietary fiber; Short Chain Fatty Acids; Biomarker Validation; Dietary Biomarker; Odd Chain Fatty Acids,,,"

Scope

Prior investigation has suggested a positive association between increased colonic propionate production and circulating odd-chain fatty acids (OCFAs; pentadecanoic acid [C15:0], heptadecanoic acid [C17:0]). As the major source of propionate in humans is the microbial fermentation of dietary fiber, OCFAs have been proposed as candidate biomarkers of dietary fiber. The objective of this study is to critically assess the plausibility, robustness, reliability, dose-response, time-response aspects of OCFAs as potential biomarkers of fermentable fibers in two independent studies using a validated analytical method.

Methods and results

OCFAs are first assessed in a fiber supplementation study, where 21 participants received 10 g dietary fiber supplementation for 7 days. OCFAs are then assessed in a highly controlled inpatient setting, which 19 participants consumed a high fiber (45.1 g per day) and a low fiber diet (13.6 g per day) for 4 days. Collectively in both studies, dietary intakes of fiber as fiber supplementations or having consumed a high fiber diet do not increase circulating levels of OCFAs. The dose and temporal relations are not observed.

Conclusion

Current study has generated new insight on the utility of OCFAs as fiber biomarkers and highlighted the importance of critical assessment of candidate biomarkers before application.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/mnfr.202100316; doi:https://doi.org/10.1002/mnfr.202100316 -37327673,https://doi.org/10.1016/j.ebiom.2023.104655,HFrEF subphenotypes based on 4210 repeatedly measured circulating proteins are driven by different biological mechanisms.,"Petersen TB, de Bakker M, Asselbergs FW, Harakalova M, Akkerhuis KM, Brugts JJ, van Ramshorst J, Lumbers RT, Ostroff RM, Katsikis PD, van der Spek PJ, Umans VA, Boersma E, Rizopoulos D, Kardys I.",,EBioMedicine,2023,2023-06-14,Y,Proteomics; Phenotypes; Biomarkers; Heart Failure; Unsupervised Machine Learning,,,"

Background

HFrEF is a heterogenous condition with high mortality. We used serial assessments of 4210 circulating proteins to identify distinct novel protein-based HFrEF subphenotypes and to investigate underlying dynamic biological mechanisms. Herewith we aimed to gain pathophysiological insights and fuel opportunities for personalised treatment.

Methods

In 382 patients, we performed trimonthly blood sampling during a median follow-up of 2.1 [IQR:1.1-2.6] years. We selected all baseline samples and two samples closest to the primary endpoint (PEP; composite of cardiovascular mortality, HF hospitalization, LVAD implantation, and heart transplantation) or censoring, and applied an aptamer-based multiplex proteomic approach. Using unsupervised machine learning methods, we derived clusters from 4210 repeatedly measured proteomic biomarkers. Sets of proteins that drove cluster allocation were analysed via an enrichment analysis. Differences in clinical characteristics and PEP occurrence were evaluated.

Findings

We identified four subphenotypes with different protein profiles, prognosis and clinical characteristics, including age (median [IQR] for subphenotypes 1-4, respectively:70 [64, 76], 68 [60, 79], 57 [47, 65], 59 [56, 66]years), EF (30 [26, 36], 26 [20, 38], 26 [22, 32], 33 [28, 37]%), and chronic renal failure (45%, 65%, 36%, 37%). Subphenotype allocation was driven by subsets of proteins associated with various biological functions, such as oxidative stress, inflammation and extracellular matrix organisation. Clinical characteristics of the subphenotypes were aligned with these associations. Subphenotypes 2 and 3 had the worst prognosis compared to subphenotype 1 (adjHR (95%CI):3.43 (1.76-6.69), and 2.88 (1.37-6.03), respectively).

Interpretation

Four circulating-protein based subphenotypes are present in HFrEF, which are driven by varying combinations of protein subsets, and have different clinical characteristics and prognosis.

Clinical trial registration

ClinicalTrials.gov Identifier: NCT01851538https://clinicaltrials.gov/ct2/show/NCT01851538.

Funding

EU/EFPIA IMI2JU BigData@Heart grant n°116074, Jaap Schouten Foundation and Noordwest Academie.",,pdf:http://www.thelancet.com/article/S2352396423002207/pdf; doi:https://doi.org/10.1016/j.ebiom.2023.104655; html:https://europepmc.org/articles/PMC10279550; pdf:https://europepmc.org/articles/PMC10279550?pdf=render 35143670,https://doi.org/10.1093/molbev/msac034,The Carbon Footprint of Bioinformatics.,"Grealey J, Lannelongue L, Saw WY, Marten J, Méric G, Ruiz-Carmona S, Inouye M.",,Molecular biology and evolution,2022,2022-03-01,Y,Bioinformatics; Genomics; Carbon Footprint; Green Algorithms,,,"Bioinformatic research relies on large-scale computational infrastructures which have a nonzero carbon footprint but so far, no study has quantified the environmental costs of bioinformatic tools and commonly run analyses. In this work, we estimate the carbon footprint of bioinformatics (in kilograms of CO2 equivalent units, kgCO2e) using the freely available Green Algorithms calculator (www.green-algorithms.org, last accessed 2022). We assessed 1) bioinformatic approaches in genome-wide association studies (GWAS), RNA sequencing, genome assembly, metagenomics, phylogenetics, and molecular simulations, as well as 2) computation strategies, such as parallelization, CPU (central processing unit) versus GPU (graphics processing unit), cloud versus local computing infrastructure, and geography. In particular, we found that biobank-scale GWAS emitted substantial kgCO2e and simple software upgrades could make it greener, for example, upgrading from BOLT-LMM v1 to v2.3 reduced carbon footprint by 73%. Moreover, switching from the average data center to a more efficient one can reduce carbon footprint by approximately 34%. Memory over-allocation can also be a substantial contributor to an algorithm's greenhouse gas emissions. The use of faster processors or greater parallelization reduces running time but can lead to greater carbon footprint. Finally, we provide guidance on how researchers can reduce power consumption and minimize kgCO2e. Overall, this work elucidates the carbon footprint of common analyses in bioinformatics and provides solutions which empower a move toward greener research.",,pdf:https://academic.oup.com/mbe/article-pdf/39/3/msac034/42692776/msac034.pdf; doi:https://doi.org/10.1093/molbev/msac034; html:https://europepmc.org/articles/PMC8892942; pdf:https://europepmc.org/articles/PMC8892942?pdf=render +37327673,https://doi.org/10.1016/j.ebiom.2023.104655,HFrEF subphenotypes based on 4210 repeatedly measured circulating proteins are driven by different biological mechanisms.,"Petersen TB, de Bakker M, Asselbergs FW, Harakalova M, Akkerhuis KM, Brugts JJ, van Ramshorst J, Lumbers RT, Ostroff RM, Katsikis PD, van der Spek PJ, Umans VA, Boersma E, Rizopoulos D, Kardys I.",,EBioMedicine,2023,2023-06-14,Y,Proteomics; Phenotypes; Biomarkers; Heart Failure; Unsupervised Machine Learning,,,"

Background

HFrEF is a heterogenous condition with high mortality. We used serial assessments of 4210 circulating proteins to identify distinct novel protein-based HFrEF subphenotypes and to investigate underlying dynamic biological mechanisms. Herewith we aimed to gain pathophysiological insights and fuel opportunities for personalised treatment.

Methods

In 382 patients, we performed trimonthly blood sampling during a median follow-up of 2.1 [IQR:1.1-2.6] years. We selected all baseline samples and two samples closest to the primary endpoint (PEP; composite of cardiovascular mortality, HF hospitalization, LVAD implantation, and heart transplantation) or censoring, and applied an aptamer-based multiplex proteomic approach. Using unsupervised machine learning methods, we derived clusters from 4210 repeatedly measured proteomic biomarkers. Sets of proteins that drove cluster allocation were analysed via an enrichment analysis. Differences in clinical characteristics and PEP occurrence were evaluated.

Findings

We identified four subphenotypes with different protein profiles, prognosis and clinical characteristics, including age (median [IQR] for subphenotypes 1-4, respectively:70 [64, 76], 68 [60, 79], 57 [47, 65], 59 [56, 66]years), EF (30 [26, 36], 26 [20, 38], 26 [22, 32], 33 [28, 37]%), and chronic renal failure (45%, 65%, 36%, 37%). Subphenotype allocation was driven by subsets of proteins associated with various biological functions, such as oxidative stress, inflammation and extracellular matrix organisation. Clinical characteristics of the subphenotypes were aligned with these associations. Subphenotypes 2 and 3 had the worst prognosis compared to subphenotype 1 (adjHR (95%CI):3.43 (1.76-6.69), and 2.88 (1.37-6.03), respectively).

Interpretation

Four circulating-protein based subphenotypes are present in HFrEF, which are driven by varying combinations of protein subsets, and have different clinical characteristics and prognosis.

Clinical trial registration

ClinicalTrials.gov Identifier: NCT01851538https://clinicaltrials.gov/ct2/show/NCT01851538.

Funding

EU/EFPIA IMI2JU BigData@Heart grant n°116074, Jaap Schouten Foundation and Noordwest Academie.",,pdf:http://www.thelancet.com/article/S2352396423002207/pdf; doi:https://doi.org/10.1016/j.ebiom.2023.104655; html:https://europepmc.org/articles/PMC10279550; pdf:https://europepmc.org/articles/PMC10279550?pdf=render 34571200,https://doi.org/10.1016/j.jaip.2021.09.026,Atopic Eczema-Associated Fracture Risk and Oral Corticosteroids: A Population-Based Cohort Study.,"Matthewman J, Mansfield KE, Prieto-Alhambra D, Mulick AR, Smeeth L, Lowe KE, Silverwood RJ, Langan SM.",,The journal of allergy and clinical immunology. In practice,2022,2021-09-24,Y,Fracture; Atopic Eczema; Atopic Dermatitis; osteoporotic fracture; Oral Corticosteroids,,,"

Background

Evidence suggests adults with atopic eczema have increased fracture risk. However, it is unclear whether oral corticosteroids explain the association.

Objective

To assess to what extent oral corticosteroids mediate the relationship between atopic eczema and fractures.

Methods

We conducted a cohort study using English primary care (Clinical Practice Research Datalink) and hospital admissions (Hospital Episode Statistics) records (1998-2016) including adults (18 years old and older) with atopic eczema matched (age, sex, and general practice) with up to 5 adults without atopic eczema. We used Cox regression to estimate hazard ratios (HRs) for specific major osteoporotic fractures (hip, spine, pelvis, or wrist) and for any-site fracture comparing individuals with atopic eczema with those without, adjusting for 6 different definitions of time-updated oral corticosteroid use (ever any prescription, ever high-dose, and recent, cumulative, current, or peak dose).

Results

We identified 526,808 individuals with atopic eczema and 2,569,030 without. We saw evidence of an association between atopic eczema and major osteoporotic fractures (eg, spine HR 1.15, 99% CI 1.08-1.22; hip HR 1.11, 99% CI 1.08-1.15) that remained after additionally adjusting for oral corticosteroids (eg, cumulative corticosteroid dose: spine HR 1.09, 99% CI 1.03-1.16; hip HR 1.09, 99% CI 1.06-1.12). Fracture rates were higher in people with severe atopic eczema than in people without even after adjusting for oral corticosteroids (eg, spine HR [99% CI]: confounder-adjusted 2.31 [1.91-2.81]; additionally adjusted for cumulative dose 1.71 [1.40-2.09]).

Conclusions

Our findings suggest that little of the association between atopic eczema and major osteoporotic fractures is explained by oral corticosteroid use.",,pdf:http://www.jaci-inpractice.org/article/S2213219821010187/pdf; doi:https://doi.org/10.1016/j.jaip.2021.09.026; html:https://europepmc.org/articles/PMC7612204; pdf:https://europepmc.org/articles/PMC7612204?pdf=render 38040454,https://doi.org/10.1101/cshperspect.a041473,Environmental Impacts of Machine Learning Applications in Protein Science.,"Lannelongue L, Inouye M.",,Cold Spring Harbor perspectives in biology,2023,2023-12-01,N,,,,"Computing tools and machine learning models play an increasingly important role in biology and are now an essential part of discoveries in protein science. The growing energy needs of modern algorithms have raised concerns in the computational science community in light of the climate emergency. In this work, we summarize the different ways in which protein science can negatively impact the environment and we present the carbon footprint of some popular protein algorithms: molecular simulations, inference of protein-protein interactions, and protein structure prediction. We show that large deep learning models such as AlphaFold and ESMFold can have carbon footprints reaching over 100 tonnes of CO2e in some cases. The magnitude of these impacts highlights the importance of monitoring and mitigating them, and we list actions scientists can take to achieve more sustainable protein computational science.",,pdf:http://cshperspectives.cshlp.org/content/15/12/a041473.full.pdf; doi:https://doi.org/10.1101/cshperspect.a041473 32616677,https://doi.org/10.1212/wnl.0000000000009924,Accuracy of identifying incident stroke cases from linked health care data in UK Biobank.,"Rannikmäe K, Ngoh K, Bush K, Al-Shahi Salman R, Doubal F, Flaig R, Henshall DE, Hutchison A, Nolan J, Osborne S, Samarasekera N, Schnier C, Whiteley W, Wilkinson T, Wilson K, Woodfield R, Zhang Q, Allen N, Sudlow CLM.",,Neurology,2020,2020-07-02,Y,,,,"

Objective

In UK Biobank (UKB), a large population-based prospective study, cases of many diseases are ascertained through linkage to routinely collected, coded national health datasets. We assessed the accuracy of these for identifying incident strokes.

Methods

In a regional UKB subpopulation (n = 17,249), we identified all participants with ≥1 code signifying a first stroke after recruitment (incident stroke-coded cases) in linked hospital admission, primary care, or death record data. Stroke physicians reviewed their full electronic patient records (EPRs) and generated reference standard diagnoses. We evaluated the number and proportion of cases that were true-positives (i.e., positive predictive value [PPV]) for all codes combined and by code source and type.

Results

Of 232 incident stroke-coded cases, 97% had EPR information available. Data sources were 30% hospital admission only, 39% primary care only, 28% hospital and primary care, and 3% death records only. While 42% of cases were coded as unspecified stroke type, review of EPRs enabled a pathologic type to be assigned in >99%. PPVs (95% confidence intervals) were 79% (73%-84%) for any stroke (89% for hospital admission codes, 80% for primary care codes) and 83% (74%-90%) for ischemic stroke. PPVs for small numbers of death record and hemorrhagic stroke codes were low but imprecise.

Conclusions

Stroke and ischemic stroke cases in UKB can be ascertained through linked health datasets with sufficient accuracy for many research studies. Further work is needed to understand the accuracy of death record and hemorrhagic stroke codes and to develop scalable approaches for better identifying stroke types.",,pdf:https://n.neurology.org/content/neurology/95/6/e697.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000009924; html:https://europepmc.org/articles/PMC7455356; pdf:https://europepmc.org/articles/PMC7455356?pdf=render 34819519,https://doi.org/10.1038/s41467-021-27164-0,Synergistic insights into human health from aptamer- and antibody-based proteomic profiling.,"Pietzner M, Wheeler E, Carrasco-Zanini J, Kerrison ND, Oerton E, Koprulu M, Luan J, Hingorani AD, Williams SA, Wareham NJ, Langenberg C.",,Nature communications,2021,2021-11-24,Y,,,,"Affinity-based proteomics has enabled scalable quantification of thousands of protein targets in blood enhancing biomarker discovery, understanding of disease mechanisms, and genetic evaluation of drug targets in humans through protein quantitative trait loci (pQTLs). Here, we integrate two partly complementary techniques-the aptamer-based SomaScan® v4 assay and the antibody-based Olink assays-to systematically assess phenotypic consequences of hundreds of pQTLs discovered for 871 protein targets across both platforms. We create a genetically anchored cross-platform proteome-phenome network comprising 547 protein-phenotype connections, 36.3% of which were only seen with one of the two platforms suggesting that both techniques capture distinct aspects of protein biology. We further highlight discordance of genetically predicted effect directions between assays, such as for PILRA and Alzheimer's disease. Our results showcase the synergistic nature of these technologies to better understand and identify disease mechanisms and provide a benchmark for future cross-platform discoveries.",,pdf:https://www.nature.com/articles/s41467-021-27164-0.pdf; doi:https://doi.org/10.1038/s41467-021-27164-0; html:https://europepmc.org/articles/PMC8613205; pdf:https://europepmc.org/articles/PMC8613205?pdf=render 36082449,https://doi.org/10.1002/ijc.34279,"Global colorectal cancer research, 2007-2021: Outputs and funding.","Begum M, Lewison G, Wang X, Dunne PD, Maughan T, Sullivan R, Lawler M.",,International journal of cancer,2023,2022-09-28,Y,Funding; Colorectal Cancer; disease burden; Research Outputs; Research Domains,,,"The purpose of this study was to provide an evidence base for colorectal cancer research activity that might influence policy, mainly at the national level. Improvements in healthcare delivery have lengthened life expectancy, but within a situation of increased cancer incidence. The disease burden of CRC has risen significantly, particularly in Africa, Asia and Latin America. Research is key to its control and reduction, but few studies have delineated the volume and funding of global research on CRC. We identified research papers in the Web of Science (WoS) from 2007 to 2021, and determined the contributions of the leading countries, the research domains studied, and their sources of funding. We identified 62 716 papers, representing 5.7% of all cancer papers. This percentage was somewhat disproportionate to the disease burden (7.7% in 2015), especially in Eastern Europe. International collaboration increased over the time period in almost all countries except in China. Genetics, surgery and prognosis were the leading research domains. However, research on palliative care and quality-of-life in CRC was lacking. In Western Europe, the main funding source was the charity sector, particularly in the UK, but in most other countries government played the leading role, especially in China and the USA. There was little support from industry. Several Asian countries provided minimal contestable funding, which may have reduced the impact of their CRC research. Certain countries must perform more CRC research overall, especially in domains such as screening, palliative care and quality-of-life. The private-non-profit sector should be an alternative source of support.",,doi:https://doi.org/10.1002/ijc.34279; doi:https://doi.org/10.1002/ijc.34279; html:https://europepmc.org/articles/PMC10086800; pdf:https://europepmc.org/articles/PMC10086800?pdf=render 32926504,https://doi.org/10.1002/pds.5121,Implementing high-dimensional propensity score principles to improve confounder adjustment in UK electronic health records.,"Tazare J, Smeeth L, Evans SJW, Williamson E, Douglas IJ.",,Pharmacoepidemiology and drug safety,2020,2020-09-14,N,Pharmacoepidemiology; Electronic Health Records; Electronic Medical Records; High-dimensional Propensity Score; Database Research; Confounder Adjustment,,,"

Purpose

Recent evidence from US claims data suggests use of high-dimensional propensity score (hd-PS) methods improve adjustment for confounding in non-randomised studies of interventions. However, it is unclear how best to apply hd-PS principles outside their original setting, given important differences between claims data and electronic health records (EHRs). We aimed to implement the hd-PS in the setting of United Kingdom (UK) EHRs.

Methods

We studied the interaction between clopidogrel and proton pump inhibitors (PPIs). Whilst previous observational studies suggested an interaction (with reduced effect of clopidogrel), case-only, genetic and randomised trial approaches showed no interaction, strongly suggesting the original observational findings were subject to confounding. We derived a cohort of clopidogrel users from the UK Clinical Practice Research Datalink linked with the Myocardial Ischaemia National Audit Project. Analyses estimated the hazard ratio (HR) for myocardial infarction (MI) comparing PPI users with non-users using a Cox model adjusting for confounders. To reflect unique characteristics of UK EHRs, we varied the application of hd-PS principles including the level of grouping within coding systems and adapting the assessment of code recurrence. Results were compared with traditional analyses.

Results

Twenty-four thousand four hundred and seventy-one patients took clopidogrel, of whom 9111 were prescribed a PPI. Traditional PS approaches obtained a HR for the association between PPI use and MI of 1.17 (95% CI: 1.00-1.35). Applying hd-PS modifications resulted in estimates closer to the expected null (HR 1.00; 95% CI: 0.78-1.28).

Conclusions

hd-PS provided improved adjustment for confounding compared with other approaches, suggesting hd-PS can be usefully applied in UK EHRs.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pds.5121; doi:https://doi.org/10.1002/pds.5121 -36812613,https://doi.org/10.1371/journal.pdig.0000190,Optimizing cardiovascular risk assessment and registration in a developing cardiovascular learning health care system: Women benefit most.,"Groenhof TKJ, Haitjema S, Lely AT, Grobbee DE, Asselbergs FW, Bots ML, UCC-CVRM and UPOD Study groups.",,PLOS digital health,2023,2023-02-08,Y,,,,"Since 2015 we organized a uniform, structured collection of a fixed set of cardiovascular risk factors according the (inter)national guidelines on cardiovascular risk management. We evaluated the current state of a developing cardiovascular towards learning healthcare system-the Utrecht Cardiovascular Cohort Cardiovascular Risk Management (UCC-CVRM)-and its potential effect on guideline adherence in cardiovascular risk management. We conducted a before-after study comparing data from patients included in UCC-CVRM (2015-2018) and patients treated in our center before UCC-CVRM (2013-2015) who would have been eligible for UCC-CVRM using the Utrecht Patient Oriented Database (UPOD). Proportions of cardiovascular risk factor measurement before and after UCC-CVRM initiation were compared, as were proportions of patients that required (change of) blood pressure, lipid, or blood glucose lowering treatment. We estimated the likelihood to miss patients with hypertension, dyslipidemia, and elevated HbA1c before UCC-CVRM for the whole cohort and stratified for sex. In the present study, patients included up to October 2018 (n = 1904) were matched with 7195 UPOD patients with similar age, sex, department of referral and diagnose description. Completeness of risk factor measurement increased, ranging from 0% -77% before to 82%-94% after UCC-CVRM initiation. Before UCC-CVRM, we found more unmeasured risk factors in women compared to men. This sex-gap resolved in UCC-CVRM. The likelihood to miss hypertension, dyslipidemia, and elevated HbA1c was reduced by 67%, 75% and 90%, respectively, after UCC-CVRM initiation. A finding more pronounced in women compared to men. In conclusion, a systematic registration of the cardiovascular risk profile substantially improves guideline adherent assessment and decreases the risk of missing patients with elevated levels with an indication for treatment. The sex-gap disappeared after UCC-CVRM initiation. Thus, an LHS approach contributes to a more inclusive insight into quality of care and prevention of cardiovascular disease (progression).",,pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000190&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000190; html:https://europepmc.org/articles/PMC9931327; pdf:https://europepmc.org/articles/PMC9931327?pdf=render 35459950,https://doi.org/10.1093/intqhc/mzac031,Modelling the effect of COVID-19 mass vaccination on acute hospital admissions.,"Booton RD, Powell AL, Turner KME, Wood RM.",,International journal for quality in health care : journal of the International Society for Quality in Health Care,2022,2022-05-01,N,Vaccination; Coronavirus; Mathematical Modelling; Bed Management; Hospital Capacity; Covid-19,,,"

Background

Managing high levels of acute COVID-19 bed occupancy can affect the quality of care provided to both affected patients and those requiring other hospital services. Mass vaccination has offered a route to reduce societal restrictions while protecting hospitals from being overwhelmed. Yet, early in the mass vaccination effort, the possible impact on future bed pressures remained subject to considerable uncertainty.

Objective

The aim of this study was to model the effect of vaccination on projections of acute and intensive care bed demand within a 1 million resident healthcare system located in South West England.

Methods

An age-structured epidemiological model of the susceptible-exposed-infectious-recovered type was fitted to local data up to the time of the study, in early March 2021. Model parameters and vaccination scenarios were calibrated through a system-wide multidisciplinary working group, comprising public health intelligence specialists, healthcare planners, epidemiologists and academics. Scenarios assumed incremental relaxations to societal restrictions according to the envisaged UK Government timeline, with all restrictions to be removed by 21 June 2021.

Results

Achieving 95% vaccine uptake in adults by 31 July 2021 would not avert the third wave in autumn 2021 but would produce a median peak bed requirement ∼6% (IQR: 1-24%) of that experienced during the second wave (January 2021). A 2-month delay in vaccine rollout would lead to significantly higher peak bed occupancy, at 66% (11-146%) of that of the second wave. If only 75% uptake was achieved (the amount typically associated with vaccination campaigns), then the second wave peak for acute and intensive care beds would be exceeded by 4% and 19%, respectively, an amount which would seriously pressure hospital capacity.

Conclusion

Modelling influenced decision-making among senior managers in setting COVID-19 bed capacity levels, as well as highlighting the importance of public health in promoting high vaccine uptake among the population. Forecast accuracy has since been supported by actual data collected following the analysis, with observed peak bed occupancy falling comfortably within the inter-quartile range of modelled projections.",,pdf:https://academic.oup.com/intqhc/article-pdf/34/2/mzac031/43704475/mzac031.pdf; doi:https://doi.org/10.1093/intqhc/mzac031 -35898465,https://doi.org/10.3389/fendo.2022.888924,Diabetic Foot Risk Classification at the Time of Type 2 Diabetes Diagnosis and Subsequent Risk of Mortality: A Population-Based Cohort Study.,"Wang Z, Hazlehurst J, Subramanian A, Tahrani AA, Hanif W, Thomas N, Singh P, Wang J, Sainsbury C, Nirantharakumar K, Crowe FL.",,Frontiers in endocrinology,2022,2022-07-11,Y,Mortality; Type 2 diabetes; Diabetic Foot Disease; Diabetic Foot Risk; Foot Risk Examination,,,"

Aim

We aimed to compare the mortality of individuals at low, moderate, and high risk of diabetic foot disease (DFD) in the context of newly diagnosed type 2 diabetes, before developing active diabetic foot problem.

Methods

This was a population-based cohort study of adults with newly diagnosed type 2 diabetes utilizing IQVIA Medical Research Data. The outcome was all-cause mortality among individuals with low, moderate, and high risk of DFD, and also in those with no record of foot assessment and those who declined foot examination.

Results

Of 225,787 individuals with newly diagnosed type 2 diabetes, 34,061 (15.1%) died during the study period from January 1, 2000 to December 31, 2019. Moderate risk and high risk of DFD were associated with increased mortality risk compared to low risk of DFD (adjusted hazard ratio [aHR] 1.50, 95% CI 1.42, 1.58; aHR 2.01, 95% CI 1.84, 2.20, respectively). Individuals who declined foot examination or who had no record also had increased mortality risk of 75% and 25% vs. those at low risk of DFD, respectively (aHR 1.75, 95% CI 1.51, 2.04; aHR 1.25, 95% CI 1.20, 1.30).

Conclusion

Individuals with new-onset type 2 diabetes who had moderate to high risk of DFD were more likely to die compared to those at low risk of DFD. The associations between declined foot examination and absence of foot examinations, and increased risk of mortality further highlight the importance of assessing foot risk as it identifies not only patients at risk of diabetic foot ulceration but also mortality.",,pdf:https://www.frontiersin.org/articles/10.3389/fendo.2022.888924/pdf; doi:https://doi.org/10.3389/fendo.2022.888924; html:https://europepmc.org/articles/PMC9309507; pdf:https://europepmc.org/articles/PMC9309507?pdf=render -34543272,https://doi.org/10.1371/journal.pcbi.1009324,Ten simple rules to make your computing more environmentally sustainable.,"Lannelongue L, Grealey J, Bateman A, Inouye M.",,PLoS computational biology,2021,2021-09-20,Y,,,,,,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009324&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1009324; html:https://europepmc.org/articles/PMC8452068; pdf:https://europepmc.org/articles/PMC8452068?pdf=render 33306026,https://doi.org/10.2196/23369,Engagement With a Behavior Change App for Alcohol Reduction: Data Visualization for Longitudinal Observational Study.,"Bell L, Garnett C, Qian T, Perski O, Williamson E, Potts HW.",,Journal of medical Internet research,2020,2020-12-11,Y,Engagement; Behavior Change; Apps; Mobile Health; Digital Health; Just-in-time Adaptive Interventions; Push Notifications; Micro-randomized Trial; Data Visualizations,,,"

Background

Behavior change apps can develop iteratively, where the app evolves into a complex, dynamic, or personalized intervention through cycles of research, development, and implementation. Understanding how existing users engage with an app (eg, frequency, amount, depth, and duration of use) can help guide further incremental improvements. We aim to explore how simple visualizations can provide a good understanding of temporal patterns of engagement, as usage data are often longitudinal and rich.

Objective

This study aims to visualize behavioral engagement with Drink Less, a behavior change app to help reduce hazardous and harmful alcohol consumption in the general adult population of the United Kingdom.

Methods

We explored behavioral engagement among 19,233 existing users of Drink Less. Users were included in the sample if they were from the United Kingdom; were 18 years or older; were interested in reducing their alcohol consumption; had a baseline Alcohol Use Disorders Identification Test score of 8 or above, indicative of excessive drinking; and had downloaded the app between May 17, 2017, and January 22, 2019 (615 days). Measures of when sessions begin, length of sessions, time to disengagement, and patterns of use were visualized with heat maps, timeline plots, k-modes clustering analyses, and Kaplan-Meier plots.

Results

The daily 11 AM notification is strongly associated with a change in engagement in the following hour; reduction in behavioral engagement over time, with 50.00% (9617/19,233) of users disengaging (defined as no use for 7 or more consecutive days) 22 days after download; identification of 3 distinct trajectories of use, namely engagers (4651/19,233, 24.18% of users), slow disengagers (3679/19,233, 19.13% of users), and fast disengagers (10,903/19,233, 56.68% of users); and limited depth of engagement with 85.076% (7,095,348/8,340,005) of screen views occurring within the Self-monitoring and Feedback module. In addition, a peak of both frequency and amount of time spent per session was observed in the evenings.

Conclusions

Visualizations play an important role in understanding engagement with behavior change apps. Here, we discuss how simple visualizations helped identify important patterns of engagement with Drink Less. Our visualizations of behavioral engagement suggest that the daily notification substantially impacts engagement. Furthermore, the visualizations suggest that a fixed notification policy can be effective for maintaining engagement for some users but ineffective for others. We conclude that optimizing the notification policy to target both effectiveness and engagement is a worthwhile investment. Our future goal is to both understand the causal effect of the notification on engagement and further optimize the notification policy within Drink Less by tailoring to contextual circumstances of individuals over time. Such tailoring will be informed from the findings of our micro-randomized trial (MRT), and these visualizations were useful in both gaining a better understanding of engagement and designing the MRT.",,pdf:https://www.jmir.org/2020/12/e23369/PDF; doi:https://doi.org/10.2196/23369; html:https://europepmc.org/articles/PMC7762688 -32788201,https://doi.org/10.1136/archdischild-2020-319027,Predictive value of indicators for identifying child maltreatment and intimate partner violence in coded electronic health records: a systematic review and meta-analysis.,"Syed S, Ashwick R, Schlosser M, Gonzalez-Izquierdo A, Li L, Gilbert R.",,Archives of disease in childhood,2021,2020-08-11,Y,Data collection; epidemiology; Child Abuse; Health Services Research; Drug Withdrawal,,,"

Objective

Electronic health records (EHRs) are routinely used to identify family violence, yet reliable evidence of their validity remains limited. We conducted a systematic review and meta-analysis to evaluate the positive predictive values (PPVs) of coded indicators in EHRs for identifying intimate partner violence (IPV) and child maltreatment (CM), including prenatal neglect.

Methods

We searched 18 electronic databases between January 1980 and May 2020 for studies comparing any coded indicator of IPV or CM including prenatal neglect defined as neonatal abstinence syndrome (NAS) or fetal alcohol syndrome (FAS), against an independent reference standard. We pooled PPVs for each indicator using random effects meta-analyses.

Results

We included 88 studies (3 875 183 individuals) involving 15 indicators for identifying CM in the prenatal period and childhood (0-18 years) and five indicators for IPV among women of reproductive age (12-50 years). Based on the International Classification of Disease system, the pooled PPV was over 80% for NAS (16 studies) but lower for FAS (<40%; seven studies). For young children, primary diagnoses of CM, specific injury presentations (eg, rib fractures and retinal haemorrhages) and assaults showed a high PPV for CM (pooled PPVs: 55.9%-87.8%). Indicators of IPV in women had a high PPV, with primary diagnoses correctly identifying IPV in >85% of cases.

Conclusions

Coded indicators in EHRs have a high likelihood of correctly classifying types of CM and IPV across the life course, providing a useful tool for assessment, support and monitoring of high-risk groups in health services and research.",,pdf:https://adc.bmj.com/content/archdischild/106/1/44.full.pdf; doi:https://doi.org/10.1136/archdischild-2020-319027; html:https://europepmc.org/articles/PMC7788194; pdf:https://europepmc.org/articles/PMC7788194?pdf=render +34543272,https://doi.org/10.1371/journal.pcbi.1009324,Ten simple rules to make your computing more environmentally sustainable.,"Lannelongue L, Grealey J, Bateman A, Inouye M.",,PLoS computational biology,2021,2021-09-20,Y,,,,,,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009324&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1009324; html:https://europepmc.org/articles/PMC8452068; pdf:https://europepmc.org/articles/PMC8452068?pdf=render +35898465,https://doi.org/10.3389/fendo.2022.888924,Diabetic Foot Risk Classification at the Time of Type 2 Diabetes Diagnosis and Subsequent Risk of Mortality: A Population-Based Cohort Study.,"Wang Z, Hazlehurst J, Subramanian A, Tahrani AA, Hanif W, Thomas N, Singh P, Wang J, Sainsbury C, Nirantharakumar K, Crowe FL.",,Frontiers in endocrinology,2022,2022-07-11,Y,Mortality; Type 2 diabetes; Diabetic Foot Disease; Diabetic Foot Risk; Foot Risk Examination,,,"

Aim

We aimed to compare the mortality of individuals at low, moderate, and high risk of diabetic foot disease (DFD) in the context of newly diagnosed type 2 diabetes, before developing active diabetic foot problem.

Methods

This was a population-based cohort study of adults with newly diagnosed type 2 diabetes utilizing IQVIA Medical Research Data. The outcome was all-cause mortality among individuals with low, moderate, and high risk of DFD, and also in those with no record of foot assessment and those who declined foot examination.

Results

Of 225,787 individuals with newly diagnosed type 2 diabetes, 34,061 (15.1%) died during the study period from January 1, 2000 to December 31, 2019. Moderate risk and high risk of DFD were associated with increased mortality risk compared to low risk of DFD (adjusted hazard ratio [aHR] 1.50, 95% CI 1.42, 1.58; aHR 2.01, 95% CI 1.84, 2.20, respectively). Individuals who declined foot examination or who had no record also had increased mortality risk of 75% and 25% vs. those at low risk of DFD, respectively (aHR 1.75, 95% CI 1.51, 2.04; aHR 1.25, 95% CI 1.20, 1.30).

Conclusion

Individuals with new-onset type 2 diabetes who had moderate to high risk of DFD were more likely to die compared to those at low risk of DFD. The associations between declined foot examination and absence of foot examinations, and increased risk of mortality further highlight the importance of assessing foot risk as it identifies not only patients at risk of diabetic foot ulceration but also mortality.",,pdf:https://www.frontiersin.org/articles/10.3389/fendo.2022.888924/pdf; doi:https://doi.org/10.3389/fendo.2022.888924; html:https://europepmc.org/articles/PMC9309507; pdf:https://europepmc.org/articles/PMC9309507?pdf=render +36812613,https://doi.org/10.1371/journal.pdig.0000190,Optimizing cardiovascular risk assessment and registration in a developing cardiovascular learning health care system: Women benefit most.,"Groenhof TKJ, Haitjema S, Lely AT, Grobbee DE, Asselbergs FW, Bots ML, UCC-CVRM and UPOD Study groups.",,PLOS digital health,2023,2023-02-08,Y,,,,"Since 2015 we organized a uniform, structured collection of a fixed set of cardiovascular risk factors according the (inter)national guidelines on cardiovascular risk management. We evaluated the current state of a developing cardiovascular towards learning healthcare system-the Utrecht Cardiovascular Cohort Cardiovascular Risk Management (UCC-CVRM)-and its potential effect on guideline adherence in cardiovascular risk management. We conducted a before-after study comparing data from patients included in UCC-CVRM (2015-2018) and patients treated in our center before UCC-CVRM (2013-2015) who would have been eligible for UCC-CVRM using the Utrecht Patient Oriented Database (UPOD). Proportions of cardiovascular risk factor measurement before and after UCC-CVRM initiation were compared, as were proportions of patients that required (change of) blood pressure, lipid, or blood glucose lowering treatment. We estimated the likelihood to miss patients with hypertension, dyslipidemia, and elevated HbA1c before UCC-CVRM for the whole cohort and stratified for sex. In the present study, patients included up to October 2018 (n = 1904) were matched with 7195 UPOD patients with similar age, sex, department of referral and diagnose description. Completeness of risk factor measurement increased, ranging from 0% -77% before to 82%-94% after UCC-CVRM initiation. Before UCC-CVRM, we found more unmeasured risk factors in women compared to men. This sex-gap resolved in UCC-CVRM. The likelihood to miss hypertension, dyslipidemia, and elevated HbA1c was reduced by 67%, 75% and 90%, respectively, after UCC-CVRM initiation. A finding more pronounced in women compared to men. In conclusion, a systematic registration of the cardiovascular risk profile substantially improves guideline adherent assessment and decreases the risk of missing patients with elevated levels with an indication for treatment. The sex-gap disappeared after UCC-CVRM initiation. Thus, an LHS approach contributes to a more inclusive insight into quality of care and prevention of cardiovascular disease (progression).",,pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000190&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000190; html:https://europepmc.org/articles/PMC9931327; pdf:https://europepmc.org/articles/PMC9931327?pdf=render 32103533,https://doi.org/10.1002/sim.8503,Propensity scores using missingness pattern information: a practical guide.,"Blake HA, Leyrat C, Mansfield KE, Seaman S, Tomlinson LA, Carpenter J, Williamson EJ.",,Statistics in medicine,2020,2020-02-27,N,Electronic Health Records; Propensity Score Analysis; Missingness Pattern; Missing Indicator; Missing Confounder Data,,,"Electronic health records are a valuable data source for investigating health-related questions, and propensity score analysis has become an increasingly popular approach to address confounding bias in such investigations. However, because electronic health records are typically routinely recorded as part of standard clinical care, there are often missing values, particularly for potential confounders. In our motivating study-using electronic health records to investigate the effect of renin-angiotensin system blockers on the risk of acute kidney injury-two key confounders, ethnicity and chronic kidney disease stage, have 59% and 53% missing data, respectively. The missingness pattern approach (MPA), a variant of the missing indicator approach, has been proposed as a method for handling partially observed confounders in propensity score analysis. In the MPA, propensity scores are estimated separately for each missingness pattern present in the data. Although the assumptions underlying the validity of the MPA are stated in the literature, it can be difficult in practice to assess their plausibility. In this article, we explore the MPA's underlying assumptions by using causal diagrams to assess their plausibility in a range of simple scenarios, drawing general conclusions about situations in which they are likely to be violated. We present a framework providing practical guidance for assessing whether the MPA's assumptions are plausible in a particular setting and thus deciding when the MPA is appropriate. We apply our framework to our motivating study, showing that the MPA's underlying assumptions appear reasonable, and we demonstrate the application of MPA to this study.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4656008/1/manuscript.pdf; doi:https://doi.org/10.1002/sim.8503; html:https://europepmc.org/articles/PMC7612316; pdf:https://europepmc.org/articles/PMC7612316?pdf=render; doi:https://doi.org/10.1002/sim.8503 -38692281,https://doi.org/10.1016/j.xgen.2024.100544,Blood-based epigenome-wide analyses of chronic low-grade inflammation across diverse population cohorts.,"Hillary RF, Ng HK, McCartney DL, Elliott HR, Walker RM, Campbell A, Huang F, Direk K, Welsh P, Sattar N, Corley J, Hayward C, McIntosh AM, Sudlow C, Evans KL, Cox SR, Chambers JC, Loh M, Relton CL, Marioni RE, Yousefi PD, Suderman M.",,Cell genomics,2024,2024-04-30,Y,Prediction; DNA methylation; C-reactive Protein; Feature Selection; Alspac; Chronic Inflammation; Helios; Sabre; Generation Scotland; Lothian Birth Cohorts,,,"Chronic inflammation is a hallmark of age-related disease states. The effectiveness of inflammatory proteins including C-reactive protein (CRP) in assessing long-term inflammation is hindered by their phasic nature. DNA methylation (DNAm) signatures of CRP may act as more reliable markers of chronic inflammation. We show that inter-individual differences in DNAm capture 50% of the variance in circulating CRP (N = 17,936, Generation Scotland). We develop a series of DNAm predictors of CRP using state-of-the-art algorithms. An elastic-net-regression-based predictor outperformed competing methods and explained 18% of phenotypic variance in the Lothian Birth Cohort of 1936 (LBC1936) cohort, doubling that of existing DNAm predictors. DNAm predictors performed comparably in four additional test cohorts (Avon Longitudinal Study of Parents and Children, Health for Life in Singapore, Southall and Brent Revisited, and LBC1921), including for individuals of diverse genetic ancestry and different age groups. The best-performing predictor surpassed assay-measured CRP and a genetic score in its associations with 26 health outcomes. Our findings forge new avenues for assessing chronic low-grade inflammation in diverse populations.",,doi:https://doi.org/10.1016/j.xgen.2024.100544; html:https://europepmc.org/articles/PMC11099341; pdf:https://europepmc.org/articles/PMC11099341?pdf=render +32788201,https://doi.org/10.1136/archdischild-2020-319027,Predictive value of indicators for identifying child maltreatment and intimate partner violence in coded electronic health records: a systematic review and meta-analysis.,"Syed S, Ashwick R, Schlosser M, Gonzalez-Izquierdo A, Li L, Gilbert R.",,Archives of disease in childhood,2021,2020-08-11,Y,Data collection; epidemiology; Child Abuse; Health Services Research; Drug Withdrawal,,,"

Objective

Electronic health records (EHRs) are routinely used to identify family violence, yet reliable evidence of their validity remains limited. We conducted a systematic review and meta-analysis to evaluate the positive predictive values (PPVs) of coded indicators in EHRs for identifying intimate partner violence (IPV) and child maltreatment (CM), including prenatal neglect.

Methods

We searched 18 electronic databases between January 1980 and May 2020 for studies comparing any coded indicator of IPV or CM including prenatal neglect defined as neonatal abstinence syndrome (NAS) or fetal alcohol syndrome (FAS), against an independent reference standard. We pooled PPVs for each indicator using random effects meta-analyses.

Results

We included 88 studies (3 875 183 individuals) involving 15 indicators for identifying CM in the prenatal period and childhood (0-18 years) and five indicators for IPV among women of reproductive age (12-50 years). Based on the International Classification of Disease system, the pooled PPV was over 80% for NAS (16 studies) but lower for FAS (<40%; seven studies). For young children, primary diagnoses of CM, specific injury presentations (eg, rib fractures and retinal haemorrhages) and assaults showed a high PPV for CM (pooled PPVs: 55.9%-87.8%). Indicators of IPV in women had a high PPV, with primary diagnoses correctly identifying IPV in >85% of cases.

Conclusions

Coded indicators in EHRs have a high likelihood of correctly classifying types of CM and IPV across the life course, providing a useful tool for assessment, support and monitoring of high-risk groups in health services and research.",,pdf:https://adc.bmj.com/content/archdischild/106/1/44.full.pdf; doi:https://doi.org/10.1136/archdischild-2020-319027; html:https://europepmc.org/articles/PMC7788194; pdf:https://europepmc.org/articles/PMC7788194?pdf=render 32657853,https://doi.org/10.1097/sap.0000000000002434,"Making the Most of Big Data in Plastic Surgery: Improving Outcomes, Protecting Patients, Informing Service Providers.","Gibson JAG, Dobbs TD, Kouzaris L, Lacey A, Thompson S, Akbari A, Hutchings HA, Lineaweaver WC, Lyons RA, Whitaker IS.",,Annals of plastic surgery,2021,2021-03-01,N,,,,"

Abstract

In medicine, ""big data"" refers to the interdisciplinary analysis of high-volume, diverse clinical and lifestyle information on large patient populations. Recent advancements in data storage and electronic record keeping have enabled the expansion of research in this field. In the United Kingdom, Big data has been highlighted as one of the government's ""8 Great Technologies,"" and the Medical Research Council has invested more than £100 million since 2012 in developing the Health Data Research UK infrastructure. The recent Royal College of Surgeons Commission of the Future of Surgery concluded that analysis of big data is one of the 4 most likely avenues to bring some of the most innovative changes to surgical practice in the 21st century.In this article, we provide an overview of the nascent field of big data analytics in plastic and highlight how it has the potential to improve outcomes, increase safety, and aid service planning.We outline the current resources available, the emerging role of big data within the subspecialties of burns, microsurgery, skin and breast cancer, and how these data can be used. We critically review the limitations and considerations raised with big data, offer suggestions regarding database optimization, and suggest future directions for research in this exciting field.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa53972/Download/53972__17281__0cb520258c2b49cdb0e751a62be92c5d.pdf; doi:https://doi.org/10.1097/SAP.0000000000002434 +38692281,https://doi.org/10.1016/j.xgen.2024.100544,Blood-based epigenome-wide analyses of chronic low-grade inflammation across diverse population cohorts.,"Hillary RF, Ng HK, McCartney DL, Elliott HR, Walker RM, Campbell A, Huang F, Direk K, Welsh P, Sattar N, Corley J, Hayward C, McIntosh AM, Sudlow C, Evans KL, Cox SR, Chambers JC, Loh M, Relton CL, Marioni RE, Yousefi PD, Suderman M.",,Cell genomics,2024,2024-04-30,Y,Prediction; DNA methylation; C-reactive Protein; Feature Selection; Alspac; Chronic Inflammation; Helios; Sabre; Generation Scotland; Lothian Birth Cohorts,,,"Chronic inflammation is a hallmark of age-related disease states. The effectiveness of inflammatory proteins including C-reactive protein (CRP) in assessing long-term inflammation is hindered by their phasic nature. DNA methylation (DNAm) signatures of CRP may act as more reliable markers of chronic inflammation. We show that inter-individual differences in DNAm capture 50% of the variance in circulating CRP (N = 17,936, Generation Scotland). We develop a series of DNAm predictors of CRP using state-of-the-art algorithms. An elastic-net-regression-based predictor outperformed competing methods and explained 18% of phenotypic variance in the Lothian Birth Cohort of 1936 (LBC1936) cohort, doubling that of existing DNAm predictors. DNAm predictors performed comparably in four additional test cohorts (Avon Longitudinal Study of Parents and Children, Health for Life in Singapore, Southall and Brent Revisited, and LBC1921), including for individuals of diverse genetic ancestry and different age groups. The best-performing predictor surpassed assay-measured CRP and a genetic score in its associations with 26 health outcomes. Our findings forge new avenues for assessing chronic low-grade inflammation in diverse populations.",,doi:https://doi.org/10.1016/j.xgen.2024.100544; html:https://europepmc.org/articles/PMC11099341; pdf:https://europepmc.org/articles/PMC11099341?pdf=render 35793336,https://doi.org/10.1371/journal.pone.0266521,"Spatiotemporal mapping of major trauma in Victoria, Australia.","Beck B, Zammit-Mangion A, Fry R, Smith K, Gabbe B.",,PloS one,2022,2022-07-06,Y,,,,"

Background

Spatiotemporal modelling techniques allow one to predict injury across time and space. However, such methods have been underutilised in injury studies. This study demonstrates the use of statistical spatiotemporal modelling in identifying areas of significantly high injury risk, and areas witnessing significantly increasing risk over time.

Methods

We performed a retrospective review of hospitalised major trauma patients from the Victorian State Trauma Registry, Australia, between 2007 and 2019. Geographical locations of injury events were mapped to the 79 local government areas (LGAs) in the state. We employed Bayesian spatiotemporal models to quantify spatial and temporal patterns, and analysed the results across a range of geographical remoteness and socioeconomic levels.

Results

There were 31,317 major trauma patients included. For major trauma overall, we observed substantial spatial variation in injury incidence and a significant 2.1% increase in injury incidence per year. Area-specific risk of injury by motor vehicle collision was higher in regional areas relative to metropolitan areas, while risk of injury by low fall was higher in metropolitan areas. Significant temporal increases were observed in injury by low fall, and the greatest increases were observed in the most disadvantaged LGAs.

Conclusions

These findings can be used to inform injury prevention initiatives, which could be designed to target areas with relatively high injury risk and with significantly increasing injury risk over time. Our finding that the greatest year-on-year increases in injury incidence were observed in the most disadvantaged areas highlights the need for a greater emphasis on reducing inequities in injury.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0266521&type=printable; doi:https://doi.org/10.1371/journal.pone.0266521; html:https://europepmc.org/articles/PMC9258853; pdf:https://europepmc.org/articles/PMC9258853?pdf=render 33147524,https://doi.org/10.1016/j.puhe.2020.08.027,Adverse childhood experiences during childhood and academic attainment at age 7 and 11 years: an electronic birth cohort study.,"Evans A, Hardcastle K, Bandyopadhyay A, Farewell D, John A, Lyons RA, Long S, Bellis MA, Paranjothy S.",,Public health,2020,2020-11-02,N,Social Inequalities; Adverse Childhood Experiences; Education Outcomes,,,"

Objectives

Adverse childhood experiences (ACEs) have a negative impact on childhood health, but their impact on education outcomes is less well known. We investigated whether or not ACEs were associated with reduced educational attainment at age 7 and 11 years.

Study design

The study design used in the study is a population-based electronic cohort study.

Methods

We analysed data from a total population electronic child cohort in Wales, UK. ACEs (exposures) were living with an adult household member with any of (i) serious mental illness, (ii) common mental disorder (CMD), (iii) an alcohol problem; (iv) child victimisation, (v) death of a household member and (vi) low family income. We used multilevel logistic regression to model exposure to these ACEs and not attaining the expected level at statutory education assessments, Key Stage (KS) 1 and KS2 separately, adjusted for known confounders including perinatal, socio-economic and school factors.

Results

There were 107,479 and 43,648 children included in the analysis, with follow-up to 6-7 years (KS1) and 10-11 years (KS2), respectively. An increased risk of not attaining the expected level at KS1 was associated with living with adult household members with CMD (adjusted odds ratio [aOR]: 1.13 [95% confidence interval [CI]: 1.09-1.17]) or an alcohol problem (adjusted odds ratio [aOR]: 1.16 [95% confidence interval [CI]: 1.10-1.22]), childhood victimisation (adjusted odds ratio [aOR]: 1.58 [95% confidence interval [CI]: 1.37-1.82]), death of a household member (adjusted odds ratio [aOR]: 1.14 [95% confidence interval [CI]: 1.04-1.25]) and low family income (adjusted odds ratio [aOR]: 1.92 [95% confidence interval [CI]: 1.84-2.01]). Similar results were observed for KS2. Children with multiple adversities had substantially increased odds of not attaining the expected level at each educational assessment.

Conclusion

The educational potential of many children may not be achieved due to exposure to adversity in childhood. Affected children who come in to contact with services should have relevant information shared between health and care services, and schools to initiate and facilitate a coordinated approach towards providing additional support and help for them to fulfil their educational potential, and subsequent economic and social participation.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa55250/Download/55250__18631__3d6d08f3b7ee4cb8ad15423815dac637.pdf; doi:https://doi.org/10.1016/j.puhe.2020.08.027 37609702,https://doi.org/10.1002/pds.5681,Adverse drug reactions and hospital admissions: Large case-control study of patients aged 65-100 years using linked English primary care and hospital data.,"van Staa TP, Pirmohamed M, Sharma A, Ashcroft DM, Buchan I.",,Pharmacoepidemiology and drug safety,2024,2023-08-23,N,Adverse drug reactions; Primary Care; Medicines; Pharmacovigilance; Polypharmacy,,,"

Background

Adverse drug reactions (ADRs) are common and a leading cause of injury. However, information on ADR risks of individual medicines is often limited. The aim of this hypothesis-generating study was to assess the relative importance of ADR-related and emergency hospital admission for large group of medication classes.

Methods

This study was a propensity-matched case-control study in English primary care. Data sources were Clinical Practice Research Databank and Aurum with longitudinal, anonymized, patient level electronic health records (EHRs) from English general practices linked to hospital records. Cases aged 65-100 with ADR-related or emergency hospital admission were matched to up to six controls by age, sex, morbidity and propensity scores for hospital admission risk. Medication groups with systemic administration as listed in the British National Formulary (used by prescribers for medication advice). Prescribing in the 84 days before the index date was assessed. Only medication groups with 50+ cases exposed were analysed. The outcomes of interest were ADR-related and emergency hospital admissions. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CI).

Results

The overall population included 121 546 cases with an ADR-related and 849 769 cases with emergency hospital admission. The percentage of hospitalizations with an ADR-related code for admission diagnosis was 1.83% and 6.58% with an ADR-related code at any time during hospitalization. A total of 137 medication groups was included in the main ADR analyses. Of these, 13 (9.5%) had statistically non-significant adjusted ORs, 58 (42.3%) statistically significant ORs between 1.0 and 1.5, 37 (27.0%) between 1.5-2.0, 18 (13.1%) between 2.0-3.0 and 11 (8.0%) 3.0 or higher. Several classes of antibiotics (including penicillins) were among medicines with largest ORs. Evaluating the 14 medications most often associated with ADRs, a strong association was found between the number of these medicines and the risk of ADR-related hospital admission (adjusted OR of 7.53 (95% CI 7.15-7.93) for those exposed to 6+ of these medicines).

Conclusions and relevance

There is a need for a regular systematic assessment of the harm-benefit ratio of medicines, harvesting the information in large healthcare databases and combining it with causality assessment of individual case histories.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pds.5681; doi:https://doi.org/10.1002/pds.5681 @@ -1025,15 +1025,15 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 36576182,https://doi.org/10.1136/bmjopen-2021-058058,Assessing machine learning for fair prediction of ADHD in school pupils using a retrospective cohort study of linked education and healthcare data.,"Ter-Minassian L, Viani N, Wickersham A, Cross L, Stewart R, Velupillai S, Downs J.",,BMJ open,2022,2022-12-05,Y,Mental health; epidemiology; Child & Adolescent Psychiatry,,,"

Objectives

Attention deficit hyperactivity disorder (ADHD) is a prevalent childhood disorder, but often goes unrecognised and untreated. To improve access to services, accurate predictions of populations at high risk of ADHD are needed for effective resource allocation. Using a unique linked health and education data resource, we examined how machine learning (ML) approaches can predict risk of ADHD.

Design

Retrospective population cohort study.

Setting

South London (2007-2013).

Participants

n=56 258 pupils with linked education and health data.

Primary outcome measures

Using area under the curve (AUC), we compared the predictive accuracy of four ML models and one neural network for ADHD diagnosis. Ethnic group and language biases were weighted using a fair pre-processing algorithm.

Results

Random forest and logistic regression prediction models provided the highest predictive accuracy for ADHD in population samples (AUC 0.86 and 0.86, respectively) and clinical samples (AUC 0.72 and 0.70). Precision-recall curve analyses were less favourable. Sociodemographic biases were effectively reduced by a fair pre-processing algorithm without loss of accuracy.

Conclusions

ML approaches using linked routinely collected education and health data offer accurate, low-cost and scalable prediction models of ADHD. These approaches could help identify areas of need and inform resource allocation. Introducing 'fairness weighting' attenuates some sociodemographic biases which would otherwise underestimate ADHD risk within minority groups.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e058058.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-058058; html:https://europepmc.org/articles/PMC9723859; pdf:https://europepmc.org/articles/PMC9723859?pdf=render 31685485,https://doi.org/10.1136/bmjopen-2019-031365,"Diagnosed prevalence of Ehlers-Danlos syndrome and hypermobility spectrum disorder in Wales, UK: a national electronic cohort study and case-control comparison.","Demmler JC, Atkinson MD, Reinhold EJ, Choy E, Lyons RA, Brophy ST.",,BMJ open,2019,2019-11-04,Y,Prevalence; Joint Hypermobility Syndrome; Ehlers-danlos Syndromes; Heritable Disorders Of Connective Tissue; Health Data Linkage; Hypermobility Spectrum Disorder,Improving Public Health,,"

Objectives

To describe the epidemiology of diagnosed hypermobility spectrum disorder (HSD) and Ehlers-Danlos syndromes (EDS) using linked electronic medical records. To examine whether these conditions remain rare and primarily affect the musculoskeletal system.

Design

Nationwide linked electronic cohort and nested case-control study.

Setting

Routinely collected data from primary care and hospital admissions in Wales, UK.

Participants

People within the primary care or hospital data systems with a coded diagnosis of EDS or joint hypermobility syndrome (JHS) between 1 July 1990 and 30 June 2017.

Main outcome measures

Combined prevalence of JHS and EDS in Wales. Additional diagnosis and prescription data in those diagnosed with EDS or JHS compared with matched controls.

Results

We found 6021 individuals (men: 30%, women: 70%) with a diagnostic code of either EDS or JHS. This gives a diagnosed point prevalence of 194.2 per 100 000 in 2016/2017 or roughly 10 cases in a practice of 5000 patients. There was a pronounced gender difference of 8.5 years (95% CI: 7.70 to 9.22) in the mean age at diagnosis. EDS or JHS was not only associated with high odds for other musculoskeletal diagnoses and drug prescriptions but also with significantly higher odds of a diagnosis in other disease categories (eg, mental health, nervous and digestive systems) and higher odds of a prescription in most disease categories (eg, gastrointestinal and cardiovascular drugs) within the 12 months before and after the first recorded diagnosis.

Conclusions

EDS and JHS (since March 2017 classified as EDS or HSD) have historically been considered rare diseases only affecting the musculoskeletal system and soft tissues. These data demonstrate that both these assertions should be reconsidered.","epidemiological study looking at the prevalence of ehlos danlos syndrome and joint hypermobility syndrome, using SAIL database for welsh population. They found a steady increase in the rates of diagnosis for these two diseases, higher odds of being on other medication, and association with other diseases categories.",pdf:https://bmjopen.bmj.com/content/bmjopen/9/11/e031365.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-031365; html:https://europepmc.org/articles/PMC6858200; pdf:https://europepmc.org/articles/PMC6858200?pdf=render 35308999,https://doi.org/,Axes of Prognosis: Identifying Subtypes of COVID-19 Outcomes.,"Whitfield E, Coffey C, Zhang H, Shi T, Wu X, Li Q, Wu H.",,AMIA ... Annual Symposium proceedings. AMIA Symposium,2021,2021-01-01,N,,,,"COVID-19 is a disease with vast impact, yet much remains unclear about patient outcomes. Most approaches to risk prediction of COVID-19 focus on binary or tertiary severity outcomes, despite the heterogeneity of the disease. In this work, we identify heterogeneous subtypes of COVID-19 outcomes by considering 'axes' of prognosis. We propose two innovative clustering approaches - 'Layered Axes' and 'Prognosis Space' - to apply on patients' outcome data. We then show how these clusters can help predict a patient's deterioration pathway on their hospital admission, using random forest classification. We illustrate this methodology on a cohort from Wuhan in early 2020. We discover interesting subgroups of poor prognosis, particularly within respiratory patients, and predict respiratory subgroup membership with high accuracy. This work could assist clinicians in identifying appropriate treatments at patients' hospital admission. Moreover, our method could be used to explore subtypes of 'long COVID' and other diseases with heterogeneous outcomes.",,html:https://europepmc.org/articles/PMC8861682; pdf:https://europepmc.org/articles/PMC8861682?pdf=render -37306981,https://doi.org/10.1001/jamaneurol.2023.1580,Independent Associations of Incident Epilepsy and Enzyme-Inducing and Non-Enzyme-Inducing Antiseizure Medications With the Development of Osteoporosis.,"Josephson CB, Gonzalez-Izquierdo A, Denaxas S, Sajobi TT, Klein KM, Wiebe S.",,JAMA neurology,2023,2023-08-01,N,,,,"

Importance

Both epilepsy and enzyme-inducing antiseizure medications (eiASMs) having varying reports of an association with increased risks for osteoporosis.

Objective

To quantify and model the independent hazards for osteoporosis associated with incident epilepsy and eiASMS and non-eiASMs.

Design, setting, and participants

This open cohort study covered the years 1998 to 2019, with a median (IQR) follow-up of 5 (1.7-11.1) years. Data were collected for 6275 patients enrolled in the Clinical Practice Research Datalink and from hospital electronic health records. No patients who met inclusion criteria (Clinical Practice Research Datalink-acceptable data, aged 18 years or older, follow-up after the Hospital Episode Statistics patient care linkage date of 1998, and free of osteoporosis at baseline) were excluded or declined.

Exposure

Incident adult-onset epilepsy using a 5-year washout and receipt of 4 consecutive ASMs.

Main outcomes and measures

The outcome was incident osteoporosis as determined through Cox proportional hazards or accelerated failure time models where appropriate. Incident epilepsy was treated as a time-varying covariate. Analyses controlled for age, sex, socioeconomic status, cancer, 1 or more years of corticosteroid use, body mass index, bariatric surgery, eating disorders, hyperthyroidism, inflammatory bowel disease, rheumatoid arthritis, smoking status, falls, fragility fractures, and osteoporosis screening tests. Subsequent analyses (1) excluded body mass index, which was missing in 30% of patients; (2) applied propensity score matching for receipt of an eiASM; (3) restricted analyses to only those with incident onset epilepsy; and (4) restricted analyses to patients who developed epilepsy at age 65 years or older. Analyses were performed between July 1 and October 31, 2022, and in February 2023 for revisions.

Results

Of 8 095 441 adults identified, 6275 had incident adult-onset epilepsy (3220 female [51%] and 3055 male [49%]; incidence rate, 62 per 100 000 person-years) with a median (IQR) age of 56 (38-73) years. When controlling for osteoporosis risk factors, incident epilepsy was independently associated with a 41% faster time to incident osteoporosis (time ratio [TR], 0.59; 95% CI, 0.52-0.67; P < .001). Both eiASMs (TR, 0.91; 95% CI, 0.87-0.95; P < .001) and non-eiASMs (TR, 0.77; 95% CI, 0.76-0.78; P < .001) were also associated with significant increased risks independent of epilepsy, accounting for 9% and 23% faster times to development of osteoporosis, respectively. The independent associations among epilepsy, eiASMs, and non-eiASMs remained consistent in propensity score-matched analyses, cohorts restricted to adult-onset epilepsy, and cohorts restricted to late-onset epilepsy.

Conclusions and relevance

These findings suggest that epilepsy is independently associated with a clinically meaningful increase in the risk for osteoporosis, as are both eiASMs and non-eiASMs. Routine screening and prophylaxis should be considered in all people with epilepsy.",,doi:https://doi.org/10.1001/jamaneurol.2023.1580 31153319,https://doi.org/10.1121/1.5100272,Developing a large scale population screening tool for the assessment of Parkinson's disease using telephone-quality voice.,"Arora S, Baghai-Ravary L, Tsanas A.",,The Journal of the Acoustical Society of America,2019,2019-05-01,N,,Applied Analytics,neurological,"Recent studies have demonstrated that analysis of laboratory-quality voice recordings can be used to accurately differentiate people diagnosed with Parkinson's disease (PD) from healthy controls (HCs). These findings could help facilitate the development of remote screening and monitoring tools for PD. In this study, 2759 telephone-quality voice recordings from 1483 PD and 15 321 recordings from 8300 HC participants were analyzed. To account for variations in phonetic backgrounds, data were acquired from seven countries. A statistical framework for analyzing voice was developed, whereby 307 dysphonia measures that quantify different properties of voice impairment, such as breathiness, roughness, monopitch, hoarse voice quality, and exaggerated vocal tremor, were computed. Feature selection algorithms were used to identify robust parsimonious feature subsets, which were used in combination with a random forests (RFs) classifier to accurately distinguish PD from HC. The best tenfold cross-validation performance was obtained using Gram-Schmidt orthogonalization and RF, leading to mean sensitivity of 64.90% (standard deviation, SD, 2.90%) and mean specificity of 67.96% (SD 2.90%). This large scale study is a step forward toward assessing the development of a reliable, cost-effective, and practical clinical decision support tool for screening the population at large for PD using telephone-quality voice.",,pdf:https://asa.scitation.org/doi/pdf/10.1121/1.5100272; doi:https://doi.org/10.1121/1.5100272; html:https://europepmc.org/articles/PMC6509044; pdf:https://europepmc.org/articles/PMC6509044?pdf=render; doi:https://doi.org/10.1121/1.5100272 +37306981,https://doi.org/10.1001/jamaneurol.2023.1580,Independent Associations of Incident Epilepsy and Enzyme-Inducing and Non-Enzyme-Inducing Antiseizure Medications With the Development of Osteoporosis.,"Josephson CB, Gonzalez-Izquierdo A, Denaxas S, Sajobi TT, Klein KM, Wiebe S.",,JAMA neurology,2023,2023-08-01,N,,,,"

Importance

Both epilepsy and enzyme-inducing antiseizure medications (eiASMs) having varying reports of an association with increased risks for osteoporosis.

Objective

To quantify and model the independent hazards for osteoporosis associated with incident epilepsy and eiASMS and non-eiASMs.

Design, setting, and participants

This open cohort study covered the years 1998 to 2019, with a median (IQR) follow-up of 5 (1.7-11.1) years. Data were collected for 6275 patients enrolled in the Clinical Practice Research Datalink and from hospital electronic health records. No patients who met inclusion criteria (Clinical Practice Research Datalink-acceptable data, aged 18 years or older, follow-up after the Hospital Episode Statistics patient care linkage date of 1998, and free of osteoporosis at baseline) were excluded or declined.

Exposure

Incident adult-onset epilepsy using a 5-year washout and receipt of 4 consecutive ASMs.

Main outcomes and measures

The outcome was incident osteoporosis as determined through Cox proportional hazards or accelerated failure time models where appropriate. Incident epilepsy was treated as a time-varying covariate. Analyses controlled for age, sex, socioeconomic status, cancer, 1 or more years of corticosteroid use, body mass index, bariatric surgery, eating disorders, hyperthyroidism, inflammatory bowel disease, rheumatoid arthritis, smoking status, falls, fragility fractures, and osteoporosis screening tests. Subsequent analyses (1) excluded body mass index, which was missing in 30% of patients; (2) applied propensity score matching for receipt of an eiASM; (3) restricted analyses to only those with incident onset epilepsy; and (4) restricted analyses to patients who developed epilepsy at age 65 years or older. Analyses were performed between July 1 and October 31, 2022, and in February 2023 for revisions.

Results

Of 8 095 441 adults identified, 6275 had incident adult-onset epilepsy (3220 female [51%] and 3055 male [49%]; incidence rate, 62 per 100 000 person-years) with a median (IQR) age of 56 (38-73) years. When controlling for osteoporosis risk factors, incident epilepsy was independently associated with a 41% faster time to incident osteoporosis (time ratio [TR], 0.59; 95% CI, 0.52-0.67; P < .001). Both eiASMs (TR, 0.91; 95% CI, 0.87-0.95; P < .001) and non-eiASMs (TR, 0.77; 95% CI, 0.76-0.78; P < .001) were also associated with significant increased risks independent of epilepsy, accounting for 9% and 23% faster times to development of osteoporosis, respectively. The independent associations among epilepsy, eiASMs, and non-eiASMs remained consistent in propensity score-matched analyses, cohorts restricted to adult-onset epilepsy, and cohorts restricted to late-onset epilepsy.

Conclusions and relevance

These findings suggest that epilepsy is independently associated with a clinically meaningful increase in the risk for osteoporosis, as are both eiASMs and non-eiASMs. Routine screening and prophylaxis should be considered in all people with epilepsy.",,doi:https://doi.org/10.1001/jamaneurol.2023.1580 31611193,https://doi.org/10.1136/archdischild-2019-317248,"Self-harm presentation across healthcare settings by sex in young people: an e-cohort study using routinely collected linked healthcare data in Wales, UK.","Marchant A, Turner S, Balbuena L, Peters E, Williams D, Lloyd K, Lyons R, John A.",,Archives of disease in childhood,2020,2019-10-14,Y,epidemiology; Child Psychiatry; Accident & Emergency; Adolescent Health; Health Service,,,"

Background

This study used individual-level linked data across general practice, emergency departments (EDs), outpatients and hospital admissions to examine contacts across settings and time by sex for self-harm in individuals aged 10-24 years old in Wales, UK.

Methods

A whole population-based e-cohort study of routinely collected healthcare data was conducted. Rates of self-harm across settings over time by sex were examined. Individuals were categorised based on the service(s) to which they presented.

Results

A total of 937 697 individuals aged 10-24 years contributed 5 369 794 person years of data from 1 January 2003 to 30 September 2015. Self-harm incidence was highest in primary care but remained stable over time (incident rate ratio (IRR)=1.0; 95% CI 0.9 to 1.1). Incidence of ED attendance increased over time (IRR=1.3; 95% CI 1.2 to 1.5) as did hospital admissions (IRR=1.4; 95% CI 1.1 to 1.6). Incidence in the 15-19 years age group was the highest across all settings. The largest increases were seen in the youngest age group. There were increases in ED attendances for both sexes; however, females are more likely than males to be admitted following this. This was most evident in individuals 10-15 years old, where 76% of females were admitted compared with just 49% of males. The majority of associated outpatient appointments were under a mental health specialty.

Conclusions

This is the first study to compare self-harm in people aged 10-24 years across primary care, EDs and hospital settings in the UK. The high rates of self-harm in primary care and for young men in EDs highlight these as important settings for intervention.",,pdf:https://adc.bmj.com/content/archdischild/105/4/347.full.pdf; doi:https://doi.org/10.1136/archdischild-2019-317248; html:https://europepmc.org/articles/PMC7146921; pdf:https://europepmc.org/articles/PMC7146921?pdf=render 35997594,https://doi.org/10.1099/mic.0.001223,Diagnostic MALDI-TOF MS can differentiate between high and low toxic Staphylococcus aureus bacteraemia isolates as a predictor of patient outcome.,"Brignoli T, Recker M, Lee WWY, Dong T, Bhamber R, Albur M, Williams P, Dowsey AW, Massey RC.",,"Microbiology (Reading, England)",2022,2022-08-01,Y,Toxicity; Staphylococcus aureus; Bacteraemia; agr; Maldi-tof Ms Diagnosis,,,"Staphylococcus aureus bacteraemia (SAB) is a major cause of blood-stream infection (BSI) in both healthcare and community settings. While the underlying comorbidities of a patient significantly contributes to their susceptibility to and outcome following SAB, recent studies show the importance of the level of cytolytic toxin production by the infecting bacterium. In this study we demonstrate that this cytotoxicity can be determined directly from the diagnostic MALDI-TOF mass spectrum generated in a routine diagnostic laboratory. With further development this information could be used to guide the management and improve the outcomes for SAB patients.",,pdf:https://research-information.bris.ac.uk/files/356539118/mic001223.pdf; doi:https://doi.org/10.1099/mic.0.001223; html:https://europepmc.org/articles/PMC10323763; pdf:https://europepmc.org/articles/PMC10323763?pdf=render 37963560,https://doi.org/10.1098/rsif.2023.0410,Spatio-temporal surveillance and early detection of SARS-CoV-2 variants of concern: a retrospective analysis.,"Cavallaro M, Dyson L, Tildesley MJ, Todkill D, Keeling MJ.",,"Journal of the Royal Society, Interface",2023,2023-11-15,Y,Disease Emergence; Anomaly Detection; Early Warning Signals; Sars-cov-2,,,"The SARS-CoV-2 pandemic has been characterized by the repeated emergence of genetically distinct virus variants of increased transmissibility and immune evasion compared to pre-existing lineages. In many countries, their containment required the intervention of public health authorities and the imposition of control measures. While the primary role of testing is to identify infection, target treatment, and limit spread (through isolation and contact tracing), a secondary benefit is in terms of surveillance and the early detection of new variants. Here we study the spatial invasion and early spread of the Alpha, Delta and Omicron (BA.1 and BA.2) variants in England from September 2020 to February 2022 using the random neighbourhood covering (RaNCover) method. This is a statistical technique for the detection of aberrations in spatial point processes, which we tailored here to community PCR (polymerase-chain-reaction) test data where the TaqPath kit provides a proxy measure of the switch between variants. Retrospectively, RaNCover detected the earliest signals associated with the four novel variants that led to large infection waves in England. With suitable data our method therefore has the potential to rapidly detect outbreaks of future SARS-CoV-2 variants, thus helping to inform targeted public health interventions.",,doi:https://doi.org/10.1098/rsif.2023.0410; html:https://europepmc.org/articles/PMC10645511; pdf:https://europepmc.org/articles/PMC10645511?pdf=render 37191413,https://doi.org/10.14336/ad.2022.1107,Conceptual Overview of Biological Age Estimation.,"Salih A, Nichols T, Szabo L, Petersen SE, Raisi-Estabragh Z.",,Aging and disease,2023,2023-06-01,Y,,,,"Chronological age is an imperfect measure of the aging process, which is affected by a wide range of genetic and environmental exposures. Biological age estimates may be derived using mathematical modelling with biomarkers set as predictors and chronological age as the output. The difference between biological and chronological age is denoted the ""age gap"" and considered a complementary indicator of aging. The utility of the ""age gap"" metric is assessed through examination of its associations with exposures of interest and the demonstration of additional information provided by this metric over chronological age alone. This paper reviews the key concepts of biological age estimation, the age gap metric, and approaches to assessment of model performance in this context. We further discuss specific challenges for the field, in particular the limited generalisability of effect sizes across studies owing to dependency of the age gap metric on pre-processing and model building methods. The discussion will be centred on brain age estimation, but the concepts are transferable to all biological age estimation.",,pdf:http://www.aginganddisease.org/EN/PDF/10.14336/AD.2022.1107; doi:https://doi.org/10.14336/AD.2022.1107; html:https://europepmc.org/articles/PMC10187689; pdf:https://europepmc.org/articles/PMC10187689?pdf=render +31765395,https://doi.org/10.1371/journal.pone.0225625,Semantic computational analysis of anticoagulation use in atrial fibrillation from real world data.,"Bean DM, Teo J, Wu H, Oliveira R, Patel R, Bendayan R, Shah AM, Dobson RJB, Scott PA.",,PloS one,2019,2019-11-25,Y,,,,"Atrial fibrillation (AF) is the most common arrhythmia and significantly increases stroke risk. This risk is effectively managed by oral anticoagulation. Recent studies using national registry data indicate increased use of anticoagulation resulting from changes in guidelines and the availability of newer drugs. The aim of this study is to develop and validate an open source risk scoring pipeline for free-text electronic health record data using natural language processing. AF patients discharged from 1st January 2011 to 1st October 2017 were identified from discharge summaries (N = 10,030, 64.6% male, average age 75.3 ± 12.3 years). A natural language processing pipeline was developed to identify risk factors in clinical text and calculate risk for ischaemic stroke (CHA2DS2-VASc) and bleeding (HAS-BLED). Scores were validated vs two independent experts for 40 patients. Automatic risk scores were in strong agreement with the two independent experts for CHA2DS2-VASc (average kappa 0.78 vs experts, compared to 0.85 between experts). Agreement was lower for HAS-BLED (average kappa 0.54 vs experts, compared to 0.74 between experts). In high-risk patients (CHA2DS2-VASc ≥2) OAC use has increased significantly over the last 7 years, driven by the availability of DOACs and the transitioning of patients from AP medication alone to OAC. Factors independently associated with OAC use included components of the CHA2DS2-VASc and HAS-BLED scores as well as discharging specialty and frailty. OAC use was highest in patients discharged under cardiology (69%). Electronic health record text can be used for automatic calculation of clinical risk scores at scale. Open source tools are available today for this task but require further validation. Analysis of routinely collected EHR data can replicate findings from large-scale curated registries.","Bean et al. looked at using clinical notes to calculate risk scores: CHADSVASC and HASBLED for 10,030 AF patients from 2011 to October 2017), they’ve validated their natural language processing algorithm with getting clinicians to calculate the risk in conventional manner for 40 of cases, the two scores were in higher agreement for stroke risk compared to HAS-BLED They’ve concluded on usefulness of NLP method in risk calculation at the large scale.",pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0225625&type=printable; doi:https://doi.org/10.1371/journal.pone.0225625; html:https://europepmc.org/articles/PMC6876873; pdf:https://europepmc.org/articles/PMC6876873?pdf=render 37717030,https://doi.org/10.1186/s13756-023-01280-6,The impact of the COVID-19 pandemic on the treatment of common infections in primary care and the change to antibiotic prescribing in England.,"Yang YT, Zhong X, Fahmi A, Watts S, Ashcroft DM, Massey J, Fisher L, MacKenna B, Mehrkar A, Bacon SCJ, Goldacre B, Hand K, van Staa T, Palin V.",,Antimicrobial resistance and infection control,2023,2023-09-16,Y,Infection; Antibiotics; Primary Care; Antibiotic Stewardship; Covid-19 Pandemic,,,"

Background

There is concern that the COVID-19 pandemic altered the management of common infections in primary care. This study aimed to evaluate infection-coded consultation rates and antibiotic use during the pandemic and how any change may have affected clinical outcomes.

Methods

With the approval of NHS England, a retrospective cohort study using the OpenSAFELY platform analysed routinely collected electronic health data from GP practices in England between January 2019 and December 2021. Infection coded consultations and antibiotic prescriptions were used estimate multiple measures over calendar months, including age-sex adjusted prescribing rates, prescribing by infection and antibiotic type, infection consultation rates, coding quality and rate of same-day antibiotic prescribing for COVID-19 infections. Interrupted time series (ITS) estimated the effect of COVID-19 pandemic on infection-coded consultation rates. The impact of the pandemic on non- COVID-19 infection-related hospitalisations was also estimated.

Results

Records from 24 million patients were included. The rate of infection-related consultations fell for all infections (mean reduction of 39% in 2020 compared to 2019 mean rate), except for UTI which remained stable. Modelling infection-related consultation rates highlighted this with an incidence rate ratio of 0.44 (95% CI 0.36-0.53) for incident consultations and 0.43 (95% CI 0.33-0.54) for prevalent consultations. Lower respiratory tract infections (LRTI) saw the largest reduction of 0.11 (95% CI 0.07-0.17). Antibiotic prescribing rates fell with a mean reduction of 118.4 items per 1000 patients in 2020, returning to pre-pandemic rates by summer 2021. Prescribing for LRTI decreased 20% and URTI increased 15.9%. Over 60% of antibiotics were issued without an associated same-day infection code, which increased during the pandemic. Infection-related hospitalisations reduced (by 62%), with the largest reduction observed for pneumonia infections (72.9%). Same-day antibiotic prescribing for COVID-19 infection increased from 1 to 10.5% between the second and third national lockdowns and rose again during 2022.

Conclusions

Changes to consultations and hospital admissions may be driven by reduced transmission of non-COVID-19 infections due to reduced social mixing and lockdowns. Inconsistencies in coding practice emphasises the need for improvement to inform new antibiotic stewardship policies and prevent resistance to novel infections.",,pdf:https://aricjournal.biomedcentral.com/counter/pdf/10.1186/s13756-023-01280-6; doi:https://doi.org/10.1186/s13756-023-01280-6; html:https://europepmc.org/articles/PMC10504725; pdf:https://europepmc.org/articles/PMC10504725?pdf=render 37194197,https://doi.org/10.1111/acps.13566,Low risk of some common cancers in women with anorexia nervosa: Evidence from a national record-linkage study.,"Seminog O, Thakrar DB, James AC, Goldacre MJ.",,Acta psychiatrica Scandinavica,2023,2023-05-16,Y,Cancer; Caloric restriction; epidemiology; Anorexia Nervosa; risk,,,"

Background

Some studies report that women with anorexia nervosa (AN) have lower risk than others of breast cancer, but increased risk of cancers of other sites. No work has been done to quantify the risk in the English population.

Methods

Retrospective cohort study using a national linked dataset of Hospital Episode Statistics for 1999-2021. We selected individuals with a hospital admission for AN, and compared their relative risk (RR) of developing site-specific cancers, with that in a reference cohort.

Results

We identified 75 cancers in 15,029 women hospitalised with AN. There was a low RR of all cancers combined at 0.75 (95%CI 0.59-0.94), and, notably, low RR for breast cancer 0.43 (0.20-0.81), cancers of secondary and ill-defined sites 0.52 (0.26-0.93). The RR for parotid gland cancer was 4.4 (1.4-10.6) within a year of first recorded diagnosis of AN. In men, we found 12 cancers in 1413 individuals hospitalised with AN, but no increased risks beyond the first year of diagnosis of AN.

Conclusions

This is the first report on the association between AN and cancers in the all-England population. The study showed low rates of breast cancer, and of all cancers combined, in women hospitalised with AN. It is possible that some of the metabolic or hormonal changes observed in AN could work as a protective factor for breast cancer. More experimental work is needed to identify and explain these factors. The new finding on the higher risk of salivary gland tumours could inform clinicians caring for patients with AN.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/acps.13566; doi:https://doi.org/10.1111/acps.13566; html:https://europepmc.org/articles/PMC10953461; pdf:https://europepmc.org/articles/PMC10953461?pdf=render -31765395,https://doi.org/10.1371/journal.pone.0225625,Semantic computational analysis of anticoagulation use in atrial fibrillation from real world data.,"Bean DM, Teo J, Wu H, Oliveira R, Patel R, Bendayan R, Shah AM, Dobson RJB, Scott PA.",,PloS one,2019,2019-11-25,Y,,,,"Atrial fibrillation (AF) is the most common arrhythmia and significantly increases stroke risk. This risk is effectively managed by oral anticoagulation. Recent studies using national registry data indicate increased use of anticoagulation resulting from changes in guidelines and the availability of newer drugs. The aim of this study is to develop and validate an open source risk scoring pipeline for free-text electronic health record data using natural language processing. AF patients discharged from 1st January 2011 to 1st October 2017 were identified from discharge summaries (N = 10,030, 64.6% male, average age 75.3 ± 12.3 years). A natural language processing pipeline was developed to identify risk factors in clinical text and calculate risk for ischaemic stroke (CHA2DS2-VASc) and bleeding (HAS-BLED). Scores were validated vs two independent experts for 40 patients. Automatic risk scores were in strong agreement with the two independent experts for CHA2DS2-VASc (average kappa 0.78 vs experts, compared to 0.85 between experts). Agreement was lower for HAS-BLED (average kappa 0.54 vs experts, compared to 0.74 between experts). In high-risk patients (CHA2DS2-VASc ≥2) OAC use has increased significantly over the last 7 years, driven by the availability of DOACs and the transitioning of patients from AP medication alone to OAC. Factors independently associated with OAC use included components of the CHA2DS2-VASc and HAS-BLED scores as well as discharging specialty and frailty. OAC use was highest in patients discharged under cardiology (69%). Electronic health record text can be used for automatic calculation of clinical risk scores at scale. Open source tools are available today for this task but require further validation. Analysis of routinely collected EHR data can replicate findings from large-scale curated registries.","Bean et al. looked at using clinical notes to calculate risk scores: CHADSVASC and HASBLED for 10,030 AF patients from 2011 to October 2017), they’ve validated their natural language processing algorithm with getting clinicians to calculate the risk in conventional manner for 40 of cases, the two scores were in higher agreement for stroke risk compared to HAS-BLED They’ve concluded on usefulness of NLP method in risk calculation at the large scale.",pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0225625&type=printable; doi:https://doi.org/10.1371/journal.pone.0225625; html:https://europepmc.org/articles/PMC6876873; pdf:https://europepmc.org/articles/PMC6876873?pdf=render 32790708,https://doi.org/10.1371/journal.pone.0237298,Clinical academic research in the time of Corona: A simulation study in England and a call for action.,"Banerjee A, Katsoulis M, Lai AG, Pasea L, Treibel TA, Manisty C, Denaxas S, Quarta G, Hemingway H, Cavalcante JL, Noursadeghi M, Moon JC.",,PloS one,2020,2020-08-13,Y,,,,"

Objectives

We aimed to model the impact of coronavirus (COVID-19) on the clinical academic response in England, and to provide recommendations for COVID-related research.

Design

A stochastic model to determine clinical academic capacity in England, incorporating the following key factors which affect the ability to conduct research in the COVID-19 climate: (i) infection growth rate and population infection rate (from UK COVID-19 statistics and WHO); (ii) strain on the healthcare system (from published model); and (iii) availability of clinical academic staff with appropriate skillsets affected by frontline clinical activity and sickness (from UK statistics).

Setting

Clinical academics in primary and secondary care in England.

Participants

Equivalent of 3200 full-time clinical academics in England.

Interventions

Four policy approaches to COVID-19 with differing population infection rates: ""Italy model"" (6%), ""mitigation"" (10%), ""relaxed mitigation"" (40%) and ""do-nothing"" (80%) scenarios. Low and high strain on the health system (no clinical academics able to do research at 10% and 5% infection rate, respectively.

Main outcome measures

Number of full-time clinical academics available to conduct clinical research during the pandemic in England.

Results

In the ""Italy model"", ""mitigation"", ""relaxed mitigation"" and ""do-nothing"" scenarios, from 5 March 2020 the duration (days) and peak infection rates (%) are 95(2.4%), 115(2.5%), 240(5.3%) and 240(16.7%) respectively. Near complete attrition of academia (87% reduction, <400 clinical academics) occurs 35 days after pandemic start for 11, 34, 62, 76 days respectively-with no clinical academics at all for 37 days in the ""do-nothing"" scenario. Restoration of normal academic workforce (80% of normal capacity) takes 11, 12, 30 and 26 weeks respectively.

Conclusions

Pandemic COVID-19 crushes the science needed at system level. National policies mitigate, but the academic community needs to adapt. We highlight six key strategies: radical prioritisation (eg 3-4 research ideas per institution), deep resourcing, non-standard leadership (repurposing of key non-frontline teams), rationalisation (profoundly simple approaches), careful site selection (eg protected sites with large academic backup) and complete suspension of academic competition with collaborative approaches.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0237298&type=printable; doi:https://doi.org/10.1371/journal.pone.0237298; html:https://europepmc.org/articles/PMC7425844; pdf:https://europepmc.org/articles/PMC7425844?pdf=render 32864476,https://doi.org/10.23889/ijpds.v5i1.1157,"Prevalence of Down's Syndrome in England, 1998-2013: Comparison of linked surveillance data and electronic health records.","Doidge JC, Morris JK, Harron KL, Stevens S, Gilbert R.",,International journal of population data science,2020,2020-01-01,Y,Prevalence; Data Linkage; Disease Surveillance; Down’s Syndrome; Electronic Health Records; Linkage Error,,,"

Introduction

Disease registers and electronic health records are valuable resources for disease surveillance and research but can be limited by variation in data quality over time. Quality may be limited in terms of the accuracy of clinical information, of the internal linkage that supports person-based analysis of most administrative datasets, or by errors in linkage between multiple datasets.

Objectives

By linking the National Down Syndrome Cytogenetic Register (NDSCR) to Hospital Episode Statistics for England (HES), we aimed to assess the quality of each and establish a consistent approach for analysis of trends in prevalence of Down's syndrome among live births in England.

Methods

Probabilistic record linkage of NDSCR to HES for the period 1998-2013 was supported by linkage of babies to mothers within HES. Comparison of prevalence estimates in England were made using NDSCR only, HES data only, and linked data. Capture-recapture analysis and quantitative bias analysis were used to account for potential errors, including false positive diagnostic codes, unrecorded diagnoses, and linkage error.

Results

Analyses of single-source data indicated increasing live birth prevalence of Down's Syndrome, particularly in the analysis of HES. Linked data indicated a contrastingly stable prevalence of 12.3 (plausible range: 11.6-12.7) cases per 10 000 live births.

Conclusion

Case ascertainment in NDSCR improved slightly over time, creating a picture of slowly increasing prevalence. The emerging epidemic suggested by HES primarily reflects improving linkage within HES (assignment of unique patient identifiers to hospital episodes). Administrative data are valuable but trends should be interpreted with caution, and with assessment of data quality over time. Data linkage with quantitative bias analysis can provide more robust estimation and, in this case, stronger evidence that prevalence is not increasing. Routine linkage of administrative and register data can enhance the value of each.",,pdf:https://ijpds.org/article/download/1157/2531; doi:https://doi.org/10.23889/ijpds.v5i1.1157; html:https://europepmc.org/articles/PMC7115985; pdf:https://europepmc.org/articles/PMC7115985?pdf=render 35317796,https://doi.org/10.1186/s12916-022-02308-1,"Correction to: Lifetime risk of cardiovascular-renal disease in type 2 diabetes: a population-based study in 473,399 individuals.","Zhang R, Mamza JB, Morris T, Godfrey G, Asselbergs FW, Denaxas S, Hemingway H, Banerjee A.",,BMC medicine,2022,2022-03-23,Y,,,,,,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-022-02308-1; doi:https://doi.org/10.1186/s12916-022-02308-1; html:https://europepmc.org/articles/PMC8941726; pdf:https://europepmc.org/articles/PMC8941726?pdf=render @@ -1041,14 +1041,14 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 31951005,https://doi.org/10.1093/jamia/ocz211,On classifying sepsis heterogeneity in the ICU: insight using machine learning.,"Ibrahim ZM, Wu H, Hamoud A, Stappen L, Dobson RJB, Agarossi A.",,Journal of the American Medical Informatics Association : JAMIA,2020,2020-03-01,Y,Sepsis; Machine Learning; Artificial Intelligence In Medicine; Sepsis Prediction; Sepsis Subtypes,Applied Analytics,,"

Objectives

Current machine learning models aiming to predict sepsis from electronic health records (EHR) do not account 20 for the heterogeneity of the condition despite its emerging importance in prognosis and treatment. This work demonstrates the added value of stratifying the types of organ dysfunction observed in patients who develop sepsis in the intensive care unit (ICU) in improving the ability to recognize patients at risk of sepsis from their EHR data.

Materials and methods

Using an ICU dataset of 13 728 records, we identify clinically significant sepsis subpopulations with distinct organ dysfunction patterns. We perform classification experiments with random forest, gradient boost trees, and support vector machines, using the identified subpopulations to distinguish patients who develop sepsis in the ICU from those who do not.

Results

The classification results show that features selected using sepsis subpopulations as background knowledge yield a superior performance in distinguishing septic from non-septic patients regardless of the classification model used. The improved performance is especially pronounced in specificity, which is a current bottleneck in sepsis prediction machine learning models.

Conclusion

Our findings can steer machine learning efforts toward more personalized models for complex conditions including sepsis.",Ibrahim et al. categorized patients in groups based on the type of organ failure. This categorization helped machine based algorithms to correctly identify those at high risk of sepsis.,pdf:https://academic.oup.com/jamia/article-pdf/27/3/437/34153319/ocz211.pdf; doi:https://doi.org/10.1093/jamia/ocz211; html:https://europepmc.org/articles/PMC7025363; pdf:https://europepmc.org/articles/PMC7025363?pdf=render 31628383,https://doi.org/10.1038/s41598-019-51562-6,Whole genome sequencing of drug resistant Mycobacterium tuberculosis isolates from a high burden tuberculosis region of North West Pakistan.,"Jabbar A, Phelan JE, de Sessions PF, Khan TA, Rahman H, Khan SN, Cantillon DM, Wildner LM, Ali S, Campino S, Waddell SJ, Clark TG.",,Scientific reports,2019,2019-10-18,Y,,,,"Tuberculosis (TB), caused by Mycobacterium tuberculosis bacteria, is a leading infectious cause of mortality worldwide, including in Pakistan. Drug resistant M. tuberculosis is an emerging threat for TB control, making it important to detect the underlying genetic mutations, and thereby inform treatment decision making and prevent transmission. Whole genome sequencing has emerged as the new diagnostic to reliably predict drug resistance within a clinically relevant time frame, and its deployment will have the greatest impact on TB control in highly endemic regions. To evaluate the mutations leading to drug resistance and to assess for evidence of the transmission of resistant strains, 81 M. tuberculosis samples from Khyber Pakhtunkhwa province (North West Pakistan) were subjected to whole genome sequencing and standard drug susceptibility testing for eleven anti-TB drugs. We found the majority of M. tuberculosis isolates were the CAS/Delhi strain-type (lineage 3; n = 57; 70.4%) and multi-drug resistant (MDR; n = 62; 76.5%). The most frequent resistance mutations were observed in the katG and rpoB genes, conferring resistance to isoniazid and rifampicin respectively. Mutations were also observed in genes conferring resistance to other first and second-line drugs, including in pncA (pyrazinamide), embB (ethambutol), gyrA (fluoroquinolones), rrs (aminoglycosides), rpsL, rrs and giB (streptomycin) loci. Whilst the majority of mutations have been reported in global datasets, we describe unreported putative resistance markers in katG, ethA (ethionamide), gyrA and gyrB (fluoroquinolones), and pncA. Analysis of the mutations revealed that acquisition of rifampicin resistance often preceded isoniazid in our isolates. We also observed a high proportion (17.6%) of pre-MDR isolates with fluoroquinolone resistance markers, potentially due to unregulated anti-TB drug use. Our isolates were compared to previously sequenced strains from Pakistan in a combined phylogenetic tree analysis. The presence of lineage 2 was only observed in our isolates. Using a cut-off of less than ten genome-wide mutation differences between isolates, a transmission analysis revealed 18 M. tuberculosis isolates clustering within eight networks, thereby providing evidence of drug-resistant TB transmission in the Khyber Pakhtunkhwa province. Overall, we have demonstrated that drug-resistant TB isolates are circulating and transmitted in North West Pakistan. Further, we have shown the usefulness of whole genome sequencing as a diagnostic tool for characterizing M. tuberculosis isolates, which will assist future epidemiological studies and disease control activities in Pakistan.",,pdf:https://www.nature.com/articles/s41598-019-51562-6.pdf; doi:https://doi.org/10.1038/s41598-019-51562-6; html:https://europepmc.org/articles/PMC6802378; pdf:https://europepmc.org/articles/PMC6802378?pdf=render 37705832,https://doi.org/10.5837/bjc.2023.003,SGLT2 inhibitors in CKD and HFpEF: two new large trials and two new meta-analyses.,"Mayne KJ, Preiss D, Herrington WG.",,The British journal of cardiology,2023,2023-02-21,N,Cardiovascular disease; Heart Failure; Chronic Kidney Disease; Sodium-Glucose Co-Transporter 2 (Sglt2) Inhibitor,,,,,doi:https://doi.org/10.5837/bjc.2023.003; html:https://europepmc.org/articles/PMC10495762; pdf:https://europepmc.org/articles/PMC10495762?pdf=render; doi:https://doi.org/10.5837/bjc.2023.003 -37897346,https://doi.org/10.1093/eurheartj/ehad727,Five critical quality criteria for artificial intelligence-based prediction models.,"van Royen FS, Asselbergs FW, Alfonso F, Vardas P, van Smeden M.",,European heart journal,2023,2023-12-01,Y,Prediction; Artificial intelligence; Diagnosis; Prognosis; Digital Health,,,"To raise the quality of clinical artificial intelligence (AI) prediction modelling studies in the cardiovascular health domain and thereby improve their impact and relevancy, the editors for digital health, innovation, and quality standards of the European Heart Journal propose five minimal quality criteria for AI-based prediction model development and validation studies: complete reporting, carefully defined intended use of the model, rigorous validation, large enough sample size, and openness of code and software.",,doi:https://doi.org/10.1093/eurheartj/ehad727; html:https://europepmc.org/articles/PMC10702458; pdf:https://europepmc.org/articles/PMC10702458?pdf=render 33851963,https://doi.org/10.1001/jamadermatol.2021.0009,Association Between Atopic Dermatitis and Educational Attainment in Denmark.,"Schmidt SAJ, Mailhac A, Darvalics B, Mulick A, Deleuran MS, Sørensen HT, Riis JL, Langan SM.",,JAMA dermatology,2021,2021-04-14,Y,,,,"

Importance

Atopic dermatitis (AD) may affect academic performance through multiple pathways, including poor concentration associated with itching, sleep deprivation, or adverse effects of medications. Because educational attainment is associated with health and well-being, any association with a prevalent condition such as AD is of major importance.

Objective

To examine whether a childhood diagnosis of AD is associated with lower educational attainment.

Design, setting, and participants

This population-based cohort study used linked routine health care data from January 1, 1977, to June 30, 2017 (end of registry follow-up), in Denmark. The study population included all children born in Denmark on June 30, 1987, or earlier with an inpatient or outpatient hospital clinic diagnosis of AD recorded before their 13th birthday (baseline) and a comparison cohort of children from the general population matched by birth year and sex. A secondary analysis included exposure-discordant full siblings as a comparison cohort to account for familial factors. Data were analyzed from September 11, 2019, to January 21, 2021.

Exposures

Hospital-diagnosed AD.

Main outcomes and measures

Estimated probability or risk of not attaining specific educational levels (lower secondary, upper secondary, and higher) by 30 years of age among children with AD compared with children in the matched general population cohort. Corresponding risk ratios (RRs) were computed using Poisson regression that was conditioned on matched sets and adjusted for age. The sibling analysis was conditioned on family and adjusted for sex and age.

Results

The study included a total of 61 153 children, 5927 in the AD cohort (3341 male [56.4%]) and 55 226 from the general population (31 182 male [56.5%]). Compared with matched children from the general population, children with AD were at increased risk of not attaining lower secondary education (150 of 5927 [2.5%] vs 924 of 55 226 [1.7%]; adjusted RR, 1.50; 95% CI, 1.26-1.78) and upper secondary education (1141 of 5777 [19.8%] vs 8690 of 52 899 [16.4%]; RR, 1.16; 95% CI, 1.09-1.24), but not higher education (2406 of 4636 [51.9%] vs 18 785 of 35 408 [53.1%]; RR, 0.95; 95% CI, 0.91-1.00). The absolute differences in probability were less than 3.5%. The comparison of 3259 children with AD and 4046 of their full siblings yielded estimates that were less pronounced than those in the main analysis (adjusted RR for lower secondary education, 1.29 [95% CI, 0.92-1.82]; adjusted RR for upper secondary education, 1.05 [95% CI, 0.93-1.18]; adjusted RR for higher education, 0.94 [95% CI, 0.87-1.02]).

Conclusions and relevance

This population-based cohort study found that hospital-diagnosed AD was associated with reduced educational attainment, but the clinical importance was uncertain owing to small absolute differences and possible confounding by familial factors in this study. Future studies should examine for replicability in other populations and variation by AD phenotype.",,pdf:https://jamanetwork.com/journals/jamadermatology/articlepdf/2778389/jamadermatology_schmidt_2021_oi_210002_1623774349.64965.pdf; doi:https://doi.org/10.1001/jamadermatol.2021.0009; html:https://europepmc.org/articles/PMC8047754 35463778,https://doi.org/10.3389/fcvm.2022.859310,Fairness in Cardiac Magnetic Resonance Imaging: Assessing Sex and Racial Bias in Deep Learning-Based Segmentation.,"Puyol-Antón E, Ruijsink B, Mariscal Harana J, Piechnik SK, Neubauer S, Petersen SE, Razavi R, Chowienczyk P, King AP.",,Frontiers in cardiovascular medicine,2022,2022-04-07,Y,Segmentation; Cardiac Magnetic Resonance; Deep Learning; Fair Ai; Inequality Fairness In Deep Learning-Based Cmr Segmentation,,,"

Background

Artificial intelligence (AI) techniques have been proposed for automation of cine CMR segmentation for functional quantification. However, in other applications AI models have been shown to have potential for sex and/or racial bias. The objective of this paper is to perform the first analysis of sex/racial bias in AI-based cine CMR segmentation using a large-scale database.

Methods

A state-of-the-art deep learning (DL) model was used for automatic segmentation of both ventricles and the myocardium from cine short-axis CMR. The dataset consisted of end-diastole and end-systole short-axis cine CMR images of 5,903 subjects from the UK Biobank database (61.5 ± 7.1 years, 52% male, 81% white). To assess sex and racial bias, we compared Dice scores and errors in measurements of biventricular volumes and function between patients grouped by race and sex. To investigate whether segmentation bias could be explained by potential confounders, a multivariate linear regression and ANCOVA were performed.

Results

Results on the overall population showed an excellent agreement between the manual and automatic segmentations. We found statistically significant differences in Dice scores between races (white ∼94% vs. minority ethnic groups 86-89%) as well as in absolute/relative errors in volumetric and functional measures, showing that the AI model was biased against minority racial groups, even after correction for possible confounders. The results of a multivariate linear regression analysis showed that no covariate could explain the Dice score bias between racial groups. However, for the Mixed and Black race groups, sex showed a weak positive association with the Dice score. The results of an ANCOVA analysis showed that race was the main factor that can explain the overall difference in Dice scores between racial groups.

Conclusion

We have shown that racial bias can exist in DL-based cine CMR segmentation models when training with a database that is sex-balanced but not race-balanced such as the UK Biobank.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2022.859310/pdf; doi:https://doi.org/10.3389/fcvm.2022.859310; html:https://europepmc.org/articles/PMC9021445; pdf:https://europepmc.org/articles/PMC9021445?pdf=render 36834176,https://doi.org/10.3390/ijerph20043477,"Non-Pharmacological Therapies for Post-Viral Syndromes, Including Long COVID: A Systematic Review.","Chandan JS, Brown KR, Simms-Williams N, Bashir NZ, Camaradou J, Heining D, Turner GM, Rivera SC, Hotham R, Minhas S, Nirantharakumar K, Sivan M, Khunti K, Raindi D, Marwaha S, Hughes SE, McMullan C, Marshall T, Calvert MJ, Haroon S, Aiyegbusi OL, TLC Study.",,International journal of environmental research and public health,2023,2023-02-16,Y,Rehabilitation; Systematic review; Pvs; Non-pharmacological Intervention; Covid-19; Long Covid; Post-covid-19 Condition; Post-acute Sequelae Of Sars-cov-2 Infection (Pasc); Post-Viral Syndromes,,,"

Background

Post-viral syndromes (PVS), including Long COVID, are symptoms sustained from weeks to years following an acute viral infection. Non-pharmacological treatments for these symptoms are poorly understood. This review summarises the evidence for the effectiveness of non-pharmacological treatments for PVS.

Methods

We conducted a systematic review to evaluate the effectiveness of non-pharmacological interventions for PVS, as compared to either standard care, alternative non-pharmacological therapy, or placebo. The outcomes of interest were changes in symptoms, exercise capacity, quality of life (including mental health and wellbeing), and work capability. We searched five databases (Embase, MEDLINE, PsycINFO, CINAHL, MedRxiv) for randomised controlled trials (RCTs) published between 1 January 2001 to 29 October 2021. The relevant outcome data were extracted, the study quality was appraised using the Cochrane risk-of-bias tool, and the findings were synthesised narratively.

Findings

Overall, five studies of five different interventions (Pilates, music therapy, telerehabilitation, resistance exercise, neuromodulation) met the inclusion criteria. Aside from music-based intervention, all other selected interventions demonstrated some support in the management of PVS in some patients.

Interpretation

In this study, we observed a lack of robust evidence evaluating the non-pharmacological treatments for PVS, including Long COVID. Considering the prevalence of prolonged symptoms following acute viral infections, there is an urgent need for clinical trials evaluating the effectiveness and cost-effectiveness of non-pharmacological treatments for patients with PVS.

Registration

The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.",,pdf:https://www.mdpi.com/1660-4601/20/4/3477/pdf?version=1677135187; doi:https://doi.org/10.3390/ijerph20043477; html:https://europepmc.org/articles/PMC9967466; pdf:https://europepmc.org/articles/PMC9967466?pdf=render +37897346,https://doi.org/10.1093/eurheartj/ehad727,Five critical quality criteria for artificial intelligence-based prediction models.,"van Royen FS, Asselbergs FW, Alfonso F, Vardas P, van Smeden M.",,European heart journal,2023,2023-12-01,Y,Prediction; Artificial intelligence; Diagnosis; Prognosis; Digital Health,,,"To raise the quality of clinical artificial intelligence (AI) prediction modelling studies in the cardiovascular health domain and thereby improve their impact and relevancy, the editors for digital health, innovation, and quality standards of the European Heart Journal propose five minimal quality criteria for AI-based prediction model development and validation studies: complete reporting, carefully defined intended use of the model, rigorous validation, large enough sample size, and openness of code and software.",,doi:https://doi.org/10.1093/eurheartj/ehad727; html:https://europepmc.org/articles/PMC10702458; pdf:https://europepmc.org/articles/PMC10702458?pdf=render 33497994,https://doi.org/10.1016/j.puhe.2020.12.003,Obesity during the COVID-19 pandemic: both cause of high risk and potential effect of lockdown? A population-based electronic health record study.,"Katsoulis M, Pasea L, Lai AG, Dobson RJB, Denaxas S, Hemingway H, Banerjee A.",,Public health,2021,2020-12-14,Y,Obesity; Diabetes; Coronavirus; Physical Activity; cardiovascular,,,"

Objectives

Obesity is a modifiable risk factor for coronavirus disease 2019 (COVID-19)-related mortality. We estimated excess mortality in obesity, both 'direct', through infection, and 'indirect', through changes in health care, and also due to potential increasing obesity during lockdown.

Study design

The study design of this study is a retrospective cohort study and causal inference methods.

Methods

In population-based electronic health records for 1,958,638 individuals in England, we estimated 1-year mortality risk ('direct' and 'indirect' effects) for obese individuals, incorporating (i) pre-COVID-19 risk by age, sex and comorbidities, (ii) population infection rate and (iii) relative impact on mortality (relative risk [RR]: 1.2, 1.5, 2.0 and 3.0). Using causal inference models, we estimated impact of change in body mass index (BMI) and physical activity during 3-month lockdown on 1-year incidence for high-risk conditions (cardiovascular diseases, diabetes, chronic obstructive pulmonary disease and chronic kidney disease), accounting for confounders.

Results

For severely obese individuals (3.5% at baseline), at 10% population infection rate, we estimated direct impact of 240 and 479 excess deaths in England at RR 1.5 and 2.0, respectively, and indirect effect of 383-767 excess deaths, assuming 40% and 80% will be affected at RR = 1.2. Owing to BMI change during the lockdown, we estimated that 97,755 (5.4%: normal weight to overweight, 5.0%: overweight to obese and 1.3%: obese to severely obese) to 434,104 individuals (15%: normal weight to overweight, 15%: overweight to obese and 6%: obese to severely obese) would be at higher risk for COVID-19 over one year.

Conclusions

Prevention of obesity and promotion of physical activity are at least as important as physical isolation of severely obese individuals during the pandemic.",,doi:https://doi.org/10.1016/j.puhe.2020.12.003; doi:https://doi.org/10.1016/j.puhe.2020.12.003; html:https://europepmc.org/articles/PMC7832229; pdf:https://europepmc.org/articles/PMC7832229?pdf=render 33516523,https://doi.org/10.1016/j.jaci.2020.12.001,"Atopic eczema in adulthood and mortality: UK population-based cohort study, 1998-2016.","Silverwood RJ, Mansfield KE, Mulick A, Wong AYS, Schmidt SAJ, Roberts A, Smeeth L, Abuabara K, Langan SM.",,The Journal of allergy and clinical immunology,2021,2021-01-27,Y,Activity; Mortality; Cohort study; United Kingdom; Primary Care; Atopic Eczema; Severity; Population-based; Electronic Health Care Records,,,"

Background

Atopic eczema affects up to 10% of adults and is becoming more common globally. Few studies have assessed whether atopic eczema increases the risk of death.

Objective

We aimed to determine whether adults with atopic eczema were at increased risk of death overall and by specific causes and to assess whether the risk varied by atopic eczema severity and activity.

Methods

The study was a population-based matched cohort study using UK primary care electronic health care records from the Clinical Practice Research Datalink with linked hospitalization data from Hospital Episode Statistics and mortality data from the Office for National Statistics from 1998 to 2016.

Results

A total of 526,736 patients with atopic eczema were matched to 2,567,872 individuals without atopic eczema. The median age at entry was 41.8 years, and the median follow-up time was 4.5 years. There was limited evidence of increased hazard for all-cause mortality in those with atopic eczema (hazard ratio = 1.04; 99% CI = 1.03-1.06), but there were somewhat stronger associations (8%-14% increased hazard) for deaths due to infectious, digestive, and genitourinary causes. Differences on the absolute scale were modest owing to low overall mortality rates. Mortality risk increased markedly with eczema severity and activity. For example, patients with severe atopic eczema had a 62% increased hazard (hazard ratio = 1.62; 99% CI = 1.54-1.71) for mortality compared with those without eczema, with the strongest associations for infectious, respiratory, and genitourinary causes.

Conclusion

The increased hazards for all-cause and cause-specific mortality were largely restricted to those with the most severe or predominantly active atopic eczema. Understanding the reasons for these increased hazards for mortality is an urgent priority.",,pdf:http://www.jacionline.org/article/S0091674920317127/pdf; doi:https://doi.org/10.1016/j.jaci.2020.12.001; html:https://europepmc.org/articles/PMC8098860; pdf:https://europepmc.org/articles/PMC8098860?pdf=render -38374065,https://doi.org/10.1038/s41467-024-45779-x,Genetic influences on circulating retinol and its relationship to human health.,"Reay WR, Kiltschewskij DJ, Di Biase MA, Gerring ZF, Kundu K, Surendran P, Greco LA, Clarke ED, Collins CE, Mondul AM, Albanes D, Cairns MJ.",,Nature communications,2024,2024-02-19,Y,,,,"Retinol is a fat-soluble vitamin that plays an essential role in many biological processes throughout the human lifespan. Here, we perform the largest genome-wide association study (GWAS) of retinol to date in up to 22,274 participants. We identify eight common variant loci associated with retinol, as well as a rare-variant signal. An integrative gene prioritisation pipeline supports novel retinol-associated genes outside of the main retinol transport complex (RBP4:TTR) related to lipid biology, energy homoeostasis, and endocrine signalling. Genetic proxies of circulating retinol were then used to estimate causal relationships with almost 20,000 clinical phenotypes via a phenome-wide Mendelian randomisation study (MR-pheWAS). The MR-pheWAS suggests that retinol may exert causal effects on inflammation, adiposity, ocular measures, the microbiome, and MRI-derived brain phenotypes, amongst several others. Conversely, circulating retinol may be causally influenced by factors including lipids and serum creatinine. Finally, we demonstrate how a retinol polygenic score could identify individuals more likely to fall outside of the normative range of circulating retinol for a given age. In summary, this study provides a comprehensive evaluation of the genetics of circulating retinol, as well as revealing traits which should be prioritised for further investigation with respect to retinol related therapies or nutritional intervention.",,pdf:https://www.nature.com/articles/s41467-024-45779-x.pdf; doi:https://doi.org/10.1038/s41467-024-45779-x; html:https://europepmc.org/articles/PMC10876955; pdf:https://europepmc.org/articles/PMC10876955?pdf=render 37814053,https://doi.org/10.1038/s41588-023-01522-8,Age-dependent topic modeling of comorbidities in UK Biobank identifies disease subtypes with differential genetic risk.,"Jiang X, Zhang MJ, Zhang Y, Durvasula A, Inouye M, Holmes C, Price AL, McVean G.",,Nature genetics,2023,2023-10-09,Y,,,,"The analysis of longitudinal data from electronic health records (EHRs) has the potential to improve clinical diagnoses and enable personalized medicine, motivating efforts to identify disease subtypes from patient comorbidity information. Here we introduce an age-dependent topic modeling (ATM) method that provides a low-rank representation of longitudinal records of hundreds of distinct diseases in large EHR datasets. We applied ATM to 282,957 UK Biobank samples, identifying 52 diseases with heterogeneous comorbidity profiles; analyses of 211,908 All of Us samples produced concordant results. We defined subtypes of the 52 heterogeneous diseases based on their comorbidity profiles and compared genetic risk across disease subtypes using polygenic risk scores (PRSs), identifying 18 disease subtypes whose PRS differed significantly from other subtypes of the same disease. We further identified specific genetic variants with subtype-dependent effects on disease risk. In conclusion, ATM identifies disease subtypes with differential genome-wide and locus-specific genetic risk profiles.",,pdf:https://www.nature.com/articles/s41588-023-01522-8.pdf; doi:https://doi.org/10.1038/s41588-023-01522-8; html:https://europepmc.org/articles/PMC10632146; pdf:https://europepmc.org/articles/PMC10632146?pdf=render +38374065,https://doi.org/10.1038/s41467-024-45779-x,Genetic influences on circulating retinol and its relationship to human health.,"Reay WR, Kiltschewskij DJ, Di Biase MA, Gerring ZF, Kundu K, Surendran P, Greco LA, Clarke ED, Collins CE, Mondul AM, Albanes D, Cairns MJ.",,Nature communications,2024,2024-02-19,Y,,,,"Retinol is a fat-soluble vitamin that plays an essential role in many biological processes throughout the human lifespan. Here, we perform the largest genome-wide association study (GWAS) of retinol to date in up to 22,274 participants. We identify eight common variant loci associated with retinol, as well as a rare-variant signal. An integrative gene prioritisation pipeline supports novel retinol-associated genes outside of the main retinol transport complex (RBP4:TTR) related to lipid biology, energy homoeostasis, and endocrine signalling. Genetic proxies of circulating retinol were then used to estimate causal relationships with almost 20,000 clinical phenotypes via a phenome-wide Mendelian randomisation study (MR-pheWAS). The MR-pheWAS suggests that retinol may exert causal effects on inflammation, adiposity, ocular measures, the microbiome, and MRI-derived brain phenotypes, amongst several others. Conversely, circulating retinol may be causally influenced by factors including lipids and serum creatinine. Finally, we demonstrate how a retinol polygenic score could identify individuals more likely to fall outside of the normative range of circulating retinol for a given age. In summary, this study provides a comprehensive evaluation of the genetics of circulating retinol, as well as revealing traits which should be prioritised for further investigation with respect to retinol related therapies or nutritional intervention.",,pdf:https://www.nature.com/articles/s41467-024-45779-x.pdf; doi:https://doi.org/10.1038/s41467-024-45779-x; html:https://europepmc.org/articles/PMC10876955; pdf:https://europepmc.org/articles/PMC10876955?pdf=render 37008054,https://doi.org/10.14336/ad.2022.0829,Identifying Dynamic Patterns of Polypharmacy for Patients with Dementia from Primary Care Electronic Health Records: A Machine Learning Driven Longitudinal Study.,"Longo E, Burnett B, Bauermeister S, Zhou SM.",,Aging and disease,2023,2023-04-01,Y,Diagnosis; Dementia; Patient Safety; Machine Learning; Polypharmacy; Electronic Health Records; Exploratory Factor Analysis,,,"It is unclear how medication use evolved before diagnosis of dementia (DoD). This study aims to identify varied patterns of polypharmacy before DoD, their prevalence and possible complications. We collected primary care e-health records for 33,451 dementia patients in Wales from 1990 to 2015. The medication uses in every 5-year period along with 20-years prior to dementia diagnosis were considered. Exploratory factor analysis was used to identify clusters of medicines for every 5-year period. The prevalence of patients taking three or more medications was 82.16%, 69.7%, 41.1% and 5.5% in the Period 1 (0-5 years before DoD) ~ Period 4 (16-20 years before DoD) respectively. The Period 1 showed 3 clusters of polypharmacy - medicines for respiratory/urinary infections, arthropathies and rheumatism, and cardio-vascular disease (CVD) (66.55%); medicines for infections, arthropathies and rheumatism (AR), cardio-metabolic disease (CMD) and depression (22.02%); and medicines for arthropathies, rheumatism and osteoarthritis (2.6%). The Period 2 showed 4 clusters of polypharmacy - medicines for infections, arthropathies, and CVD (69.7%); medicines for CVD and depression (3%); medicines for CMD and arthropathies (0.3%); and medicines for AR, and CVD (2,5%). The Period 3 showed 6 clusters of polypharmacy - medicines for infections, arthropathies, and CVD (41.1%); medicines for CVD, acute-respiratory-infection (ARI), and arthropathies (1.25%); medicines for AR (1.16%); medicines for depression, anxiety (0.06%); medicines for CMD (1.4%); and medicines for dermatologic disorders (0.9%). The Period 4 showed 3 main clusters of polypharmacy - medicines for infections, arthropathy, and CVD (5.5%); medicines for anxiety, ARI (2.4%); and medicines for ARI and CVD (2.1%). As the development towards dementia progressed, the associative diseases tended to cluster with a larger prevalence in each cluster. Farther away before DoD, the clusters of polypharmacy tended to be clearly distinct between each other, resulting in an increasing number of patterns, but in a smaller prevalence.",,doi:https://doi.org/10.14336/ad.2022.0829; doi:https://doi.org/10.14336/AD.2022.0829; html:https://europepmc.org/articles/PMC10017143; pdf:https://europepmc.org/articles/PMC10017143?pdf=render 38400634,https://doi.org/10.1093/ageing/afae021,Adherence to the Atrial fibrillation Better Care pathway and the risk of adverse health outcomes in older care home residents with atrial fibrillation: a retrospective data linkage study 2003-18.,"Ritchie LA, Harrison SL, Penson PE, Akbari A, Torabi F, Hollinghurst J, Harris D, Oke OB, Akpan A, Halcox JP, Rodgers SE, Lip GYH, Lane DA.",,Age and ageing,2024,2024-02-01,Y,Atrial fibrillation; Older People; Care Homes; Integrated Care; Health Outcomes,,,"

Background

The Atrial fibrillation Better Care (ABC) pathway is the gold-standard approach to atrial fibrillation (AF) management, but the effect of implementation on health outcomes in care home residents is unknown.

Objective

To examine associations between ABC pathway adherence and stroke, transient ischaemic attack, cardiovascular hospitalisation, major bleeding, mortality and a composite of all these outcomes in care home residents.

Methods

A retrospective cohort study of older care home residents (≥65 years) in Wales with AF was conducted between 1 January 2003 and 31 December 2018 using the Secure Anonymised Information Linkage Databank. Adherence to the ABC pathway was assessed at care home entry using pre-specified definitions. Cox proportional hazard and competing risk models were used to estimate the risk of health outcomes according to ABC adherence.

Results

From 14,493 residents (median [interquartile range] age 87.0 [82.6-91.2] years, 35.2% male) with AF, 5,531 (38.2%) were ABC pathway adherent. Pathway adherence was not significantly associated with risk of the composite outcome (adjusted hazard ratio, 95% confidence interval [CI]: 1.01 [0.97-1.05]). There was a significant independent association observed between ABC pathway adherence and a reduced risk of myocardial infarction (0.70 [0.50-0.98]), but a higher risk of haemorrhagic stroke (1.59 [1.06-2.39]). ABC pathway adherence was not significantly associated with any other individual health outcomes examined.

Conclusion

An ABC adherent approach in care home residents was not consistently associated with improved health outcomes. Findings should be interpreted with caution owing to difficulties in defining pathway adherence using routinely collected data and an individualised approach is recommended.",,doi:https://doi.org/10.1093/ageing/afae021; html:https://europepmc.org/articles/PMC10891424; pdf:https://europepmc.org/articles/PMC10891424?pdf=render 32444447,https://doi.org/10.1136/archdischild-2019-317902,Emergency paediatric critical care in England: describing trends using routine hospital data.,"Lewis KM, Parekh SM, Ramnarayan P, Gilbert R, Hardelid P, Wijlaars L.",,Archives of disease in childhood,2020,2020-05-22,Y,epidemiology; Intensive Care,,,"

Objective

To determine trends in emergency admission rates requiring different levels of critical care in hospitals with and without a paediatric intensive care unit (PICU).

Design

Birth cohort study created from Hospital Episode Statistics.

Setting

National Health Service funded hospitals in England.

Patients

8 577 680 singleton children born between 1 May 2003 and 31 April 2017.

Outcome measures

Using procedure and diagnostic codes, we assigned indicators of high dependency care (eg, non-invasive ventilation) or intensive care (eg, invasive ventilation) to emergency admissions.

Interventions

Children were followed up until their fifth birthday to estimate high dependency and intensive care admission rates in hospitals with and without a PICU. We tested the yearly trend of high dependency and intensive care admissions to hospitals without a PICU using logistic regression models.

Results

Emergency admissions requiring high dependency care in hospitals without a PICU increased from 3.30 (95% CI 3.09 to 3.51) per 10 000 child-years in 2008/2009 to 7.58 (95% CI 7.28 to 7.89) in 2016/2017 and overtook hospitals with a PICU in 2015/2016. The odds of an admission requiring high dependency care to a hospital without a PICU compared with a hospital with a PICU increased by 9% per study year (OR 1.09, 95% CI 1.08 to 1.10). The same trend was not present for admissions requiring intensive care (OR 1.01, 95% CI 0.99 to 1.03).

Conclusions

Between 2008/2009 and 2016/2017, an increasing proportion of admissions with indicators of high dependency care took place in hospitals without a PICU.",,pdf:https://adc.bmj.com/content/archdischild/105/11/1061.full.pdf; doi:https://doi.org/10.1136/archdischild-2019-317902; html:https://europepmc.org/articles/PMC7588403; pdf:https://europepmc.org/articles/PMC7588403?pdf=render @@ -1061,24 +1061,24 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 34564897,https://doi.org/10.1002/gps.5627,Living well with dementia: What is possible and how to promote it.,"Quinn C, Pickett JA, Litherland R, Morris RG, Martyr A, Clare L, On behalf of the IDEAL Programme Team.",,International journal of geriatric psychiatry,2022,2021-10-13,Y,Quality of life; Alzheimer's; Well-being; Carer; Post-diagnostic Support,,,,,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/gps.5627; doi:https://doi.org/10.1002/gps.5627; html:https://europepmc.org/articles/PMC9292841; pdf:https://europepmc.org/articles/PMC9292841?pdf=render 37850214,https://doi.org/10.1183/23120541.00110-2023,Mapping inpatient care pathways for patients with COPD: an observational study using routinely collected electronic hospital record data.,"Evison F, Cooper R, Gallier S, Missier P, Sayer AA, Sapey E, Witham MD.",,ERJ open research,2023,2023-09-01,Y,,,,"

Introduction

Respiratory specialist ward care is associated with better outcomes for patients with COPD exacerbations. We assessed patient pathways and associated factors for people admitted to hospital with COPD exacerbations.

Methods

We analysed routinely collected electronic health data for patients admitted with COPD exacerbation in 2018 to Queen Elizabeth Hospital, Birmingham, UK. We extracted data on demographics, deprivation index, Elixhauser comorbidities, ward moves, length of stay, and in-hospital and 1-year mortality. We compared care pathways with recommended care pathways (transition from initial assessment area to respiratory wards or discharge). We used Markov state transition models to derive probabilities of following recommended pathways for patient subgroups.

Results

Of 42 555 patients with unplanned admissions during 2018, 571 patients were admitted at least once with an exacerbation of COPD. The mean±sd age was 51±11 years; 313 (55%) were women, 337 (59%) lived in the most deprived neighbourhoods and 45 (9%) were from non-white ethnic backgrounds. 428 (75.0%) had ≥4 comorbidities. Age >70 years was associated with higher in-hospital and 1-year mortality, more places of care (wards) and longer length of stay; having ≥4 comorbidities was associated with higher mortality and longer length of stay. Older age was associated with a significantly lower probability of following a recommended pathway (>70 years: 0.514, 95% CI 0.458-0.571; ≤70 years: 0.636, 95% CI 0.572-0.696; p=0.004).

Conclusions

Only older age was associated with a lower chance of following recommended hospital pathways of care. Such analyses could help refine appropriate care pathways for patients with COPD exacerbations.",,pdf:https://openres.ersjournals.com/content/erjor/early/2023/08/24/23120541.00110-2023.full.pdf; doi:https://doi.org/10.1183/23120541.00110-2023; html:https://europepmc.org/articles/PMC10577591; pdf:https://europepmc.org/articles/PMC10577591?pdf=render 32954362,https://doi.org/10.1038/s43016-020-0093-y,Nutriome-metabolome relationships provide insights into dietary intake and metabolism.,"Posma JM, Garcia-Perez I, Frost G, Aljuraiban GS, Chan Q, Van Horn L, Daviglus M, Stamler J, Holmes E, Elliott P, Nicholson JK.",,Nature food,2020,2020-06-22,N,,,,"Dietary assessment traditionally relies on self-reported data which are often inaccurate and may result in erroneous diet-disease risk associations. We illustrate how urinary metabolic phenotyping can be used as alternative approach for obtaining information on dietary patterns. We used two multi-pass 24-hr dietary recalls, obtained on two occasions on average three weeks apart, paired with two 24-hr urine collections from 1,848 U.S. individuals; 67 nutrients influenced the urinary metabotype measured with 1H-NMR spectroscopy characterized by 46 structurally identified metabolites. We investigated the stability of each metabolite over time and showed that the urinary metabolic profile is more stable within individuals than reported dietary patterns. The 46 metabolites accurately predicted healthy and unhealthy dietary patterns in a free-living U.S. cohort and replicated in an independent U.K. cohort. We mapped these metabolites into a host-microbial metabolic network to identify key pathways and functions. These data can be used in future studies to evaluate how this set of diet-derived, stable, measurable bioanalytical markers are associated with disease risk. This knowledge may give new insights into biological pathways that characterize the shift from a healthy to unhealthy metabolic phenotype and hence give entry points for prevention and intervention strategies.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497842; doi:https://doi.org/10.1038/s43016-020-0093-y; html:https://europepmc.org/articles/PMC7497842; pdf:https://europepmc.org/articles/PMC7497842?pdf=render; doi:https://doi.org/10.1038/s43016-020-0093-y -34969173,https://doi.org/10.1002/ejhf.2417,"A population-based study of 92 clinically recognized risk factors for heart failure: co-occurrence, prognosis and preventive potential.","Banerjee A, Pasea L, Chung SC, Direk K, Asselbergs FW, Grobbee DE, Kotecha D, Anker SD, Dyszynski T, Tyl B, Denaxas S, Lumbers RT, Hemingway H.",,European journal of heart failure,2022,2022-01-26,Y,Risk factor; epidemiology; Heart Failure; Primary Prevention,,,"

Aims

Primary prevention strategies for heart failure (HF) have had limited success, possibly due to a wide range of underlying risk factors (RFs). Systematic evaluations of the prognostic burden and preventive potential across this wide range of risk factors are lacking. We aimed at estimating evidence, prevalence and co-occurrence for primary prevention and impact on prognosis of RFs for incident HF.

Methods and results

We systematically reviewed trials and observational evidence of primary HF prevention across 92 putative aetiologic RFs for HF identified from US and European clinical practice guidelines. We identified 170 885 individuals aged ≥30 years with incident HF from 1997 to 2017, using linked primary and secondary care UK electronic health records (EHR) and rule-based phenotypes (ICD-10, Read Version 2, OPCS-4 procedure and medication codes) for each of 92 RFs. Only 10/92 factors had high quality observational evidence for association with incident HF; 7 had effective randomized controlled trial (RCT)-based interventions for HF prevention (RCT-HF), and 6 for cardiovascular disease prevention, but not HF (RCT-CVD), and the remainder had no RCT-based preventive interventions (RCT-0). We were able to map 91/92 risk factors to EHR using 5961 terms, and 88/91 factors were represented by at least one patient. In the 5 years prior to HF diagnosis, 44.3% had ≥4 RFs. By RCT evidence, the most common RCT-HF RFs were hypertension (48.5%), stable angina (34.9%), unstable angina (16.8%), myocardial infarction (15.8%), and diabetes (15.1%); RCT-CVD RFs were smoking (46.4%) and obesity (29.9%); and RCT-0 RFs were atrial arrhythmias (17.2%), cancer (16.5%), heavy alcohol intake (14.9%). Mortality at 1 year varied across all 91 factors (lowest: pregnancy-related hormonal disorder 4.2%; highest: phaeochromocytoma 73.7%). Among new HF cases, 28.5% had no RCT-HF RFs and 38.6% had no RCT-CVD RFs. 15.6% had either no RF or only RCT-0 RFs.

Conclusion

One in six individuals with HF have no recorded RFs or RFs without trials. We provide a systematic map of primary preventive opportunities across a wide range of RFs for HF, demonstrating a high burden of co-occurrence and the need for trials tackling multiple RFs.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejhf.2417; doi:https://doi.org/10.1002/ejhf.2417; html:https://europepmc.org/articles/PMC9305958; pdf:https://europepmc.org/articles/PMC9305958?pdf=render 35130878,https://doi.org/10.1186/s12916-022-02234-2,"Lifetime risk of cardiovascular-renal disease in type 2 diabetes: a population-based study in 473,399 individuals.","Zhang R, Mamza JB, Morris T, Godfrey G, Asselbergs FW, Denaxas S, Hemingway H, Banerjee A.",,BMC medicine,2022,2022-02-07,Y,Kidney; Type 2 diabetes; lifetime; Attributable Risk; Population Health; cardiovascular,,,"

Background

Cardiovascular and renal diseases (CVRD) are major causes of mortality in individuals with type 2 diabetes (T2D). Studies of lifetime risk have neither considered all CVRD together nor the relative contribution of major risk factors to combined disease burden.

Methods

In a population-based cohort study using national electronic health records, we studied 473,399 individuals with T2D in England 2007-2018. Lifetime risk of individual and combined major adverse renal cardiovascular events, MARCE (including CV death and CVRD: heart failure; chronic kidney disease; myocardial infarction; stroke or peripheral artery disease), were estimated, accounting for baseline CVRD status and competing risk of death. We calculated population attributable risk for individual CVRD components. Ideal cardiovascular health was defined by blood pressure, cholesterol, glucose, smoking, physical activity, diet, and body mass index (i.e. modifiable risk factors).

Results

In individuals with T2D, lifetime risk of MARCE was 80% in those free from CVRD and was 97%, 93%, 98%, 89% and 91% in individuals with heart failure, chronic kidney disease, myocardial infarction, stroke and peripheral arterial disease, respectively at baseline. Among CVRD-free individuals, lifetime risk of chronic kidney disease was highest (54%), followed by CV death (41%), heart failure (29%), stroke (20%), myocardial infarction (19%) and peripheral arterial disease (9%). In those with HF only, 75% of MARCE after index T2D can be attributed to HF after adjusting for age, gender, and comorbidities. Compared with those with > 1, < 3 and ≥3 modifiable health risk behaviours, achieving ideal cardiovascular health could reduce MARCE by approximately 41.5%, 23.6% and 17.2%, respectively, in the T2D population.

Conclusions

Four out of five individuals with T2D free from CVRD, and nearly all those with history of CVRD, will develop MARCE over their lifetime. Early preventive measures in T2D patients are clinical, public health and policy priorities.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-022-02234-2; doi:https://doi.org/10.1186/s12916-022-02234-2; html:https://europepmc.org/articles/PMC8822817; pdf:https://europepmc.org/articles/PMC8822817?pdf=render +34969173,https://doi.org/10.1002/ejhf.2417,"A population-based study of 92 clinically recognized risk factors for heart failure: co-occurrence, prognosis and preventive potential.","Banerjee A, Pasea L, Chung SC, Direk K, Asselbergs FW, Grobbee DE, Kotecha D, Anker SD, Dyszynski T, Tyl B, Denaxas S, Lumbers RT, Hemingway H.",,European journal of heart failure,2022,2022-01-26,Y,Risk factor; epidemiology; Heart Failure; Primary Prevention,,,"

Aims

Primary prevention strategies for heart failure (HF) have had limited success, possibly due to a wide range of underlying risk factors (RFs). Systematic evaluations of the prognostic burden and preventive potential across this wide range of risk factors are lacking. We aimed at estimating evidence, prevalence and co-occurrence for primary prevention and impact on prognosis of RFs for incident HF.

Methods and results

We systematically reviewed trials and observational evidence of primary HF prevention across 92 putative aetiologic RFs for HF identified from US and European clinical practice guidelines. We identified 170 885 individuals aged ≥30 years with incident HF from 1997 to 2017, using linked primary and secondary care UK electronic health records (EHR) and rule-based phenotypes (ICD-10, Read Version 2, OPCS-4 procedure and medication codes) for each of 92 RFs. Only 10/92 factors had high quality observational evidence for association with incident HF; 7 had effective randomized controlled trial (RCT)-based interventions for HF prevention (RCT-HF), and 6 for cardiovascular disease prevention, but not HF (RCT-CVD), and the remainder had no RCT-based preventive interventions (RCT-0). We were able to map 91/92 risk factors to EHR using 5961 terms, and 88/91 factors were represented by at least one patient. In the 5 years prior to HF diagnosis, 44.3% had ≥4 RFs. By RCT evidence, the most common RCT-HF RFs were hypertension (48.5%), stable angina (34.9%), unstable angina (16.8%), myocardial infarction (15.8%), and diabetes (15.1%); RCT-CVD RFs were smoking (46.4%) and obesity (29.9%); and RCT-0 RFs were atrial arrhythmias (17.2%), cancer (16.5%), heavy alcohol intake (14.9%). Mortality at 1 year varied across all 91 factors (lowest: pregnancy-related hormonal disorder 4.2%; highest: phaeochromocytoma 73.7%). Among new HF cases, 28.5% had no RCT-HF RFs and 38.6% had no RCT-CVD RFs. 15.6% had either no RF or only RCT-0 RFs.

Conclusion

One in six individuals with HF have no recorded RFs or RFs without trials. We provide a systematic map of primary preventive opportunities across a wide range of RFs for HF, demonstrating a high burden of co-occurrence and the need for trials tackling multiple RFs.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejhf.2417; doi:https://doi.org/10.1002/ejhf.2417; html:https://europepmc.org/articles/PMC9305958; pdf:https://europepmc.org/articles/PMC9305958?pdf=render 36439548,https://doi.org/10.3389/fsurg.2022.870494,Development and validation of an automated basal cell carcinoma histopathology information extraction system using natural language processing.,"Ali SR, Strafford H, Dobbs TD, Fonferko-Shadrach B, Lacey AS, Pickrell WO, Hutchings HA, Whitaker IS.",,Frontiers in surgery,2022,2022-08-24,Y,Electronic Health Records (Ehrs); Natural Language Processing (Nlp); Basal Cell Carcinoma (Bcc); Non-melanoma Skin Cancer (Nmsc); Information Extraction (Ie),,,"

Introduction

Routinely collected healthcare data are a powerful research resource, but often lack detailed disease-specific information that is collected in clinical free text such as histopathology reports. We aim to use natural Language Processing (NLP) techniques to extract detailed clinical and pathological information from histopathology reports to enrich routinely collected data.

Methods

We used the general architecture for text engineering (GATE) framework to build an NLP information extraction system using rule-based techniques. During validation, we deployed our rule-based NLP pipeline on 200 previously unseen, de-identified and pseudonymised basal cell carcinoma (BCC) histopathological reports from Swansea Bay University Health Board, Wales, UK. The results of our algorithm were compared with gold standard human annotation by two independent and blinded expert clinicians involved in skin cancer care.

Results

We identified 11,224 items of information with a mean precision, recall, and F1 score of 86.0% (95% CI: 75.1-96.9), 84.2% (95% CI: 72.8-96.1), and 84.5% (95% CI: 73.0-95.1), respectively. The difference between clinician annotator F1 scores was 7.9% in comparison with 15.5% between the NLP pipeline and the gold standard corpus. Cohen's Kappa score on annotated tokens was 0.85.

Conclusion

Using an NLP rule-based approach for named entity recognition in BCC, we have been able to develop and validate a pipeline with a potential application in improving the quality of cancer registry data, supporting service planning, and enhancing the quality of routinely collected data for research.",,pdf:https://www.frontiersin.org/articles/10.3389/fsurg.2022.870494/pdf; doi:https://doi.org/10.3389/fsurg.2022.870494; html:https://europepmc.org/articles/PMC9683031; pdf:https://europepmc.org/articles/PMC9683031?pdf=render +33890864,https://doi.org/10.2196/24728,The Value of Routinely Collected Data in Evaluating Home Assessment and Modification Interventions to Prevent Falls in Older People: Systematic Literature Review.,"Daniels H, Hollinghurst J, Fry R, Clegg A, Hillcoat-Nallétamby S, Nikolova S, Rodgers SE, Williams N, Akbari A.",,JMIR aging,2021,2021-04-23,Y,Aged; Evaluation research; Systematic review; Falls; Routinely Collected Data,,,"

Background

Falls in older people commonly occur at home. Home assessment and modification (HAM) interventions can be effective in reducing falls; however, there are some concerns over the validity of evaluation findings. Routinely collected data could improve the quality of HAM evaluations and strengthen their evidence base.

Objective

The aim of this study is to conduct a systematic review of the evidence of the use of routinely collected data in the evaluations of HAM interventions.

Methods

We searched the following databases from inception until January 31, 2020: PubMed, Ovid, CINAHL, OpenGrey, CENTRAL, LILACS, and Web of Knowledge. Eligible studies were those evaluating HAMs designed to reduce falls involving participants aged 60 years or more. We included study protocols and full reports. Bias was assessed using the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool.

Results

A total of 7 eligible studies were identified in 8 papers. Government organizations provided the majority of data across studies, with health care providers and third-sector organizations also providing data. Studies used a range of demographic, clinical and health, and administrative data. The purpose of using routinely collected data spanned recruiting and creating a sample, stratification, generating independent variables or covariates, and measuring key study-related outcomes. Nonhome-based modification interventions (eg, in nursing homes) using routinely collected data were not included in this study. We included two protocols, which meant that the results of those studies were not available. MeSH headings were excluded from the PubMed search because of a reduction in specificity. This means that some studies that met the inclusion criteria may not have been identified.

Conclusions

Routine data can be used successfully in many aspects of HAM evaluations and can reduce biases and improve other important design considerations. However, the use of these data in these studies is currently not widespread. There are a number of governance barriers to be overcome to allow these types of linkage and to ensure that the use of routinely collected data in evaluations of HAM interventions is exploited to its full potential.",,pdf:https://aging.jmir.org/2021/2/e24728/PDF; doi:https://doi.org/10.2196/24728; html:https://europepmc.org/articles/PMC8105762; pdf:https://europepmc.org/articles/PMC8105762?pdf=render 38124256,https://doi.org/10.1093/ageing/afad219,New Horizons in artificial intelligence in the healthcare of older people.,"Shiwani T, Relton S, Evans R, Kale A, Heaven A, Clegg A, Ageing Data Research Collaborative (Geridata) AI group , Todd O.",,Age and ageing,2023,2023-12-01,Y,Artificial intelligence; Technology; Ageing; Health; Older People,,,"Artificial intelligence (AI) in healthcare describes algorithm-based computational techniques which manage and analyse large datasets to make inferences and predictions. There are many potential applications of AI in the care of older people, from clinical decision support systems that can support identification of delirium from clinical records to wearable devices that can predict the risk of a fall. We held four meetings of older people, clinicians and AI researchers. Three priority areas were identified for AI application in the care of older people. These included: monitoring and early diagnosis of disease, stratified care and care coordination between healthcare providers. However, the meetings also highlighted concerns that AI may exacerbate health inequity for older people through bias within AI models, lack of external validation amongst older people, infringements on privacy and autonomy, insufficient transparency of AI models and lack of safeguarding for errors. Creating effective interventions for older people requires a person-centred approach to account for the needs of older people, as well as sufficient clinical and technological governance to meet standards of generalisability, transparency and effectiveness. Education of clinicians and patients is also needed to ensure appropriate use of AI technologies, with investment in technological infrastructure required to ensure equity of access.",,doi:https://doi.org/10.1093/ageing/afad219; html:https://europepmc.org/articles/PMC10733173; pdf:https://europepmc.org/articles/PMC10733173?pdf=render -33890864,https://doi.org/10.2196/24728,The Value of Routinely Collected Data in Evaluating Home Assessment and Modification Interventions to Prevent Falls in Older People: Systematic Literature Review.,"Daniels H, Hollinghurst J, Fry R, Clegg A, Hillcoat-Nallétamby S, Nikolova S, Rodgers SE, Williams N, Akbari A.",,JMIR aging,2021,2021-04-23,Y,Aged; Evaluation research; Systematic review; Falls; Routinely Collected Data,,,"

Background

Falls in older people commonly occur at home. Home assessment and modification (HAM) interventions can be effective in reducing falls; however, there are some concerns over the validity of evaluation findings. Routinely collected data could improve the quality of HAM evaluations and strengthen their evidence base.

Objective

The aim of this study is to conduct a systematic review of the evidence of the use of routinely collected data in the evaluations of HAM interventions.

Methods

We searched the following databases from inception until January 31, 2020: PubMed, Ovid, CINAHL, OpenGrey, CENTRAL, LILACS, and Web of Knowledge. Eligible studies were those evaluating HAMs designed to reduce falls involving participants aged 60 years or more. We included study protocols and full reports. Bias was assessed using the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool.

Results

A total of 7 eligible studies were identified in 8 papers. Government organizations provided the majority of data across studies, with health care providers and third-sector organizations also providing data. Studies used a range of demographic, clinical and health, and administrative data. The purpose of using routinely collected data spanned recruiting and creating a sample, stratification, generating independent variables or covariates, and measuring key study-related outcomes. Nonhome-based modification interventions (eg, in nursing homes) using routinely collected data were not included in this study. We included two protocols, which meant that the results of those studies were not available. MeSH headings were excluded from the PubMed search because of a reduction in specificity. This means that some studies that met the inclusion criteria may not have been identified.

Conclusions

Routine data can be used successfully in many aspects of HAM evaluations and can reduce biases and improve other important design considerations. However, the use of these data in these studies is currently not widespread. There are a number of governance barriers to be overcome to allow these types of linkage and to ensure that the use of routinely collected data in evaluations of HAM interventions is exploited to its full potential.",,pdf:https://aging.jmir.org/2021/2/e24728/PDF; doi:https://doi.org/10.2196/24728; html:https://europepmc.org/articles/PMC8105762; pdf:https://europepmc.org/articles/PMC8105762?pdf=render 33414147,https://doi.org/10.1136/bmjopen-2020-041536,Estimating the COVID-19 epidemic trajectory and hospital capacity requirements in South West England: a mathematical modelling framework.,"Booton RD, MacGregor L, Vass L, Looker KJ, Hyams C, Bright PD, Harding I, Lazarus R, Hamilton F, Lawson D, Danon L, Pratt A, Wood R, Brooks-Pollock E, Turner KME.",,BMJ open,2021,2021-01-07,Y,Infection control; epidemiology; Public Health,,,"

Objectives

To develop a regional model of COVID-19 dynamics for use in estimating the number of infections, deaths and required acute and intensive care (IC) beds using the South West England (SW) as an example case.

Design

Open-source age-structured variant of a susceptible-exposed-infectious-recovered compartmental mathematical model. Latin hypercube sampling and maximum likelihood estimation were used to calibrate to cumulative cases and cumulative deaths.

Setting

SW at a time considered early in the pandemic, where National Health Service authorities required evidence to guide localised planning and support decision-making.

Participants

Publicly available data on patients with COVID-19.

Primary and secondary outcome measures

The expected numbers of infected cases, deaths due to COVID-19 infection, patient occupancy of acute and IC beds and the reproduction ('R') number over time.

Results

SW model projections indicate that, as of 11 May 2020 (when 'lockdown' measures were eased), 5793 (95% credible interval (CrI) 2003 to 12 051) individuals were still infectious (0.10% of the total SW population, 95% CrI 0.04% to 0.22%), and a total of 189 048 (95% CrI 141 580 to 277 955) had been infected with the virus (either asymptomatically or symptomatically), but recovered, which is 3.4% (95% CrI 2.5% to 5.0%) of the SW population. The total number of patients in acute and IC beds in the SW on 11 May 2020 was predicted to be 701 (95% CrI 169 to 1543) and 110 (95% CrI 8 to 464), respectively. The R value in SW was predicted to be 2.6 (95% CrI 2.0 to 3.2) prior to any interventions, with social distancing reducing this to 2.3 (95% CrI 1.8 to 2.9) and lockdown/school closures further reducing the R value to 0.6 (95% CrI 0.5 to 0.7).

Conclusions

The developed model has proved a valuable asset for regional healthcare services. The model will be used further in the SW as the pandemic evolves, and-as open-source software-is portable to healthcare systems in other geographies.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e041536.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-041536; html:https://europepmc.org/articles/PMC7797241; pdf:https://europepmc.org/articles/PMC7797241?pdf=render -37032516,https://doi.org/10.1111/aor.14537,Incidence and risk factors of late right heart failure in chronic mechanical circulatory support.,"Felix SEA, Numan L, Oerlemans MIF, Aarts E, Ramjankhan FZ, Gianoli M, Asselbergs FW, De Jonge N, Van Laake LW.",,Artificial organs,2023,2023-04-21,N,Risk factor; Mechanical Circulatory Support; Left Ventricular Assist Device; Late Right Heart Failure,,,"

Background

Late right heart failure (LRHF) is a common complication during long-term left ventricular assist device (LVAD) support. We aimed to identify risk factors for LRHF after LVAD implantation.

Methods

Patients undergoing primary LVAD implantation between 2006 and 2019 and surviving the perioperative period were included for this study (n = 261). Univariate Cox proportional hazards analysis was used to assess the association of clinical covariates and LRHF, stratified for device type. Variables with p < 0.10 entered the multivariable model. In a subset of patients with complete echocardiography or right catheterization data, this multivariable model was extended. Postoperative cardiopulmonary exercise test data were compared in patients with and without LRHF.

Results

Nineteen percentage of patients suffered from LRHF after a median of 12 months, of which 67% required hospitalization. A history of atrial fibrillation (AF) (HR: 2.06 [1.08-3.93], p = 0.029), a higher preoperative body mass index (BMI) (HR: 1.07 [1.01-1.13], p = 0.023), and intensive care unit (ICU) duration (HR: 1.03 [1.00-1.06], p = 0.025) were independent predictors of LHRF in the multivariable model. A significant relation between the severity of tricuspid regurgitation (TR) and LRHF (HR: 1.91 [1.13-3.21], p = 0.016) was found in patients with echocardiographic data. Patients with LRHF demonstrated a lower maximal workload and peak VO2 at 6 months postoperatively.

Conclusion

A history of AF, BMI, and longer ICU stay may help identify patients at high risk for LRHF. Severity of TR was significantly related to LRHF in a subset of patients.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/aor.14537; doi:https://doi.org/10.1111/aor.14537 34286192,https://doi.org/10.7861/fhj.2021-0083,Making trials part of good clinical care: lessons from the RECOVERY trial.,"Pessoa-Amorim G, Campbell M, Fletcher L, Horby P, Landray M, Mafham M, Haynes R.",,Future healthcare journal,2021,2021-07-01,N,Recovery; RANDOMISED CONTROLLED TRIALS; evidence-based medicine; Quality-by-design; Covid-19,,,"When COVID-19 hit the UK in early 2020, there were no known treatments for a condition that results in the death of around one in four patients hospitalised with this disease. Around the world, possible treatments were administered to huge numbers of patients, without any reliable assessments of safety and efficacy. The rapid generation of high-quality evidence was vital. RECOVERY is a streamlined, pragmatic, randomised controlled trial, which was set up in response to this challenge. As of April 2021, over 39,000 patients have been enrolled from 178 hospital sites in the UK. Within 100 days of its initiation, RECOVERY demonstrated that dexamethasone improves survival for patients with severe disease; a result that was rapidly implemented in the UK and internationally saving hundreds of thousands of lives. Importantly, it also showed that other widely used treatments (such as hydroxychloroquine and azithromycin) have no meaningful benefit for hospitalised patients. This was only possible through randomisation of large numbers of patients and the adoption of streamlined and pragmatic procedures focused on quality, together with widespread collaboration focused on a single goal. RECOVERY illustrates how clinical trials and healthcare can be integrated, even in a pandemic. This approach provides new opportunities to generate the evidence needed for high-quality healthcare not only for a pandemic but for the many other conditions that place a burden on patients and the healthcare system.",,pdf:https://www.rcpjournals.org/content/futurehosp/8/2/e243.full.pdf; doi:https://doi.org/10.7861/fhj.2021-0083; html:https://europepmc.org/articles/PMC8285150; pdf:https://europepmc.org/articles/PMC8285150?pdf=render; doi:https://doi.org/10.7861/fhj.2021-0083 -37549998,https://doi.org/10.1136/bjsports-2022-106460,Device-based measurement of physical activity in cardiovascular healthcare: possibilities and challenges.,"Chico TJ, Stamatakis E, Ciravegna F, Dunn J, Redwood S, Al-Lamee R, Sofat R, Gill J.",,British journal of sports medicine,2023,2023-08-07,N,Cardiovascular diseases; Health; Physical Activity,,,,,doi:https://doi.org/10.1136/bjsports-2022-106460 32060159,https://doi.org/10.1136/bmjopen-2019-034396,Data-driven discovery of changes in clinical code usage over time: a case-study on changes in cardiovascular disease recording in two English electronic health records databases (2001-2015).,"Rockenschaub P, Nguyen V, Aldridge RW, Acosta D, García-Gómez JM, Sáez C.",,BMJ open,2020,2020-02-13,Y,Cardiovascular disease; Data Quality; Electronic Health Records; Clinical Coding; Statistics & Research Methods,The Human Phenome,,"

Objectives

To demonstrate how data-driven variability methods can be used to identify changes in disease recording in two English electronic health records databases between 2001 and 2015.

Design

Repeated cross-sectional analysis that applied data-driven temporal variability methods to assess month-by-month changes in routinely collected medical data. A measure of difference between months was calculated based on joint distributions of age, gender, socioeconomic status and recorded cardiovascular diseases. Distances between months were used to identify temporal trends in data recording.

Setting

400 English primary care practices from the Clinical Practice Research Datalink (CPRD GOLD) and 451 hospital providers from the Hospital Episode Statistics (HES).

Main outcomes

The proportion of patients (CPRD GOLD) and hospital admissions (HES) with a recorded cardiovascular disease (CPRD GOLD: coronary heart disease, heart failure, peripheral arterial disease, stroke; HES: International Classification of Disease codes I20-I69/G45).

Results

Both databases showed gradual changes in cardiovascular disease recording between 2001 and 2008. The recorded prevalence of included cardiovascular diseases in CPRD GOLD increased by 47%-62%, which partially reversed after 2008. For hospital records in HES, there was a relative decrease in angina pectoris (-34.4%) and unspecified stroke (-42.3%) over the same time period, with a concomitant increase in chronic coronary heart disease (+14.3%). Multiple abrupt changes in the use of myocardial infarction codes in hospital were found in March/April 2010, 2012 and 2014, possibly linked to updates of clinical coding guidelines.

Conclusions

Identified temporal variability could be related to potentially non-medical causes such as updated coding guidelines. These artificial changes may introduce temporal correlation among diagnoses inferred from routine data, violating the assumptions of frequently used statistical methods. Temporal variability measures provide an objective and robust technique to identify, and subsequently account for, those changes in electronic health records studies without any prior knowledge of the data collection process.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/2/e034396.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-034396; html:https://europepmc.org/articles/PMC7045100; pdf:https://europepmc.org/articles/PMC7045100?pdf=render +37032516,https://doi.org/10.1111/aor.14537,Incidence and risk factors of late right heart failure in chronic mechanical circulatory support.,"Felix SEA, Numan L, Oerlemans MIF, Aarts E, Ramjankhan FZ, Gianoli M, Asselbergs FW, De Jonge N, Van Laake LW.",,Artificial organs,2023,2023-04-21,N,Risk factor; Mechanical Circulatory Support; Left Ventricular Assist Device; Late Right Heart Failure,,,"

Background

Late right heart failure (LRHF) is a common complication during long-term left ventricular assist device (LVAD) support. We aimed to identify risk factors for LRHF after LVAD implantation.

Methods

Patients undergoing primary LVAD implantation between 2006 and 2019 and surviving the perioperative period were included for this study (n = 261). Univariate Cox proportional hazards analysis was used to assess the association of clinical covariates and LRHF, stratified for device type. Variables with p < 0.10 entered the multivariable model. In a subset of patients with complete echocardiography or right catheterization data, this multivariable model was extended. Postoperative cardiopulmonary exercise test data were compared in patients with and without LRHF.

Results

Nineteen percentage of patients suffered from LRHF after a median of 12 months, of which 67% required hospitalization. A history of atrial fibrillation (AF) (HR: 2.06 [1.08-3.93], p = 0.029), a higher preoperative body mass index (BMI) (HR: 1.07 [1.01-1.13], p = 0.023), and intensive care unit (ICU) duration (HR: 1.03 [1.00-1.06], p = 0.025) were independent predictors of LHRF in the multivariable model. A significant relation between the severity of tricuspid regurgitation (TR) and LRHF (HR: 1.91 [1.13-3.21], p = 0.016) was found in patients with echocardiographic data. Patients with LRHF demonstrated a lower maximal workload and peak VO2 at 6 months postoperatively.

Conclusion

A history of AF, BMI, and longer ICU stay may help identify patients at high risk for LRHF. Severity of TR was significantly related to LRHF in a subset of patients.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/aor.14537; doi:https://doi.org/10.1111/aor.14537 33612430,https://doi.org/10.1016/s2589-7500(21)00017-0,Indirect acute effects of the COVID-19 pandemic on physical and mental health in the UK: a population-based study.,"Mansfield KE, Mathur R, Tazare J, Henderson AD, Mulick AR, Carreira H, Matthews AA, Bidulka P, Gayle A, Forbes H, Cook S, Wong AYS, Strongman H, Wing K, Warren-Gash C, Cadogan SL, Smeeth L, Hayes JF, Quint JK, McKee M, Langan SM.",,The Lancet. Digital health,2021,2021-02-18,Y,,,,"

Background

There are concerns that the response to the COVID-19 pandemic in the UK might have worsened physical and mental health, and reduced use of health services. However, the scale of the problem is unquantified, impeding development of effective mitigations. We aimed to ascertain what has happened to general practice contacts for acute physical and mental health outcomes during the pandemic.

Methods

Using de-identified electronic health records from the Clinical Research Practice Datalink (CPRD) Aurum (covering 13% of the UK population), between 2017 and 2020, we calculated weekly primary care contacts for selected acute physical and mental health conditions: anxiety, depression, self-harm (fatal and non-fatal), severe mental illness, eating disorder, obsessive-compulsive disorder, acute alcohol-related events, asthma exacerbation, chronic obstructive pulmonary disease exacerbation, acute cardiovascular events (cerebrovascular accident, heart failure, myocardial infarction, transient ischaemic attacks, unstable angina, and venous thromboembolism), and diabetic emergency. Primary care contacts included remote and face-to-face consultations, diagnoses from hospital discharge letters, and secondary care referrals, and conditions were identified through primary care records for diagnoses, symptoms, and prescribing. Our overall study population included individuals aged 11 years or older who had at least 1 year of registration with practices contributing to CPRD Aurum in the specified period, but denominator populations varied depending on the condition being analysed. We used an interrupted time-series analysis to formally quantify changes in conditions after the introduction of population-wide restrictions (defined as March 29, 2020) compared with the period before their introduction (defined as Jan 1, 2017 to March 7, 2020), with data excluded for an adjustment-to-restrictions period (March 8-28).

Findings

The overall population included 9 863 903 individuals on Jan 1, 2017, and increased to 10 226 939 by Jan 1, 2020. Primary care contacts for almost all conditions dropped considerably after the introduction of population-wide restrictions. The largest reductions were observed for contacts for diabetic emergencies (odds ratio 0·35 [95% CI 0·25-0·50]), depression (0·53 [0·52-0·53]), and self-harm (0·56 [0·54-0·58]). In the interrupted time-series analysis, with the exception of acute alcohol-related events (0·98 [0·89-1·10]), there was evidence of a reduction in contacts for all conditions (anxiety 0·67 [0·66-0·67], eating disorders 0·62 [0·59-0·66], obsessive-compulsive disorder [0·69 [0·64-0·74]], self-harm 0·56 [0·54-0·58], severe mental illness 0·80 [0·78-0·83], stroke 0·59 [0·56-0·62], transient ischaemic attack 0·63 [0·58-0·67], heart failure 0·62 [0·60-0·64], myocardial infarction 0·72 [0·68-0·77], unstable angina 0·72 [0·60-0·87], venous thromboembolism 0·94 [0·90-0·99], and asthma exacerbation 0·88 [0·86-0·90]). By July, 2020, except for unstable angina and acute alcohol-related events, contacts for all conditions had not recovered to pre-lockdown levels.

Interpretation

There were substantial reductions in primary care contacts for acute physical and mental conditions following the introduction of restrictions, with limited recovery by July, 2020. Further research is needed to ascertain whether these reductions reflect changes in disease frequency or missed opportunities for care. Maintaining health-care access should be a key priority in future public health planning, including further restrictions. The conditions we studied are sufficiently severe that any unmet need will have substantial ramifications for the people with the conditions as well as health-care provision.

Funding

Wellcome Trust Senior Fellowship, Health Data Research UK.",,pdf:http://www.thelancet.com/article/S2589750021000170/pdf; doi:https://doi.org/10.1016/S2589-7500(21)00017-0; html:https://europepmc.org/articles/PMC7985613; pdf:https://europepmc.org/articles/PMC7985613?pdf=render -34399584,https://doi.org/10.1161/strokeaha.120.032619,Risk Prediction Using Polygenic Risk Scores for Prevention of Stroke and Other Cardiovascular Diseases.,"Abraham G, Rutten-Jacobs L, Inouye M.",,Stroke,2021,2021-08-17,N,Genetics; Myocardial infarction; Cardiovascular disease; Stroke; risk assessment,,,"Early prediction of risk of cardiovascular disease (CVD), including stroke, is a cornerstone of disease prevention. Clinical risk scores have been widely used for predicting CVD risk from known risk factors. Most CVDs have a substantial genetic component, which also has been confirmed for stroke in recent gene discovery efforts. However, the role of genetics in prediction of risk of CVD, including stroke, has been limited to testing for highly penetrant monogenic disorders. In contrast, the importance of polygenic variation, the aggregated effect of many common genetic variants across the genome with individually small effects, has become more apparent in the last 5 to 10 years, and powerful polygenic risk scores for CVD have been developed. Here we review the current state of the field of polygenic risk scores for CVD including stroke, and their potential to improve CVD risk prediction. We present findings and lessons from diseases such as coronary artery disease as these will likely be useful to inform future research in stroke polygenic risk prediction.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.120.032619; doi:https://doi.org/10.1161/STROKEAHA.120.032619; html:https://europepmc.org/articles/PMC7611731; pdf:https://europepmc.org/articles/PMC7611731?pdf=render; doi:https://doi.org/10.1161/strokeaha.120.032619 +37549998,https://doi.org/10.1136/bjsports-2022-106460,Device-based measurement of physical activity in cardiovascular healthcare: possibilities and challenges.,"Chico TJ, Stamatakis E, Ciravegna F, Dunn J, Redwood S, Al-Lamee R, Sofat R, Gill J.",,British journal of sports medicine,2023,2023-08-07,N,Cardiovascular diseases; Health; Physical Activity,,,,,doi:https://doi.org/10.1136/bjsports-2022-106460 33249608,https://doi.org/10.1111/opo.12765,Authors' Reply.,"Wright DM, O'Reilly D, Azuara-Blanco A, Curran R, McMullan M, Hogg RE.",,Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists),2021,2020-11-29,N,,,,,,doi:https://doi.org/10.1111/opo.12765 +34399584,https://doi.org/10.1161/strokeaha.120.032619,Risk Prediction Using Polygenic Risk Scores for Prevention of Stroke and Other Cardiovascular Diseases.,"Abraham G, Rutten-Jacobs L, Inouye M.",,Stroke,2021,2021-08-17,N,Genetics; Myocardial infarction; Cardiovascular disease; Stroke; risk assessment,,,"Early prediction of risk of cardiovascular disease (CVD), including stroke, is a cornerstone of disease prevention. Clinical risk scores have been widely used for predicting CVD risk from known risk factors. Most CVDs have a substantial genetic component, which also has been confirmed for stroke in recent gene discovery efforts. However, the role of genetics in prediction of risk of CVD, including stroke, has been limited to testing for highly penetrant monogenic disorders. In contrast, the importance of polygenic variation, the aggregated effect of many common genetic variants across the genome with individually small effects, has become more apparent in the last 5 to 10 years, and powerful polygenic risk scores for CVD have been developed. Here we review the current state of the field of polygenic risk scores for CVD including stroke, and their potential to improve CVD risk prediction. We present findings and lessons from diseases such as coronary artery disease as these will likely be useful to inform future research in stroke polygenic risk prediction.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.120.032619; doi:https://doi.org/10.1161/STROKEAHA.120.032619; html:https://europepmc.org/articles/PMC7611731; pdf:https://europepmc.org/articles/PMC7611731?pdf=render; doi:https://doi.org/10.1161/strokeaha.120.032619 34169636,https://doi.org/10.1002/pst.2148,Assessing safety at the end of clinical trials using system organ classes: A case and comparative study.,"Carragher R, Robertson C.",,Pharmaceutical statistics,2021,2021-06-24,N,Safety; False Discovery Rate; Adverse Events; System Organ Class; Bayesian Hierarchy,,,"Recent approaches to the statistical analysis of adverse event (AE) data in clinical trials have proposed the use of groupings of related AEs, such as by system organ class (SOC). These methods have opened up the possibility of scanning large numbers of AEs while controlling for multiple comparisons, making the comparative performance of the different methods in terms of AE detection and error rates of interest to investigators. We apply two Bayesian models and two procedures for controlling the false discovery rate (FDR), which use groupings of AEs, to real clinical trial safety data. We find that while the Bayesian models are appropriate for the full data set, the error controlling methods only give similar results to the Bayesian methods when low incidence AEs are removed. A simulation study is used to compare the relative performances of the methods. We investigate the differences between the methods over full trial data sets, and over data sets with low incidence AEs and SOCs removed. We find that while the removal of low incidence AEs increases the power of the error controlling procedures, the estimated power of the Bayesian methods remains relatively constant over all data sizes. Automatic removal of low-incidence AEs however does have an effect on the error rates of all the methods, and a clinically guided approach to their removal is needed. Overall we found that the Bayesian approaches are particularly useful for scanning the large amounts of AE data gathered.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pst.2148; doi:https://doi.org/10.1002/pst.2148 32908801,https://doi.org/10.1167/tvst.9.9.38,Merging Information From Infrared and Autofluorescence Fundus Images for Monitoring of Chorioretinal Atrophic Lesions.,"Ometto G, Montesano G, Sadeghi Afgeh S, Lazaridis G, Liu X, Keane PA, Crabb DP, Denniston AK.",,Translational vision science & technology,2020,2020-08-25,Y,Autofluorescence; Segmentation; infrared; Uveitis; Multimodal,,,"

Purpose

To develop a method for automated detection and progression analysis of chorioretinal atrophic lesions using the combined information of standard infrared (IR) and autofluorescence (AF) fundus images.

Methods

Eighteen eyes (from 16 subjects) with punctate inner choroidopathy were analyzed. Macular IR and blue AF images were acquired in all eyes with a Spectralis HRA+OCT device (Heidelberg Engineering, Heidelberg, Germany). Two clinical experts manually segmented chorioretinal lesions on the AF image. AF images were aligned to the corresponding IR. Two random forest models were trained to classify pixels of lesions, one based on the AF image only, the other based on the aligned IR-AF. The models were validated using a leave-one-out cross-validation and were tested against the manual segmentation to compare their performance. A time series from one eye was identified and used to evaluate the method based on the IR-AF in a case study.

Results

The method based on the AF images correctly classified 95% of the pixels (i.e., in vs. out of the lesion) with a Dice's coefficient of 0.80. The method based on the combined IR-AF correctly classified 96% of the pixels with a Dice's coefficient of 0.84.

Conclusions

The automated segmentation of chorioretinal lesions using IR and AF shows closer alignment to manual segmentation than the same method based on AF only. Merging information from multimodal images improves the automatic and objective segmentation of chorioretinal lesions even when based on a small dataset.

Translational relevance

Merged information from multimodal images improves segmentation performance of chorioretinal lesions.",,doi:https://doi.org/10.1167/tvst.9.9.38; doi:https://doi.org/10.1167/tvst.9.9.38; html:https://europepmc.org/articles/PMC7453042; pdf:https://europepmc.org/articles/PMC7453042?pdf=render -37140153,https://doi.org/10.1093/ehjci/jead093,Determinants of post-operative left ventricular dysfunction in degenerative mitral regurgitation.,"Althunayyan AM, Alborikan S, Badiani S, Wong K, Uppal R, Patel N, Petersen SE, Lloyd G, Bhattacharyya S.",,European heart journal. Cardiovascular Imaging,2023,2023-08-01,N,Surgery; Mitral regurgitation; Mitral Valve Prolapse; Global Longitudinal Strain; Lv Volumes,,,"

Aims

Chronic degenerative mitral regurgitation leads to volume overload causing left ventricular (LV) enlargement and eventually LV impairment. Current guidelines determining thresholds for intervention are based on LV diameters and ejection fraction (LVEF). There are sparse data examining the value of LV volumes and newer markers of LV performance on outcomes of surgery in mitral valve prolapse. The aim of this study is to identify the best marker of LV impairment after mitral valve surgery.

Methods and results

Prospective, observational study of patients with mitral valve prolapse undergoing mitral valve surgery. Pre-operative LV diameters, volumes, LVEF, global longitudinal strain (GLS), and myocardial work measured. Post-operative LV impairment defined as LVEF < 50% at 1 year post-surgery. Eighty-seven patients included. Thirteen percent developed post-operative LV impairment. Patients with post-operative LV dysfunction showed significantly larger indexed LV end-systolic diameters, indexed LV end-systolic volumes (LVESVi), lower LVEF, and more abnormal GLS than patients without post-operative LV dysfunction. In multivariate analysis, LVESVi [odds ratio 1.11 (95% CI 1.01-1.23), P = 0.039] and GLS [odds ratio 1.46 (95% CI 1.00-2.14), P = 0.054] were the only independent predictors of post-operative LV dysfunction. The optimal cut-off of 36.3 mL/m2 for LVESVi had a sensitivity of 82% and specificity of 78% for detection of post-operative LV impairment.

Conclusion

Post-operative LV impairment is common. Indexed LV volumes (36.3 mL/m2) provided the best marker of post-operative LV impairment.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead093/50200028/jead093.pdf; doi:https://doi.org/10.1093/ehjci/jead093 33704068,https://doi.org/10.7554/elife.64827,Longitudinal proteomic profiling of dialysis patients with COVID-19 reveals markers of severity and predictors of death.,"Gisby J, Clarke CL, Medjeral-Thomas N, Malik TH, Papadaki A, Mortimer PM, Buang NB, Lewis S, Pereira M, Toulza F, Fagnano E, Mawhin MA, Dutton EE, Tapeng L, Richard AC, Kirk PD, Behmoaras J, Sandhu E, McAdoo SP, Prendecki MF, Pickering MC, Botto M, Willicombe M, Thomas DC, Peters JE.",,eLife,2021,2021-03-11,Y,Human; Cytokines; Proteomics; Inflammation; Medicine; Biomarkers; immunology; Longitudinal; End-stage Kidney Disease; Covid-19,,,"End-stage kidney disease (ESKD) patients are at high risk of severe COVID-19. We measured 436 circulating proteins in serial blood samples from hospitalised and non-hospitalised ESKD patients with COVID-19 (n = 256 samples from 55 patients). Comparison to 51 non-infected patients revealed 221 differentially expressed proteins, with consistent results in a separate subcohort of 46 COVID-19 patients. Two hundred and three proteins were associated with clinical severity, including IL6, markers of monocyte recruitment (e.g. CCL2, CCL7), neutrophil activation (e.g. proteinase-3), and epithelial injury (e.g. KRT19). Machine-learning identified predictors of severity including IL18BP, CTSD, GDF15, and KRT19. Survival analysis with joint models revealed 69 predictors of death. Longitudinal modelling with linear mixed models uncovered 32 proteins displaying different temporal profiles in severe versus non-severe disease, including integrins and adhesion molecules. These data implicate epithelial damage, innate immune activation, and leucocyte-endothelial interactions in the pathology of severe COVID-19 and provide a resource for identifying drug targets.",,doi:https://doi.org/10.7554/elife.64827; doi:https://doi.org/10.7554/eLife.64827; html:https://europepmc.org/articles/PMC8064756; pdf:https://europepmc.org/articles/PMC8064756?pdf=render +37140153,https://doi.org/10.1093/ehjci/jead093,Determinants of post-operative left ventricular dysfunction in degenerative mitral regurgitation.,"Althunayyan AM, Alborikan S, Badiani S, Wong K, Uppal R, Patel N, Petersen SE, Lloyd G, Bhattacharyya S.",,European heart journal. Cardiovascular Imaging,2023,2023-08-01,N,Surgery; Mitral regurgitation; Mitral Valve Prolapse; Global Longitudinal Strain; Lv Volumes,,,"

Aims

Chronic degenerative mitral regurgitation leads to volume overload causing left ventricular (LV) enlargement and eventually LV impairment. Current guidelines determining thresholds for intervention are based on LV diameters and ejection fraction (LVEF). There are sparse data examining the value of LV volumes and newer markers of LV performance on outcomes of surgery in mitral valve prolapse. The aim of this study is to identify the best marker of LV impairment after mitral valve surgery.

Methods and results

Prospective, observational study of patients with mitral valve prolapse undergoing mitral valve surgery. Pre-operative LV diameters, volumes, LVEF, global longitudinal strain (GLS), and myocardial work measured. Post-operative LV impairment defined as LVEF < 50% at 1 year post-surgery. Eighty-seven patients included. Thirteen percent developed post-operative LV impairment. Patients with post-operative LV dysfunction showed significantly larger indexed LV end-systolic diameters, indexed LV end-systolic volumes (LVESVi), lower LVEF, and more abnormal GLS than patients without post-operative LV dysfunction. In multivariate analysis, LVESVi [odds ratio 1.11 (95% CI 1.01-1.23), P = 0.039] and GLS [odds ratio 1.46 (95% CI 1.00-2.14), P = 0.054] were the only independent predictors of post-operative LV dysfunction. The optimal cut-off of 36.3 mL/m2 for LVESVi had a sensitivity of 82% and specificity of 78% for detection of post-operative LV impairment.

Conclusion

Post-operative LV impairment is common. Indexed LV volumes (36.3 mL/m2) provided the best marker of post-operative LV impairment.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead093/50200028/jead093.pdf; doi:https://doi.org/10.1093/ehjci/jead093 35667411,https://doi.org/10.1016/j.jamda.2022.05.003,Stroke in Older Adults Living in Care Homes: Results From a National Data Linkage Study in Wales.,"Harrison SL, Lip GYH, Akbari A, Torabi F, Ritchie LA, Akpan A, Halcox J, Rodgers S, Hollinghurst J, Harris D, Lane DA.",,Journal of the American Medical Directors Association,2022,2022-06-03,N,Anticoagulants; Cerebrovascular disease; Nursing Homes; Antiplatelets,,,"

Objectives

To determine the proportion of older people moving to care homes with a recent stroke, incidence of stroke after moving to a care home, mortality following stroke, and secondary stroke prevention management in older care home residents.

Design

Retrospective cohort study using population-scale individual-level linked data sources between 2003 and 2018 in the Secure Anonymized Information Linkage (SAIL) Databank.

Setting and participants

People aged ≥65 years residing in long-term care homes in Wales.

Methods

Competing risk models and logistic regression models were used to examine the association between prior stroke, incident stroke, and mortality following stroke.

Results

Of 86,602 individuals, 7.0% (n = 6055) experienced a stroke in the 12 months prior to care home entry. The incidence of stroke within 12 months after entry to a care home was 26.2 per 1000 person-years [95% confidence interval (CI) 25.0, 27.5]. Previous stroke was associated with higher risk of incident stroke after moving to a care home (subdistribution hazard ratio 1.83, 95% CI 1.57, 2.13) and 30-day mortality following stroke (odds ratio 2.18, 95% CI 1.59, 2.98). Severe frailty was not significantly associated with risk of stroke or 30-day mortality following stroke. Secondary stroke prevention included statins (51.0%), antiplatelets (61.2%), anticoagulants (52.4% of those with atrial fibrillation), and antihypertensives (92.1% of those with hypertension).

Conclusions and implications

At the time of care home entry, individuals with history of stroke in the previous 12 months are at a higher risk of incident stroke and mortality following an incident stroke. These individuals are frequently not prescribed medications for secondary stroke prevention. Further evidence is needed to determine the optimal care pathways for older people living in long-term care homes with history of stroke.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa60151/Download/60151__25104__e0e71818d5bd49acba048a3d98682425.pdf; doi:https://doi.org/10.1016/j.jamda.2022.05.003 34673925,https://doi.org/10.1093/ageing/afab201,"Do home adaptation interventions help to reduce emergency fall admissions? A national longitudinal data-linkage study of 657,536 older adults living in Wales (UK) between 2010 and 2017.","Hollinghurst J, Daniels H, Fry R, Akbari A, Rodgers S, Watkins A, Hillcoat-Nallétamby S, Williams N, Nikolova S, Meads D, Clegg A.",,Age and ageing,2022,2022-01-01,Y,Frailty; Falls; Older People; Falls Prevention,,,"

Background

falls are common in older people, but evidence for the effectiveness of preventative home adaptations is limited.

Aim

determine whether a national home adaptation service, Care&Repair Cymru (C&RC), identified individuals at risk of falls occurring at home and reduced the likelihood of falls.

Study design

retrospective longitudinal controlled non-randomised intervention cohort study.

Setting

our cohort consisted of 657,536 individuals aged 60+ living in Wales (UK) between 1 January 2010 and 31 December 2017. About 123,729 individuals received a home adaptation service.

Methods

we created a dataset with up to 41 quarterly observations per person. For each quarter, we observed if a fall occurred at home that resulted in either an emergency department or an emergency hospital admission. We analysed the data using multilevel logistic regression.

Results

compared to the control group, C&RC clients had higher odds of falling, with an odds ratio (OR [95% confidence interval]) of 1.93 [1.87, 2.00]. Falls odds was higher for females (1.44 [1.42, 1.46]), older age (1.07 [1.07, 1.07]), increased frailty (mild 1.57 [1.55, 1.60], moderate 2.31 [2.26, 2.35], severe 3.05 [2.96, 3.13]), and deprivation (most deprived compared to least: 1.16 [1.13, 1.19]). Client fall odds decreased post-intervention; OR 0.97 [0.96, 0.97] per quarter. Regional variation existed for falls (5.8%), with most variation at the individual level (31.3%).

Conclusions

C&RC identified people more likely to have an emergency fall admission occurring at home, and their service reduced the odds of falling post-intervention. Service provisioning should meet the needs of an individual and need varies by personal and regional circumstance.",,pdf:https://academic.oup.com/ageing/article-pdf/51/1/afab201/42083711/afab201.pdf; doi:https://doi.org/10.1093/ageing/afab201; html:https://europepmc.org/articles/PMC8753038; pdf:https://europepmc.org/articles/PMC8753038?pdf=render 38450564,https://doi.org/10.1089/neu.2023.0462,The Australian Traumatic Brain Injury Initiative: Systematic Review and Consensus Process to Determine the Predictive Value of Pre-existing Health Conditions for People with Moderate-Severe Traumatic Brain Injury.,"Antonic-Baker A, Auvrez C, Tao G, Bagg MK, Gadowski A, McKimmie A, Hicks AJ, Hill R, Romero L, Ponsford JL, Lannin NA, Gabbe BJ, Cameron PA, Cooper DJ, Rushworth N, Fitzgerald M, O'Brien TJ.",,Journal of neurotrauma,2024,2024-04-15,N,"Health care; Mental health; Comorbidity; Common Data Elements; Multiple Chronic Conditions; Brain Injuries, Traumatic; Outcome Assessment, Systematic Review [Publication Type]",,,"The first aim of the Australian Traumatic Brain Injury Initiative (AUS-TBI) encompasses development of a set of measures that comprehensively predict outcomes for people with moderate-severe TBI across Australia. This process engaged diverse stakeholders and information sources across six areas: social, health, and clinical factors; biological markers; treatments; and longer-term outcomes. Here, we report the systematic review of pre-existing health conditions as predictors of outcome for people with moderate-severe TBI. Standardized searches were implemented across databases until March 31, 2022. English-language reports of studies evaluating association between pre-existing health conditions and clinical outcome in at least 10 patients with moderate-severe TBI were included. A predefined algorithm was used to assign a judgement of predictive value to each observed association. The list of identified pre-existing health conditions was then discussed with key stakeholders during a consensus meeting to determine the feasibility of incorporating them into standard care. The searches retrieved 22,217 records, of which 47 articles were included. The process led to identification of 88 unique health predictors (homologized to 21 predictor categories) of 55 outcomes (homologized to 19 outcome categories). Only pre-existing health conditions with high and moderate predictive values were discussed during the consensus meeting. Following the consensus meeting, 5 out of 11 were included (migraine, mental health conditions, ≥4 pre-existing health conditions, osteoporosis, and body mass index [BMI]) as common data elements in the AUS-TBI data dictionary. Upon further discussion, 3 additional pre-existing health conditions were included. These are pre-existing heart disease, frailty score, and previous incidence of TBI.",,doi:https://doi.org/10.1089/neu.2023.0462 @@ -1111,8 +1111,8 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 38672093,https://doi.org/10.3390/biomedicines12040737,Determinants of Carotid Wall Echolucency in a Cohort of European High Cardiovascular Risk Subjects: A Cross-Sectional Analysis of IMPROVE Baseline Data.,"Frigerio B, Coggi D, Bonomi A, Amato M, Capra N, Colombo GI, Sansaro D, Ravani A, Savonen K, Giral P, Gallo A, Pirro M, Gigante B, Eriksson P, Strawbridge RJ, Mulder DJ, Tremoli E, Veglia F, Baldassarre D, IMPROVE Study Group.",,Biomedicines,2024,2024-03-26,N,Atherosclerosis; Carotid plaque; risk factors; cardiovascular; Intima–media Thickness; Gray-scale Median; Echolucency,,,"Echolucency, a measure of plaque instability associated with increased cardiovascular risk, can be assessed in both the carotid plaque and the plaque-free common carotid intima-media (IM) complex as a gray-scale median (plaque-GSM and IM-GSM, respectively). The impact of specific vascular risk factors on these two phenotypes remains uncertain, including the nature and extent of their influence. This study aims to seek the determinants of plaque-GSM and IM-GSM. Plaque-GSM and IM-GSM were measured in subjects from the IMPROVE study cohort (aged 54-79, 46% men) recruited in five European countries. Plaque-GSM was measured in subjects who had at least one IMTmax ≥ 1.5 mm (n = 2138), whereas IM-GSM was measured in all subjects included in the study (n = 3188). Multiple regression with internal cross-validation was used to find independent predictors of plaque-GSM and IM-GSM. Plaque-GSM determinants were plaque-size (IMTmax), and diastolic blood pressure. IM-GSM determinants were the thickness of plaque-free common carotid intima-media complex (PF CC-IMTmean), height, systolic blood pressure, waist/hip ratio, treatment with fibrates, mean corpuscular volume, treatment with alpha-2 inhibitors (sartans), educational level, and creatinine. Latitude, and pack-yearscode were determinants of both plaque-GSM and IM-GSM. The overall models explain 12.0% of plaque-GSM variability and 19.7% of IM-GSM variability. A significant correlation (r = 0.51) was found between plaque-GSM and IM-GSM. Our results indicate that IM-GSM is a weighty risk marker alternative to plaque-GSM, offering the advantage of being readily measurable in all subjects, including those in the early phases of atherosclerosis where plaque occurrence is relatively infrequent.",,doi:https://doi.org/10.3390/biomedicines12040737 36050271,https://doi.org/10.1016/s2589-7500(22)00151-0,CODE-EHR best-practice framework for the use of structured electronic health-care records in clinical research.,"Kotecha D, Asselbergs FW, Achenbach S, Anker SD, Atar D, Baigent C, Banerjee A, Beger B, Brobert G, Casadei B, Ceccarelli C, Cowie MR, Crea F, Cronin M, Denaxas S, Derix A, Fitzsimons D, Fredriksson M, Gale CP, Gkoutos GV, Goettsch W, Hemingway H, Ingvar M, Jonas A, Kazmierski R, Løgstrup S, Lumbers RT, Lüscher TF, McGreavy P, Piña IL, Roessig L, Steinbeisser C, Sundgren M, Tyl B, Thiel GV, Bochove KV, Vardas PE, Villanueva T, Vrana M, Weber W, Weidinger F, Windecker S, Wood A, Grobbee DE, Innovative Medicines Initiative BigData@Heart Consortium, European Society of Cardiology, and CODE-EHR International Consensus Group.",,The Lancet. Digital health,2022,2022-08-29,N,,,,"Big data is important to new developments in global clinical science that aim to improve the lives of patients. Technological advances have led to the regular use of structured electronic health-care records with the potential to address key deficits in clinical evidence that could improve patient care. The COVID-19 pandemic has shown this potential in big data and related analytics but has also revealed important limitations. Data verification, data validation, data privacy, and a mandate from the public to conduct research are important challenges to effective use of routine health-care data. The European Society of Cardiology and the BigData@Heart consortium have brought together a range of international stakeholders, including representation from patients, clinicians, scientists, regulators, journal editors, and industry members. In this Review, we propose the CODE-EHR minimum standards framework to be used by researchers and clinicians to improve the design of studies and enhance transparency of study methods. The CODE-EHR framework aims to develop robust and effective utilisation of health-care data for research purposes.",,doi:https://doi.org/10.1016/s2589-7500(22)00151-0; doi:https://doi.org/10.1016/S2589-7500(22)00151-0 37739596,https://doi.org/10.1016/j.jtha.2023.07.008,"""C1-inhibitor levels and venous thromboembolism: results from a Mendelian randomization study"": reply.","Cupido AJ, Petersen RS, Schmidt AF, Levi M, Cohn DM, Fijen LM.",,Journal of thrombosis and haemostasis : JTH,2023,2023-10-01,N,,,,,,doi:https://doi.org/10.1016/j.jtha.2023.07.008 -37440761,https://doi.org/10.1093/ehjci/jead166,Neuroticism personality traits are linked to adverse cardiovascular phenotypes in the UK Biobank.,"Mahmood A, Simon J, Cooper J, Murphy T, McCracken C, Quiroz J, Laranjo L, Aung N, Lee AM, Khanji MY, Neubauer S, Raisi-Estabragh Z, Maurovich-Horvat P, Petersen SE.",,European heart journal. Cardiovascular Imaging,2023,2023-10-01,Y,Cardiac function; Cardiac morphology; Mental health; Cardiovascular Magnetic Resonance; Neuroticism; Cardiovascular Remodelling,,,"

Aims

To evaluate the relationship between neuroticism personality traits and cardiovascular magnetic resonance (CMR) measures of cardiac morphology and function, considering potential differential associations in men and women.

Methods and results

The analysis includes 36 309 UK Biobank participants (average age = 63.9 ± 7.7 years; 47.8% men) with CMR available and neuroticism score assessed by the 12-item Eysenck Personality Questionnaire-Revised Short Form. CMR scans were performed on 1.5 Tesla scanners (MAGNETOM Aera, Siemens Healthcare, Erlangen, Germany) according to pre-defined protocols and analysed using automated pipelines. We considered measures of left ventricular (LV) and right ventricular (RV) structure and function, and indicators of arterial compliance. Multivariable linear regression was used to estimate association of neuroticism score with individual CMR metrics, with adjustment for age, sex, obesity, deprivation, smoking, diabetes, hypertension, hypercholesterolaemia, alcohol use, exercise, and education. Higher neuroticism scores were associated with smaller LV and RV end-diastolic volumes, lower LV mass, greater concentricity (higher LV mass to volume ratio), and higher native T1. Greater neuroticism was also linked to poorer LV and RV function (lower stroke volumes) and greater arterial stiffness. In sex-stratified analyses, the relationships between neuroticism and LV stroke volume, concentricity, and arterial stiffness were attenuated in women. In men, association (with exception of native T1) remained robust.

Conclusion

Greater tendency towards neuroticism personality traits is linked to smaller, poorer functioning ventricles with lower LV mass, higher myocardial fibrosis, and higher arterial stiffness. These relationships are independent of traditional vascular risk factors and are more robust in men than women.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead166/50880139/jead166.pdf; doi:https://doi.org/10.1093/ehjci/jead166; html:https://europepmc.org/articles/PMC10610755; pdf:https://europepmc.org/articles/PMC10610755?pdf=render 34088700,https://doi.org/10.2337/dc20-2518,"Type 2 Diabetes, Metabolic Traits, and Risk of Heart Failure: A Mendelian Randomization Study.","Mordi IR, Lumbers RT, Palmer CNA, Pearson ER, Sattar N, Holmes MV, Lang CC, HERMES Consortium.",,Diabetes care,2021,2021-06-04,Y,,,,"

Objective

The aim of this study was to use Mendelian randomization (MR) techniques to estimate the causal relationships between genetic liability to type 2 diabetes (T2D), glycemic traits, and risk of heart failure (HF).

Research design and methods

Summary-level data were obtained from genome-wide association studies of T2D, insulin resistance (IR), glycated hemoglobin, fasting insulin and glucose, and HF. MR was conducted using the inverse-variance weighted method. Sensitivity analyses included the MR-Egger method, weighted median and mode methods, and multivariable MR conditioning on potential mediators.

Results

Genetic liability to T2D was causally related to higher risk of HF (odds ratio [OR] 1.13 per 1-log unit higher risk of T2D; 95% CI 1.11-1.14; P < 0.001); however, sensitivity analysis revealed evidence of directional pleiotropy. The relationship between T2D and HF was attenuated when adjusted for coronary disease, BMI, LDL cholesterol, and blood pressure in multivariable MR. Genetically instrumented higher IR was associated with higher risk of HF (OR 1.19 per 1-log unit higher risk of IR; 95% CI 1.00-1.41; P = 0.041). There were no notable associations identified between fasting insulin, glucose, or glycated hemoglobin and risk of HF. Genetic liability to HF was causally linked to higher risk of T2D (OR 1.49; 95% CI 1.01-2.19; P = 0.042), although again with evidence of pleiotropy.

Conclusions

These findings suggest a possible causal role of T2D and IR in HF etiology, although the presence of both bidirectional effects and directional pleiotropy highlights potential sources of bias that must be considered.",,pdf:https://diabetesjournals.org/care/article-pdf/44/7/1699/632992/dc202518.pdf; doi:https://doi.org/10.2337/dc20-2518; html:https://europepmc.org/articles/PMC8323186; pdf:https://europepmc.org/articles/PMC8323186?pdf=render +37440761,https://doi.org/10.1093/ehjci/jead166,Neuroticism personality traits are linked to adverse cardiovascular phenotypes in the UK Biobank.,"Mahmood A, Simon J, Cooper J, Murphy T, McCracken C, Quiroz J, Laranjo L, Aung N, Lee AM, Khanji MY, Neubauer S, Raisi-Estabragh Z, Maurovich-Horvat P, Petersen SE.",,European heart journal. Cardiovascular Imaging,2023,2023-10-01,Y,Cardiac function; Cardiac morphology; Mental health; Cardiovascular Magnetic Resonance; Neuroticism; Cardiovascular Remodelling,,,"

Aims

To evaluate the relationship between neuroticism personality traits and cardiovascular magnetic resonance (CMR) measures of cardiac morphology and function, considering potential differential associations in men and women.

Methods and results

The analysis includes 36 309 UK Biobank participants (average age = 63.9 ± 7.7 years; 47.8% men) with CMR available and neuroticism score assessed by the 12-item Eysenck Personality Questionnaire-Revised Short Form. CMR scans were performed on 1.5 Tesla scanners (MAGNETOM Aera, Siemens Healthcare, Erlangen, Germany) according to pre-defined protocols and analysed using automated pipelines. We considered measures of left ventricular (LV) and right ventricular (RV) structure and function, and indicators of arterial compliance. Multivariable linear regression was used to estimate association of neuroticism score with individual CMR metrics, with adjustment for age, sex, obesity, deprivation, smoking, diabetes, hypertension, hypercholesterolaemia, alcohol use, exercise, and education. Higher neuroticism scores were associated with smaller LV and RV end-diastolic volumes, lower LV mass, greater concentricity (higher LV mass to volume ratio), and higher native T1. Greater neuroticism was also linked to poorer LV and RV function (lower stroke volumes) and greater arterial stiffness. In sex-stratified analyses, the relationships between neuroticism and LV stroke volume, concentricity, and arterial stiffness were attenuated in women. In men, association (with exception of native T1) remained robust.

Conclusion

Greater tendency towards neuroticism personality traits is linked to smaller, poorer functioning ventricles with lower LV mass, higher myocardial fibrosis, and higher arterial stiffness. These relationships are independent of traditional vascular risk factors and are more robust in men than women.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead166/50880139/jead166.pdf; doi:https://doi.org/10.1093/ehjci/jead166; html:https://europepmc.org/articles/PMC10610755; pdf:https://europepmc.org/articles/PMC10610755?pdf=render 37649471,https://doi.org/10.23889/ijpds.v6i3.1705,Data linkage can reduce the burden and increase the opportunities in the implementation of Value-Based Health Care policy: a study in patients with ulcerative colitis (PROUD-UC Study).,"Walshe J, Akbari A, Hawthorne AB, Laing H.",,International journal of population data science,2021,2021-01-01,Y,"Colitis, ulcerative; Health Policy; Patient Reported Outcome Measure; Routinely Collected Health Data; Data Science; Value-based Health Care",,,"

Introduction

Healthcare systems face rising demand and unsustainable cost pressures. In response, health policymakers are adopting Value-Based Health Care (VBHC), targeting available resources to achieve the best possible patient outcomes at the lowest possible cost and actively disinvesting in care of low-value. This requires the evaluation of longitudinal clinical and patient reported outcome measures (PROMs) at an individual-level and population-scale, which can create significant data challenges. Achieving this through routinely collected electronic health record (EHR) data-linkage could facilitate the implementation of VBHC without an unacceptable data burden on patients or health systems and release time for higher-value activities.

Objectives

Our study tested the ability to report an international, patient-centred outcome dataset (ICHOM-IBD) using only anonymised individual-level population-scale linked electronic health record (EHR) data sources, including clinical and patient-reported outcomes, in a cohort of patients with moderate-to-severe ulcerative colitis (UC), receiving biopharmaceutical therapies (""biologics"") in a single, publicly funded, healthcare system.

Results

We identified a cohort of 17,632 patients with UC in Wales and a cohort from two Health Boards of 447 patients with UC receiving biologics. 112 of these patients had completed 866 condition-specific PROMs during their biologics treatment. 44 out of 59 (74.6%) items in the ICHOM-IBD could be derived from routinely collected data of which a primary care source was essential for eight items and desirable for 21.

Conclusions

We demonstrated that it is possible to report most but not all the ICHOM-IBD outcomes using routinely collected data from multiple sources without additional system burden, potentially supporting Value-Based Health Care implementation with population data science. As digital collection of PROMs and use of condition-specific registries grow, greater utility of this approach can be anticipated. We have identified that the availability of longitudinal primary and secondary care data linked with PROMs is essential for this to be possible.",,pdf:https://ijpds.org/article/download/1705/4121; doi:https://doi.org/10.23889/ijpds.v6i3.1705; html:https://europepmc.org/articles/PMC10464864; pdf:https://europepmc.org/articles/PMC10464864?pdf=render 34671274,https://doi.org/10.3389/fphys.2021.730736,Comparing Non-invasive Inverse Electrocardiography With Invasive Endocardial and Epicardial Electroanatomical Mapping During Sinus Rhythm.,"Roudijk RW, Boonstra MJ, Brummel R, Kassenberg W, Blom LJ, Oostendorp TF, Te Riele ASJM, van der Heijden JF, Asselbergs FW, van Dam PM, Loh P.",,Frontiers in physiology,2021,2021-10-04,Y,Cardiac Arrhythmia; Sudden Cardiac Death; Electroanatomical Mapping; Electrocardiographic Imaging (Ecgi); Non-invasive Mapping; Equivalent Dipole Layer; Inverse Problem Of Electrocardiography,,,"This study presents a novel non-invasive equivalent dipole layer (EDL) based inverse electrocardiography (iECG) technique which estimates both endocardial and epicardial ventricular activation sequences. We aimed to quantitatively compare our iECG approach with invasive electro-anatomical mapping (EAM) during sinus rhythm with the objective of enabling functional substrate imaging and sudden cardiac death risk stratification in patients with cardiomyopathy. Thirteen patients (77% males, 48 ± 20 years old) referred for endocardial and epicardial EAM underwent 67-electrode body surface potential mapping and CT imaging. The EDL-based iECG approach was improved by mimicking the effects of the His-Purkinje system on ventricular activation. EAM local activation timing (LAT) maps were compared with iECG-LAT maps using absolute differences and Pearson's correlation coefficient, reported as mean ± standard deviation [95% confidence interval]. The correlation coefficient between iECG-LAT maps and EAM was 0.54 ± 0.19 [0.49-0.59] for epicardial activation, 0.50 ± 0.27 [0.41-0.58] for right ventricular endocardial activation and 0.44 ± 0.29 [0.32-0.56] for left ventricular endocardial activation. The absolute difference in timing between iECG maps and EAM was 17.4 ± 7.2 ms for epicardial maps, 19.5 ± 7.7 ms for right ventricular endocardial maps, 27.9 ± 8.7 ms for left ventricular endocardial maps. The absolute distance between right ventricular endocardial breakthrough sites was 30 ± 16 mm and 31 ± 17 mm for the left ventricle. The absolute distance for latest epicardial activation was median 12.8 [IQR: 2.9-29.3] mm. This first in-human quantitative comparison of iECG and invasive LAT-maps on both the endocardial and epicardial surface during sinus rhythm showed improved agreement, although with considerable absolute difference and moderate correlation coefficient. Non-invasive iECG requires further refinements to facilitate clinical implementation and risk stratification.",,pdf:https://www.frontiersin.org/articles/10.3389/fphys.2021.730736/pdf; doi:https://doi.org/10.3389/fphys.2021.730736; html:https://europepmc.org/articles/PMC8521153; pdf:https://europepmc.org/articles/PMC8521153?pdf=render 35673545,https://doi.org/10.12688/wellcomeopenres.17231.2,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow assay for antibody prevalence studies following vaccination: a diagnostic accuracy study.,"Cann A, Clarke C, Brown J, Thomson T, Prendecki M, Moshe M, Badhan A, Simmons B, Klaber B, Elliott P, Darzi A, Riley S, Ashby D, Martin P, Gleeson S, Willicombe M, Kelleher P, Ward H, Barclay WS, Cooke GS.",,Wellcome open research,2021,2021-01-01,Y,Antibodies; Seroprevalence; Lateral Flow; Neutralisation; Lfia; Covid-19; Sars-cov-2,,,"Background: Lateral flow immunoassays (LFIAs) are able to achieve affordable, large scale antibody testing and provide rapid results without the support of central laboratories. As part of the development of the REACT programme extensive evaluation of LFIA performance was undertaken with individuals following natural infection. Here we assess the performance of the selected LFIA to detect antibody responses in individuals who have received at least one dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Methods: This was a prospective diagnostic accuracy study. Sampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Two cohorts of patients were recruited; the first was a cohort of 108 renal transplant patients attending clinic following two doses of SARS-CoV-2 vaccine, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination and subsequent follow up. During the participants visit, finger-prick blood samples were analysed on LFIA device, while paired venous sampling was sent for serological assessment of antibodies to the spike protein (anti-S) antibodies. Anti-S IgG was detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA. A total of 186 paired samples were collected. The accuracy of Fortress LFIA in detecting IgG antibodies to SARS-CoV-2 compared to anti-spike protein detection on Abbott Assay Results: The LFIA had an estimated sensitivity of 92.0% (114/124; 95% confidence interval [CI] 85.7% to 96.1%) and specificity of 93.6% (58/62; 95% CI 84.3% to 98.2%) using the Abbott assay as reference standard (using the threshold for positivity of 7.10 BAU/ml) Conclusions: Fortress LFIA performs well in the detection of antibody responses for intended purpose of population level surveillance but does not meet criteria for individual testing.",,doi:https://doi.org/10.12688/wellcomeopenres.17231.2; html:https://europepmc.org/articles/PMC9152464; pdf:https://europepmc.org/articles/PMC9152464?pdf=render @@ -1124,12 +1124,12 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 36864090,https://doi.org/10.1038/s41598-023-30369-6,Effect of tissue-grouped regulatory variants associated to type 2 diabetes in related secondary outcomes.,"Hemerich D, Smit RAJ, Preuss M, Stalbow L, van der Laan SW, Asselbergs FW, van Setten J, Tragante V.",,Scientific reports,2023,2023-03-02,Y,,,,"Genome-wide association studies have identified over five hundred loci that contribute to variation in type 2 diabetes (T2D), an established risk factor for many diseases. However, the mechanisms and extent through which these loci contribute to subsequent outcomes remain elusive. We hypothesized that combinations of T2D-associated variants acting on tissue-specific regulatory elements might account for greater risk for tissue-specific outcomes, leading to diversity in T2D disease progression. We searched for T2D-associated variants acting on regulatory elements and expression quantitative trait loci (eQTLs) in nine tissues. We used T2D tissue-grouped variant sets as genetic instruments to conduct 2-Sample Mendelian Randomization (MR) in ten related outcomes whose risk is increased by T2D using the FinnGen cohort. We performed PheWAS analysis to investigate whether the T2D tissue-grouped variant sets had specific predicted disease signatures. We identified an average of 176 variants acting in nine tissues implicated in T2D, and an average of 30 variants acting on regulatory elements that are unique to the nine tissues of interest. In 2-Sample MR analyses, all subsets of regulatory variants acting in different tissues were associated with increased risk of the ten secondary outcomes studied on similar levels. No tissue-grouped variant set was associated with an outcome significantly more than other tissue-grouped variant sets. We did not identify different disease progression profiles based on tissue-specific regulatory and transcriptome information. Bigger sample sizes and other layers of regulatory information in critical tissues may help identify subsets of T2D variants that are implicated in certain secondary outcomes, uncovering system-specific disease progression.",,pdf:https://www.nature.com/articles/s41598-023-30369-6.pdf; doi:https://doi.org/10.1038/s41598-023-30369-6; html:https://europepmc.org/articles/PMC9981672; pdf:https://europepmc.org/articles/PMC9981672?pdf=render 35135774,https://doi.org/10.1136/bmjopen-2021-055603,"Observational retrospective study calculating health service costs of patients receiving surgery for chronic rhinosinusitis in England, using linked patient-level primary and secondary care electronic data.","Clarke CS, Williamson E, Denaxas S, Carpenter JR, Thomas M, Blackshaw H, Schilder AGM, Philpott CM, Hopkins C, Morris S, MACRO programme team.",,BMJ open,2022,2022-02-08,Y,Otolaryngology; Clinical Trials; Health Economics,,,"

Objectives

Chronic rhinosinusitis (CRS) symptoms are experienced by an estimated 11% of UK adults, and symptoms have major impacts on quality of life. Data from UK and elsewhere suggest high economic burden of CRS, but detailed cost information and economic analyses regarding surgical pathway are lacking. This paper estimates healthcare costs for patients receiving surgery for CRS in England.

Design

Observational retrospective study examining cost of healthcare of patients receiving CRS surgery.

Setting

Linked electronic health records from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics databases in England.

Participants

A phenotyping algorithm using medical ontology terms identified 'definite' CRS cases who received CRS surgery. Patients were registered with a general practice in England. Data covered the period 1997-2016. A cohort of 13 462 patients had received surgery for CRS, with 9056 (67%) having confirmed nasal polyps.

Outcome measures

Information was extracted on numbers and types of primary care prescriptions and consultations, and inpatient and outpatient hospital investigations and procedures. Resource use was costed using published sources.

Results

Total National Health Service costs in CRS surgery patients were £2173 over 1 year including surgery. Total costs per person-quarter were £1983 in the quarter containing surgery, mostly comprising surgical inpatient care costs (£1902), and around £60 per person-quarter in the 2 years before and after surgery, of which half were outpatient costs. Outpatient and primary care costs were low compared with the peak in inpatient costs at surgery. The highest outpatient expenditure was on CT scans, peaking in the quarter preceding surgery.

Conclusions

We present the first study of costs to the English healthcare system for patients receiving surgery for CRS. The total aggregate costs provide a further impetus for trials to evaluate the relative benefit of surgical intervention.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e055603.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055603; html:https://europepmc.org/articles/PMC8830221; pdf:https://europepmc.org/articles/PMC8830221?pdf=render 34985035,https://doi.org/10.1097/htr.0000000000000741,Epidemiology and 6- and 12-Month Outcomes of Intimate Partner Violence and Other Violence-Related Traumatic Brain Injury in Major Trauma: A Population-Based Trauma Registry Study.,"Gabbe BJ, Braaf S, Cameron PA, Berecki-Gisolf J.",,The Journal of head trauma rehabilitation,2022,2022-01-01,N,,,,"

Objective

To compare the epidemiology, in-hospital outcomes, and 6-month and 12-month patient-reported, outcomes of major trauma patients with intimate partner violence (IPV)-related traumatic brain injury (TBI) with other interpersonal violence (OV)-related TBI.

Setting

Victoria, Australia.

Participants

Adult (≥18 years) major trauma cases with TBI (concussion, skull fracture, or intracranial injury), injured through IPV or OV, between July 2010 and June 2020, and included on the population-based Victorian State Trauma Registry. There were 133 adult major trauma cases due to IPV and 1796 due to OV. The prevalence of TBI was 39% (n = 52) in the IPV group and 56% (n = 1010) in the OV group.

Design

Registry-based cohort study.

Main measures

Trauma care indicators and 6- and 12-month patient-reported outcomes (self-reported disability, Glasgow Outcome Scale-Extended, EQ-5D-3L, and return to work).

Results

The annual incidence (95% CI) of major trauma involving TBI was 0.11 (0.08-0.14) per 100 000 population for IPV and 2.11 (1.98-2.24) per 100 000 for OV. A higher proportion of IPV-related cases were women (73% vs 5%), had sustained a severe TBI (Glasgow Coma Scale score 3-8; 27% vs 15%), were admitted to intensive care (56% vs 37%), and died in hospital (14% vs 5%). The median (interquartile range) time to definitive care (4.7 hours vs 3.3 hours) and head computed tomographic scan (5.0 hours vs 3.1 hours) was longer in the IPV group. Follow-up rates at 6 and 12 months were 71% and 69%, respectively. The 6- and 12-month outcomes were generally poorer in the IPV-related group.

Conclusion

The incidence of IPV-related major trauma with TBI was low. However, the prevalence of severe TBI, the time to key aspects of clinical care, in-hospital mortality, and longer-term work-related disability were higher. However, power to detect differences was low due to the small number of IPV-related cases compared with the OV group.",,doi:https://doi.org/10.1097/HTR.0000000000000741 -37456658,https://doi.org/10.12688/hrbopenres.13667.1,Qualitative data sharing practices in clinical trials in the UK and Ireland: towards the production of good practice guidance.,"McCarthy M, Gillies K, Rousseau N, Wade J, Gamble C, Toomey E, Matvienko-Sikar K, Sydes M, Dowling M, Bryant V, Biesty L, Houghton C.",,HRB open research,2023,2023-02-06,Y,data sharing; Qualitative; trials; Focus Groups,,,"Background: Data sharing enables researchers to conduct novel research with previously collected datasets, thus maximising scientific findings and cost effectiveness, and reducing research waste. The value of sharing, even de-identified, quantitative data from clinical trials is well recognised with a moderated access approach recommended. While substantial challenges to sharing quantitative data remain, there are additional challenges for sharing qualitative data in trials. Incorporating the necessary information about how qualitative data will be shared into already complex trial recruitment and consent processes proves challenging. The aim of this study was to explore whether and how trial teams share qualitative data collected as part of the design, conduct, analysis, or delivery of clinical trials. Methods: Phase 1 involved semi-structured, in-depth qualitative interviews and focus groups with key trial stakeholder groups including trial managers and clinical trialists (n=3), qualitative researchers in trials (n=9), members of research funding bodies (n=2) and trial participants (n=1). Data were analysed using thematic analysis. In Phase 2, we conducted a content analysis of 16 participant information leaflets (PIL) and consent forms (CF) for trials that collected qualitative data. Results: Three key themes were identified from our Phase 1 findings: ' Understanding and experiences of the potential benefits of sharing qualitative data from trials', 'Concerns about qualitative data sharing', and ' Future guidance and funding'. In phase 2, the PILs and CFs received revealed that the benefits of data sharing for participants were only explained in two of the study documents. Conclusions: The value of sharing qualitative data was acknowledged, but there are many uncertainties as to how, when, and where to share this data. In addition, there were ethical concerns in relation to the consent process required for qualitative data sharing in trials. This study provides insight into the existing practice of qualitative data sharing in trials.",,pdf:https://hrbopenresearch.org/articles/6-10/pdf; doi:https://doi.org/10.12688/hrbopenres.13667.1; html:https://europepmc.org/articles/PMC10345597; pdf:https://europepmc.org/articles/PMC10345597?pdf=render 34847088,https://doi.org/10.1097/ede.0000000000001429,The Authors Respond.,"Katsoulis M, De Stavola B, Lai AG, Gomes M, Diaz-Ordaz K.",,"Epidemiology (Cambridge, Mass.)",2022,2022-01-01,N,,,,,,html:https://journals.lww.com/epidem/Fulltext/2022/01000/The_Authors_Respond.22.aspx; doi:https://doi.org/10.1097/EDE.0000000000001429 +37456658,https://doi.org/10.12688/hrbopenres.13667.1,Qualitative data sharing practices in clinical trials in the UK and Ireland: towards the production of good practice guidance.,"McCarthy M, Gillies K, Rousseau N, Wade J, Gamble C, Toomey E, Matvienko-Sikar K, Sydes M, Dowling M, Bryant V, Biesty L, Houghton C.",,HRB open research,2023,2023-02-06,Y,data sharing; Qualitative; trials; Focus Groups,,,"Background: Data sharing enables researchers to conduct novel research with previously collected datasets, thus maximising scientific findings and cost effectiveness, and reducing research waste. The value of sharing, even de-identified, quantitative data from clinical trials is well recognised with a moderated access approach recommended. While substantial challenges to sharing quantitative data remain, there are additional challenges for sharing qualitative data in trials. Incorporating the necessary information about how qualitative data will be shared into already complex trial recruitment and consent processes proves challenging. The aim of this study was to explore whether and how trial teams share qualitative data collected as part of the design, conduct, analysis, or delivery of clinical trials. Methods: Phase 1 involved semi-structured, in-depth qualitative interviews and focus groups with key trial stakeholder groups including trial managers and clinical trialists (n=3), qualitative researchers in trials (n=9), members of research funding bodies (n=2) and trial participants (n=1). Data were analysed using thematic analysis. In Phase 2, we conducted a content analysis of 16 participant information leaflets (PIL) and consent forms (CF) for trials that collected qualitative data. Results: Three key themes were identified from our Phase 1 findings: ' Understanding and experiences of the potential benefits of sharing qualitative data from trials', 'Concerns about qualitative data sharing', and ' Future guidance and funding'. In phase 2, the PILs and CFs received revealed that the benefits of data sharing for participants were only explained in two of the study documents. Conclusions: The value of sharing qualitative data was acknowledged, but there are many uncertainties as to how, when, and where to share this data. In addition, there were ethical concerns in relation to the consent process required for qualitative data sharing in trials. This study provides insight into the existing practice of qualitative data sharing in trials.",,pdf:https://hrbopenresearch.org/articles/6-10/pdf; doi:https://doi.org/10.12688/hrbopenres.13667.1; html:https://europepmc.org/articles/PMC10345597; pdf:https://europepmc.org/articles/PMC10345597?pdf=render 37293269,https://doi.org/10.1140/epjds/s13688-023-00394-6,Do poverty and wealth look the same the world over? A comparative study of 12 cities from five high-income countries using street images.,"Suel E, Muller E, Bennett JE, Blakely T, Doyle Y, Lynch J, Mackenbach JD, Middel A, Mizdrak A, Nathvani R, Brauer M, Ezzati M.",,EPJ data science,2023,2023-06-07,Y,Computer vision; Visual Similarity; Urban Inequalities; Street Images,,,"Urbanization and inequalities are two of the major policy themes of our time, intersecting in large cities where social and economic inequalities are particularly pronounced. Large scale street-level images are a source of city-wide visual information and allow for comparative analyses of multiple cities. Computer vision methods based on deep learning applied to street images have been shown to successfully measure inequalities in socioeconomic and environmental features, yet existing work has been within specific geographies and have not looked at how visual environments compare across different cities and countries. In this study, we aim to apply existing methods to understand whether, and to what extent, poor and wealthy groups live in visually similar neighborhoods across cities and countries. We present novel insights on similarity of neighborhoods using street-level images and deep learning methods. We analyzed 7.2 million images from 12 cities in five high-income countries, home to more than 85 million people: Auckland (New Zealand), Sydney (Australia), Toronto and Vancouver (Canada), Atlanta, Boston, Chicago, Los Angeles, New York, San Francisco, and Washington D.C. (United States of America), and London (United Kingdom). Visual features associated with neighborhood disadvantage are more distinct and unique to each city than those associated with affluence. For example, from what is visible from street images, high density poor neighborhoods located near the city center (e.g., in London) are visually distinct from poor suburban neighborhoods characterized by lower density and lower accessibility (e.g., in Atlanta). This suggests that differences between two cities is also driven by historical factors, policies, and local geography. Our results also have implications for image-based measures of inequality in cities especially when trained on data from cities that are visually distinct from target cities. We showed that these are more prone to errors for disadvantaged areas especially when transferring across cities, suggesting more attention needs to be paid to improving methods for capturing heterogeneity in poor environment across cities around the world.

Supplementary information

The online version contains supplementary material available at 10.1140/epjds/s13688-023-00394-6.",,pdf:https://epjdatascience.springeropen.com/counter/pdf/10.1140/epjds/s13688-023-00394-6; doi:https://doi.org/10.1140/epjds/s13688-023-00394-6; html:https://europepmc.org/articles/PMC10245348; pdf:https://europepmc.org/articles/PMC10245348?pdf=render 37920183,https://doi.org/10.3389/fcvm.2023.1148931,Unraveling the relationships between alpha- and beta-adrenergic modulation and the risk of heart failure.,"Baudier C, Fougerousse F, Asselbergs FW, Guedj M, Komajda M, Kotecha D, Thomas Lumbers R, Schmidt AF, Tyl B.",,Frontiers in cardiovascular medicine,2023,2023-10-18,Y,"adrenergic receptors; Beta-blockers; Mendelian Randomization; Alpha-blockers; Target Validation, Drug",,,"

Background

The effects of α and ß adrenergic receptor modulation on the risk of developing heart failure (HF) remains uncertain due to a lack of randomized controlled trials. This study aimed to estimate the effects of α and ß adrenergic receptors modulation on the risk of HF and to provide proof of principle for genetic target validation studies in HF.

Methods

Genetic variants within the cis regions encoding the adrenergic receptors α1A, α2B, ß1, and ß2 associated with blood pressure in a 757,601-participant genome-wide association study (GWAS) were selected as instruments to perform a drug target Mendelian randomization study. Effects of these variants on HF risk were derived from the HERMES GWAS (542,362 controls; 40,805 HF cases).

Results

Lower α1A or ß1 activity was associated with reduced HF risk: odds ratio (OR) 0.83 (95% CI 0.74-0.93, P = 0.001) and 0.95 (95% CI 0.93-0.97, P = 8 × 10-6). Conversely, lower α2B activity was associated with increased HF risk: OR 1.09 (95% CI 1.05-1.12, P = 3 × 10-7). No evidence of an effect of lower ß2 activity on HF risk was found: OR 0.99 (95% CI 0.92-1.07, P = 0.95). Complementary analyses showed that these effects were consistent with those on left ventricular dimensions and acted independently of any potential effect on coronary artery disease.

Conclusions

This study provides genetic evidence that α1A or ß1 receptor inhibition will likely decrease HF risk, while lower α2B activity may increase this risk. Genetic variant analysis can assist with drug development for HF prevention.",,doi:https://doi.org/10.3389/fcvm.2023.1148931; html:https://europepmc.org/articles/PMC10619754; pdf:https://europepmc.org/articles/PMC10619754?pdf=render -34798287,https://doi.org/10.1016/j.jclinepi.2021.11.023,Missing data is poorly handled and reported in prediction model studies using machine learning: a literature review.,"Nijman S, Leeuwenberg AM, Beekers I, Verkouter I, Jacobs J, Bots ML, Asselbergs FW, Moons K, Debray T.",,Journal of clinical epidemiology,2022,2021-11-16,N,Prediction; Literature review; Reporting; Missing Data; Machine Learning,,,"

Objectives

Missing data is a common problem during the development, evaluation, and implementation of prediction models. Although machine learning (ML) methods are often said to be capable of circumventing missing data, it is unclear how these methods are used in medical research. We aim to find out if and how well prediction model studies using machine learning report on their handling of missing data.

Study design and setting

We systematically searched the literature on published papers between 2018 and 2019 about primary studies developing and/or validating clinical prediction models using any supervised ML methodology across medical fields. From the retrieved studies information about the amount and nature (e.g. missing completely at random, potential reasons for missingness) of missing data and the way they were handled were extracted.

Results

We identified 152 machine learning-based clinical prediction model studies. A substantial amount of these 152 papers did not report anything on missing data (n = 56/152). A majority (n = 96/152) reported details on the handling of missing data (e.g., methods used), though many of these (n = 46/96) did not report the amount of the missingness in the data. In these 96 papers the authors only sometimes reported possible reasons for missingness (n = 7/96) and information about missing data mechanisms (n = 8/96). The most common approach for handling missing data was deletion (n = 65/96), mostly via complete-case analysis (CCA) (n = 43/96). Very few studies used multiple imputation (n = 8/96) or built-in mechanisms such as surrogate splits (n = 7/96) that directly address missing data during the development, validation, or implementation of the prediction model.

Conclusion

Though missing values are highly common in any type of medical research and certainly in the research based on routine healthcare data, a majority of the prediction model studies using machine learning does not report sufficient information on the presence and handling of missing data. Strategies in which patient data are simply omitted are unfortunately the most often used methods, even though it is generally advised against and well known that it likely causes bias and loss of analytical power in prediction model development and in the predictive accuracy estimates. Prediction model researchers should be much more aware of alternative methodologies to address missing data.",,pdf:http://www.jclinepi.com/article/S0895435621003759/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.11.023 32728709,https://doi.org/10.1093/pubmed/fdaa115,Are children who are home from school at an increased risk of child maltreatment?,"Syed S, Gilbert R.",,"Journal of public health (Oxford, England)",2021,2021-04-01,N,,,,,,pdf:https://discovery.ucl.ac.uk/10110375/1/Syed%20and%20Gilbert%20%282020%29.%20Are%20children%20who%20are%20home%20from%20school%20at%20an%20increased%20risk%20of%20child%20maltreatment.pdf; doi:https://doi.org/10.1093/pubmed/fdaa115 +34798287,https://doi.org/10.1016/j.jclinepi.2021.11.023,Missing data is poorly handled and reported in prediction model studies using machine learning: a literature review.,"Nijman S, Leeuwenberg AM, Beekers I, Verkouter I, Jacobs J, Bots ML, Asselbergs FW, Moons K, Debray T.",,Journal of clinical epidemiology,2022,2021-11-16,N,Prediction; Literature review; Reporting; Missing Data; Machine Learning,,,"

Objectives

Missing data is a common problem during the development, evaluation, and implementation of prediction models. Although machine learning (ML) methods are often said to be capable of circumventing missing data, it is unclear how these methods are used in medical research. We aim to find out if and how well prediction model studies using machine learning report on their handling of missing data.

Study design and setting

We systematically searched the literature on published papers between 2018 and 2019 about primary studies developing and/or validating clinical prediction models using any supervised ML methodology across medical fields. From the retrieved studies information about the amount and nature (e.g. missing completely at random, potential reasons for missingness) of missing data and the way they were handled were extracted.

Results

We identified 152 machine learning-based clinical prediction model studies. A substantial amount of these 152 papers did not report anything on missing data (n = 56/152). A majority (n = 96/152) reported details on the handling of missing data (e.g., methods used), though many of these (n = 46/96) did not report the amount of the missingness in the data. In these 96 papers the authors only sometimes reported possible reasons for missingness (n = 7/96) and information about missing data mechanisms (n = 8/96). The most common approach for handling missing data was deletion (n = 65/96), mostly via complete-case analysis (CCA) (n = 43/96). Very few studies used multiple imputation (n = 8/96) or built-in mechanisms such as surrogate splits (n = 7/96) that directly address missing data during the development, validation, or implementation of the prediction model.

Conclusion

Though missing values are highly common in any type of medical research and certainly in the research based on routine healthcare data, a majority of the prediction model studies using machine learning does not report sufficient information on the presence and handling of missing data. Strategies in which patient data are simply omitted are unfortunately the most often used methods, even though it is generally advised against and well known that it likely causes bias and loss of analytical power in prediction model development and in the predictive accuracy estimates. Prediction model researchers should be much more aware of alternative methodologies to address missing data.",,pdf:http://www.jclinepi.com/article/S0895435621003759/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.11.023 36936265,https://doi.org/10.1136/bmjmed-2022-000276,"Trends, variation, and clinical characteristics of recipients of antiviral drugs and neutralising monoclonal antibodies for covid-19 in community settings: retrospective, descriptive cohort study of 23.4 million people in OpenSAFELY.","Green ACA, Curtis HJ, Higgins R, Nab L, Mahalingasivam V, Smith RM, Mehrkar A, Inglesby P, Drysdale H, DeVito NJ, Croker R, Rentsch CT, Bhaskaran K, Tazare J, Zheng B, Andrews CD, Bacon SCJ, Davy S, Dillingham I, Evans D, Fisher L, Hickman G, Hopcroft LEM, Hulme WJ, Massey J, MacDonald O, Morley J, Morton CE, Park RY, Walker AJ, Ward T, Wiedemann M, Bates C, Cockburn J, Parry J, Hester F, Harper S, Douglas IJ, Evans SJW, Goldacre B, Tomlinson LA, MacKenna B.",,BMJ medicine,2023,2023-01-13,Y,Therapeutics; Community health services; Public Health; Covid-19,,,"

Objective

To ascertain patient eligibility status and describe coverage of antiviral drugs and neutralising monoclonal antibodies (nMAB) as treatment for covid-19 in community settings in England.

Design

Retrospective, descriptive cohort study, approved by NHS England.

Setting

Routine clinical data from 23.4 million people linked to data on covid-19 infection and treatment, within the OpenSAFELY-TPP database.

Participants

Outpatients with covid-19 at high risk of severe outcomes.

Interventions

Nirmatrelvir/ritonavir (paxlovid), sotrovimab, molnupiravir, casirivimab/imdevimab, or remdesivir, used in the community by covid-19 medicine delivery units.

Results

93 870 outpatients with covid-19 were identified between 11 December 2021 and 28 April 2022 to be at high risk of severe outcomes and therefore potentially eligible for antiviral or nMAB treatment (or both). Of these patients, 19 040 (20%) received treatment (sotrovimab, 9660 (51%); molnupiravir, 4620 (24%); paxlovid, 4680 (25%); casirivimab/imdevimab, 50 (<1%); and remdesivir, 30 (<1%)). The proportion of patients treated increased from 9% (190/2220) in the first week of treatment availability to 29% (460/1600) in the latest week. The proportion treated varied by high risk group, being lowest in those with liver disease (16%; 95% confidence interval 15% to 17%); by treatment type, with sotrovimab favoured over molnupiravir and paxlovid in all but three high risk groups (Down's syndrome (35%; 30% to 39%), rare neurological conditions (45%; 43% to 47%), and immune deficiencies (48%; 47% to 50%)); by age, ranging from ≥80 years (13%; 12% to 14%) to 50-59 years (23%; 22% to 23%); by ethnic group, ranging from black (11%; 10% to 12%) to white (21%; 21% to 21%); by NHS region, ranging from 13% (12% to 14%) in Yorkshire and the Humber to 25% (24% to 25%) in the East of England); and by deprivation level, ranging from 15% (14% to 15%) in the most deprived areas to 23% (23% to 24%) in the least deprived areas. Groups that also had lower coverage included unvaccinated patients (7%; 6% to 9%), those with dementia (6%; 5% to 7%), and care home residents (6%; 6% to 7%).

Conclusions

Using the OpenSAFELY platform, we were able to identify patients with covid-19 at high risk of severe outcomes who were potentially eligible to receive treatment and assess the coverage of these new treatments among these patients. In the context of a rapid deployment of a new service, the NHS analytical code used to determine eligibility could have been over-inclusive and some of the eligibility criteria not fully captured in healthcare data. However targeted activity might be needed to resolve apparent lower treatment coverage observed among certain groups, in particular (at present): different NHS regions, ethnic groups, people aged ≥80 years, those living in socioeconomically deprived areas, and care home residents.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000276.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000276; html:https://europepmc.org/articles/PMC9951378; pdf:https://europepmc.org/articles/PMC9951378?pdf=render 36719715,https://doi.org/10.2196/41248,Patterns in the Use of Heart Failure Telemonitoring: Post Hoc Analysis of the e-Vita Heart Failure Trial.,"Brons M, Ten Klooster I, van Gemert-Pijnen L, Jaarsma T, Asselbergs FW, Oerlemans MIFJ, Koudstaal S, Rutten FH.",,JMIR cardio,2023,2023-01-31,Y,Adherence; Heart Failure; Patient Monitoring; Remote Monitoring; Telemonitoring; Ehealth; Electronic Personal Health Record,,,"

Background

Research on the use of home telemonitoring data and adherence to it can provide new insights into telemonitoring for the daily management of patients with heart failure (HF).

Objective

We described the use of a telemonitoring platform-including remote patient monitoring of blood pressure, pulse, and weight-and the use of the electronic personal health record. Patient characteristics were assessed in both adherent and nonadherent patients to weight transmissions.

Methods

We used the data of the e-Vita HF study, a 3-arm parallel randomized trial performed in stable patients with HF managed in outpatient clinics in the Netherlands. In this study, data were analyzed from the participants in the intervention arm (ie, e-Vita HF platform). Adherence to weight transmissions was defined as transmitting weight ≥3 times per week for at least 42 weeks during a year.

Results

Data from 150 patients (mean age 67, SD 11 years; n=37, 25% female; n=123, 82% self-assessed New York Heart Association class I-II) were analyzed. One-year adherence to weight transmissions was 74% (n=111). Patients adherent to weight transmissions were less often hospitalized for HF in the 6 months before enrollment in the study compared to those who were nonadherent (n=9, 8% vs n=9, 23%; P=.02). The percentage of patients visiting the personal health record dropped steadily over time (n=140, 93% vs n=59, 39% at one year). With univariable analyses, there was no significant correlation between patient characteristics and adherence to weight transmissions.

Conclusions

Adherence to remote patient monitoring was high among stable patients with HF and best for weighing; however, adherence decreased over time. Clinical and demographic variables seem not related to adherence to transmitting weight.

Trial registration

ClinicalTrials.gov NCT01755988; https://clinicaltrials.gov/ct2/show/NCT01755988.",,pdf:https://cardio.jmir.org/2023/1/e41248/PDF; doi:https://doi.org/10.2196/41248; html:https://europepmc.org/articles/PMC9929726; pdf:https://europepmc.org/articles/PMC9929726?pdf=render 36013179,https://doi.org/10.3390/jpm12081230,Grip Strength Trajectories and Cognition in English and Chilean Older Adults: A Cross-Cohort Study.,"Angel B, Ajnakina O, Albala C, Lera L, Márquez C, Leipold L, Bilovich A, Dobson R, Bendayan R.",,Journal of personalized medicine,2022,2022-07-27,Y,Cognition; Longitudinal study; Older Adults; Grip Strength,,,"Growing evidence about the link between cognitive and physical decline suggests the early changes in physical functioning as a potential biomarker for cognitive impairment. Thus, we compared grip-strength trajectories over 12-16 years in three groups classified according to their cognitive status (two stable patterns, normal and impaired cognitive performance, and a declining pattern) in two representative UK and Chilean older adult samples. The samples consisted of 7069 UK (ELSA) and 1363 Chilean participants (ALEXANDROS). Linear Mixed models were performed. Adjustments included socio-demographics and health variables. The Declined and Impaired group had significantly lower grip-strength at baseline when compared to the Non-Impaired. In ELSA, the Declined and Impaired showed a faster decline in their grip strength compared to the Non-Impaired group but differences disappeared in the fully adjusted models. In ALEXANDROS, the differences were only found between the Declined and Non-Impaired and they were partially attenuated by covariates. Our study provides robust evidence of the association between grip strength and cognitive performance and how socio-economic factors might be key to understanding this association and their variability across countries. This has implications for future epidemiological research, as hand-grip strength measurements have the potential to be used as an indicator of cognitive performance.",,pdf:https://www.mdpi.com/2075-4426/12/8/1230/pdf?version=1659687887; doi:https://doi.org/10.3390/jpm12081230; html:https://europepmc.org/articles/PMC9410389; pdf:https://europepmc.org/articles/PMC9410389?pdf=render @@ -1142,90 +1142,90 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 34610958,https://doi.org/10.1136/emermed-2019-209368,Association between anticoagulants and mortality and functional outcomes in older patients with major trauma.,"Sato N, Cameron P, Mclellan S, Beck B, Gabbe B.",,Emergency medicine journal : EMJ,2021,2021-10-05,N,Research; Trauma; Geriatrics; Major Trauma Management; Death/mortality,,,"

Background

The number of trauma patients taking anticoagulants and antiplatelet agents is increasing as society ages. However, there have been limited and inconsistent reports of the association between anticoagulants and mortality and functional outcomes. This study aimed to quantify the association between anticoagulant/antiplatelet medication at the time of injury and both short-term and longer-term outcomes in older major trauma patients.

Methods

This was a population-based registry study using data from the Victorian State Trauma Registry from July 2017 to June 2018. We included patients with major trauma aged 65 years and older. The outcomes of interest were in-hospital mortality, hospital length of stay, intensive care unit length of stay and the Extended Glasgow Outcome Scale (GOS-E) at 6 months after injury. We examined the association between the outcomes and anticoagulants/antiplatelet agents at the time of injury and used multivariable logistic regression models to account for known confounders.

Results

There were 1323 older adults eligible for inclusion in the study, of which 249 (18.8%) were taking anticoagulants (n=8 were taking both anticoagulants and antiplatelet agents), 380 (28.7%) were taking antiplatelet agents and 694 (52.5%) were not using either. Any anticoagulant use was associated with higher odds of in-hospital mortality (adjusted OR (AOR), 2.38; 95% CI 1.58 to 3.59) compared with not using anticoagulants. No differences were observed in the GOS-E at 6 months after injury between any anticoagulants use, antiplatelet use and no anticoagulant use (anticoagulant AOR, 0.71; 95% CI 0.48 to 1.05, antiplatelet AOR, 1.02; 95% CI 0.73 to 1.42).

Conclusion

Anticoagulant use at the time of injury was associated with higher odds of in-hospital mortality but did not adversely impact functional outcomes at 6 months after injury. These findings demonstrate the importance of seeking an accurate history of anticoagulant use and its indication, as well as the immediate initiation of reversal therapies.",,doi:https://doi.org/10.1136/emermed-2019-209368 35896705,https://doi.org/10.1038/s41598-022-16639-9,Estimation of biological heart age using cardiovascular magnetic resonance radiomics.,"Raisi-Estabragh Z, Salih A, Gkontra P, Atehortúa A, Radeva P, Boscolo Galazzo I, Menegaz G, Harvey NC, Lekadir K, Petersen SE.",,Scientific reports,2022,2022-07-27,Y,,,,"We developed a novel interpretable biological heart age estimation model using cardiovascular magnetic resonance radiomics measures of ventricular shape and myocardial character. We included 29,996 UK Biobank participants without cardiovascular disease. Images were segmented using an automated analysis pipeline. We extracted 254 radiomics features from the left ventricle, right ventricle, and myocardium of each study. We then used Bayesian ridge regression with tenfold cross-validation to develop a heart age estimation model using the radiomics features as the model input and chronological age as the model output. We examined associations of radiomics features with heart age in men and women, observing sex-differential patterns. We subtracted actual age from model estimated heart age to calculate a ""heart age delta"", which we considered as a measure of heart aging. We performed a phenome-wide association study of 701 exposures with heart age delta. The strongest correlates of heart aging were measures of obesity, adverse serum lipid markers, hypertension, diabetes, heart rate, income, multimorbidity, musculoskeletal health, and respiratory health. This technique provides a new method for phenotypic assessment relating to cardiovascular aging; further studies are required to assess whether it provides incremental risk information over current approaches.",,pdf:https://www.nature.com/articles/s41598-022-16639-9.pdf; doi:https://doi.org/10.1038/s41598-022-16639-9; html:https://europepmc.org/articles/PMC9329281; pdf:https://europepmc.org/articles/PMC9329281?pdf=render 34427560,https://doi.org/10.1684/ejd.2021.4108,"The association between immunosuppression and skin cancer in solid organ transplant recipients: a control-matched cohort study of 2,852 patients.","Gibson JAG, Cordaro A, Dobbs TD, Griffiths R, Akbari A, Whitaker S, Hutchings HA, Lyons RA, Whitaker IS.",,European journal of dermatology : EJD,2021,2021-12-01,N,Transplant; Oncology; immunosuppression; Skin Cancer,,,"Skin cancer is more common in transplant recipients, although the quoted incidence is variable. This study investigated the incidence of skin cancer in solid organ transplant recipients (OTRs) in a national cohort and the effect of pharmacotherapeutic agents Transplant patients were identified from Patient Episode Database for Wales (PEDW) using Office of Population Census and Surveys Classifications of Interventions and Procedures-4 (OPCS-4) codes. Controls were matched to cases according to age, sex and socioeconomic status. Skin cancer data were obtained from linkage with other national data sources. Incidence was calculated per 100,000 person-years at risk (PYAR). Negative binomial regression was used to calculate adjusted incidence rate ratios (IRRs) for each organ type. During 2000-2018, 2,852 Welsh patients underwent solid organ transplantation. A total of 13,527 controls were matched from the general population. The incidence of skin cancer within the OTR cohort was 1203.2 per 100,000 PYAR vs 133.9 in the matched control group. Age, male gender and azathioprine use were all associated with an increased risk of skin cancer. Contemporary immunomodulators such as tacrolimus and mycophenolate were associated with a reduction in skin cancer risk when compared to their predecessors, cyclosporin and azathioprine. The highest adjusted IRR was observed in heart transplant recipients (IRR: 10.82; 95% CI: 3.64-32.19) and the lowest in liver transplant recipients (IRR: 2.86; 95% CI: 1.15-7.13). This study highlights the need for long-term routine skin cancer surveillance for all OTRs and the importance of using contemporary immunomodulators, when possible, for risk reduction.",,doi:https://doi.org/10.1684/ejd.2021.4108 -37218687,https://doi.org/10.1093/ehjqcco/qcad029,Sex-based differences in risk factors for incident myocardial infarction and stroke in the UK Biobank.,"Remfry E, Ardissino M, McCracken C, Szabo L, Neubauer S, Harvey NC, Mamas MA, Robson J, Petersen SE, Raisi-Estabragh Z.",,European heart journal. Quality of care & clinical outcomes,2024,2024-03-01,Y,Myocardial infarction; Stroke; Sex differences; risk factors,,,"

Aim

This study examined sex-based differences in associations of vascular risk factors with incident cardiovascular events in the UK Biobank.

Methods

Baseline participant demographic, clinical, laboratory, anthropometric, and imaging characteristics were collected. Multivariable Cox regression was used to estimate independent associations of vascular risk factors with incident myocardial infarction (MI) and ischaemic stroke for men and women. Women-to-men ratios of hazard ratios (RHRs), and related 95% confidence intervals, represent the relative effect-size magnitude by sex.

Results

Among the 363 313 participants (53.5% women), 8470 experienced MI (29.9% women) and 7705 experienced stroke (40.1% women) over 12.66 [11.93, 13.38] years of prospective follow-up. Men had greater risk factor burden and higher arterial stiffness index at baseline. Women had greater age-related decline in aortic distensibility. Older age [RHR: 1.02 (1.01-1.03)], greater deprivation [RHR: 1.02 (1.00-1.03)], hypertension [RHR: 1.14 (1.02-1.27)], and current smoking [RHR: 1.45 (1.27-1.66)] were associated with a greater excess risk of MI in women than men. Low-density lipoprotein cholesterol was associated with excess MI risk in men [RHR: 0.90 (0.84-0.95)] and apolipoprotein A (ApoA) was less protective for MI in women [RHR: 1.65 (1.01-2.71)]. Older age was associated with excess risk of stroke [RHR: 1.01 (1.00-1.02)] and ApoA was less protective for stroke in women [RHR: 2.55 (1.58-4.14)].

Conclusion

Older age, hypertension, and smoking appeared stronger drivers of cardiovascular disease in women, whereas lipid metrics appeared stronger risk determinants for men. These findings highlight the importance of sex-specific preventive strategies and suggest priority targets for intervention in men and women.",,pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcad029/50422842/qcad029.pdf; doi:https://doi.org/10.1093/ehjqcco/qcad029; html:https://europepmc.org/articles/PMC10904726; pdf:https://europepmc.org/articles/PMC10904726?pdf=render -38784722,https://doi.org/10.1093/jbmrpl/ziae058,"Bone health, cardiovascular disease, and imaging outcomes in UK Biobank: a causal analysis.","Condurache DG, D'Angelo S, Salih AM, Szabo L, McCracken C, Mahmood A, Curtis EM, Altmann A, Petersen SE, Harvey NC, Raisi-Estabragh Z.",,JBMR plus,2024,2024-04-25,Y,Cardiovascular diseases; Osteoporosis; BMD; Bone Health; Cardiovascular Magnetic Resonance; Mendelian Randomization; Cardiovascular Imaging; Heel Ultrasound,,,"This study examined the association of estimated heel bone mineral density (eBMD, derived from quantitative ultrasound) with: (1) prevalent and incident cardiovascular diseases (CVDs: ischemic heart disease (IHD), myocardial infarction (MI), heart failure (HF), non-ischemic cardiomyopathy (NICM), arrhythmia), (2) mortality (all-cause, CVD, IHD), and (3) cardiovascular magnetic resonance (CMR) measures of left ventricular and atrial structure and function and aortic distensibility, in the UK Biobank. Clinical outcomes were ascertained using health record linkage over 12.3 yr of prospective follow-up. Two-sample Mendelian randomization (MR) was conducted to assess causal associations between BMD and CMR metrics using genetic instrumental variables identified from published genome-wide association studies. The analysis included 485 257 participants (55% women, mean age 56.5 ± 8.1 yr). Higher heel eBMD was associated with lower odds of all prevalent CVDs considered. The greatest magnitude of effect was seen in association with HF and NICM, where 1-SD increase in eBMD was associated with 15% lower odds of HF and 16% lower odds of NICM. Association between eBMD and incident IHD and MI was non-significant; the strongest relationship was with incident HF (SHR: 0.90 [95% CI, 0.89-0.92]). Higher eBMD was associated with a decreased risk in all-cause, CVD, and IHD mortality, in the fully adjusted model. Higher eBMD was associated with greater aortic distensibility; associations with other CMR metrics were null. Higher heel eBMD is linked to reduced risk of a range of prevalent and incident CVD and mortality outcomes. Although observational analyses suggest associations between higher eBMD and greater aortic compliance, MR analysis did not support a causal relationship between genetically predicted BMD and CMR phenotypes. These findings support the notion that bone-cardiovascular associations reflect shared risk factors/mechanisms rather than direct causal pathways.",,doi:https://doi.org/10.1093/jbmrpl/ziae058; html:https://europepmc.org/articles/PMC11114472; pdf:https://europepmc.org/articles/PMC11114472?pdf=render 34939031,https://doi.org/10.1093/braincomms/fcab241,Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia.,"Vuksanović V, Staff RT, Morson S, Ahearn T, Bracoud L, Murray AD, Bentham P, Kipps CM, Harrington CR, Wischik CM.",,Brain communications,2021,2021-10-21,Y,Neurodegeneration; Brain Networks; Behavioural Variant Frontotemporal Dementia; Rich Club; Anatomical Subtypes,,,"The behavioural variant of frontotemporal dementia is a clinical syndrome characterized by changes in behaviour, cognition and functional ability. Although atrophy in frontal and temporal regions would appear to be a defining feature, neuroimaging studies have identified volumetric differences distributed across large parts of the cortex, giving rise to a classification into distinct neuroanatomical subtypes. Here, we extended these neuroimaging studies to examine how distributed patterns of cortical atrophy map onto brain network hubs. We used baseline structural magnetic resonance imaging data collected from 213 behavioural variant of frontotemporal dementia patients meeting consensus diagnostic criteria and having definite evidence of frontal and/or temporal lobe atrophy from a global clinical trial conducted in 70 sites in Canada, United States of America, Australia, Asia and Europe. These were compared with data from 244 healthy elderly subjects from a well-characterized cohort study. We have used statistical methods of hierarchical agglomerative clustering of 68 regional cortical and subcortical volumes (34 in each hemisphere) to determine the reproducibility of previously described neuroanatomical subtypes in a global study. We have also attempted to link the structural findings to clinical features defined systematically using well-validated clinical scales (Addenbrooke's Cognitive Examination Revised, the Mini-Mental Status Examination, the Frontotemporal Dementia Rating Scale and the Functional Assessment Questionnaire) and subscales derived from them. Whilst we can confirm that the subtypes are robust, they have limited value in explaining the clinical heterogeneity of the syndrome. We have found that a common pattern of degeneration affecting a small number of subcortical, limbic and frontal nodes within highly connected networks (most previously identified as rich club members or functional binding nodes) is shared by all the anatomical subtypes. Degeneration in these core regions is correlated with cognitive and functional impairment, but less so with behavioural impairment. These findings suggest that degeneration in highly connected basal, limbic and frontal networks is a core feature of the behavioural variant of frontotemporal dementia phenotype irrespective of neuroanatomical and clinical heterogeneity, and may underly the impairment of integration in cognition, function and behaviour responsible for the loss of insight that characterizes the syndrome.",,pdf:https://academic.oup.com/braincomms/article-pdf/3/4/fcab241/41829863/fcab241.pdf; doi:https://doi.org/10.1093/braincomms/fcab241; html:https://europepmc.org/articles/PMC8688778; pdf:https://europepmc.org/articles/PMC8688778?pdf=render -37563310,https://doi.org/10.1038/s41590-023-01588-w,Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets.,"Zhao JH, Stacey D, Eriksson N, Macdonald-Dunlop E, Hedman ÅK, Kalnapenkis A, Enroth S, Cozzetto D, Digby-Bell J, Marten J, Folkersen L, Herder C, Jonsson L, Bergen SE, Gieger C, Needham EJ, Surendran P, Estonian Biobank Research Team, Paul DS, Polasek O, Thorand B, Grallert H, Roden M, Võsa U, Esko T, Hayward C, Johansson Å, Gyllensten U, Powell N, Hansson O, Mattsson-Carlgren N, Joshi PK, Danesh J, Padyukov L, Klareskog L, Landén M, Wilson JF, Siegbahn A, Wallentin L, Mälarstig A, Butterworth AS, Peters JE.",,Nature immunology,2023,2023-08-10,Y,,,,"Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted a genome-wide protein quantitative trait locus (pQTL) study of 91 plasma proteins measured using the Olink Target platform in 14,824 participants. We identified 180 pQTLs (59 cis, 121 trans). Integration of pQTL data with eQTL and disease genome-wide association studies provided insight into pathogenesis, implicating lymphotoxin-α in multiple sclerosis. Using Mendelian randomization (MR) to assess causality in disease etiology, we identified both shared and distinct effects of specific proteins across immune-mediated diseases, including directionally discordant effects of CD40 on risk of rheumatoid arthritis versus multiple sclerosis and inflammatory bowel disease. MR implicated CXCL5 in the etiology of ulcerative colitis (UC) and we show elevated gut CXCL5 transcript expression in patients with UC. These results identify targets of existing drugs and provide a powerful resource to facilitate future drug target prioritization.",,pdf:https://www.nature.com/articles/s41590-023-01588-w.pdf; doi:https://doi.org/10.1038/s41590-023-01588-w; html:https://europepmc.org/articles/PMC10457199; pdf:https://europepmc.org/articles/PMC10457199?pdf=render +38784722,https://doi.org/10.1093/jbmrpl/ziae058,"Bone health, cardiovascular disease, and imaging outcomes in UK Biobank: a causal analysis.","Condurache DG, D'Angelo S, Salih AM, Szabo L, McCracken C, Mahmood A, Curtis EM, Altmann A, Petersen SE, Harvey NC, Raisi-Estabragh Z.",,JBMR plus,2024,2024-04-25,Y,Cardiovascular diseases; Osteoporosis; BMD; Bone Health; Cardiovascular Magnetic Resonance; Mendelian Randomization; Cardiovascular Imaging; Heel Ultrasound,,,"This study examined the association of estimated heel bone mineral density (eBMD, derived from quantitative ultrasound) with: (1) prevalent and incident cardiovascular diseases (CVDs: ischemic heart disease (IHD), myocardial infarction (MI), heart failure (HF), non-ischemic cardiomyopathy (NICM), arrhythmia), (2) mortality (all-cause, CVD, IHD), and (3) cardiovascular magnetic resonance (CMR) measures of left ventricular and atrial structure and function and aortic distensibility, in the UK Biobank. Clinical outcomes were ascertained using health record linkage over 12.3 yr of prospective follow-up. Two-sample Mendelian randomization (MR) was conducted to assess causal associations between BMD and CMR metrics using genetic instrumental variables identified from published genome-wide association studies. The analysis included 485 257 participants (55% women, mean age 56.5 ± 8.1 yr). Higher heel eBMD was associated with lower odds of all prevalent CVDs considered. The greatest magnitude of effect was seen in association with HF and NICM, where 1-SD increase in eBMD was associated with 15% lower odds of HF and 16% lower odds of NICM. Association between eBMD and incident IHD and MI was non-significant; the strongest relationship was with incident HF (SHR: 0.90 [95% CI, 0.89-0.92]). Higher eBMD was associated with a decreased risk in all-cause, CVD, and IHD mortality, in the fully adjusted model. Higher eBMD was associated with greater aortic distensibility; associations with other CMR metrics were null. Higher heel eBMD is linked to reduced risk of a range of prevalent and incident CVD and mortality outcomes. Although observational analyses suggest associations between higher eBMD and greater aortic compliance, MR analysis did not support a causal relationship between genetically predicted BMD and CMR phenotypes. These findings support the notion that bone-cardiovascular associations reflect shared risk factors/mechanisms rather than direct causal pathways.",,doi:https://doi.org/10.1093/jbmrpl/ziae058; html:https://europepmc.org/articles/PMC11114472; pdf:https://europepmc.org/articles/PMC11114472?pdf=render +37218687,https://doi.org/10.1093/ehjqcco/qcad029,Sex-based differences in risk factors for incident myocardial infarction and stroke in the UK Biobank.,"Remfry E, Ardissino M, McCracken C, Szabo L, Neubauer S, Harvey NC, Mamas MA, Robson J, Petersen SE, Raisi-Estabragh Z.",,European heart journal. Quality of care & clinical outcomes,2024,2024-03-01,Y,Myocardial infarction; Stroke; Sex differences; risk factors,,,"

Aim

This study examined sex-based differences in associations of vascular risk factors with incident cardiovascular events in the UK Biobank.

Methods

Baseline participant demographic, clinical, laboratory, anthropometric, and imaging characteristics were collected. Multivariable Cox regression was used to estimate independent associations of vascular risk factors with incident myocardial infarction (MI) and ischaemic stroke for men and women. Women-to-men ratios of hazard ratios (RHRs), and related 95% confidence intervals, represent the relative effect-size magnitude by sex.

Results

Among the 363 313 participants (53.5% women), 8470 experienced MI (29.9% women) and 7705 experienced stroke (40.1% women) over 12.66 [11.93, 13.38] years of prospective follow-up. Men had greater risk factor burden and higher arterial stiffness index at baseline. Women had greater age-related decline in aortic distensibility. Older age [RHR: 1.02 (1.01-1.03)], greater deprivation [RHR: 1.02 (1.00-1.03)], hypertension [RHR: 1.14 (1.02-1.27)], and current smoking [RHR: 1.45 (1.27-1.66)] were associated with a greater excess risk of MI in women than men. Low-density lipoprotein cholesterol was associated with excess MI risk in men [RHR: 0.90 (0.84-0.95)] and apolipoprotein A (ApoA) was less protective for MI in women [RHR: 1.65 (1.01-2.71)]. Older age was associated with excess risk of stroke [RHR: 1.01 (1.00-1.02)] and ApoA was less protective for stroke in women [RHR: 2.55 (1.58-4.14)].

Conclusion

Older age, hypertension, and smoking appeared stronger drivers of cardiovascular disease in women, whereas lipid metrics appeared stronger risk determinants for men. These findings highlight the importance of sex-specific preventive strategies and suggest priority targets for intervention in men and women.",,pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcad029/50422842/qcad029.pdf; doi:https://doi.org/10.1093/ehjqcco/qcad029; html:https://europepmc.org/articles/PMC10904726; pdf:https://europepmc.org/articles/PMC10904726?pdf=render 31748543,https://doi.org/10.1038/s41398-019-0613-4,Identification of novel common variants associated with chronic pain using conditional false discovery rate analysis with major depressive disorder and assessment of pleiotropic effects of LRFN5.,"Johnston KJA, Adams MJ, Nicholl BI, Ward J, Strawbridge RJ, McIntosh AM, Smith DJ, Bailey MES.",,Translational psychiatry,2019,2019-11-20,Y,,Understanding the Causes of Disease,,"Chronic pain is a complex trait that is moderately heritable and genetically, as well as phenotypically, correlated with major depressive disorder (MDD). Use of the conditional false discovery rate (cFDR) approach, which leverages pleiotropy identified from existing GWAS outputs, has been successful in discovering novel associated variants in related phenotypes. Here, genome-wide association study outputs for both von Korff chronic pain grade and for MDD were used to identify variants meeting a cFDR threshold for each outcome phenotype separately, as well as a conjunctional cFDR (ccFDR) threshold for both phenotypes together. Using a moderately conservative threshold, we identified a total of 11 novel single nucleotide polymorphisms (SNPs), six of which were associated with chronic pain grade and nine of which were associated with MDD. Four SNPs on chromosome 14 were associated with both chronic pain grade and MDD. SNPs associated only with chronic pain grade were located within SLC16A7 on chromosome 12. SNPs associated only with MDD were located either in a gene-dense region on chromosome 1 harbouring LINC01360, LRRIQ3, FPGT and FPGT-TNNI3K, or within/close to LRFN5 on chromosome 14. The SNPs associated with both outcomes were also located within LRFN5. Several of the SNPs on chromosomes 1 and 14 were identified as being associated with expression levels of nearby genes in the brain and central nervous system. Overall, using the cFDR approach, we identified several novel genetic loci associated with chronic pain and we describe likely pleiotropic effects of a recently identified MDD locus on chronic pain.","This study aimed to identify parts of the genome that cause chronic pain (self-reported as lasting 3+ months), or major depressive disorder (MDD) and to investigate if these two conditions share common genetic causes. They identified 11 different parts of the genome where a specific change (SNP) was linked to chronic pain (6 parts of the genome), MDD (9 parts), or symptoms shared by both conditions (4 parts). The results also suggest that one of parts of the genome that causes chronic pain may influence the development of MDD (but not vice versa), including through lifestyle factors.",pdf:https://www.nature.com/articles/s41398-019-0613-4.pdf; doi:https://doi.org/10.1038/s41398-019-0613-4; html:https://europepmc.org/articles/PMC6868167; pdf:https://europepmc.org/articles/PMC6868167?pdf=render +37563310,https://doi.org/10.1038/s41590-023-01588-w,Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets.,"Zhao JH, Stacey D, Eriksson N, Macdonald-Dunlop E, Hedman ÅK, Kalnapenkis A, Enroth S, Cozzetto D, Digby-Bell J, Marten J, Folkersen L, Herder C, Jonsson L, Bergen SE, Gieger C, Needham EJ, Surendran P, Estonian Biobank Research Team, Paul DS, Polasek O, Thorand B, Grallert H, Roden M, Võsa U, Esko T, Hayward C, Johansson Å, Gyllensten U, Powell N, Hansson O, Mattsson-Carlgren N, Joshi PK, Danesh J, Padyukov L, Klareskog L, Landén M, Wilson JF, Siegbahn A, Wallentin L, Mälarstig A, Butterworth AS, Peters JE.",,Nature immunology,2023,2023-08-10,Y,,,,"Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted a genome-wide protein quantitative trait locus (pQTL) study of 91 plasma proteins measured using the Olink Target platform in 14,824 participants. We identified 180 pQTLs (59 cis, 121 trans). Integration of pQTL data with eQTL and disease genome-wide association studies provided insight into pathogenesis, implicating lymphotoxin-α in multiple sclerosis. Using Mendelian randomization (MR) to assess causality in disease etiology, we identified both shared and distinct effects of specific proteins across immune-mediated diseases, including directionally discordant effects of CD40 on risk of rheumatoid arthritis versus multiple sclerosis and inflammatory bowel disease. MR implicated CXCL5 in the etiology of ulcerative colitis (UC) and we show elevated gut CXCL5 transcript expression in patients with UC. These results identify targets of existing drugs and provide a powerful resource to facilitate future drug target prioritization.",,pdf:https://www.nature.com/articles/s41590-023-01588-w.pdf; doi:https://doi.org/10.1038/s41590-023-01588-w; html:https://europepmc.org/articles/PMC10457199; pdf:https://europepmc.org/articles/PMC10457199?pdf=render 37986130,https://doi.org/10.1186/s41512-023-00159-9,An external validation of the Kidney Donor Risk Index in the UK transplant population in the presence of semi-competing events.,"Riley S, Tam K, Tse WY, Connor A, Wei Y.",,Diagnostic and prognostic research,2023,2023-11-21,Y,Survival analysis; Kidney transplantation; Risk Prediction; External Validation; Time-to-event Model; Competing Events,,,"

Background

Transplantation represents the optimal treatment for many patients with end-stage kidney disease. When a donor kidney is available to a waitlisted patient, clinicians responsible for the care of the potential recipient must make the decision to accept or decline the offer based upon complex and variable information about the donor, the recipient and the transplant process. A clinical prediction model may be able to support clinicians in their decision-making. The Kidney Donor Risk Index (KDRI) was developed in the United States to predict graft failure following kidney transplantation. The survival process following transplantation consists of semi-competing events where death precludes graft failure, but not vice-versa.

Methods

We externally validated the KDRI in the UK kidney transplant population and assessed whether validation under a semi-competing risks framework impacted predictive performance. Additionally, we explored whether the KDRI requires updating. We included 20,035 adult recipients of first, deceased donor, single, kidney-only transplants between January 1, 2004, and December 31, 2018, collected by the UK Transplant Registry and held by NHS Blood and Transplant. The outcomes of interest were 1- and 5-year graft failure following transplantation. In light of the semi-competing events, recipient death was handled in two ways: censoring patients at the time of death and modelling death as a competing event. Cox proportional hazard models were used to validate the KDRI when censoring graft failure by death, and cause-specific Cox models were used to account for death as a competing event.

Results

The KDRI underestimated event probabilities for those at higher risk of graft failure. For 5-year graft failure, discrimination was poorer in the semi-competing risks model (0.625, 95% CI 0.611 to 0.640;0.611, 95% CI 0.597 to 0.625), but predictions were more accurate (Brier score 0.117, 95% CI 0.112 to 0.121; 0.114, 95% CI 0.109 to 0.118). Calibration plots were similar regardless of whether the death was modelled as a competing event or not. Updating the KDRI worsened calibration, but marginally improved discrimination.

Conclusions

Predictive performance for 1-year graft failure was similar between death-censored and competing event graft failure, but differences appeared when predicting 5-year graft failure. The updated index did not have superior performance and we conclude that updating the KDRI in the present form is not required.",,doi:https://doi.org/10.1186/s41512-023-00159-9; html:https://europepmc.org/articles/PMC10662562; pdf:https://europepmc.org/articles/PMC10662562?pdf=render 33820530,https://doi.org/10.1186/s12916-021-01940-7,"Machine learning for subtype definition and risk prediction in heart failure, acute coronary syndromes and atrial fibrillation: systematic review of validity and clinical utility.","Banerjee A, Chen S, Fatemifar G, Zeina M, Lumbers RT, Mielke J, Gill S, Kotecha D, Freitag DF, Denaxas S, Hemingway H.",,BMC medicine,2021,2021-04-06,Y,Subtype; Cardiovascular disease; Systematic review; Machine Learning; Informatics; Risk Prediction,,,"

Background

Machine learning (ML) is increasingly used in research for subtype definition and risk prediction, particularly in cardiovascular diseases. No existing ML models are routinely used for cardiovascular disease management, and their phase of clinical utility is unknown, partly due to a lack of clear criteria. We evaluated ML for subtype definition and risk prediction in heart failure (HF), acute coronary syndromes (ACS) and atrial fibrillation (AF).

Methods

For ML studies of subtype definition and risk prediction, we conducted a systematic review in HF, ACS and AF, using PubMed, MEDLINE and Web of Science from January 2000 until December 2019. By adapting published criteria for diagnostic and prognostic studies, we developed a seven-domain, ML-specific checklist.

Results

Of 5918 studies identified, 97 were included. Across studies for subtype definition (n = 40) and risk prediction (n = 57), there was variation in data source, population size (median 606 and median 6769), clinical setting (outpatient, inpatient, different departments), number of covariates (median 19 and median 48) and ML methods. All studies were single disease, most were North American (n = 61/97) and only 14 studies combined definition and risk prediction. Subtype definition and risk prediction studies respectively had limitations in development (e.g. 15.0% and 78.9% of studies related to patient benefit; 15.0% and 15.8% had low patient selection bias), validation (12.5% and 5.3% externally validated) and impact (32.5% and 91.2% improved outcome prediction; no effectiveness or cost-effectiveness evaluations).

Conclusions

Studies of ML in HF, ACS and AF are limited by number and type of included covariates, ML methods, population size, country, clinical setting and focus on single diseases, not overlap or multimorbidity. Clinical utility and implementation rely on improvements in development, validation and impact, facilitated by simple checklists. We provide clear steps prior to safe implementation of machine learning in clinical practice for cardiovascular diseases and other disease areas.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-021-01940-7; doi:https://doi.org/10.1186/s12916-021-01940-7; html:https://europepmc.org/articles/PMC8022365; pdf:https://europepmc.org/articles/PMC8022365?pdf=render 32908284,https://doi.org/10.1038/s41591-020-1037-7,Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI extension.,"Cruz Rivera S, Liu X, Chan AW, Denniston AK, Calvert MJ, SPIRIT-AI and CONSORT-AI Working Group, SPIRIT-AI and CONSORT-AI Steering Group, SPIRIT-AI and CONSORT-AI Consensus Group.",,Nature medicine,2020,2020-09-09,Y,,,,"The SPIRIT 2013 statement aims to improve the completeness of clinical trial protocol reporting by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes. The SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trial protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 26 candidate items, which were consulted upon by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The SPIRIT-AI extension includes 15 new items that were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations for the handling of input and output data, the human-AI interaction and analysis of error cases. SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the design and risk of bias for a planned clinical trial.",,pdf:https://www.nature.com/articles/s41591-020-1037-7.pdf; doi:https://doi.org/10.1038/s41591-020-1037-7; html:https://europepmc.org/articles/PMC7598944; pdf:https://europepmc.org/articles/PMC7598944?pdf=render 32908283,https://doi.org/10.1038/s41591-020-1034-x,Reporting guidelines for clinical trial reports for interventions involving artificial intelligence: the CONSORT-AI extension.,"Liu X, Cruz Rivera S, Moher D, Calvert MJ, Denniston AK, SPIRIT-AI and CONSORT-AI Working Group.",,Nature medicine,2020,2020-09-09,Y,,,,"The CONSORT 2010 statement provides minimum guidelines for reporting randomized trials. Its widespread use has been instrumental in ensuring transparency in the evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate impact on health outcomes. The CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trials evaluating interventions with an AI component. It was developed in parallel with its companion statement for clinical trial protocols: SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 29 candidate items, which were assessed by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a two-day consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The CONSORT-AI extension includes 14 new items that were considered sufficiently important for AI interventions that they should be routinely reported in addition to the core CONSORT 2010 items. CONSORT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention is integrated, the handling of inputs and outputs of the AI intervention, the human-AI interaction and provision of an analysis of error cases. CONSORT-AI will help promote transparency and completeness in reporting clinical trials for AI interventions. It will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.",,pdf:https://www.nature.com/articles/s41591-020-1034-x.pdf; doi:https://doi.org/10.1038/s41591-020-1034-x; html:https://europepmc.org/articles/PMC7598943; pdf:https://europepmc.org/articles/PMC7598943?pdf=render 37143831,https://doi.org/10.1183/23120541.00591-2022,Ethnic variation in asthma healthcare utilisation and exacerbation: systematic review and meta-analysis.,"Akin-Imran A, Bajpai A, McCartan D, Heaney LG, Kee F, Redmond C, Busby J.",,ERJ open research,2023,2023-05-02,Y,,,,"

Background

Patients from ethnic minority groups (EMGs) frequently report poorer asthma outcomes; however, a broad synthesis summarising ethnic disparities is yet to be undertaken. What is the magnitude of ethnic disparities in asthma healthcare utilisation, exacerbations and mortality?

Methods

MEDLINE, Embase and Web of Science databases were searched for studies reporting ethnic variation in asthma healthcare outcomes (primary care attendance, exacerbation, emergency department (ED) visits, hospitalisation, hospital readmission, ventilation/intubation and mortality) between White patients and those from EMGs. Estimates were displayed using forest plots and random-effects models were used to calculate pooled estimates. We conducted subgroup analyses to explore heterogeneity, including by specific ethnicity (Black, Hispanic, Asian and other).

Results

65 studies, comprising 699 882 patients, were included. Most studies (92.3%) were conducted in the United States of America (USA). Patients from EMGs had evidence suggestive of lower levels of primary care attendance (OR 0.72, 95% CI 0.48-1.09), but substantially higher ED visits (OR 1.74, 95% CI 1.53-1.98), hospitalisations (OR 1.63, 95% CI 1.48-1.79) and ventilation/intubation (OR 2.67, 95% CI 1.65-4.31) when compared to White patients. In addition, we found evidence suggestive of increased hospital readmissions (OR 1.19, 95% CI 0.90-1.57) and exacerbation rates (OR 1.10, 95% CI 0.94-1.28) among EMGs. No eligible studies explored disparities in mortality. ED visits were much higher among Black and Hispanic patients, while Asian and other ethnicities had similar rates to White patients.

Conclusions

EMGs had higher secondary care utilisation and exacerbations. Despite the global importance of this issue, the majority of studies were performed in the USA. Further research into the causes of these disparities, including whether these vary by specific ethnicity, is required to aid the design of effective interventions.",,pdf:https://openres.ersjournals.com/content/erjor/early/2023/02/16/23120541.00591-2022.full.pdf; doi:https://doi.org/10.1183/23120541.00591-2022; html:https://europepmc.org/articles/PMC10152257; pdf:https://europepmc.org/articles/PMC10152257?pdf=render 37200150,https://doi.org/10.1210/clinem/dgad276,Preconception Management of Hyperthyroidism and Thyroid Status in Subsequent Pregnancy: A Population-Based Cohort Study.,"Minassian C, Allen LA, Okosieme O, Vaidya B, Taylor P.",,The Journal of clinical endocrinology and metabolism,2023,2023-10-01,Y,Pregnancy; Thyroxine; Hyperthyroidism; Thyroid stimulating hormone; TSH; Thyroid function; Ft3; Ft4; Carbimazole; Tri-iodothyronine; Ptu; Cprd,,,"

Context

Optimal thyroid status in pregnancy is essential in reducing the risk of adverse outcomes. The management of hyperthyroidism in women of reproductive age poses unique challenges and it is unclear how preconception treatment strategies impact on thyroid status in subsequent pregnancy.

Objective

We aimed to determine trends in the management of hyperthyroidism before and during pregnancy and to assess the impact of different preconception treatment strategies on maternal thyroid status.

Methods

We utilized the Clinical Practice Research Datalink database to evaluate all females aged 15-45 years with a clinical diagnosis of hyperthyroidism and a subsequent pregnancy (January 2000 to December 2017). We compared thyroid status in pregnancy according to preconception treatment, namely, (1) antithyroid drugs up to or beyond pregnancy onset, (2) definitive treatment with thyroidectomy or radioiodine before pregnancy, and (3) no treatment at pregnancy onset.

Results

Our study cohort comprised 4712 pregnancies. Thyrotropin (TSH) was measured in only 53.1% of pregnancies, of which 28.1% showed suboptimal thyroid status (TSH >4.0 mU/L or TSH <0.1 mU/L plus FT4 >reference range). Pregnancies with prior definitive treatment were more likely to have suboptimal thyroid status compared with pregnancies starting during antithyroid drug treatment (odds ratio 4.72, 95% CI 3.50-6.36). A steady decline in the use of definitive treatment before pregnancy was observed from 2000 to 2017. One-third (32.6%) of first trimester carbimazole-exposed pregnancies were switched to propylthiouracil while 6.0% of propylthiouracil-exposed pregnancies switched to carbimazole.

Conclusion

The management of women with hyperthyroidism who become pregnant is suboptimal, particularly in those with preconception definitive treatment, and needs urgent improvement. Better thyroid monitoring and prenatal counseling are needed to optimize thyroid status, reduce teratogenic drug exposure, and ultimately reduce the risk of adverse pregnancy outcomes.",,doi:https://doi.org/10.1210/clinem/dgad276; doi:https://doi.org/10.1210/clinem/dgad276; html:https://europepmc.org/articles/PMC10584009 -37729117,https://doi.org/10.1371/journal.pdig.0000309,Training and testing of a gradient boosted machine learning model to predict adverse outcome in patients presenting to emergency departments with suspected covid-19 infection in a middle-income setting.,"Fuller GW, Hasan M, Hodkinson P, McAlpine D, Goodacre S, Bath PA, Sbaffi L, Omer Y, Wallis L, Marincowitz C.",,PLOS digital health,2023,2023-09-20,Y,,,,"COVID-19 infection rates remain high in South Africa. Clinical prediction models may be helpful for rapid triage, and supporting clinical decision making, for patients with suspected COVID-19 infection. The Western Cape, South Africa, has integrated electronic health care data facilitating large-scale linked routine datasets. The aim of this study was to develop a machine learning model to predict adverse outcome in patients presenting with suspected COVID-19 suitable for use in a middle-income setting. A retrospective cohort study was conducted using linked, routine data, from patients presenting with suspected COVID-19 infection to public-sector emergency departments (EDs) in the Western Cape, South Africa between 27th August 2020 and 31st October 2021. The primary outcome was death or critical care admission at 30 days. An XGBoost machine learning model was trained and internally tested using split-sample validation. External validation was performed in 3 test cohorts: Western Cape patients presenting during the Omicron COVID-19 wave, a UK cohort during the ancestral COVID-19 wave, and a Sudanese cohort during ancestral and Eta waves. A total of 282,051 cases were included in a complete case training dataset. The prevalence of 30-day adverse outcome was 4.0%. The most important features for predicting adverse outcome were the requirement for supplemental oxygen, peripheral oxygen saturations, level of consciousness and age. Internal validation using split-sample test data revealed excellent discrimination (C-statistic 0.91, 95% CI 0.90 to 0.91) and calibration (CITL of 1.05). The model achieved C-statistics of 0.84 (95% CI 0.84 to 0.85), 0.72 (95% CI 0.71 to 0.73), and 0.62, (95% CI 0.59 to 0.65) in the Omicron, UK, and Sudanese test cohorts. Results were materially unchanged in sensitivity analyses examining missing data. An XGBoost machine learning model achieved good discrimination and calibration in prediction of adverse outcome in patients presenting with suspected COVID19 to Western Cape EDs. Performance was reduced in temporal and geographical external validation.",,pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000309&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000309; html:https://europepmc.org/articles/PMC10511129; pdf:https://europepmc.org/articles/PMC10511129?pdf=render 35151869,https://doi.org/10.1016/j.jbi.2022.104010,Patient-centric characterization of multimorbidity trajectories in patients with severe mental illnesses: A temporal bipartite network modeling approach.,"Wang T, Bendayan R, Msosa Y, Pritchard M, Roberts A, Stewart R, Dobson R.",,Journal of biomedical informatics,2022,2022-02-11,Y,Network Evolution; Multimorbidity; Severe Mental Illnesses; Disease Trajectories; Ehr Data Linkage; Temporal Bipartite Network,,,"Multimorbidity is a major factor contributing to increased mortality among people with severe mental illnesses (SMI). Previous studies either focus on estimating prevalence of a disease in a population without considering relationships between diseases or ignore heterogeneity of individual patients in examining disease progression by looking merely at aggregates across a whole cohort. Here, we present a temporal bipartite network model to jointly represent detailed information on both individual patients and diseases, which allows us to systematically characterize disease trajectories from both patient and disease centric perspectives. We apply this approach to a large set of longitudinal diagnostic records for patients with SMI collected through a data linkage between electronic health records from a large UK mental health hospital and English national hospital administrative database. We find that the resulting diagnosis networks show disassortative mixing by degree, suggesting that patients affected by a small number of diseases tend to suffer from prevalent diseases. Factors that determine the network structures include an individual's age, gender and ethnicity. Our analysis on network evolution further shows that patients and diseases become more interconnected over the illness duration of SMI, which is largely driven by the process that patients with similar attributes tend to suffer from the same conditions. Our analytic approach provides a guide for future patient-centric research on multimorbidity trajectories and contributes to achieving precision medicine.",,doi:https://doi.org/10.1016/j.jbi.2022.104010; doi:https://doi.org/10.1016/j.jbi.2022.104010; html:https://europepmc.org/articles/PMC8894882 +37729117,https://doi.org/10.1371/journal.pdig.0000309,Training and testing of a gradient boosted machine learning model to predict adverse outcome in patients presenting to emergency departments with suspected covid-19 infection in a middle-income setting.,"Fuller GW, Hasan M, Hodkinson P, McAlpine D, Goodacre S, Bath PA, Sbaffi L, Omer Y, Wallis L, Marincowitz C.",,PLOS digital health,2023,2023-09-20,Y,,,,"COVID-19 infection rates remain high in South Africa. Clinical prediction models may be helpful for rapid triage, and supporting clinical decision making, for patients with suspected COVID-19 infection. The Western Cape, South Africa, has integrated electronic health care data facilitating large-scale linked routine datasets. The aim of this study was to develop a machine learning model to predict adverse outcome in patients presenting with suspected COVID-19 suitable for use in a middle-income setting. A retrospective cohort study was conducted using linked, routine data, from patients presenting with suspected COVID-19 infection to public-sector emergency departments (EDs) in the Western Cape, South Africa between 27th August 2020 and 31st October 2021. The primary outcome was death or critical care admission at 30 days. An XGBoost machine learning model was trained and internally tested using split-sample validation. External validation was performed in 3 test cohorts: Western Cape patients presenting during the Omicron COVID-19 wave, a UK cohort during the ancestral COVID-19 wave, and a Sudanese cohort during ancestral and Eta waves. A total of 282,051 cases were included in a complete case training dataset. The prevalence of 30-day adverse outcome was 4.0%. The most important features for predicting adverse outcome were the requirement for supplemental oxygen, peripheral oxygen saturations, level of consciousness and age. Internal validation using split-sample test data revealed excellent discrimination (C-statistic 0.91, 95% CI 0.90 to 0.91) and calibration (CITL of 1.05). The model achieved C-statistics of 0.84 (95% CI 0.84 to 0.85), 0.72 (95% CI 0.71 to 0.73), and 0.62, (95% CI 0.59 to 0.65) in the Omicron, UK, and Sudanese test cohorts. Results were materially unchanged in sensitivity analyses examining missing data. An XGBoost machine learning model achieved good discrimination and calibration in prediction of adverse outcome in patients presenting with suspected COVID19 to Western Cape EDs. Performance was reduced in temporal and geographical external validation.",,pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000309&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000309; html:https://europepmc.org/articles/PMC10511129; pdf:https://europepmc.org/articles/PMC10511129?pdf=render 36644660,https://doi.org/10.1177/20552076221128677,Evaluation of prototype risk prediction tools for clinicians and people living with type 2 diabetes in North West London using the think aloud method.,"Gardner C, Wake D, Brodie D, Silverstein A, Young S, Cunningham S, Sainsbury C, Ilia M, Lucas A, Willis T, Halligan J.",,Digital health,2023,2023-01-08,Y,Artificial intelligence; Internet; Diabetes; Qualitative; risk factors; Machine Learning; Health Informatics; Behaviour Change; Personalised Medicine; Digital Health,,,"The prevalence of type 2 diabetes in North West London (NWL) is relatively high compared to other parts of the United Kingdom with outcomes suboptimal. This presents a need for more effective strategies to identify people living with type 2 diabetes who need additional support. An emerging subset of web-based interventions for diabetes self-management and population management has used artificial intelligence and machine learning models to stratify the risk of complications from diabetes and identify patients in need of immediate support. In this study, two prototype risk prediction tools on the MyWay Diabetes and MyWay Clinical platforms were evaluated with six clinicians and six people living with type 2 diabetes in NWL using the think aloud method. The results of the sessions with people living with type 2 diabetes showed that the concept of the tool was intuitive, however, more instruction on how to correctly use the risk prediction tool would be valuable. The feedback from the sessions with clinicians was that the data presented in the tool aligned with the key diabetes targets in NWL, and that this would be useful for identifying and inviting patients to the practice who are overdue for tests and at risk of complications. The findings of the evaluation have been used to support the development of the prototype risk predictions tools. This study demonstrates the value of conducting usability testing on web-based interventions designed to support the targeted management of type 2 diabetes in local communities.",,doi:https://doi.org/10.1177/20552076221128677; doi:https://doi.org/10.1177/20552076221128677; html:https://europepmc.org/articles/PMC9834412; pdf:https://europepmc.org/articles/PMC9834412?pdf=render 35792838,https://doi.org/10.1093/bioinformatics/btac453,Flashfm-ivis: interactive visualization for fine-mapping of multiple quantitative traits.,"Zhou F, Butterworth AS, Asimit JL.",,"Bioinformatics (Oxford, England)",2022,2022-09-01,Y,,,,"

Summary

flashfm-ivis provides a suite of interactive visualization plots to view potential causal genetic variants that underlie associations that are shared or distinct between multiple quantitative traits and compares results between single- and multi-trait fine-mapping. Unique features include network diagrams that show joint effects between variants for each trait and regional association plots that integrate fine-mapping results, all with user-controlled zoom features for an interactive exploration of potential causal variants across traits.

Availability and implementation

flashfm-ivis is an open-source software under the MIT license. It is available as an interactive web-based tool (http://shiny.mrc-bsu.cam.ac.uk/apps/flashfm-ivis/) and as an R package. Code and documentation are available at https://github.com/fz-cambridge/flashfm-ivis and https://zenodo.org/record/6376244#.YjnarC-l2X0. Additional features can be downloaded as standalone R libraries to encourage reuse.

Supplementary information

Supplementary information are available at Bioinformatics online.",,pdf:https://academic.oup.com/bioinformatics/article-pdf/38/17/4238/49889636/btac453.pdf; doi:https://doi.org/10.1093/bioinformatics/btac453; html:https://europepmc.org/articles/PMC9438951; pdf:https://europepmc.org/articles/PMC9438951?pdf=render 33707775,https://doi.org/10.1038/s41591-021-01266-0,Plasma metabolites to profile pathways in noncommunicable disease multimorbidity.,"Pietzner M, Stewart ID, Raffler J, Khaw KT, Michelotti GA, Kastenmüller G, Wareham NJ, Langenberg C.",,Nature medicine,2021,2021-03-11,N,,,,"Multimorbidity, the simultaneous presence of multiple chronic conditions, is an increasing global health problem and research into its determinants is of high priority. We used baseline untargeted plasma metabolomics profiling covering >1,000 metabolites as a comprehensive readout of human physiology to characterize pathways associated with and across 27 incident noncommunicable diseases (NCDs) assessed using electronic health record hospitalization and cancer registry data from over 11,000 participants (219,415 person years). We identified 420 metabolites shared between at least 2 NCDs, representing 65.5% of all 640 significant metabolite-disease associations. We integrated baseline data on over 50 diverse clinical risk factors and characteristics to identify actionable shared pathways represented by those metabolites. Our study highlights liver and kidney function, lipid and glucose metabolism, low-grade inflammation, surrogates of gut microbial diversity and specific health-related behaviors as antecedents of common NCD multimorbidity with potential for early prevention. We integrated results into an open-access webserver ( https://omicscience.org/apps/mwasdisease/ ) to facilitate future research and meta-analyses.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127079; doi:https://doi.org/10.1038/s41591-021-01266-0; html:https://europepmc.org/articles/PMC8127079; pdf:https://europepmc.org/articles/PMC8127079?pdf=render; doi:https://doi.org/10.1038/s41591-021-01266-0 30279426,https://doi.org/10.1038/s41598-018-32876-3,OligoPVP: Phenotype-driven analysis of individual genomic information to prioritize oligogenic disease variants.,"Boudellioua I, Kulmanov M, Schofield PN, Gkoutos GV, Hoehndorf R.",,Scientific reports,2018,2018-10-02,Y,,"Applied Analytics, The Human Phenome",,"An increasing number of disorders have been identified for which two or more distinct alleles in two or more genes are required to either cause the disease or to significantly modify its onset, severity or phenotype. It is difficult to discover such interactions using existing approaches. The purpose of our work is to develop and evaluate a system that can identify combinations of alleles underlying digenic and oligogenic diseases in individual whole exome or whole genome sequences. Information that links patient phenotypes to databases of gene-phenotype associations observed in clinical or non-human model organism research can provide useful information and improve variant prioritization for genetic diseases. Additional background knowledge about interactions between genes can be utilized to identify sets of variants in different genes in the same individual which may then contribute to the overall disease phenotype. We have developed OligoPVP, an algorithm that can be used to prioritize causative combinations of variants in digenic and oligogenic diseases, using whole exome or whole genome sequences together with patient phenotypes as input. We demonstrate that OligoPVP has significantly improved performance when compared to state of the art pathogenicity detection methods in the case of digenic diseases. Our results show that OligoPVP can efficiently prioritize sets of variants in digenic diseases using a phenotype-driven approach and identify etiologically important variants in whole genomes. OligoPVP naturally extends to oligogenic disease involving interactions between variants in two or more genes. It can be applied to the identification of multiple interacting candidate variants contributing to phenotype, where the action of modifier genes is suspected from pedigree analysis or failure of traditional causative variant identification.",,pdf:https://www.nature.com/articles/s41598-018-32876-3.pdf; doi:https://doi.org/10.1038/s41598-018-32876-3; html:https://europepmc.org/articles/PMC6168481; pdf:https://europepmc.org/articles/PMC6168481?pdf=render -34506014,https://doi.org/10.1007/s11605-020-04612-8,"The Impact of a Centralised Pancreatic Cancer Service: a Case Study of Wales, UK.","Mowbray NG, Griffiths R, Akbari A, Hutchings H, Jenkins G, Al-Sarireh B.",,Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract,2022,2021-09-10,N,Pancreatic cancer; Pancreatic Surgery; Centralisation,,,"

Introduction

The centralisation of pancreatic cancer (PC) services still varies worldwide. This study aimed to assess the impact that a centralisation has had on patients in South Wales, UK.

Methods

A retrospective cohort analysis of patients in South Wales, UK, with PC prior to (2004-2009), and after (2010-2014) the formation of a specialist centre. Patients were identified using record linkage of electronic health records.

Results

The overall survival (OS) of all 3413 patients with PC increased from a median (IQR) 10 weeks (3-31) to 11 weeks (4-35), p = 0.038, after centralisation. The OS of patients undergoing surgical resection or chemotherapy alone did not improve (93 weeks (39-203) vs. 90 weeks (50-95), p = 0.764 and 33 weeks (20-57) vs. 33 weeks (19-58), p = 0.793). Surgical resection and chemotherapy rates increased (6.1% vs. 9.2%, p < 0.001 and 19.7% vs. 27.0%, p < 0.001). The 30-day mortality rate trended downwards (7.2% vs. 3.6%, p = 0.186). The percentage of patients who received no treatment reduced (75.2% vs. 69.6%, p < 0.001).

Conclusion

The centralisation of PC services in South Wales is associated with a small increase in OS and a larger increase in PC treatment utilisation. It is concerning that many patients still fail to receive any treatments.",,doi:https://doi.org/10.1007/s11605-020-04612-8 32575372,https://doi.org/10.3390/genes11060668,A Knowledge-Based Machine Learning Approach to Gene Prioritisation in Amyotrophic Lateral Sclerosis.,"Bean DM, Al-Chalabi A, Dobson RJB, Iacoangeli A.",,Genes,2020,2020-06-19,Y,Amyotrophic Lateral Sclerosis; Motor Neurone Disease; Machine Learning; Gene Discovery; Gene Prioritisation; Knowledge Graph,,,"Amyotrophic lateral sclerosis is a neurodegenerative disease of the upper and lower motor neurons resulting in death from neuromuscular respiratory failure, typically within two to five years of first symptoms. Several rare disruptive gene variants have been associated with ALS and are responsible for about 15% of all cases. Although our knowledge of the genetic landscape of this disease is improving, it remains limited. Machine learning models trained on the available protein-protein interaction and phenotype-genotype association data can use our current knowledge of the disease genetics for the prediction of novel candidate genes. Here, we describe a knowledge-based machine learning method for this purpose. We trained our model on protein-protein interaction data from IntAct, gene function annotation from Gene Ontology, and known disease-gene associations from DisGeNet. Using several sets of known ALS genes from public databases and a manual review as input, we generated a list of new candidate genes for each input set. We investigated the relevance of the predicted genes in ALS by using the available summary statistics from the largest ALS genome-wide association study and by performing functional and phenotype enrichment analysis. The predicted sets were enriched for genes associated with other neurodegenerative diseases known to overlap with ALS genetically and phenotypically, as well as for biological processes associated with the disease. Moreover, using ALS genes from ClinVar and our manual review as input, the predicted sets were enriched for ALS-associated genes (ClinVar p = 0.038 and manual review p = 0.060) when used for gene prioritisation in a genome-wide association study.",,pdf:https://www.mdpi.com/2073-4425/11/6/668/pdf?version=1592549363; doi:https://doi.org/10.3390/genes11060668; html:https://europepmc.org/articles/PMC7349022; pdf:https://europepmc.org/articles/PMC7349022?pdf=render +34506014,https://doi.org/10.1007/s11605-020-04612-8,"The Impact of a Centralised Pancreatic Cancer Service: a Case Study of Wales, UK.","Mowbray NG, Griffiths R, Akbari A, Hutchings H, Jenkins G, Al-Sarireh B.",,Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract,2022,2021-09-10,N,Pancreatic cancer; Pancreatic Surgery; Centralisation,,,"

Introduction

The centralisation of pancreatic cancer (PC) services still varies worldwide. This study aimed to assess the impact that a centralisation has had on patients in South Wales, UK.

Methods

A retrospective cohort analysis of patients in South Wales, UK, with PC prior to (2004-2009), and after (2010-2014) the formation of a specialist centre. Patients were identified using record linkage of electronic health records.

Results

The overall survival (OS) of all 3413 patients with PC increased from a median (IQR) 10 weeks (3-31) to 11 weeks (4-35), p = 0.038, after centralisation. The OS of patients undergoing surgical resection or chemotherapy alone did not improve (93 weeks (39-203) vs. 90 weeks (50-95), p = 0.764 and 33 weeks (20-57) vs. 33 weeks (19-58), p = 0.793). Surgical resection and chemotherapy rates increased (6.1% vs. 9.2%, p < 0.001 and 19.7% vs. 27.0%, p < 0.001). The 30-day mortality rate trended downwards (7.2% vs. 3.6%, p = 0.186). The percentage of patients who received no treatment reduced (75.2% vs. 69.6%, p < 0.001).

Conclusion

The centralisation of PC services in South Wales is associated with a small increase in OS and a larger increase in PC treatment utilisation. It is concerning that many patients still fail to receive any treatments.",,doi:https://doi.org/10.1007/s11605-020-04612-8 36581539,https://doi.org/10.1016/j.jpsychires.2022.12.015,"Corrigendum ""Anticoagulation for atrial fibrillation in people with serious mental illness in the general hospital setting"" [J. Psychiatr. Res. 153 (2022) 167-173].","Farran D, Bean D, Wang T, Msosa Y, Casetta C, Dobson R, Teo JT, Scott P, Gaughran F.",,Journal of psychiatric research,2023,2022-12-28,N,,,,,,doi:https://doi.org/10.1016/j.jpsychires.2022.12.015; doi:https://doi.org/10.1016/j.jpsychires.2022.12.015 34516619,https://doi.org/10.1093/ehjci/jeab178,Optimal echocardiographic assessment of myocardial dysfunction for arrhythmic risk stratification in phospholamban mutation carriers.,"Taha K, Verstraelen TE, de Brouwer R, de Bruin-Bon RHACM, Cramer MJ, Te Rijdt WP, Bouma BJ, de Boer RA, Doevendans PA, Asselbergs FW, Wilde AAM, van den Berg MP, Teske AJ.",,European heart journal. Cardiovascular Imaging,2022,2022-10-01,Y,Risk stratification; ventricular arrhythmia; Phospholamban; Mechanical Dispersion; Deformation Imaging; Genetic Cardiomyopathy,,,"

Aims

Phospholamban (PLN) p.Arg14del mutation carriers are at risk of developing malignant ventricular arrhythmias (VAs) and/or heart failure. Currently, left ventricular ejection fraction (LVEF) plays an important role in risk assessment for VA in these individuals. We aimed to study the incremental prognostic value of left ventricular mechanical dispersion (LVMD) by echocardiographic deformation imaging for prediction of sustained VA in PLN p.Arg14del mutation carriers.

Methods and results

We included 243 PLN p.Arg14del mutation carriers, which were classified into three groups according to the '45/45' rule: (i) normal left ventricular (LV) function, defined as preserved LVEF ≥45% with normal LVMD ≤45 ms (n = 139), (ii) mechanical LV dysfunction, defined as preserved LVEF ≥45% with abnormal LVMD >45 ms (n = 63), and (iii) overt LV dysfunction, defined as reduced LVEF <45% (n = 41). During a median follow-up of 3.3 (interquartile range 1.8-6.0) years, sustained VA occurred in 35 individuals. The negative predictive value of having normal LV function at baseline was 99% [95% confidence interval (CI): 92-100%] for developing sustained VA. The positive predictive value of mechanical LV dysfunction was 20% (95% CI: 15-27%). Mechanical LV dysfunction was an independent predictor of sustained VA in multivariable analysis [hazard ratio adjusted for VA history: 20.48 (95% CI: 2.57-162.84)].

Conclusion

LVMD has incremental prognostic value on top of LVEF in PLN p.Arg14del mutation carriers, particularly in those with preserved LVEF. The '45/45' rule is a practical approach to echocardiographic risk stratification in this challenging group of patients. This approach may also have added value in other diseases where LVEF deterioration is a relative late marker of myocardial dysfunction.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeab178/40357499/jeab178.pdf; doi:https://doi.org/10.1093/ehjci/jeab178; html:https://europepmc.org/articles/PMC9584619; pdf:https://europepmc.org/articles/PMC9584619?pdf=render -34631820,https://doi.org/10.3389/fcvm.2021.716577,New Imaging Signatures of Cardiac Alterations in Ischaemic Heart Disease and Cerebrovascular Disease Using CMR Radiomics.,"Rauseo E, Izquierdo Morcillo C, Raisi-Estabragh Z, Gkontra P, Aung N, Lekadir K, Petersen SE.",,Frontiers in cardiovascular medicine,2021,2021-09-23,Y,Myocardial infarction; Stroke; Cerebrovascular disease; Ischaemic Heart Disease; Cardiovascular Magnetic Resonance; Radiomics; Brain-heart Axis,,,"Background: Ischaemic heart disease (IHD) and cerebrovascular disease are two closely inter-related clinical entities. Cardiovascular magnetic resonance (CMR) radiomics may capture subtle cardiac changes associated with these two diseases providing new insights into the brain-heart interactions. Objective: To define the CMR radiomics signatures for IHD and cerebrovascular disease and study their incremental value for disease discrimination over conventional CMR indices. Methods: We analysed CMR images of UK Biobank's subjects with pre-existing IHD, ischaemic cerebrovascular disease, myocardial infarction (MI), and ischaemic stroke (IS) (n = 779, 267, 525, and 107, respectively). Each disease group was compared with an equal number of healthy controls. We extracted 446 shape, first-order, and texture radiomics features from three regions of interest (right ventricle, left ventricle, and left ventricular myocardium) in end-diastole and end-systole defined from segmentation of short-axis cine images. Systematic feature selection combined with machine learning (ML) algorithms (support vector machine and random forest) and 10-fold cross-validation tests were used to build the radiomics signature for each condition. We compared the discriminatory power achieved by the radiomics signature with conventional indices for each disease group, using the area under the curve (AUC), receiver operating characteristic (ROC) analysis, and paired t-test for statistical significance. A third model combining both radiomics and conventional indices was also evaluated. Results: In all the study groups, radiomics signatures provided a significantly better disease discrimination than conventional indices, as suggested by AUC (IHD:0.82 vs. 0.75; cerebrovascular disease: 0.79 vs. 0.77; MI: 0.87 vs. 0.79, and IS: 0.81 vs. 0.72). Similar results were observed with the combined models. In IHD and MI, LV shape radiomics were dominant. However, in IS and cerebrovascular disease, the combination of shape and intensity-based features improved the disease discrimination. A notable overlap of the radiomics signatures of IHD and cerebrovascular disease was also found. Conclusions: This study demonstrates the potential value of CMR radiomics over conventional indices in detecting subtle cardiac changes associated with chronic ischaemic processes involving the brain and heart, even in the presence of more heterogeneous clinical pictures. Radiomics analysis might also improve our understanding of the complex mechanisms behind the brain-heart interactions during ischaemia.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.716577/pdf; doi:https://doi.org/10.3389/fcvm.2021.716577; html:https://europepmc.org/articles/PMC8494975; pdf:https://europepmc.org/articles/PMC8494975?pdf=render 36744612,https://doi.org/10.1111/ppe.12959,Trends in survival of children with severe congenital heart defects by gestational age at birth: A population-based study using administrative hospital data for England.,"Gimeno L, Brown K, Harron K, Peppa M, Gilbert R, Blackburn R.",,Paediatric and perinatal epidemiology,2023,2023-02-06,Y,Survival analysis; Congenital heart defects; England; trends; Gestational Age; Administrative Data,,,"

Background

Children with congenital heart defects (CHD) are twice as likely as their peers to be born preterm (<37 weeks' gestation), yet descriptions of recent trends in long-term survival by gestational age at birth (GA) are lacking.

Objectives

To quantify changes in survival to age 5 years of children in England with severe CHD by GA.

Methods

We estimated changes in survival to age five of children with severe CHD and all other children born in England between April 2004 and March 2016, overall and by GA-group using linked hospital and mortality records.

Results

Of 5,953,598 livebirths, 5.7% (339,080 of 5,953,598) were born preterm, 0.35% (20,648 of 5,953,598) died before age five and 3.6 per 1000 (21,291 of 5,953,598) had severe CHD. Adjusting for GA, under-five mortality rates fell at a similar rate between 2004-2008 and 2012-2016 for children with severe CHD (adjusted hazard ratio [HR] 0.79, 95% CI 0.71, 0.88) and all other children (HR 0.78, 95% CI 0.76, 0.81). For children with severe CHD, overall survival to age five increased from 87.5% (95% CI 86.6, 88.4) in 2004-2008 to 89.6% (95% CI 88.9, 90.3) in 2012-2016. There was strong evidence for better survival in the ≥39-week group (90.2%, 95% CI 89.1, 91.2 to 93%, 95% CI 92.4, 93.9), weaker evidence at 24-31 and 37-38 weeks and no evidence at 32-36 weeks. We estimate that 51 deaths (95% CI 24, 77) per year in children with severe CHD were averted in 2012-2016 compared to what would have been the case had 2004-2008 mortality rates persisted.

Conclusions

Nine out of 10 children with severe CHD in 2012-2016 survived to age five. The small improvement in survival over the study period was driven by increased survival in term children. Most children with severe CHD are reaching school age and may require additional support by schools and healthcare services.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/ppe.12959; doi:https://doi.org/10.1111/ppe.12959; html:https://europepmc.org/articles/PMC10946523; pdf:https://europepmc.org/articles/PMC10946523?pdf=render -32182948,https://doi.org/10.3390/cells9030665,"Dysregulated Antibody, Natural Killer Cell and Immune Mediator Profiles in Autoimmune Thyroid Diseases.","Martin TC, Ilieva KM, Visconti A, Beaumont M, Kiddle SJ, Dobson RJB, Mangino M, Lim EM, Pezer M, Steves CJ, Bell JT, Wilson SG, Lauc G, Roederer M, Walsh JP, Spector TD, Karagiannis SN.",,Cells,2020,2020-03-09,Y,Apoptosis; Genetic Variants; Antibody-dependent Cell-mediated Cytotoxicity (Adcc); Multi-omic; Autoimmune Thyroid Diseases (Aitd); Anti-thyroid Peroxidase Antibody (Tpoab),Understanding the Causes of Disease,inflammatory and immune system,"The pathogenesis of autoimmune thyroid diseases (AITD) is poorly understood and the association between different immune features and the germline variants involved in AITD are yet unclear. We previously observed systemic depletion of IgG core fucosylation and antennary α1,2 fucosylation in peripheral blood mononuclear cells in AITD, correlated with anti-thyroid peroxidase antibody (TPOAb) levels. Fucose depletion is known to potentiate strong antibody-mediated NK cell activation and enhanced target antigen-expressing cell killing. In autoimmunity, this may translate to autoantibody-mediated immune cell recruitment and attack of self-antigen expressing normal tissues. Hence, we investigated the crosstalk between immune cell traits, secreted proteins, genetic variants and the glycosylation patterns of serum IgG, in a multi-omic and cross-sectional study of 622 individuals from the TwinsUK cohort, 172 of whom were diagnosed with AITD. We observed associations between two genetic variants (rs505922 and rs687621), AITD status, the secretion of Desmoglein-2 protein, and the profile of two IgG N-glycan traits in AITD, but further studies need to be performed to better understand their crosstalk in AITD. On the other side, enhanced afucosylated IgG was positively associated with activatory CD335- CD314+ CD158b+ NK cell subsets. Increased levels of the apoptosis and inflammation markers Caspase-2 and Interleukin-1α positively associated with AITD. Two genetic variants associated with AITD, rs1521 and rs3094228, were also associated with altered expression of the thyrocyte-expressed ligands known to recognize the NK cell immunoreceptors CD314 and CD158b. Our analyses reveal a combination of heightened Fc-active IgG antibodies, effector cells, cytokines and apoptotic signals in AITD, and AITD genetic variants associated with altered expression of thyrocyte-expressed ligands to NK cell immunoreceptors. Together, TPOAb responses, dysregulated immune features, germline variants associated with immunoactivity profiles, are consistent with a positive autoreactive antibody-dependent NK cell-mediated immune response likely drawn to the thyroid gland in AITD.",,pdf:https://www.mdpi.com/2073-4409/9/3/665/pdf?version=1584361130; doi:https://doi.org/10.3390/cells9030665; html:https://europepmc.org/articles/PMC7140647; pdf:https://europepmc.org/articles/PMC7140647?pdf=render +34631820,https://doi.org/10.3389/fcvm.2021.716577,New Imaging Signatures of Cardiac Alterations in Ischaemic Heart Disease and Cerebrovascular Disease Using CMR Radiomics.,"Rauseo E, Izquierdo Morcillo C, Raisi-Estabragh Z, Gkontra P, Aung N, Lekadir K, Petersen SE.",,Frontiers in cardiovascular medicine,2021,2021-09-23,Y,Myocardial infarction; Stroke; Cerebrovascular disease; Ischaemic Heart Disease; Cardiovascular Magnetic Resonance; Radiomics; Brain-heart Axis,,,"Background: Ischaemic heart disease (IHD) and cerebrovascular disease are two closely inter-related clinical entities. Cardiovascular magnetic resonance (CMR) radiomics may capture subtle cardiac changes associated with these two diseases providing new insights into the brain-heart interactions. Objective: To define the CMR radiomics signatures for IHD and cerebrovascular disease and study their incremental value for disease discrimination over conventional CMR indices. Methods: We analysed CMR images of UK Biobank's subjects with pre-existing IHD, ischaemic cerebrovascular disease, myocardial infarction (MI), and ischaemic stroke (IS) (n = 779, 267, 525, and 107, respectively). Each disease group was compared with an equal number of healthy controls. We extracted 446 shape, first-order, and texture radiomics features from three regions of interest (right ventricle, left ventricle, and left ventricular myocardium) in end-diastole and end-systole defined from segmentation of short-axis cine images. Systematic feature selection combined with machine learning (ML) algorithms (support vector machine and random forest) and 10-fold cross-validation tests were used to build the radiomics signature for each condition. We compared the discriminatory power achieved by the radiomics signature with conventional indices for each disease group, using the area under the curve (AUC), receiver operating characteristic (ROC) analysis, and paired t-test for statistical significance. A third model combining both radiomics and conventional indices was also evaluated. Results: In all the study groups, radiomics signatures provided a significantly better disease discrimination than conventional indices, as suggested by AUC (IHD:0.82 vs. 0.75; cerebrovascular disease: 0.79 vs. 0.77; MI: 0.87 vs. 0.79, and IS: 0.81 vs. 0.72). Similar results were observed with the combined models. In IHD and MI, LV shape radiomics were dominant. However, in IS and cerebrovascular disease, the combination of shape and intensity-based features improved the disease discrimination. A notable overlap of the radiomics signatures of IHD and cerebrovascular disease was also found. Conclusions: This study demonstrates the potential value of CMR radiomics over conventional indices in detecting subtle cardiac changes associated with chronic ischaemic processes involving the brain and heart, even in the presence of more heterogeneous clinical pictures. Radiomics analysis might also improve our understanding of the complex mechanisms behind the brain-heart interactions during ischaemia.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.716577/pdf; doi:https://doi.org/10.3389/fcvm.2021.716577; html:https://europepmc.org/articles/PMC8494975; pdf:https://europepmc.org/articles/PMC8494975?pdf=render 33678589,https://doi.org/10.1016/s2589-7500(20)30317-4,Health data poverty: an assailable barrier to equitable digital health care.,"Ibrahim H, Liu X, Zariffa N, Morris AD, Denniston AK.",,The Lancet. Digital health,2021,2021-03-04,N,,,,"Data-driven digital health technologies have the power to transform health care. If these tools could be sustainably delivered at scale, they might have the potential to provide everyone, everywhere, with equitable access to expert-level care, narrowing the global health and wellbeing gap. Conversely, it is highly possible that these transformative technologies could exacerbate existing health-care inequalities instead. In this Viewpoint, we describe the problem of health data poverty: the inability for individuals, groups, or populations to benefit from a discovery or innovation due to a scarcity of data that are adequately representative. We assert that health data poverty is a threat to global health that could prevent the benefits of data-driven digital health technologies from being more widely realised and might even lead to them causing harm. We argue that the time to act is now to avoid creating a digital health divide that exacerbates existing health-care inequalities and to ensure that no one is left behind in the digital era.",,pdf:http://www.thelancet.com/article/S2589750020303174/pdf; doi:https://doi.org/10.1016/S2589-7500(20)30317-4 +32182948,https://doi.org/10.3390/cells9030665,"Dysregulated Antibody, Natural Killer Cell and Immune Mediator Profiles in Autoimmune Thyroid Diseases.","Martin TC, Ilieva KM, Visconti A, Beaumont M, Kiddle SJ, Dobson RJB, Mangino M, Lim EM, Pezer M, Steves CJ, Bell JT, Wilson SG, Lauc G, Roederer M, Walsh JP, Spector TD, Karagiannis SN.",,Cells,2020,2020-03-09,Y,Apoptosis; Genetic Variants; Antibody-dependent Cell-mediated Cytotoxicity (Adcc); Multi-omic; Autoimmune Thyroid Diseases (Aitd); Anti-thyroid Peroxidase Antibody (Tpoab),Understanding the Causes of Disease,inflammatory and immune system,"The pathogenesis of autoimmune thyroid diseases (AITD) is poorly understood and the association between different immune features and the germline variants involved in AITD are yet unclear. We previously observed systemic depletion of IgG core fucosylation and antennary α1,2 fucosylation in peripheral blood mononuclear cells in AITD, correlated with anti-thyroid peroxidase antibody (TPOAb) levels. Fucose depletion is known to potentiate strong antibody-mediated NK cell activation and enhanced target antigen-expressing cell killing. In autoimmunity, this may translate to autoantibody-mediated immune cell recruitment and attack of self-antigen expressing normal tissues. Hence, we investigated the crosstalk between immune cell traits, secreted proteins, genetic variants and the glycosylation patterns of serum IgG, in a multi-omic and cross-sectional study of 622 individuals from the TwinsUK cohort, 172 of whom were diagnosed with AITD. We observed associations between two genetic variants (rs505922 and rs687621), AITD status, the secretion of Desmoglein-2 protein, and the profile of two IgG N-glycan traits in AITD, but further studies need to be performed to better understand their crosstalk in AITD. On the other side, enhanced afucosylated IgG was positively associated with activatory CD335- CD314+ CD158b+ NK cell subsets. Increased levels of the apoptosis and inflammation markers Caspase-2 and Interleukin-1α positively associated with AITD. Two genetic variants associated with AITD, rs1521 and rs3094228, were also associated with altered expression of the thyrocyte-expressed ligands known to recognize the NK cell immunoreceptors CD314 and CD158b. Our analyses reveal a combination of heightened Fc-active IgG antibodies, effector cells, cytokines and apoptotic signals in AITD, and AITD genetic variants associated with altered expression of thyrocyte-expressed ligands to NK cell immunoreceptors. Together, TPOAb responses, dysregulated immune features, germline variants associated with immunoactivity profiles, are consistent with a positive autoreactive antibody-dependent NK cell-mediated immune response likely drawn to the thyroid gland in AITD.",,pdf:https://www.mdpi.com/2073-4409/9/3/665/pdf?version=1584361130; doi:https://doi.org/10.3390/cells9030665; html:https://europepmc.org/articles/PMC7140647; pdf:https://europepmc.org/articles/PMC7140647?pdf=render 33344049,https://doi.org/10.1167/tvst.9.13.5,Automated Segmentation of Optical Coherence Tomography Angiography Images: Benchmark Data and Clinically Relevant Metrics.,"Giarratano Y, Bianchi E, Gray C, Morris A, MacGillivray T, Dhillon B, Bernabeu MO.",,Translational vision science & technology,2020,2020-12-03,Y,Automated Segmentation; Retinal Vasculature; Optical Coherence Tomography Angiography,,,"

Purpose

To generate the first open dataset of retinal parafoveal optical coherence tomography angiography (OCTA) images with associated ground truth manual segmentations, and to establish a standard for OCTA image segmentation by surveying a broad range of state-of-the-art vessel enhancement and binarization procedures.

Methods

Handcrafted filters and neural network architectures were used to perform vessel enhancement. Thresholding methods and machine learning approaches were applied to obtain the final binarization. Evaluation was performed by using pixelwise metrics and newly proposed topological metrics. Finally, we compare the error in the computation of clinically relevant vascular network metrics (e.g., foveal avascular zone area and vessel density) across segmentation methods.

Results

Our results show that, for the set of images considered, deep learning architectures (U-Net and CS-Net) achieve the best performance (Dice = 0.89). For applications where manually segmented data are not available to retrain these approaches, our findings suggest that optimally oriented flux (OOF) is the best handcrafted filter (Dice = 0.86). Moreover, our results show up to 25% differences in vessel density accuracy depending on the segmentation method used.

Conclusions

In this study, we derive and validate the first open dataset of retinal parafoveal OCTA images with associated ground truth manual segmentations. Our findings should be taken into account when comparing the results of clinical studies and performing meta-analyses. Finally, we release our data and source code to support standardization efforts in OCTA image segmentation.

Translational relevance

This work establishes a standard for OCTA retinal image segmentation and introduces the importance of evaluating segmentation performance in terms of clinically relevant metrics.",,doi:https://doi.org/10.1167/tvst.9.13.5; doi:https://doi.org/10.1167/tvst.9.13.5; html:https://europepmc.org/articles/PMC7718823; pdf:https://europepmc.org/articles/PMC7718823?pdf=render -37703231,https://doi.org/10.1371/journal.pdig.0000334,A population-based study exploring phenotypic clusters and clinical outcomes in stroke using unsupervised machine learning approach.,"Akyea RK, Ntaios G, Kontopantelis E, Georgiopoulos G, Soria D, Asselbergs FW, Kai J, Weng SF, Qureshi N.",,PLOS digital health,2023,2023-09-13,Y,,,,"Individuals developing stroke have varying clinical characteristics, demographic, and biochemical profiles. This heterogeneity in phenotypic characteristics can impact on cardiovascular disease (CVD) morbidity and mortality outcomes. This study uses a novel clustering approach to stratify individuals with incident stroke into phenotypic clusters and evaluates the differential burden of recurrent stroke and other cardiovascular outcomes. We used linked clinical data from primary care, hospitalisations, and death records in the UK. A data-driven clustering analysis (kamila algorithm) was used in 48,114 patients aged ≥ 18 years with incident stroke, from 1-Jan-1998 to 31-Dec-2017 and no prior history of serious vascular events. Cox proportional hazards regression was used to estimate hazard ratios (HRs) for subsequent adverse outcomes, for each of the generated clusters. Adverse outcomes included coronary heart disease (CHD), recurrent stroke, peripheral vascular disease (PVD), heart failure, CVD-related and all-cause mortality. Four distinct phenotypes with varying underlying clinical characteristics were identified in patients with incident stroke. Compared with cluster 1 (n = 5,201, 10.8%), the risk of composite recurrent stroke and CVD-related mortality was higher in the other 3 clusters (cluster 2 [n = 18,655, 38.8%]: hazard ratio [HR], 1.07; 95% CI, 1.02-1.12; cluster 3 [n = 10,244, 21.3%]: HR, 1.20; 95% CI, 1.14-1.26; and cluster 4 [n = 14,014, 29.1%]: HR, 1.44; 95% CI: 1.37-1.50). Similar trends in risk were observed for composite recurrent stroke and all-cause mortality outcome, and subsequent recurrent stroke outcome. However, results were not consistent for subsequent risk in CHD, PVD, heart failure, CVD-related mortality, and all-cause mortality. In this proof of principle study, we demonstrated how a heterogenous population of patients with incident stroke can be stratified into four relatively homogenous phenotypes with differential risk of recurrent and major cardiovascular outcomes. This offers an opportunity to revisit the stratification of care for patients with incident stroke to improve patient outcomes.",,pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000334&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000334; html:https://europepmc.org/articles/PMC10499205; pdf:https://europepmc.org/articles/PMC10499205?pdf=render -34270458,https://doi.org/10.4269/ajtmh.21-0482,The Need for a Practical Approach to Evaluate the Effectiveness of COVID-19 Vaccines for Low- and Middle-Income Countries.,"Nsanzimana S, Gupta A, Uwizihiwe JP, Haggstrom J, Dron L, Arora P, Park JJH.",,The American journal of tropical medicine and hygiene,2021,2021-07-16,Y,,,,"The global demand for coronavirus disease 2019 (COVID-19) vaccines currently far outweighs the available global supply and manufacturing capacity. As a result, securing doses of vaccines for low- and middle-income countries has been challenging, particularly for African countries. Clinical trial investigation for COVID-19 vaccines has been rare in Africa, with the only randomized clinical trials (RCTs) for COVID-19 vaccines having been conducted in South Africa. In addition to addressing the current inequities in the vaccine roll-out for low- and middle-income countries, there is a need to monitor the real-world effectiveness of COVID-19 vaccines in these regions. Although RCTs are the superior method for evaluating vaccine efficacy, the feasibility of conducting RCTs to monitor COVID-19 vaccine effectiveness during mass vaccine campaigns will likely be low. There is still a need to evaluate the effectiveness of mass COVID-19 vaccine distribution in a practical manner. We discuss how target trial emulation, the application of trial design principles from RCTs to the analysis of observational data, can be used as a practical, cost-effective way to evaluate real-world effectiveness for COVID-19 vaccines. There are several study design considerations that need to be made in the analyses of observational data, such as uncontrolled confounders and selection biases. Target trial emulation accounts for these considerations to improve the analyses of observational data. The framework of target trial emulation provides a practical way to monitor the effectiveness of mass vaccine campaigns for COVID-19 using observational data.",,pdf:https://www.ajtmh.org/downloadpdf/journals/tpmd/105/3/article-p561.pdf; doi:https://doi.org/10.4269/ajtmh.21-0482; html:https://europepmc.org/articles/PMC8592367; pdf:https://europepmc.org/articles/PMC8592367?pdf=render 33085509,https://doi.org/10.7326/m20-4986,COVID-19 Mortality Risk in Down Syndrome: Results From a Cohort Study of 8 Million Adults.,"Clift AK, Coupland CAC, Keogh RH, Hemingway H, Hippisley-Cox J.",,Annals of internal medicine,2021,2020-10-21,Y,,,,,,pdf:https://europepmc.org/articles/pmc7592804?pdf=render; doi:https://doi.org/10.7326/M20-4986; html:https://europepmc.org/articles/PMC7592804; pdf:https://europepmc.org/articles/PMC7592804?pdf=render -33655079,https://doi.org/10.12688/wellcomeopenres.16304.2,Impact of baseline cases of cough and fever on UK COVID-19 diagnostic testing rates: estimates from the Bug Watch community cohort study.,"Eyre MT, Burns R, Kirkby V, Smith C, Denaxas S, Nguyen V, Hayward A, Shallcross L, Fragaszy E, Aldridge RW.",,Wellcome open research,2020,2020-01-01,Y,Fever; Cough; United Kingdom; Diagnostic Testing Capacity; Covid-19; Swab Test,,,"Background: Diagnostic testing forms a major part of the UK's response to the current coronavirus disease 2019 (COVID-19) pandemic with tests offered to anyone with a continuous cough, high temperature or anosmia. Testing capacity must be sufficient during the winter respiratory season when levels of cough and fever are high due to non-COVID-19 causes. This study aims to make predictions about the contribution of baseline cough or fever to future testing demand in the UK. Methods: In this analysis of the Bug Watch community cohort study, we estimated the incidence of cough or fever in England in 2018-2019. We then estimated the COVID-19 diagnostic testing rates required in the UK for baseline cough or fever cases for the period July 2020-June 2021. This was explored for different rates of the population requesting tests, four COVID-19 second wave scenarios and high and low baseline cough or fever incidence scenarios. Results: Under the high baseline cough or fever scenario, incidence in the UK is expected to rise rapidly from 250,708 (95%CI 181,095 - 347,080) cases per day in September to a peak of 444,660 (95%CI 353,084 - 559,988) in December. If 80% of these cases request tests, testing demand would exceed 1.4 million tests per week for five consecutive months. Demand was significantly lower in the low cough or fever incidence scenario, with 129,115 (95%CI 111,596 - 151,679) tests per day in January 2021, compared to 340,921 (95%CI 276,039 - 424,491) tests per day in the higher incidence scenario. Conclusions: Our results show that national COVID-19 testing demand is highly dependent on background cough or fever incidence. This study highlights that the UK's response to the COVID-19 pandemic must ensure that a high proportion of people with symptoms request tests, and that testing capacity is sufficient to meet the high predicted demand.",,doi:https://doi.org/10.12688/wellcomeopenres.16304.2; html:https://europepmc.org/articles/PMC7890379; pdf:https://europepmc.org/articles/PMC7890379?pdf=render +34270458,https://doi.org/10.4269/ajtmh.21-0482,The Need for a Practical Approach to Evaluate the Effectiveness of COVID-19 Vaccines for Low- and Middle-Income Countries.,"Nsanzimana S, Gupta A, Uwizihiwe JP, Haggstrom J, Dron L, Arora P, Park JJH.",,The American journal of tropical medicine and hygiene,2021,2021-07-16,Y,,,,"The global demand for coronavirus disease 2019 (COVID-19) vaccines currently far outweighs the available global supply and manufacturing capacity. As a result, securing doses of vaccines for low- and middle-income countries has been challenging, particularly for African countries. Clinical trial investigation for COVID-19 vaccines has been rare in Africa, with the only randomized clinical trials (RCTs) for COVID-19 vaccines having been conducted in South Africa. In addition to addressing the current inequities in the vaccine roll-out for low- and middle-income countries, there is a need to monitor the real-world effectiveness of COVID-19 vaccines in these regions. Although RCTs are the superior method for evaluating vaccine efficacy, the feasibility of conducting RCTs to monitor COVID-19 vaccine effectiveness during mass vaccine campaigns will likely be low. There is still a need to evaluate the effectiveness of mass COVID-19 vaccine distribution in a practical manner. We discuss how target trial emulation, the application of trial design principles from RCTs to the analysis of observational data, can be used as a practical, cost-effective way to evaluate real-world effectiveness for COVID-19 vaccines. There are several study design considerations that need to be made in the analyses of observational data, such as uncontrolled confounders and selection biases. Target trial emulation accounts for these considerations to improve the analyses of observational data. The framework of target trial emulation provides a practical way to monitor the effectiveness of mass vaccine campaigns for COVID-19 using observational data.",,pdf:https://www.ajtmh.org/downloadpdf/journals/tpmd/105/3/article-p561.pdf; doi:https://doi.org/10.4269/ajtmh.21-0482; html:https://europepmc.org/articles/PMC8592367; pdf:https://europepmc.org/articles/PMC8592367?pdf=render +37703231,https://doi.org/10.1371/journal.pdig.0000334,A population-based study exploring phenotypic clusters and clinical outcomes in stroke using unsupervised machine learning approach.,"Akyea RK, Ntaios G, Kontopantelis E, Georgiopoulos G, Soria D, Asselbergs FW, Kai J, Weng SF, Qureshi N.",,PLOS digital health,2023,2023-09-13,Y,,,,"Individuals developing stroke have varying clinical characteristics, demographic, and biochemical profiles. This heterogeneity in phenotypic characteristics can impact on cardiovascular disease (CVD) morbidity and mortality outcomes. This study uses a novel clustering approach to stratify individuals with incident stroke into phenotypic clusters and evaluates the differential burden of recurrent stroke and other cardiovascular outcomes. We used linked clinical data from primary care, hospitalisations, and death records in the UK. A data-driven clustering analysis (kamila algorithm) was used in 48,114 patients aged ≥ 18 years with incident stroke, from 1-Jan-1998 to 31-Dec-2017 and no prior history of serious vascular events. Cox proportional hazards regression was used to estimate hazard ratios (HRs) for subsequent adverse outcomes, for each of the generated clusters. Adverse outcomes included coronary heart disease (CHD), recurrent stroke, peripheral vascular disease (PVD), heart failure, CVD-related and all-cause mortality. Four distinct phenotypes with varying underlying clinical characteristics were identified in patients with incident stroke. Compared with cluster 1 (n = 5,201, 10.8%), the risk of composite recurrent stroke and CVD-related mortality was higher in the other 3 clusters (cluster 2 [n = 18,655, 38.8%]: hazard ratio [HR], 1.07; 95% CI, 1.02-1.12; cluster 3 [n = 10,244, 21.3%]: HR, 1.20; 95% CI, 1.14-1.26; and cluster 4 [n = 14,014, 29.1%]: HR, 1.44; 95% CI: 1.37-1.50). Similar trends in risk were observed for composite recurrent stroke and all-cause mortality outcome, and subsequent recurrent stroke outcome. However, results were not consistent for subsequent risk in CHD, PVD, heart failure, CVD-related mortality, and all-cause mortality. In this proof of principle study, we demonstrated how a heterogenous population of patients with incident stroke can be stratified into four relatively homogenous phenotypes with differential risk of recurrent and major cardiovascular outcomes. This offers an opportunity to revisit the stratification of care for patients with incident stroke to improve patient outcomes.",,pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000334&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000334; html:https://europepmc.org/articles/PMC10499205; pdf:https://europepmc.org/articles/PMC10499205?pdf=render 31442537,https://doi.org/10.1016/j.jaad.2019.08.039,Atopic dermatitis and risk of atrial fibrillation or flutter: A 35-year follow-up study.,"Schmidt SAJ, Olsen M, Schmidt M, Vestergaard C, Langan SM, Deleuran MS, Riis JL.",,Journal of the American Academy of Dermatology,2020,2019-08-20,Y,Validation; Atrial fibrillation; Atrial flutter; Cohort study; risk factors; Atopic Dermatitis,Understanding the Causes of Disease,,"

Background

Atopic dermatitis is characterized by chronic inflammation, which is a risk factor for atrial fibrillation.

Objective

To examine the association between hospital-diagnosed atopic dermatitis and atrial fibrillation.

Methods

Using linked population-based Danish registries, we identified persons with an inpatient or outpatient hospital diagnosis of atopic dermatitis during 1977-2013 and a comparison cohort individually matched to the atopic dermatitis cohort. We followed cohorts until death, emigration, atrial fibrillation diagnosis, or end of study (January 1, 2013). We compared 35-year risk of atrial fibrillation and estimated hazard ratios with 95% confidence intervals using Cox regression, adjusting for birth year and sex. We validated 100 atopic dermatitis diagnoses from a dermatologic department through medical record review.

Results

We included 13,126 persons with atopic dermatitis and 124,211 comparators and followed them for a median of 19.3 years. The 35-year risk of atrial fibrillation was 0.81% and 0.67%, respectively. The positive predictive value of atopic dermatitis diagnoses was 99%. The hazard ratio was 1.2 (95% confidence interval 1.0-1.6) and remained increased after adjusting for various atrial fibrillation risk factors.

Limitations

Analyses were limited to persons with moderate-to-severe atopic dermatitis, and we had no lifestyle data.

Conclusion

Patients with hospital-diagnosed atopic dermatitis have a 20% increased long-term risk of atrial fibrillation, but the absolute risk remains low.",,pdf:http://www.jaad.org/article/S0190962219326143/pdf; doi:https://doi.org/10.1016/j.jaad.2019.08.039; html:https://europepmc.org/articles/PMC7704103; pdf:https://europepmc.org/articles/PMC7704103?pdf=render +33655079,https://doi.org/10.12688/wellcomeopenres.16304.2,Impact of baseline cases of cough and fever on UK COVID-19 diagnostic testing rates: estimates from the Bug Watch community cohort study.,"Eyre MT, Burns R, Kirkby V, Smith C, Denaxas S, Nguyen V, Hayward A, Shallcross L, Fragaszy E, Aldridge RW.",,Wellcome open research,2020,2020-01-01,Y,Fever; Cough; United Kingdom; Diagnostic Testing Capacity; Covid-19; Swab Test,,,"Background: Diagnostic testing forms a major part of the UK's response to the current coronavirus disease 2019 (COVID-19) pandemic with tests offered to anyone with a continuous cough, high temperature or anosmia. Testing capacity must be sufficient during the winter respiratory season when levels of cough and fever are high due to non-COVID-19 causes. This study aims to make predictions about the contribution of baseline cough or fever to future testing demand in the UK. Methods: In this analysis of the Bug Watch community cohort study, we estimated the incidence of cough or fever in England in 2018-2019. We then estimated the COVID-19 diagnostic testing rates required in the UK for baseline cough or fever cases for the period July 2020-June 2021. This was explored for different rates of the population requesting tests, four COVID-19 second wave scenarios and high and low baseline cough or fever incidence scenarios. Results: Under the high baseline cough or fever scenario, incidence in the UK is expected to rise rapidly from 250,708 (95%CI 181,095 - 347,080) cases per day in September to a peak of 444,660 (95%CI 353,084 - 559,988) in December. If 80% of these cases request tests, testing demand would exceed 1.4 million tests per week for five consecutive months. Demand was significantly lower in the low cough or fever incidence scenario, with 129,115 (95%CI 111,596 - 151,679) tests per day in January 2021, compared to 340,921 (95%CI 276,039 - 424,491) tests per day in the higher incidence scenario. Conclusions: Our results show that national COVID-19 testing demand is highly dependent on background cough or fever incidence. This study highlights that the UK's response to the COVID-19 pandemic must ensure that a high proportion of people with symptoms request tests, and that testing capacity is sufficient to meet the high predicted demand.",,doi:https://doi.org/10.12688/wellcomeopenres.16304.2; html:https://europepmc.org/articles/PMC7890379; pdf:https://europepmc.org/articles/PMC7890379?pdf=render 35987738,https://doi.org/10.1016/j.jcmg.2022.06.017,Benefits of Machine Learning to Predict Survival Using Stress Perfusion CMR and Basic Clinical Information.,"Petersen SE, Aung N.",,JACC. Cardiovascular imaging,2022,2022-08-17,N,Machine Learning; Cardiovascular Magnetic Resonance; Vasodilator Stress Perfusion,,,,,doi:https://doi.org/10.1016/j.jcmg.2022.06.017; doi:https://doi.org/10.1016/j.jcmg.2022.06.017 37338108,https://doi.org/10.1093/eurjpc/zwad202,The relevance of competing risk adjustment in cardiovascular risk prediction models for clinical practice.,"Hageman SHJ, Dorresteijn JAN, Pennells L, van Smeden M, Bots ML, Di Angelantonio E, Visseren FLJ.",,European journal of preventive cardiology,2023,2023-11-01,N,Education; Personalized Medicine; Risk Prediction; Competing Risks; Score2,,,"

Background

Many models developed for predicting the risk of cardiovascular disease (CVD) are adjusted for the competing risk of non-CVD mortality, which has been suggested to reduce potential overestimation of cumulative incidence in populations where the risk of competing events is high. The objective was to evaluate and illustrate the clinical impact of competing risk adjustment when deriving a CVD prediction model in a high-risk population.

Methods and results

Individuals with established atherosclerotic CVD were included from the Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease (UCC-SMART). In 8355 individuals, followed for a median of 8.2 years (IQR 4.2-12.5), two similar prediction models for the estimation of 10-year residual CVD risk were derived: with competing risk adjustment using a Fine and Gray model and without competing risk adjustment using a Cox proportional hazards model. On average, predictions were higher from the Cox model. The Cox model predictions overestimated the cumulative incidence [predicted-observed ratio 1.14 (95% CI 1.09-1.20)], which was most apparent in the highest risk quartiles and in older persons. Discrimination of both models was similar. When determining treatment eligibility on thresholds of predicted risks, more individuals would be treated based on the Cox model predictions. If, for example, individuals with a predicted risk > 20% were considered eligible for treatment, 34% of the population would be treated according to the Fine and Gray model predictions and 44% according to the Cox model predictions.

Interpretation

Individual predictions from the model unadjusted for competing risks were higher, reflecting the different interpretations of both models. For models aiming to accurately predict absolute risks, especially in high-risk populations, competing risk adjustment must be considered.",,doi:https://doi.org/10.1093/eurjpc/zwad202; doi:https://doi.org/10.1093/eurjpc/zwad202 36580444,https://doi.org/10.1371/journal.pmed.1004141,Associations of genetically predicted fatty acid levels across the phenome: A mendelian randomisation study.,"Zagkos L, Dib MJ, Pinto R, Gill D, Koskeridis F, Drenos F, Markozannes G, Elliott P, Zuber V, Tsilidis K, Dehghan A, Tzoulaki I.",,PLoS medicine,2022,2022-12-29,Y,,,,"

Background

Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies and randomised controlled trials on their role in cardiovascular, inflammatory, and other diseases remains inconsistent. The objective of this study was to assess whether genetically predicted fatty acid concentrations affect the risk of disease across a wide variety of clinical health outcomes.

Methods and findings

The UK Biobank (UKB) is a large study involving over 500,000 participants aged 40 to 69 years at recruitment from 2006 to 2010. We used summary-level data for 117,143 UKB samples (base dataset), to extract genetic associations of fatty acids, and individual-level data for 322,232 UKB participants (target dataset) to conduct our discovery analysis. We studied potentially causal relationships of circulating fatty acids with 845 clinical diagnoses, using mendelian randomisation (MR) approach, within a phenome-wide association study (PheWAS) framework. Regression models in PheWAS were adjusted for sex, age, and the first 10 genetic principal components. External summary statistics were used for replication. When several fatty acids were associated with a health outcome, multivariable MR and MR-Bayesian method averaging (MR-BMA) was applied to disentangle their causal role. Genetic predisposition to higher docosahexaenoic acid (DHA) was associated with cholelithiasis and cholecystitis (odds ratio per mmol/L: 0.76, 95% confidence interval: 0.66 to 0.87). This was supported in replication analysis (FinnGen study) and by the genetically predicted omega-3 fatty acids analyses. Genetically predicted linoleic acid (LA), omega-6, polyunsaturated fatty acids (PUFAs), and total fatty acids (total FAs) showed positive associations with cardiovascular outcomes with support from replication analysis. Finally, higher genetically predicted levels of DHA (0.83, 0.73 to 0.95) and omega-3 (0.83, 0.75 to 0.92) were found to have a protective effect on obesity, which was supported using body mass index (BMI) in the GIANT consortium as replication analysis. Multivariable MR analysis suggested a direct detrimental effect of LA (1.64, 1.07 to 2.50) and omega-6 fatty acids (1.81, 1.06 to 3.09) on coronary heart disease (CHD). MR-BMA prioritised LA and omega-6 fatty acids as the top risk factors for CHD. Although we present a range of sensitivity analyses to the address MR assumptions, horizontal pleiotropy may still bias the reported associations and further evaluation in clinical trials is needed.

Conclusions

Our study suggests potentially protective effects of circulating DHA and omega-3 concentrations on cholelithiasis and cholecystitis and on obesity, highlighting the need to further assess them as prevention treatments in clinical trials. Moreover, our findings do not support the supplementation of unsaturated fatty acids for cardiovascular disease prevention.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004141&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004141; html:https://europepmc.org/articles/PMC9799317; pdf:https://europepmc.org/articles/PMC9799317?pdf=render -35440465,https://doi.org/10.3399/bjgp.2021.0689,Association between oral anticoagulants and COVID-19-related outcomes: a population-based cohort study.,"Wong AY, Tomlinson L, Brown JP, Elson W, Walker AJ, Schultze A, Morton CE, Evans D, Inglesby P, MacKenna B, Bhaskaran K, Rentsch CT, Powell E, Williamson E, Croker R, Bacon S, Hulme W, Bates C, Curtis HJ, Mehrkar A, Cockburn J, McDonald HI, Mathur R, Wing K, Forbes H, Eggo RM, Evans SJ, Smeeth L, Goldacre B, Douglas IJ, (The OpenSAFELY Collaborative).",,The British journal of general practice : the journal of the Royal College of General Practitioners,2022,2022-06-30,Y,Warfarin; Factor Xa Inhibitors; Dabigatran; Covid-19,,,"

Background

Early evidence has shown that anticoagulant reduces the risk of thrombotic events in those infected with COVID-19. However, evidence of the role of routinely prescribed oral anticoagulants (OACs) in COVID-19 outcomes is limited.

Aim

To investigate the association between OACs and COVID-19 outcomes in those with atrial fibrillation and a CHA2DS2-VASc score of 2.

Design and setting

On behalf of NHS England, a population-based cohort study was conducted.

Method

The study used primary care data and pseudonymously-linked SARS-CoV-2 antigen testing data, hospital admissions, and death records from England. Cox regression was used to estimate hazard ratios (HRs) for COVID-19 outcomes comparing people with current OAC use versus non-use, accounting for age, sex, comorbidities, other medications, deprivation, and general practice.

Results

Of 71 103 people with atrial fibrillation and a CHA2DS2-VASc score of 2, there were 52 832 current OAC users and 18 271 non-users. No difference in risk of being tested for SARS-CoV-2 was associated with current use (adjusted HR [aHR] 0.99, 95% confidence interval [CI] = 0.95 to 1.04) versus non-use. A lower risk of testing positive for SARS-CoV-2 (aHR 0.77, 95% CI = 0.63 to 0.95) and a marginally lower risk of COVID-19-related death (aHR, 0.74, 95% CI = 0.53 to 1.04) were associated with current use versus non-use.

Conclusion

Among those at low baseline stroke risk, people receiving OACs had a lower risk of testing positive for SARS-CoV-2 and severe COVID-19 outcomes than non-users; this might be explained by a causal effect of OACs in preventing severe COVID-19 outcomes or unmeasured confounding, including more cautious behaviours leading to reduced infection risk.",,pdf:https://bjgp.org/content/bjgp/early/2022/04/19/BJGP.2021.0689.full.pdf; doi:https://doi.org/10.3399/BJGP.2021.0689; html:https://europepmc.org/articles/PMC9037187; pdf:https://europepmc.org/articles/PMC9037187?pdf=render 30532623,https://doi.org/10.3897/bdj.6.e29232,"Modifier Ontologies for frequency, certainty, degree, and coverage phenotype modifier.","Endara L, Thessen AE, Cole HA, Walls R, Gkoutos G, Cao Y, Chong SS, Cui H.",,Biodiversity data journal,2018,2018-11-28,Y,Phenotype Modifiers; Modifier Ontology; Certainty Modifiers; Coverage Modifiers; Degree Modifiers; Frequency Modifiers; Literary Warrant; User Consensus; User Warrant,The Human Phenome,,"Background: When phenotypic characters are described in the literature, they may be constrained or clarified with additional information such as the location or degree of expression, these terms are called ""modifiers"". With effort underway to convert narrative character descriptions to computable data, ontologies for such modifiers are needed. Such ontologies can also be used to guide term usage in future publications. Spatial and method modifiers are the subjects of ontologies that already have been developed or are under development. In this work, frequency (e.g., rarely, usually), certainty (e.g., probably, definitely), degree (e.g., slightly, extremely), and coverage modifiers (e.g., sparsely, entirely) are collected, reviewed, and used to create two modifier ontologies with different design considerations. The basic goal is to express the sequential relationships within a type of modifiers, for example, usually is more frequent than rarely, in order to allow data annotated with ontology terms to be classified accordingly. Method: Two designs are proposed for the ontology, both using the list pattern: a closed ordered list (i.e., five-bin design) and an open ordered list design. The five-bin design puts the modifier terms into a set of 5 fixed bins with interval object properties, for example, one_level_more/less_frequently_than, where new terms can only be added as synonyms to existing classes. The open list approach starts with 5 bins, but supports the extensibility of the list via ordinal properties, for example, more/less_frequently_than, allowing new terms to be inserted as a new class anywhere in the list. The consequences of the different design decisions are discussed in the paper. CharaParser was used to extract modifiers from plant, ant, and other taxonomic descriptions. After a manual screening, 130 modifier words were selected as the candidate terms for the modifier ontologies. Four curators/experts (three biologists and one information scientist specialized in biosemantics) reviewed and categorized the terms into 20 bins using the Ontology Term Organizer (OTO) (http://biosemantics.arizona.edu/OTO). Inter-curator variations were reviewed and expressed in the final ontologies. Results: Frequency, certainty, degree, and coverage terms with complete agreement among all curators were used as class labels or exact synonyms. Terms with different interpretations were either excluded or included using ""broader synonym"" or ""not recommended"" annotation properties. These annotations explicitly allow for the user to be aware of the semantic ambiguity associated with the terms and whether they should be used with caution or avoided. Expert categorization results showed that 16 out of 20 bins contained terms with full agreements, suggesting differentiating the modifiers into 5 levels/bins balances the need to differentiate modifiers and the need for the ontology to reflect user consensus. Two ontologies, developed using the Protege ontology editor, are made available as OWL files and can be downloaded from https://github.com/biosemantics/ontologies. Contribution: We built the first two modifier ontologies following a consensus-based approach with terms commonly used in taxonomic literature. The five-bin ontology has been used in the Explorer of Taxon Concepts web toolkit to compute the similarity between characters extracted from literature to facilitate taxon concepts alignments. The two ontologies will also be used in an ontology-informed authoring tool for taxonomists to facilitate consistency in modifier term usage.",,pdf:https://bdj.pensoft.net/article/29232/download/pdf/; doi:https://doi.org/10.3897/BDJ.6.e29232; html:https://europepmc.org/articles/PMC6281706; pdf:https://europepmc.org/articles/PMC6281706?pdf=render +35440465,https://doi.org/10.3399/bjgp.2021.0689,Association between oral anticoagulants and COVID-19-related outcomes: a population-based cohort study.,"Wong AY, Tomlinson L, Brown JP, Elson W, Walker AJ, Schultze A, Morton CE, Evans D, Inglesby P, MacKenna B, Bhaskaran K, Rentsch CT, Powell E, Williamson E, Croker R, Bacon S, Hulme W, Bates C, Curtis HJ, Mehrkar A, Cockburn J, McDonald HI, Mathur R, Wing K, Forbes H, Eggo RM, Evans SJ, Smeeth L, Goldacre B, Douglas IJ, (The OpenSAFELY Collaborative).",,The British journal of general practice : the journal of the Royal College of General Practitioners,2022,2022-06-30,Y,Warfarin; Factor Xa Inhibitors; Dabigatran; Covid-19,,,"

Background

Early evidence has shown that anticoagulant reduces the risk of thrombotic events in those infected with COVID-19. However, evidence of the role of routinely prescribed oral anticoagulants (OACs) in COVID-19 outcomes is limited.

Aim

To investigate the association between OACs and COVID-19 outcomes in those with atrial fibrillation and a CHA2DS2-VASc score of 2.

Design and setting

On behalf of NHS England, a population-based cohort study was conducted.

Method

The study used primary care data and pseudonymously-linked SARS-CoV-2 antigen testing data, hospital admissions, and death records from England. Cox regression was used to estimate hazard ratios (HRs) for COVID-19 outcomes comparing people with current OAC use versus non-use, accounting for age, sex, comorbidities, other medications, deprivation, and general practice.

Results

Of 71 103 people with atrial fibrillation and a CHA2DS2-VASc score of 2, there were 52 832 current OAC users and 18 271 non-users. No difference in risk of being tested for SARS-CoV-2 was associated with current use (adjusted HR [aHR] 0.99, 95% confidence interval [CI] = 0.95 to 1.04) versus non-use. A lower risk of testing positive for SARS-CoV-2 (aHR 0.77, 95% CI = 0.63 to 0.95) and a marginally lower risk of COVID-19-related death (aHR, 0.74, 95% CI = 0.53 to 1.04) were associated with current use versus non-use.

Conclusion

Among those at low baseline stroke risk, people receiving OACs had a lower risk of testing positive for SARS-CoV-2 and severe COVID-19 outcomes than non-users; this might be explained by a causal effect of OACs in preventing severe COVID-19 outcomes or unmeasured confounding, including more cautious behaviours leading to reduced infection risk.",,pdf:https://bjgp.org/content/bjgp/early/2022/04/19/BJGP.2021.0689.full.pdf; doi:https://doi.org/10.3399/BJGP.2021.0689; html:https://europepmc.org/articles/PMC9037187; pdf:https://europepmc.org/articles/PMC9037187?pdf=render 37067859,https://doi.org/10.1136/bmjmed-2022-000245,Sex differences in cardiovascular complications and mortality in hospital patients with covid-19: registry based observational study.,"Hockham C, Linschoten M, Asselbergs FW, Ghossein C, Woodward M, Peters SAE, CAPACITY-COVID Collaborative Consortium .",,BMJ medicine,2023,2023-02-14,Y,epidemiology; Heart Failure; Cardiology; Covid-19,,,"

Objective

To assess whether the risk of cardiovascular complications of covid-19 differ between the sexes and to determine whether any sex differences in risk are reduced in individuals with pre-existing cardiovascular disease.

Design

Registry based observational study.

Setting

74 hospitals across 13 countries (eight European) participating in CAPACITY-COVID (Cardiac complicAtions in Patients With SARS Corona vIrus 2 regisTrY), from March 2020 to May 2021.

Participants

All adults (aged ≥18 years), predominantly European, admitted to hospital with highly suspected covid-19 disease or covid-19 disease confirmed by positive laboratory test results (n=11 167 patients).

Main outcome measures

Any cardiovascular complication during admission to hospital. Secondary outcomes were in-hospital mortality and individual cardiovascular complications with ≥20 events for each sex. Logistic regression was used to examine sex differences in the risk of cardiovascular outcomes, overall and grouped by pre-existing cardiovascular disease.

Results

Of 11 167 adults (median age 68 years, 40% female participants) included, 3423 (36% of whom were female participants) had pre-existing cardiovascular disease. In both sexes, the most common cardiovascular complications were supraventricular tachycardias (4% of female participants, 6% of male participants), pulmonary embolism (3% and 5%), and heart failure (decompensated or de novo) (2% in both sexes). After adjusting for age, ethnic group, pre-existing cardiovascular disease, and risk factors for cardiovascular disease, female individuals were less likely than male individuals to have a cardiovascular complication (odds ratio 0.72, 95% confidence interval 0.64 to 0.80) or die (0.65, 0.59 to 0.72). Differences between the sexes were not modified by pre-existing cardiovascular disease; for the primary outcome, the female-to-male ratio of the odds ratio in those without, compared with those with, pre-existing cardiovascular disease was 0.84 (0.67 to 1.07).

Conclusions

In patients admitted to hospital for covid-19, female participants were less likely than male participants to have a cardiovascular complication. The differences between the sexes could not be attributed to the lower prevalence of pre-existing cardiovascular disease in female individuals. The reasons for this advantage in female individuals requires further research.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000245.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000245; html:https://europepmc.org/articles/PMC10083523; pdf:https://europepmc.org/articles/PMC10083523?pdf=render -35842339,https://doi.org/10.1016/j.vaccine.2022.06.080,Linking cohort data and Welsh routine health records to investigate children at risk of delayed primary vaccination.,"Walton S, Cortina-Borja M, Dezateux C, Griffiths LJ, Tingay K, Akbari A, Bandyopadhyay A, Lyons RA, Roberts R, Bedford H.",,Vaccine,2022,2022-07-13,Y,Child; Vaccination; Dtp Vaccine; Timeliness; Child Health Systems; Millennium Cohort Study (Mcs),,,"

Background

Delayed primary vaccination is one of the strongest predictors of subsequent incomplete immunisation. Identifying children at risk of such delay may enable targeting of interventions, thus decreasing vaccine-preventable illness.

Objectives

To explore socio-demographic factors associated with delayed receipt of the Diphtheria, Tetanus and Pertussis (DTP) vaccine.

Methods

We included 1,782 children, born between 2000 and 2001, participating in the Millennium Cohort Study (MCS) and resident in Wales, whose parents gave consent for linkage to National Community Child Health Database records at the age seven years contact. We examined child, maternal, family and area characteristics associated with delayed receipt of the first dose of the DTP vaccine.

Results

98.6% received the first dose of DTP. The majority, 79.6% (n = 1,429) received it on time (between 8 and 12 weeks of age), 14.2% (n = 251) received it early (prior to 8 weeks of age) and 4.8% (n = 79) were delayed (after 12 weeks of age); 1.4% (n = 23) never received it. Delayed primary vaccination was more likely among children with older natural siblings (risk ratio 3.82, 95% confidence interval (1.97, 7.38)), children admitted to special/intensive care (3.15, (1.65, 5.99)), those whose birth weight was > 4Kg (2.02, (1.09, 3.73)) and boys (1.53, (1.01, 2.31)). There was a reduced risk of delayed vaccination with increasing maternal age (0.73, (0.53, 1.00) per 5 year increase) and for babies born to graduate mothers (0.27, (0.08, 0.90)).

Conclusions

Although the majority of infants were vaccinated in a timely manner, identification of infants at increased risk of early or delayed vaccination will enable targeting of interventions to facilitate timely immunisation. This is to our knowledge the first study exploring individual level socio-demographic factors associated with delayed primary vaccination in the UK and demonstrates the benefits of linking cohort data to routinely-collected child health data.",,doi:https://doi.org/10.1016/j.vaccine.2022.06.080; doi:https://doi.org/10.1016/j.vaccine.2022.06.080; html:https://europepmc.org/articles/PMC10499753; pdf:https://europepmc.org/articles/PMC10499753?pdf=render 36369983,https://doi.org/10.1093/eurheartj/ehac650,Fit for the future: empowering clinical trials with digital technology.,"Kotecha D, DeVore AD, Asselbergs FW.",,European heart journal,2023,2023-01-01,N,,,,,,pdf:https://discovery.ucl.ac.uk/10159909/1/Asselbergs_EHJ%20digital%20viewpoint%202022_final%20accepted.pdf; doi:https://doi.org/10.1093/eurheartj/ehac650 +35842339,https://doi.org/10.1016/j.vaccine.2022.06.080,Linking cohort data and Welsh routine health records to investigate children at risk of delayed primary vaccination.,"Walton S, Cortina-Borja M, Dezateux C, Griffiths LJ, Tingay K, Akbari A, Bandyopadhyay A, Lyons RA, Roberts R, Bedford H.",,Vaccine,2022,2022-07-13,Y,Child; Vaccination; Dtp Vaccine; Timeliness; Child Health Systems; Millennium Cohort Study (Mcs),,,"

Background

Delayed primary vaccination is one of the strongest predictors of subsequent incomplete immunisation. Identifying children at risk of such delay may enable targeting of interventions, thus decreasing vaccine-preventable illness.

Objectives

To explore socio-demographic factors associated with delayed receipt of the Diphtheria, Tetanus and Pertussis (DTP) vaccine.

Methods

We included 1,782 children, born between 2000 and 2001, participating in the Millennium Cohort Study (MCS) and resident in Wales, whose parents gave consent for linkage to National Community Child Health Database records at the age seven years contact. We examined child, maternal, family and area characteristics associated with delayed receipt of the first dose of the DTP vaccine.

Results

98.6% received the first dose of DTP. The majority, 79.6% (n = 1,429) received it on time (between 8 and 12 weeks of age), 14.2% (n = 251) received it early (prior to 8 weeks of age) and 4.8% (n = 79) were delayed (after 12 weeks of age); 1.4% (n = 23) never received it. Delayed primary vaccination was more likely among children with older natural siblings (risk ratio 3.82, 95% confidence interval (1.97, 7.38)), children admitted to special/intensive care (3.15, (1.65, 5.99)), those whose birth weight was > 4Kg (2.02, (1.09, 3.73)) and boys (1.53, (1.01, 2.31)). There was a reduced risk of delayed vaccination with increasing maternal age (0.73, (0.53, 1.00) per 5 year increase) and for babies born to graduate mothers (0.27, (0.08, 0.90)).

Conclusions

Although the majority of infants were vaccinated in a timely manner, identification of infants at increased risk of early or delayed vaccination will enable targeting of interventions to facilitate timely immunisation. This is to our knowledge the first study exploring individual level socio-demographic factors associated with delayed primary vaccination in the UK and demonstrates the benefits of linking cohort data to routinely-collected child health data.",,doi:https://doi.org/10.1016/j.vaccine.2022.06.080; doi:https://doi.org/10.1016/j.vaccine.2022.06.080; html:https://europepmc.org/articles/PMC10499753; pdf:https://europepmc.org/articles/PMC10499753?pdf=render 37740900,https://doi.org/10.1093/ageing/afad176,Interventions for reducing anticholinergic medication burden in older adults-a systematic review and meta-analysis.,"Braithwaite E, Todd OM, Atkin A, Hulatt R, Tadrous R, Alldred DP, Pirmohamed M, Walker L, Lawton R, Clegg A.",,Age and ageing,2023,2023-09-01,Y,Cognition; Meta-analysis; Systematic review; Falls; Older People; Older Adult; Anticholinergic Medication,,,"

Introduction

Anticholinergic medications block the neurotransmitter acetylcholine in the brain and peripheral nervous system. Many medications have anticholinergic properties, and the cumulative effect of these medications is termed anticholinergic burden. Increased anticholinergic burden can have short-term side effects such as dry mouth, blurred vision and urinary retention as well as long-term effects including dementia, worsening physical function and falls.

Methods

We carried out a systematic review (SR) with meta-analysis (MA) looking at randomised controlled trials addressing interventions to reduce anticholinergic burden in older adults.

Results

We identified seven papers suitable for inclusion in our SR and MA. Interventions included multi-disciplinary involvement in medication reviews and deprescribing of AC medications. Pooled data revealed no significant difference in outcomes between control and intervention group for falls (OR = 0.76, 95% CI: 0.52-1.11, n = 647), cognition (mean difference = 1.54, 95% CI: -0.04 to 3.13, n = 405), anticholinergic burden (mean difference = 0.04, 95% CI: -0.11 to 0.18, n = 710) or quality of life (mean difference = 0.04, 95% CI: -0.04 to 0.12, n = 461).

Discussion

Overall, there was no significant difference with interventions to reduce anticholinergic burden. As we did not see a significant change in anticholinergic burden scores following interventions, it is likely other outcomes would not change. Short follow-up time and lack of training and support surrounding successful deprescribing may have contributed.",,pdf:https://academic.oup.com/ageing/article-pdf/52/9/afad176/51729004/afad176.pdf; doi:https://doi.org/10.1093/ageing/afad176; html:https://europepmc.org/articles/PMC10517713; pdf:https://europepmc.org/articles/PMC10517713?pdf=render 33328049,https://doi.org/10.1016/s2589-7500(20)30219-3,Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI extension.,"Cruz Rivera S, Liu X, Chan AW, Denniston AK, Calvert MJ, SPIRIT-AI and CONSORT-AI Working Group.",,The Lancet. Digital health,2020,2020-09-09,Y,,,,"The SPIRIT 2013 statement aims to improve the completeness of clinical trial protocol reporting by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes. The SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trial protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 26 candidate items, which were consulted upon by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The SPIRIT-AI extension includes 15 new items that were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations for the handling of input and output data, the human-AI interaction and analysis of error cases. SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer reviewers, as well as the general readership, to understand, interpret, and critically appraise the design and risk of bias for a planned clinical trial.",,pdf:http://www.thelancet.com/article/S2589750020302193/pdf; doi:https://doi.org/10.1016/S2589-7500(20)30219-3; html:https://europepmc.org/articles/PMC8212701; pdf:https://europepmc.org/articles/PMC8212701?pdf=render 34871122,https://doi.org/10.1080/09638288.2021.2008526,Pain and mental health symptom patterns and treatment trajectories following road trauma: a registry-based cohort study.,"Huang S, Dipnall JF, Gabbe BJ, Giummarra MJ.",,Disability and rehabilitation,2022,2021-12-06,N,Injury; Recovery; Pain; Mental health; Healthcare Use,,,"

Purpose

This study aimed to characterise recovery from pain and mental health symptoms, and identify whether treatment use facilitates recovery.

Methods

Victorian State Trauma Registry and Victorian Orthopaedic Trauma Outcomes Registry participants without neurotrauma who had transport injury claims with the Transport Accident Commission from 2007 to 2014 were included (n = 5908). Latent transition analysis of pain Numeric Rating Scale, SF-12, and EQ-5D-3L pain and mental health items from 6 to 12 months, and 12 to 24 months post-injury were used to identify symptom transitions.

Results

Four transition groups were identified: transition to low problems by 12-months; transition to low problems at 24-months; stable low problems; and no transition from problems. Group-based trajectory modelling of pain and mental health treatments found three treatment trajectories: low/no treatment, a moderate treatment that declined to low treatment 3-12 months post-injury, and increasing treatment over time. Predictors of pain and mental health recovery transitions, identified using multinomial logistic regression, were primarily found to be non-modifiable socioeconomic and health-related characteristics (e.g., higher education, working pre-injury, and not having comorbidities), and low treatment trajectories.

Conclusions

Targeted and collaborative rehabilitation should be considered for people at risk of persistent pain or mental health symptoms to optimise their recovery, particularly patients with socioeconomic disadvantage.IMPLICATIONS FOR REHABILITATIONTwo-thirds of people experience pain and/or mental health within the first 24-months after hospitalization for road trauma, of whom only 6-7% recover by 12-months, and a further 6% recover by 24-months post-injury.There were three main trajectories of administrative records of treatments received in the first two years after injury: 76 and 83% had low treatment, 18 and 12% had moderate then declining treatment levels, and 6 and 5% had stable high treatment for pain or mental health, respectively.People who recovered from pain or mental health symptoms generally had lower treatment and higher socioeconomic position, highlighting that coordinated rehabilitation care should be prioritized for people living with socioeconomic disadvantage.",,doi:https://doi.org/10.1080/09638288.2021.2008526 34053271,https://doi.org/10.1098/rstb.2020.0266,Real-time monitoring of COVID-19 dynamics using automated trend fitting and anomaly detection.,"Jombart T, Ghozzi S, Schumacher D, Taylor TJ, Leclerc QJ, Jit M, Flasche S, Greaves F, Ward T, Eggo RM, Nightingale E, Meakin S, Brady OJ, Centre for Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Medley GF, Höhle M, Edmunds WJ.",,"Philosophical transactions of the Royal Society of London. Series B, Biological sciences",2021,2021-05-31,Y,Algorithm; Surveillance; outbreak; Machine Learning; Asmodee; Trendbreaker,,,"As several countries gradually release social distancing measures, rapid detection of new localized COVID-19 hotspots and subsequent intervention will be key to avoiding large-scale resurgence of transmission. We introduce ASMODEE (automatic selection of models and outlier detection for epidemics), a new tool for detecting sudden changes in COVID-19 incidence. Our approach relies on automatically selecting the best (fitting or predicting) model from a range of user-defined time series models, excluding the most recent data points, to characterize the main trend in an incidence. We then derive prediction intervals and classify data points outside this interval as outliers, which provides an objective criterion for identifying departures from previous trends. We also provide a method for selecting the optimal breakpoints, used to define how many recent data points are to be excluded from the trend fitting procedure. The analysis of simulated COVID-19 outbreaks suggests ASMODEE compares favourably with a state-of-art outbreak-detection algorithm while being simpler and more flexible. As such, our method could be of wider use for infectious disease surveillance. We illustrate ASMODEE using publicly available data of National Health Service (NHS) Pathways reporting potential COVID-19 cases in England at a fine spatial scale, showing that the method would have enabled the early detection of the flare-ups in Leicester and Blackburn with Darwen, two to three weeks before their respective lockdown. ASMODEE is implemented in the free R package trendbreaker. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.",,doi:https://doi.org/10.1098/rstb.2020.0266; doi:https://doi.org/10.1098/rstb.2020.0266; html:https://europepmc.org/articles/PMC8165581; pdf:https://europepmc.org/articles/PMC8165581?pdf=render 32065794,https://doi.org/10.3233/jad-191163,Working Towards a Blood-Derived Gene Expression Biomarker Specific for Alzheimer's Disease.,"Patel H, Iniesta R, Stahl D, Dobson RJB, Newhouse SJ.",,Journal of Alzheimer's disease : JAD,2020,2020-01-01,Y,Human; Biomarkers; Alzheimer’s disease; Dementia; Gene Expression; Neurodegenerative Disorders; Machine Learning; Microarray Analysis; Age-related Memory Disorders,,,"

Background

The typical approach to identify blood-derived gene expression signatures as a biomarker for Alzheimer's disease (AD) have relied on training classification models using AD and healthy controls only. This may inadvertently result in the identification of markers for general illness rather than being disease-specific.

Objective

Investigate whether incorporating additional related disorders in the classification model development process can lead to the discovery of an AD-specific gene expression signature.

Methods

Two types of XGBoost classification models were developed. The first used 160 AD and 127 healthy controls and the second used the same 160 AD with 6,318 upsampled mixed controls consisting of Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, bipolar disorder, schizophrenia, coronary artery disease, rheumatoid arthritis, chronic obstructive pulmonary disease, and cognitively healthy subjects. Both classification models were evaluated in an independent cohort consisting of 127 AD and 687 mixed controls.

Results

The AD versus healthy control models resulted in an average 48.7% sensitivity (95% CI = 34.7-64.6), 41.9% specificity (95% CI = 26.8-54.3), 13.6% PPV (95% CI = 9.9-18.5), and 81.1% NPV (95% CI = 73.3-87.7). In contrast, the mixed control models resulted in an average of 40.8% sensitivity (95% CI = 27.5-52.0), 95.3% specificity (95% CI = 93.3-97.1), 61.4% PPV (95% CI = 53.8-69.6), and 89.7% NPV (95% CI = 87.8-91.4).

Conclusions

This early work demonstrates the value of incorporating additional related disorders into the classification model developmental process, which can result in models with improved ability to distinguish AD from a heterogeneous aging population. However, further improvement to the sensitivity of the test is still required.",,pdf:https://content.iospress.com:443/download/journal-of-alzheimers-disease/jad191163?id=journal-of-alzheimers-disease%2Fjad191163; doi:https://doi.org/10.3233/JAD-191163; html:https://europepmc.org/articles/PMC7175937; pdf:https://europepmc.org/articles/PMC7175937?pdf=render 35188950,https://doi.org/10.1001/jamaneurol.2021.5420,Risk Factors and Prognosis of Early Posttraumatic Seizures in Moderate to Severe Traumatic Brain Injury.,"Laing J, Gabbe B, Chen Z, Perucca P, Kwan P, O'Brien TJ.",,JAMA neurology,2022,2022-04-01,N,,,,"

Importance

Early posttraumatic seizures (EPS) that may occur following a traumatic brain injury (TBI) are associated with poorer outcomes and development of posttraumatic epilepsy (PTE).

Objective

To evaluate risk factors for EPS, associated morbidity and mortality, and contribution to PTE.

Design, setting, and participants

Data were collected from an Australian registry-based cohort study of adults (age ≥18 years) with moderate to severe TBI from January 2005 to December 2019, with 2-year follow-up. The statewide trauma registry, conducted on an opt-out basis in Victoria (population 6.5 million), had 15 152 patients with moderate to severe TBI identified via Abbreviated Injury Scale (AIS) head severity score, with an opt-out rate less than 0.5% (opt-out n = 136).

Main outcomes and measures

EPS were identified via International Statistical Classification of Diseases, Tenth Revision, Australian Modification (ICD-10-AM) codes recorded after the acute admission. Outcome measures also included in-hospital metrics, 2-year outcomes including PTE, and post-discharge mortality. Adaptive least absolute shrinkage and selection operator (LASSO) regression was used to build a prediction model for risk factors of EPS.

Results

Among the 15 152 participants (10 457 [69%] male; median [IQR] age, 60 [35-79] y), 416 (2.7%) were identified with EPS, including 27 (0.2%) with status epilepticus. Significant risk factors on multivariable analysis for developing EPS were younger age, higher Charlson Comorbidity Index, TBI sustained from a low fall, subdural hemorrhage, subarachnoid hemorrhage, higher Injury Severity Score, and greater head injury severity, measured using the AIS and Glasgow Coma Score. After adjustment for confounders, EPS were associated with increased ICU admission and ICU length of stay, ventilation and duration, hospital length of stay, and discharge to inpatient rehabilitation rather than home, but not in-hospital mortality. Outcomes in TBI admission survivors at 24 months, including mortality (relative risk [RR] = 2.14; 95% CI, 1.32-3.46; P = .002), development of PTE (RR = 2.91; 95% CI, 2.22-3.81; P < .001), and use of antiseizure medications (RR = 2.44; 95% CI, 1.98-3.02; P < .001), were poorer for cases with EPS after adjustment for confounders. The prediction model for EPS had an area under the receiver operating characteristic curve of 0.72 (95% CI, 0.66-0.79), sensitivity of 66%, and specificity of 73% in the validation set.

Discussion

We identified important risk factors for EPS following moderate to severe TBI. Early posttraumatic seizures were associated with longer ICU and hospital admissions, ICU ventilation, and poorer 24-month outcomes including mortality and development of PTE.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861899; doi:https://doi.org/10.1001/jamaneurol.2021.5420; html:https://europepmc.org/articles/PMC8861899; doi:https://doi.org/10.1001/jamaneurol.2021.5420 -38091687,https://doi.org/10.1016/j.bjps.2023.10.106,Revisiting basal cell carcinoma clinical margins: Leveraging natural language processing and multivariate analysis with updated Royal College of Pathologists histological reporting standards.,"Ali SR, Dobbs TD, Jovic M, Strafford H, Lacey AS, Williams N, Pickrell WO, Hutchings HA, Whitaker IS.",,"Journal of plastic, reconstructive & aesthetic surgery : JPRAS",2024,2023-10-20,N,multivariate analysis; Royal College Of Pathologists; Basal Cell Carcinoma; Natural Language Processing; Clinical Margins; Histological Reporting Guidelines,,,"

Introduction

Data supporting the current British Association of Dermatologists guidelines for the management of basal cell carcinoma (BCC) are based on historic studies and do not consider the updated Royal College of Pathologists (RCPath) histological reporting standards. The aim of this study was to use natural language processing (NLP)-derived data and undertake a multivariate analysis with updated RCPath standards, providing a contemporary update on the excision margins required to achieve histological clearance in BCC.

Methods

A validated NLP information extraction model was used to perform a rapid multi-centre, pan-specialty, consecutive retrospective analysis of BCCs, managed with surgical excision using a pre-determined clinical margin, over a 17-year period (2004-2021) at Swansea Bay University Health Board. Logistic regression assessed the relationship between the peripheral and deep margins and histological clearance.

Results

We ran our NLP algorithm on 34,955 BCCs. Out of the 1447 BCCs that met the inclusion criteria, the peripheral margin clearance was not influenced by the BCC risk level (p = 0.670). A clinical peripheral margin of 6 mm achieved a 95% histological clearance rate (95% confidence interval [CI], 0.93-0.98). Tumour thickness inversely affected deep-margin histological clearance (OR 0.720, 95% CI, 0.525-0.991, p < 0.05). Depth level 2 had a 97% probability of achieving deep-margin histological clearance across all tumour thicknesses.

Conclusion

Updated RCPath reporting standards minimally impact the peripheral margin histological clearance in BCC. Larger clinical peripheral margins than those indicated by current guidelines may be necessary to achieve excision rates of ≥95%. These findings emphasise the need for continuous reassessment of clinical standards to enhance patient care.",,pdf:http://www.jprasurg.com/article/S1748681523006769/pdf; doi:https://doi.org/10.1016/j.bjps.2023.10.106 37505992,https://doi.org/10.1093/ageing/afad136,The extent of anticholinergic burden across an older Welsh population living with frailty: cross-sectional analysis of general practice records.,"Cheong VL, Mehdizadeh D, Todd OM, Gardner P, Zaman H, Clegg A, Alldred DP, Faisal M.",,Age and ageing,2023,2023-07-01,Y,Frailty; Older People; Older Adults; Routine Data; Anticholinergic Burden; Structured Medication Review,,,"

Background

Anticholinergic medicines are associated with adverse outcomes for older people. However, little is known about their use in frailty. The objectives were to (i) investigate the prevalence of anticholinergic prescribing for older patients, and (ii) examine anticholinergic burden according to frailty status.

Methods

Cross-sectional analysis of Welsh primary care data from the Secure Anonymised Information Linkage databank including patients aged ≥65 at their first GP consultation between 1 January and 31 December 2018. Frailty was identified using the electronic Frailty Index and anticholinergic burden using the Anticholinergic Cognitive Burden (ACB) scale. Descriptive analysis and logistic regression were conducted to (i) describe the type and frequency of anticholinergics prescribed; and (ii) to estimate the association between frailty and cumulative ACB score (ACB-Sum).

Results

In this study of 529,095 patients, 47.4% of patients receiving any prescription medications were prescribed at least one anticholinergic medicine. Adjusted regression analysis showed that patients with increasing frailty had higher odds of having an ACB-Sum of >3 compared with patients who were fit (mild frailty, adj OR 1.062 (95%CI 1.061-1.064), moderate frailty, adj OR 1.134 (95%CI 1.131-1.136), severe frailty, adj OR 1.208 (95%CI 1.203-1.213)).

Conclusions

Anticholinergic prescribing was high in this older population. Older people with advancing frailty are exposed to the highest anticholinergic burden despite being the most vulnerable to the associated adverse effects. Older people with advancing frailty should be considered for medicines review to prevent overaccumulation of anticholinergic medications, given the risks of functional and cognitive decline that frailty presents.",,pdf:https://academic.oup.com/ageing/article-pdf/52/7/afad136/50976589/afad136.pdf; doi:https://doi.org/10.1093/ageing/afad136; html:https://europepmc.org/articles/PMC10378723; pdf:https://europepmc.org/articles/PMC10378723?pdf=render +38091687,https://doi.org/10.1016/j.bjps.2023.10.106,Revisiting basal cell carcinoma clinical margins: Leveraging natural language processing and multivariate analysis with updated Royal College of Pathologists histological reporting standards.,"Ali SR, Dobbs TD, Jovic M, Strafford H, Lacey AS, Williams N, Pickrell WO, Hutchings HA, Whitaker IS.",,"Journal of plastic, reconstructive & aesthetic surgery : JPRAS",2024,2023-10-20,N,multivariate analysis; Royal College Of Pathologists; Basal Cell Carcinoma; Natural Language Processing; Clinical Margins; Histological Reporting Guidelines,,,"

Introduction

Data supporting the current British Association of Dermatologists guidelines for the management of basal cell carcinoma (BCC) are based on historic studies and do not consider the updated Royal College of Pathologists (RCPath) histological reporting standards. The aim of this study was to use natural language processing (NLP)-derived data and undertake a multivariate analysis with updated RCPath standards, providing a contemporary update on the excision margins required to achieve histological clearance in BCC.

Methods

A validated NLP information extraction model was used to perform a rapid multi-centre, pan-specialty, consecutive retrospective analysis of BCCs, managed with surgical excision using a pre-determined clinical margin, over a 17-year period (2004-2021) at Swansea Bay University Health Board. Logistic regression assessed the relationship between the peripheral and deep margins and histological clearance.

Results

We ran our NLP algorithm on 34,955 BCCs. Out of the 1447 BCCs that met the inclusion criteria, the peripheral margin clearance was not influenced by the BCC risk level (p = 0.670). A clinical peripheral margin of 6 mm achieved a 95% histological clearance rate (95% confidence interval [CI], 0.93-0.98). Tumour thickness inversely affected deep-margin histological clearance (OR 0.720, 95% CI, 0.525-0.991, p < 0.05). Depth level 2 had a 97% probability of achieving deep-margin histological clearance across all tumour thicknesses.

Conclusion

Updated RCPath reporting standards minimally impact the peripheral margin histological clearance in BCC. Larger clinical peripheral margins than those indicated by current guidelines may be necessary to achieve excision rates of ≥95%. These findings emphasise the need for continuous reassessment of clinical standards to enhance patient care.",,pdf:http://www.jprasurg.com/article/S1748681523006769/pdf; doi:https://doi.org/10.1016/j.bjps.2023.10.106 36707908,https://doi.org/10.1186/s13643-023-02173-w,A comparison of international modelling methods to evaluate health economics of colorectal cancer screening: a systematic review protocol.,"Adair O, McFerran E, Owen T, McKee C, Lamrock F, Lawler M.",,Systematic reviews,2023,2023-01-27,Y,Screening; Economic evaluation; Colorectal Cancer; Health Economics; Cost-effectiveness Analysis; Quality-adjusted Life Years; Cost-utility; Incremental Cost-effectiveness Ratio; Cost–benefit; Life Years Gained,,,"

Background

Colorectal cancer (CRC) is becoming an increasing health problem worldwide. However, with the help of screening, early diagnosis can reduce incidence and mortality rates. To elevate the economic burden that CRC can cause, cost-effectiveness analysis (CEA) can assist healthcare systems to make screening programmes more cost-effective and prolong survival for early-stage CRC patients. This review aims to identify different CEA modelling methods used internationally to evaluate health economics of CRC screening.

Methods

This review will systematically search electronic databases which include MEDLINE, EMBASE, Web of Science and Scopus. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidance recommendations will design the review, and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement will be used to extract relevant data from studies retrieved. Two reviewers will screen through the evidence using the PICOS (Participant, Intervention, Comparators, Outcomes, Study Design) framework, with a third reviewer to settle any disagreements. Once data extraction and quality assessment are complete, the results will be presented qualitatively and tabulated using the CHEERS checklist.

Discussion

The results obtained from the systematic review will highlight how different CRC screening programmes around the world utilise and incorporate health economic modelling methods to be more cost-effective. This information can help modellers develop CEA models which can be adapted to suit the specific screening programmes that they are evaluating.

Systematic review registration

PROSPERO CRD42022296113.",,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02173-w; doi:https://doi.org/10.1186/s13643-023-02173-w; html:https://europepmc.org/articles/PMC9883863; pdf:https://europepmc.org/articles/PMC9883863?pdf=render 34912046,https://doi.org/10.1038/s41366-021-01048-1,"30-day morbidity and mortality of sleeve gastrectomy, Roux-en-Y gastric bypass and one anastomosis gastric bypass: a propensity score-matched analysis of the GENEVA data.","Singhal R, Cardoso VR, Wiggins T, Super J, Ludwig C, Gkoutos GV, Mahawar K, GENEVA Collaborators.",,International journal of obesity (2005),2022,2021-12-15,Y,,,,"

Background

There is a paucity of data comparing 30-day morbidity and mortality of sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and one anastomosis gastric bypass (OAGB). This study aimed to compare the 30-day safety of SG, RYGB, and OAGB in propensity score-matched cohorts.

Materials and methods

This analysis utilised data collected from the GENEVA study which was a multicentre observational cohort study of bariatric and metabolic surgery (BMS) in 185 centres across 42 countries between 01/05/2022 and 31/10/2020 during the Coronavirus Disease-2019 (COVID-19) pandemic. 30-day complications were categorised according to the Clavien-Dindo classification. Patients receiving SG, RYGB, or OAGB were propensity-matched according to baseline characteristics and 30-day complications were compared between groups.

Results

In total, 6770 patients (SG 3983; OAGB 702; RYGB 2085) were included in this analysis. Prior to matching, RYGB was associated with highest 30-day complication rate (SG 5.8%; OAGB 7.5%; RYGB 8.0% (p = 0.006)). On multivariate regression modelling, Insulin-dependent type 2 diabetes mellitus and hypercholesterolaemia were associated with increased 30-day complications. Being a non-smoker was associated with reduced complication rates. When compared to SG as a reference category, RYGB, but not OAGB, was associated with an increased rate of 30-day complications. A total of 702 pairs of SG and OAGB were propensity score-matched. The complication rate in the SG group was 7.3% (n = 51) as compared to 7.5% (n = 53) in the OAGB group (p = 0.68). Similarly, 2085 pairs of SG and RYGB were propensity score-matched. The complication rate in the SG group was 6.1% (n = 127) as compared to 7.9% (n = 166) in the RYGB group (p = 0.09). And, 702 pairs of OAGB and RYGB were matched. The complication rate in both groups was the same at 7.5 % (n = 53; p = 0.07).

Conclusions

This global study found no significant difference in the 30-day morbidity and mortality of SG, RYGB, and OAGB in propensity score-matched cohorts.",,pdf:https://www.nature.com/articles/s41366-021-01048-1.pdf; doi:https://doi.org/10.1038/s41366-021-01048-1; html:https://europepmc.org/articles/PMC8671878; pdf:https://europepmc.org/articles/PMC8671878?pdf=render 37606853,https://doi.org/10.1007/s00520-023-07944-8,"The impact of the COVID-19 pandemic on community prescription of opioid and antineuropathic analgesics for cancer patients in Wales, UK.","Han J, Rolles M, Torabi F, Griffiths R, Bedston S, Akbari A, Burnett B, Lyons J, Greene G, Thomas R, Long T, Arnold C, Huws DW, Lawler M, Lyons RA.",,Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer,2023,2023-08-22,Y,Analgesia; Cancer; Pain; Primary Care; Prescription; Covid-19 Pandemic,,,"

Purpose

Public health measures instituted at the onset of the COVID-19 pandemic in the UK in 2020 had profound effects on the cancer patient pathway. We hypothesise that this may have affected analgesic prescriptions for cancer patients in primary care.

Methods

A whole-nation retrospective, observational study of opioid and antineuropathic analgesics prescribed in primary care for two cohorts of cancer patients in Wales, using linked anonymised data to evaluate the impact of the pandemic and variation between different demographic backgrounds.

Results

We found a significant increase in strong opioid prescriptions during the pandemic for patients within their first 12 months of diagnosis with a common cancer (incidence rate ratio (IRR) 1.15, 95% CI: 1.12-1.18, p < 0.001 for strong opioids) and significant increases in strong opioid and antineuropathic prescriptions for patients in the last 3 months prior to a cancer-related death (IRR = 1.06, 95% CI: 1.04-1.07, p < 0.001 for strong opioids; IRR = 1.11, 95% CI: 1.08-1.14, p < 0.001 for antineuropathics). A spike in opioid prescriptions for patients diagnosed in Q2 2020 and those who died in Q2 2020 was observed and interpreted as stockpiling. More analgesics were prescribed in more deprived quintiles. This differential was less pronounced in patients towards the end of life, which we attribute to closer professional supervision.

Conclusions

We demonstrate significant changes to community analgesic prescriptions for cancer patients related to the UK pandemic and illustrate prescription patterns linked to patients' demographic background.",,pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07944-8.pdf; doi:https://doi.org/10.1007/s00520-023-07944-8; html:https://europepmc.org/articles/PMC10444652; pdf:https://europepmc.org/articles/PMC10444652?pdf=render 38023948,https://doi.org/10.18332/ejm/171802,A qualitative study exploring healthcare workers' lived experiences of the impacts of COVID-19 policies and guidelines on maternal and reproductive healthcare services in the United Kingdom.,"Chaloner J, Qureshi I, Gogoi M, Ekezie WC, Al-Oraibi A, Wobi F, Agbonmwandolor JO, Nellums LB, Pareek M.",,European journal of midwifery,2023,2023-11-08,Y,Healthcare Workers; Vaccine Hesitancy; Redeployment; Infection Controls; Covid-19; Policies And Guidelines,,,"

Introduction

During the COVID-19 pandemic, pregnant women were regarded as vulnerable to poor health outcomes if infected with the SARS-CoV-2 (COVID-19) virus. To protect the United Kingdom's (UK) National Health Service (NHS) and pregnant patients, strict infection control policies and regulations were implemented. This study aimed to understand the impact of the COVID-19 policies and guidelines on maternal and reproductive health services during the pandemic from the experiences of healthcare workers (HCWs) caring for these patients.

Methods

This qualitative study involved HCWs from the United Kingdom Research study into Ethnicity and COVID-19 outcomes in Healthcare workers (UK-REACH) project. Semi-structured interviews and focus groups were conducted online or by telephone with 44 diverse HCWs. Transcripts were thematically analyzed following Braun and Clarke's principles of qualitative analysis.

Results

Three key themes were identified during analysis. First, infection control policies impacted appointment availability, resulting in many cancellations and delays to treatment. Telemedicine was also used extensively to reduce risks from face-to-face consultations, disadvantaging patients from minoritized ethnicities. Secondly, staff shortages and redeployments reduced availability of consultations, appointments, and sonography scans. Finally, staff and patients reported challenges accessing timely, reliable and accurate information and guidance.

Conclusions

COVID-19 demonstrated how a global health crisis can impact maternal and reproductive health services, leading to reduced service quality and surgical delays due to staff redeployment policies. Our findings underscore the implications of policy and future health crises preparedness. This includes tailored infection control policies, addressing elective surgery backlogs early and improved dissemination of relevant vaccine information.",,pdf:https://www.europeanjournalofmidwifery.eu/pdf-171802-96110?filename=A qualitative study.pdf; doi:https://doi.org/10.18332/ejm/171802; html:https://europepmc.org/articles/PMC10630987; pdf:https://europepmc.org/articles/PMC10630987?pdf=render 30659777,https://doi.org/10.1111/ijpo.12505,Are children with clinical obesity at increased risk of inpatient hospital admissions? An analysis using linked electronic health records in the UK millennium cohort study.,"Griffiths LJ, Cortina-Borja M, Bandyopadhyay A, Tingay K, De Stavola BL, Bedford H, Akbari A, Firman N, Lyons RA, Dezateux C.",,Pediatric obesity,2019,2019-01-18,Y,Obesity; Cohort study; Record Linkage; Health Service Utilization,Improving Public Health,,"

Background

Few studies have examined health service utilization of children with overweight or obesity by using linked electronic health records (EHRs).

Objective/methods

We analysed EHRs from 3269 children (1678 boys; 51.3% [weighted]) participating in the Millennium Cohort Study, living in Wales or Scotland at age seven whose parents consented to record linkage. We used height and weight measurements at age five to categorize children as obese (>98th centile) or overweight (>91st centile) (UK1990 clinical reference standards) and linked to hospital admissions, up to age 14 years, in the Patient Episode Database for Wales and Scottish Morbidity Records. Negative binomial regression models compared rates of inpatient admissions by weight status at age five.

Results

At age five, 11.5% and 6.7% of children were overweight or obese, respectively; 1221 (38%) children were subsequently admitted to hospital at least once. Admissions were not increased among children with overweight or obesity (adjusted rate ratio [RR], 95% confidence interval [CI]: 0.87, 0.68-1.10 and 1.16, 0.87-1.54, respectively).

Conclusions

In this nationally representative cohort of children in Wales and Scotland, those with overweight or obesity at entry to primary school did not have increased rates of hospital admissions in later childhood and early adolescence.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/ijpo.12505; doi:https://doi.org/10.1111/ijpo.12505; html:https://europepmc.org/articles/PMC6563186; pdf:https://europepmc.org/articles/PMC6563186?pdf=render 32771960,https://doi.org/10.1016/j.ijmedinf.2020.104237,Core competencies for clinical informaticians: A systematic review.,"Davies A, Mueller J, Moulton G.",,International journal of medical informatics,2020,2020-07-24,N,Bioinformatics; Health; Clinical; Pharmacy; Skills; Informatics; Requirements; Core Competencies; Healthcare Data Science,,,"

Background

Building on initial work carried out by the Faculty of Clinical Informatics (FCI) in the UK, the creation of a national competency framework for Clinical Informatics is required for the definition of clinical informaticians' professional attributes and skills. We aimed to systematically review the academic literature relating to competencies, skills and existing course curricula in the clinical and health related informatics domains.

Methods

Two independent reviewers searched Web of Science, EMBASE, ERIC, PubMed and CINAHL. Publications were included if they reported details of relevant competencies, skills and existing course curricula. We report findings using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement.

Results

A total of 82 publications were included. The most frequently used method was surveys (30 %) followed by narrative descriptions (28 %). Most of the publications describe curriculum design (23 %) followed by competency definition (18 %) and skills, qualifications & training (18 %). Core skills surrounding data, information systems and information management appear to be cross-cutting across the various informatics disciplines with Bioinformatics and Pharmacy Informatics expressing the most unique competency requirements.

Conclusion

We identified eight key domains that cut across the different sub-disciplines of health informatics, including data, information management, human factors, project management, research skills/knowledge, leadership and management, systems development and evaluation, and health/healthcare. Some informatics disciplines such as Nursing Informatics appear to be further ahead at achieving widespread competency standardisation. Attempts at standardisation for competencies should be tempered with flexibility to allow for local variation and requirements.",,doi:https://doi.org/10.1016/j.ijmedinf.2020.104237 -38660106,https://doi.org/10.1016/j.jacasi.2024.02.003,Depression and Incident Cardiovascular Disease.,"Pennells L, Mascie-Taylor CGN.",,JACC. Asia,2024,2024-04-03,Y,Sex difference; Depression; Cardiovascular disease; epidemiology,,,,,doi:https://doi.org/10.1016/j.jacasi.2024.02.003; html:https://europepmc.org/articles/PMC11035929; pdf:https://europepmc.org/articles/PMC11035929?pdf=render 35642867,https://doi.org/10.1111/bjhp.12606,"Perceived threat of COVID-19, attitudes towards vaccination, and vaccine hesitancy: A prospective longitudinal study in the UK.","Phillips R, Gillespie D, Hallingberg B, Evans J, Taiyari K, Torrens-Burton A, Cannings-John R, Williams D, Sheils E, Ashfield-Watt P, Akbari A, Hughes K, Thomas-Jones E, James D, Wood F.",,British journal of health psychology,2022,2022-06-01,Y,Risk Perception; Behaviour Change; Vaccine Hesitancy; Covid-19; Sars Cov2,,,"

Objectives

Using the Health Belief Model as a conceptual framework, we investigated the association between attitudes towards COVID-19, COVID-19 vaccinations, and vaccine hesitancy and change in these variables over a 9-month period in a UK cohort.

Methods

The COPE study cohort (n = 11,113) was recruited via an online survey at enrolment in March/April 2020. The study was advertised via the HealthWise Wales research registry and social media. Follow-up data were available for 6942 people at 3 months (June/July 2020) and 5037 at 12 months (March/April 2021) post-enrolment. Measures included demographics, perceived threat of COVID-19, perceived control, intention to accept or decline a COVID-19 vaccination, and attitudes towards vaccination. Logistic regression models were fitted cross-sectionally at 3 and 12 months to assess the association between motivational factors and vaccine hesitancy. Longitudinal changes in motivational variables for vaccine-hesitant and non-hesitant groups were examined using mixed-effect analysis of variance models.

Results

Fear of COVID-19, perceived susceptibility to COVID-19, and perceived personal control over COVID-19 infection transmission decreased between the 3- and 12-month surveys. Vaccine hesitancy at 12 months was independently associated with low fear of the disease and more negative attitudes towards COVID-19 vaccination. Specific barriers to COVID-19 vaccine uptake included concerns about safety and efficacy in light of its rapid development, mistrust of government and pharmaceutical companies, dislike of coercive policies, and perceived lack of relaxation in COVID-19-related restrictions as the vaccination programme progressed.

Conclusions

Decreasing fear of COVID-19, perceived susceptibility to the disease, and perceptions of personal control over reducing infection-transmission may impact future COVID-19 vaccination uptake.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa60128/Download/60128__24479__4d74009536e649b0b17180e2bfd80435.pdf; doi:https://doi.org/10.1111/bjhp.12606; html:https://europepmc.org/articles/PMC9347957; pdf:https://europepmc.org/articles/PMC9347957?pdf=render +38660106,https://doi.org/10.1016/j.jacasi.2024.02.003,Depression and Incident Cardiovascular Disease.,"Pennells L, Mascie-Taylor CGN.",,JACC. Asia,2024,2024-04-03,Y,Sex difference; Depression; Cardiovascular disease; epidemiology,,,,,doi:https://doi.org/10.1016/j.jacasi.2024.02.003; html:https://europepmc.org/articles/PMC11035929; pdf:https://europepmc.org/articles/PMC11035929?pdf=render 36501061,https://doi.org/10.3390/nu14235031,Associations of Genetically Predicted Vitamin B12 Status across the Phenome.,"Dib MJ, Ahmadi KR, Zagkos L, Gill D, Morris B, Elliott P, Dehghan A, Tzoulaki I.",,Nutrients,2022,2022-11-26,Y,Vitamin B12; Deficiency; epidemiology; Mendelian Randomisation; Pernicious Anaemia,,,"Variation in vitamin B12 levels has been associated with a range of diseases across the life-course, the causal nature of which remains elusive. We aimed to interrogate genetically predicted vitamin B12 status in relation to a plethora of clinical outcomes available in the UK Biobank. Genome-wide association study (GWAS) summary data obtained from a Danish and Icelandic cohort of 45,576 individuals were used to identify 8 genetic variants associated with vitamin B12 levels, serving as genetic instruments for vitamin B12 status in subsequent analyses. We conducted a Mendelian randomisation (MR)-phenome-wide association study (PheWAS) of vitamin B12 status with 945 distinct phenotypes in 439,738 individuals from the UK Biobank using these 8 genetic instruments to proxy alterations in vitamin B12 status. We used external GWAS summary statistics for replication of significant findings. Correction for multiple testing was taken into consideration using a 5% false discovery rate (FDR) threshold. MR analysis identified an association between higher genetically predicted vitamin B12 status and lower risk of vitamin B deficiency (including all B vitamin deficiencies), serving as a positive control outcome. We further identified associations between higher genetically predicted vitamin B12 status and a reduced risk of megaloblastic anaemia (OR = 0.35, 95% CI: 0.20-0.50) and pernicious anaemia (0.29, 0.19-0.45), which was supported in replication analyses. Our study highlights that higher genetically predicted vitamin B12 status is potentially protective of risk of vitamin B12 deficiency associated with pernicious anaemia diagnosis, and reduces risk of megaloblastic anaemia. The potential use of genetically predicted vitamin B12 status in disease diagnosis, progression and management remains to be investigated.",,pdf:https://www.mdpi.com/2072-6643/14/23/5031/pdf?version=1669449806; doi:https://doi.org/10.3390/nu14235031; html:https://europepmc.org/articles/PMC9740080; pdf:https://europepmc.org/articles/PMC9740080?pdf=render -34859617,https://doi.org/10.1002/edm2.309,The clinical profile and associated mortality in people with and without diabetes with Coronavirus disease 2019 on admission to acute hospital services.,"Gokhale K, Mostafa SA, Wang J, Tahrani AA, Sainsbury CA, Toulis KA, Thomas GN, Hassan-Smith Z, Sapey E, Gallier S, Adderley NJ, Narendran P, Bellary S, Taverner T, Ghosh S, Nirantharakumar K, Hanif W.",,"Endocrinology, diabetes & metabolism",2022,2021-12-03,Y,Diabetes; Complications; Covid-19,,,"

Introduction

To assess if in adults with COVID-19, whether those with diabetes and complications (DM+C) present with a more severe clinical profile and if that relates to increased mortality, compared to those with diabetes with no complications (DM-NC) and those without diabetes.

Methods

Service-level data was used from 996 adults with laboratory confirmed COVID-19 who presented to the Queen Elizabeth Hospital Birmingham, UK, from March to June 2020. All individuals were categorized into DM+C, DM-NC, and non-diabetes groups. Physiological and laboratory measurements in the first 5 days after admission were collated and compared among groups. Cox proportional hazards regression models were used to evaluate associations between diabetes status and the risk of mortality.

Results

Among the 996 individuals, 104 (10.4%) were DM+C, 295 (29.6%) DM-NC and 597 (59.9%) non-diabetes. There were 309 (31.0%) in-hospital deaths documented, 40 (4.0% of total cohort) were DM+C, 99 (9.9%) DM-NC and 170 (17.0%) non-diabetes. Individuals with DM+C were more likely to present with high anion gap/metabolic acidosis, features of renal impairment, and low albumin/lymphocyte count than those with DM-NC or those without diabetes. There was no significant difference in mortality rates among the groups: compared to individuals without diabetes, the adjusted HRs were 1.39 (95% CI 0.95-2.03, p = 0.093) and 1.18 (95% CI 0.90-1.54, p = 0.226) in DM+C and DM-C, respectively.

Conclusions

Those with COVID-19 and DM+C presented with a more severe clinical and biochemical profile, but this did not associate with increased mortality in this study.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/edm2.309; doi:https://doi.org/10.1002/edm2.309; html:https://europepmc.org/articles/PMC8754243; pdf:https://europepmc.org/articles/PMC8754243?pdf=render 32046816,https://doi.org/10.2807/1560-7917.es.2020.25.5.2000080,Effectiveness of airport screening at detecting travellers infected with novel coronavirus (2019-nCoV).,"Quilty BJ, Clifford S, CMMID nCoV working group2, Flasche S, Eggo RM.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2020,2020-02-01,Y,Surveillance; Effectiveness; Interventions; Emerging Infections; 2019-Ncov; Thermal Scanning; Airport Screening,,,"We evaluated effectiveness of thermal passenger screening for 2019-nCoV infection at airport exit and entry to inform public health decision-making. In our baseline scenario, we estimated that 46% (95% confidence interval: 36 to 58) of infected travellers would not be detected, depending on incubation period, sensitivity of exit and entry screening, and proportion of asymptomatic cases. Airport screening is unlikely to detect a sufficient proportion of 2019-nCoV infected travellers to avoid entry of infected travellers.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/5/eurosurv-25-5-2.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.5.2000080&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2020.25.5.2000080; html:https://europepmc.org/articles/PMC7014668; pdf:https://europepmc.org/articles/PMC7014668?pdf=render +34859617,https://doi.org/10.1002/edm2.309,The clinical profile and associated mortality in people with and without diabetes with Coronavirus disease 2019 on admission to acute hospital services.,"Gokhale K, Mostafa SA, Wang J, Tahrani AA, Sainsbury CA, Toulis KA, Thomas GN, Hassan-Smith Z, Sapey E, Gallier S, Adderley NJ, Narendran P, Bellary S, Taverner T, Ghosh S, Nirantharakumar K, Hanif W.",,"Endocrinology, diabetes & metabolism",2022,2021-12-03,Y,Diabetes; Complications; Covid-19,,,"

Introduction

To assess if in adults with COVID-19, whether those with diabetes and complications (DM+C) present with a more severe clinical profile and if that relates to increased mortality, compared to those with diabetes with no complications (DM-NC) and those without diabetes.

Methods

Service-level data was used from 996 adults with laboratory confirmed COVID-19 who presented to the Queen Elizabeth Hospital Birmingham, UK, from March to June 2020. All individuals were categorized into DM+C, DM-NC, and non-diabetes groups. Physiological and laboratory measurements in the first 5 days after admission were collated and compared among groups. Cox proportional hazards regression models were used to evaluate associations between diabetes status and the risk of mortality.

Results

Among the 996 individuals, 104 (10.4%) were DM+C, 295 (29.6%) DM-NC and 597 (59.9%) non-diabetes. There were 309 (31.0%) in-hospital deaths documented, 40 (4.0% of total cohort) were DM+C, 99 (9.9%) DM-NC and 170 (17.0%) non-diabetes. Individuals with DM+C were more likely to present with high anion gap/metabolic acidosis, features of renal impairment, and low albumin/lymphocyte count than those with DM-NC or those without diabetes. There was no significant difference in mortality rates among the groups: compared to individuals without diabetes, the adjusted HRs were 1.39 (95% CI 0.95-2.03, p = 0.093) and 1.18 (95% CI 0.90-1.54, p = 0.226) in DM+C and DM-C, respectively.

Conclusions

Those with COVID-19 and DM+C presented with a more severe clinical and biochemical profile, but this did not associate with increased mortality in this study.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/edm2.309; doi:https://doi.org/10.1002/edm2.309; html:https://europepmc.org/articles/PMC8754243; pdf:https://europepmc.org/articles/PMC8754243?pdf=render 37309807,https://doi.org/10.1093/ehjci/jead123,Characterizing the hypertensive cardiovascular phenotype in the UK Biobank.,"Elghazaly H, McCracken C, Szabo L, Malcolmson J, Manisty CH, Davies AH, Piechnik SK, Harvey NC, Neubauer S, Mohiddin SA, Petersen SE, Raisi-Estabragh Z.",,European heart journal. Cardiovascular Imaging,2023,2023-09-01,Y,Ethnicity; Cardiovascular Magnetic Resonance; Population Health; Women’s Health; Antihypertensive Therapies,,,"

Aims

To describe hypertension-related cardiovascular magnetic resonance (CMR) phenotypes in the UK Biobank considering variations across patient populations.

Methods and results

We studied 39 095 (51.5% women, mean age: 63.9 ± 7.7 years, 38.6% hypertensive) participants with CMR data available. Hypertension status was ascertained through health record linkage. Associations between hypertension and CMR metrics were estimated using multivariable linear regression adjusting for major vascular risk factors. Stratified analyses were performed by sex, ethnicity, time since hypertension diagnosis, and blood pressure (BP) control. Results are standardized beta coefficients, 95% confidence intervals, and P-values corrected for multiple testing. Hypertension was associated with concentric left ventricular (LV) hypertrophy (increased LV mass, wall thickness, concentricity index), poorer LV function (lower global function index, worse global longitudinal strain), larger left atrial (LA) volumes, lower LA ejection fraction, and lower aortic distensibility. Hypertension was linked to significantly lower myocardial native T1 and increased LV ejection fraction. Women had greater hypertension-related reduction in aortic compliance than men. The degree of hypertension-related LV hypertrophy was greatest in Black ethnicities. Increasing time since diagnosis of hypertension was linked to adverse remodelling. Hypertension-related remodelling was substantially attenuated in hypertensives with good BP control.

Conclusion

Hypertension was associated with concentric LV hypertrophy, reduced LV function, dilated poorer functioning LA, and reduced aortic compliance. Whilst the overall pattern of remodelling was consistent across populations, women had greater hypertension-related reduction in aortic compliance and Black ethnicities showed the greatest LV mass increase. Importantly, adverse cardiovascular remodelling was markedly attenuated in hypertensives with good BP control.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead123/50578622/jead123.pdf; doi:https://doi.org/10.1093/ehjci/jead123; html:https://europepmc.org/articles/PMC10531143; pdf:https://europepmc.org/articles/PMC10531143?pdf=render 37337639,https://doi.org/10.1002/ctm2.1291,Trans-ethnic polygenic risk scores for body mass index: An international hundred K+ cohorts consortium study.,"Qu HQ, Connolly JJ, Kraft P, Long J, Pereira A, Flatley C, Turman C, Prins B, Mentch F, Lotufo PA, Magnus P, Stampfer MJ, Tamimi R, Eliassen AH, Zheng W, Knudsen GPS, Helgeland O, Butterworth AS, Hakonarson H, Sleiman PM, IHCC consortium.",,Clinical and translational medicine,2023,2023-06-01,Y,Obesity; Population admixture; body mass index; Polygenic Risk Score; Trans-ethnic,,,"

Background

While polygenic risk scores hold significant promise in estimating an individual's risk of developing a complex trait such as obesity, their application in the clinic has, to date, been limited by a lack of data from non-European populations. As a collaboration model of the International Hundred K+ Cohorts Consortium (IHCC), we endeavored to develop a globally applicable trans-ethnic PRS for body mass index (BMI) through this relatively new international effort.

Methods

The polygenic risk score (PRS) model was developed, trained and tested at the Center for Applied Genomics (CAG) of The Children's Hospital of Philadelphia (CHOP) based on a BMI meta-analysis from the GIANT consortium. The validated PRS models were subsequently disseminated to the participating sites. Scores were generated by each site locally on their cohorts and summary statistics returned to CAG for final analysis.

Results

We show that in the absence of a well powered trans-ethnic GWAS from which to derive marker SNPs and effect estimates for PRS, trans-ethnic scores can be generated from European ancestry GWAS using Bayesian approaches such as LDpred, by adjusting the summary statistics using trans-ethnic linkage disequilibrium reference panels. The ported trans-ethnic scores outperform population specific-PRS across all non-European ancestry populations investigated including East Asians and three-way admixed Brazilian cohort.

Conclusions

Here we show that for a truly polygenic trait such as BMI adjusting the summary statistics of a well powered European ancestry study using trans-ethnic LD reference results in a score that is predictive across a range of ancestries including East Asians and three-way admixed Brazilians.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ctm2.1291; doi:https://doi.org/10.1002/ctm2.1291; html:https://europepmc.org/articles/PMC10280047; pdf:https://europepmc.org/articles/PMC10280047?pdf=render 32301135,https://doi.org/10.1111/opo.12685,Delayed attendance at routine eye examinations is associated with increased probability of general practitioner referral: a record linkage study in Northern Ireland.,"Wright DM, O'Reilly D, Azuara-Blanco A, Curran R, McMullan M, Hogg RE.",,Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists),2020,2020-04-16,N,epidemiology; Public Health; Optometry Services,,,"

Purpose

To investigate relationships between health and socio-economic status with delayed attendance at routine eye examinations and risk of subsequent general practitioner (GP) referral in Northern Ireland.

Methods

We constructed a cohort of 132 046 community dwelling individuals aged ≥60 years, drawing contextual information from the 2011 Northern Ireland Census. Using linked administrative records of routine eye examinations between 2009 and 2014, we calculated 311 999 examination intervals. Multinomial models were used to estimate associations between contextual factors and examination interval (classified into three groups: early recall, on-time, delayed attendance). Associations between examination interval and referral risk were estimated using logistic regression.

Results

Delayed attendance was recorded for 129 857 (41.6%) examination intervals, 53 759 (17.2%) delayed by ≥6 months. Female sex, poor general or mental health were each associated with delay, as were longer distances to optometry services among those aged ≥70 years (longest vs shortest: Relative Risk Ratio = 1.21 [1.14, 1.28]). Low income and residence in social housing were associated with reduced delay risk. There were 3347 (3.5%) and 11 401 (5.3%) GP referrals in the 60-69 and ≥70 years age groups respectively. Delayed attendance was associated with increased referral risk in both groups (Odds Ratios: 60-69 years = 1.30 [1.04, 1.61]; ≥70 years = 1.07 [1.01, 1.13]).

Conclusions

Poor health and longer distances to optometry services were associated with delayed attendance at routine eye examinations but low income was not. Delayed attendance was associated with increased GP referral risk, indicative of missed opportunities to detect potentially serious eye conditions.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/opo.12685; doi:https://doi.org/10.1111/opo.12685 37395705,https://doi.org/10.1167/tvst.12.7.3,Reliability of Optical Coherence Tomography Angiography Retinal Blood Flow Analyses.,"Courtie EF, Gilani A, Capewell N, Kale AU, Hui BTK, Liu X, Montesano G, Teussink M, Denniston AK, Veenith T, Blanch RJ.",,Translational vision science & technology,2023,2023-07-01,Y,,,,"

Purpose

Investigate the association between the optical coherence tomography angiography (OCTA) metrics derived from different analysis programs to understand the comparability of studies using these different approaches.

Methods

Secondary analysis of a prospective observational study (March 2018-September 2021). Forty-four right eyes and 42 left eyes from 44 patients were included. Patients were either undergoing upper gastrointestinal surgery with a critical care stay planned or were already in the critical care unit with sepsis. OCTA scans were obtained in an ophthalmology department or critical care setting. Fourteen OCTA metrics were compared within and between the programs, and agreement was measured by Pearson's R coefficient and intraclass correlation coefficient.

Results

Correlation was highest between all Heidelberg metrics and Fractalyse (all >0.84), and lowest between Matlab skeletonized or foveal avascular zone metrics and all other measures (e.g., skeletal fractal dimension and vessel density at -0.02). Agreement between eyes was moderate to excellent in all metrics (0.60-0.90).

Conclusions

The significant variability between metrics and programs used for OCTA analysis demonstrates that they are not interchangeable and supports a recommendation for perfusion density metrics to be reported as standard.

Translational relevance

Agreement between different OCTA analyses is variable and not interchangeable. The high agreement between non-skeletonized vessel density metrics suggests that these should be routinely reported.",,doi:https://doi.org/10.1167/tvst.12.7.3; doi:https://doi.org/10.1167/tvst.12.7.3; html:https://europepmc.org/articles/PMC10324418; pdf:https://europepmc.org/articles/PMC10324418?pdf=render -36991119,https://doi.org/10.1038/s41586-023-05844-9,An atlas of genetic scores to predict multi-omic traits.,"Xu Y, Ritchie SC, Liang Y, Timmers PRHJ, Pietzner M, Lannelongue L, Lambert SA, Tahir UA, May-Wilson S, Foguet C, Johansson Å, Surendran P, Nath AP, Persyn E, Peters JE, Oliver-Williams C, Deng S, Prins B, Luan J, Bomba L, Soranzo N, Di Angelantonio E, Pirastu N, Tai ES, van Dam RM, Parkinson H, Davenport EE, Paul DS, Yau C, Gerszten RE, Mälarstig A, Danesh J, Sim X, Langenberg C, Wilson JF, Butterworth AS, Inouye M.",,Nature,2023,2023-03-29,N,,,,"The use of omic modalities to dissect the molecular underpinnings of common diseases and traits is becoming increasingly common. But multi-omic traits can be genetically predicted, which enables highly cost-effective and powerful analyses for studies that do not have multi-omics1. Here we examine a large cohort (the INTERVAL study2; n = 50,000 participants) with extensive multi-omic data for plasma proteomics (SomaScan, n = 3,175; Olink, n = 4,822), plasma metabolomics (Metabolon HD4, n = 8,153), serum metabolomics (Nightingale, n = 37,359) and whole-blood Illumina RNA sequencing (n = 4,136), and use machine learning to train genetic scores for 17,227 molecular traits, including 10,521 that reach Bonferroni-adjusted significance. We evaluate the performance of genetic scores through external validation across cohorts of individuals of European, Asian and African American ancestries. In addition, we show the utility of these multi-omic genetic scores by quantifying the genetic control of biological pathways and by generating a synthetic multi-omic dataset of the UK Biobank3 to identify disease associations using a phenome-wide scan. We highlight a series of biological insights with regard to genetic mechanisms in metabolism and canonical pathway associations with disease; for example, JAK-STAT signalling and coronary atherosclerosis. Finally, we develop a portal ( https://www.omicspred.org/ ) to facilitate public access to all genetic scores and validation results, as well as to serve as a platform for future extensions and enhancements of multi-omic genetic scores.",,pdf:https://www.pure.ed.ac.uk/ws/files/337957796/An_atlas_of_genetic_scores_to_predict_multi_omic_traits_s41586_023_05844_9.pdf; doi:https://doi.org/10.1038/s41586-023-05844-9; html:https://europepmc.org/articles/PMC10323211; pdf:https://europepmc.org/articles/PMC10323211?pdf=render; doi:https://doi.org/10.1038/s41586-023-05844-9 31666244,https://doi.org/10.1136/archdischild-2019-317271,Behavioural difficulties in early childhood and risk of adolescent injury.,"Bandyopadhyay A, Tingay K, Akbari A, Griffiths L, Bedford H, Cortina-Borja M, Walton S, Dezateux C, Lyons RA, Brophy S.",,Archives of disease in childhood,2020,2019-10-30,Y,Hospital Admission; Routine Data; Strengths And Difficulties Questionnaire; A&e Attendance; Longitudinal Data Linkage,,,"

Objective

To evaluate long-term associations between early childhood hyperactivity and conduct problems (CP), measured using Strengths and Difficulties Questionnaire (SDQ) and risk of injury in early adolescence.

Design

Data linkage between a longitudinal birth cohort and routinely collected electronic health records.

Setting

Consenting Millennium Cohort Study (MCS) participants residing in Wales and Scotland.

Patients

3119 children who participated in the age 5 MCS interview.

Main outcome measures

Children with parent-reported SDQ scores were linked with hospital admission and Accident & Emergency (A&E) department records for injuries between ages 9 and 14 years. Negative binomial regression models adjusting for number of people in the household, lone parent, residential area, household poverty, maternal age and academic qualification, child sex, physical activity level and country of interview were fitted in the models.

Results

46% of children attended A&E or were admitted to hospital for injury, and 11% had high/abnormal scores for hyperactivity and CP. High/abnormal or borderline hyperactivity were not significantly associated with risk of injury, incidence rate ratio (IRR) with 95% CI of the high/abnormal and borderline were 0.92 (95% CI 0.74 to 1.14) and 1.16 (95% CI 0.88 to 1.52), respectively. Children with borderline CP had higher injury rates compared with those without CP (IRR 1.31, 95% CI 1.09 to 1.57).

Conclusions

Children with high/abnormal hyperactivity or CP scores were not at increased risk of injury; however, those with borderline CP had higher injury rates. Further research is needed to understand if those with difficulties receive treatment and support, which may reduce the likelihood of injuries.",,pdf:https://adc.bmj.com/content/archdischild/105/3/282.full.pdf; doi:https://doi.org/10.1136/archdischild-2019-317271; html:https://europepmc.org/articles/PMC7041499; pdf:https://europepmc.org/articles/PMC7041499?pdf=render +36991119,https://doi.org/10.1038/s41586-023-05844-9,An atlas of genetic scores to predict multi-omic traits.,"Xu Y, Ritchie SC, Liang Y, Timmers PRHJ, Pietzner M, Lannelongue L, Lambert SA, Tahir UA, May-Wilson S, Foguet C, Johansson Å, Surendran P, Nath AP, Persyn E, Peters JE, Oliver-Williams C, Deng S, Prins B, Luan J, Bomba L, Soranzo N, Di Angelantonio E, Pirastu N, Tai ES, van Dam RM, Parkinson H, Davenport EE, Paul DS, Yau C, Gerszten RE, Mälarstig A, Danesh J, Sim X, Langenberg C, Wilson JF, Butterworth AS, Inouye M.",,Nature,2023,2023-03-29,N,,,,"The use of omic modalities to dissect the molecular underpinnings of common diseases and traits is becoming increasingly common. But multi-omic traits can be genetically predicted, which enables highly cost-effective and powerful analyses for studies that do not have multi-omics1. Here we examine a large cohort (the INTERVAL study2; n = 50,000 participants) with extensive multi-omic data for plasma proteomics (SomaScan, n = 3,175; Olink, n = 4,822), plasma metabolomics (Metabolon HD4, n = 8,153), serum metabolomics (Nightingale, n = 37,359) and whole-blood Illumina RNA sequencing (n = 4,136), and use machine learning to train genetic scores for 17,227 molecular traits, including 10,521 that reach Bonferroni-adjusted significance. We evaluate the performance of genetic scores through external validation across cohorts of individuals of European, Asian and African American ancestries. In addition, we show the utility of these multi-omic genetic scores by quantifying the genetic control of biological pathways and by generating a synthetic multi-omic dataset of the UK Biobank3 to identify disease associations using a phenome-wide scan. We highlight a series of biological insights with regard to genetic mechanisms in metabolism and canonical pathway associations with disease; for example, JAK-STAT signalling and coronary atherosclerosis. Finally, we develop a portal ( https://www.omicspred.org/ ) to facilitate public access to all genetic scores and validation results, as well as to serve as a platform for future extensions and enhancements of multi-omic genetic scores.",,pdf:https://www.pure.ed.ac.uk/ws/files/337957796/An_atlas_of_genetic_scores_to_predict_multi_omic_traits_s41586_023_05844_9.pdf; doi:https://doi.org/10.1038/s41586-023-05844-9; html:https://europepmc.org/articles/PMC10323211; pdf:https://europepmc.org/articles/PMC10323211?pdf=render; doi:https://doi.org/10.1038/s41586-023-05844-9 36426221,https://doi.org/10.3389/fcvm.2022.1016032,Clinician's guide to trustworthy and responsible artificial intelligence in cardiovascular imaging.,"Szabo L, Raisi-Estabragh Z, Salih A, McCracken C, Ruiz Pujadas E, Gkontra P, Kiss M, Maurovich-Horvath P, Vago H, Merkely B, Lee AM, Lekadir K, Petersen SE.",,Frontiers in cardiovascular medicine,2022,2022-11-08,Y,Artificial intelligence; Trustworthiness; Cardiovascular Imaging; Machine Learning (Ml); Ai Risk,,,"A growing number of artificial intelligence (AI)-based systems are being proposed and developed in cardiology, driven by the increasing need to deal with the vast amount of clinical and imaging data with the ultimate aim of advancing patient care, diagnosis and prognostication. However, there is a critical gap between the development and clinical deployment of AI tools. A key consideration for implementing AI tools into real-life clinical practice is their ""trustworthiness"" by end-users. Namely, we must ensure that AI systems can be trusted and adopted by all parties involved, including clinicians and patients. Here we provide a summary of the concepts involved in developing a ""trustworthy AI system."" We describe the main risks of AI applications and potential mitigation techniques for the wider application of these promising techniques in the context of cardiovascular imaging. Finally, we show why trustworthy AI concepts are important governing forces of AI development.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2022.1016032/pdf; doi:https://doi.org/10.3389/fcvm.2022.1016032; html:https://europepmc.org/articles/PMC9681217; pdf:https://europepmc.org/articles/PMC9681217?pdf=render 34544691,https://doi.org/10.3399/bjgp.2021.0153,Identifying symptoms associated with diagnosis of pancreatic exocrine and neuroendocrine neoplasms: a nested case-control study of the UK primary care population.,"Liao W, Clift AK, Patone M, Coupland C, González-Izquierdo A, Pereira SP, Hippisley-Cox J.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2021,2021-10-28,Y,Symptom; Early diagnosis; Pancreatic neoplasms; Primary Health Care; Pancreatic Ductal Adenocarcinoma (Pdac); Pancreatic Neuroendocrine Neoplasms (Pnen),,,"

Background

Pancreatic cancer has the worst survival rate among all cancers. Almost 70% of patients in the UK were diagnosed at Stage IV.

Aim

This study aimed to investigate the symptoms associated with the diagnoses of pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine neoplasms (PNEN), and comparatively characterise the symptomatology between the two tumour types to inform earlier diagnosis.

Design and setting

A nested case-control study in primary care was conducted using data from the QResearch® database. Patients aged ≥25 years and diagnosed with PDAC or PNEN during 2000 to 2019 were included as cases. Up to 10 controls from the same general practice were matched with each case by age, sex, and calendar year using incidence density sampling.

Method

Conditional logistic regression was used to investigate the association between the 42 shortlisted symptoms and the diagnoses of PDAC and (or) PNEN in different timeframes relative to the index date, adjusting for patients' sociodemographic characteristics, lifestyle, and relevant comorbidities.

Results

A total of 23 640 patients were identified as diagnosed with PDAC and 596 with PNEN. Of the symptoms identified, 23 were significantly associated with PDAC, and nine symptoms with PNEN. The two alarm symptoms for both tumours were jaundice and gastrointestinal bleeding. The two newly identified symptoms for PDAC were thirst and dark urine. The risk of unintentional weight loss may be longer than 2 years before the diagnosis of PNEN.

Conclusion

PDAC and PNEN have overlapping symptom profiles. The QCancer® (pancreas) risk prediction model could be updated by including the newly identified symptoms and comorbidities, which could help GPs identify high-risk patients for timely investigation in primary care.",,pdf:https://bjgp.org/content/bjgp/71/712/e836.full.pdf; doi:https://doi.org/10.3399/BJGP.2021.0153; html:https://europepmc.org/articles/PMC8463137; pdf:https://europepmc.org/articles/PMC8463137?pdf=render 36543768,https://doi.org/10.1038/s41467-022-35321-2,Multi-organ imaging demonstrates the heart-brain-liver axis in UK Biobank participants.,"McCracken C, Raisi-Estabragh Z, Veldsman M, Raman B, Dennis A, Husain M, Nichols TE, Petersen SE, Neubauer S.",,Nature communications,2022,2022-12-21,Y,,,,"Medical imaging provides numerous insights into the subclinical changes that precede serious diseases such as heart disease and dementia. However, most imaging research either describes a single organ system or draws on clinical cohorts with small sample sizes. In this study, we use state-of-the-art multi-organ magnetic resonance imaging phenotypes to investigate cross-sectional relationships across the heart-brain-liver axis in 30,444 UK Biobank participants. Despite controlling for an extensive range of demographic and clinical covariates, we find significant associations between imaging-derived phenotypes of the heart (left ventricular structure, function and aortic distensibility), brain (brain volumes, white matter hyperintensities and white matter microstructure), and liver (liver fat, liver iron and fibroinflammation). Simultaneous three-organ modelling identifies differentially important pathways across the heart-brain-liver axis with evidence of both direct and indirect associations. This study describes a potentially cumulative burden of multiple-organ dysfunction and provides essential insight into multi-organ disease prevention.",,pdf:https://www.nature.com/articles/s41467-022-35321-2.pdf; doi:https://doi.org/10.1038/s41467-022-35321-2; html:https://europepmc.org/articles/PMC9772225; pdf:https://europepmc.org/articles/PMC9772225?pdf=render -38526449,https://doi.org/10.1002/clt2.12348,Ethnic differences in depression and anxiety among adults with atopic eczema: Population-based matched cohort studies within UK primary care.,"Adesanya EI, Henderson A, Hayes JF, Lewin A, Mathur R, Mulick A, Morton C, Smith C, Langan SM, Mansfield KE.",,Clinical and translational allergy,2024,2024-03-01,Y,Depression; Anxiety; epidemiology; Atopic Eczema; Ethnicity,,,"

Background

Evidence demonstrates that individuals with atopic eczema (eczema) have increased depression and anxiety; however, the role of ethnicity in these associations is poorly understood. We aimed to investigate whether associations between eczema and depression or anxiety differed between adults from white and minority ethnic groups in the UK.

Methods

We used UK Clinical Practice Research Datalink GOLD to conduct matched cohort studies of adults (≥18 years) with ethnicity recorded in primary care electronic health records (April 2006-January 2020). We matched (age, sex, practice) adults with eczema to up to five adults without. We used stratified Cox regression with an interaction between eczema and ethnicity, to estimate hazard ratios (HRs) for associations between eczema and incident depression and anxiety in individuals from white ethnic groups and a pooled minority ethnic group (adults from Black, South Asian, Mixed and Other groups).

Results

We identified separate cohorts for depression (215,073 with eczema matched to 646,539 without) and anxiety (242,598 with eczema matched to 774,113 without). After adjusting for matching variables and potential confounders (age, sex, practice, deprivation, calendar period), we found strong evidence (p < 0.01) of ethnic differences in associations between eczema and depression (minority ethnic groups: HR = 1.33, 95% CI = 1.22,1.45; white ethnic groups: HR = 1.15, 95% CI = 1.12,1.17) and anxiety (minority ethnic groups: HR = 1.41, 95% CI = 1.28,1.55; white ethnic groups: HR = 1.17, 95% CI = 1.14,1.19).

Conclusions

Adults with eczema from minority ethnic groups appear to be at increased depression and anxiety risk compared with their white counterparts. Culturally adapted mental health promotion and prevention strategies should be considered in individuals with eczema from minority ethnic groups.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/clt2.12348; doi:https://doi.org/10.1002/clt2.12348; html:https://europepmc.org/articles/PMC10962487; pdf:https://europepmc.org/articles/PMC10962487?pdf=render 31529485,https://doi.org/10.1111/bjd.18526,"The association of smoking and socioeconomic status on cutaneous melanoma: a population-based, data-linkage, case-control study.","Gibson JAG, Dobbs TD, Griffiths R, Song J, Akbari A, Whitaker S, Watkins A, Langan SM, Hutchings HA, Lyons RA, Whitaker IS.",,The British journal of dermatology,2020,2019-12-01,Y,,Improving Public Health,,"

Background

Previous studies have identified an inverse association between melanoma and smoking; however, data from population-based studies are scarce.

Objectives

To determine the association between smoking and socioeconomic (SES) on the risk of development of melanoma. Furthermore, we sought to determine the implications of smoking and SES on survival.

Methods

We conducted a population-based case-control study. Cases were identified from the Welsh Cancer Intelligence and Surveillance Unit (WCISU) during 2000-2015 and controls from the general population. Smoking and SES were obtained from data linkage with other national databases. The association of smoking status and SES on the incidence of melanoma were assessed using binary logistic regression. Multivariate survival analysis was performed on a melanoma cohort using a Cox proportional hazard model using survival as the outcome.

Results

During 2000-2015, 9636 patients developed melanoma. Smoking data were obtained for 7124 (73·9%) of these patients. There were 26 408 controls identified from the general population. Smoking was inversely associated with melanoma incidence [odds ratio (OR) 0·70, 95% confidence interval (CI) 0·65-0·76]. Smoking was associated with an increased overall mortality [hazard ratio (HR) 1·30, 95% CI 1·09-1·55], but not associated with melanoma-specific mortality. Patients with higher SES had an increased association with melanoma incidence (OR 1·58, 95% CI 1·44-1·73). Higher SES was associated with an increased chance of both overall (HR 0·67, 95% CI 0·56-0·81) and disease-specific survival (HR 0·69, 95% CI 0·53-0·90).

Conclusions

Our study has demonstrated that smoking appeared to be associated with reduced incidence of melanoma. Although smoking increases overall mortality, no association was observed with melanoma-specific mortality. Further work is required to determine if there is a biological mechanism underlying this relationship or an alternative explanation, such as survival bias. What's already known about this topic? Previous studies have been contradictory with both negative and positive associations between smoking and the incidence of melanoma reported. Previous studies have either been limited by publication bias because of selective reporting or underpowered. What does this study add? Our large study identified an inverse association between smoking status and melanoma incidence. Although smoking status was negatively associated with overall disease survival, no significant association was noted in melanoma-specific survival. Socioeconomic status remains closely associated with melanoma. Although higher socioeconomic populations are more likely to develop the disease, patients with lower socioeconomic status continue to have a worse prognosis.","This study investiages whether there is a smoking and socioeconomic status is linked to the risk of developing melanoma (a skin cancer). They used a Welsh database to find data on individuals who had melanoma and linked this data with smoking status and socioeconomic status on other national databases. They found that melanoma was less likely in those who smoked, but was associated with less chance of survival (due to health problems other than melanoma). Those in higher socioeconomic status had overall higher likelihood of survival.",pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.18526; doi:https://doi.org/10.1111/bjd.18526; html:https://europepmc.org/articles/PMC7383980; pdf:https://europepmc.org/articles/PMC7383980?pdf=render 32128788,https://doi.org/10.1111/bjd.18889,The association between partner bereavement and melanoma: cohort studies in the U.K. and Denmark.,"Wong AYS, Frøslev T, Dearing L, Forbes HJ, Mulick A, Mansfield KE, Silverwood RJ, Kjaersgaard A, Sørensen HT, Smeeth L, Lewin A, Schmidt SAJ, Langan SM.",,The British journal of dermatology,2020,2020-03-03,Y,,,,"

Background

Psychological stress is commonly cited as a risk factor for melanoma, but clinical evidence is limited.

Objectives

This study aimed to evaluate the association between partner bereavement and (i) first-time melanoma diagnosis and (ii) mortality in patients with melanoma.

Methods

We conducted two cohort studies using data from the U.K. Clinical Practice Research Datalink (1997-2017) and Danish nationwide registries (1997-2016). In study 1, we compared the risk of first melanoma diagnosis in bereaved vs. matched nonbereaved people using stratified Cox regression. In study 2 we estimated hazard ratios (HRs) for death from melanoma in bereaved compared with nonbereaved individuals with melanoma using Cox regression. We estimated HRs separately for the U.K. and for Denmark, and then pooled the data to perform a random-effects meta-analysis.

Results

In study 1, the pooled adjusted HR for the association between partner bereavement and melanoma diagnosis was 0·88 [95% confidence interval (CI) 0·84-0·92] across the entire follow-up period. In study 2, we observed increased melanoma-specific mortality in people experiencing partner bereavement across the entire follow-up period (HR 1·17, 95% CI 1·06-1·30), with the peak occurring during the first year of follow-up (HR 1·31, 95% CI 1·07-1·60).

Conclusions

We found decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. These findings may be partly explained by delayed detection resulting from the loss of a partner who could notice skin changes. Stress may play a role in melanoma progression. Our findings indicate the need for a low threshold for skin examination in individuals whose partners have died. What is already known about this topic? Psychological stress has been proposed as a risk factor for the development and progression of cancer, including melanoma, but evidence is conflicting. Clinical evidence is limited by small sample sizes, potential recall bias associated with self-report, and heterogeneous stress definitions. What does this study add? We found a decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. While stress might play a role in the progression of melanoma, an alternative explanation is that bereaved people no longer have a close person to help notice skin changes, leading to delayed melanoma detection. Linked Comment: Talaganis et al. Br J Dermatol 2020; 183:607-608.",,doi:https://doi.org/10.1111/bjd.18889; doi:https://doi.org/10.1111/bjd.18889; html:https://europepmc.org/articles/PMC7587014; pdf:https://europepmc.org/articles/PMC7587014?pdf=render +38526449,https://doi.org/10.1002/clt2.12348,Ethnic differences in depression and anxiety among adults with atopic eczema: Population-based matched cohort studies within UK primary care.,"Adesanya EI, Henderson A, Hayes JF, Lewin A, Mathur R, Mulick A, Morton C, Smith C, Langan SM, Mansfield KE.",,Clinical and translational allergy,2024,2024-03-01,Y,Depression; Anxiety; epidemiology; Atopic Eczema; Ethnicity,,,"

Background

Evidence demonstrates that individuals with atopic eczema (eczema) have increased depression and anxiety; however, the role of ethnicity in these associations is poorly understood. We aimed to investigate whether associations between eczema and depression or anxiety differed between adults from white and minority ethnic groups in the UK.

Methods

We used UK Clinical Practice Research Datalink GOLD to conduct matched cohort studies of adults (≥18 years) with ethnicity recorded in primary care electronic health records (April 2006-January 2020). We matched (age, sex, practice) adults with eczema to up to five adults without. We used stratified Cox regression with an interaction between eczema and ethnicity, to estimate hazard ratios (HRs) for associations between eczema and incident depression and anxiety in individuals from white ethnic groups and a pooled minority ethnic group (adults from Black, South Asian, Mixed and Other groups).

Results

We identified separate cohorts for depression (215,073 with eczema matched to 646,539 without) and anxiety (242,598 with eczema matched to 774,113 without). After adjusting for matching variables and potential confounders (age, sex, practice, deprivation, calendar period), we found strong evidence (p < 0.01) of ethnic differences in associations between eczema and depression (minority ethnic groups: HR = 1.33, 95% CI = 1.22,1.45; white ethnic groups: HR = 1.15, 95% CI = 1.12,1.17) and anxiety (minority ethnic groups: HR = 1.41, 95% CI = 1.28,1.55; white ethnic groups: HR = 1.17, 95% CI = 1.14,1.19).

Conclusions

Adults with eczema from minority ethnic groups appear to be at increased depression and anxiety risk compared with their white counterparts. Culturally adapted mental health promotion and prevention strategies should be considered in individuals with eczema from minority ethnic groups.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/clt2.12348; doi:https://doi.org/10.1002/clt2.12348; html:https://europepmc.org/articles/PMC10962487; pdf:https://europepmc.org/articles/PMC10962487?pdf=render 31504435,https://doi.org/10.1093/eurheartj/ehz569,Obesity causes cardiovascular diseases: adding to the weight of evidence.,"Hingorani AD, Finan C, Schmidt AF.",,European heart journal,2020,2020-01-01,N,,,,,,pdf:https://academic.oup.com/eurheartj/article-pdf/41/2/227/31731687/ehz569.pdf; doi:https://doi.org/10.1093/eurheartj/ehz569 37997097,https://doi.org/10.1016/s0140-6736(23)02103-7,The impact of risk stratification by polygenic risk and age on breast cancer screening in women aged 40-49 years: a modelling study.,"Huntley C, Torr B, Sud A, Houlston RS, Hingorani AD, Jones ME, Turnbull C.",,"Lancet (London, England)",2023,2023-11-01,N,,,,"

Background

Polygenic Risk Scores (PRSs) have been proposed as a mechanism for risk-stratification of screening, increasing efficiency and enabling extension of existing programmes to improve survival in our aging population. We sought to model the impact of three hypothetical programmes of annual breast cancer screening in women aged 40-49 years: screening the PRS-defined high-risk quintile, screening the oldest quintile, and screening the full population.

Methods

In this UK-based modelling study, we used the published estimate of the area under the curve (AUC) of a currently available breast cancer PRS (0·64) to calculate the proportion of cancers captured by the PRS-defined high-risk quintile. We used population size estimates from the Office for National Statistics alongside age-stratified incidence rates of breast cancer, and age or stage-specific survival data from the National Cancer Registry, to build our model. We used stage-specific route-to-diagnosis data to reassign stage-specific survival for screen-detected cancers. Ethics approval was not required.

Findings

The PRS-defined high-risk quintile, oldest quintile, and full population capture 37% (n=2811), 29% (n=2198), and 100% (n=7533) of breast cancers occurring in women aged 40-49 each year. Annual screening of each group using digital mammography (sensitivity 70%, specificity 92%) would identify 1968, 1538, and 5273 breast cancers per year, respectively. This corresponds to an improvement in survival of 1·4% (102 deaths averted), 1·1% (80 deaths averted) and 3·6% (274 deaths averted) compared with baseline (no screening). Full population screening would require 4 369 703 mammograms and 354 246 confirmatory tests (breast biopsies) every year, while screening the oldest quintile would require 937 850 mammograms and 76 390 biopsies. Screening the PRS-defined high-risk quintile would require 873 941 mammograms and 71 658 biopsies, in addition to a PRS for all women in the age group (4 369 703).

Interpretation

Under favourable assumptions, stratifying screening by PRS rather than age results in modest gains in survival but increases overdiagnoses, logistical complexity, and economic costs. Our study is limited by our modelling parameters (anticipated to maximise survival estimates), including complete uptake of PRS profiling and cancer screening, no interval cancers, and application of screening tools superior to those currently available in the UK. Only with randomised controlled trials, can the uptake, clinical impact, costs, and harms of PRS-stratified screening be definitively assessed.

Funding

The Wellcome Trust.",,doi:https://doi.org/10.1016/S0140-6736(23)02103-7 33990383,https://doi.org/10.1136/gutjnl-2020-323546,Multicentre derivation and validation of a colitis-associated colorectal cancer risk prediction web tool.,"Curtius K, Kabir M, Al Bakir I, Choi CHR, Hartono JL, Johnson M, East JE, Oxford IBD Cohort Study Investigators, Lindsay JO, Vega R, Thomas-Gibson S, Warusavitarne J, Wilson A, Graham TA, Hart A.",,Gut,2022,2021-05-14,Y,Dysplasia; Ulcerative colitis; Colorectal Cancer; Clinical Decision Making,,,"

Objective

Patients with ulcerative colitis (UC) diagnosed with low-grade dysplasia (LGD) have increased risk of developing advanced neoplasia (AN: high-grade dysplasia or colorectal cancer). We aimed to develop and validate a predictor of AN risk in patients with UC with LGD and create a visual web tool to effectively communicate the risk.

Design

In our retrospective multicentre validated cohort study, adult patients with UC with an index diagnosis of LGD, identified from four UK centres between 2001 and 2019, were followed until progression to AN. In the discovery cohort (n=246), a multivariate risk prediction model was derived from clinicopathological features using Cox regression. Validation used data from three external centres (n=198). The validated model was embedded in a web tool to calculate patient-specific risk.

Results

Four clinicopathological variables were significantly associated with AN progression in the discovery cohort: endoscopically visible LGD >1 cm (HR 2.7; 95% CI 1.2 to 5.9), unresectable or incomplete endoscopic resection (HR 3.4; 95% CI 1.6 to 7.4), moderate/severe histological inflammation within 5 years of LGD diagnosis (HR 3.1; 95% CI 1.5 to 6.7) and multifocality (HR 2.9; 95% CI 1.3 to 6.2). In the validation cohort, this four-variable model accurately predicted future AN cases with overall calibration Observed/Expected=1.01 (95% CI 0.64 to 1.52), and achieved 100% specificity for the lowest risk group over 13 years of available follow-up.

Conclusion

Multicohort validation confirms that patients with large, unresected, multifocal LGD and recent moderate/severe inflammation are at highest risk of developing AN. Personalised risk prediction provided via the Ulcerative Colitis-Cancer Risk Estimator ( www.UC-CaRE.uk ) can support treatment decision-making.",,pdf:https://gut.bmj.com/content/gutjnl/71/4/705.full.pdf; doi:https://doi.org/10.1136/gutjnl-2020-323546; html:https://europepmc.org/articles/PMC8921573; pdf:https://europepmc.org/articles/PMC8921573?pdf=render 37645022,https://doi.org/10.1183/20734735.0058-2023,The impact of poor housing and indoor air quality on respiratory health in children.,"Holden KA, Lee AR, Hawcutt DB, Sinha IP.",,"Breathe (Sheffield, England)",2023,2023-06-01,Y,,,,"It is becoming increasingly apparent that poor housing quality affects indoor air quality, significantly impacting on respiratory health in children and young people. Exposure to damp and/or mould in the home, cold homes and the presence of pests and pollutants all have a significant detrimental impact on child respiratory health. There is a complex relationship between features of poor-quality housing, such as being in a state of disrepair, poor ventilation, overcrowding and being cold, that favour an environment resulting in poor indoor air quality. Children living in rented (private or public) housing are more likely to come from lower-income backgrounds and are most at risk of living in substandard housing posing a serious threat to respiratory health. Children have the right to safe and adequate housing, and research has shown that either rehousing or making modifications to poor-quality housing to improve indoor air quality results in improved respiratory health. Urgent action is needed to address this threat to health. All stakeholders should understand the relationship between poor-quality housing and respiratory health in children and act, working with families, to redress this modifiable risk factor.

Educational aims

The reader should understand how housing quality and indoor air quality affect respiratory health in children.The reader should understand which children are at most risk of living in poor-quality housing.The reader should understand what policy recommendations have been made and what actions need to be undertaken to improve housing quality and respiratory health in children and young people.",,doi:https://doi.org/10.1183/20734735.0058-2023; html:https://europepmc.org/articles/PMC10461733; pdf:https://europepmc.org/articles/PMC10461733?pdf=render -38355192,https://doi.org/10.1136/bmjopen-2023-080678,How far back do we need to look to capture diagnoses in electronic health records? A retrospective observational study of hospital electronic health record data.,"Lewis J, Evison F, Doal R, Field J, Gallier S, Harris S, le Roux P, Osman M, Plummer C, Sapey E, Singer M, Sayer AA, Witham MD, ADMISSION Research Collaborative.",,BMJ open,2024,2024-02-13,Y,Hospitals; Electronic Health Records; Information Extraction,,,"

Objectives

Analysis of routinely collected electronic health data is a key tool for long-term condition research and practice for hospitalised patients. This requires accurate and complete ascertainment of a broad range of diagnoses, something not always recorded on an admission document at a single point in time. This study aimed to ascertain how far back in time electronic hospital records need to be interrogated to capture long-term condition diagnoses.

Design

Retrospective observational study of routinely collected hospital electronic health record data.

Setting

Queen Elizabeth Hospital Birmingham (UK)-linked data held by the PIONEER acute care data hub.

Participants

Patients whose first recorded admission for chronic obstructive pulmonary disease (COPD) exacerbation (n=560) or acute stroke (n=2142) was between January and December 2018 and who had a minimum of 10 years of data prior to the index date.

Outcome measures

We identified the most common International Classification of Diseases version 10-coded diagnoses received by patients with COPD and acute stroke separately. For each diagnosis, we derived the number of patients with the diagnosis recorded at least once over the full 10-year lookback period, and then compared this with shorter lookback periods from 1 year to 9 years prior to the index admission.

Results

Seven of the top 10 most common diagnoses in the COPD dataset reached >90% completeness by 6 years of lookback. Atrial fibrillation and diabetes were >90% coded with 2-3 years of lookback, but hypertension and asthma completeness continued to rise all the way out to 10 years of lookback. For stroke, 4 of the top 10 reached 90% completeness by 5 years of lookback; angina pectoris was >90% coded at 7 years and previous transient ischaemic attack completeness continued to rise out to 10 years of lookback.

Conclusion

A 7-year lookback captures most, but not all, common diagnoses. Lookback duration should be tailored to the conditions being studied.",,pdf:https://bmjopen.bmj.com/content/bmjopen/14/2/e080678.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-080678; html:https://europepmc.org/articles/PMC10868273; pdf:https://europepmc.org/articles/PMC10868273?pdf=render 35589356,https://doi.org/10.1136/bmjopen-2021-057343,"Linkage of National Congenital Heart Disease Audit data to hospital, critical care and mortality national data sets to enable research focused on quality improvement.","Espuny Pujol F, Pagel C, Brown KL, Doidge JC, Feltbower RG, Franklin RC, Gonzalez-Izquierdo A, Gould DW, Norman LJ, Stickley J, Taylor JA, Crowe S.",,BMJ open,2022,2022-05-19,Y,Congenital heart disease; Audit; Health Informatics; Statistics & Research Methods; Quality In Health Care,,,"

Objectives

To link five national data sets (three registries, two administrative) and create longitudinal healthcare trajectories for patients with congenital heart disease (CHD), describing the quality and the summary statistics of the linked data set.

Design

Bespoke linkage of record-level patient identifiers across five national data sets. Generation of spells of care defined as periods of time-overlapping events across the data sets.

Setting

National Congenital Heart Disease Audit (NCHDA) procedures in public (National Health Service; NHS) hospitals in England and Wales, paediatric and adult intensive care data sets (Paediatric Intensive Care Audit Network; PICANet and the Case Mix Programme from the Intensive Care National Audit & Research Centre; ICNARC-CMP), administrative hospital episodes (hospital episode statistics; HES inpatient, outpatient, accident and emergency; A&E) and mortality registry data.

Participants

Patients with any CHD procedure recorded in NCHDA between April 2000 and March 2017 from public hospitals.

Primary and secondary outcome measures

Primary: number of linked records, number of unique patients and number of generated spells of care. Secondary: quality and completeness of linkage.

Results

There were 143 862 records in NCHDA relating to 96 041 unique patients. We identified 65 797 linked PICANet patient admissions, 4664 linked ICNARC-CMP admissions and over 6 million linked HES episodes of care (1.1M inpatient, 4.7M outpatient). The linked data set had 4 908 153 spells of care after quality checks, with a median (IQR) of 3.4 (1.8-6.3) spells per patient-year. Where linkage was feasible (in terms of year and centre), 95.6% surgical procedure records were linked to a corresponding HES record, 93.9% paediatric (cardiac) surgery procedure records to a corresponding PICANet admission and 76.8% adult surgery procedure records to a corresponding ICNARC-CMP record.

Conclusions

We successfully linked four national data sets to the core data set of all CHD procedures performed between 2000 and 2017. This will enable a much richer analysis of longitudinal patient journeys and outcomes. We hope that our detailed description of the linkage process will be useful to others looking to link national data sets to address important research priorities.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/5/e057343.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057343; html:https://europepmc.org/articles/PMC9121475; pdf:https://europepmc.org/articles/PMC9121475?pdf=render 34230034,https://doi.org/10.1136/bmjresp-2021-000967,Increase in recruitment upon integration of trial into a clinical care pathway: an observational study.,"Yip KP, Gompertz S, Snelson C, Willson J, Madathil S, Huq SS, Rauf F, Salmon N, Tengende J, Tracey J, Cooper B, Filby K, Ball S, Parekh D, Dosanjh DPS.",,BMJ open respiratory research,2021,2021-07-01,Y,Covid-19,,,"

Introduction

Many respiratory clinical trials fail to reach their recruitment target and this problem exacerbates existing funding issues. Integration of the clinical trial recruitment process into a clinical care pathway (CCP) may represent an effective way to significantly increase recruitment numbers.

Methods

A respiratory support unit and a CCP for escalation of patients with severe COVID-19 were established on 11 January 2021. The recruitment process for the Randomised Evaluation of COVID-19 Therapy-Respiratory Support trial was integrated into the CCP on the same date. Recruitment data for the trial were collected before and after integration into the CCP.

Results

On integration of the recruitment process into a CCP, there was a significant increase in recruitment numbers. Fifty patients were recruited over 266 days before this process occurred whereas 108 patients were recruited over 49 days after this process. There was a statistically significant increase in both the proportion of recruited patients relative to the number of COVID-19 hospital admissions (change from 2.8% to 9.1%, p<0.0001) and intensive therapy unit admissions (change from 17.8% to 50.2%, p<0.001) over the same period, showing that this increase in recruitment was independent of COVID-19 prevalence.

Discussion

Integrating the trial recruitment process into a CCP can significantly boost recruitment numbers. This represents an innovative model that can be used to maximise recruitment without impacting on the financial and labour costs associated with the running of a respiratory clinical trial.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/8/1/e000967.full.pdf; doi:https://doi.org/10.1136/bmjresp-2021-000967; html:https://europepmc.org/articles/PMC8261886; pdf:https://europepmc.org/articles/PMC8261886?pdf=render +38355192,https://doi.org/10.1136/bmjopen-2023-080678,How far back do we need to look to capture diagnoses in electronic health records? A retrospective observational study of hospital electronic health record data.,"Lewis J, Evison F, Doal R, Field J, Gallier S, Harris S, le Roux P, Osman M, Plummer C, Sapey E, Singer M, Sayer AA, Witham MD, ADMISSION Research Collaborative.",,BMJ open,2024,2024-02-13,Y,Hospitals; Electronic Health Records; Information Extraction,,,"

Objectives

Analysis of routinely collected electronic health data is a key tool for long-term condition research and practice for hospitalised patients. This requires accurate and complete ascertainment of a broad range of diagnoses, something not always recorded on an admission document at a single point in time. This study aimed to ascertain how far back in time electronic hospital records need to be interrogated to capture long-term condition diagnoses.

Design

Retrospective observational study of routinely collected hospital electronic health record data.

Setting

Queen Elizabeth Hospital Birmingham (UK)-linked data held by the PIONEER acute care data hub.

Participants

Patients whose first recorded admission for chronic obstructive pulmonary disease (COPD) exacerbation (n=560) or acute stroke (n=2142) was between January and December 2018 and who had a minimum of 10 years of data prior to the index date.

Outcome measures

We identified the most common International Classification of Diseases version 10-coded diagnoses received by patients with COPD and acute stroke separately. For each diagnosis, we derived the number of patients with the diagnosis recorded at least once over the full 10-year lookback period, and then compared this with shorter lookback periods from 1 year to 9 years prior to the index admission.

Results

Seven of the top 10 most common diagnoses in the COPD dataset reached >90% completeness by 6 years of lookback. Atrial fibrillation and diabetes were >90% coded with 2-3 years of lookback, but hypertension and asthma completeness continued to rise all the way out to 10 years of lookback. For stroke, 4 of the top 10 reached 90% completeness by 5 years of lookback; angina pectoris was >90% coded at 7 years and previous transient ischaemic attack completeness continued to rise out to 10 years of lookback.

Conclusion

A 7-year lookback captures most, but not all, common diagnoses. Lookback duration should be tailored to the conditions being studied.",,pdf:https://bmjopen.bmj.com/content/bmjopen/14/2/e080678.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-080678; html:https://europepmc.org/articles/PMC10868273; pdf:https://europepmc.org/articles/PMC10868273?pdf=render 37532769,https://doi.org/10.1038/s42003-023-05171-9,Direct inference and control of genetic population structure from RNA sequencing data.,"Fachrul M, Karkey A, Shakya M, Judd LM, Harshegyi T, Sim KS, Tonks S, Dongol S, Shrestha R, Salim A, STRATAA study group, Baker S, Pollard AJ, Khor CC, Dolecek C, Basnyat B, Dunstan SJ, Holt KE, Inouye M.",,Communications biology,2023,2023-08-02,Y,,,,"RNAseq data can be used to infer genetic variants, yet its use for estimating genetic population structure remains underexplored. Here, we construct a freely available computational tool (RGStraP) to estimate RNAseq-based genetic principal components (RG-PCs) and assess whether RG-PCs can be used to control for population structure in gene expression analyses. Using whole blood samples from understudied Nepalese populations and the Geuvadis study, we show that RG-PCs had comparable results to paired array-based genotypes, with high genotype concordance and high correlations of genetic principal components, capturing subpopulations within the dataset. In differential gene expression analysis, we found that inclusion of RG-PCs as covariates reduced test statistic inflation. Our paper demonstrates that genetic population structure can be directly inferred and controlled for using RNAseq data, thus facilitating improved retrospective and future analyses of transcriptomic data.",,pdf:https://www.nature.com/articles/s42003-023-05171-9.pdf; doi:https://doi.org/10.1038/s42003-023-05171-9; html:https://europepmc.org/articles/PMC10397182; pdf:https://europepmc.org/articles/PMC10397182?pdf=render 33653753,https://doi.org/10.1136/bmjopen-2020-043290,Temporal trends in heart failure medication prescription in a population-based cohort study.,"Uijl A, Vaartjes I, Denaxas S, Hemingway H, Shah A, Cleland J, Grobbee D, Hoes A, Asselbergs FW, Koudstaal S.",,BMJ open,2021,2021-03-02,Y,Heart Failure; Public Health; Cardiac Epidemiology,,,"

Objective

We examined temporal heart failure (HF) prescription patterns in a large representative sample of real-world patients in the UK, using electronic health records (EHR).

Methods

From primary and secondary care EHR, we identified 85 732 patients with a HF diagnosis between 2002 and 2015. Almost 50% of patients with HF were women and the median age was 79.1 (IQR 70.2-85.7) years, with age at diagnosis increasing over time.

Results

We found several trends in pharmacological HF management, including increased beta blocker prescriptions over time (29% in 2002-2005 and 54% in 2013-2015), which was not observed for mineralocorticoid receptor-antagonists (MR-antagonists) (18% in 2002-2005 and 18% in 2013-2015); higher prescription rates of loop diuretics in women and elderly patients together with lower prescription rates of angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers, beta blockers or MR-antagonists in these patients; little change in medication prescription rates occurred after 6 months of HF diagnosis and, finally, patients hospitalised for HF who had no recorded follow-up in primary care had considerably lower prescription rates compared with patients with a HF diagnosis in primary care with or without HF hospitalisation.

Conclusion

In the general population, the use of MR-antagonists for HF remained low and did not change throughout 13 years of follow-up. For most patients, few changes were seen in pharmacological management of HF in the 6 months following diagnosis.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/3/e043290.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-043290; html:https://europepmc.org/articles/PMC7929882; pdf:https://europepmc.org/articles/PMC7929882?pdf=render 37074763,https://doi.org/10.2196/44237,Data-Driven Identification of Unusual Prescribing Behavior: Analysis and Use of an Interactive Data Tool Using 6 Months of Primary Care Data From 6500 Practices in England.,"Hopcroft LE, Massey J, Curtis HJ, Mackenna B, Croker R, Brown AD, O'Dwyer T, Macdonald O, Evans D, Inglesby P, Bacon SC, Goldacre B, Walker AJ.",,JMIR medical informatics,2023,2023-04-19,Y,General Practice; Prescribing; Primary Care; Electronic Health Records; Ehr; Outliers; Dashboard; Data Science,,,"

Background

Approaches to addressing unwarranted variation in health care service delivery have traditionally relied on the prospective identification of activities and outcomes, based on a hypothesis, with subsequent reporting against defined measures. Practice-level prescribing data in England are made publicly available by the National Health Service (NHS) Business Services Authority for all general practices. There is an opportunity to adopt a more data-driven approach to capture variability and identify outliers by applying hypothesis-free, data-driven algorithms to national data sets.

Objective

This study aimed to develop and apply a hypothesis-free algorithm to identify unusual prescribing behavior in primary care data at multiple administrative levels in the NHS in England and to visualize these results using organization-specific interactive dashboards, thereby demonstrating proof of concept for prioritization approaches.

Methods

Here we report a new data-driven approach to quantify how ""unusual"" the prescribing rates of a particular chemical within an organization are as compared to peer organizations, over a period of 6 months (June-December 2021). This is followed by a ranking to identify which chemicals are the most notable outliers in each organization. These outlying chemicals are calculated for all practices, primary care networks, clinical commissioning groups, and sustainability and transformation partnerships in England. Our results are presented via organization-specific interactive dashboards, the iterative development of which has been informed by user feedback.

Results

We developed interactive dashboards for every practice (n=6476) in England, highlighting the unusual prescribing of 2369 chemicals (dashboards are also provided for 42 sustainability and transformation partnerships, 106 clinical commissioning groups, and 1257 primary care networks). User feedback and internal review of case studies demonstrate that our methodology identifies prescribing behavior that sometimes warrants further investigation or is a known issue.

Conclusions

Data-driven approaches have the potential to overcome existing biases with regard to the planning and execution of audits, interventions, and policy making within NHS organizations, potentially revealing new targets for improved health care service delivery. We present our dashboards as a proof of concept for generating candidate lists to aid expert users in their interpretation of prescribing data and prioritize further investigations and qualitative research in terms of potential targets for improved performance.",,pdf:https://medinform.jmir.org/2023/1/e44237/PDF; doi:https://doi.org/10.2196/44237; html:https://europepmc.org/articles/PMC10162592 35266090,https://doi.org/10.1007/s12471-022-01677-9,The benefit of vaccination against COVID-19 outweighs the potential risk of myocarditis and pericarditis.,"Klamer TA, Linschoten M, Asselbergs FW.",,Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation,2022,2022-03-09,Y,Side effect; Myocarditis; pericarditis; Covid-19; Coronavirus Disease 2019; Covid-19 Vaccination,,,"Vaccines against coronavirus 2019 disease (COVID-19) have shown to be greatly effective in preventing viral spread, serious illness and death from this infectious disease and are therefore critical for the management of the COVID-19 pandemic. However, the listing of myocarditis and pericarditis as possible rare side effects of the messenger RNA (mRNA) vaccines against COVID-19 by regulatory agencies has sparked discussion on the vaccines' safety. The most important published cohort studies to date demonstrat that myocarditis is a very rare side effect after COVID-19 mRNA vaccination, with an incidence of approximately 1-4 cases per 100,000 vaccinated persons. Young males (16-29 years) appear to be at highest risk, predominantly after receiving the second dose. The disease course is self-limiting in a vast majority of cases: 95% of patients show a rapid resolution of symptoms and normalisation of cardiac biomarkers, electro- and echocardiographic findings within days. Importantly, the available data suggest that the incidence rate of myocarditis in the context of COVID-19 is much greater than the risk of this side effect following vaccination. We conclude that the benefit of vaccination against COVID-19 outweighs the potential risk of myocarditis and pericarditis in both adolescents and adults. Prospective follow-up of patients who have developed these complications after vaccination is required to assess long-term outcomes.",,pdf:https://link.springer.com/content/pdf/10.1007/s12471-022-01677-9.pdf; doi:https://doi.org/10.1007/s12471-022-01677-9; html:https://europepmc.org/articles/PMC8906525; pdf:https://europepmc.org/articles/PMC8906525?pdf=render +33168126,https://doi.org/10.1192/bjo.2020.42,Impact of schizophrenia genetic liability on the association between schizophrenia and physical illness: data-linkage study.,"Kendall KM, John A, Lee SC, Rees E, Pardiñas AF, Banos MDP, Owen MJ, O'Donovan MC, Kirov G, Lloyd K, Jones I, Legge SE, Walters JTR.",,BJPsych open,2020,2020-11-10,Y,Genetics; Schizophrenia; Physical Health; Psychotic Disorders,,,"

Background

Individuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia.

Aims

To link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records. To assess (a) rates of physical illness in those with schizophrenia, and (b) whether physical illness in schizophrenia is associated with genetic liability.

Method

We linked genetic data from a clinically ascertained sample of individuals with schizophrenia (Cardiff Cognition in Schizophrenia participants, n = 896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (a) rare copy number variants (CNVs), and (b) polygenic risk scores.

Results

Individuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR) = 5.34), intellectual disability (SRR = 3.11), type 2 diabetes (SRR = 2.45), congenital disorders (SRR = 1.77), ischaemic heart disease (SRR = 1.57) and smoking (SRR = 1.44) in comparison with the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorder-associated CNVs was associated with height (P = 0.015-0.017), with carriers being 7.5-7.7 cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia were associated with genetic liability for the disorder.

Conclusions

This study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased risk for physical illness in schizophrenia is not caused by genetic liability for the disorder.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/A00360A347FCC91E2E9D0B39FBDCE887/S2056472420000423a.pdf/div-class-title-impact-of-schizophrenia-genetic-liability-on-the-association-between-schizophrenia-and-physical-illness-data-linkage-study-div.pdf; doi:https://doi.org/10.1192/bjo.2020.42; html:https://europepmc.org/articles/PMC7745237; pdf:https://europepmc.org/articles/PMC7745237?pdf=render 38643104,https://doi.org/10.1186/s12891-024-07446-6,"Predictors of quality of life, functional status, depression and fatigue in early arthritis: comparison between clinically suspect arthralgia, unclassified arthritis and rheumatoid arthritis.","Torlinska B, Raza K, Filer A, Jutley G, Sahbudin I, Singh R, de Pablo P, Rankin E, Rhodes B, Amft N, Justice E, McGrath C, Baskar S, Trickey J, Calvert M, Falahee M.",,BMC musculoskeletal disorders,2024,2024-04-20,Y,Rheumatoid arthritis; Depression; Fatigue; Functional Status; Health Related Quality Of Life; Undifferentiated Arthritis; Unclassified Arthritis; Clinically Suspect Arthralgia; Pre-ra Stages; Patient-reported Outcomes Measures,,,"

Background

Rheumatoid arthritis (RA) is often preceded by symptomatic phases during which classification criteria are not fulfilled. The health burden of these ""at-risk"" stages is not well described. This study assessed health-related quality of life (HRQoL), function, fatigue and depression in newly presenting patients with clinically suspect arthralgia (CSA), unclassified arthritis (UA) or RA.

Methods

Cross-sectional analysis of baseline Patient-Reported Outcome Measures (PROMs) was conducted in patients from the Birmingham Early Arthritis Cohort. HRQoL, function, depression and fatigue at presentation were assessed using EQ-5D, HAQ-DI, PHQ-9 and FACIT-F. PROMs were compared across CSA, UA and RA and with population averages from the HSE with descriptive statistics. Multivariate linear regression assessed associations between PROMs and clinical and sociodemographic variables.

Results

Of 838 patients included in the analysis, 484 had RA, 200 had CSA and 154 had UA. Patients with RA reported worse outcomes for all PROMs than those with CSA or UA. However, ""mean EQ-5D utilities were 0.65 (95%CI: 0.61 to 0.69) in CSA, 0.61 (0.56 to 0.66) in UA and 0.47 (0.44 to 0.50) in RA, which was lower than in general and older (≥ 65 years) background populations."" In patients with CSA or UA, HRQoL was comparable to chronic conditions such as heart failure, severe COPD or mild angina. Higher BMI and older age (≥ 60 years) predicted worse depression (PHQ-9: -2.47 (-3.85 to -1.09), P < 0.001) and fatigue (FACIT-F: 5.05 (2.37 to 7.73), P < 0.001). Women were more likely to report worse function (HAQ-DI: 0.13 (0.03 to 0.21), P = 0.01) and fatigue (FACIT-F: -3.64 (-5.59 to -1.70), P < 0.001), and residents of more deprived areas experienced decreased function (HAQ-DI: 0.23 (0.10 to 0.36), P = 0.001), greater depression (PHQ-9: 1.89 (0.59 to 3.18), P = 0.004) and fatigue (FACIT-F: -2.60 (-5.11 to 0.09), P = 0.04). After adjustments for confounding factors, diagnostic category was not associated with PROMs, but disease activity and polypharmacy were associated with poorer performance across all PROMs.

Conclusions

Patient-reported outcomes were associated with disease activity and sociodemographic characteristics. Patients presenting with RA reported a higher health burden than those with CSA or UA, however HRQoL in the pre-RA groups was significantly lower than population averages.",,doi:https://doi.org/10.1186/s12891-024-07446-6; html:https://europepmc.org/articles/PMC11031996; pdf:https://europepmc.org/articles/PMC11031996?pdf=render 35271547,https://doi.org/10.1097/ta.0000000000003592,Does patient preference for online or telephone follow-up impact on response rates and data completeness following injury?,"Gabbe BJ, Hart MJ, Brown A, McLellan S, Morgan MJ, Beck B, de Steiger RS, Cameron PA.",,The journal of trauma and acute care surgery,2022,2022-03-08,N,,,,"

Background

Routine collection of patient-reported outcomes is needed to better understand recovery, benchmark between trauma centers and systems, and monitor outcomes over time. A key component of follow-up methodology is the mode of administration of outcome measures with multiple options available. We aimed to quantify patient preference and compare the response rates and data completeness for telephone and online completion in trauma patients.

Methods

A registry-based cohort study of adult (16 years and older) patients registered to the Victorian State Trauma Registry and Victorian Orthopedic Trauma Outcomes Registry from April 2020 to December 2020 was undertaken. Survivors to discharge were contacted by telephone and offered the option of telephone or online completion of 6-month follow-up using the five-level EuroQol five-dimension (EQ-5D-5L) questionnaire and the 12-item World Health Organization Disability Assessment Schedule (WHODAS). The online and telephone groups were compared for differences in characteristics, follow-up rates, and data completeness. Multivariable logistic regression was used to identify predictors of choosing online completion.

Results

Of the 3,886 patients, 51% (n = 1,994) chose online follow-up, and the follow-up rates were lower for online (77%), compared with telephone (89%), follow-up. Younger age, higher socioeconomic status, and preferred language other than English were associated with higher adjusted odds of choosing online completion. Admission to intensive care was associated with lower adjusted odds of choosing online completion. Completion rate for the EQ-5D-5L utility score was 97% for both groups. A valid total 12-WHODAS score could be calculated for 63% of online respondents compared with 86% for the telephone group.

Conclusion

More than half of trauma patients opted for online completion. Completion rates did differ depending on the questionnaire and telephone follow-up rates were higher. Nevertheless, given the wide diversity of the trauma population, the high rate of online uptake, and potential resource constraints, the study findings largely support the use of dual methods for follow-up.

Level of evidence

Prognostic/Epidemiological, Level III.",,doi:https://doi.org/10.1097/TA.0000000000003592 -33168126,https://doi.org/10.1192/bjo.2020.42,Impact of schizophrenia genetic liability on the association between schizophrenia and physical illness: data-linkage study.,"Kendall KM, John A, Lee SC, Rees E, Pardiñas AF, Banos MDP, Owen MJ, O'Donovan MC, Kirov G, Lloyd K, Jones I, Legge SE, Walters JTR.",,BJPsych open,2020,2020-11-10,Y,Genetics; Schizophrenia; Physical Health; Psychotic Disorders,,,"

Background

Individuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia.

Aims

To link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records. To assess (a) rates of physical illness in those with schizophrenia, and (b) whether physical illness in schizophrenia is associated with genetic liability.

Method

We linked genetic data from a clinically ascertained sample of individuals with schizophrenia (Cardiff Cognition in Schizophrenia participants, n = 896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (a) rare copy number variants (CNVs), and (b) polygenic risk scores.

Results

Individuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR) = 5.34), intellectual disability (SRR = 3.11), type 2 diabetes (SRR = 2.45), congenital disorders (SRR = 1.77), ischaemic heart disease (SRR = 1.57) and smoking (SRR = 1.44) in comparison with the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorder-associated CNVs was associated with height (P = 0.015-0.017), with carriers being 7.5-7.7 cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia were associated with genetic liability for the disorder.

Conclusions

This study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased risk for physical illness in schizophrenia is not caused by genetic liability for the disorder.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/A00360A347FCC91E2E9D0B39FBDCE887/S2056472420000423a.pdf/div-class-title-impact-of-schizophrenia-genetic-liability-on-the-association-between-schizophrenia-and-physical-illness-data-linkage-study-div.pdf; doi:https://doi.org/10.1192/bjo.2020.42; html:https://europepmc.org/articles/PMC7745237; pdf:https://europepmc.org/articles/PMC7745237?pdf=render 37516479,https://doi.org/10.1016/s2468-2667(23)00126-3,"Insights from linking police domestic abuse data and health data in South Wales, UK: a linked routine data analysis using decision tree classification.","Kennedy N, Win TL, Bandyopadhyay A, Kennedy J, Rowe B, McNerney C, Evans J, Hughes K, Bellis MA, Jones A, Harrington K, Moore S, Brophy S.",,The Lancet. Public health,2023,2023-08-01,N,,,,"

Background

Exposure to domestic abuse can lead to long-term negative impacts on the victim's physical and psychological wellbeing. The 1998 Crime and Disorder Act requires agencies to collaborate on crime reduction strategies, including data sharing. Although data sharing is feasible for individuals, rarely are whole-agency data linked. This study aimed to examine the knowledge obtained by integrating information from police and health-care datasets through data linkage and analyse associated risk factor clusters.

Methods

This retrospective cohort study analyses data from residents of South Wales who were victims of domestic abuse resulting in a Public Protection Notification (PPN) submission between Aug 12, 2015 and March 31, 2020. The study links these data with the victims' health records, collated within the Secure Anonymised Information Linkage databank, to examine factors associated with the outcome of an Emergency Department attendance, emergency hospital admission, or death within 12 months of the PPN submission. To assess the time to outcome for domestic abuse victims after the index PPN submission, we used Kaplan-Meier survival analysis. We used multivariable Cox regression models to identify which factors contributed the highest risk of experiencing an outcome after the index PPN submission. Finally, we created decision trees to describe specific groups of individuals who are at risk of experiencing a domestic abuse incident and subsequent outcome.

Findings

After excluding individuals with multiple PPN records, duplicates, and records with a poor matching score or missing fields, the resulting clean dataset consisted of 8709 domestic abuse victims, of whom 6257 (71·8%) were female. Within a year of a domestic abuse incident, 3650 (41·9%) individuals had an outcome. Factors associated with experiencing an outcome within 12 months of the PPN included younger victim age (hazard ratio 1·183 [95% CI 1·053-1·329], p=0·0048), further PPN submissions after the initial referral (1·383 [1·295-1·476]; p<0·0001), injury at the scene (1·484 [1·368-1·609]; p<0·0001), assessed high risk (1·600 [1·444-1·773]; p<0·0001), referral to other agencies (1·518 [1·358-1·697]; p<0·0001), history of violence (1·229 [1·134-1·333]; p<0·0001), attempted strangulation (1·311 [1·148-1·497]; p<0·0001), and pregnancy (1·372 [1·142-1·648]; p=0·0007). Health-care data before the index PPN established that previous Emergency Department and hospital admissions, smoking, smoking cessation advice, obstetric codes, and prescription of antidepressants and antibiotics were associated with having a future outcome following a domestic abuse incident.

Interpretation

The results indicate that vulnerable individuals are detectable in multiple datasets before and after involvement of the police. Operationalising these findings could reduce police callouts and future Emergency Department or hospital admissions, and improve outcomes for those who are vulnerable. Strategies include querying previous Emergency Department and hospital admissions, giving a high-risk assessment for a pregnant victim, and facilitating data linkage to identify vulnerable individuals.

Funding

National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S2468266723001263/pdf; doi:https://doi.org/10.1016/S2468-2667(23)00126-3 33475522,https://doi.org/10.2196/18229,Risk Factors and Prevalence of Dilated Cardiomyopathy in Sub-Saharan Africa: Protocol for a Systematic Review.,"Fundikira LS, Chillo P, van Laake LW, Mutagaywa RK, Schmidt AF, Kamuhabwa A, Kwesigabo G, Asselbergs FW.",,JMIR research protocols,2021,2021-01-21,Y,Dilated cardiomyopathy; Sub-Saharan Africa; Cardiomyopathy; Cardiovascular risk factors; Heart Failure,,,"

Background

Cardiomyopathies, defined as diseases involving mainly the heart muscles, are linked to an estimated 5.9 of 100,000 deaths globally. In sub-Saharan Africa, cardiomyopathies constitute 21.4% of heart failure cases, with dilated cardiomyopathy (DCM) being the most common form. The etiology of DCM is heterogeneous and is broadly categorized as genetic or nongenetic, as well as a mixed disease in which genetics interact with intrinsic and environmental factors. Factors such as age, gender, family history, and ethnicity are nonmodifiable, whereas modifiable risk factors include poor nutrition, physical inactivity, and excessive alcohol consumption, among others. However, the relative contribution of the different risk factors to the etiology of DCM is not known in sub-Saharan Africa, and the prevalence of DCM among heart failure patients has not been systematically studied in the region.

Objective

The aim of this review is to synthesize available literature from sub-Saharan Africa on the prevalence of DCM among patients with heart failure, as well as the literature on factors associated with DCM. This paper outlines the protocol that will be followed to conduct the systematic review.

Methods

A limited search of the PubMed database will be performed to identify relevant keywords contained in the title, abstract, and subject descriptors using initial search terms ""heart failure,"" ""cardiomyopathy,"" and ""sub-Saharan Africa."" These search terms and their synonyms will then be used in an extensive search in PubMed, and will address the first research question on prevalence. To address the second research question on risk factors, the terms ""heart failure,"" ""cardiomyopathy,"" and ""cardiovascular risk factors"" in ""Sub-Saharan Africa"" will be used, listing them one by one. Articles published from 2000 and in the English language will be included. Indexed articles in PubMed and Embase will be included, as well as the first 300 articles retrieved from a Google Scholar search. Collected data will be organized in Endnote and then uploaded to the Rayyan web app for systematic reviews. Two reviewers will independently select articles against the inclusion criteria. Discrepancies in reviewer selections will be resolved by an arbitrator. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for reporting systematic reviews will be applied. A map of sub-Saharan Africa with colors to show disease prevalence in each country will be included. For quantitative data, where possible, odds ratios (for categorical outcome data) or standardized mean differences (for continuous data) and their 95% CIs will be calculated.

Results

The primary outcomes will be the prevalence of DCM among patients with heart failure and cardiovascular risk factors associated with DCM in sub-Saharan Africa. The literature search will begin on January 1, 2021, and data analysis is expected to be completed by April 30, 2021.

Conclusions

This review will provide information on the current status of the prevalence and associated factors of DCM, and possibly identify gaps, including paucity of data or conflicting results that need to be addressed to improve our understanding of DCM in sub-Saharan Africa.

International registered report identifier (irrid)

PRR1-10.2196/18229.",,pdf:https://jmir.org/api/download?alt_name=resprot_v10i1e18229_app1.pdf&filename=7e28e6f3581cda60eb7faa74a1bb7968.pdf; doi:https://doi.org/10.2196/18229; html:https://europepmc.org/articles/PMC7862000 31744503,https://doi.org/10.1186/s12916-019-1438-y,"Bleeding in cardiac patients prescribed antithrombotic drugs: electronic health record phenotyping algorithms, incidence, trends and prognosis.","Pasea L, Chung SC, Pujades-Rodriguez M, Shah AD, Alvarez-Madrazo S, Allan V, Teo JT, Bean D, Sofat R, Dobson R, Banerjee A, Patel RS, Timmis A, Denaxas S, Hemingway H.",,BMC medicine,2019,2019-11-20,Y,Phenotype; Bleeding; Prognosis; Antithrombotic Therapy; Electronic Health Records,The Human Phenome,,"

Background

Clinical guidelines and public health authorities lack recommendations on scalable approaches to defining and monitoring the occurrence and severity of bleeding in populations prescribed antithrombotic therapy.

Methods

We examined linked primary care, hospital admission and death registry electronic health records (CALIBER 1998-2010, England) of patients with newly diagnosed atrial fibrillation, acute myocardial infarction, unstable angina or stable angina with the aim to develop algorithms for bleeding events. Using the developed bleeding phenotypes, Kaplan-Meier plots were used to estimate the incidence of bleeding events and we used Cox regression models to assess the prognosis for all-cause mortality, atherothrombotic events and further bleeding.

Results

We present electronic health record phenotyping algorithms for bleeding based on bleeding diagnosis in primary or hospital care, symptoms, transfusion, surgical procedures and haemoglobin values. In validation of the phenotype, we estimated a positive predictive value of 0.88 (95% CI 0.64, 0.99) for hospitalised bleeding. Amongst 128,815 patients, 27,259 (21.2%) had at least 1 bleeding event, with 5-year risks of bleeding of 29.1%, 21.9%, 25.3% and 23.4% following diagnoses of atrial fibrillation, acute myocardial infarction, unstable angina and stable angina, respectively. Rates of hospitalised bleeding per 1000 patients more than doubled from 1.02 (95% CI 0.83, 1.22) in January 1998 to 2.68 (95% CI 2.49, 2.88) in December 2009 coinciding with the increased rates of antiplatelet and vitamin K antagonist prescribing. Patients with hospitalised bleeding and primary care bleeding, with or without markers of severity, were at increased risk of all-cause mortality and atherothrombotic events compared to those with no bleeding. For example, the hazard ratio for all-cause mortality was 1.98 (95% CI 1.86, 2.11) for primary care bleeding with markers of severity and 1.99 (95% CI 1.92, 2.05) for hospitalised bleeding without markers of severity, compared to patients with no bleeding.

Conclusions

Electronic health record bleeding phenotyping algorithms offer a scalable approach to monitoring bleeding in the population. Incidence of bleeding has doubled in incidence since 1998, affects one in four cardiovascular disease patients, and is associated with poor prognosis. Efforts are required to tackle this iatrogenic epidemic.",A phenotyping algorithm is presented to monitor bleeding in primary and hospital care. Model is well presented in the document and has potential to be scalable and applied to other conditions.,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-019-1438-y; doi:https://doi.org/10.1186/s12916-019-1438-y; html:https://europepmc.org/articles/PMC6864929; pdf:https://europepmc.org/articles/PMC6864929?pdf=render @@ -1242,21 +1242,21 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 36194451,https://doi.org/10.2196/40667,Associations Between Depression Symptom Severity and Daily-Life Gait Characteristics Derived From Long-Term Acceleration Signals in Real-World Settings: Retrospective Analysis.,"Zhang Y, Folarin AA, Sun S, Cummins N, Vairavan S, Qian L, Ranjan Y, Rashid Z, Conde P, Stewart C, Laiou P, Sankesara H, Matcham F, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Simblett S, Rintala A, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BWJH, Narayan VA, Annas P, Hotopf M, Dobson RJB, RADAR-CNS Consortium.",,JMIR mHealth and uHealth,2022,2022-10-04,Y,Monitoring; Depression; Gait; Mental health; Mobile Phones; Mhealth; Mobile Health; Wearable Devices; Acceleration Signals,,,"

Background

Gait is an essential manifestation of depression. However, the gait characteristics of daily walking and their relationships with depression have yet to be fully explored.

Objective

The aim of this study was to explore associations between depression symptom severity and daily-life gait characteristics derived from acceleration signals in real-world settings.

Methods

We used two ambulatory data sets (N=71 and N=215) with acceleration signals collected by wearable devices and mobile phones, respectively. We extracted 12 daily-life gait features to describe the distribution and variance of gait cadence and force over a long-term period. Spearman coefficients and linear mixed-effects models were used to explore the associations between daily-life gait features and depression symptom severity measured by the 15-item Geriatric Depression Scale (GDS-15) and 8-item Patient Health Questionnaire (PHQ-8) self-reported questionnaires. The likelihood-ratio (LR) test was used to test whether daily-life gait features could provide additional information relative to the laboratory gait features.

Results

Higher depression symptom severity was significantly associated with lower gait cadence of high-performance walking (segments with faster walking speed) over a long-term period in both data sets. The linear regression model with long-term daily-life gait features (R2=0.30) fitted depression scores significantly better (LR test P=.001) than the model with only laboratory gait features (R2=0.06).

Conclusions

This study indicated that the significant links between daily-life walking characteristics and depression symptom severity could be captured by both wearable devices and mobile phones. The daily-life gait patterns could provide additional information for predicting depression symptom severity relative to laboratory walking. These findings may contribute to developing clinical tools to remotely monitor mental health in real-world settings.",,pdf:https://mhealth.jmir.org/2022/10/e40667/PDF; doi:https://doi.org/10.2196/40667; html:https://europepmc.org/articles/PMC9579931 37751239,https://doi.org/10.2196/49438,Design and Evaluation of an Intensive Care Unit Dashboard Built in Response to the COVID-19 Pandemic: Semistructured Interview Study.,"Wac M, Craddock I, Chantziara S, Campbell T, Santos-Rodriguez R, Davidson B, McWilliams C.",,JMIR human factors,2023,2023-09-26,Y,Design; Health; ICU; EPR; intensive care unit; Interview; Intensive Care; Critical Care; Electronic Patient Record; Participatory Design; Ehr; Electronic Health Record; Software Engineering; Clinical Information System; Cis; Thematic Analysis; Dashboard; Human-centered Design; Covid-19; Interactive Display,,,"

Background

Dashboards and interactive displays are becoming increasingly prevalent in most health care settings and have the potential to streamline access to information, consolidate disparate data sources and deliver new insights. Our research focuses on intensive care units (ICUs) which are heavily instrumented, critical care environments that generate vast amounts of data and frequently require individualized support for each patient. Consequently, clinicians experience a high cognitive load, which can translate to suboptimal performance. The global COVID-19 pandemic exacerbated this problem by generating a large number of additional hospitalizations, which necessitated a new tool that would help manage ICUs' census. In a previous study, we interviewed clinicians at the University Hospitals Bristol and Weston National Health Service Foundation Trust to capture the requirements for bespoke dashboards that would alleviate this problem.

Objective

This study aims to design, implement, and evaluate an ICU dashboard to allow for monitoring of the high volume of patients in need of critical care, particularly tailored to high-demand situations, such as those seen during the COVID-19 pandemic.

Methods

Building upon the previously gathered requirements, we developed a dashboard, integrated it within the ICU of a National Health Service trust, and allowed all staff to access our tool. For evaluation purposes, participants were recruited and interviewed following a 25-day period during which they were able to use the dashboard clinically. The semistructured interviews followed a topic guide aimed at capturing the usability of the dashboard, supplemented with additional questions asked post hoc to probe themes established during the interview. Interview transcripts were analyzed using a thematic analysis framework that combined inductive and deductive approaches and integrated the Technology Acceptance Model.

Results

A total of 10 participants with 4 different roles in the ICU (6 consultants, 2 junior doctors, 1 nurse, and 1 advanced clinical practitioner) participated in the interviews. Our analysis generated 4 key topics that prevailed across the data: our dashboard met the usability requirements of the participants and was found useful and intuitive; participants perceived that it impacted their delivery of patient care by improving the access to the information and better equipping them to do their job; the tool was used in a variety of ways and for different reasons and tasks; and there were barriers to integration of our dashboard into practice, including familiarity with existing systems, which stifled the adoption of our tool.

Conclusions

Our findings show that the perceived utility of the dashboard had a positive impact on the clinicians' workflows in the ICU. Improving access to information translated into more efficient patient care and transformed some of the existing processes. The introduction of our tool was met with positive reception, but its integration during the COVID-19 pandemic limited its adoption into practice.",,doi:https://doi.org/10.2196/49438; doi:https://doi.org/10.2196/49438; html:https://europepmc.org/articles/PMC10565627 32518842,https://doi.org/10.12688/wellcomeopenres.15786.1,Inferring the number of COVID-19 cases from recently reported deaths.,"Jombart T, van Zandvoort K, Russell TW, Jarvis CI, Gimma A, Abbott S, Clifford S, Funk S, Gibbs H, Liu Y, Pearson CAB, Bosse NI, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Eggo RM, Kucharski AJ, Edmunds WJ.",,Wellcome open research,2020,2020-04-27,Y,Estimation; Statistics; epidemics; outbreak; Modelling; Covid-19; Sars-cov-2,,,"We estimate the number of COVID-19 cases from newly reported deaths in a population without previous reports. Our results suggest that by the time a single death occurs, hundreds to thousands of cases are likely to be present in that population. This suggests containment via contact tracing will be challenging at this point, and other response strategies should be considered. Our approach is implemented in a publicly available, user-friendly, online tool.",,doi:https://doi.org/10.12688/wellcomeopenres.15786.1; html:https://europepmc.org/articles/PMC7255910; pdf:https://europepmc.org/articles/PMC7255910?pdf=render -34304048,https://doi.org/10.1016/j.ebiom.2021.103485,Shorter leukocyte telomere length is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank.,"Wang Q, Codd V, Raisi-Estabragh Z, Musicha C, Bountziouka V, Kaptoge S, Allara E, Angelantonio ED, Butterworth AS, Wood AM, Thompson JR, Petersen SE, Harvey NC, Danesh JN, Samani NJ, Nelson CP.",,EBioMedicine,2021,2021-07-23,Y,,,,"Background Older age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain whether leucocyte telomere length (LTL), previously proposed as a marker of biological age, is also associated with COVID-19 outcomes. Methods We associated LTL values obtained from participants recruited into UK Biobank (UKB) during 2006-2010 with adverse COVID-19 outcomes recorded by 30 November 2020, defined as a composite of any of the following: hospital admission, need for critical care, respiratory support, or mortality. Using information on 130 LTL-associated genetic variants, we conducted exploratory Mendelian randomisation (MR) analyses in UKB to evaluate whether observational associations might reflect cause-and-effect relationships. Findings Of 6775 participants in UKB who tested positive for infection with SARS-CoV-2 in the community, there were 914 (13.5%) with adverse COVID-19 outcomes. The odds ratio (OR) for adverse COVID-19 outcomes was 1·17 (95% CI 1·05-1·30; P = 0·004) per 1-SD shorter usual LTL, after adjustment for age, sex and ethnicity. Similar ORs were observed in analyses that: adjusted for additional risk factors; disaggregated the composite outcome and reduced the scope for selection or collider bias. In MR analyses, the OR for adverse COVID-19 outcomes was directionally concordant but non-significant. Interpretation Shorter LTL is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including age. Further data are needed to determine whether this association reflects causality. Funding UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation.",,pdf:http://www.thelancet.com/article/S2352396421002784/pdf; doi:https://doi.org/10.1016/j.ebiom.2021.103485; html:https://europepmc.org/articles/PMC8299112; pdf:https://europepmc.org/articles/PMC8299112?pdf=render 30969971,https://doi.org/10.1371/journal.pone.0213435,Are active children and young people at increased risk of injuries resulting in hospital admission or accident and emergency department attendance? Analysis of linked cohort and electronic hospital records in Wales and Scotland.,"Griffiths LJ, Cortina-Borja M, Tingay K, Bandyopadhyay A, Akbari A, DeStavola BL, Bedford H, Lyons RA, Dezateux C.",,PloS one,2019,2019-04-10,Y,,Improving Public Health,,"

Introduction

Children and young people (CYP) are encouraged to increase time spent being physically active, especially in moderate and vigorous intensity pursuits. However, there is limited evidence on the prospective association of activity levels with injuries resulting in use of hospital services. We examined the relationship between objectively-measured physical activity (PA) and subsequent injuries resulting in hospital admissions or accident and emergency department (A&E) attendances, using linked electronic hospital records (EHR) from a nationally representative prospective cohort of CYP in Wales and Scotland.

Methods

We analysed accelerometer-based estimates of moderate to vigorous (MVPA) and vigorous PA (VPA) from 1,585 (777 [46%] boys) seven-year-old Millennium Cohort Study members, living in Wales or Scotland, whose parents consented to linkage of cohort records to EHRs up until their 14th birthday. Negative binomial regression models adjusted by potential individual, household and area-level confounders, were fitted to estimate associations between average daily minutes of MVPA, and VPA (in 10-minute increments), and number of injury-related hospital admissions and/or A&E attendances from age nine to 14 years.

Results

CYP spent a median of 59.5 and 18.1 minutes in MVPA and VPA/day respectively, with boys significantly more active than girls; 47.3% of children experienced at least one injury-related admission or A&E attendance during the study period. Rates of injury-related hospital admission and/or A&E attendance were positively associated with MVPA and VPA in boys but not in girls: respective adjusted incidence rate ratios (95% CI) for boys: 1.09 (1.01, 1.17) and 1.16 (1.00, 1.34), and for girls: 0.94 (0.86, 1.03) and 0.85 (0.69, 1.04).

Conclusion

Boys but not girls who engage in more intense PA at age seven years are at higher risk of injury-related hospital admission or A&E attendance when aged nine to 14 years than their less active peers. This may reflect gender differences in the type and associated risks of activities undertaken. EHRs can make a useful contribution to injury surveillance and prevention if routinely augmented with information on context and setting of the injuries sustained. Injury prevention initiatives should not discourage engagement in PA and outdoor play given their over-riding health and social benefits.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0213435&type=printable; doi:https://doi.org/10.1371/journal.pone.0213435; html:https://europepmc.org/articles/PMC6457613; pdf:https://europepmc.org/articles/PMC6457613?pdf=render +34304048,https://doi.org/10.1016/j.ebiom.2021.103485,Shorter leukocyte telomere length is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank.,"Wang Q, Codd V, Raisi-Estabragh Z, Musicha C, Bountziouka V, Kaptoge S, Allara E, Angelantonio ED, Butterworth AS, Wood AM, Thompson JR, Petersen SE, Harvey NC, Danesh JN, Samani NJ, Nelson CP.",,EBioMedicine,2021,2021-07-23,Y,,,,"Background Older age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain whether leucocyte telomere length (LTL), previously proposed as a marker of biological age, is also associated with COVID-19 outcomes. Methods We associated LTL values obtained from participants recruited into UK Biobank (UKB) during 2006-2010 with adverse COVID-19 outcomes recorded by 30 November 2020, defined as a composite of any of the following: hospital admission, need for critical care, respiratory support, or mortality. Using information on 130 LTL-associated genetic variants, we conducted exploratory Mendelian randomisation (MR) analyses in UKB to evaluate whether observational associations might reflect cause-and-effect relationships. Findings Of 6775 participants in UKB who tested positive for infection with SARS-CoV-2 in the community, there were 914 (13.5%) with adverse COVID-19 outcomes. The odds ratio (OR) for adverse COVID-19 outcomes was 1·17 (95% CI 1·05-1·30; P = 0·004) per 1-SD shorter usual LTL, after adjustment for age, sex and ethnicity. Similar ORs were observed in analyses that: adjusted for additional risk factors; disaggregated the composite outcome and reduced the scope for selection or collider bias. In MR analyses, the OR for adverse COVID-19 outcomes was directionally concordant but non-significant. Interpretation Shorter LTL is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including age. Further data are needed to determine whether this association reflects causality. Funding UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation.",,pdf:http://www.thelancet.com/article/S2352396421002784/pdf; doi:https://doi.org/10.1016/j.ebiom.2021.103485; html:https://europepmc.org/articles/PMC8299112; pdf:https://europepmc.org/articles/PMC8299112?pdf=render 32249120,https://doi.org/10.1016/j.schres.2020.03.044,"Area deprivation, urbanicity, severe mental illness and social drift - A population-based linkage study using routinely collected primary and secondary care data.","Lee SC, DelPozo-Banos M, Lloyd K, Jones I, Walters JTR, Owen MJ, O'Donovan M, John A.",,Schizophrenia research,2020,2020-04-02,N,Schizophrenia; Bipolar disorder; Deprivation; Severe Mental Illness; Urbanicity; Social Drift,Improving Public Health,mental health,"We investigated whether associations between area deprivation, urbanicity and elevated risk of severe mental illnesses (SMIs, including schizophrenia and bipolar disorder) is accounted for by social drift or social causation. We extracted primary and secondary care electronic health records from 2004 to 2015 from a population of 3.9 million. We identified prevalent and incident individuals with SMIs and their level of deprivation and urbanicity using the Welsh Index of Multiple Deprivation (WIMD) and urban/rural indicator. The presence of social drift was determined by whether odds ratios (ORs) from logistic regression is greater than the incidence rate ratios (IRRs) from Poisson regression. Additionally, we performed longitudinal analysis to measure the proportion of change in deprivation level and rural/urban residence 10 years after an incident diagnosis of SMI and compared it to the general population using standardised rate ratios (SRRs). Prevalence and incidence of SMIs were significantly associated with deprivation and urbanicity (all ORs and IRRs significantly >1). ORs and IRRs were similar across all conditions and cohorts (ranging from 1.1 to 1.4). Results from the longitudinal analysis showed individuals with SMIs are more likely to move compared to the general population. However, they did not preferentially move to more deprived or urban areas. There was little evidence of downward social drift over a 10-year period. These findings have implications for the allocation of resources, service configuration and access to services in deprived communities, as well as, for broader public health interventions addressing poverty, and social and environmental contexts.",,doi:https://doi.org/10.1016/j.schres.2020.03.044; doi:https://doi.org/10.1016/j.schres.2020.03.044 35650647,https://doi.org/10.1186/s41512-022-00124-y,A scoping methodological review of simulation studies comparing statistical and machine learning approaches to risk prediction for time-to-event data.,"Smith H, Sweeting M, Morris T, Crowther MJ.",,Diagnostic and prognostic research,2022,2022-06-02,Y,Survival analysis; Machine Learning; Simulation Studies; Clinical Risk Prediction; Prognostic Modelling,,,"

Background

There is substantial interest in the adaptation and application of so-called machine learning approaches to prognostic modelling of censored time-to-event data. These methods must be compared and evaluated against existing methods in a variety of scenarios to determine their predictive performance. A scoping review of how machine learning methods have been compared to traditional survival models is important to identify the comparisons that have been made and issues where they are lacking, biased towards one approach or misleading.

Methods

We conducted a scoping review of research articles published between 1 January 2000 and 2 December 2020 using PubMed. Eligible articles were those that used simulation studies to compare statistical and machine learning methods for risk prediction with a time-to-event outcome in a medical/healthcare setting. We focus on data-generating mechanisms (DGMs), the methods that have been compared, the estimands of the simulation studies, and the performance measures used to evaluate them.

Results

A total of ten articles were identified as eligible for the review. Six of the articles evaluated a method that was developed by the authors, four of which were machine learning methods, and the results almost always stated that this developed method's performance was equivalent to or better than the other methods compared. Comparisons were often biased towards the novel approach, with the majority only comparing against a basic Cox proportional hazards model, and in scenarios where it is clear it would not perform well. In many of the articles reviewed, key information was unclear, such as the number of simulation repetitions and how performance measures were calculated.

Conclusion

It is vital that method comparisons are unbiased and comprehensive, and this should be the goal even if realising it is difficult. Fully assessing how newly developed methods perform and how they compare to a variety of traditional statistical methods for prognostic modelling is imperative as these methods are already being applied in clinical contexts. Evaluations of the performance and usefulness of recently developed methods for risk prediction should be continued and reporting standards improved as these methods become increasingly popular.",,pdf:https://diagnprognres.biomedcentral.com/track/pdf/10.1186/s41512-022-00124-y; doi:https://doi.org/10.1186/s41512-022-00124-y; html:https://europepmc.org/articles/PMC9161606; pdf:https://europepmc.org/articles/PMC9161606?pdf=render 34781301,https://doi.org/10.1159/000520674,"Identification and Mapping Real-World Data Sources for Heart Failure, Acute Coronary Syndrome, and Atrial Fibrillation.","Studer R, Sartini C, Suzart-Woischnik K, Agrawal R, Natani H, Gill SK, Wirta SB, Asselbergs FW, Dobson R, Denaxas S, Kotecha D.",,Cardiology,2022,2021-11-15,N,Data Sources; cardiovascular; Real-world Data; Real-world Evidence,,,"

Background

Transparent and robust real-world evidence sources are increasingly important for global health, including cardiovascular (CV) diseases. We aimed to identify global real-world data (RWD) sources for heart failure (HF), acute coronary syndrome (ACS), and atrial fibrillation (AF).

Methods

We conducted a systematic review of publications with RWD pertaining to HF, ACS, and AF (2010-2018), generating a list of unique data sources. Metadata were extracted based on the source type (e.g., electronic health records, genomics, and clinical data), study design, population size, clinical characteristics, follow-up duration, outcomes, and assessment of data availability for future studies and linkage.

Results

Overall, 11,889 publications were retrieved for HF, 10,729 for ACS, and 6,262 for AF. From these, 322 (HF), 287 (ACS), and 220 (AF) data sources were selected for detailed review. The majority of data sources had near complete data on demographic variables (HF: 94%, ACS: 99%, and AF: 100%) and considerable data on comorbidities (HF: 77%, ACS: 93%, and AF: 97%). The least reported data categories were drug codes (HF, ACS, and AF: 10%) and caregiver involvement (HF: 6%, ACS: 1%, and AF: 1%). Only a minority of data sources provided information on access to data for other researchers (11%) or whether data could be linked to other data sources to maximize clinical impact (20%). The list and metadata for the RWD sources are publicly available at www.escardio.org/bigdata.

Conclusions

This review has created a comprehensive resource of CV data sources, providing new avenues to improve future real-world research and to achieve better patient outcomes.",,pdf:https://www.karger.com/Article/Pdf/520674; doi:https://doi.org/10.1159/000520674; html:https://europepmc.org/articles/PMC8985014; doi:https://doi.org/10.1159/000520674 -38346686,https://doi.org/10.1093/ageing/afae004,The impact of digital technology in care homes on unplanned secondary care usage and associated costs.,"Garner A, Lewis J, Dixon S, Preston N, Caiado CCS, Hanratty B, Jones M, Knight J, Mason SM.",,Age and ageing,2024,2024-02-01,Y,Older People; Emergency Medicine; Care Homes; Long-term Care; Telehealth; Routinely Collected Data,,,"

Background

A substantial number of Emergency Department (ED) attendances by care home residents are potentially avoidable. Health Call Digital Care Homes is an app-based technology that aims to streamline residents' care by recording their observations such as vital parameters electronically. Observations are triaged by remote clinical staff. This study assessed the effectiveness of the Health Call technology to reduce unplanned secondary care usage and associated costs.

Methods

A retrospective analysis of health outcomes and economic impact based on an intervention. The study involved 118 care homes across the North East of UK from 2018 to 2021. Routinely collected NHS secondary care data from County Durham and Darlington NHS Foundation Trust was linked with data from the Health Call app. Three outcomes were modelled monthly using Generalised Linear Mixed Models: counts of emergency attendances, emergency admissions and length of stay of emergency admissions. A similar approach was taken for costs. The impact of Health Call was tested on each outcome using the models.

Findings

Data from 8,702 residents were used in the analysis. Results show Health Call reduces the number of emergency attendances by 11% [6-15%], emergency admissions by 25% [20-39%] and length of stay by 11% [3-18%] (with an additional month-by-month decrease of 28% [24-34%]). The cost analysis found a cost reduction of £57 per resident in 2018, increasing to £113 in 2021.

Interpretation

The introduction of a digital technology, such as Health Call, could significantly reduce contacts with and costs resulting from unplanned secondary care usage by care home residents.",,pdf:https://academic.oup.com/ageing/article-pdf/53/2/afae004/56661196/afae004.pdf; doi:https://doi.org/10.1093/ageing/afae004; html:https://europepmc.org/articles/PMC10861323; pdf:https://europepmc.org/articles/PMC10861323?pdf=render 37389932,https://doi.org/10.2196/44126,Barriers to and Facilitators of Using Remote Measurement Technology in the Long-Term Monitoring of Individuals With ADHD: Interview Study.,"Denyer H, Deng Q, Adanijo A, Asherson P, Bilbow A, Folarin A, Groom MJ, Hollis C, Wykes T, Dobson RJ, Kuntsi J, Simblett S.",,JMIR formative research,2023,2023-06-30,Y,Mobile phone; ADHD; Qualitative analysis; Engagement; Attention-deficit/hyperactivity Disorder; Barriers And Facilitators; Remote Measurement Technology,,,"

Background

Remote measurement technology (RMT) has the potential to address current research and clinical challenges of attention-deficit/hyperactivity disorder (ADHD) symptoms and its co-occurring mental health problems. Despite research using RMT already being successfully applied to other populations, adherence and attrition are potential obstacles when applying RMT to a disorder such as ADHD. Hypothetical views and attitudes toward using RMT in a population with ADHD have previously been explored; however, to our knowledge, there is no previous research that has used qualitative methods to understand the barriers to and facilitators of using RMT in individuals with ADHD following participation in a remote monitoring period.

Objective

We aimed to evaluate the barriers to and facilitators of using RMT in individuals with ADHD compared with a group of people who did not have a diagnosis of ADHD. We also aimed to explore participants' views on using RMT for 1 or 2 years in future studies.

Methods

In total, 20 individuals with ADHD and 20 individuals without ADHD were followed up for 10 weeks using RMT that involved active (questionnaires and cognitive tasks) and passive (smartphone sensors and wearable devices) monitoring; 10 adolescents and adults with ADHD and 12 individuals in a comparison group completed semistructured qualitative interviews at the end of the study period. The interviews focused on potential barriers to and facilitators of using RMT in adults with ADHD. A framework methodology was used to explore the data qualitatively.

Results

Barriers to and facilitators of using RMT were categorized as health-related, user-related, and technology-related factors across both participant groups. When comparing themes that emerged across the participant groups, both individuals with and without ADHD experienced similar barriers and facilitators in using RMT. The participants agreed that RMT can provide useful objective data. However, slight differences between the participant groups were identified as barriers to RMT across all major themes. Individuals with ADHD described the impact that their ADHD symptoms had on participating (health-related theme), commented on the perceived cost of completing the cognitive tasks (user-related theme), and described more technical challenges (technology-related theme) than individuals without ADHD. Hypothetical views on future studies using RMT in individuals with ADHD for 1 or 2 years were positive.

Conclusions

Individuals with ADHD agreed that RMT, which uses repeated measurements with ongoing active and passive monitoring, can provide useful objective data. Although themes overlapped with previous research on barriers to and facilitators of engagement with RMT (eg, depression and epilepsy) and with a comparison group, there are unique considerations for people with ADHD, for example, understanding the impact that ADHD symptoms may have on engaging with RMT. Researchers need to continue working with people with ADHD to develop future RMT studies for longer periods.",,pdf:https://formative.jmir.org/2023/1/e44126/PDF; doi:https://doi.org/10.2196/44126; html:https://europepmc.org/articles/PMC10365629; pdf:https://europepmc.org/articles/PMC10365629?pdf=render -35471746,https://doi.org/10.1186/s13613-022-01011-x,The resilient intensive care unit.,"Salluh JIF, Kurtz P, Bastos LSL, Quintairos A, Zampieri FG, Bozza FA.",,Annals of intensive care,2022,2022-04-26,Y,,,,"

Background

The COVID-19 pandemic tested the capacity of intensive care units (ICU) to respond to a crisis and demonstrated their fragility. Unsurprisingly, higher than usual mortality rates, lengths of stay (LOS), and ICU-acquired complications occurred during the pandemic. However, worse outcomes were not universal nor constant across ICUs and significant variation in outcomes was reported, demonstrating that some ICUs could adequately manage the surge of COVID-19.

Methods

In the present editorial, we discuss the concept of a resilient Intensive Care Unit, including which metrics can be used to address the capacity to respond, sustain results and incorporate new practices that lead to improvement.

Results

We believe that a resiliency analysis adds a component of preparedness to the usual ICU performance evaluation and outcomes metrics to be used during the crisis and in regular times.

Conclusions

The COVID-19 pandemic demonstrated the need for a resilient health system. Although this concept has been discussed for health systems, it was not tested in intensive care. Future studies should evaluate this concept to improve ICU organization for standard and pandemic times.",,pdf:https://annalsofintensivecare.springeropen.com/track/pdf/10.1186/s13613-022-01011-x; doi:https://doi.org/10.1186/s13613-022-01011-x; html:https://europepmc.org/articles/PMC9038989; pdf:https://europepmc.org/articles/PMC9038989?pdf=render +38346686,https://doi.org/10.1093/ageing/afae004,The impact of digital technology in care homes on unplanned secondary care usage and associated costs.,"Garner A, Lewis J, Dixon S, Preston N, Caiado CCS, Hanratty B, Jones M, Knight J, Mason SM.",,Age and ageing,2024,2024-02-01,Y,Older People; Emergency Medicine; Care Homes; Long-term Care; Telehealth; Routinely Collected Data,,,"

Background

A substantial number of Emergency Department (ED) attendances by care home residents are potentially avoidable. Health Call Digital Care Homes is an app-based technology that aims to streamline residents' care by recording their observations such as vital parameters electronically. Observations are triaged by remote clinical staff. This study assessed the effectiveness of the Health Call technology to reduce unplanned secondary care usage and associated costs.

Methods

A retrospective analysis of health outcomes and economic impact based on an intervention. The study involved 118 care homes across the North East of UK from 2018 to 2021. Routinely collected NHS secondary care data from County Durham and Darlington NHS Foundation Trust was linked with data from the Health Call app. Three outcomes were modelled monthly using Generalised Linear Mixed Models: counts of emergency attendances, emergency admissions and length of stay of emergency admissions. A similar approach was taken for costs. The impact of Health Call was tested on each outcome using the models.

Findings

Data from 8,702 residents were used in the analysis. Results show Health Call reduces the number of emergency attendances by 11% [6-15%], emergency admissions by 25% [20-39%] and length of stay by 11% [3-18%] (with an additional month-by-month decrease of 28% [24-34%]). The cost analysis found a cost reduction of £57 per resident in 2018, increasing to £113 in 2021.

Interpretation

The introduction of a digital technology, such as Health Call, could significantly reduce contacts with and costs resulting from unplanned secondary care usage by care home residents.",,pdf:https://academic.oup.com/ageing/article-pdf/53/2/afae004/56661196/afae004.pdf; doi:https://doi.org/10.1093/ageing/afae004; html:https://europepmc.org/articles/PMC10861323; pdf:https://europepmc.org/articles/PMC10861323?pdf=render 29457906,https://doi.org/10.1021/acs.jproteome.7b00879,Optimized Phenotypic Biomarker Discovery and Confounder Elimination via Covariate-Adjusted Projection to Latent Structures from Metabolic Spectroscopy Data.,"Posma JM, Garcia-Perez I, Ebbels TMD, Lindon JC, Stamler J, Elliott P, Holmes E, Nicholson JK.",,Journal of proteome research,2018,2018-02-27,Y,Chemometrics; multivariate data analysis; Biomarker Discovery; Sampling Bias; Covariate Adjustment; Metabolic Phenotyping; Random Matrix Theory; Reanalysis; Monte Carlo Cross-validation; Confounder Elimination,Applied Analytics,,"Metabolism is altered by genetics, diet, disease status, environment, and many other factors. Modeling either one of these is often done without considering the effects of the other covariates. Attributing differences in metabolic profile to one of these factors needs to be done while controlling for the metabolic influence of the rest. We describe here a data analysis framework and novel confounder-adjustment algorithm for multivariate analysis of metabolic profiling data. Using simulated data, we show that similar numbers of true associations and significantly less false positives are found compared to other commonly used methods. Covariate-adjusted projections to latent structures (CA-PLS) are exemplified here using a large-scale metabolic phenotyping study of two Chinese populations at different risks for cardiovascular disease. Using CA-PLS, we find that some previously reported differences are actually associated with external factors and discover a number of previously unreported biomarkers linked to different metabolic pathways. CA-PLS can be applied to any multivariate data where confounding may be an issue and the confounder-adjustment procedure is translatable to other multivariate regression techniques.",,pdf:https://pubs.acs.org/doi/pdf/10.1021/acs.jproteome.7b00879; doi:https://doi.org/10.1021/acs.jproteome.7b00879; html:https://europepmc.org/articles/PMC5891819; pdf:https://europepmc.org/articles/PMC5891819?pdf=render +35471746,https://doi.org/10.1186/s13613-022-01011-x,The resilient intensive care unit.,"Salluh JIF, Kurtz P, Bastos LSL, Quintairos A, Zampieri FG, Bozza FA.",,Annals of intensive care,2022,2022-04-26,Y,,,,"

Background

The COVID-19 pandemic tested the capacity of intensive care units (ICU) to respond to a crisis and demonstrated their fragility. Unsurprisingly, higher than usual mortality rates, lengths of stay (LOS), and ICU-acquired complications occurred during the pandemic. However, worse outcomes were not universal nor constant across ICUs and significant variation in outcomes was reported, demonstrating that some ICUs could adequately manage the surge of COVID-19.

Methods

In the present editorial, we discuss the concept of a resilient Intensive Care Unit, including which metrics can be used to address the capacity to respond, sustain results and incorporate new practices that lead to improvement.

Results

We believe that a resiliency analysis adds a component of preparedness to the usual ICU performance evaluation and outcomes metrics to be used during the crisis and in regular times.

Conclusions

The COVID-19 pandemic demonstrated the need for a resilient health system. Although this concept has been discussed for health systems, it was not tested in intensive care. Future studies should evaluate this concept to improve ICU organization for standard and pandemic times.",,pdf:https://annalsofintensivecare.springeropen.com/track/pdf/10.1186/s13613-022-01011-x; doi:https://doi.org/10.1186/s13613-022-01011-x; html:https://europepmc.org/articles/PMC9038989; pdf:https://europepmc.org/articles/PMC9038989?pdf=render 35487738,https://doi.org/10.1136/bmjopen-2021-057017,Variation in the estimated prevalence of multimorbidity: systematic review and meta-analysis of 193 international studies.,"Ho IS, Azcoaga-Lorenzo A, Akbari A, Davies J, Hodgins P, Khunti K, Kadam U, Lyons R, McCowan C, Mercer SW, Nirantharakumar K, Guthrie B.",,BMJ open,2022,2022-04-29,Y,epidemiology; Geriatric Medicine; General Medicine (See Internal Medicine),,,"

Objective

(1) To estimate the pooled prevalence of multimorbidity in all age groups, globally. (2) To examine how measurement of multimorbidity impacted the estimated prevalence.

Methods

In this systematic review and meta-analysis, we conducted searches in nine bibliographic databases (PsycINFO, Embase, Global Health, Medline, Scopus, Web of Science, Cochrane Library, CINAHL and ProQuest Dissertations and Theses Global) for prevalence studies published between database inception and 21 January 2020. Studies reporting the prevalence of multimorbidity (in all age groups and in community, primary care, care home and hospital settings) were included. Studies with an index condition or those that did not include people with no long-term conditions in the denominator were excluded. Retrieved studies were independently reviewed by two reviewers, and relevant data were extracted using predesigned pro forma. We used meta-analysis to pool the estimated prevalence of multimorbidity across studies, and used random-effects meta-regression and subgroup analysis to examine the association of heterogeneous prevalence estimates with study and measure characteristics.

Results

13 807 titles were screened, of which 193 met inclusion criteria for meta-analysis. The pooled prevalence of multimorbidity was 42.4% (95% CI 38.9% to 46.0%) with high heterogeneity (I2 >99%). In adjusted meta-regression models, participant mean age and the number of conditions included in a measure accounted for 47.8% of heterogeneity in effect sizes. The estimated prevalence of multimorbidity was significantly higher in studies with older adults and those that included larger numbers of conditions. There was no significant difference in estimated prevalence between low-income or middle-income countries (36.8%) and high-income countries (44.3%), or between self-report (40.0%) and administrative/clinical databases (52.7%).

Conclusions

The pooled prevalence of multimorbidity was significantly higher in older populations and when studies included a larger number of baseline conditions. The findings suggest that, to improve study comparability and quality of reporting, future studies should use a common core conditions set for multimorbidity measurement and report multimorbidity prevalence stratified by sociodemographics.PROSPERO registration numberCRD42020172409.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057017.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057017; html:https://europepmc.org/articles/PMC9058768; pdf:https://europepmc.org/articles/PMC9058768?pdf=render -38388919,https://doi.org/10.1186/s12913-024-10716-7,"Spatio-temporal modelling of referrals to outpatient respiratory clinics in the integrated care system of the Morecambe Bay area, England.","Mountain R, Knight J, Heys K, Giorgi E, Gatheral T.",,BMC health services research,2024,2024-02-22,Y,Spatio-temporal; Integrated Care; Chronic Respiratory Disease; Routinely Collected Data; Outpatient Referrals,,,"

Background

Promoting integrated care is a key goal of the NHS Long Term Plan to improve population respiratory health, yet there is limited data-driven evidence of its effectiveness. The Morecambe Bay Respiratory Network is an integrated care initiative operating in the North-West of England since 2017. A key target area has been reducing referrals to outpatient respiratory clinics by upskilling primary care teams. This study aims to explore space-time patterns in referrals from general practice in the Morecambe Bay area to evaluate the impact of the initiative.

Methods

Data on referrals to outpatient clinics and chronic respiratory disease patient counts between 2012-2020 were obtained from the Morecambe Bay Community Data Warehouse, a large store of routinely collected healthcare data. For analysis, the data is aggregated by year and small area geography. The methodology comprises of two parts. The first explores the issues that can arise when using routinely collected primary care data for space-time analysis and applies spatio-temporal conditional autoregressive modelling to adjust for data complexities. The second part models the rate of outpatient referral via a Poisson generalised linear mixed model that adjusts for changes in demographic factors and number of respiratory disease patients.

Results

The first year of the Morecambe Bay Respiratory Network was not associated with a significant difference in referral rate. However, the second and third years saw significant reductions in areas that had received intervention, with full intervention associated with a 31.8% (95% CI 17.0-43.9) and 40.5% (95% CI 27.5-50.9) decrease in referral rate in 2018 and 2019, respectively.

Conclusions

Routinely collected data can be used to robustly evaluate key outcome measures of integrated care. The results demonstrate that effective integrated care has real potential to ease the burden on respiratory outpatient services by reducing the need for an onward referral. This is of great relevance given the current pressure on outpatient services globally, particularly long waiting lists following the COVID-19 pandemic and the need for more innovative models of care.",,doi:https://doi.org/10.1186/s12913-024-10716-7; html:https://europepmc.org/articles/PMC10882730; pdf:https://europepmc.org/articles/PMC10882730?pdf=render 34459398,https://doi.org/10.3233/jad-210462,Assessing Genetic Overlap and Causality Between Blood Plasma Proteins and Alzheimer's Disease.,"Handy A, Lord J, Green R, Xu J, Aarsland D, Velayudhan L, Hye A, Dobson R, Proitsi P, Alzheimer’s Disease Neuroimaging initiative, AddNeuroMed, and the GERAD1 Consortium.",,Journal of Alzheimer's disease : JAD,2021,2021-01-01,Y,Apolipoprotein E; Blood proteins; Alzheimer’s disease; C-reactive Protein; Apolipoprotein B-100; Insulin-like Growth Factor Binding Protein 2; Vitamin D-binding Protein; Mendelian Randomization Analysis; Polygenic Trait,,,"

Background

Blood plasma proteins have been associated with Alzheimer's disease (AD), but understanding which proteins are on the causal pathway remains challenging.

Objective

Investigate the genetic overlap between candidate proteins and AD using polygenic risk scores (PRS) and interrogate their causal relationship using bi-directional Mendelian randomization (MR).

Methods

Following a literature review, 31 proteins were selected for PRS analysis. PRS were constructed for prioritized proteins with and without the apolipoprotein E region (APOE+/-PRS) and tested for association with AD status across three cohorts (n = 6,244). An AD PRS was also tested for association with protein levels in one cohort (n = 410). Proteins showing association with AD were taken forward for MR.

Results

For APOE ɛ3, apolipoprotein B-100, and C-reactive protein (CRP), protein APOE+ PRS were associated with AD below Bonferroni significance (pBonf, p < 0.00017). No protein APOE- PRS or AD PRS (APOE+/-) passed pBonf. However, vitamin D-binding protein (protein PRS APOE-, p = 0.009) and insulin-like growth factor-binding protein 2 (AD APOE- PRS p = 0.025, protein APOE- PRS p = 0.045) displayed suggestive signals and were selected for MR. In bi-directional MR, none of the five proteins demonstrated a causal association (p < 0.05) in either direction.

Conclusion

Apolipoproteins and CRP PRS are associated with AD and provide a genetic signal linked to a specific, accessible risk factor. While evidence of causality was limited, this study was conducted in a moderate sample size and provides a framework for larger samples with greater statistical power.",,pdf:https://content.iospress.com:443/download/journal-of-alzheimers-disease/jad210462?id=journal-of-alzheimers-disease%2Fjad210462; doi:https://doi.org/10.3233/JAD-210462; html:https://europepmc.org/articles/PMC8609677; pdf:https://europepmc.org/articles/PMC8609677?pdf=render +38388919,https://doi.org/10.1186/s12913-024-10716-7,"Spatio-temporal modelling of referrals to outpatient respiratory clinics in the integrated care system of the Morecambe Bay area, England.","Mountain R, Knight J, Heys K, Giorgi E, Gatheral T.",,BMC health services research,2024,2024-02-22,Y,Spatio-temporal; Integrated Care; Chronic Respiratory Disease; Routinely Collected Data; Outpatient Referrals,,,"

Background

Promoting integrated care is a key goal of the NHS Long Term Plan to improve population respiratory health, yet there is limited data-driven evidence of its effectiveness. The Morecambe Bay Respiratory Network is an integrated care initiative operating in the North-West of England since 2017. A key target area has been reducing referrals to outpatient respiratory clinics by upskilling primary care teams. This study aims to explore space-time patterns in referrals from general practice in the Morecambe Bay area to evaluate the impact of the initiative.

Methods

Data on referrals to outpatient clinics and chronic respiratory disease patient counts between 2012-2020 were obtained from the Morecambe Bay Community Data Warehouse, a large store of routinely collected healthcare data. For analysis, the data is aggregated by year and small area geography. The methodology comprises of two parts. The first explores the issues that can arise when using routinely collected primary care data for space-time analysis and applies spatio-temporal conditional autoregressive modelling to adjust for data complexities. The second part models the rate of outpatient referral via a Poisson generalised linear mixed model that adjusts for changes in demographic factors and number of respiratory disease patients.

Results

The first year of the Morecambe Bay Respiratory Network was not associated with a significant difference in referral rate. However, the second and third years saw significant reductions in areas that had received intervention, with full intervention associated with a 31.8% (95% CI 17.0-43.9) and 40.5% (95% CI 27.5-50.9) decrease in referral rate in 2018 and 2019, respectively.

Conclusions

Routinely collected data can be used to robustly evaluate key outcome measures of integrated care. The results demonstrate that effective integrated care has real potential to ease the burden on respiratory outpatient services by reducing the need for an onward referral. This is of great relevance given the current pressure on outpatient services globally, particularly long waiting lists following the COVID-19 pandemic and the need for more innovative models of care.",,doi:https://doi.org/10.1186/s12913-024-10716-7; html:https://europepmc.org/articles/PMC10882730; pdf:https://europepmc.org/articles/PMC10882730?pdf=render 34639458,https://doi.org/10.3390/ijerph181910156,Health-Related Quality of Life (HRQoL) Outcomes Following Injury in Childhood and Adolescence Using EuroQol (EQ-5D) Responses with Pooled Longitudinal Data.,"Dipnall JF, Rivara FP, Lyons RA, Ameratunga S, Brussoni M, Lecky FE, Bradley C, Beck B, Lyons J, Schneeberg A, Harrison JE, Gabbe BJ.",,International journal of environmental research and public health,2021,2021-09-27,Y,Trauma; Children; Injury; Pediatric; Adolescents; Disability; Health-related Quality Of Life; Health Outcomes; Eq-5d,,,"

Background

Injury is a leading contributor to the global disease burden in children, affecting their health-related quality of life (HRQoL)-yet valid estimates of burden are absent.

Methods

This study pooled longitudinal data from five cohort studies of pediatric injury survivors (5-17 years) at baseline, 1-, 4-, 6-, 12-, and 24- months (n = 2334). HRQoL post-injury was measured using the 3-level EQ-5D utility score (EQ-5D) and five health states (mobility, self-care, activity, pain, anxiety and depression (anxiety)).

Results

Mean EQ-5D post-injury did not return to baseline level (0.95) by 24 months (0.88) and was lower for females over time (-0.04, 95%CI -0.05, -0.02). A decreased adjusted risk ratio over time (ARR) was observed for intentional injuries (pain: 0.85, 95%CI 0.73,0.98; anxiety: 0.62, 95%CI 0.49,0.78); spinal cord injuries (mobility: 0.61, 95%CI 0.45,0.83), self-care: 0.76, 95%CI 0.63,0.91, activity: 0.64, 95%CI 0.47,0.88); moderate/severe traumatic brain injury (activity: 0.83, 95%CI 0.71,0.96). ARRs were also low for certain fractures, with various health states affected.

Conclusions

HRQoL outcomes over time for children and adolescents post-injury differed across key demographic and injury related attributes. HRQoL did not reach levels consistent with full health by 24 months with recovery plateauing from 6 to 24 months. Tailored interventions are required to respond to the varying post-injury recovery trajectories in this population.",,doi:https://doi.org/10.3390/ijerph181910156; html:https://europepmc.org/articles/PMC8507627; pdf:https://europepmc.org/articles/PMC8507627?pdf=render -36932161,https://doi.org/10.1038/s41433-023-02478-z,Evaluating patient-reported outcome measures (PROMs) for future clinical trials in adult patients with optic neuritis.,"Panthagani J, O'Donovan C, Aiyegbusi OL, Liu X, Bayliss S, Calvert M, Pesudovs K, Denniston AK, Moore DJ, Braithwaite T.",,"Eye (London, England)",2023,2023-03-17,Y,,,,"

Objective

To search for and critically appraise the psychometric quality of patient-reported outcome measures (PROMs) developed or validated in optic neuritis, in order to support high-quality research and care.

Methods

We systematically searched MEDLINE(Ovid), Embase(Ovid), PsycINFO(Ovid) and CINAHLPlus(EBSCO), and additional grey literature to November 2021, to identify PROM development or validation studies applicable to optic neuritis associated with any systemic or neurologic disease in adults. We included instruments developed using classic test theory or Rasch analysis approaches. We used established quality criteria to assess content development, validity, reliability, and responsiveness, grading multiple domains from A (high quality) to C (low quality).

Results

From 3142 screened abstracts we identified five PROM instruments potentially applicable to optic neuritis: three differing versions of the National Eye Institute (NEI)-Visual Function Questionnaire (VFQ): the 51-item VFQ; the 25-item VFQ and a 10-item neuro-ophthalmology supplement; and the Impact of Visual Impairment Scale (IVIS), a constituent of the Multiple Sclerosis Quality of Life Inventory (MSQLI) handbook, derived from the Functional Assessment of Multiple Sclerosis (FAMS). Psychometric appraisal revealed the NEI-VFQ-51 and 10-item neuro module had some relevant content development but weak psychometric development, and the FAMS had stronger psychometric development using Rasch Analysis, but was only somewhat relevant to optic neuritis. We identified no content or psychometric development for IVIS.

Conclusion

There is unmet need for a PROM with strong content and psychometric development applicable to optic neuritis for use in virtual care pathways and clinical trials to support drug marketing authorisation.",,pdf:https://www.nature.com/articles/s41433-023-02478-z.pdf; doi:https://doi.org/10.1038/s41433-023-02478-z; html:https://europepmc.org/articles/PMC10022552; pdf:https://europepmc.org/articles/PMC10022552?pdf=render 30999919,https://doi.org/10.1186/s12911-019-0805-0,Identifying clinically important COPD sub-types using data-driven approaches in primary care population based electronic health records.,"Pikoula M, Quint JK, Nissen F, Hemingway H, Smeeth L, Denaxas S.",,BMC medical informatics and decision making,2019,2019-04-18,Y,Cluster analysis; Electronic Health Records; Copd Exacerbations; Copd Epidemiology,The Human Phenome,,"

Background

COPD is a highly heterogeneous disease composed of different phenotypes with different aetiological and prognostic profiles and current classification systems do not fully capture this heterogeneity. In this study we sought to discover, describe and validate COPD subtypes using cluster analysis on data derived from electronic health records.

Methods

We applied two unsupervised learning algorithms (k-means and hierarchical clustering) in 30,961 current and former smokers diagnosed with COPD, using linked national structured electronic health records in England available through the CALIBER resource. We used 15 clinical features, including risk factors and comorbidities and performed dimensionality reduction using multiple correspondence analysis. We compared the association between cluster membership and COPD exacerbations and respiratory and cardiovascular death with 10,736 deaths recorded over 146,466 person-years of follow-up. We also implemented and tested a process to assign unseen patients into clusters using a decision tree classifier.

Results

We identified and characterized five COPD patient clusters with distinct patient characteristics with respect to demographics, comorbidities, risk of death and exacerbations. The four subgroups were associated with 1) anxiety/depression; 2) severe airflow obstruction and frailty; 3) cardiovascular disease and diabetes and 4) obesity/atopy. A fifth cluster was associated with low prevalence of most comorbid conditions.

Conclusions

COPD patients can be sub-classified into groups with differing risk factors, comorbidities, and prognosis, based on data included in their primary care records. The identified clusters confirm findings of previous clustering studies and draw attention to anxiety and depression as important drivers of the disease in young, female patients.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-019-0805-0; doi:https://doi.org/10.1186/s12911-019-0805-0; html:https://europepmc.org/articles/PMC6472089; pdf:https://europepmc.org/articles/PMC6472089?pdf=render +36932161,https://doi.org/10.1038/s41433-023-02478-z,Evaluating patient-reported outcome measures (PROMs) for future clinical trials in adult patients with optic neuritis.,"Panthagani J, O'Donovan C, Aiyegbusi OL, Liu X, Bayliss S, Calvert M, Pesudovs K, Denniston AK, Moore DJ, Braithwaite T.",,"Eye (London, England)",2023,2023-03-17,Y,,,,"

Objective

To search for and critically appraise the psychometric quality of patient-reported outcome measures (PROMs) developed or validated in optic neuritis, in order to support high-quality research and care.

Methods

We systematically searched MEDLINE(Ovid), Embase(Ovid), PsycINFO(Ovid) and CINAHLPlus(EBSCO), and additional grey literature to November 2021, to identify PROM development or validation studies applicable to optic neuritis associated with any systemic or neurologic disease in adults. We included instruments developed using classic test theory or Rasch analysis approaches. We used established quality criteria to assess content development, validity, reliability, and responsiveness, grading multiple domains from A (high quality) to C (low quality).

Results

From 3142 screened abstracts we identified five PROM instruments potentially applicable to optic neuritis: three differing versions of the National Eye Institute (NEI)-Visual Function Questionnaire (VFQ): the 51-item VFQ; the 25-item VFQ and a 10-item neuro-ophthalmology supplement; and the Impact of Visual Impairment Scale (IVIS), a constituent of the Multiple Sclerosis Quality of Life Inventory (MSQLI) handbook, derived from the Functional Assessment of Multiple Sclerosis (FAMS). Psychometric appraisal revealed the NEI-VFQ-51 and 10-item neuro module had some relevant content development but weak psychometric development, and the FAMS had stronger psychometric development using Rasch Analysis, but was only somewhat relevant to optic neuritis. We identified no content or psychometric development for IVIS.

Conclusion

There is unmet need for a PROM with strong content and psychometric development applicable to optic neuritis for use in virtual care pathways and clinical trials to support drug marketing authorisation.",,pdf:https://www.nature.com/articles/s41433-023-02478-z.pdf; doi:https://doi.org/10.1038/s41433-023-02478-z; html:https://europepmc.org/articles/PMC10022552; pdf:https://europepmc.org/articles/PMC10022552?pdf=render 37225263,https://doi.org/10.1136/bmjgast-2023-001139,Delphi consensus survey: the opinions of patients living with refractory ulcerative proctitis and the health care professionals who care for them.,"Kyriacou M, Radford S, Moran GW, Focus group collaborators group.",,BMJ open gastroenterology,2023,2023-05-01,Y,Ulcerative colitis; Inflammatory Bowel Disease; Adjuvant Treatment,,,"

Background

Refractory ulcerative proctitis presents a huge clinical challenge not only for the patients living with this chronic, progressive condition but also for the professionals who care for them. Currently, there is limited research and evidence-based guidance, resulting in many patients living with the symptomatic burden of disease and reduced quality of life. The aim of this study was to establish a consensus on the thoughts and opinions related to refractory proctitis disease burden and best practice for management.

Methods

A three-round Delphi consensus survey was conducted among patients living with refractory proctitis and the healthcare experts with knowledge on this disease from the UK. A brainstorming stage involving a focus group where the participants came up with an initial list of statements was completed. Following this, there were three rounds of Delphi surveys in which the participants were asked to rank the importance of the statements and provide any additional comments or clarifications. Calculation of mean scores, analysis of comments and revisions were performed to produce a final list of statements.

Results

In total, 14 statements were suggested by the focus group at the initial brainstorming stage. Following completion of three Delphi survey rounds, all 14 statements reached consensus following appropriate revision.

Conclusions

We established consensus on the thoughts and opinions related to refractory proctitis from both the experts who manage this disease and the patients living with it. This represents the first step towards developing clinical research data and ultimately the evidence needed for best practice management guidance of this condition.",,pdf:https://bmjopengastro.bmj.com/content/bmjgast/10/1/e001139.full.pdf; doi:https://doi.org/10.1136/bmjgast-2023-001139; html:https://europepmc.org/articles/PMC10230891; pdf:https://europepmc.org/articles/PMC10230891?pdf=render 37394283,https://doi.org/10.1002/ehf2.14444,Survival after HeartMate 3 left ventricular assist device implantation: real-world data from Europe.,"Numan L, Schramm R, Oerlemans MIFJ, van der Kaaij NP, Aarts E, Ramjankhan FZ, Oppelaar AM, Morshuis M, Guenther SPW, Zimpfer D, Riebandt J, Wiedemann D, Asselbergs FW, Van Laake LW.",,ESC heart failure,2023,2023-07-02,Y,,,,,,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14444; doi:https://doi.org/10.1002/ehf2.14444; html:https://europepmc.org/articles/PMC10375103; pdf:https://europepmc.org/articles/PMC10375103?pdf=render 35403174,https://doi.org/10.14218/jctp.2022.00003,Changing Trends in the Proportional Incidence and Five-year Net Survival of Screened and Non-screened Breast Cancers among Women During 1995-2011 in England.,"Wu H, Wong K, Lu SE, Broggio J, Zhang L.",,Journal of clinical and translational pathology,2022,2022-03-18,Y,Screening; Breast cancer; incidence; trends; Net Survival,,,"

Background and objectives

Uptake of breast cancer screening has been decreasing in England since 2007. However, the associated factors are unclear. On the other hand, survival among breast cancer patients have recently increased. We conducted a quasi-experimental analysis to test whether the trend-change in proportional incidence of non-screened cancers coincided with that in five-year net-survival.

Methods

We extracted population-based proportional incidence and age-standardized five-year net-survival data from Public Health England that included English women with invasive breast cancer diagnosed during 1995-2011 (linked to death certificates, followed through 2016). Piece-wise log-linear models with change-point/joinpoint were used to estimate temporal trends.

Results

Among 254,063 women in England with invasive breast cancer diagnosed during 1995-2011, there was downward-to-upward trend-change in proportional incidence of non-screened breast cancers (annual percent change [APC]=5.6 after 2007 versus APC=-3.5 before 2007, p<0.001) in diagnosis-year 2007, when a steeper upward-trend in age-standardized five-year net survival started (APC=5.7 after 2007/2008 versus APC=0.3 before 2007/2008, p<0.001). Net-survival difference of screened versus non-screened cancers also significantly narrowed (18% in 2007/2008 versus 5% in 2011). Similar associations were found in all strata of race, cancer stage, grade, and histology, except in Black patients or patients with stage I, stage III, or grade I cancer.

Conclusions

There was a downward-to-upward trend-change in proportional incidence of non-screened breast cancers in 2007 that coincided with a steeper upward-trend in age-standardized five-year net survival among English women in 2007. Survival benefits of breast cancer screening decreased during 2007-2011. The data support reduction of breast cancer screening in some patients, but future validation studies are warranted.",,pdf:https://publinestorage.blob.core.windows.net/journals/JCTP.2022.2(1).23.00003.pdf; doi:https://doi.org/10.14218/jctp.2022.00003; html:https://europepmc.org/articles/PMC8994161; pdf:https://europepmc.org/articles/PMC8994161?pdf=render @@ -1269,20 +1269,20 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 36357675,https://doi.org/10.1038/s41591-022-02046-0,Rare and common genetic determinants of metabolic individuality and their effects on human health.,"Surendran P, Stewart ID, Au Yeung VPW, Pietzner M, Raffler J, Wörheide MA, Li C, Smith RF, Wittemans LBL, Bomba L, Menni C, Zierer J, Rossi N, Sheridan PA, Watkins NA, Mangino M, Hysi PG, Di Angelantonio E, Falchi M, Spector TD, Soranzo N, Michelotti GA, Arlt W, Lotta LA, Denaxas S, Hemingway H, Gamazon ER, Howson JMM, Wood AM, Danesh J, Wareham NJ, Kastenmüller G, Fauman EB, Suhre K, Butterworth AS, Langenberg C.",,Nature medicine,2022,2022-11-10,Y,,,,"Garrod's concept of 'chemical individuality' has contributed to comprehension of the molecular origins of human diseases. Untargeted high-throughput metabolomic technologies provide an in-depth snapshot of human metabolism at scale. We studied the genetic architecture of the human plasma metabolome using 913 metabolites assayed in 19,994 individuals and identified 2,599 variant-metabolite associations (P < 1.25 × 10-11) within 330 genomic regions, with rare variants (minor allele frequency ≤ 1%) explaining 9.4% of associations. Jointly modeling metabolites in each region, we identified 423 regional, co-regulated, variant-metabolite clusters called genetically influenced metabotypes. We assigned causal genes for 62.4% of these genetically influenced metabotypes, providing new insights into fundamental metabolite physiology and clinical relevance, including metabolite-guided discovery of potential adverse drug effects (DPYD and SRD5A2). We show strong enrichment of inborn errors of metabolism-causing genes, with examples of metabolite associations and clinical phenotypes of non-pathogenic variant carriers matching characteristics of the inborn errors of metabolism. Systematic, phenotypic follow-up of metabolite-specific genetic scores revealed multiple potential etiological relationships.",,pdf:https://www.nature.com/articles/s41591-022-02046-0.pdf; doi:https://doi.org/10.1038/s41591-022-02046-0; html:https://europepmc.org/articles/PMC9671801; pdf:https://europepmc.org/articles/PMC9671801?pdf=render 36648036,https://doi.org/10.1016/j.jcmg.2022.06.011,Incident Clinical and Mortality Associations of Myocardial Native T1 in the UK Biobank.,"Raisi-Estabragh Z, McCracken C, Hann E, Condurache DG, Harvey NC, Munroe PB, Ferreira VM, Neubauer S, Piechnik SK, Petersen SE.",,JACC. Cardiovascular imaging,2023,2022-09-14,Y,Mortality; Cardiovascular disease; Cardiac Magnetic Resonance; Native T1 Mapping; Incident Events,,,"

Background

Cardiac magnetic resonance native T1-mapping provides noninvasive, quantitative, and contrast-free myocardial characterization. However, its predictive value in population cohorts has not been studied.

Objectives

The associations of native T1 with incident events were evaluated in 42,308 UK Biobank participants over 3.17 ± 1.53 years of prospective follow-up.

Methods

Native T1-mapping was performed in 1 midventricular short-axis slice using the Shortened Modified Look-Locker Inversion recovery technique (WIP780B) in 1.5-T scanners (Siemens Healthcare). Global myocardial T1 was calculated using an automated tool. Associations of T1 with: 1) prevalent risk factors (eg, diabetes, hypertension, and high cholesterol); 2) prevalent and incident diseases (eg, any cardiovascular disease [CVD], any brain disease, valvular heart disease, heart failure, nonischemic cardiomyopathies, cardiac arrhythmias, atrial fibrillation [AF], myocardial infarction, ischemic heart disease [IHD], and stroke); and 3) mortality (eg, all-cause, CVD, and IHD) were examined. Results are reported as odds ratios (ORs) or HRs per SD increment of T1 value with 95% CIs and corrected P values, from logistic and Cox proportional hazards regression models.

Results

Higher myocardial T1 was associated with greater odds of a range of prevalent conditions (eg, any CVD, brain disease, heart failure, nonischemic cardiomyopathies, AF, stroke, and diabetes). The strongest relationships were with heart failure (OR: 1.41 [95% CI: 1.26-1.57]; P = 1.60 × 10-9) and nonischemic cardiomyopathies (OR: 1.40 [95% CI: 1.16-1.66]; P = 2.42 × 10-4). Native T1 was positively associated with incident AF (HR: 1.25 [95% CI: 1.10-1.43]; P = 9.19 × 10-4), incident heart failure (HR: 1.47 [95% CI: 1.31-1.65]; P = 4.79 × 10-11), all-cause mortality (HR: 1.24 [95% CI: 1.12-1.36]; P = 1.51 × 10-5), CVD mortality (HR: 1.40 [95% CI: 1.14-1.73]; P = 0.0014), and IHD mortality (HR: 1.36 [95% CI: 1.03-1.80]; P = 0.0310).

Conclusions

This large population study demonstrates the utility of myocardial native T1-mapping for disease discrimination and outcome prediction.",,doi:https://doi.org/10.1016/j.jcmg.2022.06.011; doi:https://doi.org/10.1016/j.jcmg.2022.06.011; html:https://europepmc.org/articles/PMC10102720; pdf:https://europepmc.org/articles/PMC10102720?pdf=render 34873584,https://doi.org/10.1016/j.eclinm.2021.101212,Disentangling post-vaccination symptoms from early COVID-19.,"Canas LS, Österdahl MF, Deng J, Hu C, Selvachandran S, Polidori L, May A, Molteni E, Murray B, Chen L, Kerfoot E, Klaser K, Antonelli M, Hammers A, Spector T, Ourselin S, Steves C, Sudre CH, Modat M, Duncan EL.",,EClinicalMedicine,2021,2021-12-01,Y,"Vaccination; Side-effects; Early Detection; Mobile Technology; Self-reported Symptoms; Auc, Area Under The Curve; Bmi, Body Mass Index; Ci, Confidence Interval; Roc, Receiver Operating Curve; Lr, Logistic Regression; Iqr, Inter Quartile Range; Rf, Random Forest; Covid-19, Coronavirus Disease 2019; Covid-19 Detection; Rtpcr, Reverse Transcription Polymerase Chain Reaction; Severe Acute Respiratory Syndrome‐Related Coronavirus 2 (Sars-Cov-2); Lfat, Lateral Flow Antigen Test; Css, Covid Symptoms Study; Di, Data Invalid; Kcl, King's College London; Nhs Uk, National Health Service Of The United Kingdom; O-az, Oxford-astrazeneca Adenovirus-vectored Vaccine; Pb, Pfizer-bointech Mrna Vaccine; Sars-cov-2, Severe Acute Respiratory Syndrome-related Coronavirus-2; Uk, United Kingdom Of Great Britain And Nothern Ireland; Bmem, Bayesian Mixed-effect Model",,,"

Background

Identifying and testing individuals likely to have SARS-CoV-2 is critical for infection control, including post-vaccination. Vaccination is a major public health strategy to reduce SARS-CoV-2 infection globally. Some individuals experience systemic symptoms post-vaccination, which overlap with COVID-19 symptoms. This study compared early post-vaccination symptoms in individuals who subsequently tested positive or negative for SARS-CoV-2, using data from the COVID Symptom Study (CSS) app.

Methods

We conducted a prospective observational study in 1,072,313 UK CSS participants who were asymptomatic when vaccinated with Pfizer-BioNTech mRNA vaccine (BNT162b2) or Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19) between 8 December 2020 and 17 May 2021, who subsequently reported symptoms within seven days (N=362,770) (other than local symptoms at injection site) and were tested for SARS-CoV-2 (N=14,842), aiming to differentiate vaccination side-effects per se from superimposed SARS-CoV-2 infection. The post-vaccination symptoms and SARS-CoV-2 test results were contemporaneously logged by participants. Demographic and clinical information (including comorbidities) were recorded. Symptom profiles in individuals testing positive were compared with a 1:1 matched population testing negative, including using machine learning and multiple models considering UK testing criteria.

Findings

Differentiating post-vaccination side-effects alone from early COVID-19 was challenging, with a sensitivity in identification of individuals testing positive of 0.6 at best. Most of these individuals did not have fever, persistent cough, or anosmia/dysosmia, requisite symptoms for accessing UK testing; and many only had systemic symptoms commonly seen post-vaccination in individuals negative for SARS-CoV-2 (headache, myalgia, and fatigue).

Interpretation

Post-vaccination symptoms per se cannot be differentiated from COVID-19 with clinical robustness, either using symptom profiles or machine-derived models. Individuals presenting with systemic symptoms post-vaccination should be tested for SARS-CoV-2 or quarantining, to prevent community spread.

Funding

UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK National Institute for Health Research, UK Medical Research Council and British Heart Foundation, Chronic Disease Research Foundation, Zoe Limited.",,doi:https://doi.org/10.1016/j.eclinm.2021.101212; doi:https://doi.org/10.1016/j.eclinm.2021.101212; html:https://europepmc.org/articles/PMC8635464; pdf:https://europepmc.org/articles/PMC8635464?pdf=render -37658971,https://doi.org/10.1007/s11897-023-00626-w,Multimorbidity in Heart Failure: Leveraging Cluster Analysis to Guide Tailored Treatment Strategies.,"van de Veerdonk MC, Savarese G, Handoko ML, Beulens JWJ, Asselbergs F, Uijl A.",,Current heart failure reports,2023,2023-09-02,Y,Clustering; Phenotyping; Heart Failure; Machine Learning; Treatment Response; Precision Medicine,,,"

Review purpose

This review summarises key findings on treatment effects within phenotypical clusters of patients with heart failure (HF), making a distinction between patients with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF).

Findings

Treatment response differed among clusters; ACE inhibitors were beneficial in all HFrEF phenotypes, while only some studies show similar beneficial prognostic effects in HFpEF patients. Beta-blockers had favourable effects in all HFrEF patients but not in HFpEF phenotypes and tended to worsen prognosis in older, cardiorenal patients. Mineralocorticoid receptor antagonists had more favourable prognostic effects in young, obese males and metabolic HFpEF patients. While a phenotype-guided approach is a promising solution for individualised treatment strategies, there are several aspects that still require improvements before such an approach could be implemented in clinical practice. Stronger evidence from clinical trials and real-world data may assist in establishing a phenotype-guided treatment approach for patient with HF in the future.",,pdf:https://link.springer.com/content/pdf/10.1007/s11897-023-00626-w.pdf; doi:https://doi.org/10.1007/s11897-023-00626-w; html:https://europepmc.org/articles/PMC10589138; pdf:https://europepmc.org/articles/PMC10589138?pdf=render 36137640,https://doi.org/10.1136/bmjopen-2022-064586,Myocardial infarction and stroke subsequent to urinary tract infection (MISSOURI): protocol for a self-controlled case series using linked electronic health records.,"Reeve NF, Best V, Gillespie D, Hughes K, Lugg-Widger FV, Cannings-John R, Torabi F, Wootton M, Akbari A, Ahmed H.",,BMJ open,2022,2022-09-22,Y,Myocardial infarction; Stroke; Urinary tract infections,,,"

Introduction

There is increasing interest in the relationship between acute infections and acute cardiovascular events. Most previous research has focused on understanding whether the risk of acute cardiovascular events increases following a respiratory tract infection. The relationship between urinary tract infections (UTIs) and acute cardiovascular events is less well studied. Therefore, the aim of this study is to determine whether there is a causal relationship between UTI and acute myocardial infarction (MI) or stroke.

Methods and analysis

We will undertake a self-controlled case series study using linked anonymised general practice, hospital admission and microbiology data held within the Secure Anonymised Information Linkage (SAIL) Databank. Self-controlled case series is a relatively novel study design where individuals act as their own controls, thereby inherently controlling for time-invariant confounders. Only individuals who experience an exposure and outcome of interest are included.We will identify individuals in the SAIL Databank who have a hospital admission record for acute MI or stroke during the study period of 2010-2020. Individuals will need to be aged 30-100 during the study period and be Welsh residents for inclusion. UTI will be identified using general practice, microbiology and hospital admissions data. We will calculate the incidence of MI and stroke in predefined risk periods following an UTI and in 'baseline' periods (without UTI exposure) and use conditional Poisson regression models to derive incidence rate ratios.

Ethics and dissemination

Data access, research permissions and approvals have been obtained from the SAIL independent Information Governance Review Panel, project number 0972. Findings will be disseminated through conferences, blogs, social media threads and peer-reviewed journals. Results will be of interest internationally to primary and secondary care clinicians who manage UTIs and may inform future clinical trials of preventative therapy.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e064586.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-064586; html:https://europepmc.org/articles/PMC9511592; pdf:https://europepmc.org/articles/PMC9511592?pdf=render +37658971,https://doi.org/10.1007/s11897-023-00626-w,Multimorbidity in Heart Failure: Leveraging Cluster Analysis to Guide Tailored Treatment Strategies.,"van de Veerdonk MC, Savarese G, Handoko ML, Beulens JWJ, Asselbergs F, Uijl A.",,Current heart failure reports,2023,2023-09-02,Y,Clustering; Phenotyping; Heart Failure; Machine Learning; Treatment Response; Precision Medicine,,,"

Review purpose

This review summarises key findings on treatment effects within phenotypical clusters of patients with heart failure (HF), making a distinction between patients with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF).

Findings

Treatment response differed among clusters; ACE inhibitors were beneficial in all HFrEF phenotypes, while only some studies show similar beneficial prognostic effects in HFpEF patients. Beta-blockers had favourable effects in all HFrEF patients but not in HFpEF phenotypes and tended to worsen prognosis in older, cardiorenal patients. Mineralocorticoid receptor antagonists had more favourable prognostic effects in young, obese males and metabolic HFpEF patients. While a phenotype-guided approach is a promising solution for individualised treatment strategies, there are several aspects that still require improvements before such an approach could be implemented in clinical practice. Stronger evidence from clinical trials and real-world data may assist in establishing a phenotype-guided treatment approach for patient with HF in the future.",,pdf:https://link.springer.com/content/pdf/10.1007/s11897-023-00626-w.pdf; doi:https://doi.org/10.1007/s11897-023-00626-w; html:https://europepmc.org/articles/PMC10589138; pdf:https://europepmc.org/articles/PMC10589138?pdf=render 32975552,https://doi.org/10.1001/jamapediatrics.2020.4573,Susceptibility to SARS-CoV-2 Infection Among Children and Adolescents Compared With Adults: A Systematic Review and Meta-analysis.,"Viner RM, Mytton OT, Bonell C, Melendez-Torres GJ, Ward J, Hudson L, Waddington C, Thomas J, Russell S, van der Klis F, Koirala A, Ladhani S, Panovska-Griffiths J, Davies NG, Booy R, Eggo RM.",,JAMA pediatrics,2021,2021-02-01,N,,,,"

Importance

The degree to which children and adolescents are infected by and transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. The role of children and adolescents in transmission of SARS-CoV-2 is dependent on susceptibility, symptoms, viral load, social contact patterns, and behavior.

Objective

To systematically review the susceptibility to and transmission of SARS-CoV-2 among children and adolescents compared with adults.

Data sources

PubMed and medRxiv were searched from database inception to July 28, 2020, and a total of 13 926 studies were identified, with additional studies identified through hand searching of cited references and professional contacts.

Study selection

Studies that provided data on the prevalence of SARS-CoV-2 in children and adolescents (younger than 20 years) compared with adults (20 years and older) derived from contact tracing or population screening were included. Single-household studies were excluded.

Data extraction and synthesis

PRISMA guidelines for abstracting data were followed, which was performed independently by 2 reviewers. Quality was assessed using a critical appraisal checklist for prevalence studies. Random-effects meta-analysis was undertaken.

Main outcomes and measures

Secondary infection rate (contact-tracing studies) or prevalence or seroprevalence (population screening studies) among children and adolescents compared with adults.

Results

A total of 32 studies comprising 41 640 children and adolescents and 268 945 adults met inclusion criteria, including 18 contact-tracing studies and 14 population screening studies. The pooled odds ratio of being an infected contact in children compared with adults was 0.56 (95% CI, 0.37-0.85), with substantial heterogeneity (I2 = 94.6%). Three school-based contact-tracing studies found minimal transmission from child or teacher index cases. Findings from population screening studies were heterogenous and were not suitable for meta-analysis. Most studies were consistent with lower seroprevalence in children compared with adults, although seroprevalence in adolescents appeared similar to adults.

Conclusions and relevance

In this meta-analysis, there is preliminary evidence that children and adolescents have lower susceptibility to SARS-CoV-2, with an odds ratio of 0.56 for being an infected contact compared with adults. There is weak evidence that children and adolescents play a lesser role than adults in transmission of SARS-CoV-2 at a population level. This study provides no information on the infectivity of children.",,html:https://europepmc.org/articles/pmc7519436; doi:https://doi.org/10.1001/jamapediatrics.2020.4573; html:https://europepmc.org/articles/PMC7519436; doi:https://doi.org/10.1001/jamapediatrics.2020.4573 33096553,https://doi.org/10.1093/ajcn/nqaa266,"Association between diet and periodontitis: a cross-sectional study of 10,000 NHANES participants.","Wright DM, McKenna G, Nugent A, Winning L, Linden GJ, Woodside JV.",,The American journal of clinical nutrition,2020,2020-12-01,N,Diet; Periodontitis; Nhanes; Robust Regression; Treelet Transformation,,,"

Background

Periodontitis is a major cause of tooth loss globally. Risk factors include age, smoking, and diabetes. Intake of specific nutrients has been associated with periodontitis risk but there has been little research into the influence of overall diet, potentially more relevant when formulating dietary recommendations.

Objectives

We aimed to investigate potential associations between diet and periodontitis using novel statistical techniques for dietary pattern analysis.

Methods

Two 24-h dietary recalls and periodontal examination data from the cross-sectional US NHANES, 2009-2014 (n = 10,010), were used. Dietary patterns were extracted using treelet transformation, a data-driven hierarchical clustering and dimension reduction technique. Associations between each pattern [treelet component (TC)] and extent of periodontitis [proportion of sites with clinical attachment loss (CAL) ≥ 3 mm] were estimated using robust logistic quantile regression, adjusting for age, sex, ethnicity, education level, smoking, BMI, and diabetes.

Results

Eight TCs explained 21% of the variation in diet, 1 of which (TC1) was associated with CAL extent. High TC1 scores represented a diet rich in salad, fruit, vegetables, poultry and seafood, and plain water or tea to drink. There was a substantial negative gradient in CAL extent from the lowest to the highest decile of TC1 (median proportion of sites with CAL ≥ 3 mm: decile 1 = 19.1%, decile 10 = 8.1%; OR, decile 10 compared with decile 1: 0.67; 95% CI: 0.46, 0.99).

Conclusions

Most dietary patterns identified were not associated with periodontitis extent. One pattern, however, rich in salad, fruit, and vegetables and with plain water or tea to drink, was associated with lower CAL extent. Treelet transformation may be a useful approach for calculating dietary patterns in nutrition research.",,pdf:https://academic.oup.com/ajcn/article-pdf/112/6/1485/34844146/nqaa266.pdf; doi:https://doi.org/10.1093/ajcn/nqaa266 35537476,https://doi.org/10.1177/01410768221095245,Indirect effects of the pandemic: highlighting the need for data-driven policy and preparedness.,"Banerjee A, Sudlow C, Lawler M.",,Journal of the Royal Society of Medicine,2022,2022-05-10,Y,,,,,,pdf:https://journals.sagepub.com/doi/pdf/10.1177/01410768221095245; doi:https://doi.org/10.1177/01410768221095245; html:https://europepmc.org/articles/PMC9234890; pdf:https://europepmc.org/articles/PMC9234890?pdf=render -38778017,https://doi.org/10.1038/s41541-024-00878-0,Influence of individuals' determinants including vaccine type on cellular and humoral responses to SARS-CoV-2 vaccination.,"Chambers ES, Cai W, Vivaldi G, Jolliffe DA, Perdek N, Li W, Faustini SE, Gibbons JM, Pade C, Richter AG, Coussens AK, Martineau AR.",,NPJ vaccines,2024,2024-05-22,Y,,,,"Vaccine development targeting SARS-CoV-2 in 2020 was of critical importance in reducing COVID-19 severity and mortality. In the U.K. during the initial roll-out most individuals either received two doses of Pfizer COVID-19 vaccine (BNT162b2) or the adenovirus-based vaccine from Oxford/AstraZeneca (ChAdOx1-nCoV-19). There are conflicting data as to the impact of age, sex and body habitus on cellular and humoral responses to vaccination, and most studies in this area have focused on determinants of mRNA vaccine immunogenicity. Here, we studied a cohort of participants in a population-based longitudinal study (COVIDENCE UK) to determine the influence of age, sex, body mass index (BMI) and pre-vaccination anti-Spike (anti-S) antibody status on vaccine-induced humoral and cellular immune responses to two doses of BNT162b2 or ChAdOx-n-CoV-19 vaccination. Younger age and pre-vaccination anti-S seropositivity were both associated with stronger antibody responses to vaccination. BNT162b2 generated higher neutralising and anti-S antibody titres to vaccination than ChAdOx1-nCoV-19, but cellular responses to the two vaccines were no different. Irrespective of vaccine type, increasing age was also associated with decreased frequency of cytokine double-positive CD4+T cells. Increasing BMI was associated with reduced frequency of SARS-CoV-2-specific TNF+CD8% T cells for both vaccines. Together, our findings demonstrate that increasing age and BMI are associated with attenuated cellular and humoral responses to SARS-CoV-2 vaccination. Whilst both vaccines induced T cell responses, BNT162b2 induced significantly elevated humoral immune response as compared to ChAdOx-n-CoV-19.",,pdf:https://www.nature.com/articles/s41541-024-00878-0.pdf; doi:https://doi.org/10.1038/s41541-024-00878-0; html:https://europepmc.org/articles/PMC11111746; pdf:https://europepmc.org/articles/PMC11111746?pdf=render 34125897,https://doi.org/10.1093/nar/gkab449,DGLinker: flexible knowledge-graph prediction of disease-gene associations.,"Hu J, Lepore R, Dobson RJB, Al-Chalabi A, M Bean D, Iacoangeli A.",,Nucleic acids research,2021,2021-07-01,Y,,,,"As a result of the advent of high-throughput technologies, there has been rapid progress in our understanding of the genetics underlying biological processes. However, despite such advances, the genetic landscape of human diseases has only marginally been disclosed. Exploiting the present availability of large amounts of biological and phenotypic data, we can use our current understanding of disease genetics to train machine learning models to predict novel genetic factors associated with the disease. To this end, we developed DGLinker, a webserver for the prediction of novel candidate genes for human diseases given a set of known disease genes. DGLinker has a user-friendly interface that allows non-expert users to exploit biomedical information from a wide range of biological and phenotypic databases, and/or to upload their own data, to generate a knowledge-graph and use machine learning to predict new disease-associated genes. The webserver includes tools to explore and interpret the results and generates publication-ready figures. DGLinker is available at https://dglinker.rosalind.kcl.ac.uk. The webserver is free and open to all users without the need for registration.",,doi:https://doi.org/10.1093/nar/gkab449; doi:https://doi.org/10.1093/nar/gkab449; html:https://europepmc.org/articles/PMC8262728; pdf:https://europepmc.org/articles/PMC8262728?pdf=render +38778017,https://doi.org/10.1038/s41541-024-00878-0,Influence of individuals' determinants including vaccine type on cellular and humoral responses to SARS-CoV-2 vaccination.,"Chambers ES, Cai W, Vivaldi G, Jolliffe DA, Perdek N, Li W, Faustini SE, Gibbons JM, Pade C, Richter AG, Coussens AK, Martineau AR.",,NPJ vaccines,2024,2024-05-22,Y,,,,"Vaccine development targeting SARS-CoV-2 in 2020 was of critical importance in reducing COVID-19 severity and mortality. In the U.K. during the initial roll-out most individuals either received two doses of Pfizer COVID-19 vaccine (BNT162b2) or the adenovirus-based vaccine from Oxford/AstraZeneca (ChAdOx1-nCoV-19). There are conflicting data as to the impact of age, sex and body habitus on cellular and humoral responses to vaccination, and most studies in this area have focused on determinants of mRNA vaccine immunogenicity. Here, we studied a cohort of participants in a population-based longitudinal study (COVIDENCE UK) to determine the influence of age, sex, body mass index (BMI) and pre-vaccination anti-Spike (anti-S) antibody status on vaccine-induced humoral and cellular immune responses to two doses of BNT162b2 or ChAdOx-n-CoV-19 vaccination. Younger age and pre-vaccination anti-S seropositivity were both associated with stronger antibody responses to vaccination. BNT162b2 generated higher neutralising and anti-S antibody titres to vaccination than ChAdOx1-nCoV-19, but cellular responses to the two vaccines were no different. Irrespective of vaccine type, increasing age was also associated with decreased frequency of cytokine double-positive CD4+T cells. Increasing BMI was associated with reduced frequency of SARS-CoV-2-specific TNF+CD8% T cells for both vaccines. Together, our findings demonstrate that increasing age and BMI are associated with attenuated cellular and humoral responses to SARS-CoV-2 vaccination. Whilst both vaccines induced T cell responses, BNT162b2 induced significantly elevated humoral immune response as compared to ChAdOx-n-CoV-19.",,pdf:https://www.nature.com/articles/s41541-024-00878-0.pdf; doi:https://doi.org/10.1038/s41541-024-00878-0; html:https://europepmc.org/articles/PMC11111746; pdf:https://europepmc.org/articles/PMC11111746?pdf=render 32894757,https://doi.org/10.1093/ageing/afaa138,Short physical performance battery as a practical tool to assess mortality risk in chronic obstructive pulmonary disease.,"Fermont JM, Mohan D, Fisk M, Bolton CE, Macnee W, Cockcroft JR, McEniery C, Fuld J, Cheriyan J, Tal-Singer R, Müllerova H, Wood AM, Wilkinson IB, Polkey MI, ERICA consortium.",,Age and ageing,2021,2021-05-01,Y,Mortality; Skeletal muscle; Biomarkers; Older People; chronic obstructive pulmonary disease,,,"

Rationale

chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and common in older adults. The BODE Index is the most recognised mortality risk score in COPD but includes a 6-minute walk test (6MWT) that is seldom available in practise; the BODE Index may be better adopted if the 6MWT was replaced.

Objectives

we investigated whether a modified BODE Index in which 6MWT was replaced by an alternative measure of physical capacity, specifically the short physical performance battery (SPPB) or components, retained its predictive ability for mortality in individuals with COPD.

Methods

we analysed 630 COPD patients from the ERICA cohort study for whom UK Office for National Statistics verified mortality data were available. Variables tested at baseline included spirometry, 6MWT, SPPB and its components (4-m gait speed test [4MGS], chair stand and balance). Predictive models were developed using stratified multivariable Cox regression, and assessed by C-indices and calibration plots with 10-fold cross-validation and replication.

Results

during median 2 years of follow-up, 60 (10%) individuals died. There was no significant difference between the discriminative ability of BODE6MWT (C-index 0.709, 95% confidence interval [CI], 0.680-0.737), BODESPPB (C-index 0.683, 95% CI, 0.647-0.712), BODE4MGS (C-index 0.676, 95% CI, 0.643-0.700) and BODEBALANCE (C-index 0.686, 95% CI, 0.651-0.713) for predicting mortality.

Conclusions

the SPPB, and its 4MGS and balance components, can potentially be used as an alternative to the 6MWT in the BODE Index without significant loss of predictive ability in all-cause mortality.",,pdf:https://academic.oup.com/ageing/article-pdf/50/3/795/37807880/afaa138.pdf; doi:https://doi.org/10.1093/ageing/afaa138; html:https://europepmc.org/articles/PMC8098797; pdf:https://europepmc.org/articles/PMC8098797?pdf=render 36660920,https://doi.org/10.1093/ehjci/jeac270,The role of obesity-related cardiovascular remodelling in mediating incident cardiovascular outcomes: a population-based observational study.,"Szabo L, McCracken C, Cooper J, Rider OJ, Vago H, Merkely B, Harvey NC, Neubauer S, Petersen SE, Raisi-Estabragh Z.",,European heart journal. Cardiovascular Imaging,2023,2023-06-01,Y,Obesity; body mass index; Mediation; Cardiac Magnetic Resonance Imaging; Cardiovascular Remodelling; Waist-to-hip Ratio; Disease Mechanisms; Incident Cardiovascular Outcomes,,,"

Aims

We examined associations of obesity with incident cardiovascular outcomes and cardiovascular magnetic resonance (CMR) phenotypes, integrating information from body mass index (BMI) and waist-to-hip ratio (WHR). Then, we used multiple mediation to define the role of obesity-related cardiac remodelling in driving obesity-outcome associations, independent of cardiometabolic diseases.

Methods and results

In 491 606 UK Biobank participants, using Cox proportional hazard models, greater obesity (higher WHR, higher BMI) was linked to significantly greater risk of incident ischaemic heart disease, atrial fibrillation (AF), heart failure (HF), all-cause mortality, and cardiovascular disease (CVD) mortality. In combined stratification by BMI and WHR thresholds, elevated WHR was associated with greater risk of adverse outcomes at any BMI level. Individuals with overweight BMI but normal WHR had weaker disease associations. In the subset of participants with CMR (n = 31 107), using linear regression, greater obesity was associated with higher left ventricular (LV) mass, greater LV concentricity, poorer LV systolic function, lower myocardial native T1, larger left atrial (LA) volumes, poorer LA function, and lower aortic distensibility. Of note, higher BMI was linked to higher, whilst greater WHR was linked to lower LV end-diastolic volume (LVEDV). In Cox models, greater LVEDV and LV mass (LVM) were linked to increased risk of CVD, most importantly HF and an increased LA maximal volume was the key predictive measure of new-onset AF. In multiple mediation analyses, hypertension and adverse LV remodelling (higher LVM, greater concentricity) were major independent mediators of the obesity-outcome associations. Atrial remodelling and native T1 were additional mediators in the associations of obesity with AF and HF, respectively.

Conclusions

We demonstrate associations of obesity with adverse cardiovascular phenotypes and their significant independent role in mediating obesity-outcome relationships. In addition, our findings support the integrated use of BMI and WHR to evaluate obesity-related cardiovascular risk.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeac270/48798234/jeac270.pdf; doi:https://doi.org/10.1093/ehjci/jeac270; html:https://europepmc.org/articles/PMC10284050; pdf:https://europepmc.org/articles/PMC10284050?pdf=render 33655501,https://doi.org/10.1111/bjd.19885,Four childhood atopic dermatitis subtypes identified from trajectory and severity of disease and internally validated in a large UK birth cohort.,"Mulick AR, Mansfield KE, Silverwood RJ, Budu-Aggrey A, Roberts A, Custovic A, Pearce N, Irvine AD, Smeeth L, Abuabara K, Langan SM.",,The British journal of dermatology,2021,2021-05-09,N,,,,"

Background

Atopic dermatitis (AD) disease activity and severity is highly variable during childhood. Early attempts to identify subtypes based on disease trajectory have assessed AD presence over time without incorporating severity.

Objectives

To identify childhood AD subtypes from symptom severity and trajectories, and determine associations with genetic risk factors, comorbidities and demographic and environmental variables.

Methods

We split data from children in the Avon Longitudinal Study of Parents and Children birth cohort into development and validation sets. To identify subtypes, we ran latent class analyses in the development set on AD symptom reports up to age 14 years. We regressed identified subtypes on nongenetic variables in mutually adjusted, multiply imputed (genetic: unadjusted, complete case) multinomial regression analyses. We repeated analyses in the validation set and report confirmed results.

Results

There were 11 866 children who contributed to analyses. We identified one Unaffected/Rare class (66% of children) and four AD subtypes: Severe-Frequent (4%), Moderate-Frequent (7%), Moderate-Declining (11%) and Mild-Intermittent (12%). Symptom patterns within the first two subtypes appeared more homogeneous than the last two. Filaggrin (FLG) null mutations, an AD polygenic risk score (PRS), being female, parental AD and comorbid asthma were associated with higher risk for some or all subtypes; FLG, AD-PRS and asthma associations were stronger along a subtype gradient arranged by increasing severity and frequency; FLG and AD-PRS further differentiated some phenotypes from each other.

Conclusions

Considering severity and AD trajectories leads to four well-defined and recognizable subtypes. The differential associations of risk factors among and between subtypes is novel and requires further research.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4660846/7/Mulick_etal_2021_Four-childhood-atopic-dermatitis-subtypes.pdf; doi:https://doi.org/10.1111/bjd.19885; html:https://europepmc.org/articles/PMC8410876; pdf:https://europepmc.org/articles/PMC8410876?pdf=render; doi:https://doi.org/10.1111/bjd.19885 -35277454,https://doi.org/10.1136/heartjnl-2021-320417,Smartphone detection of atrial fibrillation using photoplethysmography: a systematic review and meta-analysis.,"Gill S, Bunting KV, Sartini C, Cardoso VR, Ghoreishi N, Uh HW, Williams JA, Suzart-Woischnik K, Banerjee A, Asselbergs FW, Eijkemans M, Gkoutos GV, Kotecha D.",,Heart (British Cardiac Society),2022,2022-09-26,Y,Atrial fibrillation; Photoplethysmography; Smartphone,,,"

Objectives

Timely diagnosis of atrial fibrillation (AF) is essential to reduce complications from this increasingly common condition. We sought to assess the diagnostic accuracy of smartphone camera photoplethysmography (PPG) compared with conventional electrocardiogram (ECG) for AF detection.

Methods

This is a systematic review of MEDLINE, EMBASE and Cochrane (1980-December 2020), including any study or abstract, where smartphone PPG was compared with a reference ECG (1, 3 or 12-lead). Random effects meta-analysis was performed to pool sensitivity/specificity and identify publication bias, with study quality assessed using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) risk of bias tool.

Results

28 studies were included (10 full-text publications and 18 abstracts), providing 31 comparisons of smartphone PPG versus ECG for AF detection. 11 404 participants were included (2950 in AF), with most studies being small and based in secondary care. Sensitivity and specificity for AF detection were high, ranging from 81% to 100%, and from 85% to 100%, respectively. 20 comparisons from 17 studies were meta-analysed, including 6891 participants (2299 with AF); the pooled sensitivity was 94% (95% CI 92% to 95%) and specificity 97% (96%-98%), with substantial heterogeneity (p<0.01). Studies were of poor quality overall and none met all the QUADAS-2 criteria, with particular issues regarding selection bias and the potential for publication bias.

Conclusion

PPG provides a non-invasive, patient-led screening tool for AF. However, current evidence is limited to small, biased, low-quality studies with unrealistically high sensitivity and specificity. Further studies are needed, preferably independent from manufacturers, in order to advise clinicians on the true value of PPG technology for AF detection.",,pdf:https://heart.bmj.com/content/heartjnl/early/2022/03/10/heartjnl-2021-320417.full.pdf; doi:https://doi.org/10.1136/heartjnl-2021-320417; html:https://europepmc.org/articles/PMC9554073; pdf:https://europepmc.org/articles/PMC9554073?pdf=render 35038301,https://doi.org/10.2196/30523,Requirements for a Bespoke Intensive Care Unit Dashboard in Response to the COVID-19 Pandemic: Semistructured Interview Study.,"Davidson B, Ferrer Portillo KM, Wac M, McWilliams C, Bourdeaux C, Craddock I.",,JMIR human factors,2022,2022-04-13,Y,Development; Monitoring; Design; Disease monitoring; ICU; Interview; Intensive Care; Critical Care; Ehealth; Dashboard; Human-centered Design; Covid-19,,,"

Background

Intensive care units (ICUs) around the world are in high demand due to patients with COVID-19 requiring hospitalization. As researchers at the University of Bristol, we were approached to develop a bespoke data visualization dashboard to assist two local ICUs during the pandemic that will centralize disparate data sources in the ICU to help reduce the cognitive load on busy ICU staff in the ever-evolving pandemic.

Objective

The aim of this study was to conduct interviews with ICU staff in University Hospitals Bristol and Weston National Health Service Foundation Trust to elicit requirements for a bespoke dashboard to monitor the high volume of patients, particularly during the COVID-19 pandemic.

Methods

We conducted six semistructured interviews with clinical staff to obtain an overview of their requirements for the dashboard and to ensure its ultimate suitability for end users. Interview questions aimed to understand the job roles undertaken in the ICU, potential uses of the dashboard, specific issues associated with managing COVID-19 patients, key data of interest, and any concerns about the introduction of a dashboard into the ICU.

Results

From our interviews, we found the following design requirements: (1) a flexible dashboard, where the functionality can be updated quickly and effectively to respond to emerging information about the management of this new disease; (2) a mobile dashboard, which allows staff to move around on wards with a dashboard, thus potentially replacing paper forms to enable detailed and consistent data entry; (3) a customizable and intuitive dashboard, where individual users would be able to customize the appearance of the dashboard to suit their role; (4) real-time data and trend analysis via informative data visualizations that help busy ICU staff to understand a patient's clinical trajectory; and (5) the ability to manage tasks and staff, tracking both staff and patient movements, handovers, and task monitoring to ensure the highest quality of care.

Conclusions

The findings of this study confirm that digital solutions for ICU use would potentially reduce the cognitive load of ICU staff and reduce clinical errors at a time of notably high demand of intensive health care.",,pdf:https://humanfactors.jmir.org/2022/2/e30523/PDF; doi:https://doi.org/10.2196/30523; html:https://europepmc.org/articles/PMC9009380 -33634927,https://doi.org/10.1111/ans.16649,Risk factors for surgical site infections following spinal column trauma in an Australian trauma hospital.,"Baroun-Agob L, Liew S, Gabbe B.",,ANZ journal of surgery,2021,2021-02-26,N,Spine; Trauma; Risk factor; Surgical Wound Infection; Orthopaedic Surgery,,,"

Background

There is limited, and often conflicting, data in the literature about the prevalence and risk factors for surgical site infections (SSI) in spine surgery patients, with the majority consisting of elective spine surgery cohorts. Furthermore, there is no reported Australian data regarding rates of SSI in a spinal trauma cohort. The aim of this study is to identify factors associated with SSI following spinal column trauma.

Methods

Adult (16+ years) patients that underwent surgery following emergency admission for spinal trauma between January 2010 and December 2016 at a major trauma centre in Melbourne, Australia, were identified through the Victorian Orthopaedic Trauma Outcomes Registry. The presence of an SSI was confirmed from the electronic medical record. Patient and clinical factors were analysed by SSI status. Generalized Estimating Equations were used to model predictors of SSI, with a P-value <0.05 deemed significant.

Results

Data for 458 patients and 520 surgical wounds were collected. Twenty-six (5.7%) patients developed an SSI. Staphylococcus aureus was the most common microorganism with methicillin-sensitive S. aureus found in 46% of SSI cases. A posterior surgical approach and same site reoperation were predictors of SSI with adjusted odds ratios (95% confidence intervals) of 4.26 (1.22-14.80, P = 0.02) and 4.99 (1.10-22.58, P = 0.04), respectively.

Conclusions

A posterior surgical approach and same site reoperation increased the risk of SSI after spinal trauma. Further research into modifiable associations within these and other factors will help mitigate the risk of SSI and hence decrease the personal and financial costs of this potentially devastating complication.",,doi:https://doi.org/10.1111/ans.16649 +35277454,https://doi.org/10.1136/heartjnl-2021-320417,Smartphone detection of atrial fibrillation using photoplethysmography: a systematic review and meta-analysis.,"Gill S, Bunting KV, Sartini C, Cardoso VR, Ghoreishi N, Uh HW, Williams JA, Suzart-Woischnik K, Banerjee A, Asselbergs FW, Eijkemans M, Gkoutos GV, Kotecha D.",,Heart (British Cardiac Society),2022,2022-09-26,Y,Atrial fibrillation; Photoplethysmography; Smartphone,,,"

Objectives

Timely diagnosis of atrial fibrillation (AF) is essential to reduce complications from this increasingly common condition. We sought to assess the diagnostic accuracy of smartphone camera photoplethysmography (PPG) compared with conventional electrocardiogram (ECG) for AF detection.

Methods

This is a systematic review of MEDLINE, EMBASE and Cochrane (1980-December 2020), including any study or abstract, where smartphone PPG was compared with a reference ECG (1, 3 or 12-lead). Random effects meta-analysis was performed to pool sensitivity/specificity and identify publication bias, with study quality assessed using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) risk of bias tool.

Results

28 studies were included (10 full-text publications and 18 abstracts), providing 31 comparisons of smartphone PPG versus ECG for AF detection. 11 404 participants were included (2950 in AF), with most studies being small and based in secondary care. Sensitivity and specificity for AF detection were high, ranging from 81% to 100%, and from 85% to 100%, respectively. 20 comparisons from 17 studies were meta-analysed, including 6891 participants (2299 with AF); the pooled sensitivity was 94% (95% CI 92% to 95%) and specificity 97% (96%-98%), with substantial heterogeneity (p<0.01). Studies were of poor quality overall and none met all the QUADAS-2 criteria, with particular issues regarding selection bias and the potential for publication bias.

Conclusion

PPG provides a non-invasive, patient-led screening tool for AF. However, current evidence is limited to small, biased, low-quality studies with unrealistically high sensitivity and specificity. Further studies are needed, preferably independent from manufacturers, in order to advise clinicians on the true value of PPG technology for AF detection.",,pdf:https://heart.bmj.com/content/heartjnl/early/2022/03/10/heartjnl-2021-320417.full.pdf; doi:https://doi.org/10.1136/heartjnl-2021-320417; html:https://europepmc.org/articles/PMC9554073; pdf:https://europepmc.org/articles/PMC9554073?pdf=render 31194737,https://doi.org/10.1371/journal.pgen.1008164,Genome-wide association study of multisite chronic pain in UK Biobank.,"Johnston KJA, Adams MJ, Nicholl BI, Ward J, Strawbridge RJ, Ferguson A, McIntosh AM, Bailey MES, Smith DJ.",,PLoS genetics,2019,2019-06-13,Y,,Understanding the Causes of Disease,,"Chronic pain is highly prevalent worldwide and represents a significant socioeconomic and public health burden. Several aspects of chronic pain, for example back pain and a severity-related phenotype 'chronic pain grade', have been shown previously to be complex heritable traits with a polygenic component. Additional pain-related phenotypes capturing aspects of an individual's overall sensitivity to experiencing and reporting chronic pain have also been suggested as a focus for investigation. We made use of a measure of the number of sites of chronic pain in individuals within the UK general population. This measure, termed Multisite Chronic Pain (MCP), is a complex trait and its genetic architecture has not previously been investigated. To address this, we carried out a large-scale genome-wide association study (GWAS) of MCP in ~380,000 UK Biobank participants. Our findings were consistent with MCP having a significant polygenic component, with a Single Nucleotide Polymorphism (SNP) heritability of 10.2%. In total 76 independent lead SNPs at 39 risk loci were associated with MCP. Additional gene-level association analyses identified neurogenesis, synaptic plasticity, nervous system development, cell-cycle progression and apoptosis genes as enriched for genetic association with MCP. Genetic correlations were observed between MCP and a range of psychiatric, autoimmune and anthropometric traits, including major depressive disorder (MDD), asthma and Body Mass Index (BMI). Furthermore, in Mendelian randomisation (MR) analyses a causal effect of MCP on MDD was observed. Additionally, a polygenic risk score (PRS) for MCP was found to significantly predict chronic widespread pain (pain all over the body), indicating the existence of genetic variants contributing to both of these pain phenotypes. Overall, our findings support the proposition that chronic pain involves a strong nervous system component with implications for our understanding of the physiology of chronic pain. These discoveries may also inform the future development of novel treatment approaches.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1008164&type=printable; doi:https://doi.org/10.1371/journal.pgen.1008164; html:https://europepmc.org/articles/PMC6592570; pdf:https://europepmc.org/articles/PMC6592570?pdf=render +33634927,https://doi.org/10.1111/ans.16649,Risk factors for surgical site infections following spinal column trauma in an Australian trauma hospital.,"Baroun-Agob L, Liew S, Gabbe B.",,ANZ journal of surgery,2021,2021-02-26,N,Spine; Trauma; Risk factor; Surgical Wound Infection; Orthopaedic Surgery,,,"

Background

There is limited, and often conflicting, data in the literature about the prevalence and risk factors for surgical site infections (SSI) in spine surgery patients, with the majority consisting of elective spine surgery cohorts. Furthermore, there is no reported Australian data regarding rates of SSI in a spinal trauma cohort. The aim of this study is to identify factors associated with SSI following spinal column trauma.

Methods

Adult (16+ years) patients that underwent surgery following emergency admission for spinal trauma between January 2010 and December 2016 at a major trauma centre in Melbourne, Australia, were identified through the Victorian Orthopaedic Trauma Outcomes Registry. The presence of an SSI was confirmed from the electronic medical record. Patient and clinical factors were analysed by SSI status. Generalized Estimating Equations were used to model predictors of SSI, with a P-value <0.05 deemed significant.

Results

Data for 458 patients and 520 surgical wounds were collected. Twenty-six (5.7%) patients developed an SSI. Staphylococcus aureus was the most common microorganism with methicillin-sensitive S. aureus found in 46% of SSI cases. A posterior surgical approach and same site reoperation were predictors of SSI with adjusted odds ratios (95% confidence intervals) of 4.26 (1.22-14.80, P = 0.02) and 4.99 (1.10-22.58, P = 0.04), respectively.

Conclusions

A posterior surgical approach and same site reoperation increased the risk of SSI after spinal trauma. Further research into modifiable associations within these and other factors will help mitigate the risk of SSI and hence decrease the personal and financial costs of this potentially devastating complication.",,doi:https://doi.org/10.1111/ans.16649 36224187,https://doi.org/10.1038/s41467-022-33826-4,Key considerations to reduce or address respondent burden in patient-reported outcome (PRO) data collection.,"Aiyegbusi OL, Roydhouse J, Rivera SC, Kamudoni P, Schache P, Wilson R, Stephens R, Calvert M.",,Nature communications,2022,2022-10-12,Y,,,,"Patient-reported outcomes (PROs) are used in clinical trials to provide evidence of the benefits and risks of interventions from a patient perspective and to inform regulatory decisions and health policy. The collection of PROs in routine practice can facilitate monitoring of patient symptoms; identification of unmet needs; prioritisation and/or tailoring of treatment to the needs of individual patients and inform value-based healthcare initiatives. However, respondent burden needs to be carefully considered and addressed to avoid high rates of missing data and poor reporting of PRO results, which may lead to poor quality data for regulatory decision making and/or clinical care.",,pdf:https://www.nature.com/articles/s41467-022-33826-4.pdf; doi:https://doi.org/10.1038/s41467-022-33826-4; html:https://europepmc.org/articles/PMC9556436; pdf:https://europepmc.org/articles/PMC9556436?pdf=render 37311637,https://doi.org/10.1136/bmjopen-2023-071973,Number and timing of primary cleft lip and palate repair surgeries in England: whole nation study of electronic health records before and during the COVID-19 pandemic.,"Etoori D, Park MH, Blackburn RM, Fitzsimons KJ, Butterworth S, Medina J, Mc Grath-Lone L, Russell C, van der Meulen J.",,BMJ open,2023,2023-06-13,Y,epidemiology; Paediatric Surgery; Covid-19,,,"

Objective

To quantify differences in number and timing of first primary cleft lip and palate (CLP) repair procedures during the first year of the COVID-19 pandemic (1 April 2020 to 31 March 2021; 2020/2021) compared with the preceding year (1 April 2019 to 31 March 2020; 2019/2021).

Design

National observational study of administrative hospital data.

Setting

National Health Service hospitals in England.

Study population

Children <5 years undergoing primary repair for an orofacial cleft Population Consensus and Surveys Classification of Interventions and Procedures-fourth revisions (OPCS-4) codes F031, F291).

Main exposure

Procedure date (2020/2021 vs 2019/2020).

Main outcomes

Numbers and timing (age in months) of first primary CLP procedures.

Results

1716 CLP primary repair procedures were included in the analysis. In 2020/2021, 774 CLP procedures were carried out compared with 942 in 2019/2020, a reduction of 17.8% (95% CI 9.5% to 25.4%). The reduction varied over time in 2020/2021, with no surgeries at all during the first 2 months (April and May 2020). Compared with 2019/2020, first primary lip repair procedures performed in 2020/2021 were delayed by 1.6 months on average (95% CI 0.9 to 2.2 months). Delays in primary palate repairs were smaller on average but varied across the nine geographical regions.

Conclusion

There were significant reductions in the number and delays in timing of first primary CLP repair procedures in England during the first year of the pandemic, which may affect long-term outcomes.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/6/e071973.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-071973; html:https://europepmc.org/articles/PMC10276964; pdf:https://europepmc.org/articles/PMC10276964?pdf=render 37230417,https://doi.org/10.1016/j.jtha.2023.05.012,C1-inhibitor levels and venous thromboembolism: results from a Mendelian randomization study.,"Cupido AJ, Petersen RS, Schmidt AF, Levi M, Cohn DM, Fijen LM.",,Journal of thrombosis and haemostasis : JTH,2023,2023-05-23,N,,,,,,doi:https://doi.org/10.1016/j.jtha.2023.05.012 @@ -1292,12 +1292,12 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 30181555,https://doi.org/10.1038/s41398-018-0236-1,"Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression.","Strawbridge RJ, Ward J, Lyall LM, Tunbridge EM, Cullen B, Graham N, Ferguson A, Johnston KJA, Lyall DM, Mackay D, Cavanagh J, Howard DM, Adams MJ, Deary I, Escott-Price V, O'Donovan M, McIntosh AM, Bailey MES, Pell JP, Harrison PJ, Smith DJ.",,Translational psychiatry,2018,2018-09-04,Y,,Understanding the Causes of Disease,,"Risk-taking behaviour is an important component of several psychiatric disorders, including attention-deficit hyperactivity disorder, schizophrenia and bipolar disorder. Previously, two genetic loci have been associated with self-reported risk taking and significant genetic overlap with psychiatric disorders was identified within a subsample of UK Biobank. Using the white British participants of the full UK Biobank cohort (n = 83,677 risk takers versus 244,662 controls) for our primary analysis, we conducted a genome-wide association study of self-reported risk-taking behaviour. In secondary analyses, we assessed sex-specific effects, trans-ethnic heterogeneity and genetic overlap with psychiatric traits. We also investigated the impact of risk-taking-associated SNPs on both gene expression and structural brain imaging. We identified 10 independent loci for risk-taking behaviour, of which eight were novel and two replicated previous findings. In addition, we found two further sex-specific risk-taking loci. There were strong positive genetic correlations between risk-taking and attention-deficit hyperactivity disorder, bipolar disorder and schizophrenia. Index genetic variants demonstrated effects generally consistent with the discovery analysis in individuals of non-British White, South Asian, African-Caribbean or mixed ethnicity. Polygenic risk scores comprising alleles associated with increased risk taking were associated with lower white matter integrity. Genotype-specific expression pattern analyses highlighted DPYSL5, CGREF1 and C15orf59 as plausible candidate genes. Overall, our findings substantially advance our understanding of the biology of risk-taking behaviour, including the possibility of sex-specific contributions, and reveal consistency across ethnicities. We further highlight several putative novel candidate genes, which may mediate these genetic effects.",,pdf:https://www.nature.com/articles/s41398-018-0236-1.pdf; doi:https://doi.org/10.1038/s41398-018-0236-1; html:https://europepmc.org/articles/PMC6123450; pdf:https://europepmc.org/articles/PMC6123450?pdf=render 37679551,https://doi.org/10.1038/s41590-023-01635-6,Author Correction: Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets.,"Zhao JH, Stacey D, Eriksson N, Macdonald-Dunlop E, Hedman ÅK, Kalnapenkis A, Enroth S, Cozzetto D, Digby-Bell J, Marten J, Folkersen L, Herder C, Jonsson L, Bergen SE, Gieger C, Needham EJ, Surendran P, Estonian Biobank Research Team, Paul DS, Polasek O, Thorand B, Grallert H, Roden M, Võsa U, Esko T, Hayward C, Johansson Å, Gyllensten U, Powell N, Hansson O, Mattsson-Carlgren N, Joshi PK, Danesh J, Padyukov L, Klareskog L, Landén M, Wilson JF, Siegbahn A, Wallentin L, Mälarstig A, Butterworth AS, Peters JE.",,Nature immunology,2023,2023-11-01,Y,,,,,,doi:https://doi.org/10.1038/s41590-023-01635-6; html:https://europepmc.org/articles/PMC10602847; pdf:https://europepmc.org/articles/PMC10602847?pdf=render 34137744,https://doi.org/10.1097/ta.0000000000003317,Association between type 2 diabetes and long-term outcomes in middle-aged and older trauma patients.,"Daly SL, Gabbe BJ, Climie RE, Ekegren CL.",,The journal of trauma and acute care surgery,2022,2022-01-01,N,,,,"

Background

Diabetes is associated with increased hospital complications and mortality following trauma. However, there is limited research on the longer-term recovery of trauma patients with diabetes. The aim of this study was to explore the association between type 2 diabetes (T2D) and in-hospital and 24-month outcomes in major trauma patients.

Methods

In this cohort study using the Victorian State Trauma Registry, middle-aged and older adults (≥45 years) with major trauma were followed up at 24 months postinjury. Logistic regression (univariable and multivariable) analyses were used to determine the association between diabetes status and 24-month patient-reported outcomes. In-hospital outcomes were compared between groups using χ2 tests.

Results

Of the 11,490 participants who survived to hospital discharge, 8,493 survived to 24 months postinjury and were followed up at that time point: 953 people (11%) with and 7540 (89%) without T2D. People with T2D had a higher in-hospital death rate (19%) compared with people without T2D (16%; p < 0.001). After adjusting for confounders, people with T2D had poorer outcomes 24 months postinjury than people without T2D, with respect to functional recovery (Glasgow Outcome Scale Extended) (adjusted odds ratio [AOR], 0.58; 95% confidence interval [CI], 0.48-0.69) and return to work/study (AOR, 0.51; 95% CI, 0.37-0.71]). People with T2D experienced higher odds of problems with mobility (AOR, 1.92; 95% CI, 1.60-2.30), self-care (AOR, 1.94; 95% CI, 1.64, 2.29), usual activities (AOR, 1.50; 95% CI, 1.26-1.79), pain and discomfort (AOR, 1.75; 95% CI, 1.49-2.07), anxiety and depression (AOR, 1.45; 95% CI, 1.24, 1.70), and self-reported disability (AOR, 1.51; 95% CI, 1.28-1.79) than people without T2D.

Conclusion

Major trauma patients with T2D have a poorer prognosis than patients without T2D, both during their hospital admission and 24 months postinjury. Patients with T2D may need additional health care and support following trauma to reach their recovery potential.

Level of evidence

Prognostic, level III.",,doi:https://doi.org/10.1097/TA.0000000000003317 -37750555,https://doi.org/10.1161/jaha.123.030766,Impact of New Cardiovascular Events on Quality of Life and Hospital Costs in People With Cardiovascular Disease in the United Kingdom and United States.,"Lui JNM, Williams C, Keng MJ, Hopewell JC, Sammons E, Chen F, Gray A, Bowman L, Landray SMJ, Mihaylova B, REVEAL Collaborative Group.",,Journal of the American Heart Association,2023,2023-09-26,Y,Cardiovascular diseases; Quality of life; United States; United Kingdom; Secondary Prevention; Health Care Costs,,,"

Background

Despite optimized risk factor control, people with prior cardiovascular disease remain at high cardiovascular disease risk. We assess the immediate- and longer-term impacts of new vascular and nonvascular events on quality of life (QoL) and hospital costs among participants in the REVEAL (Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification) trial in secondary prevention.

Methods and results

Data on demographic and clinical characteristics, health-related quality of life (QoL: EuroQoL 5-Dimension-5-Level), adverse events, and hospital admissions during the 4-year follow-up of the 21 820 participants recruited in Europe and North America informed assessments of the impacts of new adverse events on QoL and hospital costs from the UK and US health systems' perspectives using generalized linear regression models. Reductions in QoL were estimated in the years of event occurrence for nonhemorrhagic stroke (-0.067 [United Kingdom], -0.069 [US]), heart failure admission (-0.072 [United Kingdom], -0.103 [US]), incident cancer (-0.064 [United Kingdom], -0.068 [US]), and noncoronary revascularization (-0.071 [United Kingdom], -0.061 [US]), as well as in subsequent years following these events. Myocardial infarction and coronary revascularization (CRV) procedures were not found to affect QoL. All adverse events were associated with additional hospital costs in the years of events and in subsequent years, with the highest additional costs in the years of noncoronary revascularization (£5830 [United Kingdom], $14 133 [US Medicare]), of myocardial infarction with urgent CRV procedure (£5614, $24722), and of urgent/nonurgent CRV procedure without myocardial infarction (£4674/£4651 and $15 251/$17 539).

Conclusions

Stroke, heart failure, and noncoronary revascularization procedures substantially reduce QoL, and all cardiovascular disease events increase hospital costs. These estimates are useful in informing cost-effectiveness of interventions to reduce cardiovascular disease risk in secondary prevention.

Registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252953; https://www.Isrctn.com. Unique identifier: ISRCTN48678192; https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.030766; doi:https://doi.org/10.1161/JAHA.123.030766; html:https://europepmc.org/articles/PMC7615160; pdf:https://europepmc.org/articles/PMC7615160?pdf=render 35025917,https://doi.org/10.1371/journal.pone.0261142,Inpatient COVID-19 mortality has reduced over time: Results from an observational cohort.,"Bechman K, Yates M, Mann K, Nagra D, Smith LJ, Rutherford AI, Patel A, Periselneris J, Walder D, Dobson RJB, Kraljevic Z, Teo JHT, Bernal W, Barker R, Galloway JB, Norton S.",,PloS one,2022,2022-01-13,Y,,,,"

Background

The Covid-19 pandemic in the United Kingdom has seen two waves; the first starting in March 2020 and the second in late October 2020. It is not known whether outcomes for those admitted with severe Covid were different in the first and second waves.

Methods

The study population comprised all patients admitted to a 1,500-bed London Hospital Trust between March 2020 and March 2021, who tested positive for Covid-19 by PCR within 3-days of admissions. Primary outcome was death within 28-days of admission. Socio-demographics (age, sex, ethnicity), hypertension, diabetes, obesity, baseline physiological observations, CRP, neutrophil, chest x-ray abnormality, remdesivir and dexamethasone were incorporated as co-variates. Proportional subhazards models compared mortality risk between wave 1 and wave 2. Cox-proportional hazard model with propensity score adjustment were used to compare mortality in patients prescribed remdesivir and dexamethasone.

Results

There were 3,949 COVID-19 admissions, 3,195 hospital discharges and 733 deaths. There were notable differences in age, ethnicity, comorbidities, and admission disease severity between wave 1 and wave 2. Twenty-eight-day mortality was higher during wave 1 (26.1% versus 13.1%). Mortality risk adjusted for co-variates was significantly lower in wave 2 compared to wave 1 [adjSHR 0.49 (0.37, 0.65) p<0.001]. Analysis of treatment impact did not show statistically different effects of remdesivir [HR 0.84 (95%CI 0.65, 1.08), p = 0.17] or dexamethasone [HR 0.97 (95%CI 0.70, 1.35) p = 0.87].

Conclusion

There has been substantial improvements in COVID-19 mortality in the second wave, even accounting for demographics, comorbidity, and disease severity. Neither dexamethasone nor remdesivir appeared to be key explanatory factors, although there may be unmeasured confounding present.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0261142&type=printable; doi:https://doi.org/10.1371/journal.pone.0261142; html:https://europepmc.org/articles/PMC8757902; pdf:https://europepmc.org/articles/PMC8757902?pdf=render +37750555,https://doi.org/10.1161/jaha.123.030766,Impact of New Cardiovascular Events on Quality of Life and Hospital Costs in People With Cardiovascular Disease in the United Kingdom and United States.,"Lui JNM, Williams C, Keng MJ, Hopewell JC, Sammons E, Chen F, Gray A, Bowman L, Landray SMJ, Mihaylova B, REVEAL Collaborative Group.",,Journal of the American Heart Association,2023,2023-09-26,Y,Cardiovascular diseases; Quality of life; United States; United Kingdom; Secondary Prevention; Health Care Costs,,,"

Background

Despite optimized risk factor control, people with prior cardiovascular disease remain at high cardiovascular disease risk. We assess the immediate- and longer-term impacts of new vascular and nonvascular events on quality of life (QoL) and hospital costs among participants in the REVEAL (Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification) trial in secondary prevention.

Methods and results

Data on demographic and clinical characteristics, health-related quality of life (QoL: EuroQoL 5-Dimension-5-Level), adverse events, and hospital admissions during the 4-year follow-up of the 21 820 participants recruited in Europe and North America informed assessments of the impacts of new adverse events on QoL and hospital costs from the UK and US health systems' perspectives using generalized linear regression models. Reductions in QoL were estimated in the years of event occurrence for nonhemorrhagic stroke (-0.067 [United Kingdom], -0.069 [US]), heart failure admission (-0.072 [United Kingdom], -0.103 [US]), incident cancer (-0.064 [United Kingdom], -0.068 [US]), and noncoronary revascularization (-0.071 [United Kingdom], -0.061 [US]), as well as in subsequent years following these events. Myocardial infarction and coronary revascularization (CRV) procedures were not found to affect QoL. All adverse events were associated with additional hospital costs in the years of events and in subsequent years, with the highest additional costs in the years of noncoronary revascularization (£5830 [United Kingdom], $14 133 [US Medicare]), of myocardial infarction with urgent CRV procedure (£5614, $24722), and of urgent/nonurgent CRV procedure without myocardial infarction (£4674/£4651 and $15 251/$17 539).

Conclusions

Stroke, heart failure, and noncoronary revascularization procedures substantially reduce QoL, and all cardiovascular disease events increase hospital costs. These estimates are useful in informing cost-effectiveness of interventions to reduce cardiovascular disease risk in secondary prevention.

Registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252953; https://www.Isrctn.com. Unique identifier: ISRCTN48678192; https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.030766; doi:https://doi.org/10.1161/JAHA.123.030766; html:https://europepmc.org/articles/PMC7615160; pdf:https://europepmc.org/articles/PMC7615160?pdf=render 37124165,https://doi.org/10.1016/j.ufug.2023.127934,"Effects of the onset of the COVID-19 pandemic restrictions on park crime in London, England: An interrupted time series analysis.","Hajna S, Cummins S.",,Urban forestry & urban greening,2023,2023-04-11,Y,Parks; Crimes; Covid-19,,,"

Introduction

Park crimes may have increased during the COVID-19 pandemic as a result of lockdowns that limited the number of capable guardians in public spaces. Despite this, the impacts of the lockdowns on park crimes remain unknown. To help us understand the societal impacts of policies implemented during this period, we assessed how the onset of the COVID-19 restrictions impacted urban park crime levels in London, England.

Methods

We identified crimes that occurred in publicly accessible parks and gardens in the Greater London Authority (England, UK) between March 1, 2019 and February 28, 2021 by overlaying open-access crime data with greenspace data supplied by the Greater Information for Greater London service. Using interrupted time series analyses, we estimated seasonality-adjusted associations between the onset of COVID-19 restrictions and park crimes.

Results

Overall (1565.7, 95% confidence intervals [CI] 1021.9 to 2109.5) and antisocial behaviour crimes (1772.7, 95% CI 823.6-2721.7) increased in London parks during the first full month of COVID-19 restrictions (April 2020). There were no notable trends in park crimes in London prior to the onset of restrictions, but overall and antisocial behaviour crimes decreased after the onset of restrictions at a rate of 156.4 (95% CI -220.25 to -92.51) and 164.7 (95% CI -280.68 to -48.74) crimes/months, respectively.

Conclusions

Overall park crimes increased during the first full month of the COVID-19 restrictions, largely driven by an increase in antisocial behaviours. Additional research is needed to identify the specific misdemeanours that accounted for this rise in antisocial behaviours and to investigate their downstream impacts (e.g. increases in policing costs or decreases in perceived park safety).",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10088280; doi:https://doi.org/10.1016/j.ufug.2023.127934; html:https://europepmc.org/articles/PMC10088280; pdf:https://europepmc.org/articles/PMC10088280?pdf=render 36713101,https://doi.org/10.1093/ehjdh/ztab082,A data mining-based cross-industry process for predicting major bleeding in mechanical circulatory support.,"Felix SEA, Bagheri A, Ramjankhan FR, Spruit MR, Oberski D, de Jonge N, van Laake LW, Suyker WJL, Asselbergs FW.",,European heart journal. Digital health,2021,2021-10-01,Y,Prediction; Bleeding; data mining; Mechanical Circulatory Support; Cross-Industry Standard Process For Data Mining (Crisp-Dm),,,"

Aims

Over a third of patients, treated with mechanical circulatory support (MCS) for end-stage heart failure, experience major bleeding. Currently, the prediction of a major bleeding in the near future is difficult because of many contributing factors. Predictive analytics using data mining could help calculating the risk of bleeding; however, its application is generally reserved for experienced researchers on this subject. We propose an easily applicable data mining tool to predict major bleeding in MCS patients.

Methods and results

All data of electronic health records of MCS patients in the University Medical Centre Utrecht were included. Based on the cross-industry standard process for data mining (CRISP-DM) methodology, an application named Auto-Crisp was developed. Auto-Crisp was used to evaluate the predictive models for a major bleeding in the next 3, 7, and 30 days after the first 30 days post-operatively following MCS implantation. The performance of the predictive models is investigated by the area under the curve (AUC) evaluation measure. In 25.6% of 273 patients, a total of 142 major bleedings occurred during a median follow-up period of 542 [interquartile range (IQR) 205-1044] days. The best predictive models assessed by Auto-Crisp had AUC values of 0.792, 0.788, and 0.776 for bleedings in the next 3, 7, and 30 days, respectively.

Conclusion

The Auto-Crisp-based predictive model created in this study had an acceptable performance to predict major bleeding in MCS patients in the near future. However, further validation of the application is needed to evaluate Auto-Crisp in other research projects.",,pdf:https://academic.oup.com/ehjdh/article-pdf/2/4/635/41972750/ztab082.pdf; doi:https://doi.org/10.1093/ehjdh/ztab082; html:https://europepmc.org/articles/PMC9707970; pdf:https://europepmc.org/articles/PMC9707970?pdf=render -35816976,https://doi.org/10.1016/j.jpsychires.2022.06.044,Anticoagulation for atrial fibrillation in people with serious mental illness in the general hospital setting.,"Farran D, Bean D, Wang T, Msosa Y, Casetta C, Dobson R, Teo JT, Scott P, Gaughran F.",,Journal of psychiatric research,2022,2022-06-28,N,Atrial fibrillation; Warfarin; Serious Mental Illness; Oral Anticoagulation; Doacs,,,"

Objective

People with serious mental illnesses (SMI) have an increased risk of stroke compared to the general population. This study aims to evaluate oral anticoagulation prescription trends in atrial fibrillation (AF) patients with and without a comorbid SMI.

Methods

An open-source retrieval system for clinical data (CogStack) was used to identify a cohort of AF patients with SMI who ever had an inpatient admission to King's College Hospital from 2011 to 2020. A Natural Language Processing pipeline was used to calculate CHA2DS2-VASc and HASBLED risk scores from Electronic Health Records free text. Antithrombotic prescriptions of warfarin and Direct acting oral anti-coagulants (DOACs) (apixaban, rivaroxaban, dabigatran, edoxaban) were extracted from discharge summaries.

Results

Among patients included in the study (n = 16 916), 2.7% had a recorded co-morbid SMI diagnosis. Compared to non-SMI patients, those with SMI had significantly higher CHA2DS2-VASc (mean (SD): 5.3 (1.96) vs 4.7 (2.08), p < 0.001) and HASBLED scores (mean (SD): 3.2 (1.27) vs 2.5 (1.29), p < 0.001). Among AF patients having a CHA2DS2-VASc ≥2, those with co-morbid SMI were less likely than non-SMI patients to be prescribed an OAC (44% vs 54%, p < 0.001). However, there was no evidence of a significant difference between the two groups since 2019.

Conclusion

Over recent years, DOAC prescription rates have increased among AF patients with SMI in acute hospitals. More research is needed to confirm whether the introduction of DOACs has reduced OAC treatment gaps in people with serious mental illness and to assess whether the use of DOACs has improved health outcomes in this population.",,doi:https://doi.org/10.1016/j.jpsychires.2022.06.044; doi:https://doi.org/10.1016/j.jpsychires.2022.06.044 33543581,https://doi.org/10.1111/ans.16578,Outcomes of surgical site infections following spinal column trauma.,"Baroun-Agob L, Liew S, Gabbe B.",,ANZ journal of surgery,2021,2021-02-05,N,Spine; Trauma; Surgical Wound Infection; Orthopaedic Surgery; Patient-reported Outcome Measures,,,"

Background

Surgical site infections (SSI) are an undesirable outcome of spinal surgery for both the patient and healthcare system. To date, few studies have investigated the impact of SSI on patient-reported and clinical outcomes. Sepsis and readmission are potential sequelae of SSI, with sepsis potentially being life threatening. This study aimed to assess the association between SSI and patient outcomes in a spinal trauma cohort.

Methods

Adult (16+ years) patients who underwent emergency spinal surgery due to trauma between January 2010 and December 2016 at a major trauma centre in Melbourne, Australia, were identified through the Victorian Orthopaedic Trauma Outcomes Registry. The presence of an SSI was abstracted from the electronic medical record and outcomes were compared between patients with and without an SSI. Clinical outcomes were obtained from the medical record, and patient-reported outcomes at 6 and 12 months were obtained from the Victorian Orthopaedic Trauma Outcomes Registry. Chi-squared tests were used to compare patient outcomes between groups.

Results

Of the 458 included patients, 26 (5.7%) developed an SSI. Patient-reported outcomes at 6 and 12 months were not different between the groups. An SSI was associated with sepsis (χ21 = 24.20, P < 0.01), readmission (χ21 = 215.34, P < 0.01), revision surgery (χ21 = 171.21, P < 0.01) and removal of implants (χ21 = 4.31, P = 0.04) within 12 months of discharge.

Conclusion

These findings indicate that spine trauma SSIs are not associated with patient-reported outcomes and may not have lasting effects on patients. Larger studies are required to assess further follow-up and support our findings and possibly distinguish outcomes between superficial and deep SSI.",,doi:https://doi.org/10.1111/ans.16578 +35816976,https://doi.org/10.1016/j.jpsychires.2022.06.044,Anticoagulation for atrial fibrillation in people with serious mental illness in the general hospital setting.,"Farran D, Bean D, Wang T, Msosa Y, Casetta C, Dobson R, Teo JT, Scott P, Gaughran F.",,Journal of psychiatric research,2022,2022-06-28,N,Atrial fibrillation; Warfarin; Serious Mental Illness; Oral Anticoagulation; Doacs,,,"

Objective

People with serious mental illnesses (SMI) have an increased risk of stroke compared to the general population. This study aims to evaluate oral anticoagulation prescription trends in atrial fibrillation (AF) patients with and without a comorbid SMI.

Methods

An open-source retrieval system for clinical data (CogStack) was used to identify a cohort of AF patients with SMI who ever had an inpatient admission to King's College Hospital from 2011 to 2020. A Natural Language Processing pipeline was used to calculate CHA2DS2-VASc and HASBLED risk scores from Electronic Health Records free text. Antithrombotic prescriptions of warfarin and Direct acting oral anti-coagulants (DOACs) (apixaban, rivaroxaban, dabigatran, edoxaban) were extracted from discharge summaries.

Results

Among patients included in the study (n = 16 916), 2.7% had a recorded co-morbid SMI diagnosis. Compared to non-SMI patients, those with SMI had significantly higher CHA2DS2-VASc (mean (SD): 5.3 (1.96) vs 4.7 (2.08), p < 0.001) and HASBLED scores (mean (SD): 3.2 (1.27) vs 2.5 (1.29), p < 0.001). Among AF patients having a CHA2DS2-VASc ≥2, those with co-morbid SMI were less likely than non-SMI patients to be prescribed an OAC (44% vs 54%, p < 0.001). However, there was no evidence of a significant difference between the two groups since 2019.

Conclusion

Over recent years, DOAC prescription rates have increased among AF patients with SMI in acute hospitals. More research is needed to confirm whether the introduction of DOACs has reduced OAC treatment gaps in people with serious mental illness and to assess whether the use of DOACs has improved health outcomes in this population.",,doi:https://doi.org/10.1016/j.jpsychires.2022.06.044; doi:https://doi.org/10.1016/j.jpsychires.2022.06.044 36332947,https://doi.org/10.1136/bmjopen-2022-061843,Numbers and types of neurological emergencies in England and the influence of socioeconomic deprivation: a retrospective analysis of hospital episode statistics data.,"Jackson M, Szczepaniak M, Wall J, Maskery M, Mummery C, Morrish P, Williams A, Knight J, Emsley HCA.",,BMJ open,2022,2022-11-04,Y,Epilepsy; Neurology; Public Health,,,"

Objectives

In this first large-scale analysis of neurological emergency admissions in England, we determine the number and types of emergency admissions with neurological emergency diagnostic codes, how many are under the care of a neurologist or neurosurgeon and how such admissions vary by levels of deprivation.

Design

Retrospective empirical research employing a derived list of neurological emergency diagnostic codes SETTING: This study used the Hospital Episode Statistics data set for the financial year 2019/2020 based on 17 million in-year inpatient admissions in England including 6.5 million (100%) emergency admissions with any diagnosis codes.

Results

There were 1.4 million (21.2%) emergency inpatient admissions with a mention of any neurological code, approx. 248 455 (3.8%) with mention of a specific neurological emergency code from the derived list, and 72 485 (1.1%) included such a code as the primary reason for admission. The highest number of in-year admissions for adults was for epilepsy (145 995), with epilepsy as the primary diagnostic code in 15 945 (10.9%). Acute nerve root/spinal cord syndrome (41 215), head injury (29 235) and subarachnoid haemorrhage (18 505) accounted for the next three highest number of admissions. 3230 (1.4%) in-year emergency hospital admissions with mention of a neurological emergency code were under the care of a neurologist or neurosurgeon, with only 1315 (0.9%) admissions with mention of an epilepsy code under a neurologist. There was significant variation for epilepsy and functional neurological disorders (FNDs) in particular by Index of Multiple Deprivation decile. The association between deprivation and epilepsy and FND was significant with p-values of 2.5e-6 and 1.5e-8, respectively.

Conclusions

This study has identified important findings in relation to the burden of neurological emergency admissions but further work is needed, with greater clinical engagement in diagnostic coding, to better understand the implications for workforce and changes to service delivery needing to be implemented.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e061843.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-061843; html:https://europepmc.org/articles/PMC9639083; pdf:https://europepmc.org/articles/PMC9639083?pdf=render 33517835,https://doi.org/10.1080/17457300.2021.1876736,Identify the key characteristics of pedestrian collisions through in-depth interviews: a pilot study.,"Perkins M, Casalaz S, Mitra B, Gabbe B, Brown J, Oxley J, Cameron P, Beck B.",,International journal of injury control and safety promotion,2021,2021-01-31,N,Behaviour; Public Health; Pedestrian,,,"This study aimed to assess the feasibility of recruiting injured pedestrians from the emergency department of a major trauma centre, using an in-depth interview shortly post collision. Convenience sampling was used to prospectively recruit injured pedestrians from the Alfred Hospital Emergency and Trauma Centre. Of the 102 injured pedestrians, 39 met eligibility criteria and of these, 30 (77%) consented and completed the questionnaire. Over half of the collisions occurred at an intersection (57%), and of these the most common pre-impact vehicle manoeuvre was a vehicle turning into the street the pedestrian was crossing. In-depth interview during the early post-crash period was a feasible and effective method of collecting detailed data in an accessible sample. However, only 38% of patients met eligibility criteria. To enhance representativeness, supplementing interview data with police-reported crash data, recruiting from hospital wards and crash location assessment is recommended.",,pdf:https://figshare.com/articles/journal_contribution/Identify_the_key_characteristics_of_pedestrian_collisions_through_in-depth_interviews_a_pilot_study/13671482/1/files/26241158.pdf; doi:https://doi.org/10.1080/17457300.2021.1876736 35508365,https://doi.org/10.1136/injuryprev-2021-044513,Prevalence of alcohol and other drug use in patients presenting to hospital for fall-related injuries: a systematic review.,"Lau G, Ang JY, Kim N, Gabbe BJ, Mitra B, Dietze PM, Reeder S, Beck B.",,Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention,2022,2022-05-04,N,Drugs; Alcohol; Fall; Systematic review; Metanalysis,,,"

Background

Alcohol and other drug (AOD) use is a key preventable risk factor for serious injuries. Prevention strategies to date have largely focused on transport injuries, despite AOD use being a significant risk factor for other injury causes, including falls. This systematic review aimed to report the prevalence of AOD use in patients presenting to hospital for fall-related injuries.

Methods

This systematic review includes studies published in English after the year 2010 that objectively measured the prevalence of AOD use in patients presenting to hospital for a fall-related injury. Screening, data extraction and risk of bias assessments were completed by two independent reviewers. Data were presented using narrative synthesis and, where appropriate, meta-analyses.

Results

A total of 12 707 records were screened. Full texts were retrieved for 2042 records, of which 29 were included. Four studies reported the combined prevalence of any alcohol and/or drug use, generating a pooled prevalence estimate of 37% (95% CI 25% to 49%). Twenty-two records reported on the prevalence of acute alcohol use alone and nine reported specifically on the prevalence of drugs other than alcohol, with prevalence ranging from 2% to 57% and 7% to 46%, respectively. The variation in prevalence estimates likely resulted from differences in toxicology testing methods across studies.

Conclusions

AOD exposure was common in hospitalised fall-related injuries. However, research addressing prevalence across different types of falls and the use of drugs other than alcohol was limited. Future research should address these areas to improve our understanding of which populations should be targeted in AOD and injury prevention strategies .

Prospero registration number

CRD42020188746.",,doi:https://doi.org/10.1136/injuryprev-2021-044513 @@ -1316,11 +1316,11 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 32895316,https://doi.org/10.1136/thoraxjnl-2020-215566,We need a robust evidence base to unravel the relationship between sex hormones and asthma.,"Sheikh A, Mukherjee M.",,Thorax,2020,2020-09-07,N,Asthma,,,,,pdf:https://thorax.bmj.com/content/thoraxjnl/75/10/826.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2020-215566 38142238,https://doi.org/10.1093/ije/dyad175,Cohort Profile: The Cardiovascular Research Data Catalogue.,"Reinikainen J, Palosaari T, Canosa-Valls AJ, Schmidt CO, Wissa R, Chadalavada S, Codó L, Gelpí JL, Joseph B, van der Lugt A, Pacella E, Petersen SE, Pujadas ER, Szabo L, Zeller T, Niiranen T, Lekadir K, Kuulasmaa K.",,International journal of epidemiology,2024,2024-02-01,N,,,,,,doi:https://doi.org/10.1093/ije/dyad175 33644414,https://doi.org/10.23889/ijpds.v5i3.1371,Public involvement & engagement in the work of a data safe haven: a case study of the SAIL Databank.,"Jones KH, Heys S, Thompson R, Cross L, Ford D.",,International journal of population data science,2020,2020-08-24,Y,Public Engagement; Data Safe Haven,,,"

Background

The SAIL Databank is a data safe haven established in 2007 at Swansea University (Wales). It was set up to create new opportunities for research using routinely-collected health and other public service datasets in linkable anonymised form. SAIL forms the bedrock of other Population Data Science initiatives made possible by the data and safe haven environment.

Aim

The aim of this paper is to provide an overview of public involvement & engagement in connection with the SAIL Databank and related Population Data Science initiatives.

Approach

We have a public involvement & engagement policy for SAIL in the context of Population Data Science. We established a Consumer Panel to provide advice on the work of SAIL and associated initiatives, including on proposed uses of SAIL data. We reviewed the topics discussed and provide examples of advice to researchers. We carried out a survey with members on their experiences of being on the Panel and their perceptions of the work of SAIL. We have a programme of wider public engagement and provide illustrations of this work.

Discussion

We summarise what this paper adds and some lessons learned. In the rapidly developing area of Population Data Science it is important that people feel welcome, that they are encouraged to ask questions and are provided with digestible information and adequate consideration time. Citizens have provided us with valuable anticipated and unanticipated opinions and novel viewpoints. We seek to take a pragmatic approach, prioritising the communication modes that allow maximum public input commensurate with the purpose of the activity.

Conclusion

This paper has set out our policy, rationale, scope and practical approaches to public involvement & engagement for SAIL and our related Population Data Science initiatives. Although there will be jurisdictional, cultural and organizational differences, we believe that the material covered in this paper will be of interest to other data focused enterprises across the world.",,pdf:https://ijpds.org/article/download/1371/2815; doi:https://doi.org/10.23889/ijpds.v5i3.1371; html:https://europepmc.org/articles/PMC7893854; pdf:https://europepmc.org/articles/PMC7893854?pdf=render -37284234,https://doi.org/10.1140/epjds/s13688-023-00391-9,"The shock, the coping, the resilience: smartphone application use reveals Covid-19 lockdown effects on human behaviors.","Liu XF, Wang ZZ, Xu XK, Wu Y, Zhao Z, Deng H, Wang P, Chao N, Huang YC.",,EPJ data science,2023,2023-06-05,Y,Human behaviors; Natural Experiment; Lockdown; Smartphone Apps; Covid-19,,,"Human mobility restriction policies have been widely used to contain the coronavirus disease-19 (COVID-19). However, a critical question is how these policies affect individuals' behavioral and psychological well-being during and after confinement periods. Here, we analyze China's five most stringent city-level lockdowns in 2021, treating them as natural experiments that allow for examining behavioral changes in millions of people through smartphone application use. We made three fundamental observations. First, the use of physical and economic activity-related apps experienced a steep decline, yet apps that provide daily necessities maintained normal usage. Second, apps that fulfilled lower-level human needs, such as working, socializing, information seeking, and entertainment, saw an immediate and substantial increase in screen time. Those that satisfied higher-level needs, such as education, only attracted delayed attention. Third, human behaviors demonstrated resilience as most routines resumed after the lockdowns were lifted. Nonetheless, long-term lifestyle changes were observed, as significant numbers of people chose to continue working and learning online, becoming ""digital residents."" This study also demonstrates the capability of smartphone screen time analytics in the study of human behaviors.

Supplementary information

The online version contains supplementary material available at 10.1140/epjds/s13688-023-00391-9.",,doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; html:https://europepmc.org/articles/PMC10240109; pdf:https://europepmc.org/articles/PMC10240109?pdf=render 33789468,https://doi.org/10.1302/0301-620x.103b4.bjj-2020-1647.r1,Outcomes of severe lower limb injury with Mangled Extremity Severity Score ≥ 7.,"Hoogervorst LA, Hart MJ, Simpson PM, Kimmel LA, Oppy A, Edwards ER, Gabbe BJ.",,The bone & joint journal,2021,2021-04-01,N,Injury; Lower limb; Return To Work; Salvage; Functional Outcomes; Mess; Gos-e; Eq-5d-3l; Surgical Amputation; 2-Year,,,"

Aims

Complex fractures of the femur and tibia with associated severe soft tissue injury are often devastating for the individual. The aim of this study was to describe the two-year patient-reported outcomes of patients in a civilian population who sustained a complex fracture of the femur or tibia with a Mangled Extremity Severity Score (MESS) of ≥ 7, whereby the score ranges from 2 (lowest severity) to 11 (highest severity).

Methods

Patients aged ≥ 16 years with a fractured femur or tibia and a MESS of ≥ 7 were extracted from the Victorian Orthopaedic Trauma Outcomes Registry (January 2007 to December 2018). Cases were grouped into surgical amputation or limb salvage. Descriptive analysis were used to examine return to work rates, three-level EuroQol five-dimension questionnaire (EQ-5D-3L), and Glasgow Outcome Scale-Extended (GOS-E) outcomes at 12 and 24 months post-injury.

Results

In all, 111 patients were included: 90 (81%) patients who underwent salvage and 21 (19%) patients with surgical amputation. The mean age of patients was 45.8 years (SD 15.8), 93 (84%) were male, 37 (33%) were involved in motor vehicle collisions, and the mean MESS score was 8.2 (SD 1.4). Two-year outcomes in the cohort were poor: six (7%) patients achieved a GOS-E good recovery, the mean EQ-5D-3L summary score was 0.52 (SD 0.27), and 17 (20%) patients had returned to work.

Conclusion

A small proportion of patients with severe lower limb injury (MESS ≥ 7) achieved a good level of function 24 months post-injury. Further follow-up is needed to better understand the long-term trajectory of these patients, including delayed amputation, hospital readmissions, and healthcare utilization. Cite this article: Bone Joint J 2021;103-B(4):769-774.",,doi:https://doi.org/10.1302/0301-620X.103B4.BJJ-2020-1647.R1 +37284234,https://doi.org/10.1140/epjds/s13688-023-00391-9,"The shock, the coping, the resilience: smartphone application use reveals Covid-19 lockdown effects on human behaviors.","Liu XF, Wang ZZ, Xu XK, Wu Y, Zhao Z, Deng H, Wang P, Chao N, Huang YC.",,EPJ data science,2023,2023-06-05,Y,Human behaviors; Natural Experiment; Lockdown; Smartphone Apps; Covid-19,,,"Human mobility restriction policies have been widely used to contain the coronavirus disease-19 (COVID-19). However, a critical question is how these policies affect individuals' behavioral and psychological well-being during and after confinement periods. Here, we analyze China's five most stringent city-level lockdowns in 2021, treating them as natural experiments that allow for examining behavioral changes in millions of people through smartphone application use. We made three fundamental observations. First, the use of physical and economic activity-related apps experienced a steep decline, yet apps that provide daily necessities maintained normal usage. Second, apps that fulfilled lower-level human needs, such as working, socializing, information seeking, and entertainment, saw an immediate and substantial increase in screen time. Those that satisfied higher-level needs, such as education, only attracted delayed attention. Third, human behaviors demonstrated resilience as most routines resumed after the lockdowns were lifted. Nonetheless, long-term lifestyle changes were observed, as significant numbers of people chose to continue working and learning online, becoming ""digital residents."" This study also demonstrates the capability of smartphone screen time analytics in the study of human behaviors.

Supplementary information

The online version contains supplementary material available at 10.1140/epjds/s13688-023-00391-9.",,doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; html:https://europepmc.org/articles/PMC10240109; pdf:https://europepmc.org/articles/PMC10240109?pdf=render +32831176,https://doi.org/10.7554/elife.58699,The contribution of asymptomatic SARS-CoV-2 infections to transmission on the Diamond Princess cruise ship.,"Emery JC, Russell TW, Liu Y, Hellewell J, Pearson CA, CMMID COVID-19 Working Group, Knight GM, Eggo RM, Kucharski AJ, Kucharski AJ, Funk S, Flasche S, Houben RM.",,eLife,2020,2020-08-24,Y,Human; Microbiology; Transmission; Infectious disease; epidemiology; Global Health; Asymptomatic Infections; Subclinical Infections; Covid-19; Sars-cov-2,,,"A key unknown for SARS-CoV-2 is how asymptomatic infections contribute to transmission. We used a transmission model with asymptomatic and presymptomatic states, calibrated to data on disease onset and test frequency from the Diamond Princess cruise ship outbreak, to quantify the contribution of asymptomatic infections to transmission. The model estimated that 74% (70-78%, 95% posterior interval) of infections proceeded asymptomatically. Despite intense testing, 53% (51-56%) of infections remained undetected, most of them asymptomatic. Asymptomatic individuals were the source for 69% (20-85%) of all infections. The data did not allow identification of the infectiousness of asymptomatic infections, however low ranges (0-25%) required a net reproduction number for individuals progressing through presymptomatic and symptomatic stages of at least 15. Asymptomatic SARS-CoV-2 infections may contribute substantially to transmission. Control measures, and models projecting their potential impact, need to look beyond the symptomatic cases if they are to understand and address ongoing transmission.",,doi:https://doi.org/10.7554/elife.58699; doi:https://doi.org/10.7554/eLife.58699; html:https://europepmc.org/articles/PMC7527238; pdf:https://europepmc.org/articles/PMC7527238?pdf=render 32616598,https://doi.org/10.1183/13993003.01809-2020,Using imaging to combat a pandemic: rationale for developing the UK National COVID-19 Chest Imaging Database.,"Jacob J, Alexander D, Baillie JK, Berka R, Bertolli O, Blackwood J, Buchan I, Bloomfield C, Cushnan D, Docherty A, Edey A, Favaro A, Gleeson F, Halling-Brown M, Hare S, Jefferson E, Johnstone A, Kirby M, McStay R, Nair A, Openshaw PJM, Parker G, Reilly G, Robinson G, Roditi G, Rodrigues JCL, Sebire N, Semple MG, Sudlow C, Woznitza N, Joshi I.",,The European respiratory journal,2020,2020-08-13,Y,,,,,,pdf:https://erj.ersjournals.com/content/erj/56/2/2001809.full.pdf; doi:https://doi.org/10.1183/13993003.01809-2020; html:https://europepmc.org/articles/PMC7331656; pdf:https://europepmc.org/articles/PMC7331656?pdf=render 35776955,https://doi.org/10.1093/ehjqcco/qcac039,One step closer to quantifying 'clinical likelihood' in pre-test probability.,"Weir-McCall JR, Williams MC, Wood A.",,European heart journal. Quality of care & clinical outcomes,2022,2022-09-01,N,,,,,,doi:https://doi.org/10.1093/ehjqcco/qcac039; html:https://europepmc.org/articles/PMC9442847; pdf:https://europepmc.org/articles/PMC9442847?pdf=render; doi:https://doi.org/10.1093/ehjqcco/qcac039 -32831176,https://doi.org/10.7554/elife.58699,The contribution of asymptomatic SARS-CoV-2 infections to transmission on the Diamond Princess cruise ship.,"Emery JC, Russell TW, Liu Y, Hellewell J, Pearson CA, CMMID COVID-19 Working Group, Knight GM, Eggo RM, Kucharski AJ, Kucharski AJ, Funk S, Flasche S, Houben RM.",,eLife,2020,2020-08-24,Y,Human; Microbiology; Transmission; Infectious disease; epidemiology; Global Health; Asymptomatic Infections; Subclinical Infections; Covid-19; Sars-cov-2,,,"A key unknown for SARS-CoV-2 is how asymptomatic infections contribute to transmission. We used a transmission model with asymptomatic and presymptomatic states, calibrated to data on disease onset and test frequency from the Diamond Princess cruise ship outbreak, to quantify the contribution of asymptomatic infections to transmission. The model estimated that 74% (70-78%, 95% posterior interval) of infections proceeded asymptomatically. Despite intense testing, 53% (51-56%) of infections remained undetected, most of them asymptomatic. Asymptomatic individuals were the source for 69% (20-85%) of all infections. The data did not allow identification of the infectiousness of asymptomatic infections, however low ranges (0-25%) required a net reproduction number for individuals progressing through presymptomatic and symptomatic stages of at least 15. Asymptomatic SARS-CoV-2 infections may contribute substantially to transmission. Control measures, and models projecting their potential impact, need to look beyond the symptomatic cases if they are to understand and address ongoing transmission.",,doi:https://doi.org/10.7554/elife.58699; doi:https://doi.org/10.7554/eLife.58699; html:https://europepmc.org/articles/PMC7527238; pdf:https://europepmc.org/articles/PMC7527238?pdf=render 36403308,https://doi.org/10.1016/j.media.2022.102678,DragNet: Learning-based deformable registration for realistic cardiac MR sequence generation from a single frame.,"Zakeri A, Hokmabadi A, Bi N, Wijesinghe I, Nix MG, Petersen SE, Frangi AF, Taylor ZA, Gooya A.",,Medical image analysis,2023,2022-11-02,N,Uncertainty Estimation; Uk Biobank; Deep Learning; Deformable Temporal Image Registration; Sequential Image Data Generation; Variational Recurrent Neural Networks,,,"Deformable image registration (DIR) can be used to track cardiac motion. Conventional DIR algorithms aim to establish a dense and non-linear correspondence between independent pairs of images. They are, nevertheless, computationally intensive and do not consider temporal dependencies to regulate the estimated motion in a cardiac cycle. In this paper, leveraging deep learning methods, we formulate a novel hierarchical probabilistic model, termed DragNet, for fast and reliable spatio-temporal registration in cine cardiac magnetic resonance (CMR) images and for generating synthetic heart motion sequences. DragNet is a variational inference framework, which takes an image from the sequence in combination with the hidden states of a recurrent neural network (RNN) as inputs to an inference network per time step. As part of this framework, we condition the prior probability of the latent variables on the hidden states of the RNN utilised to capture temporal dependencies. We further condition the posterior of the motion field on a latent variable from hierarchy and features from the moving image. Subsequently, the RNN updates the hidden state variables based on the feature maps of the fixed image and the latent variables. Different from traditional methods, DragNet performs registration on unseen sequences in a forward pass, which significantly expedites the registration process. Besides, DragNet enables generating a large number of realistic synthetic image sequences given only one frame, where the corresponding deformations are also retrieved. The probabilistic framework allows for computing spatio-temporal uncertainties in the estimated motion fields. Our results show that DragNet performance is comparable with state-of-the-art methods in terms of registration accuracy, with the advantage of offering analytical pixel-wise motion uncertainty estimation across a cardiac cycle and being a motion generator. We will make our code publicly available.",,doi:https://doi.org/10.1016/j.media.2022.102678; doi:https://doi.org/10.1016/j.media.2022.102678 32485082,https://doi.org/10.1002/ejhf.1924,Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are not associated with severe COVID-19 infection in a multi-site UK acute hospital trust.,"Bean DM, Kraljevic Z, Searle T, Bendayan R, Kevin O, Pickles A, Folarin A, Roguski L, Noor K, Shek A, Zakeri R, Shah AM, Teo JTH, Dobson RJB.",,European journal of heart failure,2020,2020-06-01,Y,Hypertension; Angiotensin-converting enzyme inhibitors; Disease Outcome; Covid-19,,,"

Aims

The SARS-CoV-2 virus binds to the angiotensin-converting enzyme 2 (ACE2) receptor for cell entry. It has been suggested that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB), which are commonly used in patients with hypertension or diabetes and may raise tissue ACE2 levels, could increase the risk of severe COVID-19 infection.

Methods and results

We evaluated this hypothesis in a consecutive cohort of 1200 acute inpatients with COVID-19 at two hospitals with a multi-ethnic catchment population in London (UK). The mean age was 68 ± 17 years (57% male) and 74% of patients had at least one comorbidity. Overall, 415 patients (34.6%) reached the primary endpoint of death or transfer to a critical care unit for organ support within 21 days of symptom onset. A total of 399 patients (33.3%) were taking ACEi or ARB. Patients on ACEi/ARB were significantly older and had more comorbidities. The odds ratio for the primary endpoint in patients on ACEi and ARB, after adjustment for age, sex and co-morbidities, was 0.63 (95% confidence interval 0.47-0.84, P < 0.01).

Conclusions

There was no evidence for increased severity of COVID-19 in hospitalised patients on chronic treatment with ACEi or ARB. A trend towards a beneficial effect of ACEi/ARB requires further evaluation in larger meta-analyses and randomised clinical trials.","This study aimed to determine whether or not two specific types of medication (ACE inhibitors and angiotensin-2 blockers - ACEi/ARB) used for hypertension or diabetes are associated with increased risk of severe COVID-19 infection in a sample of 1,200 inpatients (one third of whom were taking the medications under investigation) in two London hospitals. The researchers used data from electonic medical notes and electronic health records. The patients who were taking the medication were, on average, older and had more underlying health conditions than patients who were not. After accounting for these differences in patient health the researchers found that the risk of severe COVID infection was not higher for patients taking ACEi/ARB. This finding is important for patients because it suggests that they should continue to take ACEi/ARB that have been presecribed to them.",pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejhf.1924; doi:https://doi.org/10.1002/ejhf.1924; html:https://europepmc.org/articles/PMC7301045; pdf:https://europepmc.org/articles/PMC7301045?pdf=render 35699189,https://doi.org/10.1161/jaha.121.024248,Low-Density Lipoprotein Cholesterol Attributable Cardiovascular Disease Risk Is Sex Specific.,"Cupido AJ, Asselbergs FW, Schmidt AF, Hovingh GK.",,Journal of the American Heart Association,2022,2022-06-14,Y,Genetics; Cardiovascular disease; Risk factor; Sex‐differences,,,"Background Epidemiological studies show that women are generally at lower risk for cardiovascular disease than men. Here, we investigated the sex-specific differential effect of genetically increased low-density lipoprotein cholesterol (LDL-C) on cardiovascular disease (CVD) and other lipid-associated diseases. Methods and Results This is a 2-sample Mendelian randomization study that uses individual participant data from 425 043 participants from the UK Biobank, including 229 279 female participants. An 80-variant LDL-C weighted genetic score was generated. Linear and logistic regression models with interactions were used to identify differences between sex-specific LDL-C effects on lipids, carotid-intima media thickness, and multiple cardiovascular outcomes such as CVD, ischemic heart disease, peripheral artery disease, heart failure, aortic valve disease, type 2 diabetes, atrial fibrillation, and aortic aneurysm and dissection. After correction for multiple testing, we observed that the genetically increased LDL-C effect on CVD events was sex specific: per SD genetically increased LDL-C, female participants had a higher LDL-C increase but an attenuated CVD risk increase compared with male participants (LDL-C: female participants 0.71 mmol/L, 95% CI, 0.70-0.72 and male participants 0.57 mmol/L, 95% CI, 0.56-0.59. P for interaction: 5.03×10-60; CVD: female participants: odds ratio [OR], 1.32; 95% CI 1.24-1.40 and male participants: OR, 1.52; 95% CI, 1.46-1.58. P for interaction: 9.88×10-5). We also observed attenuated risks for ischemic heart disease and (nominally for) heart failure in female participants, and genetically increased LDL-C results in higher risk for aortic valve disease in female participants compared with male participants. Genetically increased LDL-C was also associated with an attenuated carotid-intima media thickness increase in female participants. We did not observe other significant attenuations. Sensitivity analyses with an unweighted genetic score and sex-specific weighted genetic scores showed similar results. Conclusions We found that genetically increased LDL-C has a sex-specific differential effect on the risk for cardiovascular disease, ischemic heart disease, heart failure, and aortic valve stenosis. Our observations provide evidence that LDL-C might be a less important determinant of CVD in women compared with men, suggesting that male patients might benefit more from LDL-C targeted therapies for CVD management than female patients and warranting investigations into the sex-specific relative contribution of risk factors for CVD.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.024248; doi:https://doi.org/10.1161/JAHA.121.024248; html:https://europepmc.org/articles/PMC9238661; pdf:https://europepmc.org/articles/PMC9238661?pdf=render @@ -1329,13 +1329,13 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 34244270,https://doi.org/10.1136/bmjopen-2020-048008,Protocol for development of a reporting guideline (TRIPOD-AI) and risk of bias tool (PROBAST-AI) for diagnostic and prognostic prediction model studies based on artificial intelligence.,"Collins GS, Dhiman P, Andaur Navarro CL, Ma J, Hooft L, Reitsma JB, Logullo P, Beam AL, Peng L, Van Calster B, van Smeden M, Riley RD, Moons KG.",,BMJ open,2021,2021-07-09,Y,epidemiology; Statistics & Research Methods; General Medicine (See Internal Medicine),,,"

Introduction

The Transparent Reporting of a multivariable prediction model of Individual Prognosis Or Diagnosis (TRIPOD) statement and the Prediction model Risk Of Bias ASsessment Tool (PROBAST) were both published to improve the reporting and critical appraisal of prediction model studies for diagnosis and prognosis. This paper describes the processes and methods that will be used to develop an extension to the TRIPOD statement (TRIPOD-artificial intelligence, AI) and the PROBAST (PROBAST-AI) tool for prediction model studies that applied machine learning techniques.

Methods and analysis

TRIPOD-AI and PROBAST-AI will be developed following published guidance from the EQUATOR Network, and will comprise five stages. Stage 1 will comprise two systematic reviews (across all medical fields and specifically in oncology) to examine the quality of reporting in published machine-learning-based prediction model studies. In stage 2, we will consult a diverse group of key stakeholders using a Delphi process to identify items to be considered for inclusion in TRIPOD-AI and PROBAST-AI. Stage 3 will be virtual consensus meetings to consolidate and prioritise key items to be included in TRIPOD-AI and PROBAST-AI. Stage 4 will involve developing the TRIPOD-AI checklist and the PROBAST-AI tool, and writing the accompanying explanation and elaboration papers. In the final stage, stage 5, we will disseminate TRIPOD-AI and PROBAST-AI via journals, conferences, blogs, websites (including TRIPOD, PROBAST and EQUATOR Network) and social media. TRIPOD-AI will provide researchers working on prediction model studies based on machine learning with a reporting guideline that can help them report key details that readers need to evaluate the study quality and interpret its findings, potentially reducing research waste. We anticipate PROBAST-AI will help researchers, clinicians, systematic reviewers and policymakers critically appraise the design, conduct and analysis of machine learning based prediction model studies, with a robust standardised tool for bias evaluation.

Ethics and dissemination

Ethical approval has been granted by the Central University Research Ethics Committee, University of Oxford on 10-December-2020 (R73034/RE001). Findings from this study will be disseminated through peer-review publications.

Prospero registration number

CRD42019140361 and CRD42019161764.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/7/e048008.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-048008; html:https://europepmc.org/articles/PMC8273461; pdf:https://europepmc.org/articles/PMC8273461?pdf=render PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USING PRE-PANDEMIC RISK OF MORTALITY IN INDIVIDUALS WITH CHRONIC KIDNEY DISEASE,"Dashtban M, Mizani M, Gonazalez-Izquierdo A, Corbett R, Denaxas S, Quint J, Mamza J, Morris T, Hemingway H, Sudlow C, Banerjee A.",,Kidney international reports,2022,2022-02-01,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855010/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855010/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC8855010; pdf:https://europepmc.org/articles/PMC8855010?pdf=render 35264566,https://doi.org/10.1038/s41467-022-28729-3,Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus.,"Stacey D, Chen L, Stanczyk PJ, Howson JMM, Mason AM, Burgess S, MacDonald S, Langdown J, McKinney H, Downes K, Farahi N, Peters JE, Basu S, Pankow JS, Tang W, Pankratz N, Sabater-Lleal M, de Vries PS, Smith NL, CHARGE Hemostasis Working Group, Gelinas AD, Schneider DJ, Janjic N, Samani NJ, Ye S, Summers C, Chilvers ER, Danesh J, Paul DS.",,Nature communications,2022,2022-03-09,Y,,,,"Many individual genetic risk loci have been associated with multiple common human diseases. However, the molecular basis of this pleiotropy often remains unclear. We present an integrative approach to reveal the molecular mechanism underlying the PROCR locus, associated with lower coronary artery disease (CAD) risk but higher venous thromboembolism (VTE) risk. We identify PROCR-p.Ser219Gly as the likely causal variant at the locus and protein C as a causal factor. Using genetic analyses, human recall-by-genotype and in vitro experimentation, we demonstrate that PROCR-219Gly increases plasma levels of (activated) protein C through endothelial protein C receptor (EPCR) ectodomain shedding in endothelial cells, attenuating leukocyte-endothelial cell adhesion and vascular inflammation. We also associate PROCR-219Gly with an increased pro-thrombotic state via coagulation factor VII, a ligand of EPCR. Our study, which links PROCR-219Gly to CAD through anti-inflammatory mechanisms and to VTE through pro-thrombotic mechanisms, provides a framework to reveal the mechanisms underlying similar cross-phenotype associations.",,pdf:https://www.nature.com/articles/s41467-022-28729-3.pdf; doi:https://doi.org/10.1038/s41467-022-28729-3; html:https://europepmc.org/articles/PMC8907312; pdf:https://europepmc.org/articles/PMC8907312?pdf=render -37990330,https://doi.org/10.1186/s13063-023-07763-6,"Correction: Medicines and Healthcare products Regulatory Agency's ""Consultation on proposals for legislative changes for clinical trials"": a response from the Trials Methodology Research Partnership Adaptive Designs Working Group, with a focus on data sharing.","Law M, Couturier DL, Choodari-Oskooei B, Crout P, Gamble C, Jacko P, Pallmann P, Pilling M, Robertson DS, Robling M, Sydes MR, Villar SS, Wason J, Wheeler G, Williamson SF, Yap C, Jaki T.",,Trials,2023,2023-11-21,Y,,,,,,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07763-6; doi:https://doi.org/10.1186/s13063-023-07763-6; html:https://europepmc.org/articles/PMC10664262; pdf:https://europepmc.org/articles/PMC10664262?pdf=render -37987834,https://doi.org/10.1007/s00330-023-10311-0,Radiomics of pericardial fat: a new frontier in heart failure discrimination and prediction.,"Szabo L, Salih A, Pujadas ER, Bard A, McCracken C, Ardissino M, Antoniades C, Vago H, Maurovich-Horvat P, Merkely B, Neubauer S, Lekadir K, Petersen SE, Raisi-Estabragh Z.",,European radiology,2023,2023-11-21,N,Pericardium; Adipose tissue; Magnetic Resonance Imaging; Machine Learning; Radiomics,,,"

Objectives

To use pericardial adipose tissue (PAT) radiomics phenotyping to differentiate existing and predict future heart failure (HF) cases in the UK Biobank.

Methods

PAT segmentations were derived from cardiovascular magnetic resonance (CMR) studies using an automated quality-controlled model to define the region-of-interest for radiomics analysis. Prevalent (present at time of imaging) and incident (first occurrence after imaging) HF were ascertained using health record linkage. We created balanced cohorts of non-HF individuals for comparison. PyRadiomics was utilised to extract 104 radiomics features, of which 28 were chosen after excluding highly correlated ones (0.8). These features, plus sex and age, served as predictors in binary classification models trained separately to detect (1) prevalent and (2) incident HF. We tested seven modeling methods using tenfold nested cross-validation and examined feature importance with explainability methods.

Results

We studied 1204 participants in total, 297 participants with prevalent (60 ± 7 years, 21% female) and 305 with incident (61 ± 6 years, 32% female) HF, and an equal number of non-HF comparators. We achieved good discriminative performance for both prevalent (voting classifier; AUC: 0.76; F1 score: 0.70) and incident (light gradient boosting machine: AUC: 0.74; F1 score: 0.68) HF. Our radiomics models showed marginally better performance compared to PAT area alone. Increased PAT size (maximum 2D diameter in a given column or slice) and texture heterogeneity (sum entropy) were important features for prevalent and incident HF classification models.

Conclusions

The amount and character of PAT discriminate individuals with prevalent HF and predict incidence of future HF.

Clinical relevance statement

This study presents an innovative application of pericardial adipose tissue (PAT) radiomics phenotyping as a predictive tool for heart failure (HF), a major public health concern. By leveraging advanced machine learning methods, the research uncovers that the quantity and characteristics of PAT can be used to identify existing cases of HF and predict future occurrences. The enhanced performance of these radiomics models over PAT area alone supports the potential for better personalised care through earlier detection and prevention of HF.

Key points

•PAT radiomics applied to CMR was used for the first time to derive binary machine learning classifiers to develop models for discrimination of prevalence and prediction of incident heart failure. •Models using PAT area provided acceptable discrimination between cases of prevalent or incident heart failure and comparator groups. •An increased PAT volume (increased diameter using shape features) and greater texture heterogeneity captured by radiomics texture features (increased sum entropy) can be used as an additional classifier marker for heart failure.",,pdf:https://link.springer.com/content/pdf/10.1007/s00330-023-10311-0.pdf; doi:https://doi.org/10.1007/s00330-023-10311-0 29944675,https://doi.org/10.1371/journal.pone.0199026,"The diagnosis, burden and prognosis of dementia: A record-linkage cohort study in England.","Pujades-Rodriguez M, Assi V, Gonzalez-Izquierdo A, Wilkinson T, Schnier C, Sudlow C, Hemingway H, Whiteley WN.",,PloS one,2018,2018-06-26,Y,,The Human Phenome,,"

Objectives

Electronic health records (EHR) might be a useful resource to study the risk factors and clinical care of people with dementia. We sought to determine the diagnostic validity of dementia captured in linked EHR.

Methods and findings

A cohort of adults in linked primary care, hospital, disease registry and mortality records in England, [CALIBER (CArdiovascular disease research using LInked Bespoke studies and Electronic health Records)]. The proportion of individuals with dementia, Alzheimer's disease, vascular and rare dementia in each data source was determined. A comparison was made of symptoms and care between people with dementia and age-, sex- and general practice-matched controls, using conditional logistic regression. The lifetime risk and prevalence of dementia and mortality rates in people with and without dementia were estimated with random-effects Poisson models. There were 47,386 people with dementia: 12,633 with Alzheimer's disease, 9540 with vascular and 1539 with rare dementia. Seventy-four percent of cases had corroborating evidence of dementia. People with dementia were more likely to live in a deprived area (conditional OR 1.26;95%CI:1.20-1.31 most vs least deprived), have documented memory impairment (cOR = 11.97;95%CI:11.24-12.75), falls (cOR = 2.36;95%CI:2.31-2.41), depression (cOR = 2.03; 95%CI:1.98-2.09) or anxiety (cOR = 1.27; 95%CI:1.23-1.32). The lifetime risk of dementia at age 65 was 9.2% (95%CI:9.0%-9.4%), in men and 14.9% (95%CI:14.7%-15.1%) in women. The population prevalence of recorded dementia increased from 0.3% in 2000 to 0.7% in 2010. A higher mortality rate was observed in people with than without dementia (IRR = 1.56;95%CI:1.54-1.58).

Conclusions

Most people with a record of dementia in linked UK EHR had some corroborating evidence for diagnosis. The estimated 10-year risk of dementia was higher than published population-based estimations. EHR are therefore a promising source of data for dementia research.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0199026&type=printable; doi:https://doi.org/10.1371/journal.pone.0199026; html:https://europepmc.org/articles/PMC6019102; pdf:https://europepmc.org/articles/PMC6019102?pdf=render +37987834,https://doi.org/10.1007/s00330-023-10311-0,Radiomics of pericardial fat: a new frontier in heart failure discrimination and prediction.,"Szabo L, Salih A, Pujadas ER, Bard A, McCracken C, Ardissino M, Antoniades C, Vago H, Maurovich-Horvat P, Merkely B, Neubauer S, Lekadir K, Petersen SE, Raisi-Estabragh Z.",,European radiology,2023,2023-11-21,N,Pericardium; Adipose tissue; Magnetic Resonance Imaging; Machine Learning; Radiomics,,,"

Objectives

To use pericardial adipose tissue (PAT) radiomics phenotyping to differentiate existing and predict future heart failure (HF) cases in the UK Biobank.

Methods

PAT segmentations were derived from cardiovascular magnetic resonance (CMR) studies using an automated quality-controlled model to define the region-of-interest for radiomics analysis. Prevalent (present at time of imaging) and incident (first occurrence after imaging) HF were ascertained using health record linkage. We created balanced cohorts of non-HF individuals for comparison. PyRadiomics was utilised to extract 104 radiomics features, of which 28 were chosen after excluding highly correlated ones (0.8). These features, plus sex and age, served as predictors in binary classification models trained separately to detect (1) prevalent and (2) incident HF. We tested seven modeling methods using tenfold nested cross-validation and examined feature importance with explainability methods.

Results

We studied 1204 participants in total, 297 participants with prevalent (60 ± 7 years, 21% female) and 305 with incident (61 ± 6 years, 32% female) HF, and an equal number of non-HF comparators. We achieved good discriminative performance for both prevalent (voting classifier; AUC: 0.76; F1 score: 0.70) and incident (light gradient boosting machine: AUC: 0.74; F1 score: 0.68) HF. Our radiomics models showed marginally better performance compared to PAT area alone. Increased PAT size (maximum 2D diameter in a given column or slice) and texture heterogeneity (sum entropy) were important features for prevalent and incident HF classification models.

Conclusions

The amount and character of PAT discriminate individuals with prevalent HF and predict incidence of future HF.

Clinical relevance statement

This study presents an innovative application of pericardial adipose tissue (PAT) radiomics phenotyping as a predictive tool for heart failure (HF), a major public health concern. By leveraging advanced machine learning methods, the research uncovers that the quantity and characteristics of PAT can be used to identify existing cases of HF and predict future occurrences. The enhanced performance of these radiomics models over PAT area alone supports the potential for better personalised care through earlier detection and prevention of HF.

Key points

•PAT radiomics applied to CMR was used for the first time to derive binary machine learning classifiers to develop models for discrimination of prevalence and prediction of incident heart failure. •Models using PAT area provided acceptable discrimination between cases of prevalent or incident heart failure and comparator groups. •An increased PAT volume (increased diameter using shape features) and greater texture heterogeneity captured by radiomics texture features (increased sum entropy) can be used as an additional classifier marker for heart failure.",,pdf:https://link.springer.com/content/pdf/10.1007/s00330-023-10311-0.pdf; doi:https://doi.org/10.1007/s00330-023-10311-0 37285143,https://doi.org/10.1001/jamacardio.2023.1290,Diagnostic and Prognostic Value of Stress Cardiovascular Magnetic Resonance Imaging in Patients With Known or Suspected Coronary Artery Disease: A Systematic Review and Meta-analysis.,"Ricci F, Khanji MY, Bisaccia G, Cipriani A, Di Cesare A, Ceriello L, Mantini C, Zimarino M, Fedorowski A, Gallina S, Petersen SE, Bucciarelli-Ducci C.",,JAMA cardiology,2023,2023-07-01,N,,,,"

Importance

The clinical utility of stress cardiovascular magnetic resonance imaging (CMR) in stable chest pain is still debated, and the low-risk period for adverse cardiovascular (CV) events after a negative test result is unknown.

Objective

To provide contemporary quantitative data synthesis of the diagnostic accuracy and prognostic value of stress CMR in stable chest pain.

Data sources

PubMed and Embase databases, the Cochrane Database of Systematic Reviews, PROSPERO, and the ClinicalTrials.gov registry were searched for potentially relevant articles from January 1, 2000, through December 31, 2021.

Study selection

Selected studies evaluated CMR and reported estimates of diagnostic accuracy and/or raw data of adverse CV events for participants with either positive or negative stress CMR results. Prespecified combinations of keywords related to the diagnostic accuracy and prognostic value of stress CMR were used. A total of 3144 records were evaluated for title and abstract; of those, 235 articles were included in the full-text assessment of eligibility. After exclusions, 64 studies (74 470 total patients) published from October 29, 2002, through October 19, 2021, were included.

Data extraction and synthesis

This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Main outcomes and measures

Diagnostic odds ratios (DORs), sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), odds ratio (OR), and annualized event rate (AER) for all-cause death, CV death, and major adverse cardiovascular events (MACEs) defined as the composite of myocardial infarction and CV death.

Results

A total of 33 diagnostic studies pooling 7814 individuals and 31 prognostic studies pooling 67 080 individuals (mean [SD] follow-up, 3.5 [2.1] years; range, 0.9-8.8 years; 381 357 person-years) were identified. Stress CMR yielded a DOR of 26.4 (95% CI, 10.6-65.9), a sensitivity of 81% (95% CI, 68%-89%), a specificity of 86% (95% CI, 75%-93%), and an AUROC of 0.84 (95% CI, 0.77-0.89) for the detection of functionally obstructive coronary artery disease. In the subgroup analysis, stress CMR yielded higher diagnostic accuracy in the setting of suspected coronary artery disease (DOR, 53.4; 95% CI, 27.7-103.0) or when using 3-T imaging (DOR, 33.2; 95% CI, 19.9-55.4). The presence of stress-inducible ischemia was associated with higher all-cause mortality (OR, 1.97; 95% CI, 1.69-2.31), CV mortality (OR, 6.40; 95% CI, 4.48-9.14), and MACEs (OR, 5.33; 95% CI, 4.04-7.04). The presence of late gadolinium enhancement (LGE) was associated with higher all-cause mortality (OR, 2.22; 95% CI, 1.99-2.47), CV mortality (OR, 6.03; 95% CI, 2.76-13.13), and increased risk of MACEs (OR, 5.42; 95% CI, 3.42-8.60). After a negative test result, pooled AERs for CV death were less than 1.0%.

Conclusion and relevance

In this study, stress CMR yielded high diagnostic accuracy and delivered robust prognostication, particularly when 3-T scanners were used. While inducible myocardial ischemia and LGE were associated with higher mortality and risk of MACEs, normal stress CMR results were associated with a lower risk of MACEs for at least 3.5 years.",,doi:https://doi.org/10.1001/jamacardio.2023.1290 33130851,https://doi.org/10.1093/ije/dyaa216,High-throughput multivariable Mendelian randomization analysis prioritizes apolipoprotein B as key lipid risk factor for coronary artery disease.,"Zuber V, Gill D, Ala-Korpela M, Langenberg C, Butterworth A, Bottolo L, Burgess S.",,International journal of epidemiology,2021,2021-07-01,Y,Lipoproteins; Apolipoprotein B; Metabolomics; blood lipids; coronary artery disease; Mendelian Randomization; Risk Factor Selection,,,"

Background

Genetic variants can be used to prioritize risk factors as potential therapeutic targets via Mendelian randomization (MR). An agnostic statistical framework using Bayesian model averaging (MR-BMA) can disentangle the causal role of correlated risk factors with shared genetic predictors. Here, our objective is to identify lipoprotein measures as mediators between lipid-associated genetic variants and coronary artery disease (CAD) for the purpose of detecting therapeutic targets for CAD.

Methods

As risk factors we consider 30 lipoprotein measures and metabolites derived from a high-throughput metabolomics study including 24 925 participants. We fit multivariable MR models of genetic associations with CAD estimated in 453 595 participants (including 113 937 cases) regressed on genetic associations with the risk factors. MR-BMA assigns to each combination of risk factors a model score quantifying how well the genetic associations with CAD are explained. Risk factors are ranked by their marginal score and selected using false-discovery rate (FDR) criteria. We perform supplementary and sensitivity analyses varying the dataset for genetic associations with CAD.

Results

In the main analysis, the top combination of risk factors ranked by the model score contains apolipoprotein B (ApoB) only. ApoB is also the highest ranked risk factor with respect to the marginal score (FDR <0.005). Additionally, ApoB is selected in all sensitivity analyses. No other measure of cholesterol or triglyceride is consistently selected otherwise.

Conclusions

Our agnostic genetic investigation prioritizes ApoB across all datasets considered, suggesting that ApoB, representing the total number of hepatic-derived lipoprotein particles, is the primary lipid determinant of CAD.",,doi:https://doi.org/10.1093/ije/dyaa216; doi:https://doi.org/10.1093/ije/dyaa216; html:https://europepmc.org/articles/PMC8271202; pdf:https://europepmc.org/articles/PMC8271202?pdf=render -36264615,https://doi.org/10.1161/circgen.122.003704,Prevalence and Disease Expression of Pathogenic and Likely Pathogenic Variants Associated With Inherited Cardiomyopathies in the General Population.,"Bourfiss M, van Vugt M, Alasiri AI, Ruijsink B, van Setten J, Schmidt AF, Dooijes D, Puyol-Antón E, Velthuis BK, van Tintelen JP, Te Riele ASJM, Baas AF, Asselbergs FW.",,Circulation. Genomic and precision medicine,2022,2022-10-20,Y,Genetics; Dilated cardiomyopathy; hypertrophic cardiomyopathy; Arrhythmogenic Right Ventricular Cardiomyopathy; Whole Exome Sequencing,,,"

Background

Pathogenic and likely pathogenic variants associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy (DCM), and hypertrophic cardiomyopathy (HCM) are recommended to be reported as secondary findings in genome sequencing studies. This provides opportunities for early diagnosis, but also fuels uncertainty in variant carriers (G+), since disease penetrance is incomplete. We assessed the prevalence and disease expression of G+ in the general population.

Methods

We identified pathogenic and likely pathogenic variants associated with ARVC, DCM and/or HCM in 200 643 UK Biobank individuals, who underwent whole exome sequencing. We calculated the prevalence of G+ and analyzed the frequency of cardiomyopathy/heart failure diagnosis. In undiagnosed individuals, we analyzed early signs of disease expression using available electrocardiography and cardiac magnetic resonance imaging data.

Results

We found a prevalence of 1:578, 1:251, and 1:149 for pathogenic and likely pathogenic variants associated with ARVC, DCM and HCM respectively. Compared with controls, cardiovascular mortality was higher in DCM G+ (odds ratio 1.67 [95% CI 1.04; 2.59], P=0.030), but similar in ARVC and HCM G+ (P≥0.100). Cardiomyopathy or heart failure diagnosis were more frequent in DCM G+ (odds ratio 3.66 [95% CI 2.24; 5.81], P=4.9×10-7) and HCM G+ (odds ratio 3.03 [95% CI 1.98; 4.56], P=5.8×10-7), but comparable in ARVC G+ (P=0.172). In contrast, ARVC G+ had more ventricular arrhythmias (P=3.3×10-4). In undiagnosed individuals, left ventricular ejection fraction was reduced in DCM G+ (P=0.009).

Conclusions

In the general population, pathogenic and likely pathogenic variants associated with ARVC, DCM, or HCM are not uncommon. Although G+ have increased mortality and morbidity, disease penetrance in these carriers from the general population remains low (1.2-3.1%). Follow-up decisions in case of incidental findings should not be based solely on a variant, but on multiple factors, including family history and disease expression.",,pdf:https://discovery.ucl.ac.uk/10160737/3/Asselbergs_hcg-15-e003704.pdf; doi:https://doi.org/10.1161/CIRCGEN.122.003704; html:https://europepmc.org/articles/PMC9770140; pdf:https://europepmc.org/articles/PMC9770140?pdf=render +37990330,https://doi.org/10.1186/s13063-023-07763-6,"Correction: Medicines and Healthcare products Regulatory Agency's ""Consultation on proposals for legislative changes for clinical trials"": a response from the Trials Methodology Research Partnership Adaptive Designs Working Group, with a focus on data sharing.","Law M, Couturier DL, Choodari-Oskooei B, Crout P, Gamble C, Jacko P, Pallmann P, Pilling M, Robertson DS, Robling M, Sydes MR, Villar SS, Wason J, Wheeler G, Williamson SF, Yap C, Jaki T.",,Trials,2023,2023-11-21,Y,,,,,,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07763-6; doi:https://doi.org/10.1186/s13063-023-07763-6; html:https://europepmc.org/articles/PMC10664262; pdf:https://europepmc.org/articles/PMC10664262?pdf=render 35684987,https://doi.org/10.1111/camh.12571,Assessing the feasibility of a web-based outcome measurement system in child and adolescent mental health services - myHealthE a randomised controlled feasibility pilot study.,"Morris AC, Ibrahim Z, Heslin M, Moghraby OS, Stringaris A, Grant IM, Zalewski L, Pritchard M, Stewart R, Hotopf M, Pickles A, Dobson RJB, Simonoff E, Downs J.",,Child and adolescent mental health,2023,2022-06-09,Y,Child And Adolescent Mental Health; Remote Monitoring; Acceptability; Patient-reported Outcome Measures,,,"

Background

Interest in internet-based patient reported outcome measure (PROM) collection is increasing. The NHS myHealthE (MHE) web-based monitoring system was developed to address the limitations of paper-based PROM completion. MHE provides a simple and secure way for families accessing Child and Adolescent Mental Health Services to report clinical information and track their child's progress. This study aimed to assess whether MHE improves the completion of the Strengths and Difficulties Questionnaire (SDQ) compared with paper collection. Secondary objectives were to explore caregiver satisfaction and application acceptability.

Methods

A 12-week single-blinded randomised controlled feasibility pilot trial of MHE was conducted with 196 families accessing neurodevelopmental services in south London to examine whether electronic questionnaires are completed more readily than paper-based questionnaires over a 3-month period. Follow up process evaluation phone calls with a subset (n = 8) of caregivers explored system satisfaction and usability.

Results

MHE group assignment was significantly associated with an increased probability of completing an SDQ-P in the study period (adjusted hazard ratio (HR) 12.1, 95% CI 4.7-31.0; p = <.001). Of those caregivers' who received the MHE invitation (n = 68) 69.1% completed an SDQ using the platform compared to 8.8% in the control group (n = 68). The system was well received by caregivers, who cited numerous benefits of using MHE, for example, real-time feedback and ease of completion.

Conclusions

MHE holds promise for improving PROM completion rates. Research is needed to refine MHE, evaluate large-scale MHE implementation, cost effectiveness and explore factors associated with differences in electronic questionnaire uptake.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/camh.12571; doi:https://doi.org/10.1111/camh.12571; html:https://europepmc.org/articles/PMC10083915; pdf:https://europepmc.org/articles/PMC10083915?pdf=render +36264615,https://doi.org/10.1161/circgen.122.003704,Prevalence and Disease Expression of Pathogenic and Likely Pathogenic Variants Associated With Inherited Cardiomyopathies in the General Population.,"Bourfiss M, van Vugt M, Alasiri AI, Ruijsink B, van Setten J, Schmidt AF, Dooijes D, Puyol-Antón E, Velthuis BK, van Tintelen JP, Te Riele ASJM, Baas AF, Asselbergs FW.",,Circulation. Genomic and precision medicine,2022,2022-10-20,Y,Genetics; Dilated cardiomyopathy; hypertrophic cardiomyopathy; Arrhythmogenic Right Ventricular Cardiomyopathy; Whole Exome Sequencing,,,"

Background

Pathogenic and likely pathogenic variants associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy (DCM), and hypertrophic cardiomyopathy (HCM) are recommended to be reported as secondary findings in genome sequencing studies. This provides opportunities for early diagnosis, but also fuels uncertainty in variant carriers (G+), since disease penetrance is incomplete. We assessed the prevalence and disease expression of G+ in the general population.

Methods

We identified pathogenic and likely pathogenic variants associated with ARVC, DCM and/or HCM in 200 643 UK Biobank individuals, who underwent whole exome sequencing. We calculated the prevalence of G+ and analyzed the frequency of cardiomyopathy/heart failure diagnosis. In undiagnosed individuals, we analyzed early signs of disease expression using available electrocardiography and cardiac magnetic resonance imaging data.

Results

We found a prevalence of 1:578, 1:251, and 1:149 for pathogenic and likely pathogenic variants associated with ARVC, DCM and HCM respectively. Compared with controls, cardiovascular mortality was higher in DCM G+ (odds ratio 1.67 [95% CI 1.04; 2.59], P=0.030), but similar in ARVC and HCM G+ (P≥0.100). Cardiomyopathy or heart failure diagnosis were more frequent in DCM G+ (odds ratio 3.66 [95% CI 2.24; 5.81], P=4.9×10-7) and HCM G+ (odds ratio 3.03 [95% CI 1.98; 4.56], P=5.8×10-7), but comparable in ARVC G+ (P=0.172). In contrast, ARVC G+ had more ventricular arrhythmias (P=3.3×10-4). In undiagnosed individuals, left ventricular ejection fraction was reduced in DCM G+ (P=0.009).

Conclusions

In the general population, pathogenic and likely pathogenic variants associated with ARVC, DCM, or HCM are not uncommon. Although G+ have increased mortality and morbidity, disease penetrance in these carriers from the general population remains low (1.2-3.1%). Follow-up decisions in case of incidental findings should not be based solely on a variant, but on multiple factors, including family history and disease expression.",,pdf:https://discovery.ucl.ac.uk/10160737/3/Asselbergs_hcg-15-e003704.pdf; doi:https://doi.org/10.1161/CIRCGEN.122.003704; html:https://europepmc.org/articles/PMC9770140; pdf:https://europepmc.org/articles/PMC9770140?pdf=render 37706486,https://doi.org/10.1080/09638288.2023.2254235,Stepped collaborative care for pain and posttraumatic stress disorder after major trauma: a randomized controlled feasibility trial.,"Giummarra MJ, Reeder S, Williams S, Devlin A, Knol R, Ponsford J, Arnold CA, Konstantatos A, Gabbe BJ, Clarke H, Katz J, Mitchell F, Robinson E, Zatzick D.",,Disability and rehabilitation,2023,2023-09-14,N,Trauma; Injury; Recovery; Pain; Hospitalization; Ptsd; Brief Intervention,,,"

Purpose

To examine feasibility and acceptability of providing stepped collaborative care case management targeting posttraumatic stress disorder (PTSD) and pain symptoms after major traumatic injury.

Materials and methods

Participants were major trauma survivors in Victoria, Australia, at risk of persistent pain or PTSD with high baseline symptoms. Participants were block-randomized, stratified by compensation-status, to the usual care (n = 15) or intervention (n = 17) group (46% of eligible patients). The intervention was adapted from existing stepped collaborative care interventions with input from interdisciplinary experts and people with lived experience in trauma and disability. The proactive case management intervention targeted PTSD and pain management for 6-months using motivational interviewing, cognitive behavioral therapy strategies, and collaborative care. Qualitative interviews explored intervention acceptability.

Results

Intervention participants received a median of 7 h case manager contact and reported that they valued the supportive and non-judgmental listening, and timely access to effective strategies, resources, and treatments post-injury from the case manager. Participants reported few disadvantages from participation, and positive impacts on symptoms and recovery outcomes consistent with the reduction in PTSD and pain symptoms measured at 1-, 3- and 6-months.

Conclusions

Stepped collaborative care was low-cost, feasible, and acceptable to people at risk of PTSD or pain after major trauma.IMPLICATIONS FOR REHABILITATIONAfter hospitalization for injury, people can experience difficulty accessing timely support to manage posttraumatic stress, pain and other concerns.Stepped case management-based interventions that provide individualized support and collaborative care have reduced posttraumatic stress symptom severity for patients admitted to American trauma centers.We showed that this model of care could be adapted to target pain and mental health in the trauma system in Victoria, Australia.The intervention was low cost, acceptable and highly valued by most participants who perceived that it helped them use strategies to better manage post-traumatic symptoms, and to access clinicians and treatments relevant to their needs.",,pdf:https://www.tandfonline.com/doi/pdf/10.1080/09638288.2023.2254235?needAccess=true; doi:https://doi.org/10.1080/09638288.2023.2254235 33382071,https://doi.org/10.1093/schbul/sbaa176,Corrigendum to: Using Natural Language Processing on Electronic Health Records to Enhance Detection and Prediction of Psychosis Risk.,,,Schizophrenia bulletin,2021,2021-03-01,N,,,,,,pdf:https://academic.oup.com/schizophreniabulletin/article-pdf/47/2/575/36620724/sbaa176.pdf; doi:https://doi.org/10.1093/schbul/sbaa176; html:https://europepmc.org/articles/PMC7965055; pdf:https://europepmc.org/articles/PMC7965055?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa176 31529100,https://doi.org/10.1093/pm/pnz209,"Pain, Anxiety, and Depression in the First Two Years Following Transport-Related Major Trauma: A Population-Based, Prospective Registry Cohort Study.","Giummarra MJ, Simpson P, Gabbe BJ.",,"Pain medicine (Malden, Mass.)",2020,2020-02-01,N,Trauma; Injury; Prognostic; Recovery; Motor Vehicle,,,"

Objectives

This study aimed to characterize the population prevalence of pain and mental health problems postinjury and to identify risk factors that could improve service delivery to optimize recovery of at-risk patients.

Methods

This population-based registry cohort study included 5,350 adult survivors of transport-related major trauma injuries from the Victorian State Trauma Registry. Outcome profiles were generated separately for pain and mental health outcomes using the ""pain or discomfort"" and ""anxiety or depression"" items of the EuroQol Five Dimensions Three-Level questionnaire at six, 12, and 24 months postinjury. Profiles were ""resilient"" (no problems at every follow-up), ""recovered"" (problems at six- and/or 12-month follow-up that later resolved), ""worsening"" (problems at 12 and/or 24 months after no problems at six and/or 12 months), and ""persistent"" (problems at every follow-up).

Results

Most participants had persistent (pain/discomfort, N = 2,171, 39.7%; anxiety/depression, N = 1,428, 26.2%) and resilient profiles (pain/discomfort, N = 1,220, 22.3%; anxiety/depression, N = 2,055, 37.7%), followed by recovered (pain/discomfort, N = 1,116, 20.4%; anxiety/depression, N = 1,025, 18.8%) and worsening profiles (pain/discomfort, N = 956, 17.5%; anxiety/depression, N = 948, 17.4%). Adjusted multinomial logistic regressions showed increased risk of problems (persistent, worsening, or resolved) vs no problems (resilient) in relation to female sex, middle age, neighborhood disadvantage, pre-injury unemployment, pre-injury disability, and spinal cord injury. People living in rural areas, motorcyclists, pedal cyclists, and people with head, chest, and abdominal injuries had lower risk of problems.

Discussion

Targeted interventions delivered to people with the risk factors identified may help to attenuate the severity and impact of pain and mental health problems after transport injury.",,pdf:https://academic.oup.com/painmedicine/article-pdf/21/2/291/32739506/pnz209.pdf; doi:https://doi.org/10.1093/pm/pnz209 @@ -1354,8 +1354,8 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 31349307,https://doi.org/10.3233/shti190058,Phenotyping UK Electronic Health Records from 15 Million Individuals for Precision Medicine: The CALIBER Resource.,"Denaxas S, Gonzalez-Izquierdo A, Fitzpatrick N, Direk K, Hemingway H.",,Studies in health technology and informatics,2019,2019-07-01,N,Prognosis; Phenotyping; Data Linkage; Electronic Health Records; Biomedical Informatics,,,"Electronic health records (EHR) are increasingly being used for observational research at scale. In the UK, we have established the CALIBER research resource which utilizes national primary and hospital EHR data sources and enables researchers to create and validate longitudinal disease phenotypes at scale. In this work, we will describe the core components of the resource and provide results from three exemplar research studies on high-resolution epidemiology, disease risk prediction and subtype discovery which demonstrate both the opportunities and challenges of using EHR for research.",,doi:https://doi.org/10.3233/SHTI190058 36810251,https://doi.org/10.1172/jci.insight.156643,Development of antidrug antibodies against adalimumab maps to variation within the HLA-DR peptide-binding groove.,"Tsakok T, Saklatvala J, Rispens T, Loeff FC, de Vries A, Allen MH, Barbosa IA, Baudry D, Dasandi T, Duckworth M, Meynell F, Russell A, Chapman A, McBride S, McKenna K, Perera G, Ramsay H, Ramesh R, Sands K, Shipman A, Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP) Study Group, Burden AD, Griffiths CE, Reynolds NJ, Warren RB, Mahil S, Barker J, Dand N, Smith C, Simpson MA.",,JCI insight,2023,2023-02-22,Y,Genetics; Drug therapy; Molecular genetics; Therapeutics; adaptive immunity,,,"Targeted biologic therapies can elicit an undesirable host immune response characterized by the development of antidrug antibodies (ADA), an important cause of treatment failure. The most widely used biologic across immune-mediated diseases is adalimumab, a tumor necrosis factor inhibitor. This study aimed to identify genetic variants that contribute to the development of ADA against adalimumab, thereby influencing treatment failure. In patients with psoriasis on their first course of adalimumab, in whom serum ADA had been evaluated 6-36 months after starting treatment, we observed a genome-wide association with ADA against adalimumab within the major histocompatibility complex (MHC). The association signal mapped to the presence of tryptophan at position 9 and lysine at position 71 of the HLA-DR peptide-binding groove, with both residues conferring protection against ADA. Underscoring their clinical relevance, these residues were also protective against treatment failure. Our findings highlight antigenic peptide presentation via MHC class II as a critical mechanism in the development of ADA against biologic therapies and downstream treatment response.",,pdf:http://insight.jci.org/articles/view/156643/files/pdf; doi:https://doi.org/10.1172/jci.insight.156643; html:https://europepmc.org/articles/PMC9977494; pdf:https://europepmc.org/articles/PMC9977494?pdf=render 36721180,https://doi.org/10.1186/s12961-022-00956-6,Tracking health system performance in times of crisis using routine health data: lessons learned from a multicountry consortium.,"Turcotte-Tremblay AM, Leerapan B, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bauhoff S, Doubova SV, Gadeka DD, Dulal M, Gage A, Gordon-Strachan G, Haile-Mariam D, Joseph JP, Kaewkamjornchai P, Kapoor NR, Gelaw SK, Kim MK, Kruk ME, Kubota S, Margozzini P, Mehata S, Mthethwa L, Nega A, Oh J, Park SK, Passi-Solar A, Perez Cuevas RE, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Arsenault C.",,Health research policy and systems,2023,2023-01-31,Y,Quality Of Care; Health Systems; Routine Health Information Systems; Covid-19,,,"COVID-19 has prompted the use of readily available administrative data to track health system performance in times of crisis and to monitor disruptions in essential healthcare services. In this commentary we describe our experience working with these data and lessons learned across countries. Since April 2020, the Quality Evidence for Health System Transformation (QuEST) network has used administrative data and routine health information systems (RHIS) to assess health system performance during COVID-19 in Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, Republic of Korea and Thailand. We compiled a large set of indicators related to common health conditions for the purpose of multicountry comparisons. The study compiled 73 indicators. A total of 43% of the indicators compiled pertained to reproductive, maternal, newborn and child health (RMNCH). Only 12% of the indicators were related to hypertension, diabetes or cancer care. We also found few indicators related to mental health services and outcomes within these data systems. Moreover, 72% of the indicators compiled were related to volume of services delivered, 18% to health outcomes and only 10% to the quality of processes of care. While several datasets were complete or near-complete censuses of all health facilities in the country, others excluded some facility types or population groups. In some countries, RHIS did not capture services delivered through non-visit or nonconventional care during COVID-19, such as telemedicine. We propose the following recommendations to improve the analysis of administrative and RHIS data to track health system performance in times of crisis: ensure the scope of health conditions covered is aligned with the burden of disease, increase the number of indicators related to quality of care and health outcomes; incorporate data on nonconventional care such as telehealth; continue improving data quality and expand reporting from private sector facilities; move towards collecting patient-level data through electronic health records to facilitate quality-of-care assessment and equity analyses; implement more resilient and standardized health information technologies; reduce delays and loosen restrictions for researchers to access the data; complement routine data with patient-reported data; and employ mixed methods to better understand the underlying causes of service disruptions.",,pdf:https://health-policy-systems.biomedcentral.com/counter/pdf/10.1186/s12961-022-00956-6; doi:https://doi.org/10.1186/s12961-022-00956-6; html:https://europepmc.org/articles/PMC9888332; pdf:https://europepmc.org/articles/PMC9888332?pdf=render -35396183,https://doi.org/10.1016/s2589-7500(22)00003-6,The medical algorithmic audit.,"Liu X, Glocker B, McCradden MM, Ghassemi M, Denniston AK, Oakden-Rayner L.",,The Lancet. Digital health,2022,2022-04-05,N,,,,"Artificial intelligence systems for health care, like any other medical device, have the potential to fail. However, specific qualities of artificial intelligence systems, such as the tendency to learn spurious correlates in training data, poor generalisability to new deployment settings, and a paucity of reliable explainability mechanisms, mean they can yield unpredictable errors that might be entirely missed without proactive investigation. We propose a medical algorithmic audit framework that guides the auditor through a process of considering potential algorithmic errors in the context of a clinical task, mapping the components that might contribute to the occurrence of errors, and anticipating their potential consequences. We suggest several approaches for testing algorithmic errors, including exploratory error analysis, subgroup testing, and adversarial testing, and provide examples from our own work and previous studies. The medical algorithmic audit is a tool that can be used to better understand the weaknesses of an artificial intelligence system and put in place mechanisms to mitigate their impact. We propose that safety monitoring and medical algorithmic auditing should be a joint responsibility between users and developers, and encourage the use of feedback mechanisms between these groups to promote learning and maintain safe deployment of artificial intelligence systems.",,pdf:http://www.thelancet.com/article/S2589750022000036/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00003-6 31446406,https://doi.org/10.1136/bmjopen-2018-027577,Global health competencies in UK postgraduate medical training: a scoping review and curricular content analysis.,"Al-Shakarchi N, Obolensky L, Walpole S, Hemingway H, Banerjee A.",,BMJ open,2019,2019-08-24,Y,Global Health; Competencies; Postgraduate Medical Training,,,"

Objective

To assess global health (GH) training in all postgraduate medical education in the UK.

Design

Mixed methodology: scoping review and curricular content analysis using two GH competency frameworks.

Setting and participants

A scoping review (until December 2017) was used to develop a framework of GH competencies for doctors. National postgraduate medical training curricula were analysed against this and a prior framework for GH competencies. The number of core competencies addressed and/or appearing in each programme was recorded.

Outcomes

The scoping review identified eight relevant publications. A 16-competency framework was developed and, with a prior 5-competency framework, used to analyse each of 71 postgraduate medical curricula. Curricula were examined by a team of researchers and relevant learning outcomes were coded as one of the 5 or 16 core competencies. The number of core competencies in each programme was recorded.

Results

Using the 5-competency and 16-competency frameworks, 23 and 20, respectively, out of 71 programmes contained no global health competencies, most notably the Foundation Programme (equivalent to internship), a compulsory programme for UK medical graduates. Of a possible 16 competencies, the mean number across all 71 programmes was 1.73 (95% CI 1.42 to 2.04) and the highest number were in paediatrics and infectious diseases, each with five competencies. Of the 16 core competencies, global burden of disease and socioeconomic determinants of health were the two most cited with 47 and 35 citations, respectively. 8/16 competencies were not cited in any curriculum.

Conclusions

Equity of care and the challenges of practising in an increasingly globalised world necessitate GH competencies for all doctors. Across the whole of postgraduate training, the majority of UK doctors are receiving minimal or no training in GH. Our GH competency framework can be used to map and plan integration across postgraduate programmes.",,pdf:https://bmjopen.bmj.com/content/bmjopen/9/8/e027577.full.pdf; doi:https://doi.org/10.1136/bmjopen-2018-027577; html:https://europepmc.org/articles/PMC6720244; pdf:https://europepmc.org/articles/PMC6720244?pdf=render +35396183,https://doi.org/10.1016/s2589-7500(22)00003-6,The medical algorithmic audit.,"Liu X, Glocker B, McCradden MM, Ghassemi M, Denniston AK, Oakden-Rayner L.",,The Lancet. Digital health,2022,2022-04-05,N,,,,"Artificial intelligence systems for health care, like any other medical device, have the potential to fail. However, specific qualities of artificial intelligence systems, such as the tendency to learn spurious correlates in training data, poor generalisability to new deployment settings, and a paucity of reliable explainability mechanisms, mean they can yield unpredictable errors that might be entirely missed without proactive investigation. We propose a medical algorithmic audit framework that guides the auditor through a process of considering potential algorithmic errors in the context of a clinical task, mapping the components that might contribute to the occurrence of errors, and anticipating their potential consequences. We suggest several approaches for testing algorithmic errors, including exploratory error analysis, subgroup testing, and adversarial testing, and provide examples from our own work and previous studies. The medical algorithmic audit is a tool that can be used to better understand the weaknesses of an artificial intelligence system and put in place mechanisms to mitigate their impact. We propose that safety monitoring and medical algorithmic auditing should be a joint responsibility between users and developers, and encourage the use of feedback mechanisms between these groups to promote learning and maintain safe deployment of artificial intelligence systems.",,pdf:http://www.thelancet.com/article/S2589750022000036/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00003-6 34751629,https://doi.org/10.1080/09638288.2021.1998671,Long-term health and mobility of older adults following traumatic injury: a qualitative longitudinal study.,"Reeder S, Ameratunga S, Ponsford J, Fitzgerald M, Lyons R, Nunn A, Ekegren C, Cameron P, Gabbe B.",,Disability and rehabilitation,2022,2021-11-09,N,Ageing; Recovery; Qualitative; Disability; Older Adult; Traumatic Injury,,,"

Purpose

The aim of this study was to explore older adults' experiences of and approaches to managing their long-term health and mobility after traumatic injury.

Methods

A longitudinal qualitative study was undertaken with older adults following traumatic injury in Victoria, Australia. Fifteen participants (≥65 years) were interviewed at three years post-injury (n = 15), and re-interviewed at four (n = 14) and five years (n = 12) post-injury. Using a framework approach, a longitudinal thematic analysis was performed.

Results

Older age at the time of injury was identified by participants as a key factor influencing their recovery. Many participants reported actively attempting to regain their strength and fitness in the first five years following injury. However, their age, injury impacts, other health conditions, and weight gain made it difficult to achieve recovery goals. Many older adults reported a decline in their physical function over time. While these experiences and persistent disability constrained or changed the quality of social relationships, community participation, and independence, several participants described adapting to their functional limitations, and managing their secondary conditions over time.

Conclusion

In our cohort, the intertwined combination of ageing, injury, and comorbid conditions negatively affected health and mobility, reinforcing the need for preventative strategies.Implications for rehabilitationOlder adults recovering from traumatic injury may benefit from specialised care pathways that offer long-term and tailored therapies, with programs and services specific to their needs and goals.An integrated service approach by injury insurers, health care, primary care, disability, and aged care could more clearly identify and effectively address the individual needs and goals of older adults with complex conditions.Health and social services that work with people with injuries to develop personalised coping strategies can reduce anxiety related to uncertainty about the future, promote well-being, and support participation in valued activities.",,doi:https://doi.org/10.1080/09638288.2021.1998671 37438684,https://doi.org/10.1186/s12874-023-01935-3,Estimating medication adherence from Electronic Health Records: comparing methods for mining and processing asthma treatment prescriptions.,"Tibble H, Sheikh A, Tsanas A.",,BMC medical research methodology,2023,2023-07-12,Y,Adherence; Asthma; Compliance; corticosteroid; Electronic Health Records,,,"

Background

Medication adherence is usually defined as the extent of the agreement between the medication regimen agreed to by patients with their healthcare provider and the real-world implementation. Proactive identification of those with poor adherence may be useful to identify those with poor disease control and offers the opportunity for ameliorative action. Adherence can be estimated from Electronic Health Records (EHRs) by comparing medication dispensing records to the prescribed regimen. Several methods have been developed in the literature to infer adherence from EHRs, however there is no clear consensus on what should be considered the gold standard in each use case. Our objectives were to critically evaluate different measures of medication adherence in a large longitudinal Scottish EHR dataset. We used asthma, a chronic condition with high prevalence and high rates of non-adherence, as a case study.

Methods

Over 1.6 million asthma controllers were prescribed for our cohort of 91,334 individuals, between January 2009 and March 2017. Eight adherence measures were calculated, and different approaches to estimating the amount of medication supply available at any time were compared.

Results

Estimates from different measures of adherence varied substantially. Three of the main drivers of the differences between adherence measures were the expected duration (if taken as in accordance with the dose directions), whether there was overlapping supply between prescriptions, and whether treatment had been discontinued. However, there are also wider, study-related, factors which are crucial to consider when comparing the adherence measures.

Conclusions

We evaluated the limitations of various medication adherence measures, and highlight key considerations about the underlying data, condition, and population to guide researchers choose appropriate adherence measures. This guidance will enable researchers to make more informed decisions about the methodology they employ, ensuring that adherence is captured in the most meaningful way for their particular application needs.",,pdf:https://bmcmedresmethodol.biomedcentral.com/counter/pdf/10.1186/s12874-023-01935-3; doi:https://doi.org/10.1186/s12874-023-01935-3; html:https://europepmc.org/articles/PMC10337150; pdf:https://europepmc.org/articles/PMC10337150?pdf=render 34139439,https://doi.org/10.1016/j.compbiomed.2021.104542,Development and application of the ocular immune-mediated inflammatory diseases ontology enhanced with synonyms from online patient support forum conversation.,"Pendleton SC, Slater K, Karwath A, Gilbert RM, Davis N, Pesudovs K, Liu X, Denniston AK, Gkoutos GV, Braithwaite T.",,Computers in biology and medicine,2021,2021-06-08,Y,Inflammation; Uveitis; Ontology; Patient Voice; Sentiment,,,"

Background

Unstructured text created by patients represents a rich, but relatively inaccessible resource for advancing patient-centred care. This study aimed to develop an ontology for ocular immune-mediated inflammatory diseases (OcIMIDo), as a tool to facilitate data extraction and analysis, illustrating its application to online patient support forum data.

Methods

We developed OcIMIDo using clinical guidelines, domain expertise, and cross-references to classes from other biomedical ontologies. We developed an approach to add patient-preferred synonyms text-mined from oliviasvision.org online forum, using statistical ranking. We validated the approach with split-sampling and comparison to manual extraction. Using OcIMIDo, we then explored the frequency of OcIMIDo classes and synonyms, and their potential association with natural language sentiment expressed in each online forum post.

Findings

OcIMIDo (version 1.2) includes 661 classes, describing anatomy, clinical phenotype, disease activity status, complications, investigations, interventions and functional impacts. It contains 1661 relationships and axioms, 2851 annotations, including 1131 database cross-references, and 187 patient-preferred synonyms. To illustrate OcIMIDo's potential applications, we explored 9031 forum posts, revealing frequent mention of different clinical phenotypes, treatments, and complications. Language sentiment analysis of each post was generally positive (median 0.12, IQR 0.01-0.24). In multivariable logistic regression, the odds of a post expressing negative sentiment were significantly associated with first posts as compared to replies (OR 3.3, 95% CI 2.8 to 3.9, p < 0.001).

Conclusion

We report the development and validation of a new ontology for inflammatory eye diseases, which includes patient-preferred synonyms, and can be used to explore unstructured patient or physician-reported text data, with many potential applications.",,doi:https://doi.org/10.1016/j.compbiomed.2021.104542; doi:https://doi.org/10.1016/j.compbiomed.2021.104542; html:https://europepmc.org/articles/PMC8404035 @@ -1370,13 +1370,13 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 37269003,https://doi.org/10.1186/s13643-023-02261-x,Non-adherence and non-persistence to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy: a systematic review and meta-analysis.,"Shahzad H, Mahmood S, McGee S, Hubbard J, Haque S, Paudyal V, Denniston AK, Hill LJ, Jalal Z.",,Systematic reviews,2023,2023-06-02,Y,Meta-analysis; Intravitreal; Anti-vegf; Non-adherence; Macular; Non-persistence; Covid-19,,,"

Background

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections play a key role in treating a range of macular diseases. The effectiveness of these therapies is dependent on patients' adherence (the extent to which a patient takes their medicines as per agreed recommendations from the healthcare provider) and persistence (continuation of the treatment for the prescribed duration) to their prescribed treatment regimens. The aim of this systematic review was to demonstrate the need for further investigation into the prevalence of, and factors contributing to, patient-led non-adherence and non-persistence, thus facilitating improved clinical outcomes.

Methods

Systematic searches were conducted in Google Scholar, Web of Science, PubMed, MEDLINE, and the Cochrane Library. Studies in English conducted before February 2023 that reported the level of, and/or barriers to, non-adherence or non-persistence to intravitreal anti-VEGF ocular disease therapy were included. Duplicate papers, literature reviews, expert opinion articles, case studies, and case series were excluded following screening by two independent authors.

Results

Data from a total of 409,215 patients across 52 studies were analysed. Treatment regimens included pro re nata, monthly and treat-and-extend protocols; study durations ranged from 4 months to 8 years. Of the 52 studies, 22 included a breakdown of reasons for patient non-adherence/non-persistence. Patient-led non-adherence varied between 17.5 and 35.0% depending on the definition used. Overall pooled prevalence of patient-led treatment non-persistence was 30.0% (P = 0.000). Reasons for non-adherence/non-persistence included dissatisfaction with treatment results (29.9%), financial burden (19%), older age/comorbidities (15.5%), difficulty booking appointments (8.5%), travel distance/social isolation (7.9%), lack of time (5.8%), satisfaction with the perceived improvement in their condition (4.4%), fear of injection (4.0%), loss of motivation (4.0%), apathy towards eyesight (2.5%), dissatisfaction with facilities 2.3%, and discomfort/pain (0.3%). Three studies found non-adherence rates between 51.6 and 68.8% during the COVID-19 pandemic, in part due to fear of exposure to COVID-19 and difficulties travelling during lockdown.

Discussion

Results suggest high levels of patient-led non-adherence/non-persistence to anti-VEGF therapy, mostly due to dissatisfaction with treatment results, a combination of comorbidities, loss of motivation and the burden of travel. This study provides key information on prevalence and factors contributing to non-adherence/non-persistence in anti-VEGF treatment for macular diseases, aiding identification of at-risk individuals to improve real-world visual outcomes. Improvements in the literature can be achieved by establishing uniform definitions and standard timescales for what constitutes non-adherence/non-persistence.

Systematic review registration

PROSPERO CRD42020216205.",,doi:https://doi.org/10.1186/s13643-023-02261-x; doi:https://doi.org/10.1186/s13643-023-02261-x; html:https://europepmc.org/articles/PMC10237080; pdf:https://europepmc.org/articles/PMC10237080?pdf=render 36809311,https://doi.org/10.1093/ejendo/lvad024,The ultra-acute steroid response to traumatic injury: a cohort study.,"Bentley C, Hazeldine J, Bravo L, Taylor AE, Gilligan LC, Shaheen F, Acharjee A, Gkoutos G, Foster MA, Arlt W, Lord JM.",,European journal of endocrinology,2023,2023-03-01,N,Steroids; Mass spectrometry; Glucocorticoids; Major Trauma; 11-Oxygenated Androgens,,,"

Objective

Trauma-induced steroid changes have been studied post-hospital admission, resulting in a lack of understanding of the speed and extent of the immediate endocrine response to injury. The Golden Hour study was designed to capture the ultra-acute response to traumatic injury.

Design

We conducted an observational cohort study including adult male trauma patients <60 years, with blood samples drawn ≤1 h of major trauma by pre-hospital emergency responders.

Methods

We recruited 31 adult male trauma patients (mean age 28 [range 19-59] years) with a mean injury severity score (ISS) of 16 (IQR 10-21). The median time to first sample was 35 (range 14-56) min, with follow-up samples collected 4-12 and 48-72 h post-injury. Serum steroids in patients and age- and sex-matched healthy controls (HCs) (n = 34) were analysed by tandem mass spectrometry.

Results

Within 1 h of injury, we observed an increase in glucocorticoid and adrenal androgen biosynthesis. Cortisol and 11-hydroxyandrostendione increased rapidly, whilst cortisone and 11-ketoandrostenedione decreased, reflective of increased cortisol and 11-oxygenated androgen precursor biosynthesis by 11β-hydroxylase and increased cortisol activation by 11β-hydroxysteroid dehydrogenase type 1. Active classic gonadal androgens testosterone and 5α-dihydrotestosterone decreased, whilst the active 11-oxygenated androgen 11-ketotestosterone maintained pre-injury levels.

Conclusions

Changes in steroid biosynthesis and metabolism occur within minutes of traumatic injury. Studies that address whether ultra-early changes in steroid metabolism are associated with patient outcomes are now required.",,pdf:https://academic.oup.com/ejendo/article-pdf/188/3/290/49630912/lvad024.pdf; doi:https://doi.org/10.1093/ejendo/lvad024 37538142,https://doi.org/10.1093/ehjdh/ztad037,Predicting left ventricular hypertrophy from the 12-lead electrocardiogram in the UK Biobank imaging study using machine learning.,"Naderi H, Ramírez J, van Duijvenboden S, Pujadas ER, Aung N, Wang L, Anwar Ahmed Chahal C, Lekadir K, Petersen SE, Munroe PB.",,European heart journal. Digital health,2023,2023-06-01,Y,Electrocardiogram; Left ventricular hypertrophy; Cardiovascular Screening; Machine Learning; Cardiovascular Magnetic Resonance Imaging,,,"

Aims

Left ventricular hypertrophy (LVH) is an established, independent predictor of cardiovascular disease. Indices derived from the electrocardiogram (ECG) have been used to infer the presence of LVH with limited sensitivity. This study aimed to classify LVH defined by cardiovascular magnetic resonance (CMR) imaging using the 12-lead ECG for cost-effective patient stratification.

Methods and results

We extracted ECG biomarkers with a known physiological association with LVH from the 12-lead ECG of 37 534 participants in the UK Biobank imaging study. Classification models integrating ECG biomarkers and clinical variables were built using logistic regression, support vector machine (SVM) and random forest (RF). The dataset was split into 80% training and 20% test sets for performance evaluation. Ten-fold cross validation was applied with further validation testing performed by separating data based on UK Biobank imaging centres. QRS amplitude and blood pressure (P < 0.001) were the features most strongly associated with LVH. Classification with logistic regression had an accuracy of 81% [sensitivity 70%, specificity 81%, Area under the receiver operator curve (AUC) 0.86], SVM 81% accuracy (sensitivity 72%, specificity 81%, AUC 0.85) and RF 72% accuracy (sensitivity 74%, specificity 72%, AUC 0.83). ECG biomarkers enhanced model performance of all classifiers, compared to using clinical variables alone. Validation testing by UK Biobank imaging centres demonstrated robustness of our models.

Conclusion

A combination of ECG biomarkers and clinical variables were able to predict LVH defined by CMR. Our findings provide support for the ECG as an inexpensive screening tool to risk stratify patients with LVH as a prelude to advanced imaging.",,pdf:https://academic.oup.com/ehjdh/advance-article-pdf/doi/10.1093/ehjdh/ztad037/50634764/ztad037.pdf; doi:https://doi.org/10.1093/ehjdh/ztad037; html:https://europepmc.org/articles/PMC10393938; pdf:https://europepmc.org/articles/PMC10393938?pdf=render -36289925,https://doi.org/10.3390/biomedicines10102662,"Temporal Evolution of Multiday, Epileptic Functional Networks Prior to Seizure Occurrence.","Laiou P, Biondi A, Bruno E, Viana PF, Winston JS, Rashid Z, Ranjan Y, Conde P, Stewart C, Sun S, Zhang Y, Folarin A, Dobson RJB, Schulze-Bonhage A, Dümpelmann M, Richardson MP, Radar-Cns Consortium.",,Biomedicines,2022,2022-10-21,Y,Epilepsy; EEG; Graph theory; ECG; Functional Network; Seizure Lateralization; Evolving Network,,,"Epilepsy is one of the most common neurological disorders, characterized by the occurrence of repeated seizures. Given that epilepsy is considered a network disorder, tools derived from network neuroscience may confer the valuable ability to quantify the properties of epileptic brain networks. In this study, we use well-established brain network metrics (i.e., mean strength, variance of strength, eigenvector centrality, betweenness centrality) to characterize the temporal evolution of epileptic functional networks over several days prior to seizure occurrence. We infer the networks using long-term electroencephalographic recordings from 12 people with epilepsy. We found that brain network metrics are variable across days and show a circadian periodicity. In addition, we found that in 9 out of 12 patients the distribution of the variance of strength in the day (or even two last days) prior to seizure occurrence is significantly different compared to the corresponding distributions on all previous days. Our results suggest that brain network metrics computed fromelectroencephalographic recordings could potentially be used to characterize brain network changes that occur prior to seizures, and ultimately contribute to seizure warning systems.",,pdf:https://www.mdpi.com/2227-9059/10/10/2662/pdf?version=1666684470; doi:https://doi.org/10.3390/biomedicines10102662; html:https://europepmc.org/articles/PMC9599905; pdf:https://europepmc.org/articles/PMC9599905?pdf=render 31558464,https://doi.org/10.1136/bmjopen-2019-033013,Long-term impact of giving antibiotics before skin incision versus after cord clamping on children born by caesarean section: protocol for a longitudinal study based on UK electronic health records.,"Šumilo D, Nirantharakumar K, Willis BH, Rudge G, Martin J, Gokhale K, Thayakaran R, Adderley NJ, Chandan JS, Okoth K, Hewston R, Skrybant M, Deeks JJ, Brocklehurst P.",,BMJ open,2019,2019-09-26,Y,Child; Asthma; Caesarean section; Eczema; Antibiotic Prophylaxis; Immune System Diseases,,,"

Introduction

In the UK, about a quarter of women give birth by caesarean section (CS) and are offered prophylactic broad-spectrum antibiotics to reduce the risk of maternal postpartum infection. In 2011, national guidance was changed from recommending antibiotics after the umbilical cord was cut to giving antibiotics prior to skin incision based on evidence that earlier administration reduces maternal infectious morbidity. Although antibiotics cross the placenta, there are no known short-term harms to the baby. This study aims to address the research gap on longer term impact of these antibiotics on child health.

Methods and analysis

A controlled interrupted time series study will use anonymised mother-baby linked routine electronic health records for children born during 2006-2018 recorded in UK primary care (The Health Improvement Network, THIN and Clinical Practice Research Datalink, CPRD) and secondary care (Hospital Episode Statistics, HES) databases. The primary outcomes of interest are asthma and eczema, two common allergy-related diseases in childhood. In-utero exposure to antibiotics immediately prior to CS will be compared with no exposure when given after cord clamping. The risk of outcomes in children delivered by CS will also be compared with a control cohort delivered vaginally to account for time effects. We will use all available data from THIN, CPRD and HES with estimated power of 80% and 90% to detect relative increase in risk of asthma of 16% and 18%, respectively at the 5% significance level.

Ethics and dissemination

Ethical approval has been obtained from the University of Birmingham Ethical Review Committee with scientific approvals obtained from the independent scientific advisory committees from the Medicines and Healthcare products Regulatory Agency for CPRD and the data provider, IQVIA for THIN. The results will be published in peer-reviewed journals, presented at national and international conferences and disseminated to stakeholders.",,pdf:https://bmjopen.bmj.com/content/bmjopen/9/9/e033013.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-033013; html:https://europepmc.org/articles/PMC6773283; pdf:https://europepmc.org/articles/PMC6773283?pdf=render +36289925,https://doi.org/10.3390/biomedicines10102662,"Temporal Evolution of Multiday, Epileptic Functional Networks Prior to Seizure Occurrence.","Laiou P, Biondi A, Bruno E, Viana PF, Winston JS, Rashid Z, Ranjan Y, Conde P, Stewart C, Sun S, Zhang Y, Folarin A, Dobson RJB, Schulze-Bonhage A, Dümpelmann M, Richardson MP, Radar-Cns Consortium.",,Biomedicines,2022,2022-10-21,Y,Epilepsy; EEG; Graph theory; ECG; Functional Network; Seizure Lateralization; Evolving Network,,,"Epilepsy is one of the most common neurological disorders, characterized by the occurrence of repeated seizures. Given that epilepsy is considered a network disorder, tools derived from network neuroscience may confer the valuable ability to quantify the properties of epileptic brain networks. In this study, we use well-established brain network metrics (i.e., mean strength, variance of strength, eigenvector centrality, betweenness centrality) to characterize the temporal evolution of epileptic functional networks over several days prior to seizure occurrence. We infer the networks using long-term electroencephalographic recordings from 12 people with epilepsy. We found that brain network metrics are variable across days and show a circadian periodicity. In addition, we found that in 9 out of 12 patients the distribution of the variance of strength in the day (or even two last days) prior to seizure occurrence is significantly different compared to the corresponding distributions on all previous days. Our results suggest that brain network metrics computed fromelectroencephalographic recordings could potentially be used to characterize brain network changes that occur prior to seizures, and ultimately contribute to seizure warning systems.",,pdf:https://www.mdpi.com/2227-9059/10/10/2662/pdf?version=1666684470; doi:https://doi.org/10.3390/biomedicines10102662; html:https://europepmc.org/articles/PMC9599905; pdf:https://europepmc.org/articles/PMC9599905?pdf=render 34386668,https://doi.org/10.1016/j.ekir.2021.05.031,Impact of Using Risk-Based Stratification on Referral of Patients With Chronic Kidney Disease From Primary Care to Specialist Care in the United Kingdom.,"Bhachu HK, Cockwell P, Subramanian A, Adderley NJ, Gokhale K, Fenton A, Kyte D, Nirantharakumar K, Calvert M.",,Kidney international reports,2021,2021-06-01,Y,Cross-sectional study; Chronic Kidney Disease; Guidelines; Disease Progression; Patient Referral; Kidney Failure Risk Equation,,,"

Introduction

The externally validated Kidney Failure Risk Equation (KFRE) for predicting risk of end-stage renal disease (ESRD) has been developed, but its potential impact in a population on referrals for patients with chronic kidney disease (CKD) from primary to specialty nephrology care is not known.

Methods

A cross-sectional population-based study of individuals in United Kingdom primary care registered in The Health Improvement Network database was conducted. National Institute of Health and Care Excellence (NICE) 2014 CKD guidelines versus the 4-variable KFRE set at a >3% risk of ESRD at 5 years were applied to patients identified with CKD stage 3-5 between January 1, 2016, and March 31, 2017.

Results

In all, 39,476 (36.6%) of 107,962 adults with CKD stage 3-5 had a urine albumin:creatinine ratio (ACR) available and entered into the primary analysis. Of that, 7566 (19.2%) patients fulfilled NICE criteria for referral, 2386 (31.5%) of whom had a ≤3% 5-year risk of ESRD. Also 8663 (21.9%) patients had a >3% 5-year risk of ESRD, 3483 (40.2%) of whom did not fulfill NICE criteria; this represents 8.8% of the primary population. By using the KFRE threshold rather than NICE criteria for referral, 5869 patients (14.9% of the primary analysis population) would have been reallocated between primary and specialist care. Imputational analysis was used for missing ACR measurements and showed similar results.

Conclusions

A risk-based referral approach would lead to a substantial reallocation of patients between primary care and specialist nephrology care with only a small increase in numbers eligible, ensuring those at higher risk of progression are identified.",,pdf:http://pure-oai.bham.ac.uk/ws/files/145543032/1_s2.0_S2468024921012146_main.pdf; doi:https://doi.org/10.1016/j.ekir.2021.05.031; html:https://europepmc.org/articles/PMC8343777; pdf:https://europepmc.org/articles/PMC8343777?pdf=render 35440446,https://doi.org/10.1136/bmjopen-2021-052514,Protocol for the COG-UK hospital-onset COVID-19 infection (HOCI) multicentre interventional clinical study: evaluating the efficacy of rapid genome sequencing of SARS-CoV-2 in limiting the spread of COVID-19 in UK NHS hospitals.,"Blackstone J, Stirrup O, Mapp F, Panca M, Copas A, Flowers P, Hockey L, Price J, Partridge D, Peters C, de Silva T, Nebbia G, Snell LB, McComish R, COVID-19 Genomics UK (COG-UK) Consortium, Breuer J.",,BMJ open,2022,2022-04-19,Y,Molecular biology; Infection control; epidemiology; Covid-19,,,"

Objectives

Nosocomial transmission of SARS-CoV-2 has been a significant cause of mortality in National Health Service (NHS) hospitals during the COVID-19 pandemic. The COG-UK Consortium Hospital-Onset COVID-19 Infections (COG-UK HOCI) study aims to evaluate whether the use of rapid whole-genome sequencing of SARS-CoV-2, supported by a novel probabilistic reporting methodology, can inform infection prevention and control (IPC) practice within NHS hospital settings.

Design

Multicentre, prospective, interventional, superiority study.

Setting

14 participating NHS hospitals over winter-spring 2020/2021 in the UK.

Participants

Eligible patients must be admitted to hospital with first-confirmed SARS-CoV-2 PCR-positive test result >48 hour from time of admission, where COVID-19 diagnosis not suspected on admission. The projected sample size is 2380 patients.

Intervention

The intervention is the return of a sequence report, within 48 hours in one phase (rapid local lab processing) and within 5-10 days in a second phase (mimicking central lab), comparing the viral genome from an eligible study participant with others within and outside the hospital site.

Primary and secondary outcome measures

The primary outcomes are incidence of Public Health England (PHE)/IPC-defined SARS-CoV-2 hospital-acquired infection during the baseline and two interventional phases, and proportion of hospital-onset cases with genomic evidence of transmission linkage following implementation of the intervention where such linkage was not suspected by initial IPC investigation. Secondary outcomes include incidence of hospital outbreaks, with and without sequencing data; actual and desirable changes to IPC actions; periods of healthcare worker (HCW) absence. Health economic analysis will be conducted to determine cost benefit of the intervention. A process evaluation using qualitative interviews with HCWs will be conducted alongside the study.

Trial registration number

ISRCTN50212645. Pre-results stage. This manuscript is based on protocol V.6.0. 2 September 2021.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e052514.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-052514; html:https://europepmc.org/articles/PMC9019828; pdf:https://europepmc.org/articles/PMC9019828?pdf=render -38692709,https://doi.org/10.1136/bmjresp-2023-001746,"Risk factors for asthma-related hospital and intensive care admissions in children, adolescents and adults: a cohort study using primary and secondary care data.","Simms-Williams N, Nagakumar P, Thayakaran R, Adderley NJ, Hotham R, Mansur AH, Nirantharakumar K, Haroon S.",,BMJ open respiratory research,2024,2024-05-01,Y,Asthma; Asthma Epidemiology,,,"

Background

Asthma remains a common cause of hospital admissions across the life course. We estimated the contribution of key risk factors to asthma-related hospital and intensive care unit (ICU) admissions in children, adolescents and adults.

Methods

This was a UK-based cohort study using linked primary care (Clinical Practice Research Datalink Aurum) and secondary care (Hospital Episode Statistics Admitted Patient Care) data. Patients were eligible if they were aged 5 years and older and had been diagnosed with asthma. This included 90 989 children aged 5-11 years, 114 927 adolescents aged 12-17 years and 1 179 410 adults aged 18 years or older. The primary outcome was asthma-related hospital admissions from 1 January 2017 to 31 December 2019. The secondary outcome was asthma-related ICU admissions. Incidence rate ratios adjusted for demographic and clinical risk factors were estimated using negative binomial models. Population attributable fraction (PAF) was estimated for modifiable risk factors.

Results

Younger age groups, females and those from ethnic minority and lower socioeconomic backgrounds had an increased risk of asthma-related hospital admissions. Increasing medication burden, including excessive use of short-acting bronchodilators, was also strongly associated with the primary outcome. Similar risk factors were observed for asthma-related ICU admissions. The key potentially modifiable or treatable risk factors were smoking in adolescents and adults (PAF 6.8%, 95% CI 0.9% to 12.3% and 4.3%, 95% CI 3.0% to 5.7%, respectively), and obesity (PAF 23.3%, 95% CI 20.5% to 26.1%), depression (11.1%, 95% CI 9.1% to 13.1%), gastro-oesophageal reflux disease (2.3%, 95% CI 1.2% to 3.4%), anxiety (2.0%, 95% CI 0.5% to 3.6%) and chronic rhinosinusitis (0.8%, 95% CI 0.3% to 1.3%) in adults.

Conclusions

There are significant sociodemographic inequalities in the rates of asthma-related hospital and ICU admissions. Treating age-specific modifiable risk factors should be considered an integral part of asthma management, which could potentially reduce the rate of avoidable hospital admissions.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/11/1/e001746.full.pdf; doi:https://doi.org/10.1136/bmjresp-2023-001746; html:https://europepmc.org/articles/PMC11086188; pdf:https://europepmc.org/articles/PMC11086188?pdf=render 36285341,https://doi.org/10.1080/17434440.2022.2132147,Data-driven monitoring in patients on left ventricular assist device support.,"Numan L, Moazeni M, Oerlemans MIFJ, Aarts E, Van Der Kaaij NP, Asselbergs FW, Van Laake LW.",,Expert review of medical devices,2022,2022-09-01,N,Prediction; Circadian rhythm; Algorithms; Remote Monitoring; Left Ventricular Assist Device; Lvad,,,"

Introduction

Despite an increasing population of patients supported with a left ventricular assist device (LVAD), it remains a complex therapy, and patients are frequently admitted. Therefore, a strict follow-up including frequent hospital visits, patient self-management and telemonitoring is needed.

Areas covered

The current review describes the principles of LVADs, the possibilities of (tele)monitoring using noninvasive and invasive devices. Furthermore, possibilities, challenges, and future perspectives in this emerging field are discussed.

Expert opinion

Several studies described initial experiences on telemonitoring in LVAD patients, using mobile phone applications to collect clinical data and pump data. This may replace frequent hospital visits in near future. In addition, algorithms were developed aiming to early detect pump thrombosis or driveline infections. Since not all complications are reflected by pump parameters, data from different sources should be combined to detect a broader spectrum of complications in an early stage. We need to focus on the development of sophisticated but understandable algorithms and infrastructure combining different data sources, while addressing essential aspects such as data safety, privacy, and cost-effectiveness.",,doi:https://doi.org/10.1080/17434440.2022.2132147; doi:https://doi.org/10.1080/17434440.2022.2132147 32861307,https://doi.org/10.1016/s0140-6736(20)30930-2,Invasive versus non-invasive management of older patients with non-ST elevation myocardial infarction (SENIOR-NSTEMI): a cohort study based on routine clinical data.,"Kaura A, Sterne JAC, Trickey A, Abbott S, Mulla A, Glampson B, Panoulas V, Davies J, Woods K, Omigie J, Shah AD, Channon KM, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs FW, O'Sullivan M, Lord GM, Melikian N, Johnson T, Francis DP, Shah AM, Perera D, Kharbanda R, Patel RS, Mayet J.",,"Lancet (London, England)",2020,2020-08-01,Y,,,,"

Background

Previous trials suggest lower long-term risk of mortality after invasive rather than non-invasive management of patients with non-ST elevation myocardial infarction (NSTEMI), but the trials excluded very elderly patients. We aimed to estimate the effect of invasive versus non-invasive management within 3 days of peak troponin concentration on the survival of patients aged 80 years or older with NSTEMI.

Methods

Routine clinical data for this study were obtained from five collaborating hospitals hosting NIHR Biomedical Research Centres in the UK (all tertiary centres with emergency departments). Eligible patients were 80 years old or older when they underwent troponin measurements and were diagnosed with NSTEMI between 2010 (2008 for University College Hospital) and 2017. Propensity scores (patients' estimated probability of receiving invasive management) based on pretreatment variables were derived using logistic regression; patients with high probabilities of non-invasive or invasive management were excluded. Patients who died within 3 days of peak troponin concentration without receiving invasive management were assigned to the invasive or non-invasive management groups based on their propensity scores, to mitigate immortal time bias. We estimated mortality hazard ratios comparing invasive with non-invasive management, and compared the rate of hospital admissions for heart failure.

Findings

Of the 1976 patients with NSTEMI, 101 died within 3 days of their peak troponin concentration and 375 were excluded because of extreme propensity scores. The remaining 1500 patients had a median age of 86 (IQR 82-89) years of whom (845 [56%] received non-invasive management. During median follow-up of 3·0 (IQR 1·2-4·8) years, 613 (41%) patients died. The adjusted cumulative 5-year mortality was 36% in the invasive management group and 55% in the non-invasive management group (adjusted hazard ratio 0·68, 95% CI 0·55-0·84). Invasive management was associated with lower incidence of hospital admissions for heart failure (adjusted rate ratio compared with non-invasive management 0·67, 95% CI 0·48-0·93).

Interpretation

The survival advantage of invasive compared with non-invasive management appears to extend to patients with NSTEMI who are aged 80 years or older.

Funding

NIHR Imperial Biomedical Research Centre, as part of the NIHR Health Informatics Collaborative.",,pdf:http://www.thelancet.com/article/S0140673620309302/pdf; doi:https://doi.org/10.1016/S0140-6736(20)30930-2; html:https://europepmc.org/articles/PMC7456783; pdf:https://europepmc.org/articles/PMC7456783?pdf=render +38692709,https://doi.org/10.1136/bmjresp-2023-001746,"Risk factors for asthma-related hospital and intensive care admissions in children, adolescents and adults: a cohort study using primary and secondary care data.","Simms-Williams N, Nagakumar P, Thayakaran R, Adderley NJ, Hotham R, Mansur AH, Nirantharakumar K, Haroon S.",,BMJ open respiratory research,2024,2024-05-01,Y,Asthma; Asthma Epidemiology,,,"

Background

Asthma remains a common cause of hospital admissions across the life course. We estimated the contribution of key risk factors to asthma-related hospital and intensive care unit (ICU) admissions in children, adolescents and adults.

Methods

This was a UK-based cohort study using linked primary care (Clinical Practice Research Datalink Aurum) and secondary care (Hospital Episode Statistics Admitted Patient Care) data. Patients were eligible if they were aged 5 years and older and had been diagnosed with asthma. This included 90 989 children aged 5-11 years, 114 927 adolescents aged 12-17 years and 1 179 410 adults aged 18 years or older. The primary outcome was asthma-related hospital admissions from 1 January 2017 to 31 December 2019. The secondary outcome was asthma-related ICU admissions. Incidence rate ratios adjusted for demographic and clinical risk factors were estimated using negative binomial models. Population attributable fraction (PAF) was estimated for modifiable risk factors.

Results

Younger age groups, females and those from ethnic minority and lower socioeconomic backgrounds had an increased risk of asthma-related hospital admissions. Increasing medication burden, including excessive use of short-acting bronchodilators, was also strongly associated with the primary outcome. Similar risk factors were observed for asthma-related ICU admissions. The key potentially modifiable or treatable risk factors were smoking in adolescents and adults (PAF 6.8%, 95% CI 0.9% to 12.3% and 4.3%, 95% CI 3.0% to 5.7%, respectively), and obesity (PAF 23.3%, 95% CI 20.5% to 26.1%), depression (11.1%, 95% CI 9.1% to 13.1%), gastro-oesophageal reflux disease (2.3%, 95% CI 1.2% to 3.4%), anxiety (2.0%, 95% CI 0.5% to 3.6%) and chronic rhinosinusitis (0.8%, 95% CI 0.3% to 1.3%) in adults.

Conclusions

There are significant sociodemographic inequalities in the rates of asthma-related hospital and ICU admissions. Treating age-specific modifiable risk factors should be considered an integral part of asthma management, which could potentially reduce the rate of avoidable hospital admissions.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/11/1/e001746.full.pdf; doi:https://doi.org/10.1136/bmjresp-2023-001746; html:https://europepmc.org/articles/PMC11086188; pdf:https://europepmc.org/articles/PMC11086188?pdf=render 36576811,https://doi.org/10.1001/jamacardio.2022.4466,Predictive Utility of a Coronary Artery Disease Polygenic Risk Score in Primary Prevention.,"Marston NA, Pirruccello JP, Melloni GEM, Koyama S, Kamanu FK, Weng LC, Roselli C, Kamatani Y, Komuro I, Aragam KG, Butterworth AS, Ito K, Lubitz SA, Ellinor PT, Sabatine MS, Ruff CT.",,JAMA cardiology,2023,2023-02-01,N,,,,"

Importance

The clinical utility of polygenic risk scores (PRS) for coronary artery disease (CAD) has not yet been established.

Objective

To investigate the ability of a CAD PRS to potentially guide statin initiation in primary prevention after accounting for age and clinical risk.

Design, setting, and participants

This was a longitudinal cohort study with enrollment starting on January 1, 2006, and ending on December 31, 2010, with data updated to mid-2021, using data from the UK Biobank, a long-term population study of UK citizens. A replication analysis was performed in Biobank Japan. The analysis included all patients without a history of CAD and who were not taking lipid-lowering therapy. Data were analyzed from January 1 to June 30, 2022.

Exposures

Polygenic risk for CAD was defined as low (bottom 20%), intermediate, and high (top 20%) using a CAD PRS including 241 genome-wide significant single-nucleotide variations (SNVs). The pooled cohort equations were used to estimate 10-year atherosclerotic cardiovascular disease (ASCVD) risk and classify individuals as low (<5%), borderline (5-<7.5%), intermediate (7.5-<20%), or high risk (≥20%).

Main outcomes and measures

Myocardial infarction (MI) and ASCVD events (defined as incident clinical CAD [including MI], stroke, or CV death).

Results

A total of 330 201 patients (median [IQR] age, 57 [40-74] years; 189 107 female individuals [57%]) were included from the UK Biobank. Over the 10-year follow-up, 4454 individuals had an MI. The CAD PRS was significantly associated with the risk of MI in all age groups but had significantly stronger risk prediction at younger ages (age <50 years: hazard ratio [HR] per 1 SD of PRS, 1.72; 95% CI, 1.56-1.89; age 50-60 years: HR, 1.46; 95% CI, 1.38-1.53; age >60 years: HR, 1.42; 95% CI, 1.37-1.48; P for interaction <.001). In patients younger than 50 years, those with high PRS had a 3- to 4-fold increased associated risk of MI compared with those in the low PRS category. A significant interaction between CAD PRS and age was replicated in Biobank Japan. When CAD PRS testing was added to the clinical ASCVD risk score in individuals younger than 50 years, 591 of 4373 patients (20%) with borderline risk were risk stratified into intermediate risk, warranting initiation of statin therapy and 3198 of 7477 patients (20%) with both borderline or intermediate risk were stratified as low risk, thus not warranting therapy.

Conclusions and relevance

Results of this cohort study suggest that the predictive ability of a CAD PRS was greater in younger individuals and can be used to better identify patients with borderline and intermediate clinical risk who should initiate statin therapy.",,doi:https://doi.org/10.1001/jamacardio.2022.4466; html:https://europepmc.org/articles/PMC9857431; doi:https://doi.org/10.1001/jamacardio.2022.4466 37101398,https://doi.org/10.1002/ejhf.2868,Sex differences in the generalizability of randomized clinical trials in heart failure with reduced ejection fraction.,"Schroeder M, Lim YMF, Savarese G, Suzart-Woischnik K, Baudier C, Dyszynski T, Vaartjes I, Eijkemans MJC, Uijl A, Herrera R, Vradi E, Brugts JJ, Brunner-La Rocca HP, Blanc-Guillemaud V, Waechter S, Couvelard F, Tyl B, Fatoba S, Hoes AW, Lund LH, Gerlinger C, Asselbergs FW, Grobbee DE, Cronin M, Koudstaal S.",,European journal of heart failure,2023,2023-05-18,N,Heart Failure; Randomized Clinical Trial; Females; Enrichment Strategies; Standardized Mortality Ratios; Real-world Evidence,,,"

Aims

In order to understand how sex differences impact the generalizability of randomized clinical trials (RCTs) in patients with heart failure (HF) and reduced ejection fraction (HFrEF), we sought to compare clinical characteristics and clinical outcomes between RCTs and HF observational registries stratified by sex.

Methods and results

Data from two HF registries and five HFrEF RCTs were used to create three subpopulations: one RCT population (n = 16 917; 21.7% females), registry patients eligible for RCT inclusion (n = 26 104; 31.8% females), and registry patients ineligible for RCT inclusion (n = 20 810; 30.2% females). Clinical endpoints included all-cause mortality, cardiovascular mortality, and first HF hospitalization at 1 year. Males and females were equally eligible for trial enrolment (56.9% of females and 55.1% of males in the registries). One-year mortality rates were 5.6%, 14.0%, and 28.6% for females and 6.9%, 10.7%, and 24.6% for males in the RCT, RCT-eligible, and RCT-ineligible groups, respectively. After adjusting for 11 HF prognostic variables, RCT females showed higher survival compared to RCT-eligible females (standardized mortality ratio [SMR] 0.72; 95% confidence interval [CI] 0.62-0.83), while RCT males showed higher adjusted mortality rates compared to RCT-eligible males (SMR 1.16; 95% CI 1.09-1.24). Similar results were also found for cardiovascular mortality (SMR 0.89; 95% CI 0.76-1.03 for females, SMR 1.43; 95% CI 1.33-1.53 for males).

Conclusion

Generalizability of HFrEF RCTs differed substantially between the sexes, with females having lower trial participation and female trial participants having lower mortality rates compared to similar females in the registries, while males had higher than expected cardiovascular mortality rates in RCTs compared to similar males in registries.",,doi:https://doi.org/10.1002/ejhf.2868; doi:https://doi.org/10.1002/ejhf.2868 35452565,https://doi.org/10.1002/cpz1.373,The COPILOT Raw Illumina Genotyping QC Protocol.,"Patel H, Lee SH, Breen G, Menzel S, Ojewunmi O, Dobson RJB.",,Current protocols,2022,2022-04-01,N,Genotyping; Gwas; Illumina; Docker; Qc Pipeline,,,"The Illumina genotyping microarrays generate data in image format, which is processed by the platform-specific software GenomeStudio, followed by an array of complex bioinformatics analyses that rely on various software, different programming languages, and numerous dependencies to be installed and configured correctly. The entire process can be time-consuming, can lead to reproducibility errors, and can be a daunting task for bioinformaticians. To address this, we introduce the COPILOT protocol, which has been successfully used to transform raw Illumina genotype intensity data into high-quality analysis-ready data on tens of thousands of human patient samples that have been genotyped on a variety of Illumina genotyping arrays. This includes processing both mainstream and custom content genotyping chips with over 4 million markers per sample. The COPILOT QC protocol consists of two distinct tandem procedures to process raw Illumina genotyping data. The first protocol is an up-to-date process to systematically QC raw Illumina microarray genotyping data using the Illumina-specific GenomeStudio software. The second protocol takes the output from the first protocol and further processes the data through the COPILOT (Containerised wOrkflow for Processing ILlumina genOtyping daTa) containerized QC pipeline, to automate an array of complex bioinformatics analyses to improve data quality through a secondary clustering algorithm and to automatically identify typical Genome-Wide Association Study (GWAS) data issues, including gender discrepancies, heterozygosity outliers, related individuals, and population outliers, through ancestry estimation. The data is returned to the user in analysis-ready PLINK binary format and is accompanied by a comprehensive and interactive HTML summary report file which quickly helps the user understand the data and guides the user for further data analyses. The COPILOT protocol and containerized pipeline are also available at https://khp-informatics.github.io/COPILOT/index.html. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Processing raw Illumina genotyping data using GenomeStudio Basic Protocol 2: COPILOT: A containerised workflow for processing Illumina genotyping data.",,pdf:https://discovery.ucl.ac.uk/10149151/1/Dobson_The%20COPILOT%20Raw%20Illumina%20Genotyping%20QC%20Protocol_VoR.pdf; doi:https://doi.org/10.1002/cpz1.373 @@ -1393,12 +1393,12 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 36355406,https://doi.org/10.2196/40707,Effectiveness of a Web-Based Intervention to Prevent Anxiety in the Children of Parents With Anxiety: Protocol for a Randomized Controlled Trial.,"Dunn A, Alvarez J, Arbon A, Bremner S, Elsby-Pearson C, Emsley R, Jones C, Lawrence P, Lester KJ, Majdandžić M, Morson N, Perry N, Simner J, Thomson A, Cartwright-Hatton S.",,JMIR research protocols,2022,2022-11-10,Y,Child; Parent; Youth; Anxiety; Pediatric; Mental health; Randomized controlled trial; Parenting; Rct; Online; Mental Well-being; Online Intervention; Digital Intervention,,,"

Background

Anxiety is the most common childhood mental health condition and is associated with impaired child outcomes, including increased risk of mental health difficulties in adulthood. Anxiety runs in families: when a parent has anxiety, their child has a 50% higher chance of developing it themselves. Environmental factors are predominant in the intergenerational transmission of anxiety and, of these, parenting processes play a major role. Interventions that target parents to support them to limit the impact of any anxiogenic parenting behaviors are associated with reduced anxiety in their children. A brief UK-based group intervention delivered to parents within the UK National Health Service led to a 16% reduction in children meeting the criteria for an anxiety disorder. However, this intervention is not widely accessible. To widen access, a 9-module web-based version of this intervention has been developed. This course comprises psychoeducation and home practice delivered through text, video, animations, and practice tasks.

Objective

This study seeks to evaluate the feasibility of delivering this web-based intervention and assess its effectiveness in reducing child anxiety symptoms.

Methods

 This is the protocol for a randomized controlled trial (RCT) of a community sample of 1754 parents with self-identified high levels of anxiety with a child aged 2-11 years. Parents in the intervention arm will receive access to the web-based course, which they undertake at a self-determined rate. The control arm receives no intervention. Follow-up data collection is at months 6 and months 9-21. Intention-to-treat analysis will be conducted on outcomes including child anxiety, child mental health symptoms, and well-being; parental anxiety and well-being; and parenting behaviors.

Results

Funding was received in April 2020, and recruitment started in February 2021 and is projected to end in October 2022. A total of 1350 participants have been recruited as of May 2022.

Conclusions

The results of this RCT will provide evidence on the utility of a web-based course in preventing intergenerational transmission of anxiety and increase the understanding of familial anxiety.

Trial registration

ClinicalTrials.gov NCT04755933; https://clinicaltrials.gov/ct2/show/NCT04755933.

International registered report identifier (irrid)

DERR1-10.2196/40707.",,pdf:https://jmir.org/api/download?alt_name=resprot_v11i11e40707_app2.pdf&filename=4e6914231a45b12439d1932b760a7c34.pdf; doi:https://doi.org/10.2196/40707; html:https://europepmc.org/articles/PMC9693706 37757876,https://doi.org/10.1097/ede.0000000000001649,Comparative Effectiveness of Dynamic Treatment Strategies for Medication Use and Dosage: Emulating a Target Trial Using Observational Data.,"Birnie K, Tomson C, Caskey FJ, Ben-Shlomo Y, Nitsch D, Casula A, Murray EJ, Sterne JAC.",,"Epidemiology (Cambridge, Mass.)",2023,2023-09-26,N,,,,"

Background

Availability of detailed data from electronic health records (EHRs) has increased the potential to examine the comparative effectiveness of dynamic treatment strategies using observational data. Inverse probability (IP) weighting of dynamic marginal structural models can control for time-varying confounders. However, IP weights for continuous treatments may be sensitive to model choice.

Methods

We describe a target trial comparing strategies for treating anemia with darbepoetin in hemodialysis patients using EHR data from the UK Renal Registry 2004 to 2016. Patients received a specified dose (microgram/week) or did not receive darbepoetin. We compared 4 methods for modeling time-varying treatment: (A) logistic regression for zero dose, standard linear regression for log dose; (B) logistic regression for zero dose, heteroscedastic linear regression for log dose; (C) logistic regression for zero dose, heteroscedastic linear regression for log dose, multinomial regression for patients who recently received very low or high doses; and (D) ordinal logistic regression.

Results

For this dataset, method (C) was the only approach that provided a robust estimate of the mortality hazard ratio (HR), with less-extreme weights in a fully weighted analysis and no substantial change of the HR point estimate after weight truncation. After truncating IP weights at the 95th percentile, estimates were similar across the methods.

Conclusions

EHR data can be used to emulate target trials estimating the comparative effectiveness of dynamic strategies adjusting treatment to evolving patient characteristics. However, model checking, monitoring of large weights, and adaptation of model strategies to account for these is essential if an aspect of treatment is continuous.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7615288; doi:https://doi.org/10.1097/EDE.0000000000001649; html:https://europepmc.org/articles/PMC7615288; pdf:https://europepmc.org/articles/PMC7615288?pdf=render; doi:https://doi.org/10.1097/ede.0000000000001649 34907415,https://doi.org/10.1093/ehjci/jeab266,Left atrial structure and function are associated with cardiovascular outcomes independent of left ventricular measures: a UK Biobank CMR study.,"Raisi-Estabragh Z, McCracken C, Condurache D, Aung N, Vargas JD, Naderi H, Munroe PB, Neubauer S, Harvey NC, Petersen SE.",,European heart journal. Cardiovascular Imaging,2022,2022-08-01,Y,Mortality; Atrial fibrillation; Stroke; Ischaemic Heart Disease; Cardiovascular Magnetic Resonance; Left ventricle; Vascular Risk Factors; Cardiovascular Outcomes; Lef; T Atrium,,,"

Aims

We evaluated the associations of left atrial (LA) structure and function with prevalent and incident cardiovascular disease (CVD), independent of left ventricular (LV) metrics, in 25 896 UK Biobank participants.

Methods and results

We estimated the association of cardiovascular magnetic resonance (CMR) metrics [LA maximum volume (LAV), LA ejection fraction (LAEF), LV mass : LV end-diastolic volume ratio (LVM : LVEDV), global longitudinal strain, and LV global function index (LVGFI)] with vascular risk factors (hypertension, diabetes, high cholesterol, and smoking), prevalent and incident CVDs [atrial fibrillation (AF), stroke, ischaemic heart disease (IHD), myocardial infarction], all-cause mortality, and CVD mortality. We created uncorrelated CMR variables using orthogonal principal component analysis rotation. All five CMR metrics were simultaneously entered into multivariable regression models adjusted for sex, age, ethnicity, deprivation, education, body size, and physical activity. Lower LAEF was associated with diabetes, smoking, and all the prevalent and incident CVDs. Diabetes, smoking, and high cholesterol were associated with smaller LAV. Hypertension, IHD, AF (incident and prevalent), incident stroke, and CVD mortality were associated with larger LAV. LV and LA metrics were both independently informative in associations with prevalent disease, however LAEF showed the most consistent associations with incident CVDs. Lower LVGFI was associated with greater all-cause and CVD mortality. In secondary analyses, compared with LVGFI, LV ejection fraction showed similar but less consistent disease associations.

Conclusion

LA structure and function measures (LAEF and LAV) demonstrate significant associations with key prevalent and incident cardiovascular outcomes, independent of LV metrics. These measures have potential clinical utility for disease discrimination and outcome prediction.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeab266/41764801/jeab266.pdf; doi:https://doi.org/10.1093/ehjci/jeab266; html:https://europepmc.org/articles/PMC9365306; pdf:https://europepmc.org/articles/PMC9365306?pdf=render -37319288,https://doi.org/10.1371/journal.pone.0287264,Evaluation of data processing pipelines on real-world electronic health records data for the purpose of measuring patient similarity.,"Pikoula M, Kallis C, Madjiheurem S, Quint JK, Bafadhel M, Denaxas S.",,PloS one,2023,2023-06-15,Y,,,,"

Background

The ever-growing size, breadth, and availability of patient data allows for a wide variety of clinical features to serve as inputs for phenotype discovery using cluster analysis. Data of mixed types in particular are not straightforward to combine into a single feature vector, and techniques used to address this can be biased towards certain data types in ways that are not immediately obvious or intended. In this context, the process of constructing clinically meaningful patient representations from complex datasets has not been systematically evaluated.

Aims

Our aim was to a) outline and b) implement an analytical framework to evaluate distinct methods of constructing patient representations from routine electronic health record data for the purpose of measuring patient similarity. We applied the analysis on a patient cohort diagnosed with chronic obstructive pulmonary disease.

Methods

Using data from the CALIBER data resource, we extracted clinically relevant features for a cohort of patients diagnosed with chronic obstructive pulmonary disease. We used four different data processing pipelines to construct lower dimensional patient representations from which we calculated patient similarity scores. We described the resulting representations, ranked the influence of each individual feature on patient similarity and evaluated the effect of different pipelines on clustering outcomes. Experts evaluated the resulting representations by rating the clinical relevance of similar patient suggestions with regard to a reference patient.

Results

Each of the four pipelines resulted in similarity scores primarily driven by a unique set of features. It was demonstrated that data transformations according to each pipeline prior to clustering can result in a variation of clustering results of over 40%. The most appropriate pipeline was selected on the basis of feature ranking and clinical expertise. There was moderate agreement between clinicians as measured by Cohen's kappa coefficient.

Conclusions

Data transformation has downstream and unforeseen consequences in cluster analysis. Rather than viewing this process as a black box, we have shown ways to quantitatively and qualitatively evaluate and select the appropriate preprocessing pipeline.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287264&type=printable; doi:https://doi.org/10.1371/journal.pone.0287264; html:https://europepmc.org/articles/PMC10270623; pdf:https://europepmc.org/articles/PMC10270623?pdf=render 32856398,https://doi.org/10.1111/1742-6723.13604,To intubate or not to intubate? Predictors of inhalation injury in burn-injured patients before arrival at the burn centre.,"Dyson K, Baker P, Garcia N, Braun A, Aung M, Pilcher D, Smith K, Cleland H, Gabbe B.",,Emergency medicine Australasia : EMA,2021,2020-08-27,N,Burn; Pre-hospital; Inhalation Injury; Endotracheal Intubation,,,"

Objective

Inhalation injury occurs in approximately 10-20% of burn patients and is associated with increased mortality. There is no clear method of identifying patients at risk of inhalation injury or requiring intubation in the pre-hospital setting. Our objective was to identify pre-burn centre factors associated with inhalation injury confirmed on bronchoscopy, and to develop a prognostic model for inhalation injury.

Methods

We analysed acute admissions from the Victorian Adult Burns Service and Ambulance Victoria electronic patient care records for 1 July 2009 to 30 June 2016. We defined inhalation injury as an Abbreviated Injury Scale of >1 on bronchoscopy. A multivariable logistic regression prediction model was developed based on pre-burn centre factors.

Results

Emergency medical services transported 1148 patients who were admitted to the burn centre. The median age of patients was 39 years and most patients had <10% total body surface area (%TBSA) burned. The prevalence of confirmed inhalation injury was 11%. Increasing %TBSA burned, flame, enclosed space, face burns, hoarse voice, soot in mouth and shortness of breath were predictive of inhalation injury. The model provided excellent discrimination (area under curve 0.87, 95% confidence interval 0.84-0.91). A lower proportion of patients intubated at a non-burn centre had an inhalation injury (33%) compared to patients intubated by emergency medical services (54%) and in the burn centre (58%).

Conclusions

A model to predict inhalation injury in burn-injured patients was developed with excellent discrimination. This model requires prospective testing but could form an integral part of clinician decision-making.",,doi:https://doi.org/10.1111/1742-6723.13604 +37319288,https://doi.org/10.1371/journal.pone.0287264,Evaluation of data processing pipelines on real-world electronic health records data for the purpose of measuring patient similarity.,"Pikoula M, Kallis C, Madjiheurem S, Quint JK, Bafadhel M, Denaxas S.",,PloS one,2023,2023-06-15,Y,,,,"

Background

The ever-growing size, breadth, and availability of patient data allows for a wide variety of clinical features to serve as inputs for phenotype discovery using cluster analysis. Data of mixed types in particular are not straightforward to combine into a single feature vector, and techniques used to address this can be biased towards certain data types in ways that are not immediately obvious or intended. In this context, the process of constructing clinically meaningful patient representations from complex datasets has not been systematically evaluated.

Aims

Our aim was to a) outline and b) implement an analytical framework to evaluate distinct methods of constructing patient representations from routine electronic health record data for the purpose of measuring patient similarity. We applied the analysis on a patient cohort diagnosed with chronic obstructive pulmonary disease.

Methods

Using data from the CALIBER data resource, we extracted clinically relevant features for a cohort of patients diagnosed with chronic obstructive pulmonary disease. We used four different data processing pipelines to construct lower dimensional patient representations from which we calculated patient similarity scores. We described the resulting representations, ranked the influence of each individual feature on patient similarity and evaluated the effect of different pipelines on clustering outcomes. Experts evaluated the resulting representations by rating the clinical relevance of similar patient suggestions with regard to a reference patient.

Results

Each of the four pipelines resulted in similarity scores primarily driven by a unique set of features. It was demonstrated that data transformations according to each pipeline prior to clustering can result in a variation of clustering results of over 40%. The most appropriate pipeline was selected on the basis of feature ranking and clinical expertise. There was moderate agreement between clinicians as measured by Cohen's kappa coefficient.

Conclusions

Data transformation has downstream and unforeseen consequences in cluster analysis. Rather than viewing this process as a black box, we have shown ways to quantitatively and qualitatively evaluate and select the appropriate preprocessing pipeline.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287264&type=printable; doi:https://doi.org/10.1371/journal.pone.0287264; html:https://europepmc.org/articles/PMC10270623; pdf:https://europepmc.org/articles/PMC10270623?pdf=render 32352158,https://doi.org/10.1002/bjs.11580,Author response to: Comment on: Impact of bariatric surgery on cardiovascular outcomes and mortality: a population-based cohort study.,"Adderley N, Singh P, Tahrani AA, Nirantharakumar K.",,The British journal of surgery,2020,2020-04-30,N,,,,,,pdf:https://academic.oup.com/bjs/article-pdf/107/7/e220/35705126/bjs11580.pdf; doi:https://doi.org/10.1002/bjs.11580 32426117,https://doi.org/10.7189/jogh.10.010348,Novel approaches to estimate compliance with lockdown measures in the COVID-19 pandemic.,"Sheikh A, Sheikh Z, Sheikh A.",,Journal of global health,2020,2020-06-01,Y,,,,,This is a summary of new methods for estimating phyiscal distancing and compliance with lockdown. I haven't scored the content because it isn't primary research.,doi:https://doi.org/10.7189/jogh.10.010348; doi:https://doi.org/10.7189/jogh.10.010348; html:https://europepmc.org/articles/PMC7211415; pdf:https://europepmc.org/articles/PMC7211415?pdf=render -35202588,https://doi.org/10.1016/s2213-8587(22)00015-8,Dose-response relationships for vitamin D and all-cause mortality - Authors' reply.,"Burgess S, Butterworth AS.",,The lancet. Diabetes & endocrinology,2022,2022-03-01,N,,,,,,pdf:http://www.thelancet.com/article/S2213858722000158/pdf; doi:https://doi.org/10.1016/S2213-8587(22)00015-8 34304930,https://doi.org/10.1016/j.burns.2021.06.007,Trends in Victorian burn injuries 2008-2017.,"Cleland H, Fernando DT, Gabbe BJ.",,Burns : journal of the International Society for Burn Injuries,2022,2021-07-07,N,Burns Mortality; Burns Epidemiology; Burns Australia,,,"

Objectives

To describe incidence and characteristics of hospital presentations and deaths due to burn injury in the Australian state of Victoria from 2008 to 2017 and identify trends in incidence and patterns.

Methods

Three population-based datasets were used to ascertain burn-related hospital admissions, emergency department presentations, and deaths. These were the Victorian Admitted Episodes Dataset (VAED), Victorian Emergency Minimum Dataset (VEMD), and the Cause of Death-Unit Record File (COD-URF), respectively. Descriptive statistics on demographics (age and gender), burn injury characteristics (intent, cause, burn size and body region) and hospital burden (length of stay (LOS) and costs) were used to present the profile of patients. Incidence rates by age, gender and intent were calculated. Trend analysis on incidence was carried out using forced Poisson Regression models with the natural logarithm of the annual populations as an offset. Incident rate ratios were used to interpret the models. Risk ratios were used to compare the risk differences between population sub-groups. A negative binomial model was used to test the association between LOS and age and the total body surface area (TBSA) of the burn.

Results

Overall males had higher rates of death, admission and ED presentation. For adults, the elderly had the highest rates of deaths and admissions while for children, the very young had highest rates for admissions and presentations. Exposure to smoke, fire and flames was the most common cause of deaths, and contact with heat and hot substances was most common among ED presentations. The elderly and those with Total Body Surface Area (TBSA) burn ≥20% had a higher risk of longer hospital stay. Rates of severe burns and deaths from burns remained stable during the study period in the setting of an annual 2% increase in population. Paediatric hospital admission rates decreased over time.

Conclusion

The risk of sustaining burn injury, the types of burn and outcomes, varied by age and gender. We found evidence of a limited decrease in burn injury rates in some sub-groups: appropriate and effective targeted prevention strategies for burns are needed to avoid the significant short and long-term suffering experienced.",,doi:https://doi.org/10.1016/j.burns.2021.06.007 +35202588,https://doi.org/10.1016/s2213-8587(22)00015-8,Dose-response relationships for vitamin D and all-cause mortality - Authors' reply.,"Burgess S, Butterworth AS.",,The lancet. Diabetes & endocrinology,2022,2022-03-01,N,,,,,,pdf:http://www.thelancet.com/article/S2213858722000158/pdf; doi:https://doi.org/10.1016/S2213-8587(22)00015-8 37730605,https://doi.org/10.1186/s12889-023-16523-9,Inequalities and mental health during the Coronavirus pandemic in the UK: a mixed-methods exploration.,"Lombardo C, Guo L, Solomon S, Crepaz-Keay D, McDaid S, Thorpe L, Martin S, John A, Morton A, Davidson G, Kousoulis AA, Van Bortel T.",,BMC public health,2023,2023-09-20,Y,Coronavirus; Mental health; Pandemic; United Kingdom; Inequalities; Social Determinants; Inequity; Adult Population; Covid-19,,,"

Background

The World Health Organisation declared the novel Coronavirus disease (COVID-19) a global pandemic on 11th March 2020. Since then, the world has been firmly in its grip. At the time of writing, there were more than 767,972,961 million confirmed cases and over 6,950,655 million deaths. While the main policy focus has been on controlling the virus and ensuring vaccine roll-out and uptake, the population mental health impacts of the pandemic are expected to be long-term, with certain population groups affected more than others.

Methods

The overall objectives of our 'Coronavirus: Mental Health and the Pandemic' study were to explore UK adults' experiences of the Coronavirus pandemic and to gain insights into the mental health impacts, population-level changes over time, current and future mental health needs, and how these can best be addressed. The wider mixed-methods study consisted of repeated cross-sectional surveys and embedded qualitative sub-studies including in-depth interviews and focus group discussions with the wider UK adult population. For this particular inequalities and mental health sub-study, we used mixed methods data from our cross-sectional surveys and we carried out three Focus Group Discussions with a maximum variation sample from across the UK adult population. The discussions covered the broader topic of 'Inequalities and mental health during the Coronavirus pandemic in the UK' and took place online between April and August 2020. Focus Groups transcripts were analysed using thematic analysis in NVIVO. Cross-sectional survey data were analysed using STATA for descriptive statistics.

Results

Three broad main themes emerged, each supporting a number of sub-themes: (1) Impacts of the pandemic; (2) Moving forward: needs and recommendations; (3) Coping mechanisms and resilience. Findings showed that participants described their experiences of the pandemic in relation to its impact on themselves and on different groups of people. Their experiences illustrated how the pandemic and subsequent measures had exacerbated existing inequalities and created new ones, and triggered various emotional responses. Participants also described their coping strategies and what worked and did not work for them, as well as support needs and recommendations for moving forward through, and out of, the pandemic; all of which are valuable learnings to be considered in policy making for improving mental health and for ensuring future preparedness.

Conclusions

The pandemic is taking a long-term toll on the nations' mental health which will continue to have impacts for years to come. It is therefore crucial to learn the vital lessons learned from this pandemic. Specific as well as whole-government policies need to respond to this, address inequalities and the different needs across the life-course and across society, and take a holistic approach to mental health improvement across the UK.",,pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-023-16523-9; doi:https://doi.org/10.1186/s12889-023-16523-9; html:https://europepmc.org/articles/PMC10510114; pdf:https://europepmc.org/articles/PMC10510114?pdf=render 37884627,https://doi.org/10.1038/s41591-023-02608-w,The value of standards for health datasets in artificial intelligence-based applications.,"Arora A, Alderman JE, Palmer J, Ganapathi S, Laws E, McCradden MD, Oakden-Rayner L, Pfohl SR, Ghassemi M, McKay F, Treanor D, Rostamzadeh N, Mateen B, Gath J, Adebajo AO, Kuku S, Matin R, Heller K, Sapey E, Sebire NJ, Cole-Lewis H, Calvert M, Denniston A, Liu X.",,Nature medicine,2023,2023-10-26,Y,,,,"Artificial intelligence as a medical device is increasingly being applied to healthcare for diagnosis, risk stratification and resource allocation. However, a growing body of evidence has highlighted the risk of algorithmic bias, which may perpetuate existing health inequity. This problem arises in part because of systemic inequalities in dataset curation, unequal opportunity to participate in research and inequalities of access. This study aims to explore existing standards, frameworks and best practices for ensuring adequate data diversity in health datasets. Exploring the body of existing literature and expert views is an important step towards the development of consensus-based guidelines. The study comprises two parts: a systematic review of existing standards, frameworks and best practices for healthcare datasets; and a survey and thematic analysis of stakeholder views of bias, health equity and best practices for artificial intelligence as a medical device. We found that the need for dataset diversity was well described in literature, and experts generally favored the development of a robust set of guidelines, but there were mixed views about how these could be implemented practically. The outputs of this study will be used to inform the development of standards for transparency of data diversity in health datasets (the STANDING Together initiative).",,pdf:https://www.nature.com/articles/s41591-023-02608-w.pdf; doi:https://doi.org/10.1038/s41591-023-02608-w; html:https://europepmc.org/articles/PMC10667100; pdf:https://europepmc.org/articles/PMC10667100?pdf=render 34145643,https://doi.org/10.1111/jdv.17450,Describing the burden of the COVID-19 pandemic in people with psoriasis: findings from a global cross-sectional study.,"Mahil SK, Yates M, Yiu ZZN, Langan SM, Tsakok T, Dand N, Mason KJ, McAteer H, Meynell F, Coker B, Vincent A, Urmston D, Vesty A, Kelly J, Lancelot C, Moorhead L, Bachelez H, Capon F, Contreras CR, De La Cruz C, Di Meglio P, Gisondi P, Jullien D, Lambert J, Naldi L, Norton S, Puig L, Spuls P, Torres T, Warren RB, Waweru H, Weinman J, Brown MA, Galloway JB, Griffiths CM, Barker JN, Smith CH, PsoProtect study group.",,Journal of the European Academy of Dermatology and Venereology : JEADV,2021,2021-08-19,Y,,,,,,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jdv.17450; doi:https://doi.org/10.1111/jdv.17450; html:https://europepmc.org/articles/PMC8447018; pdf:https://europepmc.org/articles/PMC8447018?pdf=render @@ -1410,8 +1410,8 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 37408046,https://doi.org/10.1186/s40545-023-00590-9,Delivering the precision oncology paradigm: reduced R&D costs and greater return on investment through a companion diagnostic informed precision oncology medicines approach.,"Henderson RH, French D, Stewart E, Smart D, Idica A, Redmond S, Eckstein M, Clark J, Sullivan R, Keeling P, Lawler M.",,Journal of pharmaceutical policy and practice,2023,2023-07-05,Y,,,,"

Background

Precision oncology medicines represent a paradigm shift compared to non-precision oncology medicines in cancer therapy, in some situations delivering more clinical benefit, and potentially lowering healthcare costs. We determined whether employing a companion diagnostic (CDx) approach during oncology medicines development delivers effective therapies that are within the cost constraints of current health systems. R&D costs of developing a medicine are subject to debate, with average estimates ranging from $765 million (m) to $4.6 billion (b). Our aim was to determine whether precision oncology medicines are cheaper to bring from R&D to market; a secondary goal was to determine whether precision oncology medicines have a greater return on investment (ROI).

Method

Data on oncology medicines approved between 1997 and 2020 by the US Food and Drug Administration (FDA) were analysed from the Securities and Exchange Commission (SEC) filings. Data were compiled from 10-K, 10-Q, and 20-F financial performance filings on medicines' development costs through their R&D lifetime. Clinical trial data were split into clinical trial phases 1-3 and probability of success (POS) of trials was calculated, along with preclinical costs. Cost-of-capital (CoC) approach was applied and, if appropriate, a tax rebate was subtracted from the total.

Results

Data on 42 precision and 29 non-precision oncology medicines from 56 companies listed by the National Cancer Institute which had complete data available were analysed. Estimated mean cost to deliver a new oncology medicine was $4.4b (95% CI, $3.6-5.2b). Costs to bring a precision oncology medicine to market were $1.1b less ($3.5b; 95% CI, $2.7-4.5b) compared to non-precision oncology medicines ($4.6b; 95% CI, $3.5-6.1b). The key driver of costs was POS of clinical trials, accounting for a difference of $591.3 m. Additional data analysis illustrated that there was a 27% increase in return on investment (ROI) of precision oncology medicines over non-precision oncology medicines.

Conclusion

Our results provide an accurate estimate of the R&D spend required to bring an oncology medicine to market. Deployment of a CDx at the earliest stage substantially lowers the cost associated with oncology medicines development, potentially making them available to more patients, while staying within the cost constraints of cancer health systems.",,pdf:https://joppp.biomedcentral.com/counter/pdf/10.1186/s40545-023-00590-9; doi:https://doi.org/10.1186/s40545-023-00590-9; html:https://europepmc.org/articles/PMC10320864; pdf:https://europepmc.org/articles/PMC10320864?pdf=render 38279797,https://doi.org/10.1089/neu.2023.0465,The Australian Traumatic Brain Injury Initiative: Systematic Review of the Effect of Acute Interventions on Outcome for People With Moderate-Severe Traumatic Brain Injury.,"Keeves J, Gadowski A, McKimmie A, Bagg MK, Antonic-Baker A, Hicks AJ, Clarke N, Brown A, McNamara R, Reeder S, Roman C, Jeffcote T, Romero L, Hill R, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Rushworth N, Fitzgerald M, Gabbe BJ, Cooper DJ.",,Journal of neurotrauma,2024,2024-04-08,N,"Common Data Elements; Brain Injuries, Traumatic; Outcome Assessment, Health Care; Systematic Review [Publication Type]; Emergency Medical Services, Critical Care, Early Medical Intervention",,,"The Australian Traumatic Brain Injury Initiative (AUS-TBI) is developing a data resource to enable improved outcome prediction for people with moderate-severe TBI (msTBI) across Australia. Fundamental to this resource is the collaboratively designed data dictionary. This systematic review and consultation aimed to identify acute interventions with potential to modify clinical outcomes for people after msTBI, for inclusion in a data dictionary. Standardized searches were implemented across bibliographic databases from inception through April 2022. English-language reports of randomized controlled trials (RCTs) evaluating any association between any acute intervention and clinical outcome in at least 100 patients with msTBI, were included. A predefined algorithm was used to assign a value to each observed association. Consultation with AUS-TBI clinicians and researchers formed the consensus process for interventions to be included in a single data dictionary. Searches retrieved 14,455 records, of which 124 full-length RCTs were screened, with 35 studies included. These studies evaluated 26 unique acute interventions across 21 unique clinical outcomes. Only 4 interventions were considered to have medium modifying value for any outcome from the review, with an additional 8 interventions agreed upon through the consensus process. The interventions with medium value were tranexamic acid and phenytoin, which had a positive effect on an outcome; and decompressive craniectomy surgery and hypothermia, which negatively affected outcomes. From the systematic review and consensus process, 12 interventions were identified as potential modifiers to be included in the AUS-TBI national data resource.",,doi:https://doi.org/10.1089/neu.2023.0465 37190768,https://doi.org/10.1017/s2045796023000276,The mental health of all children in contact with social services: a population-wide record-linkage study in Northern Ireland.,"McKenna S, O'Reilly D, Maguire A.",,Epidemiology and psychiatric sciences,2023,2023-05-16,Y,Mental health; Data Linkage; Children’s Social Care,,,"

Aims

Children in contact with social services are at high risk for mental ill health, but it is not known what proportion of the child population has contact with social services or how risk varies within this group compared to unexposed peers. We aim to quantify the extent and nature of contact with social services within the child population in Northern Ireland (NI) and the association with mental ill health. We also examine which social care experiences identify those most at risk.

Methods

This is a population-based record-linkage study of 497,269 children (aged under 18 years) alive and resident in NI in 2015 using routinely collected health and social care data. Exposure was categorized as (1) no contact, (2) referred but assessed as not in need (NIN), (3) child in need (CIN) and (4) child in care (CIC). Multilevel logistic regression analyses estimated odds ratios (ORs) for mental ill health indicated by receipt of psychotropic medication (antidepressants, anxiolytics, antipsychotics and hypnotics), psychiatric hospital admission and hospital-presenting self-harm or ideation.

Results

Over one in six children (17.2%, n = 85,792) were currently or previously in contact with social services, and almost one child in every 20 (4.8%, n = 23,975) had contact in 2015. Likelihood of any mental ill health outcome increased incrementally with the level of contact with social services relative to unexposed peers: NIN (OR 5.90 [95% confidence interval (CI) 5.10-6.83]), CIN (OR 5.99 [95% CI 5.50-6.53]) and CIC (OR 12.60 [95% CI 10.63-14.95]). All tiers of contact, number of referrals, number of care episodes and placement type were strongly associated with the likelihood of mental ill health.

Conclusion

Children who have contact with social services account for a large and disproportionate amount of mental ill health in the child population. Likelihood of poor mental health across indicators is highest in care experienced children but also extends to the much larger population of children in contact with social services but never in care. Findings suggest a need for targeted mental health screening and enhanced support for all children in contact with social services.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/A60E6D761449A937DCE08F3A075B236D/S2045796023000276a.pdf/div-class-title-the-mental-health-of-all-children-in-contact-with-social-services-a-population-wide-record-linkage-study-in-northern-ireland-div.pdf; doi:https://doi.org/10.1017/S2045796023000276; html:https://europepmc.org/articles/PMC10227534; pdf:https://europepmc.org/articles/PMC10227534?pdf=render -38326875,https://doi.org/10.1186/s13059-024-03172-3,"IDHwt glioblastomas can be stratified by their transcriptional response to standard treatment, with implications for targeted therapy.","Tanner G, Barrow R, Ajaib S, Al-Jabri M, Ahmed N, Pollock S, Finetti M, Rippaus N, Bruns AF, Syed K, Poulter JA, Matthews L, Hughes T, Wilson E, Johnson C, Varn FS, Brüning-Richardson A, Hogg C, Droop A, Gusnanto A, Care MA, Cutillo L, Westhead DR, Short SC, Jenkinson MD, Brodbelt A, Chakrabarty A, Ismail A, Verhaak RGW, Stead LF.",,Genome biology,2024,2024-02-07,Y,,,,"

Background

Glioblastoma (GBM) brain tumors lacking IDH1 mutations (IDHwt) have the worst prognosis of all brain neoplasms. Patients receive surgery and chemoradiotherapy but tumors almost always fatally recur.

Results

Using RNA sequencing data from 107 pairs of pre- and post-standard treatment locally recurrent IDHwt GBM tumors, we identify two responder subtypes based on longitudinal changes in gene expression. In two thirds of patients, a specific subset of genes is upregulated from primary to recurrence (Up responders), and in one third, the same genes are downregulated (Down responders), specifically in neoplastic cells. Characterization of the responder subtypes indicates subtype-specific adaptive treatment resistance mechanisms that are associated with distinct changes in the tumor microenvironment. In Up responders, recurrent tumors are enriched in quiescent proneural GBM stem cells and differentiated neoplastic cells, with increased interaction with the surrounding normal brain and neurotransmitter signaling, whereas Down responders commonly undergo mesenchymal transition. ChIP-sequencing data from longitudinal GBM tumors suggests that the observed transcriptional reprogramming could be driven by Polycomb-based chromatin remodeling rather than DNA methylation.

Conclusions

We show that the responder subtype is cancer-cell intrinsic, recapitulated in in vitro GBM cell models, and influenced by the presence of the tumor microenvironment. Stratifying GBM tumors by responder subtype may lead to more effective treatment.",,pdf:https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-024-03172-3; doi:https://doi.org/10.1186/s13059-024-03172-3; html:https://europepmc.org/articles/PMC10848526; pdf:https://europepmc.org/articles/PMC10848526?pdf=render 36198485,https://doi.org/10.1136/jech-2021-217986,Characteristics of enrolment in an intensive home-visiting programme among eligible first-time adolescent mothers in England: a linked administrative data cohort study.,"Cavallaro FL, Gilbert R, Wijlaars LP, Kennedy E, Howarth E, Kendall S, van der Meulen J, Calin MA, Reed L, Harron K.",,Journal of epidemiology and community health,2022,2022-10-05,Y,Adolescent; Public Health; Child Health,,,"

Background

Intensive home visiting for adolescent mothers may help reduce health disparities. Given limited resources, such interventions need to be effectively targeted. We evaluated which mothers were enrolled in the Family Nurse Partnership (FNP), an intensive home-visiting service for first-time young mothers commissioned in >130 local authorities in England since 2007.

Methods

We created a population-based cohort of first-time mothers aged 13-19 years giving birth in English National Health Service hospitals between 1 April 2010 and 31 March 2017, using administrative hospital data linked with FNP programme, educational and social care data. Mothers living in a local authority with an active FNP site were eligible. We described variation in enrolment rates across sites, and identified maternal and FNP site characteristics associated with enrolment.

Results

Of 110 520 eligible mothers, 25 680 (23.2% (95% CI: 23.0% to 23.5%)) were enrolled. Enrolment rates varied substantially across 122 sites (range: 11%-68%), and areas with greater numbers of first-time adolescent mothers achieved lower enrolment rates. Mothers aged 13-15 years were most likely to be enrolled (52%). However, only 26% of adolescent mothers with markers of vulnerability (including living in the most deprived areas and ever having been looked after as a child) were enrolled.

Conclusion

A substantial proportion of first-time adolescent mothers with vulnerability markers were not enrolled in FNP. Variation in enrolment across sites indicates insufficient commissioning of places that is not proportional to level of need, with mothers in areas with large numbers of other adolescent mothers least likely to receive support.",,pdf:https://jech.bmj.com/content/jech/76/12/991.full.pdf; doi:https://doi.org/10.1136/jech-2021-217986; html:https://europepmc.org/articles/PMC9664100; pdf:https://europepmc.org/articles/PMC9664100?pdf=render +38326875,https://doi.org/10.1186/s13059-024-03172-3,"IDHwt glioblastomas can be stratified by their transcriptional response to standard treatment, with implications for targeted therapy.","Tanner G, Barrow R, Ajaib S, Al-Jabri M, Ahmed N, Pollock S, Finetti M, Rippaus N, Bruns AF, Syed K, Poulter JA, Matthews L, Hughes T, Wilson E, Johnson C, Varn FS, Brüning-Richardson A, Hogg C, Droop A, Gusnanto A, Care MA, Cutillo L, Westhead DR, Short SC, Jenkinson MD, Brodbelt A, Chakrabarty A, Ismail A, Verhaak RGW, Stead LF.",,Genome biology,2024,2024-02-07,Y,,,,"

Background

Glioblastoma (GBM) brain tumors lacking IDH1 mutations (IDHwt) have the worst prognosis of all brain neoplasms. Patients receive surgery and chemoradiotherapy but tumors almost always fatally recur.

Results

Using RNA sequencing data from 107 pairs of pre- and post-standard treatment locally recurrent IDHwt GBM tumors, we identify two responder subtypes based on longitudinal changes in gene expression. In two thirds of patients, a specific subset of genes is upregulated from primary to recurrence (Up responders), and in one third, the same genes are downregulated (Down responders), specifically in neoplastic cells. Characterization of the responder subtypes indicates subtype-specific adaptive treatment resistance mechanisms that are associated with distinct changes in the tumor microenvironment. In Up responders, recurrent tumors are enriched in quiescent proneural GBM stem cells and differentiated neoplastic cells, with increased interaction with the surrounding normal brain and neurotransmitter signaling, whereas Down responders commonly undergo mesenchymal transition. ChIP-sequencing data from longitudinal GBM tumors suggests that the observed transcriptional reprogramming could be driven by Polycomb-based chromatin remodeling rather than DNA methylation.

Conclusions

We show that the responder subtype is cancer-cell intrinsic, recapitulated in in vitro GBM cell models, and influenced by the presence of the tumor microenvironment. Stratifying GBM tumors by responder subtype may lead to more effective treatment.",,pdf:https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-024-03172-3; doi:https://doi.org/10.1186/s13059-024-03172-3; html:https://europepmc.org/articles/PMC10848526; pdf:https://europepmc.org/articles/PMC10848526?pdf=render 33240510,https://doi.org/10.15420/aer.2020.26,Big Data and Artificial Intelligence: Opportunities and Threats in Electrophysiology.,"van de Leur RR, Boonstra MJ, Bagheri A, Roudijk RW, Sammani A, Taha K, Doevendans PA, van der Harst P, van Dam PM, Hassink RJ, van Es R, Asselbergs FW.",,Arrhythmia & electrophysiology review,2020,2020-11-01,Y,Artificial intelligence; Electrophysiology; Neural networks; ECG; Cardiology; Big Data; Deep Learning,,,"The combination of big data and artificial intelligence (AI) is having an increasing impact on the field of electrophysiology. Algorithms are created to improve the automated diagnosis of clinical ECGs or ambulatory rhythm devices. Furthermore, the use of AI during invasive electrophysiological studies or combining several diagnostic modalities into AI algorithms to aid diagnostics are being investigated. However, the clinical performance and applicability of created algorithms are yet unknown. In this narrative review, opportunities and threats of AI in the field of electrophysiology are described, mainly focusing on ECGs. Current opportunities are discussed with their potential clinical benefits as well as the challenges. Challenges in data acquisition, model performance, (external) validity, clinical implementation, algorithm interpretation as well as the ethical aspects of AI research are discussed. This article aims to guide clinicians in the evaluation of new AI applications for electrophysiology before their clinical implementation.",,doi:https://doi.org/10.15420/aer.2020.26; doi:https://doi.org/10.15420/aer.2020.26; html:https://europepmc.org/articles/PMC7675143; pdf:https://europepmc.org/articles/PMC7675143?pdf=render 37072241,https://doi.org/10.1136/heartjnl-2022-321888,Incident cardiovascular events and imaging phenotypes in UK Biobank participants with past cancer.,"Raisi-Estabragh Z, Cooper J, McCracken C, Crosbie EJ, Walter FM, Manisty CH, Robson J, Mamas MA, Harvey NC, Neubauer S, Petersen SE.",,Heart (British Cardiac Society),2023,2023-06-14,Y,epidemiology; Magnetic Resonance Imaging,,,"

Objectives

To evaluate incident cardiovascular outcomes and imaging phenotypes in UK Biobank participants with previous cancer.

Methods

Cancer and cardiovascular disease (CVD) diagnoses were ascertained using health record linkage. Participants with cancer history (breast, lung, prostate, colorectal, uterus, haematological) were propensity matched on vascular risk factors to non-cancer controls. Competing risk regression was used to calculate subdistribution HRs (SHRs) for associations of cancer history with incident CVD (ischaemic heart disease (IHD), non-ischaemic cardiomyopathy (NICM), heart failure (HF), atrial fibrillation/flutter, stroke, pericarditis, venous thromboembolism (VTE)) and mortality outcomes (any CVD, IHD, HF/NICM, stroke, hypertensive disease) over 11.8±1.7 years of prospective follow-up. Linear regression was used to assess associations of cancer history with left ventricular (LV) and left atrial metrics.

Results

We studied 18 714 participants (67% women, age: 62 (IQR: 57-66) years, 97% white ethnicities) with cancer history, including 1354 individuals with cardiovascular magnetic resonance. Participants with cancer had high burden of vascular risk factors and prevalent CVDs. Haematological cancer was associated with increased risk of all incident CVDs considered (SHRs: 1.92-3.56), larger chamber volumes, lower ejection fractions, and poorer LV strain. Breast cancer was associated with increased risk of selected CVDs (NICM, HF, pericarditis and VTE; SHRs: 1.34-2.03), HF/NICM death, hypertensive disease death, lower LV ejection fraction, and lower LV global function index. Lung cancer was associated with increased risk of pericarditis, HF, and CVD death. Prostate cancer was linked to increased VTE risk.

Conclusions

Cancer history is linked to increased risk of incident CVDs and adverse cardiac remodelling independent of shared vascular risk factors.",,pdf:https://heart.bmj.com/content/heartjnl/early/2023/03/21/heartjnl-2022-321888.full.pdf; doi:https://doi.org/10.1136/heartjnl-2022-321888; html:https://europepmc.org/articles/PMC10314020; pdf:https://europepmc.org/articles/PMC10314020?pdf=render 32379357,https://doi.org/10.1002/sim.8563,A Bayesian hierarchical approach for multiple outcomes in routinely collected healthcare data.,"Carragher R, Mueller T, Bennie M, Robertson C.",,Statistics in medicine,2020,2020-05-07,N,Observational Study; Multiple Outcomes; Direct Oral Anticoagulants; Safety Outcomes; Bayesian Hierarchy,,,"Clinical trials are the standard approach for evaluating new treatments, but may lack the power to assess rare outcomes. Trial results are also necessarily restricted to the population considered in the study. The availability of routinely collected healthcare data provides a source of information on the performance of treatments beyond that offered by clinical trials, but the analysis of this type of data presents a number of challenges. Hierarchical methods, which take advantage of known relationships between clinical outcomes, while accounting for bias, may be a suitable statistical approach for the analysis of this data. A study of direct oral anticoagulants in Scotland is discussed and used to motivate a modeling approach. A Bayesian hierarchical model, which allows a stratification of the population into clusters with similar characteristics, is proposed and applied to the direct oral anticoagulant study data. A simulation study is used to assess its performance in terms of outcome detection and error rates.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/sim.8563; doi:https://doi.org/10.1002/sim.8563 @@ -1419,16 +1419,16 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 35765237,https://doi.org/10.1111/1747-0080.12746,An investigation of early enteral nutrition provision in major burn patients in Australia and New Zealand.,"Kurmis R, Nicholls C, Singer Y, Edgar DW, Wood FM, Gabbe BJ, Tracy LM.",,Nutrition & dietetics: the journal of the Dietitians Association of Australia,2022,2022-06-28,Y,Burns; Parenteral nutrition; enteral nutrition,,,"

Aims

Early enteral nutrition (provided within 24 h of admission) is the optimal form of nutritional support for major burn injuries. The aim of this study was to (i) audit early enteral nutrition practices, (ii) identify characteristics of patients who received early enteral nutrition, and (iii) investigate whether early enteral nutrition was associated with in-hospital outcomes.

Methods

An analysis of prospectively collected data from the Burns Registry of Australia and New Zealand was conducted. Specifically, this study focused on major burns patients (defined as burns affecting more than 20% and 15% total body surface area for adult paediatric patients, respectively) admitted to a specialist burn service between 1 July 2016 and 30 June 2019.

Results

Data from 474 major burns patients (88 paediatric patients) revealed 69% received early enteral nutrition. Paediatric patients who received early enteral nutrition were younger than their counterparts who did not receive the same support (p = 0.04). Adult patients who received early enteral nutrition sustained larger burns (p < 0.001). Early enteral nutrition was not associated with in-hospital mortality following major burn injury in adult patients in either unadjusted (p = 0.77) or confounder-adjusted (p = 0.69) analyses.

Conclusions

Approximately two-thirds of patients with major burn injuries received early enteral nutrition. Early enteral nutrition was not associated with in-hospital mortality following major burn injury. Further research should focus on modifiable reasons why major burns patients do not receive enteral nutrition within 24 h of admission.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9796319; doi:https://doi.org/10.1111/1747-0080.12746; html:https://europepmc.org/articles/PMC9796319; pdf:https://europepmc.org/articles/PMC9796319?pdf=render 34849869,https://doi.org/10.1093/gigascience/giab076,An overview of the National COVID-19 Chest Imaging Database: data quality and cohort analysis.,"Cushnan D, Bennett O, Berka R, Bertolli O, Chopra A, Dorgham S, Favaro A, Ganepola T, Halling-Brown M, Imreh G, Jacob J, Jefferson E, Lemarchand F, Schofield D, Wyatt JC, NCCID Collaborative.",,GigaScience,2021,2021-11-01,Y,Medical imaging; Machine Learning; Thoracic Imaging; Covid-19; Sars-cov2,,,"

Background

The National COVID-19 Chest Imaging Database (NCCID) is a centralized database containing mainly chest X-rays and computed tomography scans from patients across the UK. The objective of the initiative is to support a better understanding of the coronavirus SARS-CoV-2 disease (COVID-19) and the development of machine learning technologies that will improve care for patients hospitalized with a severe COVID-19 infection. This article introduces the training dataset, including a snapshot analysis covering the completeness of clinical data, and availability of image data for the various use-cases (diagnosis, prognosis, longitudinal risk). An additional cohort analysis measures how well the NCCID represents the wider COVID-19-affected UK population in terms of geographic, demographic, and temporal coverage.

Findings

The NCCID offers high-quality DICOM images acquired across a variety of imaging machinery; multiple time points including historical images are available for a subset of patients. This volume and variety make the database well suited to development of diagnostic/prognostic models for COVID-associated respiratory conditions. Historical images and clinical data may aid long-term risk stratification, particularly as availability of comorbidity data increases through linkage to other resources. The cohort analysis revealed good alignment to general UK COVID-19 statistics for some categories, e.g., sex, whilst identifying areas for improvements to data collection methods, particularly geographic coverage.

Conclusion

The NCCID is a growing resource that provides researchers with a large, high-quality database that can be leveraged both to support the response to the COVID-19 pandemic and as a test bed for building clinically viable medical imaging models.",,pdf:https://academic.oup.com/gigascience/article-pdf/10/11/giab076/41395024/giab076.pdf; doi:https://doi.org/10.1093/gigascience/giab076; html:https://europepmc.org/articles/PMC8633457; pdf:https://europepmc.org/articles/PMC8633457?pdf=render 33560181,https://doi.org/10.1177/0272989x21994035,The Value of Triage during Periods of Intense COVID-19 Demand: Simulation Modeling Study.,"Wood RM, Pratt AC, Kenward C, McWilliams CJ, Booton RD, Thomas MJ, Bourdeaux CP, Vasilakis C.",,Medical decision making : an international journal of the Society for Medical Decision Making,2021,2021-02-09,N,Computer simulation; Coronavirus; Intensive Care; Critical Care; Triage; Covid-19,,,"

Background

During the COVID-19 pandemic, many intensive care units have been overwhelmed by unprecedented levels of demand. Notwithstanding ethical considerations, the prioritization of patients with better prognoses may support a more effective use of available capacity in maximizing aggregate outcomes. This has prompted various proposed triage criteria, although in none of these has an objective assessment been made in terms of impact on number of lives and life-years saved.

Design

An open-source computer simulation model was constructed for approximating the intensive care admission and discharge dynamics under triage. The model was calibrated from observational data for 9505 patient admissions to UK intensive care units. To explore triage efficacy under various conditions, scenario analysis was performed using a range of demand trajectories corresponding to differing nonpharmaceutical interventions.

Results

Triaging patients at the point of expressed demand had negligible effect on deaths but reduces life-years lost by up to 8.4% (95% confidence interval: 2.6% to 18.7%). Greater value may be possible through ""reverse triage"", that is, promptly discharging any patient not meeting the criteria if admission cannot otherwise be guaranteed for one who does. Under such policy, life-years lost can be reduced by 11.7% (2.8% to 25.8%), which represents 23.0% (5.4% to 50.1%) of what is operationally feasible with no limit on capacity and in the absence of improved clinical treatments.

Conclusions

The effect of simple triage is limited by a tradeoff between reduced deaths within intensive care (due to improved outcomes) and increased deaths resulting from declined admission (due to lower throughput given the longer lengths of stay of survivors). Improvements can be found through reverse triage, at the expense of potentially complex ethical considerations.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/0272989X21994035; doi:https://doi.org/10.1177/0272989X21994035 -37217302,https://doi.org/10.1136/emermed-2022-212827,External validation of triage tools for adults with suspected COVID-19 in a middle-income setting: an observational cohort study.,"Marincowitz C, Sbaffi L, Hasan M, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Omer Y, Wallis LA.",,Emergency medicine journal : EMJ,2023,2023-05-22,Y,risk management; Triage; Covid-19,,,"

Background

Tools proposed to triage ED acuity in suspected COVID-19 were derived and validated in higher income settings during early waves of the pandemic. We estimated the accuracy of seven risk-stratification tools recommended to predict severe illness in the Western Cape, South Africa.

Methods

An observational cohort study using routinely collected data from EDs across the Western Cape, from 27 August 2020 to 11 March 2022, was conducted to assess the performance of the PRIEST (Pandemic Respiratory Infection Emergency System Triage) tool, NEWS2 (National Early Warning Score, version 2), TEWS (Triage Early Warning Score), the WHO algorithm, CRB-65, Quick COVID-19 Severity Index and PMEWS (Pandemic Medical Early Warning Score) in suspected COVID-19. The primary outcome was intubation or non-invasive ventilation, death or intensive care unit admission at 30 days.

Results

Of the 446 084 patients, 15 397 (3.45%, 95% CI 34% to 35.1%) experienced the primary outcome. Clinical decision-making for inpatient admission achieved a sensitivity of 0.77 (95% CI 0.76 to 0.78), specificity of 0.88 (95% CI 0.87 to 0.88) and the negative predictive value (NPV) of 0.99 (95% CI 0.99 to 0.99). NEWS2, PMEWS and PRIEST scores achieved good estimated discrimination (C-statistic 0.79 to 0.82) and identified patients at risk of adverse outcomes at recommended cut-offs with moderate sensitivity (>0.8) and specificity ranging from 0.41 to 0.64. Use of the tools at recommended thresholds would have more than doubled admissions, with only a 0.01% reduction in false negative triage.

Conclusion

No risk score outperformed existing clinical decision-making in determining the need for inpatient admission based on prediction of the primary outcome in this setting. Use of the PRIEST score at a threshold of one point higher than the previously recommended best approximated existing clinical accuracy.",,pdf:https://emj.bmj.com/content/emermed/early/2023/05/22/emermed-2022-212827.full.pdf; doi:https://doi.org/10.1136/emermed-2022-212827; html:https://europepmc.org/articles/PMC10359554; pdf:https://europepmc.org/articles/PMC10359554?pdf=render 35028631,https://doi.org/10.1016/s2666-7568(21)00281-6,The importance of blood pressure thresholds versus predicted cardiovascular risk on subsequent rates of cardiovascular disease: a cohort study in English primary care.,"Herrett E, Strongman H, Gadd S, Tomlinson L, Nitsch D, Bhaskaran K, Williamson E, van Staa T, Sofat R, Timmis A, Wells S, Smeeth L, Jackson R.",,The lancet. Healthy longevity,2022,2022-01-01,Y,,,,"

Background

For five decades, blood pressure lowering treatment has been recommended for patients with hypertension (currently defined as blood pressure of ≥140/90 mm Hg). In the past 20 years, guidelines for treatment began incorporating predicted absolute cardiovascular disease risk (predicted risk) and reducing blood pressure thresholds. The blood pressure threshold at which to start treatment has become a secondary consideration in some countries. We aimed to provide descriptive data to assess the relative importance of blood pressure thresholds versus predicted risk on the subsequent rate of cardiovascular disease to inform treatment decisions.

Methods

In this English population-based cohort study, we used linked data from the Clinical Practice Research Datalink (CPRD) GOLD, Hospital Episode Statistics Admitted Patient Care, and the Office for National Statistics mortality data, and area-based deprivation indices (Townsend scores). Eligible patients were aged 30-79 years on Jan 1, 2011 (cohort entry date) and could be linked to hospital, mortality, and deprivation data. Patients were followed up until death, end of CPRD follow-up, or Nov 31, 2018. We examined three outcomes: cardiovascular disease, markers of potential target organ damage, and incident dementia without a known cause. The rate of each outcome was estimated and stratified by systolic blood pressure and predicted 10-year risk of cardiovascular disease (QRISK2 algorithm).

Findings

Between Jan 1, 2011, and Nov 31, 2018, 1 098 991 patients were included in the cohort and followed up for a median of 4·3 years (IQR 2·6-6·0; total follow-up of 4·6 million person-years). Median age at entry was 52 years (IQR 42-62) and 629 711 (57·3%) patients were female. There were 51 996 cardiovascular disease events and the overall rate of cardiovascular disease was 11·2 per 1000 person-years (95% CI 11·1-11·3). Median QRISK2 10-year predicted risk was 4·6% (IQR 1·4-12·0) and mean systolic blood pressure before cohort entry was 129·1 mm Hg (SD 15·7). Within strata of predicted risk, the effect of increasing systolic blood pressure on outcomes was small. For example, in the group with 10·0-19·9% predicted risk, rates of all cardiovascular disease rose from 20·1 to 23·6 per 1000 person-years between systolic blood pressures less than 110 mm Hg and 180 and higher mm Hg. But among patients with systolic blood pressure 140·0-149·9 mm Hg, rates rose from 6·9 to 52·3 per 1000 person-years between those with less than 10·0% risk and those with 30·0% or higher predicted risk.

Interpretation

For a wide range of blood pressures, the rate of cardiovascular disease and effectiveness of blood pressure drug treatment was mainly determined by predicted risk, with blood pressure thresholds 140/90 mm Hg or 160/100 mm Hg-ubiquitous in most countries-adding little useful information. When medium-term predicted risk is low, there is no urgency to initiate drug treatment, allowing time to attempt non-pharmacological blood pressure reduction.

Funding

National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S2666756821002816/pdf; doi:https://doi.org/10.1016/S2666-7568(21)00281-6; html:https://europepmc.org/articles/PMC8732286 +37217302,https://doi.org/10.1136/emermed-2022-212827,External validation of triage tools for adults with suspected COVID-19 in a middle-income setting: an observational cohort study.,"Marincowitz C, Sbaffi L, Hasan M, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Omer Y, Wallis LA.",,Emergency medicine journal : EMJ,2023,2023-05-22,Y,risk management; Triage; Covid-19,,,"

Background

Tools proposed to triage ED acuity in suspected COVID-19 were derived and validated in higher income settings during early waves of the pandemic. We estimated the accuracy of seven risk-stratification tools recommended to predict severe illness in the Western Cape, South Africa.

Methods

An observational cohort study using routinely collected data from EDs across the Western Cape, from 27 August 2020 to 11 March 2022, was conducted to assess the performance of the PRIEST (Pandemic Respiratory Infection Emergency System Triage) tool, NEWS2 (National Early Warning Score, version 2), TEWS (Triage Early Warning Score), the WHO algorithm, CRB-65, Quick COVID-19 Severity Index and PMEWS (Pandemic Medical Early Warning Score) in suspected COVID-19. The primary outcome was intubation or non-invasive ventilation, death or intensive care unit admission at 30 days.

Results

Of the 446 084 patients, 15 397 (3.45%, 95% CI 34% to 35.1%) experienced the primary outcome. Clinical decision-making for inpatient admission achieved a sensitivity of 0.77 (95% CI 0.76 to 0.78), specificity of 0.88 (95% CI 0.87 to 0.88) and the negative predictive value (NPV) of 0.99 (95% CI 0.99 to 0.99). NEWS2, PMEWS and PRIEST scores achieved good estimated discrimination (C-statistic 0.79 to 0.82) and identified patients at risk of adverse outcomes at recommended cut-offs with moderate sensitivity (>0.8) and specificity ranging from 0.41 to 0.64. Use of the tools at recommended thresholds would have more than doubled admissions, with only a 0.01% reduction in false negative triage.

Conclusion

No risk score outperformed existing clinical decision-making in determining the need for inpatient admission based on prediction of the primary outcome in this setting. Use of the PRIEST score at a threshold of one point higher than the previously recommended best approximated existing clinical accuracy.",,pdf:https://emj.bmj.com/content/emermed/early/2023/05/22/emermed-2022-212827.full.pdf; doi:https://doi.org/10.1136/emermed-2022-212827; html:https://europepmc.org/articles/PMC10359554; pdf:https://europepmc.org/articles/PMC10359554?pdf=render 33289226,https://doi.org/10.1111/ans.16426,Association between gender and outcomes of acute burns patients.,"Perkins M, Abesamis GM, Cleland H, Gabbe BJ, Tracy LM.",,ANZ journal of surgery,2020,2020-12-01,N,Burns; Gender; Outcomes,,,"

Background

Burn injuries are a complex and serious public health concern. Where the total body surface area of the burn exceeds 50%, mortality rates as high as 48% have been reported. While the association between gender and burn injury outcomes has been explored, findings are inconsistent.

Methods

Adult patients (>15 years) admitted between 1 July 2009 and 30 June 2018 to intensive care units of burn centres that provide specialist burn care in Australia and New Zealand were included. Raw mortality rates were examined and a multivariable Cox proportional hazards regression was used to investigate the association between gender and time to in-hospital death.

Results

There were 2227 eligible burn injury admissions. Men comprised the majority (77.6%). The proportion of women who died in hospital was greater than men and the adjusted odds of in-hospital mortality were 34% lower in men (odds ratio 0.66; 95% confidence interval (CI) 0.45-0.98). The unadjusted rate of in-hospital mortality for men was 44% lower than women (hazard ratio 0.56; 95% CI 0.41-0.76). After adjusting for confounders, there was no association between gender and survival time (hazard ratio 0.76; 95% CI 0.54-1.06).

Conclusion

After adjustment for key differences in case-mix between men and women, there was an association between gender and in-hospital mortality and no association between gender and time to death. Our findings indicate that the worse outcomes observed for women are associated with different age and patterns of injury, and provide further information to direct and inform targeted prevention measures for vulnerable populations.",,doi:https://doi.org/10.1111/ans.16426 34095541,https://doi.org/10.23889/ijpds.v4i2.1134,A Profile of the SAIL Databank on the UK Secure Research Platform.,"Jones KH, Ford DV, Thompson S, Lyons RA.",,International journal of population data science,2019,2019-11-20,Y,,,,"

Background

The Secure Anonymised Information Linkage (SAIL) Databank is a national data safe haven of de identified datasets principally about the population of Wales, made available in anonymised form to researchers across the world. It was established to enable the vast arrays of data collected about individuals in the course of health and other public service delivery to be made available to answer important questions that could not otherwise be addressed without prohibitive effort. The SAIL Databank is the bedrock of other funded centres relying on the data for research.

Approach

SAIL is a data repository surrounded by a suite of physical, technical and procedural control measures embodying a proportionate privacy-by-design governance model, informed by public engagement, to safeguard the data and facilitate data utility. SAIL operates on the UK Secure Research Platform (SeRP), which is a customisable technology and analysis platform. Researchers access anonymised data via this secure research environment, from which results can be released following scrutiny for disclosure risk. SAIL data are being used in multiple research areas to evaluate the impact of health and social exposures and policy interventions.

Discussion

Lessons learned and their applications include: managing evolving legislative and regulatory requirements; employing multiple, tiered security mechanisms; working hard to increase analytical capacity efficiency; and developing a multi-faceted programme of public engagement. Further work includes: incorporating new data types; enabling alternative means of data access; and developing further efficiencies across our operations.

Conclusion

SAIL represents an ongoing programme of work to develop and maintain an extensive, whole population data resource for research. Its privacy-by-design model and UK SeRP technology have received international acclaim, and we continually endeavour to demonstrate trustworthiness to support data provider assurance and public acceptability in data use. We strive for further improvement and continue a mutual learning process with our contemporaries in this rapidly developing field.",,pdf:https://ijpds.org/article/download/1134/2643; doi:https://doi.org/10.23889/ijpds.v4i2.1134; html:https://europepmc.org/articles/PMC8142954; pdf:https://europepmc.org/articles/PMC8142954?pdf=render 38746859,https://doi.org/10.1183/23120541.00430-2023,"Prevalence, incidence and healthcare burden of eosinophilic granulomatosis with polyangiitis in the UK.","Hwee J, Harper L, Fu Q, Nirantharakumar K, Mu G, Jakes RW.",,ERJ open research,2024,2024-05-13,Y,,,,"

Background

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare but serious disease characterised by the combination of small-to-medium vessel vasculitis, blood and tissue eosinophilia, and asthma and/or sinonasal disease. This study estimated the prevalence and incidence of diagnosed EGPA in the United Kingdom (UK), and described the demographics, clinical characteristics and healthcare resource utilisation (HCRU) of this population.

Methods

This retrospective longitudinal study of patients with newly diagnosed EGPA (index) (2005-2019) used the Clinical Practice Research Datalink AURUM and Hospital Episode Statistics databases. The primary outcomes were the annual prevalence (2005-2019) and incidence (2006-2019) of EGPA, and secondary outcomes included patient demographics and clinical characteristics, and HCRU in the year pre- and post-index (diagnosis).

Results

Populations of patients with EGPA comprised 940 prevalent cases and 502 incident cases, of which 377 were linked to Hospital Episode Statistics. EGPA prevalence increased from 22.7 to 45.6 cases per 1 000 000 (2005-2019), driven by patients aged ≥18 years. Incidence ranged from 2.3 to 4.0 per 1 000 000 person-years (2006-2019). Pre-index, the most common clinical symptoms were respiratory related, and the most common comorbidities were asthma (80.6%) and nasal polyps (32.1%). Post-index, 19.1% had an EGPA-related inpatient stay (median length of stay 11.0 days) and 38.7% had five or more oral corticosteroid (OCS) prescriptions with a mean OCS possession ratio per patient of 47.0%.

Conclusions

Although EGPA incidence in the UK remains relatively stable, prevalence is increasing, and HCRU and OCS use remain frequent, suggesting considerable healthcare burden for patients with EGPA.",,doi:https://doi.org/10.1183/23120541.00430-2023; html:https://europepmc.org/articles/PMC11089387; pdf:https://europepmc.org/articles/PMC11089387?pdf=render -38725371,https://doi.org/10.1192/bjo.2024.23,"Contacts with primary and secondary healthcare before suicide by those under the care of mental health services: case-control, whole-population-based study using person-level linked routine data in Wales, UK during 2000-2015.","DelPozo-Banos M, Rodway C, Lee SC, Rouquette OY, Ibrahim S, Lloyd K, Appleby L, Kapur N, John A.",,BJPsych open,2024,2024-05-10,Y,Suicide; Mental Health Services; Primary Care; Secondary Care; Electronic Health Records,,,"

Background

People under the care of mental health services are at increased risk of suicide. Existing studies are small in scale and lack comparisons.

Aims

To identify opportunities for suicide prevention and underpinning data enhancement in people with recent contact with mental health services.

Method

This population-based study includes people who died by suicide in the year following a mental health services contact in Wales, 2001-2015 (cases), paired with similar patients who did not die by suicide (controls). We linked the National Confidential Inquiry into Suicide and Safety in Mental Health and the Suicide Information Database - Cymru with primary and secondary healthcare records. We present results of conditional logistic regression.

Results

We matched 1031 cases with 5155 controls. In the year before their death, 98.3% of cases were in contact with healthcare services, and 28.5% presented with self-harm. Cases had more emergency department contacts (odds ratio 2.4, 95% CI 2.1-2.7) and emergency hospital admissions (odds ratio 1.5, 95% CI 1.4-1.7), but fewer primary care contacts (odds ratio 0.7, 95% CI 0.6-0.9) and out-patient appointments (odds ratio 0.2, 95% CI 0.2-0.3) than controls. Odds ratios were larger in females than males for injury and poisoning (odds ratio: 3.3 (95% CI 2.5-4.5) v. 2.6 (95% CI 2.1-3.1)).

Conclusions

We may be missing existing opportunities to intervene, particularly in emergency departments and hospital admissions with self-harm presentations and with unattributed self-harm, especially in females. Prevention efforts should focus on strengthening routine care contacts, responding to emergency contacts and better self-harm care. There are benefits to enhancing clinical audit systems with routinely collected data.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/4C20CD00C92C75F4F0B4FACD8418B244/S2056472424000231a.pdf/div-class-title-contacts-with-primary-and-secondary-healthcare-before-suicide-by-those-under-the-care-of-mental-health-services-case-control-whole-population-based-study-using-person-level-linked-routine-data-in-wales-uk-during-2000-2015-div.pdf; doi:https://doi.org/10.1192/bjo.2024.23; html:https://europepmc.org/articles/PMC11094447; pdf:https://europepmc.org/articles/PMC11094447?pdf=render 33830993,https://doi.org/10.1371/journal.pgen.1009428,Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank.,"Johnston KJA, Ward J, Ray PR, Adams MJ, McIntosh AM, Smith BH, Strawbridge RJ, Price TJ, Smith DJ, Nicholl BI, Bailey MES.",,PLoS genetics,2021,2021-04-08,Y,,,,"Chronic pain is highly prevalent worldwide and imparts a significant socioeconomic and public health burden. Factors influencing susceptibility to, and mechanisms of, chronic pain development, are not fully understood, but sex is thought to play a significant role, and chronic pain is more prevalent in women than in men. To investigate sex differences in chronic pain, we carried out a sex-stratified genome-wide association study of Multisite Chronic Pain (MCP), a derived chronic pain phenotype, in UK Biobank on 178,556 men and 209,093 women, as well as investigating sex-specific genetic correlations with a range of psychiatric, autoimmune and anthropometric phenotypes and the relationship between sex-specific polygenic risk scores for MCP and chronic widespread pain. We also assessed whether MCP-associated genes showed expression pattern enrichment across tissues. A total of 123 SNPs at five independent loci were significantly associated with MCP in men. In women, a total of 286 genome-wide significant SNPs at ten independent loci were discovered. Meta-analysis of sex-stratified GWAS outputs revealed a further 87 independent associated SNPs. Gene-level analyses revealed sex-specific MCP associations, with 31 genes significantly associated in females, 37 genes associated in males, and a single gene, DCC, associated in both sexes. We found evidence for sex-specific pleiotropy and risk for MCP was found to be associated with chronic widespread pain in a sex-differential manner. Male and female MCP were highly genetically correlated, but at an rg of significantly less than 1 (0.92). All 37 male MCP-associated genes and all but one of 31 female MCP-associated genes were found to be expressed in the dorsal root ganglion, and there was a degree of enrichment for expression in sex-specific tissues. Overall, the findings indicate that sex differences in chronic pain exist at the SNP, gene and transcript abundance level, and highlight possible sex-specific pleiotropy for MCP. Results support the proposition of a strong central nervous-system component to chronic pain in both sexes, additionally highlighting a potential role for the DRG and nociception.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009428&type=printable; doi:https://doi.org/10.1371/journal.pgen.1009428; html:https://europepmc.org/articles/PMC8031124; pdf:https://europepmc.org/articles/PMC8031124?pdf=render +38725371,https://doi.org/10.1192/bjo.2024.23,"Contacts with primary and secondary healthcare before suicide by those under the care of mental health services: case-control, whole-population-based study using person-level linked routine data in Wales, UK during 2000-2015.","DelPozo-Banos M, Rodway C, Lee SC, Rouquette OY, Ibrahim S, Lloyd K, Appleby L, Kapur N, John A.",,BJPsych open,2024,2024-05-10,Y,Suicide; Mental Health Services; Primary Care; Secondary Care; Electronic Health Records,,,"

Background

People under the care of mental health services are at increased risk of suicide. Existing studies are small in scale and lack comparisons.

Aims

To identify opportunities for suicide prevention and underpinning data enhancement in people with recent contact with mental health services.

Method

This population-based study includes people who died by suicide in the year following a mental health services contact in Wales, 2001-2015 (cases), paired with similar patients who did not die by suicide (controls). We linked the National Confidential Inquiry into Suicide and Safety in Mental Health and the Suicide Information Database - Cymru with primary and secondary healthcare records. We present results of conditional logistic regression.

Results

We matched 1031 cases with 5155 controls. In the year before their death, 98.3% of cases were in contact with healthcare services, and 28.5% presented with self-harm. Cases had more emergency department contacts (odds ratio 2.4, 95% CI 2.1-2.7) and emergency hospital admissions (odds ratio 1.5, 95% CI 1.4-1.7), but fewer primary care contacts (odds ratio 0.7, 95% CI 0.6-0.9) and out-patient appointments (odds ratio 0.2, 95% CI 0.2-0.3) than controls. Odds ratios were larger in females than males for injury and poisoning (odds ratio: 3.3 (95% CI 2.5-4.5) v. 2.6 (95% CI 2.1-3.1)).

Conclusions

We may be missing existing opportunities to intervene, particularly in emergency departments and hospital admissions with self-harm presentations and with unattributed self-harm, especially in females. Prevention efforts should focus on strengthening routine care contacts, responding to emergency contacts and better self-harm care. There are benefits to enhancing clinical audit systems with routinely collected data.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/4C20CD00C92C75F4F0B4FACD8418B244/S2056472424000231a.pdf/div-class-title-contacts-with-primary-and-secondary-healthcare-before-suicide-by-those-under-the-care-of-mental-health-services-case-control-whole-population-based-study-using-person-level-linked-routine-data-in-wales-uk-during-2000-2015-div.pdf; doi:https://doi.org/10.1192/bjo.2024.23; html:https://europepmc.org/articles/PMC11094447; pdf:https://europepmc.org/articles/PMC11094447?pdf=render 35536740,https://doi.org/10.1136/bmjopen-2021-052884,Gaps in antihypertensive and statin treatments and benefits of optimisation: a modelling study in a 1 million ethnically diverse urban population in UK.,"Wu R, Rison SCG, Raisi-Estabragh Z, Dostal I, Carvalho C, Robson J, Mihaylova B.",,BMJ open,2021,2021-12-30,Y,Hypertension; Preventive Medicine; Ischaemic Heart Disease; Primary Care; Health Policy; Quality In Health Care,,,"

Objectives

To characterise gaps in antihypertensive treatment in people with hypertension and statin treatment in people with cardiovascular diseases (CVD) in a large urban population and quantify the health and economic impacts of their optimisation.

Design

A cross-sectional population study and a long-term CVD decision model.

Setting

Primary care, UK.

Participants

All adults with diagnosed hypertension or CVD in a population of about 1 million people, served by 123 primary care practices in London, UK in 2019.

Interventions

Following UK clinical guidelines, all adults with diagnosed hypertension were categorised into optimal, suboptimal and untreated groups with respect to their antihypertensive treatment, and all adults with diagnosed CVD were categorised in the same manner with respect to their statin treatment.

Outcomes

Proportion of patients suboptimally treated or untreated. Projected cardiovascular events avoided, years and quality-adjusted life years (QALYs) gained and healthcare costs saved with optimised treatments.

Results

21 954 of the 91 828 adults with hypertension (24%; mean age 59 years; 49% women) and 9062 of the 23 723 adults with CVD (38%; mean age 69 years; 43% women) were not optimally treated with antihypertensive or statin treatment, respectively. Per 1000 additional patients optimised over 5 years, hypertension treatment is projected to prevent 25 (95% CI 16 to 32) major vascular events (MVEs) and 7 (3 to 10) vascular deaths, statin treatment, 28 (22 to 33) MVEs and 6 (4 to 7) vascular deaths. Over their lifespan, a patient with uncontrolled hypertension aged 60-69 years is projected to gain 0.64 (95% CI 0.36 to 0.87) QALYs with optimised hypertension treatment, and a similarly aged patient with previous CVD not optimally treated with statin is projected to gain 0.3 (0.24 to 0.37) QALYs with optimised statin treatment. In both cases, the hospital cost savings minus extra medication costs were about £1100 per person over remaining lifespan.

Conclusions

Optimising cardiovascular treatments can cost-effectively reduce cardiovascular risk and improve life expectancy.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/12/e052884.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-052884; html:https://europepmc.org/articles/PMC8719215; pdf:https://europepmc.org/articles/PMC8719215?pdf=render -38345865,https://doi.org/10.1113/jp284597,Reduced plakoglobin increases the risk of sodium current defects and atrial conduction abnormalities in response to androgenic anabolic steroid abuse.,"Sommerfeld LC, Holmes AP, Yu TY, O'Shea C, Kavanagh DM, Pike JM, Wright T, Syeda F, Aljehani A, Kew T, Cardoso VR, Kabir SN, Hepburn C, Menon PR, Broadway-Stringer S, O'Reilly M, Witten A, Fortmueller L, Lutz S, Kulle A, Gkoutos GV, Pavlovic D, Arlt W, Lavery GG, Steeds R, Gehmlich K, Stoll M, Kirchhof P, Fabritz L.",,The Journal of physiology,2024,2024-02-12,N,Testosterone; Conduction velocity; Nav1.5; Desmosome; Arrhythmogenic Right Ventricular Cardiomyopathy; Cardiac Atria,,,"Androgenic anabolic steroids (AAS) are commonly abused by young men. Male sex and increased AAS levels are associated with earlier and more severe manifestation of common cardiac conditions, such as atrial fibrillation, and rare ones, such as arrhythmogenic right ventricular cardiomyopathy (ARVC). Clinical observations suggest a potential atrial involvement in ARVC. Arrhythmogenic right ventricular cardiomyopathy is caused by desmosomal gene defects, including reduced plakoglobin expression. Here, we analysed clinical records from 146 ARVC patients to identify that ARVC is more common in males than females. Patients with ARVC also had an increased incidence of atrial arrhythmias and P wave changes. To study desmosomal vulnerability and the effects of AAS on the atria, young adult male mice, heterozygously deficient for plakoglobin (Plako+/- ), and wild type (WT) littermates were chronically exposed to 5α-dihydrotestosterone (DHT) or placebo. The DHT increased atrial expression of pro-hypertrophic, fibrotic and inflammatory transcripts. In mice with reduced plakoglobin, DHT exaggerated P wave abnormalities, atrial conduction slowing, sodium current depletion, action potential amplitude reduction and the fall in action potential depolarization rate. Super-resolution microscopy revealed a decrease in NaV 1.5 membrane clustering in Plako+/- atrial cardiomyocytes after DHT exposure. In summary, AAS combined with plakoglobin deficiency cause pathological atrial electrical remodelling in young male hearts. Male sex is likely to increase the risk of atrial arrhythmia, particularly in those with desmosomal gene variants. This risk is likely to be exaggerated further by AAS use. KEY POINTS: Androgenic male sex hormones, such as testosterone, might increase the risk of atrial fibrillation in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), which is often caused by desmosomal gene defects (e.g. reduced plakoglobin expression). In this study, we observed a significantly higher proportion of males who had ARVC compared with females, and atrial arrhythmias and P wave changes represented a common observation in advanced ARVC stages. In mice with reduced plakoglobin expression, chronic administration of 5α-dihydrotestosterone led to P wave abnormalities, atrial conduction slowing, sodium current depletion and a decrease in membrane-localized NaV 1.5 clusters. 5α-Dihydrotestosterone, therefore, represents a stimulus aggravating the pro-arrhythmic phenotype in carriers of desmosomal mutations and can affect atrial electrical function.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1113/JP284597; doi:https://doi.org/10.1113/JP284597 33531486,https://doi.org/10.1038/s41467-021-21370-6,Author Correction: Genetic architecture of host proteins involved in SARS-CoV-2 infection.,"Pietzner M, Wheeler E, Carrasco-Zanini J, Raffler J, Kerrison ND, Oerton E, Auyeung VPW, Luan J, Finan C, Casas JP, Ostroff R, Williams SA, Kastenmüller G, Ralser M, Gamazon ER, Wareham NJ, Hingorani AD, Langenberg C.",,Nature communications,2021,2021-02-02,Y,,,,,,pdf:https://www.nature.com/articles/s41467-021-21370-6.pdf; doi:https://doi.org/10.1038/s41467-021-21370-6; html:https://europepmc.org/articles/PMC7854714; pdf:https://europepmc.org/articles/PMC7854714?pdf=render +38345865,https://doi.org/10.1113/jp284597,Reduced plakoglobin increases the risk of sodium current defects and atrial conduction abnormalities in response to androgenic anabolic steroid abuse.,"Sommerfeld LC, Holmes AP, Yu TY, O'Shea C, Kavanagh DM, Pike JM, Wright T, Syeda F, Aljehani A, Kew T, Cardoso VR, Kabir SN, Hepburn C, Menon PR, Broadway-Stringer S, O'Reilly M, Witten A, Fortmueller L, Lutz S, Kulle A, Gkoutos GV, Pavlovic D, Arlt W, Lavery GG, Steeds R, Gehmlich K, Stoll M, Kirchhof P, Fabritz L.",,The Journal of physiology,2024,2024-02-12,N,Testosterone; Conduction velocity; Nav1.5; Desmosome; Arrhythmogenic Right Ventricular Cardiomyopathy; Cardiac Atria,,,"Androgenic anabolic steroids (AAS) are commonly abused by young men. Male sex and increased AAS levels are associated with earlier and more severe manifestation of common cardiac conditions, such as atrial fibrillation, and rare ones, such as arrhythmogenic right ventricular cardiomyopathy (ARVC). Clinical observations suggest a potential atrial involvement in ARVC. Arrhythmogenic right ventricular cardiomyopathy is caused by desmosomal gene defects, including reduced plakoglobin expression. Here, we analysed clinical records from 146 ARVC patients to identify that ARVC is more common in males than females. Patients with ARVC also had an increased incidence of atrial arrhythmias and P wave changes. To study desmosomal vulnerability and the effects of AAS on the atria, young adult male mice, heterozygously deficient for plakoglobin (Plako+/- ), and wild type (WT) littermates were chronically exposed to 5α-dihydrotestosterone (DHT) or placebo. The DHT increased atrial expression of pro-hypertrophic, fibrotic and inflammatory transcripts. In mice with reduced plakoglobin, DHT exaggerated P wave abnormalities, atrial conduction slowing, sodium current depletion, action potential amplitude reduction and the fall in action potential depolarization rate. Super-resolution microscopy revealed a decrease in NaV 1.5 membrane clustering in Plako+/- atrial cardiomyocytes after DHT exposure. In summary, AAS combined with plakoglobin deficiency cause pathological atrial electrical remodelling in young male hearts. Male sex is likely to increase the risk of atrial arrhythmia, particularly in those with desmosomal gene variants. This risk is likely to be exaggerated further by AAS use. KEY POINTS: Androgenic male sex hormones, such as testosterone, might increase the risk of atrial fibrillation in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), which is often caused by desmosomal gene defects (e.g. reduced plakoglobin expression). In this study, we observed a significantly higher proportion of males who had ARVC compared with females, and atrial arrhythmias and P wave changes represented a common observation in advanced ARVC stages. In mice with reduced plakoglobin expression, chronic administration of 5α-dihydrotestosterone led to P wave abnormalities, atrial conduction slowing, sodium current depletion and a decrease in membrane-localized NaV 1.5 clusters. 5α-Dihydrotestosterone, therefore, represents a stimulus aggravating the pro-arrhythmic phenotype in carriers of desmosomal mutations and can affect atrial electrical function.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1113/JP284597; doi:https://doi.org/10.1113/JP284597 36929968,https://doi.org/10.1016/s0140-6736(22)02235-8,Impact of the temporary suspension of the Bowel Screening Wales programme on inequalities during the COVID-19 pandemic: a retrospective register-based study.,"Bright D, Song J, Hillier S, Huws DW, Greene G, Hodgson K, Akbari A, Griffiths R, Davies AR, Gjini A.",,"Lancet (London, England)",2022,2022-11-24,Y,,,,"

Background

Response to the COVID-19 pandemic resulted in the temporary disruption of routine services in the UK National Health Service, including cancer screening. Following the reintroduction of services, we explored the impact on inequalities in uptake of the Bowel Screening Wales (BSW) programme to identify groups who might benefit from tailored intervention.

Methods

BSW records were linked to electronic health record and administrative data within the Secured Anonymised Information Linkage (SAIL) Databank Trusted Research Environment. We examined uptake in the first 3 months (from August to October, 2020) of invitations following the reintroduction of the BSW programme compared with the same period in the preceding 3 years. We analysed inequalities in uptake by sex, age group, income deprivation quintile, urban and rural location, ethnic group, and uptake between different periods using logistic regression models.

Findings

Overall uptake remained above the 60% Welsh standard during the COVID-19 pandemic period of 2020-21 but declined compared with the pre-pandemic period of 2019-20 (60·4% vs 62·7%; p<0·001). During the COVID-19 pandemic period of 2020-21, uptake declined for most demographic groups, except for older individuals (70-74 years) and those in the most deprived quintile. Variation by sex, age, income deprivation, and ethnic groups was observed in all periods studied. Among low-uptake groups, including males, younger individuals (60-64 years), those living in most deprived areas, and ethnic minorities, uptake remains below the 60% Welsh standard.

Interpretation

Despite the disruption, uptake remained above the Welsh standard and inequalities did not worsen after the programme resumed activities. However, variations associated with sex, age, deprivation, and ethnicity remain. These findings need to be considered in targeting strategies to improve uptake and informed choice in colorectal cancer screening such as co-producing information products with low-uptake groups and upscaling the use of GP-endorsed invitations and reminder letters for bowel screening.

Funding

Health Data Research UK, UK Medical Research Council, Administrative Data Research UK, and Health and Care Research Wales.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9691043; doi:https://doi.org/10.1016/S0140-6736(22)02235-8; html:https://europepmc.org/articles/PMC9691043; pdf:https://europepmc.org/articles/PMC9691043?pdf=render 33728815,https://doi.org/10.1002/art.41709,Epidemiology of Scleritis in the United Kingdom From 1997 to 2018: Population-Based Analysis of 11 Million Patients and Association Between Scleritis and Infectious and Immune-Mediated Inflammatory Disease.,"Braithwaite T, Adderley NJ, Subramanian A, Galloway J, Kempen JH, Gokhale K, Cope AP, Dick AD, Nirantharakumar K, Denniston AK.",,"Arthritis & rheumatology (Hoboken, N.J.)",2021,2021-06-06,N,,,,"

Objective

To estimate 22-year trends in the prevalence and incidence of scleritis, and the associations of scleritis with infectious and immune-mediated inflammatory diseases (I-IMIDs) in the UK.

Methods

The retrospective cross-sectional and population cohort study (1997-2018) included 10,939,823 patients (2,946 incident scleritis cases) in The Health Improvement Network, a nationally representative primary care records database. The case-control and matched cohort study (1995-2019) included 3,005 incident scleritis cases and 12,020 control patients matched by age, sex, region, and Townsend deprivation index. Data were analyzed using multivariable Poisson regression, multivariable logistic regression, and Cox proportional hazards multivariable models adjusted for age, sex, Townsend deprivation index, race/ethnicity, smoking status, nation within the UK, and body mass index. Incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) were calculated.

Results

Scleritis incidence rates per 100,000 person-years declined from 4.23 (95% CI 2.16-6.31) to 2.79 (95% CI 2.19-3.39) between 1997 and 2018. The prevalence of scleritis per 100,000 person-years was 93.62 (95% CI 90.17-97.07) in 2018 (61,650 UK patients). Among 2,946 patients with incident scleritis, 1,831 (62.2%) were female, the mean ± SD age was 44.9 ± 17.6 years (range 1-93), and 1,257 (88.8%) were White. Higher risk of incident scleritis was associated with female sex (adjusted IRR 1.53 [95% CI 1.43-1.66], P < 0.001), Black race/ethnicity (adjusted IRR 1.52 [95% CI 1.14-2.01], P = 0.004 compared to White race/ethnicity), or South Asian race/ethnicity (adjusted IRR 1.50 [95% CI 1.19-1.90], P < 0.001 compared to White race/ethnicity), and older age (peak adjusted IRR 4.95 [95% CI 3.99-6.14], P < 0.001 for patients ages 51-60 years versus those ages ≤10 years). Compared to controls, scleritis patients had a 2-fold increased risk of a prior I-IMID diagnosis (17 I-IMIDs, P < 0.001) and significantly increased risk of subsequent diagnosis (13 I-IMIDs). The I-IMIDs most strongly associated with scleritis included granulomatosis with polyangiitis, Behçet's disease, and Sjögren's syndrome.

Conclusion

From 1997 through 2018, the UK incidence of scleritis declined from 4.23 to 2.79/100,000 person-years. Incident scleritis was associated with 19 I-IMIDs, providing data for rational investigation and cross-specialty engagement.",,doi:https://doi.org/10.1002/art.41709; doi:https://doi.org/10.1002/art.41709 34948912,https://doi.org/10.3390/ijerph182413304,Development and Validation of a Primary Care Electronic Health Record Phenotype to Study Migration and Health in the UK.,"Pathak N, Zhang CX, Boukari Y, Burns R, Mathur R, Gonzalez-Izquierdo A, Denaxas S, Sonnenberg P, Hayward A, Aldridge RW.",,International journal of environmental research and public health,2021,2021-12-17,Y,Migration; Phenotype; Validation; Algorithm; Primary Care; Clinical Practice Research Datalink,,,"International migrants comprised 14% of the UK's population in 2020; however, their health is rarely studied at a population level using primary care electronic health records due to difficulties in their identification. We developed a migration phenotype using country of birth, visa status, non-English main/first language and non-UK-origin codes and applied it to the Clinical Practice Research Datalink (CPRD) GOLD database of 16,071,111 primary care patients between 1997 and 2018. We compared the completeness and representativeness of the identified migrant population to Office for National Statistics (ONS) country-of-birth and 2011 census data by year, age, sex, geographic region of birth and ethnicity. Between 1997 to 2018, 403,768 migrants (2.51% of the CPRD GOLD population) were identified: 178,749 (1.11%) had foreign-country-of-birth or visa -status codes, 216,731 (1.35%) non-English-main/first-language codes, and 8288 (0.05%) non-UK-origin codes. The cohort was similarly distributed versus ONS data by sex and region of birth. Migration recording improved over time and younger migrants were better represented than those aged ≥50. The validated phenotype identified a large migrant cohort for use in migration health research in CPRD GOLD to inform healthcare policy and practice. The under-recording of migration status in earlier years and older ages necessitates cautious interpretation of future studies in these groups.",,pdf:https://www.mdpi.com/1660-4601/18/24/13304/pdf?version=1639728813; doi:https://doi.org/10.3390/ijerph182413304; html:https://europepmc.org/articles/PMC8707886; pdf:https://europepmc.org/articles/PMC8707886?pdf=render @@ -1439,8 +1439,8 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 36828608,https://doi.org/10.1016/s2589-7500(22)00249-7,The role of patient-reported outcome measures in trials of artificial intelligence health technologies: a systematic evaluation of ClinicalTrials.gov records (1997-2022).,"Pearce FJ, Cruz Rivera S, Liu X, Manna E, Denniston AK, Calvert MJ.",,The Lancet. Digital health,2023,2023-03-01,N,,,,"The extent to which patient-reported outcome measures (PROMs) are used in clinical trials for artificial intelligence (AI) technologies is unknown. In this systematic evaluation, we aim to establish how PROMs are being used to assess AI health technologies. We searched ClinicalTrials.gov for interventional trials registered from inception to Sept 20, 2022, and included trials that tested an AI health technology. We excluded observational studies, patient registries, and expanded access reports. We extracted data regarding the form, function, and intended use population of the AI health technology, in addition to the PROMs used and whether PROMs were incorporated as an input or output in the AI model. The search identified 2958 trials, of which 627 were included in the analysis. 152 (24%) of the included trials used one or more PROM, visual analogue scale, patient-reported experience measure, or usability measure as a trial endpoint. The type of AI health technologies used by these trials included AI-enabled smart devices, clinical decision support systems, and chatbots. The number of clinical trials of AI health technologies registered on ClinicalTrials.gov and the proportion of trials that used PROMs increased from registry inception to 2022. The most common clinical areas AI health technologies were designed for were digestive system health for non-PROM trials and musculoskeletal health (followed by mental and behavioural health) for PROM trials, with PROMs commonly used in clinical areas for which assessment of health-related quality of life and symptom burden is particularly important. Additionally, AI-enabled smart devices were the most common applications tested in trials that used at least one PROM. 24 trials tested AI models that captured PROM data as an input for the AI model. PROM use in clinical trials of AI health technologies falls behind PROM use in all clinical trials. Trial records having inadequate detail regarding the PROMs used or the type of AI health technology tested was a limitation of this systematic evaluation and might have contributed to inaccuracies in the data synthesised. Overall, the use of PROMs in the function and assessment of AI health technologies is not only possible, but is a powerful way of showing that, even in the most technologically advanced health-care systems, patients' perspectives remain central.",,doi:https://doi.org/10.1016/s2589-7500(22)00249-7; doi:https://doi.org/10.1016/S2589-7500(22)00249-7 36854461,https://doi.org/10.1136/bmj-2022-073149,Realistic expectations are key to realising the benefits of polygenic scores.,"Sud A, Horton RH, Hingorani AD, Tzoulaki I, Turnbull C, Houlston RS, Lucassen A.",,BMJ (Clinical research ed.),2023,2023-02-28,Y,,,,,,pdf:https://www.bmj.com/content/bmj/380/bmj-2022-073149.full.pdf; doi:https://doi.org/10.1136/bmj-2022-073149; html:https://europepmc.org/articles/PMC9973128 35144240,https://doi.org/10.2196/32543,Artificial Intelligence-Enabled Social Media Analysis for Pharmacovigilance of COVID-19 Vaccinations in the United Kingdom: Observational Study.,"Hussain Z, Sheikh Z, Tahir A, Dashtipour K, Gogate M, Sheikh A, Hussain A.",,JMIR public health and surveillance,2022,2022-05-27,Y,Artificial intelligence; Vaccination; Public Health; Health Informatics; Natural Language Processing; Facebook; Social Media; Twitter; Sentiment Analysis; Infodemiology; Deep Learning; Covid-19,,,"

Background

The rollout of vaccines for COVID-19 in the United Kingdom started in December 2020. Uptake has been high, and there has been a subsequent reduction in infections, hospitalizations, and deaths among vaccinated individuals. However, vaccine hesitancy remains a concern, in particular relating to adverse effects following immunization (AEFIs). Social media analysis has the potential to inform policy makers about AEFIs being discussed by the public as well as public attitudes toward the national immunization campaign.

Objective

We sought to assess the frequency and nature of AEFI-related mentions on social media in the United Kingdom and to provide insights on public sentiments toward COVID-19 vaccines.

Methods

We extracted and analyzed over 121,406 relevant Twitter and Facebook posts, from December 8, 2020, to April 30, 2021. These were thematically filtered using a 2-step approach, initially using COVID-19-related keywords and then using vaccine- and manufacturer-related keywords. We identified AEFI-related keywords and modeled their word frequency to monitor their trends over 2-week periods. We also adapted and utilized our recently developed hybrid ensemble model, which combines state-of-the-art lexicon rule-based and deep learning-based approaches, to analyze sentiment trends relating to the main vaccines available in the United Kingdom.

Results

Our COVID-19 AEFI search strategy identified 46,762 unique Facebook posts by 14,346 users and 74,644 tweets (excluding retweets) by 36,446 users over the 4-month period. We identified an increasing trend in the number of mentions for each AEFI on social media over the study period. The most frequent AEFI mentions were found to be symptoms related to appetite (n=79,132, 14%), allergy (n=53,924, 9%), injection site (n=56,152, 10%), and clots (n=43,907, 8%). We also found some rarely reported AEFIs such as Bell palsy (n=11,909, 2%) and Guillain-Barre syndrome (n=9576, 2%) being discussed as frequently as more well-known side effects like headache (n=10,641, 2%), fever (n=12,707, 2%), and diarrhea (n=16,559, 3%). Overall, we found public sentiment toward vaccines and their manufacturers to be largely positive (58%), with a near equal split between negative (22%) and neutral (19%) sentiments. The sentiment trend was relatively steady over time and had minor variations, likely based on political and regulatory announcements and debates.

Conclusions

The most frequently discussed COVID-19 AEFIs on social media were found to be broadly consistent with those reported in the literature and by government pharmacovigilance. We also detected potential safety signals from our analysis that have been detected elsewhere and are currently being investigated. As such, we believe our findings support the use of social media analysis to provide a complementary data source to conventional knowledge sources being used for pharmacovigilance purposes.",,pdf:https://publichealth.jmir.org/2022/5/e32543/PDF; doi:https://doi.org/10.2196/32543; html:https://europepmc.org/articles/PMC9150729 -37813531,https://doi.org/10.1136/bmjopen-2023-073162,Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.,"Subramanian A, Lee SI, Hemali Sudasinghe SPB, Wambua S, Phillips K, Singh M, Azcoaga-Lorenzo A, Cockburn N, Wang J, Fagbamigbe A, Usman M, Damase-Michel C, Yau C, Kent L, McCowan C, OReilly D, Santorelli G, Hope H, Kennedy J, Mhereeg M, Abel KM, Eastwood KA, Black M, Loane M, Moss N, Brophy S, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",,BMJ open,2023,2023-10-09,Y,Obstetrics; epidemiology; Maternal Medicine,,,"

Introduction

Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy.

Methods and analysis

Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3 months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation.

Ethics and dissemination

Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/10/e073162.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-073162; html:https://europepmc.org/articles/PMC10565241; pdf:https://europepmc.org/articles/PMC10565241?pdf=render 34409990,https://doi.org/10.1093/dote/doab058,Demographic and lifestyle risk factors for gastroesophageal reflux disease and Barrett's esophagus in Australia.,"Wang SE, Kendall BJ, Hodge AM, Dixon-Suen SC, Dashti SG, Makalic E, Williamson EM, Thomas RJS, Giles GG, English DR.",,Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus,2022,2022-01-01,N,Risk factor; Barrett’s esophagus; epidemiology; Gastroesophageal Reflux (Gerd),,,"We examined demographic and lifestyle risk factors for incidence of gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) in an Australian cohort of 20,975 participants aged 40-63 at recruitment (1990-1994). Information on GERD and BE was collected between 2007 and 2010. GERD symptoms were defined as self-reported heartburn or acid regurgitation. BE was defined as endoscopically confirmed columnar-lined esophagus. Risk factors for developing GERD symptoms, BE diagnosis, age at symptom onset, and age at BE diagnosis were quantified using regression. During a mean follow-up of 15.8 years, risk of GERD symptoms was 7.5% (n = 1,318) for daily, 7.5% (n = 1,333) for 2-6 days/week, and 4.3% (n = 751) for 1 day/week. There were 210 (1.0%) endoscopically diagnosed BE cases, of whom 141 had histologically confirmed esophageal intestinal metaplasia. Female sex, younger age, lower socioeconomic position (SEP) and educational attainment, and former smoking were associated with higher GERD risk. Male sex and smoking were associated with earlier GERD symptom onset. Men, older participants, those with higher SEP, and former smokers were at higher BE risk. There was some evidence higher SEP was associated with earlier BE diagnosis. GERD and BE had different demographic risk factors but shared similar lifestyle factors. Earlier GERD symptom onset for men and smokers might have contributed to higher BE risk. The SEP patterns observed for GERD and BE suggest potential inequity in access to care. These findings would be important in the development of clinical risk prediction models for early detection of BE.",,pdf:https://academic.oup.com/dote/article-pdf/35/1/doab058/42098674/doab058.pdf; doi:https://doi.org/10.1093/dote/doab058 +37813531,https://doi.org/10.1136/bmjopen-2023-073162,Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.,"Subramanian A, Lee SI, Hemali Sudasinghe SPB, Wambua S, Phillips K, Singh M, Azcoaga-Lorenzo A, Cockburn N, Wang J, Fagbamigbe A, Usman M, Damase-Michel C, Yau C, Kent L, McCowan C, OReilly D, Santorelli G, Hope H, Kennedy J, Mhereeg M, Abel KM, Eastwood KA, Black M, Loane M, Moss N, Brophy S, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",,BMJ open,2023,2023-10-09,Y,Obstetrics; epidemiology; Maternal Medicine,,,"

Introduction

Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy.

Methods and analysis

Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3 months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation.

Ethics and dissemination

Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/10/e073162.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-073162; html:https://europepmc.org/articles/PMC10565241; pdf:https://europepmc.org/articles/PMC10565241?pdf=render 33500288,https://doi.org/10.1136/bmjopen-2020-042945,Hospital bed capacity and usage across secondary healthcare providers in England during the first wave of the COVID-19 pandemic: a descriptive analysis.,"Mateen BA, Wilde H, Dennis JM, Duncan A, Thomas N, McGovern A, Denaxas S, Keeling M, Vollmer S.",,BMJ open,2021,2021-01-26,Y,Public Health; Health Policy; Intensive & Critical Care; Covid-19,,,"

Objective

In this study, we describe the pattern of bed occupancy across England during the peak of the first wave of the COVID-19 pandemic.

Design

Descriptive survey.

Setting

All non-specialist secondary care providers in England from 27 March27to 5 June 2020.

Participants

Acute (non-specialist) trusts with a type 1 (ie, 24 hours/day, consultant-led) accident and emergency department (n=125), Nightingale (field) hospitals (n=7) and independent sector secondary care providers (n=195).

Main outcome measures

Two thresholds for 'safe occupancy' were used: 85% as per the Royal College of Emergency Medicine and 92% as per NHS Improvement.

Results

At peak availability, there were 2711 additional beds compatible with mechanical ventilation across England, reflecting a 53% increase in capacity, and occupancy never exceeded 62%. A consequence of the repurposing of beds meant that at the trough there were 8.7% (8508) fewer general and acute beds across England, but occupancy never exceeded 72%. The closest to full occupancy of general and acute bed (surge) capacity that any trust in England reached was 99.8% . For beds compatible with mechanical ventilation there were 326 trust-days (3.7%) spent above 85% of surge capacity and 154 trust-days (1.8%) spent above 92%. 23 trusts spent a cumulative 81 days at 100% saturation of their surge ventilator bed capacity (median number of days per trust=1, range: 1-17). However, only three sustainability and transformation partnerships (aggregates of geographically co-located trusts) reached 100% saturation of their mechanical ventilation beds.

Conclusions

Throughout the first wave of the pandemic, an adequate supply of all bed types existed at a national level. However, due to an unequal distribution of bed utilisation, many trusts spent a significant period operating above 'safe-occupancy' thresholds despite substantial capacity in geographically co-located trusts, a key operational issue to address in preparing for future waves.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e042945.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-042945; html:https://europepmc.org/articles/PMC7843315; pdf:https://europepmc.org/articles/PMC7843315?pdf=render 34734970,https://doi.org/10.1001/jamaophthalmol.2021.4601,"Association of Smoking, Alcohol Consumption, Blood Pressure, Body Mass Index, and Glycemic Risk Factors With Age-Related Macular Degeneration: A Mendelian Randomization Study.","Kuan V, Warwick A, Hingorani A, Tufail A, Cipriani V, Burgess S, Sofat R, International AMD Genomics Consortium (IAMDGC).",,JAMA ophthalmology,2021,2021-12-01,Y,,,,"

Importance

Advanced age-related macular degeneration (AMD) is a leading cause of blindness in Western countries. Causal, modifiable risk factors need to be identified to develop preventive measures for advanced AMD.

Objective

To assess whether smoking, alcohol consumption, blood pressure, body mass index, and glycemic traits are associated with increased risk of advanced AMD.

Design, setting, participants

This study used 2-sample mendelian randomization. Genetic instruments composed of variants associated with risk factors at genome-wide significance (P < 5 × 10-8) were obtained from published genome-wide association studies. Summary-level statistics for these instruments were obtained for advanced AMD from the International AMD Genomics Consortium 2016 data set, which consisted of 16 144 individuals with AMD and 17 832 control individuals. Data were analyzed from July 2020 to September 2021.

Exposures

Smoking initiation, smoking cessation, lifetime smoking, age at smoking initiation, alcoholic drinks per week, body mass index, systolic and diastolic blood pressure, type 2 diabetes, glycated hemoglobin, fasting glucose, and fasting insulin.

Main outcomes and measures

Advanced AMD and its subtypes, geographic atrophy (GA), and neovascular AMD.

Results

A 1-SD increase in logodds of genetically predicted smoking initiation was associated with higher risk of advanced AMD (odds ratio [OR], 1.26; 95% CI, 1.13-1.40; P < .001), while a 1-SD increase in logodds of genetically predicted smoking cessation (former vs current smoking) was associated with lower risk of advanced AMD (OR, 0.66; 95% CI, 0.50-0.87; P = .003). Genetically predicted increased lifetime smoking was associated with increased risk of advanced AMD (OR per 1-SD increase in lifetime smoking behavior, 1.32; 95% CI, 1.09-1.59; P = .004). Genetically predicted alcohol consumption was associated with higher risk of GA (OR per 1-SD increase of log-transformed alcoholic drinks per week, 2.70; 95% CI, 1.48-4.94; P = .001). There was insufficient evidence to suggest that genetically predicted blood pressure, body mass index, and glycemic traits were associated with advanced AMD.

Conclusions and relevance

This study provides genetic evidence that increased alcohol intake may be a causal risk factor for GA. As there are currently no known treatments for GA, this finding has important public health implications. These results also support previous observational studies associating smoking behavior with risk of advanced AMD, thus reinforcing existing public health messages regarding the risk of blindness associated with smoking.",,pdf:https://jamanetwork.com/journals/jamaophthalmology/articlepdf/2785704/jamaophthalmology_kuan_2021_oi_210068_1639510445.31311.pdf; doi:https://doi.org/10.1001/jamaophthalmol.2021.4601; html:https://europepmc.org/articles/PMC8569599 35869974,https://doi.org/10.1093/ndt/gfac224,Care processes and outcomes of deprivation across the clinical course of kidney disease: findings from a high-income country with universal healthcare.,"Sawhney S, Blakeman T, Blana D, Boyers D, Fluck N, Nath M, Methven S, Rzewuska M, Black C.",,"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",2023,2023-05-01,Y,Prognosis; epidemiology; Health Inequalities; Ckd; Aki; Care Processes,,,"

Background

No single study contrasts the extent and consequences of inequity of kidney care across the clinical course of kidney disease.

Methods

This population study of Grampian (UK) followed incident presentations of acute kidney injury (AKI) and incident estimated glomerular filtration rate (eGFR) thresholds of <60, <45 and <30 mL/min/1.73 m2 in separate cohorts (2011-2021). The key exposure was area-level deprivation (lowest quintile of the Scottish Index of Multiple Deprivation). Outcomes were care processes (monitoring, prescribing, appointments, unscheduled care), long-term mortality and kidney failure. Modelling involved multivariable logistic regression, negative binomial regression and cause-specific Cox models with and without adjustment of comorbidities.

Results

There were 41 313, 51 190, 32 171 and 17 781 new presentations of AKI and eGFR thresholds <60, <45 and <30  mL/min/1.73 m2. A total of 6.1-7.8% of the population was from deprived areas and (versus all others) presented on average 5 years younger, with more diabetes and pulmonary and liver disease. Those from deprived areas were more likely to present initially in hospital, less likely to receive community monitoring, less likely to attend appointments and more likely to have an unplanned emergency department or hospital admission episode. Deprivation had the greatest association with long-term kidney failure at the eGFR <60 mL/min/1.73 m2 threshold {adjusted hazard ratio [HR] 1.48 [95% confidence interval (CI) 1.17-1.87]} and this association decreased with advancing disease severity [HR 1.09 (95% CI 0.93-1.28) at eGFR <30 mL/min/1.73 m2), with a similar pattern for mortality. Across all analyses the most detrimental associations of deprivation were an eGFR threshold <60 mL/min/1.73 m2, AKI, males and those <65 years of age.

Conclusions

Even in a high-income country with universal healthcare, serious and consistent inequities in kidney care exist. The poorer care and outcomes with area-level deprivation were greater earlier in the disease course.",,pdf:https://academic.oup.com/ndt/advance-article-pdf/doi/10.1093/ndt/gfac224/45505736/gfac224.pdf; doi:https://doi.org/10.1093/ndt/gfac224; html:https://europepmc.org/articles/PMC10157789; pdf:https://europepmc.org/articles/PMC10157789?pdf=render @@ -1459,48 +1459,48 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 34253559,https://doi.org/10.1136/jech-2021-216689,"Long-term trends in population-based hospitalisation rates for myocardial infarction in England: a national database study of 3.5 million admissions, 1968-2016.","Wright FL, Townsend N, Greenland M, Goldacre MJ, Smolina K, Lacey B, Nedkoff L.",,Journal of epidemiology and community health,2022,2021-07-12,Y,epidemiology; Ischaemic Heart Disease; Record Linkage,,,"

Aim

To analyse the timing and scale of temporal changes in rates of hospitalised myocardial infarction (MI) in England by age and sex from 1968 to 2016.

Methods

MI admissions for adults aged 15-84 years were identified from electronic hospital data. We calculated age-standardised and age-specific rates, and examined trends using joinpoint.

Results

From 1968 to 2016, there were 3.5 million admissions for MI in England (68% men). Rates increased in the early years of the study in both men and women, peaked in the mid-1980s (355 per 100 000 population in men; 127 in women) and declined by 38.8% in men and 37.4% in women from 1990 to 2011. From 2012, however, modest increases were observed in both sexes. Long-term trends in rates over the study period varied by age and sex, with those aged 70 years and older having the greatest and most sustained increases in the early years (1968-1985). During subsequent years, rates decreased in most age groups until 2010-2011. The exception was younger women (35-49 years) and men (15-34 years) who experienced significant increases from the mid-1990s to 2007 (range +2.1%/year to 4.7%/year). From 2012 onwards, rates increased in all age groups except the oldest, with the most marked increases in men aged 15-34 years (7.2%/year) and women aged 40-49 (6.9%-7.3%/year) .

Conclusion

Despite substantial declines in hospital admission rates for MI in England since 1990, the burden of annual admissions remains high. Continued surveillance of trends and coronary disease preventive strategies are warranted.",,pdf:https://jech.bmj.com/content/jech/76/1/45.full.pdf; doi:https://doi.org/10.1136/jech-2021-216689; html:https://europepmc.org/articles/PMC8666807; pdf:https://europepmc.org/articles/PMC8666807?pdf=render 36855161,https://doi.org/10.1186/s13073-023-01161-y,Refining epigenetic prediction of chronological and biological age.,"Bernabeu E, McCartney DL, Gadd DA, Hillary RF, Lu AT, Murphy L, Wrobel N, Campbell A, Harris SE, Liewald D, Hayward C, Sudlow C, Cox SR, Evans KL, Horvath S, McIntosh AM, Robinson MR, Vallejos CA, Marioni RE.",,Genome medicine,2023,2023-02-28,Y,,,,"

Background

Epigenetic clocks can track both chronological age (cAge) and biological age (bAge). The latter is typically defined by physiological biomarkers and risk of adverse health outcomes, including all-cause mortality. As cohort sample sizes increase, estimates of cAge and bAge become more precise. Here, we aim to develop accurate epigenetic predictors of cAge and bAge, whilst improving our understanding of their epigenomic architecture.

Methods

First, we perform large-scale (N = 18,413) epigenome-wide association studies (EWAS) of chronological age and all-cause mortality. Next, to create a cAge predictor, we use methylation data from 24,674 participants from the Generation Scotland study, the Lothian Birth Cohorts (LBC) of 1921 and 1936, and 8 other cohorts with publicly available data. In addition, we train a predictor of time to all-cause mortality as a proxy for bAge using the Generation Scotland cohort (1214 observed deaths). For this purpose, we use epigenetic surrogates (EpiScores) for 109 plasma proteins and the 8 component parts of GrimAge, one of the current best epigenetic predictors of survival. We test this bAge predictor in four external cohorts (LBC1921, LBC1936, the Framingham Heart Study and the Women's Health Initiative study).

Results

Through the inclusion of linear and non-linear age-CpG associations from the EWAS, feature pre-selection in advance of elastic net regression, and a leave-one-cohort-out (LOCO) cross-validation framework, we obtain cAge prediction with a median absolute error equal to 2.3 years. Our bAge predictor was found to slightly outperform GrimAge in terms of the strength of its association to survival (HRGrimAge = 1.47 [1.40, 1.54] with p = 1.08 × 10-52, and HRbAge = 1.52 [1.44, 1.59] with p = 2.20 × 10-60). Finally, we introduce MethylBrowsR, an online tool to visualise epigenome-wide CpG-age associations.

Conclusions

The integration of multiple large datasets, EpiScores, non-linear DNAm effects, and new approaches to feature selection has facilitated improvements to the blood-based epigenetic prediction of biological and chronological age.",,pdf:https://genomemedicine.biomedcentral.com/counter/pdf/10.1186/s13073-023-01161-y; doi:https://doi.org/10.1186/s13073-023-01161-y; html:https://europepmc.org/articles/PMC9976489; pdf:https://europepmc.org/articles/PMC9976489?pdf=render 32571619,https://doi.org/10.1016/j.schres.2020.05.007,Real-world implementation of precision psychiatry: Transdiagnostic risk calculator for the automatic detection of individuals at-risk of psychosis.,"Oliver D, Spada G, Colling C, Broadbent M, Baldwin H, Patel R, Stewart R, Stahl D, Dobson R, McGuire P, Fusar-Poli P.",,Schizophrenia research,2021,2020-06-19,Y,Feasibility; Implementation; Risk Calculator; Precision Psychiatry; Psychosis;transdiagnostic,,,"

Background

Risk estimation models integrated into Electronic Health Records (EHRs) can deliver innovative approaches in psychiatry, but clinicians' endorsement and their real-world usability are unknown. This study aimed to investigate the real-world feasibility of implementing an individualised, transdiagnostic risk calculator to automatically screen EHRs and detect individuals at-risk for psychosis.

Methods

Feasibility implementation study encompassing an in-vitro phase (March 2018 to May 2018) and in-vivo phase (May 2018 to April 2019). The in-vitro phase addressed implementation barriers and embedded the risk calculator (predictors: age, gender, ethnicity, index cluster diagnosis, age*gender) into the local EHR. The in-vivo phase investigated the real-world feasibility of screening individuals accessing secondary mental healthcare at the South London and Maudsley NHS Trust. The primary outcome was adherence of clinicians to automatic EHR screening, defined by the proportion of clinicians who responded to alerts from the risk calculator, over those contacted.

Results

In-vitro phase: implementation barriers were identified/overcome with clinician and service user engagement, and the calculator was successfully integrated into the local EHR through the CogStack platform. In-vivo phase: 3722 individuals were automatically screened and 115 were detected. Clinician adherence was 74% without outreach and 85% with outreach. One-third of clinicians responded to the first email (37.1%) or phone calls (33.7%). Among those detected, cumulative risk of developing psychosis was 12% at six-month follow-up.

Conclusion

This is the first implementation study suggesting that combining precision psychiatry and EHR methods to improve detection of individuals with emerging psychosis is feasible. Future psychiatric implementation research is urgently needed.",,doi:https://doi.org/10.1016/j.schres.2020.05.007; doi:https://doi.org/10.1016/j.schres.2020.05.007; html:https://europepmc.org/articles/PMC7875179 -35623313,https://doi.org/10.1016/j.ejrad.2022.110366,Comparison of state-of-the-art machine and deep learning algorithms to classify proximal humeral fractures using radiology text.,"Dipnall JF, Lu J, Gabbe BJ, Cosic F, Edwards E, Page R, Du L.",,European journal of radiology,2022,2022-05-20,N,Classification; Radiology; Machine Learning; Natural Language Processing; Proximal Humeral Fracture; Deep Learning; Neer; Bert,,,"

Introduction

Proximal humeral fractures account for a significant proportion of all fractures. Detailed accurate classification of the type and severity of the fracture is a key component of clinical decision making, treatment and plays an important role in orthopaedic trauma research. This research aimed to assess the performance of Machine Learning (ML) multiclass classification algorithms to classify proximal humeral fractures using radiology text data.

Materials and methods

Data from adult (16 + years) patients admitted to a major trauma centre for management of their proximal humerus fracture from January 2010 to January 2019 were used (1,324). Six input text datasets were used for classification: X-ray and/or CT scan reports (primary) and concatenation of patient age and/or patient sex. One of seven Neer class labels were classified. Models were evaluated using accuracy, recall, precision, F1, and One-versus-rest scores.

Results

A number of statistical ML algorithms performed acceptably and one of the BERT models, exhibiting good accuracy of 61% and an excellent one-versus-rest score above 0.8. The highest precision, recall and F1 scores were 50%, 39% and 39% respectively, being considered reasonable scores with the sparse text data used and in the context of machine learning.

Conclusion

ML and BERT algorithms based on routine unstructured X-ray and CT text reports, combined with the demographics of the patient, show promise in Neer classification of proximal humeral fractures to aid research. Use of these algorithms shows potential to speed up the classification task and assist radiologist, surgeons and researchers.",,doi:https://doi.org/10.1016/j.ejrad.2022.110366 33903145,https://doi.org/10.1136/bjophthalmol-2020-318570,Testing the performance of risk prediction models to determine progression to referable diabetic retinopathy in an Irish type 2 diabetes cohort.,"Smith JJ, Wright DM, Stratton IM, Scanlon PH, Lois N.",,The British journal of ophthalmology,2022,2021-04-26,Y,Retina; Vision; Imaging; Macula; Eye (Globe),,,"

Background /aims

To evaluate the performance of existing prediction models to determine risk of progression to referable diabetic retinopathy (RDR) using data from a prospective Irish cohort of people with type 2 diabetes (T2D).

Methods

A cohort of 939 people with T2D followed prospectively was used to test the performance of risk prediction models developed in Gloucester, UK, and Iceland. Observed risk of progression to RDR in the Irish cohort was compared with that derived from each of the prediction models evaluated. Receiver operating characteristic curves assessed models' performance.

Results

The cohort was followed for a total of 2929 person years during which 2906 screening episodes occurred. Among 939 individuals followed, there were 40 referrals (4%) for diabetic maculopathy, pre-proliferative DR and proliferative DR. The original Gloucester model, which includes results of two consecutive retinal screenings; a model incorporating, in addition, systemic biomarkers (HbA1c and serum cholesterol); and a model including results of one retinopathy screening, HbA1c, total cholesterol and duration of diabetes, had acceptable discriminatory power (area under the curve (AUC) of 0.69, 0.76 and 0.77, respectively). The Icelandic model, which combined retinopathy grading, duration and type of diabetes, HbA1c and systolic blood pressure, performed very similarly (AUC of 0.74).

Conclusion

In an Irish cohort of people with T2D, the prediction models tested had an acceptable performance identifying those at risk of progression to RDR. These risk models would be useful in establishing more personalised screening intervals for people with T2D.",,pdf:https://bjo.bmj.com/content/bjophthalmol/early/2021/04/25/bjophthalmol-2020-318570.full.pdf; doi:https://doi.org/10.1136/bjophthalmol-2020-318570; html:https://europepmc.org/articles/PMC9340042; pdf:https://europepmc.org/articles/PMC9340042?pdf=render +35623313,https://doi.org/10.1016/j.ejrad.2022.110366,Comparison of state-of-the-art machine and deep learning algorithms to classify proximal humeral fractures using radiology text.,"Dipnall JF, Lu J, Gabbe BJ, Cosic F, Edwards E, Page R, Du L.",,European journal of radiology,2022,2022-05-20,N,Classification; Radiology; Machine Learning; Natural Language Processing; Proximal Humeral Fracture; Deep Learning; Neer; Bert,,,"

Introduction

Proximal humeral fractures account for a significant proportion of all fractures. Detailed accurate classification of the type and severity of the fracture is a key component of clinical decision making, treatment and plays an important role in orthopaedic trauma research. This research aimed to assess the performance of Machine Learning (ML) multiclass classification algorithms to classify proximal humeral fractures using radiology text data.

Materials and methods

Data from adult (16 + years) patients admitted to a major trauma centre for management of their proximal humerus fracture from January 2010 to January 2019 were used (1,324). Six input text datasets were used for classification: X-ray and/or CT scan reports (primary) and concatenation of patient age and/or patient sex. One of seven Neer class labels were classified. Models were evaluated using accuracy, recall, precision, F1, and One-versus-rest scores.

Results

A number of statistical ML algorithms performed acceptably and one of the BERT models, exhibiting good accuracy of 61% and an excellent one-versus-rest score above 0.8. The highest precision, recall and F1 scores were 50%, 39% and 39% respectively, being considered reasonable scores with the sparse text data used and in the context of machine learning.

Conclusion

ML and BERT algorithms based on routine unstructured X-ray and CT text reports, combined with the demographics of the patient, show promise in Neer classification of proximal humeral fractures to aid research. Use of these algorithms shows potential to speed up the classification task and assist radiologist, surgeons and researchers.",,doi:https://doi.org/10.1016/j.ejrad.2022.110366 33127858,https://doi.org/10.1681/asn.2020050679,Conventional and Genetic Evidence on the Association between Adiposity and CKD.,"Zhu P, Herrington WG, Haynes R, Emberson J, Landray MJ, Sudlow CLM, Woodward M, Baigent C, Lewington S, Staplin N.",,Journal of the American Society of Nephrology : JASN,2021,2020-10-30,N,Obesity; body mass index; Chronic Kidney Disease; Mendelian Randomization; Central Adiposity; Epidemiology And Outcomes,,,"

Background

The size of any causal contribution of central and general adiposity to CKD risk and the underlying mechanism of mediation are unknown.

Methods

Data from 281,228 UK Biobank participants were used to estimate the relevance of waist-to-hip ratio and body mass index (BMI) to CKD prevalence. Conventional approaches used logistic regression. Genetic analyses used Mendelian randomization (MR) and data from 394 waist-to-hip ratio and 773 BMI-associated loci. Models assessed the role of known mediators (diabetes mellitus and BP) by adjusting for measured values (conventional analyses) or genetic associations of the selected loci (multivariable MR).

Results

Evidence of CKD was found in 18,034 (6.4%) participants. Each 0.06 higher measured waist-to-hip ratio and each 5-kg/m2 increase in BMI were associated with 69% (odds ratio, 1.69; 95% CI, 1.64 to 1.74) and 58% (1.58; 1.55 to 1.62) higher odds of CKD, respectively. In analogous MR analyses, each 0.06-genetically-predicted higher waist-to-hip ratio was associated with a 29% (1.29; 1.20 to 1.38) increased odds of CKD, and each 5-kg/m2 genetically-predicted higher BMI was associated with a 49% (1.49; 1.39 to 1.59) increased odds. After adjusting for diabetes and measured BP, chi-squared values for associations for waist-to-hip ratio and BMI fell by 56%. In contrast, mediator adjustment using multivariable MR found 83% and 69% reductions in chi-squared values for genetically-predicted waist-to-hip ratio and BMI models, respectively.

Conclusions

Genetic analyses suggest that conventional associations between central and general adiposity with CKD are largely causal. However, conventional approaches underestimate mediating roles of diabetes, BP, and their correlates. Genetic approaches suggest these mediators explain most of adiposity-CKD-associated risk.",,pdf:https://jasn.asnjournals.org/content/jnephrol/32/1/127.full.pdf; doi:https://doi.org/10.1681/ASN.2020050679; html:https://europepmc.org/articles/PMC7894659; doi:https://doi.org/10.1681/asn.2020050679 -38170504,https://doi.org/10.1001/jamacardio.2023.4994,Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia.,"Schuermans A, Truong B, Ardissino M, Bhukar R, Slob EAW, Nakao T, Dron JS, Small AM, Cho SMJ, Yu Z, Hornsby W, Antoine T, Lannery K, Postupaka D, Gray KJ, Yan Q, Butterworth AS, Burgess S, Wood MJ, Scott NS, Harrington CM, Sarma AA, Lau ES, Roh JD, Januzzi JL, Natarajan P, Honigberg MC.",,JAMA cardiology,2024,2024-03-01,Y,,,,"

Importance

Hypertensive disorders of pregnancy (HDPs), including gestational hypertension and preeclampsia, are important contributors to maternal morbidity and mortality worldwide. In addition, women with HDPs face an elevated long-term risk of cardiovascular disease.

Objective

To identify proteins in the circulation associated with HDPs.

Design, setting, and participants

Two-sample mendelian randomization (MR) tested the associations of genetic instruments for cardiovascular disease-related proteins with gestational hypertension and preeclampsia. In downstream analyses, a systematic review of observational data was conducted to evaluate the identified proteins' dynamics across gestation in hypertensive vs normotensive pregnancies, and phenome-wide MR analyses were performed to identify potential non-HDP-related effects associated with the prioritized proteins. Genetic association data for cardiovascular disease-related proteins were obtained from the Systematic and Combined Analysis of Olink Proteins (SCALLOP) consortium. Genetic association data for the HDPs were obtained from recent European-ancestry genome-wide association study meta-analyses for gestational hypertension and preeclampsia. Study data were analyzed October 2022 to October 2023.

Exposures

Genetic instruments for 90 candidate proteins implicated in cardiovascular diseases, constructed using cis-protein quantitative trait loci (cis-pQTLs).

Main outcomes and measures

Gestational hypertension and preeclampsia.

Results

Genetic association data for cardiovascular disease-related proteins were obtained from 21 758 participants from the SCALLOP consortium. Genetic association data for the HDPs were obtained from 393 238 female individuals (8636 cases and 384 602 controls) for gestational hypertension and 606 903 female individuals (16 032 cases and 590 871 controls) for preeclampsia. Seventy-five of 90 proteins (83.3%) had at least 1 valid cis-pQTL. Of those, 10 proteins (13.3%) were significantly associated with HDPs. Four were robust to sensitivity analyses for gestational hypertension (cluster of differentiation 40, eosinophil cationic protein [ECP], galectin 3, N-terminal pro-brain natriuretic peptide [NT-proBNP]), and 2 were robust for preeclampsia (cystatin B, heat shock protein 27 [HSP27]). Consistent with the MR findings, observational data revealed that lower NT-proBNP (0.76- to 0.88-fold difference vs no HDPs) and higher HSP27 (2.40-fold difference vs no HDPs) levels during the first trimester of pregnancy were associated with increased risk of HDPs, as were higher levels of ECP (1.60-fold difference vs no HDPs). Phenome-wide MR analyses identified 37 unique non-HDP-related protein-disease associations, suggesting potential on-target effects associated with interventions lowering HDP risk through the identified proteins.

Conclusions and relevance

Study findings suggest genetic associations of 4 cardiovascular disease-related proteins with gestational hypertension and 2 associated with preeclampsia. Future studies are required to test the efficacy of targeting the corresponding pathways to reduce HDP risk.",,doi:https://doi.org/10.1001/jamacardio.2023.4994; html:https://europepmc.org/articles/PMC10765315; pdf:https://europepmc.org/articles/PMC10765315?pdf=render 34761838,https://doi.org/10.1002/biof.1801,Neutrophil to lymphocyte ratio is not related to carotid atherosclerosis progression and cardiovascular events in the primary prevention of cardiovascular disease: Results from the IMPROVE study.,"Mannarino MR, Bianconi V, Gigante B, Strawbridge RJ, Savonen K, Kurl S, Giral P, Smit A, Eriksson P, Tremoli E, Veglia F, Baldassarre D, Pirro M, IMPROVE study group.",,"BioFactors (Oxford, England)",2022,2021-11-11,Y,Lymphocyte; neutrophil; cardiovascular; Carotid; Prospective; Imt; Nlr,,,"Inflammation is a component of the pathogenesis of atherosclerosis and is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). The neutrophil to lymphocyte ratio (NLR) is a possible inflammation metric for the detection of ASCVD risk, although results of prospective studies are highly inconsistent on this topic. We investigated the cross-sectional relationship between NLR and carotid intima-media thickness (cIMT) in subjects at moderate-to-high ASCVD risk. The prospective association between NLR, cIMT progression, and incident vascular events (VEs) was also explored. In 3341 subjects from the IMT-Progression as Predictors of VEs (IMPROVE) study, we analyzed the association between NLR, cIMT, and its 15-month progression. The association between NLR and incident VEs was also investigated. NLR was positively associated with cross-sectional measures of cIMT, but not with cIMT progression. The association between NLR and cross-sectional cIMT measures was abolished when adjusted for confounders. No association was found between NRL and incident VEs. Similarly, there were no significant differences in the hazard ratios (HRs) of VEs across NLR quartiles. NLR was neither associated with the presence and progression of carotid atherosclerosis, nor with the risk of VEs. Our findings do not support the role of NLR as a predictor of the risk of atherosclerosis progression and ASCVD events in subjects at moderate-to-high ASCVD risk, in primary prevention. However, the usefulness of NLR for patients at a different level of ASCVD risk cannot be inferred from this study.",,pdf:https://air.unimi.it/bitstream/2434/890337/2/0127%20IMPROVE%20mannarino%20Neutrophil%20to%20lymphocyte%20e%20suppl%20.pdf; doi:https://doi.org/10.1002/biof.1801; html:https://europepmc.org/articles/PMC9299016; pdf:https://europepmc.org/articles/PMC9299016?pdf=render 36346654,https://doi.org/10.2196/38168,Developing an Automated Assessment of In-session Patient Activation for Psychological Therapy: Codevelopment Approach.,"Malins S, Figueredo G, Jilani T, Long Y, Andrews J, Rawsthorne M, Manolescu C, Clos J, Higton F, Waldram D, Hunt D, Perez Vallejos E, Moghaddam N.",,JMIR medical informatics,2022,2022-11-08,Y,Mental health; Machine Learning; Cognitive Behavioral Therapy; Natural Language Processing; Multimorbidity; Responsible Artificial Intelligence,,,"

Background

Patient activation is defined as a patient's confidence and perceived ability to manage their own health. Patient activation has been a consistent predictor of long-term health and care costs, particularly for people with multiple long-term health conditions. However, there is currently no means of measuring patient activation from what is said in health care consultations. This may be particularly important for psychological therapy because most current methods for evaluating therapy content cannot be used routinely due to time and cost restraints. Natural language processing (NLP) has been used increasingly to classify and evaluate the contents of psychological therapy. This aims to make the routine, systematic evaluation of psychological therapy contents more accessible in terms of time and cost restraints. However, comparatively little attention has been paid to algorithmic trust and interpretability, with few studies in the field involving end users or stakeholders in algorithm development.

Objective

This study applied a responsible design to use NLP in the development of an artificial intelligence model to automate the ratings assigned by a psychological therapy process measure: the consultation interactions coding scheme (CICS). The CICS assesses the level of patient activation observable from turn-by-turn psychological therapy interactions.

Methods

With consent, 128 sessions of remotely delivered cognitive behavioral therapy from 53 participants experiencing multiple physical and mental health problems were anonymously transcribed and rated by trained human CICS coders. Using participatory methodology, a multidisciplinary team proposed candidate language features that they thought would discriminate between high and low patient activation. The team included service-user researchers, psychological therapists, applied linguists, digital research experts, artificial intelligence ethics researchers, and NLP researchers. Identified language features were extracted from the transcripts alongside demographic features, and machine learning was applied using k-nearest neighbors and bagged trees algorithms to assess whether in-session patient activation and interaction types could be accurately classified.

Results

The k-nearest neighbors classifier obtained 73% accuracy (82% precision and 80% recall) in a test data set. The bagged trees classifier obtained 81% accuracy for test data (87% precision and 75% recall) in differentiating between interactions rated high in patient activation and those rated low or neutral.

Conclusions

Coproduced language features identified through a multidisciplinary collaboration can be used to discriminate among psychological therapy session contents based on patient activation among patients experiencing multiple long-term physical and mental health conditions.",,pdf:https://medinform.jmir.org/2022/11/e38168/PDF; doi:https://doi.org/10.2196/38168; html:https://europepmc.org/articles/PMC9682451 37612010,https://doi.org/10.1016/j.jacc.2023.05.065,Monitoring of Myocardial Involvement in Early Arrhythmogenic Right Ventricular Cardiomyopathy Across the Age Spectrum.,"Kirkels FP, van Osta N, Rootwelt-Norberg C, Chivulescu M, van Loon T, Aabel EW, Castrini AI, Lie ØH, Asselbergs FW, Delhaas T, Cramer MJ, Teske AJ, Haugaa KH, Lumens J.",,Journal of the American College of Cardiology,2023,2023-08-01,N,Early Detection; Arvc; Family Screening; Deformation Imaging; Digital Twin; Arrhythmogenic Cardiomyopathy,,,"

Background

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of primarily the right ventricular myocardium, a substrate for life-threatening ventricular arrhythmias (VAs). Repeated cardiac imaging of at-risk relatives is important for early disease detection. However, it is not known whether screening should be age-tailored.

Objectives

The goal of this study was to assess the need for age-tailoring of follow-up protocols in early ARVC by evaluating myocardial disease progression in different age groups.

Methods

We divided patients with early-stage ARVC and genotype-positive relatives without overt structural disease and VA at first evaluation into 3 groups: age <30 years, 30 to 50 years, and ≥50 years. Longitudinal biventricular deformation characteristics were used to monitor disease progression. To link deformation abnormalities to underlying myocardial disease substrates, Digital Twins were created using an imaging-based computational modeling framework.

Results

We included 313 echocardiographic assessments from 82 subjects (57% female, age 39 ± 17 years, 10% probands) during 6.7 ± 3.3 years of follow-up. Left ventricular global longitudinal strain slightly deteriorated similarly in all age groups (0.1%-point per year [95% CI: 0.05-0.15]). Disease progression in all age groups was more pronounced in the right ventricular lateral wall, expressed by worsening in longitudinal strain (0.6%-point per year [95% CI: 0.46-0.70]) and local differences in myocardial contractility, compliance, and activation delay in the Digital Twin. Six patients experienced VA during follow-up.

Conclusions

Disease progression was similar in all age groups, and sustained VA also occurred in patients aged >50 years without overt ARVC phenotype at first evaluation. Unlike recommended by current guidelines, our study suggests that follow-up of ARVC patients and relatives should not stop at older age.",,doi:https://doi.org/10.1016/j.jacc.2023.05.065 35804579,https://doi.org/10.3390/ani12131679,Genetic Basis of Dilated Cardiomyopathy in Dogs and Its Potential as a Bidirectional Model.,"Gaar-Humphreys KR, Spanjersberg TCF, Santarelli G, Grinwis GCM, Szatmári V, Roelen BAJ, Vink A, van Tintelen JP, Asselbergs FW, Fieten H, Harakalova M, van Steenbeek FG.",,Animals : an open access journal from MDPI,2022,2022-06-29,Y,cardiovascular; Human Induced Pluripotent Stem Cells; Fibrofatty Infiltration; Canine Induced Pluripotent Stem Cells; Attenuated Wavy Fibers,,,"Cardiac disease is a leading cause of death for both humans and dogs. Genetic cardiomyopathies, including dilated cardiomyopathy (DCM), account for a proportion of these cases in both species. Patients may suffer from ventricular enlargement and systolic dysfunction resulting in congestive heart failure and ventricular arrhythmias with high risk for sudden cardiac death. Although canine DCM has similar disease progression and subtypes as in humans, only a few candidate genes have been found to be associated with DCM while the genetic background of human DCM has been more thoroughly studied. Additionally, experimental disease models using induced pluripotent stem cells have been widely adopted in the study of human genetic cardiomyopathy but have not yet been fully adapted for the in-depth study of canine genetic cardiomyopathies. The clinical presentation of DCM is extremely heterogeneous for both species with differences occurring based on sex predisposition, age of onset, and the rate of disease progression. Both genetic predisposition and environmental factors play a role in disease development which are identical in dogs and humans in contrast to other experimental animals. Interestingly, different dog breeds have been shown to develop distinct DCM phenotypes, and this presents a unique opportunity for modeling as there are multiple breed-specific models for DCM with less genetic variance than human DCM. A better understanding of DCM in dogs has the potential for improved selection for breeding and could lead to better overall care and treatment for human and canine DCM patients. At the same time, progress in research made for human DCM can have a positive impact on the care given to dogs affected by DCM. Therefore, this review will analyze the feasibility of canines as a naturally occurring bidirectional disease model for DCM in both species. The histopathology of the myocardium in canine DCM will be evaluated in three different breeds compared to control tissue, and the known genetics that contributes to both canine and human DCM will be summarized. Lastly, the prospect of canine iPSCs as a novel method to uncover the contributions of genetic variants to the pathogenesis of canine DCM will be introduced along with the applications for disease modeling and treatment.",,pdf:https://www.mdpi.com/2076-2615/12/13/1679/pdf?version=1656561768; doi:https://doi.org/10.3390/ani12131679; html:https://europepmc.org/articles/PMC9265105; pdf:https://europepmc.org/articles/PMC9265105?pdf=render +38170504,https://doi.org/10.1001/jamacardio.2023.4994,Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia.,"Schuermans A, Truong B, Ardissino M, Bhukar R, Slob EAW, Nakao T, Dron JS, Small AM, Cho SMJ, Yu Z, Hornsby W, Antoine T, Lannery K, Postupaka D, Gray KJ, Yan Q, Butterworth AS, Burgess S, Wood MJ, Scott NS, Harrington CM, Sarma AA, Lau ES, Roh JD, Januzzi JL, Natarajan P, Honigberg MC.",,JAMA cardiology,2024,2024-03-01,Y,,,,"

Importance

Hypertensive disorders of pregnancy (HDPs), including gestational hypertension and preeclampsia, are important contributors to maternal morbidity and mortality worldwide. In addition, women with HDPs face an elevated long-term risk of cardiovascular disease.

Objective

To identify proteins in the circulation associated with HDPs.

Design, setting, and participants

Two-sample mendelian randomization (MR) tested the associations of genetic instruments for cardiovascular disease-related proteins with gestational hypertension and preeclampsia. In downstream analyses, a systematic review of observational data was conducted to evaluate the identified proteins' dynamics across gestation in hypertensive vs normotensive pregnancies, and phenome-wide MR analyses were performed to identify potential non-HDP-related effects associated with the prioritized proteins. Genetic association data for cardiovascular disease-related proteins were obtained from the Systematic and Combined Analysis of Olink Proteins (SCALLOP) consortium. Genetic association data for the HDPs were obtained from recent European-ancestry genome-wide association study meta-analyses for gestational hypertension and preeclampsia. Study data were analyzed October 2022 to October 2023.

Exposures

Genetic instruments for 90 candidate proteins implicated in cardiovascular diseases, constructed using cis-protein quantitative trait loci (cis-pQTLs).

Main outcomes and measures

Gestational hypertension and preeclampsia.

Results

Genetic association data for cardiovascular disease-related proteins were obtained from 21 758 participants from the SCALLOP consortium. Genetic association data for the HDPs were obtained from 393 238 female individuals (8636 cases and 384 602 controls) for gestational hypertension and 606 903 female individuals (16 032 cases and 590 871 controls) for preeclampsia. Seventy-five of 90 proteins (83.3%) had at least 1 valid cis-pQTL. Of those, 10 proteins (13.3%) were significantly associated with HDPs. Four were robust to sensitivity analyses for gestational hypertension (cluster of differentiation 40, eosinophil cationic protein [ECP], galectin 3, N-terminal pro-brain natriuretic peptide [NT-proBNP]), and 2 were robust for preeclampsia (cystatin B, heat shock protein 27 [HSP27]). Consistent with the MR findings, observational data revealed that lower NT-proBNP (0.76- to 0.88-fold difference vs no HDPs) and higher HSP27 (2.40-fold difference vs no HDPs) levels during the first trimester of pregnancy were associated with increased risk of HDPs, as were higher levels of ECP (1.60-fold difference vs no HDPs). Phenome-wide MR analyses identified 37 unique non-HDP-related protein-disease associations, suggesting potential on-target effects associated with interventions lowering HDP risk through the identified proteins.

Conclusions and relevance

Study findings suggest genetic associations of 4 cardiovascular disease-related proteins with gestational hypertension and 2 associated with preeclampsia. Future studies are required to test the efficacy of targeting the corresponding pathways to reduce HDP risk.",,doi:https://doi.org/10.1001/jamacardio.2023.4994; html:https://europepmc.org/articles/PMC10765315; pdf:https://europepmc.org/articles/PMC10765315?pdf=render 34772649,https://doi.org/10.1016/s2589-7500(21)00252-1,Characteristics of publicly available skin cancer image datasets: a systematic review.,"Wen D, Khan SM, Ji Xu A, Ibrahim H, Smith L, Caballero J, Zepeda L, de Blas Perez C, Denniston AK, Liu X, Matin RN.",,The Lancet. Digital health,2022,2021-11-09,N,,,,"Publicly available skin image datasets are increasingly used to develop machine learning algorithms for skin cancer diagnosis. However, the total number of datasets and their respective content is currently unclear. This systematic review aimed to identify and evaluate all publicly available skin image datasets used for skin cancer diagnosis by exploring their characteristics, data access requirements, and associated image metadata. A combined MEDLINE, Google, and Google Dataset search identified 21 open access datasets containing 106 950 skin lesion images, 17 open access atlases, eight regulated access datasets, and three regulated access atlases. Images and accompanying data from open access datasets were evaluated by two independent reviewers. Among the 14 datasets that reported country of origin, most (11 [79%]) originated from Europe, North America, and Oceania exclusively. Most datasets (19 [91%]) contained dermoscopic images or macroscopic photographs only. Clinical information was available regarding age for 81 662 images (76·4%), sex for 82 848 (77·5%), and body site for 79 561 (74·4%). Subject ethnicity data were available for 1415 images (1·3%), and Fitzpatrick skin type data for 2236 (2·1%). There was limited and variable reporting of characteristics and metadata among datasets, with substantial under-representation of darker skin types. This is the first systematic review to characterise publicly available skin image datasets, highlighting limited applicability to real-life clinical settings and restricted population representation, precluding generalisability. Quality standards for characteristics and metadata reporting for skin image datasets are needed.",,pdf:http://www.thelancet.com/article/S2589750021002521/pdf; doi:https://doi.org/10.1016/S2589-7500(21)00252-1 37477360,https://doi.org/10.1097/ypg.0000000000000349,Schizophrenia polygenic risk score and type 2 diabetes onset in older adults with no schizophrenia diagnosis.,"Shamsutdinova D, Ajnakina O, Roberts A, Stahl D.",,Psychiatric genetics,2023,2023-07-04,Y,,,,"

Objectives

An association between type 2 diabetes (T2DM) and schizophrenia has long been observed, and recent research revealed presence of shared genetic factors. However, epidemiological evidence was inconsistent, some reported insignificant contribution of genetic factors to T2DM-schizophrenia comorbidity. Prior works studied people with schizophrenia, particularly, antipsychotic-naive patients, or those during the first psychotic experience to limit schizophrenia-related environmental factors. In contrast, we controlled such factors by utilizing a general population sample of individuals undiagnosed with schizophrenia. We hypothesized that if schizophrenia genetics impact T2DM development and such impact is not fully mediated by schizophrenia-related environment, people with high polygenic schizophrenia risk would exhibit elevated T2DM incidence.

Methods

Using a population-representative sample of adults aged ≥50 from English Longitudinal Study of Ageing ( n  = 5968, 493 T2DM cases, average follow-up 8.7 years), we investigated if schizophrenia polygenic risk score (PGS-SZ) is associated with T2DM onset. A proportional hazards model with interval censoring was adjusted for age and sex (Model 1), and age, sex, BMI, hypertension, cardiovascular diseases, exercise, smoking, depressive symptoms and T2DM polygenic risk score (Model 2). According to the power calculations, hazard rates > 1.14 per standard deviation in PGS-SZ could be detected.

Results

We did not observe a significant association between PGS-SZ and T2DM incidence (hazard ratio 1.04; 95% CI 0.93-1.15; and 1.01, 95% CI 0.94-1.09).

Conclusion

Our results suggest low contribution of the intrinsic biological mechanisms driven by the polygenic risk of schizophrenia on future T2DM onset. Further research is needed.",,html:https://journals.lww.com/psychgenetics/fulltext/9900/schizophrenia_polygenic_risk_score_and_type_2.34.aspx; doi:https://doi.org/10.1097/YPG.0000000000000349; html:https://europepmc.org/articles/PMC10501355; pdf:https://europepmc.org/articles/PMC10501355?pdf=render 38045440,https://doi.org/10.1093/ehjdh/ztad056,Machine learning-based biomarker profile derived from 4210 serially measured proteins predicts clinical outcome of patients with heart failure.,"de Bakker M, Petersen TB, Rueten-Budde AJ, Akkerhuis KM, Umans VA, Brugts JJ, Germans T, Reinders MJT, Katsikis PD, van der Spek PJ, Ostroff R, She R, Lanfear D, Asselbergs FW, Boersma E, Rizopoulos D, Kardys I.",,European heart journal. Digital health,2023,2023-10-04,Y,Prediction; Proteomics; Heart Failure; NT-proBNP; Repeated Measurements; Elastic Net,,,"

Aims

Risk assessment tools are needed for timely identification of patients with heart failure (HF) with reduced ejection fraction (HFrEF) who are at high risk of adverse events. In this study, we aim to derive a small set out of 4210 repeatedly measured proteins, which, along with clinical characteristics and established biomarkers, carry optimal prognostic capacity for adverse events, in patients with HFrEF.

Methods and results

In 382 patients, we performed repeated blood sampling (median follow-up: 2.1 years) and applied an aptamer-based multiplex proteomic approach. We used machine learning to select the optimal set of predictors for the primary endpoint (PEP: composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization). The association between repeated measures of selected proteins and PEP was investigated by multivariable joint models. Internal validation (cross-validated c-index) and external validation (Henry Ford HF PharmacoGenomic Registry cohort) were performed. Nine proteins were selected in addition to the MAGGIC risk score, N-terminal pro-hormone B-type natriuretic peptide, and troponin T: suppression of tumourigenicity 2, tryptophanyl-tRNA synthetase cytoplasmic, histone H2A Type 3, angiotensinogen, deltex-1, thrombospondin-4, ADAMTS-like protein 2, anthrax toxin receptor 1, and cathepsin D. N-terminal pro-hormone B-type natriuretic peptide and angiotensinogen showed the strongest associations [hazard ratio (95% confidence interval): 1.96 (1.17-3.40) and 0.66 (0.49-0.88), respectively]. The multivariable model yielded a c-index of 0.85 upon internal validation and c-indices up to 0.80 upon external validation. The c-index was higher than that of a model containing established risk factors (P = 0.021).

Conclusion

Nine serially measured proteins captured the most essential prognostic information for the occurrence of adverse events in patients with HFrEF, and provided incremental value for HF prognostication beyond established risk factors. These proteins could be used for dynamic, individual risk assessment in a prospective setting. These findings also illustrate the potential value of relatively 'novel' biomarkers for prognostication.

Clinical trial registration

https://clinicaltrials.gov/ct2/show/NCT01851538?term=nCT01851538&draw=2&rank=1 24.",,doi:https://doi.org/10.1093/ehjdh/ztad056; html:https://europepmc.org/articles/PMC10689916; pdf:https://europepmc.org/articles/PMC10689916?pdf=render 31500613,https://doi.org/10.1186/s12911-019-0908-7,A validated natural language processing algorithm for brain imaging phenotypes from radiology reports in UK electronic health records.,"Wheater E, Mair G, Sudlow C, Alex B, Grover C, Whiteley W.",,BMC medical informatics and decision making,2019,2019-09-09,Y,Stroke; Phenotyping; Brain imaging; Radiology; Natural Language Processing; Radiology Reports,"Applied Analytics, Better Care",,"

Background

Manual coding of phenotypes in brain radiology reports is time consuming. We developed a natural language processing (NLP) algorithm to enable automatic identification of brain imaging in radiology reports performed in routine clinical practice in the UK National Health Service (NHS).

Methods

We used anonymized text brain imaging reports from a cohort study of stroke/TIA patients and from a regional hospital to develop and test an NLP algorithm. Two experts marked up text in 1692 reports for 24 cerebrovascular and other neurological phenotypes. We developed and tested a rule-based NLP algorithm first within the cohort study, and further evaluated it in the reports from the regional hospital.

Results

The agreement between expert readers was excellent (Cohen's κ =0.93) in both datasets. In the final test dataset (n = 700) in unseen regional hospital reports, the algorithm had very good performance for a report of any ischaemic stroke [sensitivity 89% (95% CI:81-94); positive predictive value (PPV) 85% (76-90); specificity 100% (95% CI:0.99-1.00)]; any haemorrhagic stroke [sensitivity 96% (95% CI: 80-99), PPV 72% (95% CI:55-84); specificity 100% (95% CI:0.99-1.00)]; brain tumours [sensitivity 96% (CI:87-99); PPV 84% (73-91); specificity: 100% (95% CI:0.99-1.00)] and cerebral small vessel disease and cerebral atrophy (sensitivity, PPV and specificity all > 97%). We obtained few reports of subarachnoid haemorrhage, microbleeds or subdural haematomas. In 110,695 reports from NHS Tayside, atrophy (n = 28,757, 26%), small vessel disease (15,015, 14%) and old, deep ischaemic strokes (10,636, 10%) were the commonest findings.

Conclusions

An NLP algorithm can be developed in UK NHS radiology records to allow identification of cohorts of patients with important brain imaging phenotypes at a scale that would otherwise not be possible.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-019-0908-7; doi:https://doi.org/10.1186/s12911-019-0908-7; html:https://europepmc.org/articles/PMC6734359; pdf:https://europepmc.org/articles/PMC6734359?pdf=render 32838035,https://doi.org/10.1002/lrh2.10236,Rapid translation of clinical guidelines into executable knowledge: A case study of COVID-19 and online demonstration.,"Fox J, Khan O, Curtis H, Wright A, Pal C, Cockburn N, Cooper J, Chandan JS, Nirantharakumar K.",,Learning health systems,2021,2020-07-14,Y,Artificial intelligence; Covid‐19; Rapid Learning Systems,,,"

Introduction

We report a pathfinder study of AI/knowledge engineering methods to rapidly formalise COVID-19 guidelines into an executable model of decision making and care pathways. The knowledge source for the study was material published by BMJ Best Practice in March 2020.

Methods

The PROforma guideline modelling language and OpenClinical.net authoring and publishing platform were used to create a data model for care of COVID-19 patients together with executable models of rules, decisions and plans that interpret patient data and give personalised care advice.

Results

PROforma and OpenClinical.net proved to be an effective combination for rapidly creating the COVID-19 model; the Pathfinder 1 demonstrator is available for assessment at https://www.openclinical.net/index.php?id=746.

Conclusions

This is believed to be the first use of AI/knowledge engineering methods for disseminating best-practice in COVID-19 care. It demonstrates a novel and promising approach to the rapid translation of clinical guidelines into point of care services, and a foundation for rapid learning systems in many areas of healthcare.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/lrh2.10236; doi:https://doi.org/10.1002/lrh2.10236; html:https://europepmc.org/articles/PMC7323421; pdf:https://europepmc.org/articles/PMC7323421?pdf=render 34390586,https://doi.org/10.1111/ejn.15423,Spectral clustering based on structural magnetic resonance imaging and its relationship with major depressive disorder and cognitive ability.,"Yeung HW, Shen X, Stolicyn A, de Nooij L, Harris MA, Romaniuk L, Buchanan CR, Waiter GD, Sandu AL, McNeil CJ, Murray A, Steele JD, Campbell A, Porteous D, Lawrie SM, McIntosh AM, Cox SR, Smith KM, Whalley HC.",,The European journal of neuroscience,2021,2021-09-02,N,Cognition; Clustering; Machine Learning; Major Depressive Disorder; Structural Neuroimaging; Markov Stability,,,"There is increasing interest in using data-driven unsupervised methods to identify structural underpinnings of common mental illnesses, including major depressive disorder (MDD) and associated traits such as cognition. However, studies are often limited to severe clinical cases with small sample sizes and most do not include replication. Here, we examine two relatively large samples with structural magnetic resonance imaging (MRI), measures of lifetime MDD and cognitive variables: Generation Scotland (GS subsample, N = 980) and UK Biobank (UKB, N = 8,900), for discovery and replication, using an exploratory approach. Regional measures of FreeSurfer derived cortical thickness (CT), cortical surface area (CSA), cortical volume (CV) and subcortical volume (subCV) were input into a clustering process, controlling for common covariates. The main analysis steps involved constructing participant K-nearest neighbour graphs and graph partitioning with Markov stability to determine optimal clustering of participants. Resultant clusters were (1) checked whether they were replicated in an independent cohort and (2) tested for associations with depression status and cognitive measures. Participants separated into two clusters based on structural brain measurements in GS subsample, with large Cohen's d effect sizes between clusters in higher order cortical regions, commonly associated with executive function and decision making. Clustering was replicated in the UKB sample, with high correlations of cluster effect sizes for CT, CSA, CV and subCV between cohorts across regions. The identified clusters were not significantly different with respect to MDD case-control status in either cohort (GS subsample: pFDR  = .2239-.6585; UKB: pFDR  = .2003-.7690). Significant differences in general cognitive ability were, however, found between the clusters for both datasets, for CSA, CV and subCV (GS subsample: d = 0.2529-.3490, pFDR  < .005; UKB: d = 0.0868-0.1070, pFDR  < .005). Our results suggest that there are replicable natural groupings of participants based on cortical and subcortical brain measures, which may be related to differences in cognitive performance, but not to the MDD case-control status.",,pdf:https://discovery.dundee.ac.uk/files/66344502/ejn.15423.pdf; doi:https://doi.org/10.1111/ejn.15423 -36344532,https://doi.org/10.1038/s41598-022-21663-w,Atrial fibrillation prediction by combining ECG markers and CMR radiomics.,"Pujadas ER, Raisi-Estabragh Z, Szabo L, Morcillo CI, Campello VM, Martin-Isla C, Vago H, Merkely B, Harvey NC, Petersen SE, Lekadir K.",,Scientific reports,2022,2022-11-07,Y,,,,"Atrial fibrillation (AF) is the most common cardiac arrhythmia. It is associated with a higher risk of important adverse health outcomes such as stroke and death. AF is linked to distinct electro-anatomic alterations. The main tool for AF diagnosis is the Electrocardiogram (ECG). However, an ECG recorded at a single time point may not detect individuals with paroxysmal AF. In this study, we developed machine learning models for discrimination of prevalent AF using a combination of image-derived radiomics phenotypes and ECG features. Thus, we characterize the phenotypes of prevalent AF in terms of ECG and imaging alterations. Moreover, we explore sex-differential remodelling by building sex-specific models. Our integrative model including radiomics and ECG together resulted in a better performance than ECG alone, particularly in women. ECG had a lower performance in women than men (AUC: 0.77 vs 0.88, p < 0.05) but adding radiomics features, the accuracy of the model was able to improve significantly. The sensitivity also increased considerably in women by adding the radiomics (0.68 vs 0.79, p < 0.05) having a higher detection of AF events. Our findings provide novel insights into AF-related electro-anatomic remodelling and its variations by sex. The integrative radiomics-ECG model also presents a potential novel approach for earlier detection of AF.",,pdf:https://www.nature.com/articles/s41598-022-21663-w.pdf; doi:https://doi.org/10.1038/s41598-022-21663-w; html:https://europepmc.org/articles/PMC9640662; pdf:https://europepmc.org/articles/PMC9640662?pdf=render 34850874,https://doi.org/10.1093/gigascience/giab083,Erratum to: An overview of the National COVID-19 Chest Imaging Database: data quality and cohort analysis.,"Cushnan D, Bennett O, Berka R, Bertolli O, Chopra A, Dorgham S, Favaro A, Ganepola T, Halling-Brown M, Imreh G, Jacob J, Jefferson E, Lemarchand F, Schofield D, Wyatt JC, Collaborative NCCID.",,GigaScience,2021,2021-12-01,Y,,,,,,pdf:https://academic.oup.com/gigascience/article-pdf/10/12/giab083/41395049/giab083.pdf; doi:https://doi.org/10.1093/gigascience/giab083; html:https://europepmc.org/articles/PMC8634578; pdf:https://europepmc.org/articles/PMC8634578?pdf=render -36798028,https://doi.org/10.1002/ehf2.14308,Identifying patients at risk: multi-centre comparison of HeartMate 3 and HeartWare left ventricular assist devices.,"Numan L, Zimpfer D, Zadok OIB, Aarts E, Morshuis M, Guenther SPW, Riebandt J, Wiedemann D, Ramjankhan FZ, Oppelaar AM, Ben-Gal T, Ben-Avraham B, Asselbergs FW, Schramm R, Van Laake LW.",,ESC heart failure,2023,2023-02-16,Y,Mechanical Circulatory Support; Left Ventricular Assist Device; End-stage Heart Failure; Lvad; Centrifugal Continuous Flow Pump,,,"

Aims

Since the withdrawal of HeartWare (HVAD) from the global market, there is an ongoing discussion if and which patients require prophylactically exchange for a HeartMate 3 (HM3). Therefore, it is important to study outcome differences between HVAD and HM3 patients. Because centres differ in patient selection and standard of care, we performed a propensity score (PS)-based study including centres that implanted both devices and aimed to identify which HVAD patients are at highest risk.

Methods and results

We performed an international multi-centre study (n = 1021) including centres that implanted HVAD and HM3. PS-matching was performed using clinical variables and the implanting centre. Survival and complications were compared. As a sensitivity analysis, PS-adjusted Cox regression was performed. Landmark analysis with conditional survival >2 years was conducted to evaluate long-term survival differences. To identify which HVAD patients may benefit from a HM3 upgrade, Cox regression using pre-operative variables and their interaction with device type was performed. Survival was significantly better for HM3 patients (P < 0.01) in 458 matched patients, with a median follow-up of 23 months. Within the matched cohort, HM3 patients had a median age of 58 years, and 83% were male, 80% of the HVAD patients were male, with a median age of 59 years. PS-adjusted Cox regression confirmed a significantly better survival for HM3 patients when compared with HVAD, with a HR of 1.46 (95% confidence interval 1.14-1.85, P < 0.01). Pump thrombosis (P < 0.01) and ischaemic stroke (P < 0.01) occurred less in HM3 patients. No difference was found for haemorrhagic stroke, right heart failure, driveline infection, and major bleeding. Landmark-analysis confirmed a significant difference in conditional survival >2 years after implantation (P = 0.03). None of the pre-operative variable interactions in the Cox regression were significant.

Conclusions

HM3 patients have a significantly better survival and a lower incidence of ischaemic strokes and pump thrombosis than HVAD patients. This survival difference persisted after 2 years of implantation. Additional research using post-operative variables is warranted to identify which HVAD patients need an upgrade to HM3 or expedited transplantation.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14308; doi:https://doi.org/10.1002/ehf2.14308; html:https://europepmc.org/articles/PMC10192248; pdf:https://europepmc.org/articles/PMC10192248?pdf=render +36344532,https://doi.org/10.1038/s41598-022-21663-w,Atrial fibrillation prediction by combining ECG markers and CMR radiomics.,"Pujadas ER, Raisi-Estabragh Z, Szabo L, Morcillo CI, Campello VM, Martin-Isla C, Vago H, Merkely B, Harvey NC, Petersen SE, Lekadir K.",,Scientific reports,2022,2022-11-07,Y,,,,"Atrial fibrillation (AF) is the most common cardiac arrhythmia. It is associated with a higher risk of important adverse health outcomes such as stroke and death. AF is linked to distinct electro-anatomic alterations. The main tool for AF diagnosis is the Electrocardiogram (ECG). However, an ECG recorded at a single time point may not detect individuals with paroxysmal AF. In this study, we developed machine learning models for discrimination of prevalent AF using a combination of image-derived radiomics phenotypes and ECG features. Thus, we characterize the phenotypes of prevalent AF in terms of ECG and imaging alterations. Moreover, we explore sex-differential remodelling by building sex-specific models. Our integrative model including radiomics and ECG together resulted in a better performance than ECG alone, particularly in women. ECG had a lower performance in women than men (AUC: 0.77 vs 0.88, p < 0.05) but adding radiomics features, the accuracy of the model was able to improve significantly. The sensitivity also increased considerably in women by adding the radiomics (0.68 vs 0.79, p < 0.05) having a higher detection of AF events. Our findings provide novel insights into AF-related electro-anatomic remodelling and its variations by sex. The integrative radiomics-ECG model also presents a potential novel approach for earlier detection of AF.",,pdf:https://www.nature.com/articles/s41598-022-21663-w.pdf; doi:https://doi.org/10.1038/s41598-022-21663-w; html:https://europepmc.org/articles/PMC9640662; pdf:https://europepmc.org/articles/PMC9640662?pdf=render PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated with multi-mode transportation networks in China,"Xu X, Liu X, Wang L, Wu Y, Lu X, Wang X, Pei S.",,Fundamental Research,2022,2022-04-22,Y,Complex Network; Spatial Spread; Human Mobility; Transportation Networks; Covid-19,,,"The spatial spread of COVID-19 during early 2020 in China was primarily driven by outbound travelers leaving the epicenter, Wuhan, Hubei province. Existing studies focus on the influence of aggregated out-bound population flows originating from Wuhan; however, the impacts of different modes of transportation and the network structure of transportation systems on the early spread of COVID-19 in China are not well understood. Here, we assess the roles of the road, railway, and air transportation networks in driving the spatial spread of COVID-19 in China. We find that the short-range spread within Hubei province was dominated by ground traffic, notably, the railway transportation. In contrast, long-range spread to cities in other provinces was mediated by multiple factors, including a higher risk of case importation associated with air transportation and a larger outbreak size in hub cities located at the center of transportation networks. We further show that, although the dissemination of SARS-CoV-2 across countries and continents is determined by the worldwide air transportation network, the early geographic dispersal of COVID-19 within China is better predicted by the railway traffic. Given the recent emergence of multiple more transmissible variants of SARS-CoV-2, our findings can support a better assessment of the spread risk of those variants and improve future pandemic preparedness and responses. Graphical abstract Image, graphical abstract.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023380/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023380/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9023380; pdf:https://europepmc.org/articles/PMC9023380?pdf=render +36798028,https://doi.org/10.1002/ehf2.14308,Identifying patients at risk: multi-centre comparison of HeartMate 3 and HeartWare left ventricular assist devices.,"Numan L, Zimpfer D, Zadok OIB, Aarts E, Morshuis M, Guenther SPW, Riebandt J, Wiedemann D, Ramjankhan FZ, Oppelaar AM, Ben-Gal T, Ben-Avraham B, Asselbergs FW, Schramm R, Van Laake LW.",,ESC heart failure,2023,2023-02-16,Y,Mechanical Circulatory Support; Left Ventricular Assist Device; End-stage Heart Failure; Lvad; Centrifugal Continuous Flow Pump,,,"

Aims

Since the withdrawal of HeartWare (HVAD) from the global market, there is an ongoing discussion if and which patients require prophylactically exchange for a HeartMate 3 (HM3). Therefore, it is important to study outcome differences between HVAD and HM3 patients. Because centres differ in patient selection and standard of care, we performed a propensity score (PS)-based study including centres that implanted both devices and aimed to identify which HVAD patients are at highest risk.

Methods and results

We performed an international multi-centre study (n = 1021) including centres that implanted HVAD and HM3. PS-matching was performed using clinical variables and the implanting centre. Survival and complications were compared. As a sensitivity analysis, PS-adjusted Cox regression was performed. Landmark analysis with conditional survival >2 years was conducted to evaluate long-term survival differences. To identify which HVAD patients may benefit from a HM3 upgrade, Cox regression using pre-operative variables and their interaction with device type was performed. Survival was significantly better for HM3 patients (P < 0.01) in 458 matched patients, with a median follow-up of 23 months. Within the matched cohort, HM3 patients had a median age of 58 years, and 83% were male, 80% of the HVAD patients were male, with a median age of 59 years. PS-adjusted Cox regression confirmed a significantly better survival for HM3 patients when compared with HVAD, with a HR of 1.46 (95% confidence interval 1.14-1.85, P < 0.01). Pump thrombosis (P < 0.01) and ischaemic stroke (P < 0.01) occurred less in HM3 patients. No difference was found for haemorrhagic stroke, right heart failure, driveline infection, and major bleeding. Landmark-analysis confirmed a significant difference in conditional survival >2 years after implantation (P = 0.03). None of the pre-operative variable interactions in the Cox regression were significant.

Conclusions

HM3 patients have a significantly better survival and a lower incidence of ischaemic strokes and pump thrombosis than HVAD patients. This survival difference persisted after 2 years of implantation. Additional research using post-operative variables is warranted to identify which HVAD patients need an upgrade to HM3 or expedited transplantation.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14308; doi:https://doi.org/10.1002/ehf2.14308; html:https://europepmc.org/articles/PMC10192248; pdf:https://europepmc.org/articles/PMC10192248?pdf=render 33144367,https://doi.org/10.3399/bjgpopen20x101109,Evaluating a cardiovascular disease risk management care continuum within a learning healthcare system: a prospective cohort study.,"Groenhof TKJ, Lely AT, Haitjema S, Nathoe HM, Kortekaas MF, Asselbergs FW, Bots ML, Hollander M, UCC CVRM study group.",,BJGP open,2020,2020-12-15,Y,Cardiovascular diseases; Continuity Of Patient Care; Learning Healthcare System; Cardiovascular Risk Management,,,"

Background

Many patients now present with multimorbidity and chronicity of disease. This means that multidisciplinary management in a care continuum, integrating primary care and hospital care services, is needed to ensure high quality care.

Aim

To evaluate cardiovascular risk management (CVRM) via linkage of health data sources, as an example of a multidisciplinary continuum within a learning healthcare system (LHS).

Design & setting

In this prospective cohort study, data were linked from the Utrecht Cardiovascular Cohort (UCC) to the Julius General Practitioners' Network (JGPN) database. UCC offers structured CVRM at referral to the University Medical Centre (UMC) Utrecht. JGPN consists of electronic health record (EHR) data from referring GPs.

Method

The cardiovascular risk factors were extracted for each patient 13 months before referral (JGPN), at UCC inclusion, and during 12 months follow-up (JGPN). The following areas were assessed: registration of risk factors; detection of risk factor(s) requiring treatment at UCC; communication of risk factors and actionable suggestions from the specialist to the GP; and change of management during follow-up.

Results

In 52% of patients, ≥1 risk factors were registered (that is, extractable from structured fields within routine care health records) before UCC. In 12%-72% of patients, risk factor(s) existed that required (change or start of) treatment at UCC inclusion. Specialist communication included the complete risk profile in 67% of letters, but lacked actionable suggestions in 86%. In 29% of patients, at least one risk factor was registered after UCC. Change in management in GP records was seen in 21%-58% of them.

Conclusion

Evaluation of a multidisciplinary LHS is possible via linkage of health data sources. Efforts have to be made to improve registration in primary care, as well as communication on findings and actionable suggestions for follow-up to bridge the gap in the CVRM continuum.",,pdf:https://bjgpopen.org/content/bjgpoa/4/5/bjgpopen20X101109.full.pdf; doi:https://doi.org/10.3399/bjgpopen20X101109; html:https://europepmc.org/articles/PMC7880177; pdf:https://europepmc.org/articles/PMC7880177?pdf=render -38763167,https://doi.org/10.1164/rccm.202312-2289oc,Impact of High Dose Early Mobilization on Outcomes for Patients with Diabetes: A Secondary Analysis of the TEAM Trial.,"Serpa Neto A, Bailey M, Seller D, Agli A, Bellomo R, Brickell K, Broadley T, Buhr H, Gabbe BJ, Gould DW, Harrold M, Higgins AM, Hurford S, Iwashyna TJ, Nichol AD, Presneill JJ, Schaller SJ, Sivasuthan J, Tipping CJ, Poole A, Parke R, Bradley S, Webb S, Zoungas S, Young PJ, Hodgson CL.",,American journal of respiratory and critical care medicine,2024,2024-05-19,N,Mortality; Mechanical ventilation; Physiotherapy; Clinical Trial,,,"

Rationale

Patients with diabetes represent almost 20% of all ICU admissions and might respond differently to high dose early active mobilization.

Objectives

To assess whether diabetes modified the relationship between the dose of early mobilization on clinical outcomes in the TEAM trial.

Methods

All TEAM trial patients were included. The primary outcome was days alive and out of hospital at day 180. Secondary outcomes included 180-day mortality and long-term functional outcomes at day 180. Logistic and median regression models were used to explore the effect of high dose early mobilization on outcomes by diabetes status.

Measurements and main results

All 741 patients from the original trial were included. Of these, 159 patients (21.4%) had diabetes. Patients with diabetes had a lower number of days alive and out of hospital at day 180 (124 [0-153] vs. 147 [82-164], p = 0.013), and higher 180-day mortality (30% vs. 18%, p = 0.044). In patients receiving high dose early mobilization, days alive and out of hospital at day 180 was 73.0 (0.0 - 144.5) in patients with diabetes and 146.5 (95.8 - 163.0) in patients without diabetes (p for interaction = 0.108). However, in patients with diabetes, high dose early mobilization increased the odds of mortality at 180 days (adjusted odds ratio 3.47; 95% confidence interval [CI], 1.67-7.61, p value for interaction, 0.001).

Conclusions

In this secondary analysis of the TEAM trial, in patients with diabetes, a high dose early mobilization strategy did not significantly decrease the number of days alive and out of hospital at day 180 but it increased 180-day mortality.",,doi:https://doi.org/10.1164/rccm.202312-2289OC 36082669,https://doi.org/10.1161/hypertensionaha.122.19354,"Determining the Relationship Between Blood Pressure, Kidney Function, and Chronic Kidney Disease: Insights From Genetic Epidemiology.","Staplin N, Herrington WG, Murgia F, Ibrahim M, Bull KR, Judge PK, Ng SYA, Turner M, Zhu D, Emberson J, Landray MJ, Baigent C, Haynes R, Hopewell JC.",,"Hypertension (Dallas, Tex. : 1979)",2022,2022-09-09,Y,Blood pressure; Chronic; creatinine; epidemiology; Renal Insufficiency,,,"

Background

It is well established that decreased kidney function can increase blood pressure (BP), but it is unproven whether moderately elevated BP causes chronic kidney disease (CKD) or glomerular hyperfiltration.

Methods

311 119 White British UK Biobank participants were included in logistic regression analyses to estimate the odds of CKD (defined as long-term kidney replacement therapy, estimated glomerular filtration rate [eGFR]< 60mL/min/1.73m2, or urinary albumin:creatinine ratio ≥3 mg/mmol) associated with higher genetically predicted BP using genetic risk scores comprising 219 systolic and 223 diastolic BP loci. Analyses estimating associations with clinical categories of eGFR and urinary albumin:creatinine ratio were also conducted, with an eGFR ≥120 mL (min·1.73m2) considered evidence of glomerular hyperfiltration.

Results

21 623 participants had CKD: 7781 with reduced eGFR and 15 500 with albuminuria. 1828 participants had an eGFR ≥120 mL/min/1.73m2. Each genetically predicted 10 mmHg higher systolic BP and 5 mmHg higher diastolic BP were associated with a 37% (95% CI, 1.29-1.45) and 19% (1.14-1.25) higher odds of CKD, respectively. Associations were evident for both the reduced eGFR and albuminuria components of the CKD outcome. The odds of hyperfiltration (versus an eGFR ≥60 and <90 mL/min/1.73m2 were 49% higher (95% CI, 1.21-1.84) for each genetically predicted 10 mmHg higher systolic BP. Associations with CKD and hyperfiltration were similar irrespective of preexisting diabetes, vascular disease, or different levels of adiposity.

Conclusions

In this general population, genetic epidemiological evidence supports a causal role of life-long differences in BP for decreased kidney function, glomerular hyperfiltration, and albuminuria. Physiological autoregulation may not afford complete renal protection against the moderate BP elevations.",,pdf:https://ora.ox.ac.uk/objects/uuid:aefe90da-8a81-4cfa-981a-bb36eca6faa3/files/r6w924c60k; doi:https://doi.org/10.1161/HYPERTENSIONAHA.122.19354; html:https://europepmc.org/articles/PMC9640248; pdf:https://europepmc.org/articles/PMC9640248?pdf=render +38763167,https://doi.org/10.1164/rccm.202312-2289oc,Impact of High Dose Early Mobilization on Outcomes for Patients with Diabetes: A Secondary Analysis of the TEAM Trial.,"Serpa Neto A, Bailey M, Seller D, Agli A, Bellomo R, Brickell K, Broadley T, Buhr H, Gabbe BJ, Gould DW, Harrold M, Higgins AM, Hurford S, Iwashyna TJ, Nichol AD, Presneill JJ, Schaller SJ, Sivasuthan J, Tipping CJ, Poole A, Parke R, Bradley S, Webb S, Zoungas S, Young PJ, Hodgson CL.",,American journal of respiratory and critical care medicine,2024,2024-05-19,N,Mortality; Mechanical ventilation; Physiotherapy; Clinical Trial,,,"

Rationale

Patients with diabetes represent almost 20% of all ICU admissions and might respond differently to high dose early active mobilization.

Objectives

To assess whether diabetes modified the relationship between the dose of early mobilization on clinical outcomes in the TEAM trial.

Methods

All TEAM trial patients were included. The primary outcome was days alive and out of hospital at day 180. Secondary outcomes included 180-day mortality and long-term functional outcomes at day 180. Logistic and median regression models were used to explore the effect of high dose early mobilization on outcomes by diabetes status.

Measurements and main results

All 741 patients from the original trial were included. Of these, 159 patients (21.4%) had diabetes. Patients with diabetes had a lower number of days alive and out of hospital at day 180 (124 [0-153] vs. 147 [82-164], p = 0.013), and higher 180-day mortality (30% vs. 18%, p = 0.044). In patients receiving high dose early mobilization, days alive and out of hospital at day 180 was 73.0 (0.0 - 144.5) in patients with diabetes and 146.5 (95.8 - 163.0) in patients without diabetes (p for interaction = 0.108). However, in patients with diabetes, high dose early mobilization increased the odds of mortality at 180 days (adjusted odds ratio 3.47; 95% confidence interval [CI], 1.67-7.61, p value for interaction, 0.001).

Conclusions

In this secondary analysis of the TEAM trial, in patients with diabetes, a high dose early mobilization strategy did not significantly decrease the number of days alive and out of hospital at day 180 but it increased 180-day mortality.",,doi:https://doi.org/10.1164/rccm.202312-2289OC 30648344,https://doi.org/10.1002/cnm.3180,A semi-active human digital twin model for detecting severity of carotid stenoses from head vibration-A coupled computational mechanics and computer vision method.,"Chakshu NK, Carson J, Sazonov I, Nithiarasu P.",,International journal for numerical methods in biomedical engineering,2019,2019-02-20,Y,Computer vision; Blood flow; Systemic Circulation; Carotid Stenoses; Digital Twin; Biomechanical Vibrations; Face Video,Applied Analytics,,"In this work, we propose a methodology to detect the severity of carotid stenosis from a video of a human face with the help of a coupled blood flow and head vibration model. This semi-active digital twin model is an attempt to link noninvasive video of a patient face to the percentage of carotid occlusion. The pulsatile nature of blood flow through the carotid arteries induces a subtle head vibration. This vibration is a potential indicator of carotid stenosis severity, and it is exploited in the present study. A head vibration model has been proposed in the present work that is linked to the forces generated by blood flow with or without occlusion. The model is used to generate a large number of virtual head vibration data for different degrees of occlusion. In order to determine the in vivo head vibration, a computer vision algorithm is adopted to use human face videos. The in vivo vibrations are compared against the virtual vibration data generated from the coupled computational blood flow/vibration model. A comparison of the in vivo vibration is made against the virtual data to find the best fit between in vivo and virtual data. The preliminary results on healthy subjects and a patient clearly indicate that the model is accurate and it possesses the potential for detecting approximate severity of carotid artery stenoses.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cnm.3180; doi:https://doi.org/10.1002/cnm.3180; html:https://europepmc.org/articles/PMC6593817; pdf:https://europepmc.org/articles/PMC6593817?pdf=render 34095527,https://doi.org/10.23889/ijpds.v4i1.581,Electronic Longitudinal Alcohol Study in Communities (ELAStiC) Wales - protocol for platform development.,"Trefan L, Akbari A, Paranjothy S, Farewell DM, Gartner A, Fone D, Greene J, Evans A, Smith A, Adekanmbi V, Kennedy J, Lyons RA, Moore SC.",,International journal of population data science,2019,2019-05-20,Y,,,,"

Introduction

Excessive alcohol consumption has adverse effects on health and there is a recognised need for the longitudinal analysis of population data to improve our understanding of the patterns of alcohol use, harms to consumers and those in their immediate environment. The UK has a number of linkable, longitudinal databases that if assembled properly could support valuable research on this topic.

Aims and objectives

This paper describes the development of a broad set of cross-linked cohorts, e-cohorts, surveys and linked electronic healthcare records (EHRs) to construct an alcohol-specific analytical platform in the United Kingdom using datasets on the population of Wales.The objective of this paper is to provide a description of existing key datasets integrated with existing, routinely collected electronic health data on a secure platform, and relevant derived variables to enable population-based research on alcohol-related harm in Wales. We illustrate our use of these data with some exemplar research questions that are currently under investigation.

Methods

Record-linkage of routine and observational datasets. Routine data includes hospital admissions, general practice, and cohorts specific to children. Two observational studies were included. Routine socioeconomic descriptors and mortality data were also linked.

Conclusion

We described a record-linked, population-based research protocol for alcohol related harm on a secure platform. As the datasets used here are available in many countries, ELAStiC provides a template for setting up similar initiatives in other countries. We have also defined a number of alcohol specific variables using routinely-collected available data that can be used in other epidemiological studies into alcohol related outcomes. With over 10 years of longitudinal data, it will help to understand alcohol-related disease and health trajectories across the lifespan.",,pdf:https://ijpds.org/article/download/581/2923; doi:https://doi.org/10.23889/ijpds.v4i1.581; html:https://europepmc.org/articles/PMC8142962; pdf:https://europepmc.org/articles/PMC8142962?pdf=render 34275648,https://doi.org/10.1016/j.injury.2021.06.037,Patterns and predictors of personal responsibility attributions after major trauma.,"Lau G, Gabbe BJ, Giummarra MJ.",,Injury,2021,2021-07-06,N,"wounds and injuries; Insurance, Accident; Violence; Guilt; Accidental Injuries; Liability, Legal",,,"

Background

External responsibility attributions after injury are associated with worse recovery. However, there remains limited understanding of who accepts personal responsibilityfor their injury and whether or how responsibility attributions change over time.

Methods

This prospective cohort study included patients who received care from recovery co-ordinators following serious injury and admission to a major trauma centre in Victoria, Australia (n=850). Self-reported personal responsibility attributions (totally, partially, not responsible, or did not know) were collected at three timepoints (admission, discharge, and six months post-injury) and linked to demographic, injury and clinical characteristics from the Victorian State Trauma Registry.

Results

Mixed effects multinomial analyses revealed that female sex (adjusted relative risk ratio, aRRR=3.11-4.66) and compensable injury (aRRR=7.83-15.27) were associated with reporting lower personal responsibility relative to total responsibility. Falls and motorcyclists had decreased risk of reporting lower personal responsibility than non-drivers (motor vehicle/motorcycle passengers, cyclists and pedestrians) (aRRR=0.11-0.19). More than one-third of participants changed their personal responsibility attribution within six months post-injury. Kappa analyses revealed fair to moderate agreement between the three timepoints (kappa=0.38-0.59), and Stuart-Maxwell tests showed unidirectional bias towards reporting lower levels of personal responsibility between admission and discharge (p<0.001). No demographic, health or injury characteristics predicted a change in responsibility attributions in logistic regression analyses.

Conclusions

Personal responsibility attributions often change over time. Therefore, responsibility attributions should not be considered static, and attributions made at different times post-injury should not be used interchangeably in research or clinical settings. Given that external responsibility attributions are associated with worse post-injury outcomes, potential interventions to optimise recovery should be prioritised for patients who predominantly report lower levels of personal responsibility, especially women and people with compensable injuries. Meanwhile, factors associated with high levels of personal responsibility highlight opportunities to implement targeted injury prevention strategies.",,doi:https://doi.org/10.1016/j.injury.2021.06.037 -35796550,https://doi.org/10.1093/hmg/ddac153,The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians: a Mendelian randomization study.,"Borges MC, Haycock P, Zheng J, Hemani G, Howe LJ, Schmidt AF, Staley JR, Lumbers RT, Henry A, Lemaitre RN, Gaunt TR, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA.",,Human molecular genetics,2022,2022-11-01,N,,,,"Despite early interest, the evidence linking fatty acids to cardiovascular diseases (CVDs) remains controversial. We used Mendelian randomization to explore the involvement of polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids biosynthesis in the etiology of several CVD endpoints in up to 1 153 768 European (maximum 123 668 cases) and 212 453 East Asian (maximum 29 319 cases) ancestry individuals. As instruments, we selected single nucleotide polymorphisms mapping to genes with well-known roles in PUFA (i.e. FADS1/2 and ELOVL2) and MUFA (i.e. SCD) biosynthesis. Our findings suggest that higher PUFA biosynthesis rate (proxied by rs174576 near FADS1/2) is related to higher odds of multiple CVDs, particularly ischemic stroke, peripheral artery disease and venous thromboembolism, whereas higher MUFA biosynthesis rate (proxied by rs603424 near SCD) is related to lower odds of coronary artery disease among Europeans. Results were unclear for East Asians as most effect estimates were imprecise. By triangulating multiple approaches (i.e. uni-/multi-variable Mendelian randomization, a phenome-wide scan, genetic colocalization and within-sibling analyses), our results are compatible with higher low-density lipoprotein (LDL) cholesterol (and possibly glucose) being a downstream effect of higher PUFA biosynthesis rate. Our findings indicate that PUFA and MUFA biosynthesis are involved in the etiology of CVDs and suggest LDL cholesterol as a potential mediating trait between PUFA biosynthesis and CVDs risk.",,pdf:https://academic.oup.com/hmg/advance-article-pdf/doi/10.1093/hmg/ddac153/45277324/ddac153.pdf; doi:https://doi.org/10.1093/hmg/ddac153 37477803,https://doi.org/10.1007/s11897-023-00615-z,Discovering Distinct Phenotypical Clusters in Heart Failure Across the Ejection Fraction Spectrum: a Systematic Review.,"Meijs C, Handoko ML, Savarese G, Vernooij RWM, Vaartjes I, Banerjee A, Koudstaal S, Brugts JJ, Asselbergs FW, Uijl A.",,Current heart failure reports,2023,2023-07-21,Y,Clustering; Phenotyping; Heart Failure; Machine Learning; Precision Medicine,,,"

Review purpose

This systematic review aims to summarise clustering studies in heart failure (HF) and guide future clinical trial design and implementation in routine clinical practice.

Findings

34 studies were identified (n = 19 in HF with preserved ejection fraction (HFpEF)). There was significant heterogeneity invariables and techniques used. However, 149/165 described clusters could be assigned to one of nine phenotypes: 1) young, low comorbidity burden; 2) metabolic; 3) cardio-renal; 4) atrial fibrillation (AF); 5) elderly female AF; 6) hypertensive-comorbidity; 7) ischaemic-male; 8) valvular disease; and 9) devices. There was room for improvement on important methodological topics for all clustering studies such as external validation and transparency of the modelling process. The large overlap between the phenotypes of the clustering studies shows that clustering is a robust approach for discovering clinically distinct phenotypes. However, future studies should invest in a phenotype model that can be implemented in routine clinical practice and future clinical trial design. HF = heart failure, EF = ejection fraction, HFpEF = heart failure with preserved ejection fraction, HFrEF = heart failure with reduced ejection fraction, CKD = chronic kidney disease, AF = atrial fibrillation, IHD = ischaemic heart disease, CAD = coronary artery disease, ICD = implantable cardioverter-defibrillator, CRT = cardiac resynchronization therapy, NT-proBNP = N-terminal pro b-type natriuretic peptide, BMI = Body Mass Index, COPD = Chronic obstructive pulmonary disease.",,pdf:https://link.springer.com/content/pdf/10.1007/s11897-023-00615-z.pdf; doi:https://doi.org/10.1007/s11897-023-00615-z; html:https://europepmc.org/articles/PMC10589200; pdf:https://europepmc.org/articles/PMC10589200?pdf=render +35796550,https://doi.org/10.1093/hmg/ddac153,The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians: a Mendelian randomization study.,"Borges MC, Haycock P, Zheng J, Hemani G, Howe LJ, Schmidt AF, Staley JR, Lumbers RT, Henry A, Lemaitre RN, Gaunt TR, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA.",,Human molecular genetics,2022,2022-11-01,N,,,,"Despite early interest, the evidence linking fatty acids to cardiovascular diseases (CVDs) remains controversial. We used Mendelian randomization to explore the involvement of polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids biosynthesis in the etiology of several CVD endpoints in up to 1 153 768 European (maximum 123 668 cases) and 212 453 East Asian (maximum 29 319 cases) ancestry individuals. As instruments, we selected single nucleotide polymorphisms mapping to genes with well-known roles in PUFA (i.e. FADS1/2 and ELOVL2) and MUFA (i.e. SCD) biosynthesis. Our findings suggest that higher PUFA biosynthesis rate (proxied by rs174576 near FADS1/2) is related to higher odds of multiple CVDs, particularly ischemic stroke, peripheral artery disease and venous thromboembolism, whereas higher MUFA biosynthesis rate (proxied by rs603424 near SCD) is related to lower odds of coronary artery disease among Europeans. Results were unclear for East Asians as most effect estimates were imprecise. By triangulating multiple approaches (i.e. uni-/multi-variable Mendelian randomization, a phenome-wide scan, genetic colocalization and within-sibling analyses), our results are compatible with higher low-density lipoprotein (LDL) cholesterol (and possibly glucose) being a downstream effect of higher PUFA biosynthesis rate. Our findings indicate that PUFA and MUFA biosynthesis are involved in the etiology of CVDs and suggest LDL cholesterol as a potential mediating trait between PUFA biosynthesis and CVDs risk.",,pdf:https://academic.oup.com/hmg/advance-article-pdf/doi/10.1093/hmg/ddac153/45277324/ddac153.pdf; doi:https://doi.org/10.1093/hmg/ddac153 +35089148,https://doi.org/10.2196/28095,The Association Between Home Stay and Symptom Severity in Major Depressive Disorder: Preliminary Findings From a Multicenter Observational Study Using Geolocation Data From Smartphones.,"Laiou P, Kaliukhovich DA, Folarin AA, Ranjan Y, Rashid Z, Conde P, Stewart C, Sun S, Zhang Y, Matcham F, Ivan A, Lavelle G, Siddi S, Lamers F, Penninx BW, Haro JM, Annas P, Cummins N, Vairavan S, Manyakov NV, Narayan VA, Dobson RJ, Hotopf M, RADAR-CNS.",,JMIR mHealth and uHealth,2022,2022-01-28,Y,GPS; Mobile phone; Major Depressive Disorder; Smartphone; Phq-8; Home Stay,,,"

Background

Most smartphones and wearables are currently equipped with location sensing (using GPS and mobile network information), which enables continuous location tracking of their users. Several studies have reported that various mobility metrics, as well as home stay, that is, the amount of time an individual spends at home in a day, are associated with symptom severity in people with major depressive disorder (MDD). Owing to the use of small and homogeneous cohorts of participants, it is uncertain whether the findings reported in those studies generalize to a broader population of individuals with MDD symptoms.

Objective

The objective of this study is to examine the relationship between the overall severity of depressive symptoms, as assessed by the 8-item Patient Health Questionnaire, and median daily home stay over the 2 weeks preceding the completion of a questionnaire in individuals with MDD.

Methods

We used questionnaire and geolocation data of 164 participants with MDD collected in the observational Remote Assessment of Disease and Relapse-Major Depressive Disorder study. The participants were recruited from three study sites: King's College London in the United Kingdom (109/164, 66.5%); Vrije Universiteit Medisch Centrum in Amsterdam, the Netherlands (17/164, 10.4%); and Centro de Investigación Biomédica en Red in Barcelona, Spain (38/164, 23.2%). We used a linear regression model and a resampling technique (n=100 draws) to investigate the relationship between home stay and the overall severity of MDD symptoms. Participant age at enrollment, gender, occupational status, and geolocation data quality metrics were included in the model as additional explanatory variables. The 95% 2-sided CIs were used to evaluate the significance of model variables.

Results

Participant age and severity of MDD symptoms were found to be significantly related to home stay, with older (95% CI 0.161-0.325) and more severely affected individuals (95% CI 0.015-0.184) spending more time at home. The association between home stay and symptoms severity appeared to be stronger on weekdays (95% CI 0.023-0.178, median 0.098; home stay: 25th-75th percentiles 17.8-22.8, median 20.9 hours a day) than on weekends (95% CI -0.079 to 0.149, median 0.052; home stay: 25th-75th percentiles 19.7-23.5, median 22.3 hours a day). Furthermore, we found a significant modulation of home stay by occupational status, with employment reducing home stay (employed participants: 25th-75th percentiles 16.1-22.1, median 19.7 hours a day; unemployed participants: 25th-75th percentiles 20.4-23.5, median 22.6 hours a day).

Conclusions

Our findings suggest that home stay is associated with symptom severity in MDD and demonstrate the importance of accounting for confounding factors in future studies. In addition, they illustrate that passive sensing of individuals with depression is feasible and could provide clinically relevant information to monitor the course of illness in patients with MDD.",,pdf:https://mhealth.jmir.org/2022/1/e28095/PDF; doi:https://doi.org/10.2196/28095; html:https://europepmc.org/articles/PMC8838593 36692937,https://doi.org/10.2196/42866,The Feasibility of Implementing Remote Measurement Technologies in Psychological Treatment for Depression: Mixed Methods Study on Engagement.,"de Angel V, Adeleye F, Zhang Y, Cummins N, Munir S, Lewis S, Laporta Puyal E, Matcham F, Sun S, Folarin AA, Ranjan Y, Conde P, Rashid Z, Dobson R, Hotopf M.",,JMIR mental health,2023,2023-01-24,Y,Depression; Mobile phone; Anxiety; Smartphone; Mhealth; Mobile Health; Wearable Devices; Digital Health; Digital Phenotyping; Passive Sensing,,,"

Background

Remote measurement technologies (RMTs) such as smartphones and wearables can help improve treatment for depression by providing objective, continuous, and ecologically valid insights into mood and behavior. Engagement with RMTs is varied and highly context dependent; however, few studies have investigated their feasibility in the context of treatment.

Objective

A mixed methods design was used to evaluate engagement with active and passive data collection via RMT in people with depression undergoing psychotherapy. We evaluated the effects of treatment on 2 different types of engagement: study attrition (engagement with study protocol) and patterns of missing data (engagement with digital devices), which we termed data availability. Qualitative interviews were conducted to help interpret the differences in engagement.

Methods

A total of 66 people undergoing psychological therapy for depression were followed up for 7 months. Active data were gathered from weekly questionnaires and speech and cognitive tasks, and passive data were gathered from smartphone sensors and a Fitbit (Fitbit Inc) wearable device.

Results

The overall retention rate was 60%. Higher-intensity treatment (χ21=4.6; P=.03) and higher baseline anxiety (t56.28=-2.80, 2-tailed; P=.007) were associated with attrition, but depression severity was not (t50.4=-0.18; P=.86). A trend toward significance was found for the association between longer treatments and increased attrition (U=339.5; P=.05). Data availability was higher for active data than for passive data initially but declined at a sharper rate (90%-30% drop in 7 months). As for passive data, wearable data availability fell from a maximum of 80% to 45% at 7 months but showed higher overall data availability than smartphone-based data, which remained stable at the range of 20%-40% throughout. Missing data were more prevalent among GPS location data, followed by among Bluetooth data, then among accelerometry data. As for active data, speech and cognitive tasks had lower completion rates than clinical questionnaires. The participants in treatment provided less Fitbit data but more active data than those on the waiting list.

Conclusions

Different data streams showed varied patterns of missing data, despite being gathered from the same device. Longer and more complex treatments and clinical characteristics such as higher baseline anxiety may reduce long-term engagement with RMTs, and different devices may show opposite patterns of missingness during treatment. This has implications for the scalability and uptake of RMTs in health care settings, the generalizability and accuracy of the data collected by these methods, feature construction, and the appropriateness of RMT use in the long term.",,pdf:https://mental.jmir.org/2023/1/e42866/PDF; doi:https://doi.org/10.2196/42866; html:https://europepmc.org/articles/PMC9906314 38214281,https://doi.org/10.1161/jaha.123.031646,Acute Coronary Syndrome Subphenotypes Based on Repeated Biomarker Measurements in Relation to Long-Term Mortality Risk.,"de Bakker M, Scholte NTB, Oemrawsingh RM, Umans VA, Kietselaer B, Schotborgh C, Ronner E, Lenderink T, Aksoy I, van der Harst P, Asselbergs FW, Maas A, Oude Ophuis AJ, Krenning B, de Winter RJ, The SHK, Wardeh AJ, Hermans W, Cramer GE, van Schaik RH, de Rijke YB, Akkerhuis KM, Kardys I, Boersma E, BIOMArCS Investigators †.",,Journal of the American Heart Association,2024,2024-01-12,Y,Death; Phenotypes; acute coronary syndrome; Repeated Measurements; Cardiovascular Biomarkers,,,"

Background

We aimed to identify patients with subphenotypes of postacute coronary syndrome (ACS) using repeated measurements of high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 in the year after the index admission, and to investigate their association with long-term mortality risk.

Methods and results

BIOMArCS (BIOMarker Study to Identify the Acute Risk of a Coronary Syndrome) was an observational study of patients with ACS, who underwent high-frequency blood sampling for 1 year. Biomarkers were measured in a median of 16 repeated samples per individual. Cluster analysis was performed to identify biomarker-based subphenotypes in 723 patients without a repeat ACS in the first year. Patients with a repeat ACS (N=36) were considered a separate cluster. Differences in all-cause death were evaluated using accelerated failure time models (median follow-up, 9.1 years; 141 deaths). Three biomarker-based clusters were identified: cluster 1 showed low and stable biomarker concentrations, cluster 2 had elevated concentrations that subsequently decreased, and cluster 3 showed persistently elevated concentrations. The temporal biomarker patterns of patients in cluster 3 were similar to those with a repeat ACS during the first year. Clusters 1 and 2 had a similar and favorable long-term mortality risk. Cluster 3 had the highest mortality risk. The adjusted survival time ratio was 0.64 (95% CI, 0.44-0.93; P=0.018) compared with cluster 1, and 0.71 (95% CI, 0.39-1.32; P=0.281) compared with patients with a repeat ACS.

Conclusions

Patients with subphenotypes of post-ACS with different all-cause mortality risks during long-term follow-up can be identified on the basis of repeatedly measured cardiovascular biomarkers. Patients with persistently elevated biomarkers have the worst outcomes, regardless of whether they experienced a repeat ACS in the first year.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.031646; doi:https://doi.org/10.1161/JAHA.123.031646; html:https://europepmc.org/articles/PMC10926784; pdf:https://europepmc.org/articles/PMC10926784?pdf=render -35089148,https://doi.org/10.2196/28095,The Association Between Home Stay and Symptom Severity in Major Depressive Disorder: Preliminary Findings From a Multicenter Observational Study Using Geolocation Data From Smartphones.,"Laiou P, Kaliukhovich DA, Folarin AA, Ranjan Y, Rashid Z, Conde P, Stewart C, Sun S, Zhang Y, Matcham F, Ivan A, Lavelle G, Siddi S, Lamers F, Penninx BW, Haro JM, Annas P, Cummins N, Vairavan S, Manyakov NV, Narayan VA, Dobson RJ, Hotopf M, RADAR-CNS.",,JMIR mHealth and uHealth,2022,2022-01-28,Y,GPS; Mobile phone; Major Depressive Disorder; Smartphone; Phq-8; Home Stay,,,"

Background

Most smartphones and wearables are currently equipped with location sensing (using GPS and mobile network information), which enables continuous location tracking of their users. Several studies have reported that various mobility metrics, as well as home stay, that is, the amount of time an individual spends at home in a day, are associated with symptom severity in people with major depressive disorder (MDD). Owing to the use of small and homogeneous cohorts of participants, it is uncertain whether the findings reported in those studies generalize to a broader population of individuals with MDD symptoms.

Objective

The objective of this study is to examine the relationship between the overall severity of depressive symptoms, as assessed by the 8-item Patient Health Questionnaire, and median daily home stay over the 2 weeks preceding the completion of a questionnaire in individuals with MDD.

Methods

We used questionnaire and geolocation data of 164 participants with MDD collected in the observational Remote Assessment of Disease and Relapse-Major Depressive Disorder study. The participants were recruited from three study sites: King's College London in the United Kingdom (109/164, 66.5%); Vrije Universiteit Medisch Centrum in Amsterdam, the Netherlands (17/164, 10.4%); and Centro de Investigación Biomédica en Red in Barcelona, Spain (38/164, 23.2%). We used a linear regression model and a resampling technique (n=100 draws) to investigate the relationship between home stay and the overall severity of MDD symptoms. Participant age at enrollment, gender, occupational status, and geolocation data quality metrics were included in the model as additional explanatory variables. The 95% 2-sided CIs were used to evaluate the significance of model variables.

Results

Participant age and severity of MDD symptoms were found to be significantly related to home stay, with older (95% CI 0.161-0.325) and more severely affected individuals (95% CI 0.015-0.184) spending more time at home. The association between home stay and symptoms severity appeared to be stronger on weekdays (95% CI 0.023-0.178, median 0.098; home stay: 25th-75th percentiles 17.8-22.8, median 20.9 hours a day) than on weekends (95% CI -0.079 to 0.149, median 0.052; home stay: 25th-75th percentiles 19.7-23.5, median 22.3 hours a day). Furthermore, we found a significant modulation of home stay by occupational status, with employment reducing home stay (employed participants: 25th-75th percentiles 16.1-22.1, median 19.7 hours a day; unemployed participants: 25th-75th percentiles 20.4-23.5, median 22.6 hours a day).

Conclusions

Our findings suggest that home stay is associated with symptom severity in MDD and demonstrate the importance of accounting for confounding factors in future studies. In addition, they illustrate that passive sensing of individuals with depression is feasible and could provide clinically relevant information to monitor the course of illness in patients with MDD.",,pdf:https://mhealth.jmir.org/2022/1/e28095/PDF; doi:https://doi.org/10.2196/28095; html:https://europepmc.org/articles/PMC8838593 37993464,https://doi.org/10.1038/s41467-023-43434-5,Structure of the N-RNA/P interface indicates mode of L/P recruitment to the nucleocapsid of human metapneumovirus.,"Whitehead JD, Decool H, Leyrat C, Carrique L, Fix J, Eléouët JF, Galloux M, Renner M.",,Nature communications,2023,2023-11-22,Y,,,,"Human metapneumovirus (HMPV) is a major cause of respiratory illness in young children. The HMPV polymerase (L) binds an obligate cofactor, the phosphoprotein (P). During replication and transcription, the L/P complex traverses the viral RNA genome, which is encapsidated within nucleoproteins (N). An essential interaction between N and a C-terminal region of P tethers the L/P polymerase to the template. This N-P interaction is also involved in the formation of cytoplasmic viral factories in infected cells, called inclusion bodies. To define how the polymerase component P recognizes N-encapsidated RNA (N-RNA) we employed cryogenic electron microscopy (cryo-EM) and molecular dynamics simulations, coupled to activity assays and imaging of inclusion bodies in cells. We report a 2.9 Å resolution structure of a triple-complex between multimeric N, bound to both RNA and the C-terminal region of P. Furthermore, we also present cryo-EM structures of assembled N in different oligomeric states, highlighting the plasticity of N. Combined with our functional assays, these structural data delineate in molecular detail how P attaches to N-RNA whilst retaining substantial conformational dynamics. Moreover, the N-RNA-P triple complex structure provides a molecular blueprint for the design of therapeutics to potentially disrupt the attachment of L/P to its template.",,pdf:https://www.nature.com/articles/s41467-023-43434-5.pdf; doi:https://doi.org/10.1038/s41467-023-43434-5; html:https://europepmc.org/articles/PMC10665349; pdf:https://europepmc.org/articles/PMC10665349?pdf=render 37538742,https://doi.org/10.1098/rsos.221469,Bayesian inference of polymerase dynamics over the exclusion process.,"Cavallaro M, Wang Y, Hebenstreit D, Dutta R.",,Royal Society open science,2023,2023-08-02,Y,Gene Expression; Bayesian Statistics; Particle Transport; Non-equilbrium Physics,,,"Transcription is a complex phenomenon that permits the conversion of genetic information into phenotype by means of an enzyme called RNA polymerase, which erratically moves along and scans the DNA template. We perform Bayesian inference over a paradigmatic mechanistic model of non-equilibrium statistical physics, i.e. the asymmetric exclusion processes in the hydrodynamic limit, assuming a Gaussian process prior for the polymerase progression rate as a latent variable. Our framework allows us to infer the speed of polymerases during transcription given their spatial distribution, while avoiding the explicit inversion of the system's dynamics. The results, which show processing rates strongly varying with genomic position and minor role of traffic-like congestion, may have strong implications for the understanding of gene expression.",,doi:https://doi.org/10.1098/rsos.221469; doi:https://doi.org/10.1098/rsos.221469; html:https://europepmc.org/articles/PMC10394410; pdf:https://europepmc.org/articles/PMC10394410?pdf=render 31822919,https://doi.org/10.1093/pubmed/fdz172,"Unmet needs of women with GDM: a health needs assessment in Sandwell, West Midlands.","Plant N, Šumilo D, Chapman R, Webber J, Saravanan P, Nirantharakumar K.",,"Journal of public health (Oxford, England)",2020,2020-11-01,N,United Kingdom; Needs Assessment; Gestational Diabetes,,,"

Background

Gestational diabetes mellitus (GDM) affects over 4% of pregnancies in England. We investigated GDM epidemiology within ethnically diverse population and the current offer of services to women with previous GDM to reduce their type 2 diabetes mellitus (T2DM) risk.

Methods

(i) Analysis of routinely collected maternity data examining GDM incidence and risk factors; (ii) local authority self-assessment questionnaire on public health interventions targeting women with previous GDM and (iii) service development discussions regarding the current pathway and areas for improvement.

Results

Of 9390 births between 2014 and 2018, 6.8% had a record of GDM. High body mass index (BMI), maternal age, and ethnicity (South Asian and some mixed ethnic backgrounds) were independent predictors of GDM. There were no public health commissioned services specifically targeting women with previous GDM. Weaknesses in transition from secondary to primary care and areas for improvement when screening for GDM were identified.

Conclusions

GDM burden in this population was high. Awareness should be raised on the importance of regular glucose testing and lifestyle modification to delay or prevent progression to T2DM, particularly within high risk groups. The potential for health visitors to contribute to this should be explored. Commissioners should review evidence to develop a flexible lifestyle services model to meet the specific needs of these women.",,pdf:https://academic.oup.com/jpubhealth/article-pdf/42/4/e516/34469316/fdz172.pdf; doi:https://doi.org/10.1093/pubmed/fdz172 -33866023,https://doi.org/10.1016/j.oret.2021.04.001,Evolving Treatment Patterns and Outcomes of Neovascular Age-Related Macular Degeneration Over a Decade.,"Schwartz R, Warwick A, Olvera-Barrios A, Pikoula M, Lee AY, Denaxas S, Taylor P, Egan C, Chakravarthy U, Lip PL, Tufail A, of the UK EMR Users Group.",,Ophthalmology. Retina,2021,2021-04-16,N,AMD; Ranibizumab; Anti-vegf; Aflibercept; Electronic Health Records; Etdrs; Early Treatment Diabetic Retinopathy Study,,,"

Purpose

Management of neovascular age-related macular degeneration (nAMD) has evolved over the last decade with several treatment regimens and medications. This study describes the treatment patterns and visual outcomes over 10 years in a large cohort of patients.

Design

Retrospective analysis of electronic health records from 27 National Health Service secondary care healthcare providers in the UK.

Participants

Treatment-naïve patients receiving at least 3 intravitreal anti-vascular endothelial growth factor (VEGF) injections for nAMD in their first 6 months of follow-up were included. Patients with missing data for age or gender and those aged less than 55 years were excluded.

Methods

Eyes with at least 3 years of follow-up were grouped by years of treatment initiation, and 3-year outcomes were compared between the groups. Data were generated during routine clinical care between September 2008 and December 2018.

Main outcome measures

Visual acuity (VA), number of injections, and number of visits.

Results

A total of 15 810 eyes of 13 705 patients receiving 195 104 injections were included. Visual acuity improved from baseline during the first year, but decreased thereafter, resulting in loss of visual gains. This trend remained consistent throughout the past decade. Although an increasing proportion of eyes remained in the driving standard, this was driven by better presenting VA over the decade. The number of injections decreased substantially between the first and subsequent years, from a mean of 6.25 in year 1 to 3 in year 2 and 2.5 in year 3, without improvement over the decade. In a multivariable regression analysis, final VA improved by 0.24 letters for each year since 2008, and younger age and baseline VA were significantly associated with VA at 3 years.

Conclusions

Our findings show that despite improvement in functional VA over the years, primarily driven by improving baseline VA, patients continue to lose vision after the first year of treatment, with only marginal change over the past decade. The data suggest these results may be related to suboptimal treatment patterns, which have not improved over the years. Rethinking treatment strategies may be warranted, possibly on a national level or through the introduction of longer-acting therapies.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165682; doi:https://doi.org/10.1016/j.oret.2021.04.001; html:https://europepmc.org/articles/PMC9165682; pdf:https://europepmc.org/articles/PMC9165682?pdf=render; doi:https://doi.org/10.1016/j.oret.2021.04.001 35748342,https://doi.org/10.1093/ije/dyac130,Linkage of multiple electronic health record datasets using a 'spine linkage' approach compared with all 'pairwise linkages'.,"Blake HA, Sharples LD, Harron K, van der Meulen JH, Walker K.",,International journal of epidemiology,2023,2023-02-01,Y,Electronic Health Records; Record Linkage; Pairwise Linkage; Spine Linkage Approach,,,"

Background

Methods for linking records between two datasets are well established. However, guidance is needed for linking more than two datasets. Using all 'pairwise linkages'-linking each dataset to every other dataset-is the most inclusive, but resource-intensive, approach. The 'spine' approach links each dataset to a designated 'spine dataset', reducing the number of linkages, but potentially reducing linkage quality.

Methods

We compared the pairwise and spine linkage approaches using real-world data on patients undergoing emergency bowel cancer surgery between 31 October 2013 and 30 April 2018. We linked an administrative hospital dataset (Hospital Episode Statistics; HES) capturing patients admitted to hospitals in England, and two clinical datasets comprising patients diagnosed with bowel cancer and patients undergoing emergency bowel surgery.

Results

The spine linkage approach, with HES as the spine dataset, created an analysis cohort of 15 826 patients, equating to 98.3% of the 16 100 patients identified using the pairwise linkage approach. There were no systematic differences in patient characteristics between these analysis cohorts. Associations of patient and tumour characteristics with mortality, complications and length of stay were not sensitive to the linkage approach. When eligibility criteria were applied before linkage, spine linkage included 14 509 patients (90.0% compared with pairwise linkage).

Conclusion

Spine linkage can be used as an efficient alternative to pairwise linkage if case ascertainment in the spine dataset and data quality of linkage variables are high. These aspects should be systematically evaluated in the nominated spine dataset before spine linkage is used to create the analysis cohort.",,pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac130/44245961/dyac130.pdf; doi:https://doi.org/10.1093/ije/dyac130; html:https://europepmc.org/articles/PMC9908066; pdf:https://europepmc.org/articles/PMC9908066?pdf=render +33866023,https://doi.org/10.1016/j.oret.2021.04.001,Evolving Treatment Patterns and Outcomes of Neovascular Age-Related Macular Degeneration Over a Decade.,"Schwartz R, Warwick A, Olvera-Barrios A, Pikoula M, Lee AY, Denaxas S, Taylor P, Egan C, Chakravarthy U, Lip PL, Tufail A, of the UK EMR Users Group.",,Ophthalmology. Retina,2021,2021-04-16,N,AMD; Ranibizumab; Anti-vegf; Aflibercept; Electronic Health Records; Etdrs; Early Treatment Diabetic Retinopathy Study,,,"

Purpose

Management of neovascular age-related macular degeneration (nAMD) has evolved over the last decade with several treatment regimens and medications. This study describes the treatment patterns and visual outcomes over 10 years in a large cohort of patients.

Design

Retrospective analysis of electronic health records from 27 National Health Service secondary care healthcare providers in the UK.

Participants

Treatment-naïve patients receiving at least 3 intravitreal anti-vascular endothelial growth factor (VEGF) injections for nAMD in their first 6 months of follow-up were included. Patients with missing data for age or gender and those aged less than 55 years were excluded.

Methods

Eyes with at least 3 years of follow-up were grouped by years of treatment initiation, and 3-year outcomes were compared between the groups. Data were generated during routine clinical care between September 2008 and December 2018.

Main outcome measures

Visual acuity (VA), number of injections, and number of visits.

Results

A total of 15 810 eyes of 13 705 patients receiving 195 104 injections were included. Visual acuity improved from baseline during the first year, but decreased thereafter, resulting in loss of visual gains. This trend remained consistent throughout the past decade. Although an increasing proportion of eyes remained in the driving standard, this was driven by better presenting VA over the decade. The number of injections decreased substantially between the first and subsequent years, from a mean of 6.25 in year 1 to 3 in year 2 and 2.5 in year 3, without improvement over the decade. In a multivariable regression analysis, final VA improved by 0.24 letters for each year since 2008, and younger age and baseline VA were significantly associated with VA at 3 years.

Conclusions

Our findings show that despite improvement in functional VA over the years, primarily driven by improving baseline VA, patients continue to lose vision after the first year of treatment, with only marginal change over the past decade. The data suggest these results may be related to suboptimal treatment patterns, which have not improved over the years. Rethinking treatment strategies may be warranted, possibly on a national level or through the introduction of longer-acting therapies.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165682; doi:https://doi.org/10.1016/j.oret.2021.04.001; html:https://europepmc.org/articles/PMC9165682; pdf:https://europepmc.org/articles/PMC9165682?pdf=render; doi:https://doi.org/10.1016/j.oret.2021.04.001 32651323,https://doi.org/10.3233/jad-200338,"Alzheimer's Disease Susceptibility Gene Apolipoprotein E (APOE) and Blood Biomarkers in UK Biobank (N = 395,769).","Ferguson AC, Tank R, Lyall LM, Ward J, Celis-Morales C, Strawbridge R, Ho F, Whelan CD, Gill J, Welsh P, Anderson JJ, Mark PB, Mackay DF, Smith DJ, Pell JP, Cavanagh J, Sattar N, Lyall DM.",,Journal of Alzheimer's disease : JAD,2020,2020-01-01,N,Cholesterol; apoE; Alzheimer’s disease; Dementia; Uk Biobank,,,"

Background

Alzheimer's disease (AD) is a neurodegenerative condition where the underlying etiology is still unclear. Investigating the potential influence of apolipoprotein E (APOE), a major genetic risk factor, on common blood biomarkers could provide a greater understanding of the mechanisms of AD and dementia risk.

Objective

Our objective was to conduct the largest (to date) single-protocol investigation of blood biomarkers in the context of APOE genotype, in UK Biobank.

Methods

After quality control and exclusions, data on 395,769 participants of White European ancestry were available for analysis. Linear regressions were used to test potential associations between APOE genotypes and biomarkers.

Results

Several biomarkers significantly associated with APOEɛ4 'risk' and ɛ2 'protective' genotypes (versus neutral ɛ3/ɛ3). Most associations supported previous data: for example, ɛ4 genotype was associated with elevated low-density lipoprotein cholesterol (LDL) (standardized beta [b] = 0.150 standard deviations [SDs] per allele, p < 0.001) and ɛ2 with lower LDL (b = -0.456 SDs, p < 0.001). There were however instances of associations found in unexpected directions: e.g., ɛ4 and increased insulin-like growth factor (IGF-1) (b = 0.017, p < 0.001) where lower levels have been previously suggested as an AD risk factor.

Conclusion

These findings highlight biomarker differences in non-demented people at genetic risk for dementia. The evidence herein supports previous hypotheses of involvement from cardiometabolic and neuroinflammatory pathways.",,pdf:https://eprints.gla.ac.uk/217500/1/217500.pdf; doi:https://doi.org/10.3233/JAD-200338 36701266,https://doi.org/10.1371/journal.pmed.1004036,"Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.","Vinther JL, Cadman T, Avraam D, Ekstrøm CT, Sørensen TIA, Elhakeem A, Santos AC, Pinot de Moira A, Heude B, Iñiguez C, Pizzi C, Simons E, Voerman E, Corpeleijn E, Zariouh F, Santorelli G, Inskip HM, Barros H, Carson J, Harris JR, Nader JL, Ronkainen J, Strandberg-Larsen K, Santa-Marina L, Calas L, Cederkvist L, Popovic M, Charles MA, Welten M, Vrijheid M, Azad M, Subbarao P, Burton P, Mandhane PJ, Huang RC, Wilson RC, Haakma S, Fernández-Barrés S, Turvey S, Santos S, Tough SC, Tough SC, Sebert S, Moraes TJ, Salika T, Jaddoe VWV, Lawlor DA, Nybo Andersen AM.",,PLoS medicine,2023,2023-01-26,Y,,,,"

Background

Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence.

Methods and findings

We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries.

Conclusions

This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004036&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004036; html:https://europepmc.org/articles/PMC9879424; pdf:https://europepmc.org/articles/PMC9879424?pdf=render -37735103,https://doi.org/10.1136/bmjresp-2023-001895,"Preterm birth, birth weight, infant weight gain and their associations with childhood asthma and spirometry: a cross-sectional observational study in Nairobi, Kenya.","Meme H, Amukoye E, Bowyer C, Chakaya J, Dobson R, Fuld J, Gray CM, Kiplimo R, Lesosky M, Mortimer K, Ndombi A, Obasi A, Orina F, Quint JK, Semple S, West SE, Zurba L, Devereux G.",,BMJ open respiratory research,2023,2023-09-01,Y,Asthma; Paediatric Lung Disaese; Asthma Epidemiology,,,"

Background

In sub-Saharan Africa, the origins of asthma and high prevalence of abnormal lung function remain unclear. In high-income countries (HICs), associations between birth measurements and childhood asthma and lung function highlight the importance of antenatal and early life factors in the aetiology of asthma and abnormal lung function in children. We present here the first study in sub-Saharan Africa to relate birth characteristics to both childhood respiratory symptoms and lung function.

Methods

Children attending schools in two socioeconomically contrasting but geographically close areas of Nairobi, Kenya, were recruited to a cross-sectional study of childhood asthma and lung function. Questionnaires quantified respiratory symptoms and preterm birth; lung function was measured by spirometry; and parents were invited to bring the child's immunisation booklet containing records of birth weight and serial weights in the first year.

Results

2373 children participated, 52% girls, median age (IQR), 10 years (8-13). Spirometry data were available for 1622. Child immunisation booklets were available for 500 and birth weight and infant weight gain data were available for 323 and 494 children, respectively. In multivariable analyses, preterm birth was associated with the childhood symptoms 'wheeze in the last 12 months'; OR 1.64, (95% CI 1.03 to 2.62), p=0.038; and 'trouble breathing' 3.18 (95% CI 2.27 to 4.45), p<0.001. Birth weight (kg) was associated with forced expiratory volume in 1 s z-score, regression coefficient (β) 0.30 (0.08, 0.52), p=0.008, FVC z-score 0.29 (95% CI 0.08 to 0.51); p=0.008 and restricted spirometry, OR 0.11 (95% CI 0.02 to 0.78), p=0.027.

Conclusion

These associations are in keeping with those in HICs and highlight antenatal factors in the aetiology of asthma and lung function abnormalities in sub-Saharan Africa.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/10/1/e001895.full.pdf; doi:https://doi.org/10.1136/bmjresp-2023-001895; html:https://europepmc.org/articles/PMC10514609; pdf:https://europepmc.org/articles/PMC10514609?pdf=render 32142356,https://doi.org/10.1164/rccm.201902-0286oc,"Prenatal, Early-Life, and Childhood Exposure to Air Pollution and Lung Function: The ALSPAC Cohort.","Cai Y, Hansell AL, Granell R, Blangiardo M, Zottoli M, Fecht D, Gulliver J, Henderson AJ, Elliott P.",,American journal of respiratory and critical care medicine,2020,2020-07-01,N,Air pollution; Children; Traffic; Alspac; Respiratory Health,,,"Rationale: Exposure to air pollution during intrauterine development and through childhood may have lasting effects on respiratory health.Objectives: To investigate lung function at ages 8 and 15 years in relation to air pollution exposures during pregnancy, infancy, and childhood in a UK population-based birth cohort.Methods: Individual exposures to source-specific particulate matter ≤10 μm in aerodynamic diameter (PM10) during each trimester, 0-6 months, 7-12 months (1990-1993), and up to age 15 years (1991-2008) were examined in relation to FEV1% predicted and FVC% predicted at ages 8 (n = 5,276) and 15 (n = 3,446) years using linear regression models adjusted for potential confounders. A profile regression model was used to identify sensitive time periods.Measurements and Main Results: We did not find clear evidence of a sensitive exposure period for PM10 from road traffic. At age 8 years, 1 μg/m3 higher exposure during the first trimester was associated with lower FEV1% predicted (-0.826; 95% confidence interval [CI], -1.357 to -0.296) and FVC% predicted (-0.817; 95% CI, -1.357 to -0.276), but similar associations were seen for exposures for other trimesters, 0-6 months, 7-12 months, and 0-7 years. Associations were stronger among boys, as well as children whose mother had a lower education level or smoked during pregnancy. For PM10 from all sources, the third trimester was associated with lower FVC% predicted (-1.312; 95% CI, -2.100 to -0.525). At age 15 years, no adverse associations with lung function were seen.Conclusions: Exposure to road-traffic PM10 during pregnancy may result in small but significant reductions in lung function at age 8 years.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328307; doi:https://doi.org/10.1164/rccm.201902-0286OC; html:https://europepmc.org/articles/PMC7328307; pdf:https://europepmc.org/articles/PMC7328307?pdf=render; doi:https://doi.org/10.1164/rccm.201902-0286oc 30745170,https://doi.org/10.1016/j.ebiom.2019.02.005,"Identification of novel genome-wide associations for suicidality in UK Biobank, genetic correlation with psychiatric disorders and polygenic association with completed suicide.","Strawbridge RJ, Ward J, Ferguson A, Graham N, Shaw RJ, Cullen B, Pearsall R, Lyall LM, Johnston KJA, Niedzwiedz CL, Pell JP, Mackay D, Martin JL, Lyall DM, Bailey MES, Smith DJ.",,EBioMedicine,2019,2019-02-08,Y,,Understanding the Causes of Disease,,"

Background

Suicide is a major issue for global public health. Suicidality describes a broad spectrum of thoughts and behaviours, some of which are common in the general population. Although suicide results from a complex interaction of multiple social and psychological factors, predisposition to suicidality is at least partly genetic.

Methods

Ordinal genome-wide association study of suicidality in the UK Biobank cohort comparing: 'no suicidality' controls (N = 83,557); 'thoughts that life was not worth living' (N = 21,063); 'ever contemplated self-harm' (N = 13,038); 'act of deliberate self-harm in the past' (N = 2498); and 'previous suicide attempt' (N = 2666).

Outcomes

We identified three novel genome-wide significant loci for suicidality (on chromosomes nine, 11 and 13) and moderate-to-strong genetic correlations between suicidality and a range of psychiatric disorders, most notably depression (rg 0·81).

Interpretation

These findings provide new information about genetic variants relating to increased risk of suicidal thoughts and behaviours. Future work should assess the extent to which polygenic risk scores for suicidality, in combination with non-genetic risk factors, may be useful for stratified approaches to suicide prevention at a population level. FUND: UKRI Innovation-HDR-UK Fellowship (MR/S003061/1). MRC Mental Health Data Pathfinder Award (MC_PC_17217). MRC Doctoral Training Programme Studentship at the University of Glasgow (MR/K501335/1). MRC Doctoral Training Programme Studentship at the Universities of Glasgow and Edinburgh. UKRI Innovation Fellowship (MR/R024774/1).",,pdf:http://www.thelancet.com/article/S2352396419300775/pdf; doi:https://doi.org/10.1016/j.ebiom.2019.02.005; html:https://europepmc.org/articles/PMC6442001; pdf:https://europepmc.org/articles/PMC6442001?pdf=render +37735103,https://doi.org/10.1136/bmjresp-2023-001895,"Preterm birth, birth weight, infant weight gain and their associations with childhood asthma and spirometry: a cross-sectional observational study in Nairobi, Kenya.","Meme H, Amukoye E, Bowyer C, Chakaya J, Dobson R, Fuld J, Gray CM, Kiplimo R, Lesosky M, Mortimer K, Ndombi A, Obasi A, Orina F, Quint JK, Semple S, West SE, Zurba L, Devereux G.",,BMJ open respiratory research,2023,2023-09-01,Y,Asthma; Paediatric Lung Disaese; Asthma Epidemiology,,,"

Background

In sub-Saharan Africa, the origins of asthma and high prevalence of abnormal lung function remain unclear. In high-income countries (HICs), associations between birth measurements and childhood asthma and lung function highlight the importance of antenatal and early life factors in the aetiology of asthma and abnormal lung function in children. We present here the first study in sub-Saharan Africa to relate birth characteristics to both childhood respiratory symptoms and lung function.

Methods

Children attending schools in two socioeconomically contrasting but geographically close areas of Nairobi, Kenya, were recruited to a cross-sectional study of childhood asthma and lung function. Questionnaires quantified respiratory symptoms and preterm birth; lung function was measured by spirometry; and parents were invited to bring the child's immunisation booklet containing records of birth weight and serial weights in the first year.

Results

2373 children participated, 52% girls, median age (IQR), 10 years (8-13). Spirometry data were available for 1622. Child immunisation booklets were available for 500 and birth weight and infant weight gain data were available for 323 and 494 children, respectively. In multivariable analyses, preterm birth was associated with the childhood symptoms 'wheeze in the last 12 months'; OR 1.64, (95% CI 1.03 to 2.62), p=0.038; and 'trouble breathing' 3.18 (95% CI 2.27 to 4.45), p<0.001. Birth weight (kg) was associated with forced expiratory volume in 1 s z-score, regression coefficient (β) 0.30 (0.08, 0.52), p=0.008, FVC z-score 0.29 (95% CI 0.08 to 0.51); p=0.008 and restricted spirometry, OR 0.11 (95% CI 0.02 to 0.78), p=0.027.

Conclusion

These associations are in keeping with those in HICs and highlight antenatal factors in the aetiology of asthma and lung function abnormalities in sub-Saharan Africa.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/10/1/e001895.full.pdf; doi:https://doi.org/10.1136/bmjresp-2023-001895; html:https://europepmc.org/articles/PMC10514609; pdf:https://europepmc.org/articles/PMC10514609?pdf=render 37653496,https://doi.org/10.1186/s12933-023-01963-9,Empagliflozin is associated with lower cardiovascular risk compared with dipeptidyl peptidase-4 inhibitors in adults with and without cardiovascular disease: EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study results from Europe and Asia.,"Vistisen D, Carstensen B, Elisabetta P, Lanzinger S, Tan EC, Yabe D, Kim DJ, Sheu WH, Melzer-Cohen C, Holl RW, Núñez J, Ha KH, Halvorsen S, Langslet G, Karasik A, Nyström T, Niskanen L, Guleria S, Klement R, Carrasco M, Foersch J, Shay C, Koeneman L, Hoti F, Farsani SF, Khunti K, Zaccardi F, Subramanian A, Nirantharakumar K, EMPRISE EU, East Asia Study Group.",,Cardiovascular diabetology,2023,2023-08-31,Y,Cardiovascular disease; Type 2 diabetes; Heart Failure; Comparative Effectiveness; Dipeptidyl Peptidase-4 Inhibitors; Empagliflozin,,,"

Background

Studies that have reported lower risk for cardiovascular outcomes in users of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) are limited by residual cofounding and lack of information on prior cardiovascular disease (CVD). This study compared risk of cardiovascular events in patients within routine care settings in Europe and Asia with type 2 diabetes (T2D) initiating empagliflozin compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) stratified by pre-existing CVD and history of heart failure (HF).

Methods and results

Adults initiating empagliflozin and DPP-4i in 2014-2018/19 from 11 countries in Europe and Asia were compared using propensity score matching and Cox proportional hazards regression to assess differences in rates of primary outcomes: hospitalisation for heart failure (HHF), myocardial infarction (MI), stroke; and secondary outcomes: cardiovascular mortality (CVM), coronary revascularisation procedure, composite outcome including HHF or CVM, and 3-point major adverse cardiovascular events (MACE: MI, stroke and CVM). Country-specific results were meta-analysed and pooled hazard ratios (HR) with 95% confidence intervals (CI) from random-effects models are presented. In total, 85,244 empagliflozin/DPP4i PS-matched patient pairs were included with overall mean follow-up of 0.7 years. Among those with pre-existing CVD, lower risk was observed for HHF (HR 0.74; 95% CI 0.64-0.86), CVM (HR 0.55; 95% CI 0.38-0.80), HHF or CVM (HR 0.57; 95% CI 0.48-0.67) and stroke (HR 0.79; 95% CI 0.67-0.94) in patients initiating empagliflozin vs DPP-4i. Similar patterns were observed among patients without pre-existing CVD and those with and without pre-existing HF.

Conclusion

These results from diverse patient populations in routine care settings across Europe and Asia demonstrate that initiation of empagliflozin compared to DPP-4i results in favourable cardioprotective effects regardless of pre-existing CVD or HF status.",,pdf:https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-023-01963-9; doi:https://doi.org/10.1186/s12933-023-01963-9; html:https://europepmc.org/articles/PMC10472675; pdf:https://europepmc.org/articles/PMC10472675?pdf=render -35743743,https://doi.org/10.3390/jpm12060958,Immune Cell Networks Uncover Candidate Biomarkers of Melanoma Immunotherapy Response.,"Vo DHT, McGleave G, Overton IM.",,Journal of personalized medicine,2022,2022-06-11,Y,Melanoma; Immunotherapy; Ovarian carcinoma; Biomarker; Network Biology; Systems Immunology; Nivolumab; Systems Medicine; Immune Checkpoint; Precision Oncology,,,"The therapeutic activation of antitumour immunity by immune checkpoint inhibitors (ICIs) is a significant advance in cancer medicine, not least due to the prospect of long-term remission. However, many patients are unresponsive to ICI therapy and may experience serious side effects; companion biomarkers are urgently needed to help inform ICI prescribing decisions. We present the IMMUNETS networks of gene coregulation in five key immune cell types and their application to interrogate control of nivolumab response in advanced melanoma cohorts. The results evidence a role for each of the IMMUNETS cell types in ICI response and in driving tumour clearance with independent cohorts from TCGA. As expected, 'immune hot' status, including T cell proliferation, correlates with response to first-line ICI therapy. Genes regulated in NK, dendritic, and B cells are the most prominent discriminators of nivolumab response in patients that had previously progressed on another ICI. Multivariate analysis controlling for tumour stage and age highlights CIITA and IKZF3 as candidate prognostic biomarkers. IMMUNETS provide a resource for network biology, enabling context-specific analysis of immune components in orthogonal datasets. Overall, our results illuminate the relationship between the tumour microenvironment and clinical trajectories, with potential implications for precision medicine.",,pdf:https://www.mdpi.com/2075-4426/12/6/958/pdf?version=1655284846; doi:https://doi.org/10.3390/jpm12060958; html:https://europepmc.org/articles/PMC9225330; pdf:https://europepmc.org/articles/PMC9225330?pdf=render 35004880,https://doi.org/10.3389/fcvm.2021.763361,"Cardiac Magnetic Resonance Radiomics Reveal Differential Impact of Sex, Age, and Vascular Risk Factors on Cardiac Structure and Myocardial Tissue.","Raisi-Estabragh Z, Jaggi A, Gkontra P, McCracken C, Aung N, Munroe PB, Neubauer S, Harvey NC, Lekadir K, Petersen SE.",,Frontiers in cardiovascular medicine,2021,2021-12-22,Y,Hypertension; Diabetes; Smoking; Sex differences; High cholesterol; Cardiovascular Magnetic Resonance; Healthy Individuals; Radiomics,,,"Background: Cardiovascular magnetic resonance (CMR) radiomics analysis provides multiple quantifiers of ventricular shape and myocardial texture, which may be used for detailed cardiovascular phenotyping. Objectives: We studied variation in CMR radiomics phenotypes by age and sex in healthy UK Biobank participants. Then, we examined independent associations of classical vascular risk factors (VRFs: smoking, diabetes, hypertension, high cholesterol) with CMR radiomics features, considering potential sex and age differential relationships. Design: Image acquisition was with 1.5 Tesla scanners (MAGNETOM Aera, Siemens). Three regions of interest were segmented from short axis stack images using an automated pipeline: right ventricle, left ventricle, myocardium. We extracted 237 radiomics features from each study using Pyradiomics. In a healthy subset of participants (n = 14,902) without cardiovascular disease or VRFs, we estimated independent associations of age and sex with each radiomics feature using linear regression models adjusted for body size. We then created a sample comprising individuals with at least one VRF matched to an equal number of healthy participants (n = 27,400). We linearly modelled each radiomics feature against age, sex, body size, and all the VRFs. Bonferroni adjustment for multiple testing was applied to all p-values. To aid interpretation, we organised the results into six feature clusters. Results: Amongst the healthy subset, men had larger ventricles with dimmer and less texturally complex myocardium than women. Increasing age was associated with smaller ventricles and greater variation in myocardial intensities. Broadly, all the VRFs were associated with dimmer, less varied signal intensities, greater uniformity of local intensity levels, and greater relative presence of low signal intensity areas within the myocardium. Diabetes and high cholesterol were also associated with smaller ventricular size, this association was of greater magnitude in men than women. The pattern of alteration of radiomics features with the VRFs was broadly consistent in men and women. However, the associations between intensity based radiomics features with both diabetes and hypertension were more prominent in women than men. Conclusions: We demonstrate novel independent associations of sex, age, and major VRFs with CMR radiomics phenotypes. Further studies into the nature and clinical significance of these phenotypes are needed.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.763361/pdf; doi:https://doi.org/10.3389/fcvm.2021.763361; html:https://europepmc.org/articles/PMC8727756; pdf:https://europepmc.org/articles/PMC8727756?pdf=render +35743743,https://doi.org/10.3390/jpm12060958,Immune Cell Networks Uncover Candidate Biomarkers of Melanoma Immunotherapy Response.,"Vo DHT, McGleave G, Overton IM.",,Journal of personalized medicine,2022,2022-06-11,Y,Melanoma; Immunotherapy; Ovarian carcinoma; Biomarker; Network Biology; Systems Immunology; Nivolumab; Systems Medicine; Immune Checkpoint; Precision Oncology,,,"The therapeutic activation of antitumour immunity by immune checkpoint inhibitors (ICIs) is a significant advance in cancer medicine, not least due to the prospect of long-term remission. However, many patients are unresponsive to ICI therapy and may experience serious side effects; companion biomarkers are urgently needed to help inform ICI prescribing decisions. We present the IMMUNETS networks of gene coregulation in five key immune cell types and their application to interrogate control of nivolumab response in advanced melanoma cohorts. The results evidence a role for each of the IMMUNETS cell types in ICI response and in driving tumour clearance with independent cohorts from TCGA. As expected, 'immune hot' status, including T cell proliferation, correlates with response to first-line ICI therapy. Genes regulated in NK, dendritic, and B cells are the most prominent discriminators of nivolumab response in patients that had previously progressed on another ICI. Multivariate analysis controlling for tumour stage and age highlights CIITA and IKZF3 as candidate prognostic biomarkers. IMMUNETS provide a resource for network biology, enabling context-specific analysis of immune components in orthogonal datasets. Overall, our results illuminate the relationship between the tumour microenvironment and clinical trajectories, with potential implications for precision medicine.",,pdf:https://www.mdpi.com/2075-4426/12/6/958/pdf?version=1655284846; doi:https://doi.org/10.3390/jpm12060958; html:https://europepmc.org/articles/PMC9225330; pdf:https://europepmc.org/articles/PMC9225330?pdf=render 36469091,https://doi.org/10.1093/ageing/afac252,Prevalence and outcomes of atrial fibrillation in older people living in care homes in Wales: a routine data linkage study 2003-2018.,"Ritchie LA, Harrison SL, Penson PE, Akbari A, Torabi F, Hollinghurst J, Harris D, Oke OB, Akpan A, Halcox JP, Rodgers SE, Lip GYH, Lane DA.",,Age and ageing,2022,2022-12-01,N,Prevalence; Atrial fibrillation; Stroke; Older People; Care Homes; Health Outcomes,,,"

Objective

To determine atrial fibrillation (AF) prevalence and temporal trends, and examine associations between AF and risk of adverse health outcomes in older care home residents.

Methods

Retrospective cohort study using anonymised linked data from the Secure Anonymised Information Linkage Databank on CARE home residents in Wales with AF (SAIL CARE-AF) between 2003 and 2018. Fine-Gray competing risk models were used to estimate the risk of health outcomes with mortality as a competing risk. Cox regression analyses were used to estimate the risk of mortality.

Results

There were 86,602 older care home residents (median age 86.0 years [interquartile range 80.8-90.6]) who entered a care home between 2003 and 2018. When the pre-care home entry data extraction was standardised, the overall prevalence of AF was 17.4% (95% confidence interval 17.1-17.8) between 2010 and 2018. There was no significant change in the age- and sex-standardised prevalence of AF from 16.8% (15.9-17.9) in 2010 to 17.0% (16.1-18.0) in 2018. Residents with AF had a significantly higher risk of cardiovascular mortality (adjusted hazard ratio [HR] 1.27 [1.17-1.37], P < 0.001), all-cause mortality (adjusted HR 1.14 [1.11-1.17], P < 0.001), ischaemic stroke (adjusted sub-distribution HR 1.55 [1.36-1.76], P < 0.001) and cardiovascular hospitalisation (adjusted sub-distribution HR 1.28 [1.22-1.34], P < 0.001).

Conclusions

Older care home residents with AF have an increased risk of adverse health outcomes, even when higher mortality rates and other confounders are accounted for. This re-iterates the need for appropriate oral anticoagulant prescription and optimal management of cardiovascular co-morbidities, irrespective of frailty status and predicted life expectancy.",,pdf:https://academic.oup.com/ageing/article-pdf/51/12/afac252/47589319/afac252.pdf; doi:https://doi.org/10.1093/ageing/afac252 30940752,https://doi.org/10.1136/bmjopen-2018-023232,Using natural language processing to extract structured epilepsy data from unstructured clinic letters: development and validation of the ExECT (extraction of epilepsy clinical text) system.,"Fonferko-Shadrach B, Lacey AS, Roberts A, Akbari A, Thompson S, Ford DV, Lyons RA, Rees MI, Pickrell WO.",,BMJ open,2019,2019-04-01,Y,Epilepsy; Validation; Information Extraction; Natural Language Processing,Applied Analytics,,"

Objective

Routinely collected healthcare data are a powerful research resource but often lack detailed disease-specific information that is collected in clinical free text, for example, clinic letters. We aim to use natural language processing techniques to extract detailed clinical information from epilepsy clinic letters to enrich routinely collected data.

Design

We used the general architecture for text engineering (GATE) framework to build an information extraction system, ExECT (extraction of epilepsy clinical text), combining rule-based and statistical techniques. We extracted nine categories of epilepsy information in addition to clinic date and date of birth across 200 clinic letters. We compared the results of our algorithm with a manual review of the letters by an epilepsy clinician.

Setting

De-identified and pseudonymised epilepsy clinic letters from a Health Board serving half a million residents in Wales, UK.

Results

We identified 1925 items of information with overall precision, recall and F1 score of 91.4%, 81.4% and 86.1%, respectively. Precision and recall for epilepsy-specific categories were: epilepsy diagnosis (88.1%, 89.0%), epilepsy type (89.8%, 79.8%), focal seizures (96.2%, 69.7%), generalised seizures (88.8%, 52.3%), seizure frequency (86.3%-53.6%), medication (96.1%, 94.0%), CT (55.6%, 58.8%), MRI (82.4%, 68.8%) and electroencephalogram (81.5%, 75.3%).

Conclusions

We have built an automated clinical text extraction system that can accurately extract epilepsy information from free text in clinic letters. This can enhance routinely collected data for research in the UK. The information extracted with ExECT such as epilepsy type, seizure frequency and neurological investigations are often missing from routinely collected data. We propose that our algorithm can bridge this data gap enabling further epilepsy research opportunities. While many of the rules in our pipeline were tailored to extract epilepsy specific information, our methods can be applied to other diseases and also can be used in clinical practice to record patient information in a structured manner.",,pdf:https://bmjopen.bmj.com/content/bmjopen/9/4/e023232.full.pdf; doi:https://doi.org/10.1136/bmjopen-2018-023232; html:https://europepmc.org/articles/PMC6500195; pdf:https://europepmc.org/articles/PMC6500195?pdf=render 32524641,https://doi.org/10.1002/sim.8556,Selective recruitment designs for improving observational studies using electronic health records.,"Barrett JE, Cakiroglu A, Bunce C, Shah A, Denaxas S.",,Statistics in medicine,2020,2020-06-10,Y,Electronic Health Records; Observational Study; Optimal Experimental Design; Selective Recruitment,,,"Large-scale electronic health records (EHRs) present an opportunity to quickly identify suitable individuals in order to directly invite them to participate in an observational study. EHRs can contain data from millions of individuals, raising the question of how to optimally select a cohort of size n from a larger pool of size N. In this article, we propose a simple selective recruitment protocol that selects a cohort in which covariates of interest tend to have a uniform distribution. We show that selectively recruited cohorts potentially offer greater statistical power and more accurate parameter estimates than randomly selected cohorts. Our protocol can be applied to studies with multiple categorical and continuous covariates. We apply our protocol to a numerically simulated prospective observational study using an EHR database of stable acute coronary disease patients from 82 089 individuals in the U.K. Selective recruitment designs require a smaller sample size, leading to more efficient and cost-effective studies.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/sim.8556; doi:https://doi.org/10.1002/sim.8556; html:https://europepmc.org/articles/PMC8432147; pdf:https://europepmc.org/articles/PMC8432147?pdf=render @@ -1508,29 +1508,29 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 31714636,https://doi.org/10.1002/ana.25642,Lipid lowering and Alzheimer disease risk: A mendelian randomization study.,"Williams DM, Finan C, Schmidt AF, Burgess S, Hingorani AD.",,Annals of neurology,2020,2020-01-01,Y,,,,"

Objective

To examine whether genetic variation affecting the expression or function of lipid-lowering drug targets is associated with Alzheimer disease (AD) risk, to evaluate the potential impact of long-term exposure to corresponding therapeutics.

Methods

We conducted Mendelian randomization analyses using variants in genes that encode the protein targets of several approved lipid-lowering drug classes: HMGCR (encoding the target for statins), PCSK9 (encoding the target for PCSK9 inhibitors, eg, evolocumab and alirocumab), NPC1L1 (encoding the target for ezetimibe), and APOB (encoding the target of mipomersen). Variants were weighted by associations with low-density lipoprotein cholesterol (LDL-C) using data from lipid genetics consortia (n up to 295,826). We meta-analyzed Mendelian randomization estimates for regional variants weighted by LDL-C on AD risk from 2 large samples (total n = 24,718 cases, 56,685 controls).

Results

Models for HMGCR, APOB, and NPC1L1 did not suggest that the use of related lipid-lowering drug classes would affect AD risk. In contrast, genetically instrumented exposure to PCSK9 inhibitors was predicted to increase AD risk in both of the AD samples (combined odds ratio per standard deviation lower LDL-C inducible by the drug target = 1.45, 95% confidence interval = 1.23-1.69). This risk increase was opposite to, although more modest than, the degree of protection from coronary artery disease predicted by these same methods for PCSK9 inhibition.

Interpretation

We did not identify genetic support for the repurposing of statins, ezetimibe, or mipomersen for AD prevention. Notwithstanding caveats to this genetic evidence, pharmacovigilance for AD risk among users of PCSK9 inhibitors may be warranted. ANN NEUROL 2020;87:30-39.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ana.25642; doi:https://doi.org/10.1002/ana.25642; html:https://europepmc.org/articles/PMC6944510; pdf:https://europepmc.org/articles/PMC6944510?pdf=render 35297548,https://doi.org/10.1002/humu.24369,"Beacon v2 and Beacon networks: A ""lingua franca"" for federated data discovery in biomedical genomics, and beyond.","Rambla J, Baudis M, Ariosa R, Beck T, Fromont LA, Navarro A, Paloots R, Rueda M, Saunders G, Singh B, Spalding JD, Törnroos J, Vasallo C, Veal CD, Brookes AJ.",,Human mutation,2022,2022-04-08,Y,data sharing; Clinical Genomics; Beacon; Data Discovery; Rest Api; Ga4gh,,,"Beacon is a basic data discovery protocol issued by the Global Alliance for Genomics and Health (GA4GH). The main goal addressed by version 1 of the Beacon protocol was to test the feasibility of broadly sharing human genomic data, through providing simple ""yes"" or ""no"" responses to queries about the presence of a given variant in datasets hosted by Beacon providers. The popularity of this concept has fostered the design of a version 2, that better serves real-world requirements and addresses the needs of clinical genomics research and healthcare, as assessed by several contributing projects and organizations. Particularly, rare disease genetics and cancer research will benefit from new case level and genomic variant level requests and the enabling of richer phenotype and clinical queries as well as support for fuzzy searches. Beacon is designed as a ""lingua franca"" to bridge data collections hosted in software solutions with different and rich interfaces. Beacon version 2 works alongside popular standards like Phenopackets, OMOP, or FHIR, allowing implementing consortia to return matches in beacon responses and provide a handover to their preferred data exchange format. The protocol is being explored by other research domains and is being tested in several international projects.",,pdf:http://repositori.upf.edu/bitstream/10230/53310/1/Rambla_2022.pdf; doi:https://doi.org/10.1002/humu.24369; html:https://europepmc.org/articles/PMC9322265; pdf:https://europepmc.org/articles/PMC9322265?pdf=render 34873059,https://doi.org/10.1073/pnas.2108395118,How immunity from and interaction with seasonal coronaviruses can shape SARS-CoV-2 epidemiology.,"Waterlow NR, van Leeuwen E, Davies NG, CMMID COVID-19 Working Group, Flasche S, Eggo RM.",,Proceedings of the National Academy of Sciences of the United States of America,2021,2021-12-01,Y,Immunity; Coronaviruses; Cross-protection; Covid-19; Sars-cov-2,,,"We hypothesized that cross-protection from seasonal epidemics of human coronaviruses (HCoVs) could have affected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, including generating reduced susceptibility in children. To determine what the prepandemic distribution of immunity to HCoVs was, we fitted a mathematical model to 6 y of seasonal coronavirus surveillance data from England and Wales. We estimated a duration of immunity to seasonal HCoVs of 7.8 y (95% CI 6.3 to 8.1) and show that, while cross-protection between HCoV and SARS-CoV-2 may contribute to the age distribution, it is insufficient to explain the age pattern of SARS-CoV-2 infections in the first wave of the pandemic in England and Wales. Projections from our model illustrate how different strengths of cross-protection between circulating coronaviruses could determine the frequency and magnitude of SARS-CoV-2 epidemics over the coming decade, as well as the potential impact of cross-protection on future seasonal coronavirus transmission.",,doi:https://doi.org/10.1073/pnas.2108395118; doi:https://doi.org/10.1073/pnas.2108395118; html:https://europepmc.org/articles/PMC8670441; pdf:https://europepmc.org/articles/PMC8670441?pdf=render -37573145,https://doi.org/10.1093/ndt/gfad180,Recovery of kidney function after acute kidney disease-a multi-cohort analysis.,"Sawhney S, Ball W, Bell S, Black C, Christiansen CF, Heide-Jørgensen U, Jensen SK, Lambourg E, Ronksley PE, Tan Z, Tonelli M, James MT.",,"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",2024,2024-02-01,Y,Recovery; Prognosis; epidemiology; Ckd; Aki,,,"

Background

There are no consensus definitions for evaluating kidney function recovery after acute kidney injury (AKI) and acute kidney disease (AKD), nor is it clear how recovery varies across populations and clinical subsets. We present a federated analysis of four population-based cohorts from Canada, Denmark and Scotland, 2011-18.

Methods

We identified incident AKD defined by serum creatinine changes within 48 h, 7 days and 90 days based on KDIGO AKI and AKD criteria. Separately, we applied changes up to 365 days to address widely used e-alert implementations that extend beyond the KDIGO AKI and AKD timeframes. Kidney recovery was based on resolution of AKD and a subsequent creatinine measurement below 1.2× baseline. We evaluated transitions between non-recovery, recovery and death up to 1 year; within age, sex and comorbidity subgroups; between subset AKD definitions; and across cohorts.

Results

There were 464 868 incident cases, median age 67-75 years. At 1 year, results were consistent across cohorts, with pooled mortalities for creatinine changes within 48 h, 7 days, 90 days and 365 days (and 95% confidence interval) of 40% (34%-45%), 40% (34%-46%), 37% (31%-42%) and 22% (16%-29%) respectively, and non-recovery of kidney function of 19% (15%-23%), 30% (24%-35%), 25% (21%-29%) and 37% (30%-43%), respectively. Recovery by 14 and 90 days was frequently not sustained at 1 year. Older males and those with heart failure or cancer were more likely to die than to experience sustained non-recovery, whereas the converse was true for younger females and those with diabetes.

Conclusion

Consistently across multiple cohorts, based on 1-year mortality and non-recovery, KDIGO AKD (up to 90 days) is at least prognostically similar to KDIGO AKI (7 days), and covers more people. Outcomes associated with AKD vary by age, sex and comorbidities such that older males are more likely to die, and younger females are less likely to recover.",,pdf:https://academic.oup.com/ndt/advance-article-pdf/doi/10.1093/ndt/gfad180/51104398/gfad180.pdf; doi:https://doi.org/10.1093/ndt/gfad180; html:https://europepmc.org/articles/PMC10899778; pdf:https://europepmc.org/articles/PMC10899778?pdf=render 33735069,https://doi.org/10.1016/s2589-7500(20)30240-5,"A global review of publicly available datasets for ophthalmological imaging: barriers to access, usability, and generalisability.","Khan SM, Liu X, Nath S, Korot E, Faes L, Wagner SK, Keane PA, Sebire NJ, Burton MJ, Denniston AK.",,The Lancet. Digital health,2021,2020-10-01,N,,,,"Health data that are publicly available are valuable resources for digital health research. Several public datasets containing ophthalmological imaging have been frequently used in machine learning research; however, the total number of datasets containing ophthalmological health information and their respective content is unclear. This Review aimed to identify all publicly available ophthalmological imaging datasets, detail their accessibility, describe which diseases and populations are represented, and report on the completeness of the associated metadata. With the use of MEDLINE, Google's search engine, and Google Dataset Search, we identified 94 open access datasets containing 507 724 images and 125 videos from 122 364 patients. Most datasets originated from Asia, North America, and Europe. Disease populations were unevenly represented, with glaucoma, diabetic retinopathy, and age-related macular degeneration disproportionately overrepresented in comparison with other eye diseases. The reporting of basic demographic characteristics such as age, sex, and ethnicity was poor, even at the aggregate level. This Review provides greater visibility for ophthalmological datasets that are publicly available as powerful resources for research. Our paper also exposes an increasing divide in the representation of different population and disease groups in health data repositories. The improved reporting of metadata would enable researchers to access the most appropriate datasets for their needs and maximise the potential of such resources.",,pdf:http://www.thelancet.com/article/S2589750020302405/pdf; doi:https://doi.org/10.1016/S2589-7500(20)30240-5 +37573145,https://doi.org/10.1093/ndt/gfad180,Recovery of kidney function after acute kidney disease-a multi-cohort analysis.,"Sawhney S, Ball W, Bell S, Black C, Christiansen CF, Heide-Jørgensen U, Jensen SK, Lambourg E, Ronksley PE, Tan Z, Tonelli M, James MT.",,"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",2024,2024-02-01,Y,Recovery; Prognosis; epidemiology; Ckd; Aki,,,"

Background

There are no consensus definitions for evaluating kidney function recovery after acute kidney injury (AKI) and acute kidney disease (AKD), nor is it clear how recovery varies across populations and clinical subsets. We present a federated analysis of four population-based cohorts from Canada, Denmark and Scotland, 2011-18.

Methods

We identified incident AKD defined by serum creatinine changes within 48 h, 7 days and 90 days based on KDIGO AKI and AKD criteria. Separately, we applied changes up to 365 days to address widely used e-alert implementations that extend beyond the KDIGO AKI and AKD timeframes. Kidney recovery was based on resolution of AKD and a subsequent creatinine measurement below 1.2× baseline. We evaluated transitions between non-recovery, recovery and death up to 1 year; within age, sex and comorbidity subgroups; between subset AKD definitions; and across cohorts.

Results

There were 464 868 incident cases, median age 67-75 years. At 1 year, results were consistent across cohorts, with pooled mortalities for creatinine changes within 48 h, 7 days, 90 days and 365 days (and 95% confidence interval) of 40% (34%-45%), 40% (34%-46%), 37% (31%-42%) and 22% (16%-29%) respectively, and non-recovery of kidney function of 19% (15%-23%), 30% (24%-35%), 25% (21%-29%) and 37% (30%-43%), respectively. Recovery by 14 and 90 days was frequently not sustained at 1 year. Older males and those with heart failure or cancer were more likely to die than to experience sustained non-recovery, whereas the converse was true for younger females and those with diabetes.

Conclusion

Consistently across multiple cohorts, based on 1-year mortality and non-recovery, KDIGO AKD (up to 90 days) is at least prognostically similar to KDIGO AKI (7 days), and covers more people. Outcomes associated with AKD vary by age, sex and comorbidities such that older males are more likely to die, and younger females are less likely to recover.",,pdf:https://academic.oup.com/ndt/advance-article-pdf/doi/10.1093/ndt/gfad180/51104398/gfad180.pdf; doi:https://doi.org/10.1093/ndt/gfad180; html:https://europepmc.org/articles/PMC10899778; pdf:https://europepmc.org/articles/PMC10899778?pdf=render 30928915,https://doi.org/10.1136/injuryprev-2018-043085,Comparison of revised Functional Capacity Index scores with Abbreviated Injury Scale 2008 scores in predicting 12-month severe trauma outcomes.,"Palmer CS, Cameron PA, Gabbe BJ.",,Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention,2020,2019-03-30,N,Trauma Registry; Trauma Scoring; Functional Outcomes; Prediction Models; Abbreviated Injury Scale; Major Trauma; Functional Capacity Index; 12-Month Outcomes,,,"

Introduction

Anatomical injury as measured by the AIS often accounts for only a small proportion of variability in outcomes after injury. The predictive Functional Capacity Index (FCI) appended to the 2008 AIS claims to provide a widely available method of predicting 12-month function following injury.

Objectives

To determine the extent to which AIS-based and FCI-based scoring is able to add to a simple predictive model of 12-month function following severe injury.

Methods

Adult trauma patients were drawn from the population-based Victorian State Trauma Registry. Major trauma and severely injured orthopaedic trauma patients were followed up via telephone interview including Glasgow Outcome Scale-Extended, the EQ-5D-3L and return to work status. A battery of AIS-based and FCI-based scores, and a simple count of AIS-coded injuries were added in turn to a base model using age and gender.

Results

A total of 20 813 patients survived to 12 months and had at least one functional outcome recorded, representing 85% follow-up. Predictions using the base model varied substantially across outcome measures. Irrespective of the method used to classify the severity of injury, adding injury severity to the model significantly, but only slightly improved model fit. Across the outcomes evaluated, no method of injury severity assessment consistently outperformed any other.

Conclusions

Anatomical injury is a predictor of trauma outcome. However, injury severity as described by the FCI does not consistently improve discrimination, or even provide the best discrimination compared with AIS-based severity scores or a simple injury count.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa50163/Download/0050163-25062019060819.pdf; doi:https://doi.org/10.1136/injuryprev-2018-043085 37348153,https://doi.org/10.1016/j.amjcard.2023.05.039,Clinical and Prognostic Implications of Cardiopulmonary Exercise Stress Echocardiography in Asymptomatic Degenerative Mitral Regurgitation.,"Althunayyan A, Alborikan S, Badiani S, Wong K, Uppal R, Patel N, Petersen SE, Lloyd G, Bhattacharyya S.",,The American journal of cardiology,2023,2023-06-20,N,,,,"The current guidelines recommend intervention in severe degenerative mitral regurgitation (MR) in symptomatic patients or asymptomatic patients with left ventricular dilatation or dysfunction. The insidious onset of symptoms may mean that patients do not report their symptoms. The role of systematic exercise testing for symptoms in MR is not clearly defined. A total of 97 patients with moderate to severe asymptomatic MR underwent exercise echocardiography combined with cardiopulmonary exercise testing. The predictors of exercise-induced dyspnea, symptom-free survival, and mitral valve intervention were identified. A total of 18 patients (19%) developed limiting dyspnea on exercise. Spontaneous symptom-free survival at 24 months was significantly higher in those without exercise-induced symptoms than those with exercise-induced symptoms, p <0.0001. The only independent predictors of spontaneous symptoms at 2 years were effective regurgitant orifice area (odds ratio 27.45, 95% confidence interval [CI] 1.43 to 528.40, p = 0.03) and exercise-induced symptoms (odds ratio 11.56, 95% CI 1.71 to 78.09, p = 0.01). The only independent predictor of surgery was indexed left ventricular systolic volumes (odds ratio 1.17, 95% CI 1.04 to 1.30, p = 0.006). Where only the patients who underwent surgery due to symptoms were included, the only independent predictor was exercise-induced symptoms (odds ratio 13.94, 95% CI 1.39 to 140.27, p = 0.025). In conclusion, in patients with primary asymptomatic degenerative MR, 1/5 develop revealed symptoms during exercise. This predicts a subsequent development of spontaneous symptoms and mitral valve intervention due to symptoms.",,doi:https://doi.org/10.1016/j.amjcard.2023.05.039 -37419925,https://doi.org/10.1038/s41467-023-38930-7,Optimal strategies for learning multi-ancestry polygenic scores vary across traits.,"Lehmann B, Mackintosh M, McVean G, Holmes C.",,Nature communications,2023,2023-07-07,Y,,,,"Polygenic scores (PGSs) are individual-level measures that aggregate the genome-wide genetic predisposition to a given trait. As PGS have predominantly been developed using European-ancestry samples, trait prediction using such European ancestry-derived PGS is less accurate in non-European ancestry individuals. Although there has been recent progress in combining multiple PGS trained on distinct populations, the problem of how to maximize performance given a multiple-ancestry cohort is largely unexplored. Here, we investigate the effect of sample size and ancestry composition on PGS performance for fifteen traits in UK Biobank. For some traits, PGS estimated using a relatively small African-ancestry training set outperformed, on an African-ancestry test set, PGS estimated using a much larger European-ancestry only training set. We observe similar, but not identical, results when considering other minority-ancestry groups within UK Biobank. Our results emphasise the importance of targeted data collection from underrepresented groups in order to address existing disparities in PGS performance.",,pdf:https://www.nature.com/articles/s41467-023-38930-7.pdf; doi:https://doi.org/10.1038/s41467-023-38930-7; html:https://europepmc.org/articles/PMC10328935; pdf:https://europepmc.org/articles/PMC10328935?pdf=render 33328453,https://doi.org/10.1038/s41467-020-19996-z,Genetic architecture of host proteins involved in SARS-CoV-2 infection.,"Pietzner M, Wheeler E, Carrasco-Zanini J, Raffler J, Kerrison ND, Oerton E, Auyeung VPW, Luan J, Finan C, Casas JP, Ostroff R, Williams SA, Kastenmüller G, Ralser M, Gamazon ER, Wareham NJ, Hingorani AD, Langenberg C.",,Nature communications,2020,2020-12-16,Y,,,,"Understanding the genetic architecture of host proteins interacting with SARS-CoV-2 or mediating the maladaptive host response to COVID-19 can help to identify new or repurpose existing drugs targeting those proteins. We present a genetic discovery study of 179 such host proteins among 10,708 individuals using an aptamer-based technique. We identify 220 host DNA sequence variants acting in cis (MAF 0.01-49.9%) and explaining 0.3-70.9% of the variance of 97 of these proteins, including 45 with no previously known protein quantitative trait loci (pQTL) and 38 encoding current drug targets. Systematic characterization of pQTLs across the phenome identified protein-drug-disease links and evidence that putative viral interaction partners such as MARK3 affect immune response. Our results accelerate the evaluation and prioritization of new drug development programmes and repurposing of trials to prevent, treat or reduce adverse outcomes. Rapid sharing and detailed interrogation of results is facilitated through an interactive webserver ( https://omicscience.org/apps/covidpgwas/ ).",,pdf:https://www.nature.com/articles/s41467-020-19996-z.pdf; doi:https://doi.org/10.1038/s41467-020-19996-z; html:https://europepmc.org/articles/PMC7744536; pdf:https://europepmc.org/articles/PMC7744536?pdf=render -31413164,https://doi.org/10.1183/13993003.00476-2019,Allergic diseases and long-term risk of autoimmune disorders: longitudinal cohort study and cluster analysis.,"Krishna MT, Subramanian A, Adderley NJ, Zemedikun DT, Gkoutos GV, Nirantharakumar K.",,The European respiratory journal,2019,2019-11-14,N,,,,"

Introduction

The association between allergic diseases and autoimmune disorders is not well established. Our objective was to determine incidence rates of autoimmune disorders in allergic rhinitis/conjunctivitis (ARC), atopic eczema and asthma, and to investigate for co-occurring patterns.

Methods

This was a retrospective cohort study (1990-2018) employing data extracted from The Health Improvement Network (UK primary care database). The exposure group comprised ARC, atopic eczema and asthma (all ages). For each exposed patient, up to two randomly selected age- and sex-matched controls with no documented allergic disease were used. Adjusted incidence rate ratios (aIRRs) were calculated using Poisson regression. A cross-sectional study was also conducted employing Association Rule Mining (ARM) to investigate disease clusters.

Results

782 320, 1 393 570 and 1 049 868 patients with ARC, atopic eczema and asthma, respectively, were included. aIRRs of systemic lupus erythematosus (SLE), Sjögren's syndrome, vitiligo, rheumatoid arthritis, psoriasis, pernicious anaemia, inflammatory bowel disease, coeliac disease and autoimmune thyroiditis were uniformly higher in the three allergic diseases compared with controls. Specifically, aIRRs of SLE (1.45) and Sjögren's syndrome (1.88) were higher in ARC; aIRRs of SLE (1.44), Sjögren's syndrome (1.61) and myasthenia (1.56) were higher in asthma; and aIRRs of SLE (1.86), Sjögren's syndrome (1.48), vitiligo (1.54) and psoriasis (2.41) were higher in atopic eczema. There was no significant effect of the three allergic diseases on multiple sclerosis or of ARC and atopic eczema on myasthenia. Using ARM, allergic diseases clustered with multiple autoimmune disorders. Three age- and sex-related clusters were identified, with a relatively complex pattern in females ≥55 years old.

Conclusions

The long-term risks of autoimmune disorders are significantly higher in patients with allergic diseases. Allergic diseases and autoimmune disorders show age- and sex-related clustering patterns.",,pdf:https://erj.ersjournals.com/content/erj/54/5/1900476.full.pdf; doi:https://doi.org/10.1183/13993003.00476-2019 +37419925,https://doi.org/10.1038/s41467-023-38930-7,Optimal strategies for learning multi-ancestry polygenic scores vary across traits.,"Lehmann B, Mackintosh M, McVean G, Holmes C.",,Nature communications,2023,2023-07-07,Y,,,,"Polygenic scores (PGSs) are individual-level measures that aggregate the genome-wide genetic predisposition to a given trait. As PGS have predominantly been developed using European-ancestry samples, trait prediction using such European ancestry-derived PGS is less accurate in non-European ancestry individuals. Although there has been recent progress in combining multiple PGS trained on distinct populations, the problem of how to maximize performance given a multiple-ancestry cohort is largely unexplored. Here, we investigate the effect of sample size and ancestry composition on PGS performance for fifteen traits in UK Biobank. For some traits, PGS estimated using a relatively small African-ancestry training set outperformed, on an African-ancestry test set, PGS estimated using a much larger European-ancestry only training set. We observe similar, but not identical, results when considering other minority-ancestry groups within UK Biobank. Our results emphasise the importance of targeted data collection from underrepresented groups in order to address existing disparities in PGS performance.",,pdf:https://www.nature.com/articles/s41467-023-38930-7.pdf; doi:https://doi.org/10.1038/s41467-023-38930-7; html:https://europepmc.org/articles/PMC10328935; pdf:https://europepmc.org/articles/PMC10328935?pdf=render 31711543,https://doi.org/10.1186/s13326-019-0214-4,Natural language processing for disease phenotyping in UK primary care records for research: a pilot study in myocardial infarction and death.,"Shah AD, Bailey E, Williams T, Denaxas S, Dobson R, Hemingway H.",,Journal of biomedical semantics,2019,2019-11-12,Y,Myocardial infarction; Chest pain; Primary Care; Natural Language Processing; Free Text,Applied Analytics,,"

Background

Free text in electronic health records (EHR) may contain additional phenotypic information beyond structured (coded) information. For major health events - heart attack and death - there is a lack of studies evaluating the extent to which free text in the primary care record might add information. Our objectives were to describe the contribution of free text in primary care to the recording of information about myocardial infarction (MI), including subtype, left ventricular function, laboratory results and symptoms; and recording of cause of death. We used the CALIBER EHR research platform which contains primary care data from the Clinical Practice Research Datalink (CPRD) linked to hospital admission data, the MINAP registry of acute coronary syndromes and the death registry. In CALIBER we randomly selected 2000 patients with MI and 1800 deaths. We implemented a rule-based natural language engine, the Freetext Matching Algorithm, on site at CPRD to analyse free text in the primary care record without raw data being released to researchers. We analysed text recorded within 90 days before or 90 days after the MI, and on or after the date of death.

Results

We extracted 10,927 diagnoses, 3658 test results, 3313 statements of negation, and 850 suspected diagnoses from the myocardial infarction patients. Inclusion of free text increased the recorded proportion of patients with chest pain in the week prior to MI from 19 to 27%, and differentiated between MI subtypes in a quarter more patients than structured data alone. Cause of death was incompletely recorded in primary care; in 36% the cause was in coded data and in 21% it was in free text. Only 47% of patients had exactly the same cause of death in primary care and the death registry, but this did not differ between coded and free text causes of death.

Conclusions

Among patients who suffer MI or die, unstructured free text in primary care records contains much information that is potentially useful for research such as symptoms, investigation results and specific diagnoses. Access to large scale unstructured data in electronic health records (millions of patients) might yield important insights.", NLP methods were used to analyse free text from hospital records for people with MI. They analysed text recorded within 90 days bfore or 90 days after the MI and found that free text in hospital records contains unformation useful for diagnoses,pdf:https://jbiomedsem.biomedcentral.com/track/pdf/10.1186/s13326-019-0214-4; doi:https://doi.org/10.1186/s13326-019-0214-4; html:https://europepmc.org/articles/PMC6849160; pdf:https://europepmc.org/articles/PMC6849160?pdf=render -38416429,https://doi.org/10.1056/nejmoa2311330,Cognition and Memory after Covid-19 in a Large Community Sample.,"Hampshire A, Azor A, Atchison C, Trender W, Hellyer PJ, Giunchiglia V, Husain M, Cooke GS, Cooper E, Lound A, Donnelly CA, Chadeau-Hyam M, Ward H, Elliott P.",,The New England journal of medicine,2024,2024-02-01,Y,,,,"

Background

Cognitive symptoms after coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are well-recognized. Whether objectively measurable cognitive deficits exist and how long they persist are unclear.

Methods

We invited 800,000 adults in a study in England to complete an online assessment of cognitive function. We estimated a global cognitive score across eight tasks. We hypothesized that participants with persistent symptoms (lasting ≥12 weeks) after infection onset would have objectively measurable global cognitive deficits and that impairments in executive functioning and memory would be observed in such participants, especially in those who reported recent poor memory or difficulty thinking or concentrating (""brain fog"").

Results

Of the 141,583 participants who started the online cognitive assessment, 112,964 completed it. In a multiple regression analysis, participants who had recovered from Covid-19 in whom symptoms had resolved in less than 4 weeks or at least 12 weeks had similar small deficits in global cognition as compared with those in the no-Covid-19 group, who had not been infected with SARS-CoV-2 or had unconfirmed infection (-0.23 SD [95% confidence interval {CI}, -0.33 to -0.13] and -0.24 SD [95% CI, -0.36 to -0.12], respectively); larger deficits as compared with the no-Covid-19 group were seen in participants with unresolved persistent symptoms (-0.42 SD; 95% CI, -0.53 to -0.31). Larger deficits were seen in participants who had SARS-CoV-2 infection during periods in which the original virus or the B.1.1.7 variant was predominant than in those infected with later variants (e.g., -0.17 SD for the B.1.1.7 variant vs. the B.1.1.529 variant; 95% CI, -0.20 to -0.13) and in participants who had been hospitalized than in those who had not been hospitalized (e.g., intensive care unit admission, -0.35 SD; 95% CI, -0.49 to -0.20). Results of the analyses were similar to those of propensity-score-matching analyses. In a comparison of the group that had unresolved persistent symptoms with the no-Covid-19 group, memory, reasoning, and executive function tasks were associated with the largest deficits (-0.33 to -0.20 SD); these tasks correlated weakly with recent symptoms, including poor memory and brain fog. No adverse events were reported.

Conclusions

Participants with resolved persistent symptoms after Covid-19 had objectively measured cognitive function similar to that in participants with shorter-duration symptoms, although short-duration Covid-19 was still associated with small cognitive deficits after recovery. Longer-term persistence of cognitive deficits and any clinical implications remain uncertain. (Funded by the National Institute for Health and Care Research and others.).",,pdf:https://www.nejm.org/doi/pdf/10.1056/NEJMoa2311330?articleTools=true; doi:https://doi.org/10.1056/NEJMoa2311330; html:https://europepmc.org/articles/PMC7615803; pdf:https://europepmc.org/articles/PMC7615803?pdf=render +31413164,https://doi.org/10.1183/13993003.00476-2019,Allergic diseases and long-term risk of autoimmune disorders: longitudinal cohort study and cluster analysis.,"Krishna MT, Subramanian A, Adderley NJ, Zemedikun DT, Gkoutos GV, Nirantharakumar K.",,The European respiratory journal,2019,2019-11-14,N,,,,"

Introduction

The association between allergic diseases and autoimmune disorders is not well established. Our objective was to determine incidence rates of autoimmune disorders in allergic rhinitis/conjunctivitis (ARC), atopic eczema and asthma, and to investigate for co-occurring patterns.

Methods

This was a retrospective cohort study (1990-2018) employing data extracted from The Health Improvement Network (UK primary care database). The exposure group comprised ARC, atopic eczema and asthma (all ages). For each exposed patient, up to two randomly selected age- and sex-matched controls with no documented allergic disease were used. Adjusted incidence rate ratios (aIRRs) were calculated using Poisson regression. A cross-sectional study was also conducted employing Association Rule Mining (ARM) to investigate disease clusters.

Results

782 320, 1 393 570 and 1 049 868 patients with ARC, atopic eczema and asthma, respectively, were included. aIRRs of systemic lupus erythematosus (SLE), Sjögren's syndrome, vitiligo, rheumatoid arthritis, psoriasis, pernicious anaemia, inflammatory bowel disease, coeliac disease and autoimmune thyroiditis were uniformly higher in the three allergic diseases compared with controls. Specifically, aIRRs of SLE (1.45) and Sjögren's syndrome (1.88) were higher in ARC; aIRRs of SLE (1.44), Sjögren's syndrome (1.61) and myasthenia (1.56) were higher in asthma; and aIRRs of SLE (1.86), Sjögren's syndrome (1.48), vitiligo (1.54) and psoriasis (2.41) were higher in atopic eczema. There was no significant effect of the three allergic diseases on multiple sclerosis or of ARC and atopic eczema on myasthenia. Using ARM, allergic diseases clustered with multiple autoimmune disorders. Three age- and sex-related clusters were identified, with a relatively complex pattern in females ≥55 years old.

Conclusions

The long-term risks of autoimmune disorders are significantly higher in patients with allergic diseases. Allergic diseases and autoimmune disorders show age- and sex-related clustering patterns.",,pdf:https://erj.ersjournals.com/content/erj/54/5/1900476.full.pdf; doi:https://doi.org/10.1183/13993003.00476-2019 33719753,https://doi.org/10.1080/13607863.2021.1893270,Cognition in informal caregivers: evidence from an English population study.,"García-Castro FJ, Bendayan R, Dobson RJB, Blanca MJ.",,Aging & mental health,2022,2021-03-14,N,Older Adults; Executive Function; Verbal Memory; Caregiving Duration,,,"

Background and objectives

The relationship between caregiving and cognition remains unclear. We investigate this association comparing four cognitive tasks and exploring the role of potential explanatory pathways such as healthy behaviours (healthy caregiver hypothesis) and depression (stress process model).

Research design and methods

Respondents were from English Longitudinal Study of Ageing (ELSA) (N = 8910). Cognitive tasks included immediate and delayed word recall, verbal fluency and serial 7 subtraction. Series of hierarchical linear regressions were performed. Adjustments included socio-demographics, health related variables, health behaviours and depression.

Results

Being a caregiver was positively associated with immediate and delayed recall, verbal fluency but not with serial 7. For immediate and delayed recall, these associations were partially attenuated when adjusting for health behaviours, and depression. For verbal fluency, associations were partially attenuated when adjusting for depression but fully attenuated when adjusting for health behaviours. No associations were found for serial 7.

Discussion and implications

Our findings show that caregivers have higher level of memory and executive function compared to non-caregivers. For memory, we found that although health behaviours and depression can have a role in this association, they do not fully explain it. However, health behaviours seem to have a clear role in the association with executive function. Public health and policy do not need to target specifically cognitive function but other areas as the promotion of healthy behaviours and psychological adjustment such as preventing depression and promoting physical activity in caregivers.",,pdf:https://www.tandfonline.com/doi/pdf/10.1080/13607863.2021.1893270?needAccess=true; doi:https://doi.org/10.1080/13607863.2021.1893270 32579178,https://doi.org/10.1001/jamadermatol.2020.1948,Association Between Atopic Eczema and Cancer in England and Denmark.,"Mansfield KE, Schmidt SAJ, Darvalics B, Mulick A, Abuabara K, Wong AYS, Sørensen HT, Smeeth L, Bhaskaran K, Dos Santos Silva I, Silverwood RJ, Langan SM.",,JAMA dermatology,2020,2020-10-01,Y,,,,"

Importance

Associations between atopic eczema and cancer are unclear, with competing theories that increased immune surveillance decreases cancer risk and that immune stimulation increases cancer risk. Establishing baseline cancer risk in people with atopic eczema is important before exploring the association between new biologic drugs for atopic eczema and cancer risk.

Objective

To investigate whether atopic eczema is associated with cancer.

Design, setting, and participants

Matched cohort studies were conducted from January 2, 1998, to March 31, 2016, in England and from January 1, 1982, to June 30, 2016, in Denmark. We conducted our analyses between July 2018 and July 2019. The setting was English primary care and nationwide Danish data. Participants with atopic eczema (adults only in England and any age in Denmark) were matched on age, sex, and calendar period (as well as primary care practice in England only) to those without atopic eczema.

Exposure

Atopic eczema.

Main outcomes and measures

Overall cancer risk and risk of specific cancers were compared in people with and without atopic eczema.

Results

In England, matched cohorts included 471 970 individuals with atopic eczema (median [IQR] age, 41.1 [24.9-60.7] years; 276 510 [58.6%] female) and 2 239 775 individuals without atopic eczema (median [IQR] age, 39.8 [25.9-58.4] years; 1 301 074 [58.1%] female). In Denmark, matched cohorts included 44 945 individuals with atopic eczema (median [IQR] age, 13.7 [1.7-21.1] years; 22 826 [50.8%] female) and 445 673 individuals without atopic eczema (median [IQR] age, 13.5 [1.7-20.8] years; 226 323 [50.8%] female). Little evidence was found of associations between atopic eczema and overall cancer (adjusted hazard ratio [HR], 1.04; 99% CI, 1.02-1.06 in England and 1.05; 99% CI, 0.95-1.16 in Denmark) or for most specific cancers. However, noncutaneous lymphoma risk was increased in people with atopic eczema in England (adjusted HR, 1.19; 99% CI, 1.07-1.34 for non-Hodgkin lymphoma [NHL] and 1.48; 99% CI, 1.07-2.04 for Hodgkin lymphoma). Lymphoma risk was increased in people with greater eczema severity vs those without atopic eczema (NHL adjusted HR, 1.06; 99% CI, 0.90-1.25 for mild eczema; 1.24; 99% CI, 1.04-1.48 for moderate eczema; and 2.08; 99% CI, 1.42-3.04 for severe eczema). Danish point estimates also showed increased lymphoma risk in people with moderate to severe eczema compared with those without atopic eczema (minimally adjusted HR, 1.31; 99% CI, 0.76-2.26 for NHL and 1.35; 99% CI, 0.65-2.82 for Hodgkin lymphoma), but the 99% CIs were wide.

Conclusions and relevance

The findings from 2 large population-based studies performed in different settings do not support associations between atopic eczema and most cancers. However, an association was observed between atopic eczema and lymphoma, particularly NHL, that increased with eczema severity. This finding warrants further study as new immunomodulatory systemic therapeutics are brought to market that may alter cancer risk.",,pdf:https://jamanetwork.com/journals/jamadermatology/articlepdf/2767601/jamadermatology_mansfield_2020_oi_200037_1602515656.45058.pdf; doi:https://doi.org/10.1001/jamadermatol.2020.1948; html:https://europepmc.org/articles/PMC7315391 32611631,https://doi.org/10.1212/wnl.0000000000009814,"Genetically determined blood pressure, antihypertensive drug classes, and risk of stroke subtypes.","Georgakis MK, Gill D, Webb AJS, Evangelou E, Elliott P, Sudlow CLM, Dehghan A, Malik R, Tzoulaki I, Dichgans M.",,Neurology,2020,2020-07-01,Y,,,,"

Objective

We employed Mendelian randomization to explore whether the effects of blood pressure (BP) and BP-lowering through different antihypertensive drug classes on stroke risk vary by stroke etiology.

Methods

We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drug targets from genome-wide association studies (GWAS) on 757,601 individuals. Applying 2-sample Mendelian randomization, we examined associations with any stroke (67,162 cases; 454,450 controls), ischemic stroke and its subtypes (large artery, cardioembolic, small vessel stroke), intracerebral hemorrhage (ICH, deep and lobar), and the related small vessel disease phenotype of white matter hyperintensities (WMH).

Results

Genetic predisposition to higher systolic and diastolic BP was associated with higher risk of any stroke, ischemic stroke, and ICH. We found associations between genetically determined BP and all ischemic stroke subtypes with a higher risk of large artery and small vessel stroke compared to cardioembolic stroke, as well as associations with deep, but not lobar ICH. Genetic proxies for calcium channel blockers, but not β-blockers, were associated with lower risk of any stroke and ischemic stroke. Proxies for calcium channel blockers showed particularly strong associations with small vessel stroke and the related radiologic phenotype of WMH.

Conclusions

This study supports a causal role of hypertension in all major stroke subtypes except lobar ICH. We find differences in the effects of BP and BP-lowering through antihypertensive drug classes between stroke subtypes and identify calcium channel blockade as a promising strategy for preventing manifestations of cerebral small vessel disease.",,pdf:https://n.neurology.org/content/neurology/95/4/e353.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000009814; html:https://europepmc.org/articles/PMC7455321; pdf:https://europepmc.org/articles/PMC7455321?pdf=render +38416429,https://doi.org/10.1056/nejmoa2311330,Cognition and Memory after Covid-19 in a Large Community Sample.,"Hampshire A, Azor A, Atchison C, Trender W, Hellyer PJ, Giunchiglia V, Husain M, Cooke GS, Cooper E, Lound A, Donnelly CA, Chadeau-Hyam M, Ward H, Elliott P.",,The New England journal of medicine,2024,2024-02-01,Y,,,,"

Background

Cognitive symptoms after coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are well-recognized. Whether objectively measurable cognitive deficits exist and how long they persist are unclear.

Methods

We invited 800,000 adults in a study in England to complete an online assessment of cognitive function. We estimated a global cognitive score across eight tasks. We hypothesized that participants with persistent symptoms (lasting ≥12 weeks) after infection onset would have objectively measurable global cognitive deficits and that impairments in executive functioning and memory would be observed in such participants, especially in those who reported recent poor memory or difficulty thinking or concentrating (""brain fog"").

Results

Of the 141,583 participants who started the online cognitive assessment, 112,964 completed it. In a multiple regression analysis, participants who had recovered from Covid-19 in whom symptoms had resolved in less than 4 weeks or at least 12 weeks had similar small deficits in global cognition as compared with those in the no-Covid-19 group, who had not been infected with SARS-CoV-2 or had unconfirmed infection (-0.23 SD [95% confidence interval {CI}, -0.33 to -0.13] and -0.24 SD [95% CI, -0.36 to -0.12], respectively); larger deficits as compared with the no-Covid-19 group were seen in participants with unresolved persistent symptoms (-0.42 SD; 95% CI, -0.53 to -0.31). Larger deficits were seen in participants who had SARS-CoV-2 infection during periods in which the original virus or the B.1.1.7 variant was predominant than in those infected with later variants (e.g., -0.17 SD for the B.1.1.7 variant vs. the B.1.1.529 variant; 95% CI, -0.20 to -0.13) and in participants who had been hospitalized than in those who had not been hospitalized (e.g., intensive care unit admission, -0.35 SD; 95% CI, -0.49 to -0.20). Results of the analyses were similar to those of propensity-score-matching analyses. In a comparison of the group that had unresolved persistent symptoms with the no-Covid-19 group, memory, reasoning, and executive function tasks were associated with the largest deficits (-0.33 to -0.20 SD); these tasks correlated weakly with recent symptoms, including poor memory and brain fog. No adverse events were reported.

Conclusions

Participants with resolved persistent symptoms after Covid-19 had objectively measured cognitive function similar to that in participants with shorter-duration symptoms, although short-duration Covid-19 was still associated with small cognitive deficits after recovery. Longer-term persistence of cognitive deficits and any clinical implications remain uncertain. (Funded by the National Institute for Health and Care Research and others.).",,pdf:https://www.nejm.org/doi/pdf/10.1056/NEJMoa2311330?articleTools=true; doi:https://doi.org/10.1056/NEJMoa2311330; html:https://europepmc.org/articles/PMC7615803; pdf:https://europepmc.org/articles/PMC7615803?pdf=render 35259281,https://doi.org/10.1111/acel.13524,Biological mechanisms of aging predict age-related disease co-occurrence in patients.,"Fraser HC, Kuan V, Johnen R, Zwierzyna M, Hingorani AD, Beyer A, Partridge L.",,Aging cell,2022,2022-03-08,Y,Aging; Genetics; Age-related Disease; Multimorbidity; Aging Hallmarks,,,"Genetic, environmental, and pharmacological interventions into the aging process can confer resistance to multiple age-related diseases in laboratory animals, including rhesus monkeys. These findings imply that individual mechanisms of aging might contribute to the co-occurrence of age-related diseases in humans and could be targeted to prevent these conditions simultaneously. To address this question, we text mined 917,645 literature abstracts followed by manual curation and found strong, non-random associations between age-related diseases and aging mechanisms in humans, confirmed by gene set enrichment analysis of GWAS data. Integration of these associations with clinical data from 3.01 million patients showed that age-related diseases associated with each of five aging mechanisms were more likely than chance to be present together in patients. Genetic evidence revealed that innate and adaptive immunity, the intrinsic apoptotic signaling pathway and activity of the ERK1/2 pathway were associated with multiple aging mechanisms and diverse age-related diseases. Mechanisms of aging hence contribute both together and individually to age-related disease co-occurrence in humans and could potentially be targeted accordingly to prevent multimorbidity.",,pdf:https://discovery.ucl.ac.uk/10145565/1/Hignorani_Biological%20mechanisms%20of%20aging%20predict%20age-related%20disease%20co-occurrence%20in%20patients_AOP.pdf; doi:https://doi.org/10.1111/acel.13524; html:https://europepmc.org/articles/PMC9009120; pdf:https://europepmc.org/articles/PMC9009120?pdf=render 33053479,https://doi.org/10.1016/j.chiabu.2020.104760,Characterizing newborn and older infant entries into care in England between 2006 and 2014.,"Pearson RJ, Jay MA, O'Donnell M, Wijlaars L, Gilbert R.",,Child abuse & neglect,2020,2020-10-11,Y,Longitudinal data; Infancy; Latent Class Analysis; Entry Into Care; Out-of-court Arrangements,,,"

Background

The risk of entry to state care during infancy is increasing, both here in England and abroad, with most entering within a week of birth ('newborns'). However, little is known about these infants or of their pathways through care over early childhood.

Objective

To characterize infant entries to care in England.

Participants and setting

All children in England who first entered care during infancy, between April 2006 and March 2014 (n = 42,000).

Methods

We compared sociodemographic and care characteristics for infants entering care over the study period by age at first entry (newborn: <1wks, older infant 1-51wks). Among those who entered before April 2010, we further characterized care over follow-up (i.e. 4 years from first entry) and employed latent class analysis to uncover any common pathways through care.

Results

Almost 40 % of infants first entered care as a newborn. Most infants first entered care under s 20 arrangements (i.e. out-of-court, 60 % of newborns vs 47 % of older infants). Among infants entering before April 2010, most were adopted over follow-up (60 % vs 37 %), though many were restored to parental care (20 % vs 32 %) or exited care to live with extended family (13 % vs 19 %). One in six infants (17.7 %) had particularly unstable care trajectories over early childhood, typified by three or more placements or failed reunification.

Conclusions

Evidence-based strengthening of pre-birth social work support is needed to improve preventive interventions before birth, to more effectively target infant placement into care. Linkages between child protection records and information on parents are needed to inform preventive strategies.",,doi:https://doi.org/10.1016/j.chiabu.2020.104760; doi:https://doi.org/10.1016/j.chiabu.2020.104760; html:https://europepmc.org/articles/PMC7718112 -37393610,https://doi.org/10.1016/j.xpro.2023.102392,Protocol for the automatic extraction of epidemiological information via a pre-trained language model.,"Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wang Z, Cao Y, Wong ZSY, Xu XK, Sun Y.",,STAR protocols,2023,2023-07-01,Y,Health Sciences; Clinical Protocol; Computer Sciences,,,"The lack of systems to automatically extract epidemiological fields from open-access COVID-19 cases restricts the timeliness of formulating prevention measures. Here we present a protocol for using CCIE, a COVID-19 Cases Information Extraction system based on the pre-trained language model.1 We describe steps for preparing supervised training data and executing python scripts for named entity recognition and text category classification. We then detail the use of machine evaluation and manual validation to illustrate the effectiveness of CCIE. For complete details on the use and execution of this protocol, please refer to Wang et al.2.",,doi:https://doi.org/10.1016/j.xpro.2023.102392; doi:https://doi.org/10.1016/j.xpro.2023.102392; html:https://europepmc.org/articles/PMC10328978; pdf:https://europepmc.org/articles/PMC10328978?pdf=render 33824583,https://doi.org/10.2147/copd.s298585,There is No Fast Track to Identify Fast Decliners in Alpha-1 Antitrypsin Deficiency by Spirometry: A Longitudinal Study of Repeated Measurements.,"Stockley JA, Stockley RA, Sapey E.",,International journal of chronic obstructive pulmonary disease,2021,2021-03-29,Y,Lung function; decline; Alpha-1 Antitrypsin Deficiency; Obstructive Airways Disease,,,"

Background

It is known that lung function decline in Alpha-1 Antitrypsin Deficiency (AATD) varies. Those with a rapid decline are at highest risk of poorer outcomes but may benefit most from targeted treatments including augmentation therapy. Current evidence suggests rapid decliners can be identified after 3 years of serial follow-up. It would be advantageous to identify these patients over a shorter time period, especially in mild disease.

Methods

Post-bronchodilator spirometry was performed every 6 months for a total of 18 months (4 measurements) by PiZZ AATD patients (ex- or never-smokers) either without spirometric COPD or with mild COPD. Where possible, retrospective spirometry data were included. Decline was assessed using 2 (baseline and 6 month) or four measurements (including baseline, 6, 12 and 18 months) and compared to retrospective decline rates using annual measurements over 3 years.

Results

Seventy-two PiZZ AATD patients were included, with 27 having at least three years of retrospective, annual spirometry. 18-month progression obtained by linear regression showed variable degrees of change with 29 showing no decline, 8 showing slow decline and 35 showing rapid decline. Bland-Altman plots showed that there was no overall agreement between predicted rate of decline using data obtained over 6 months and that obtained over 18 months. Furthermore, there was no agreement between rate of decline from either 6 or 18 months' data when compared to data collected over 3 years. The positive predictive value for rapid decline with 18 months of data compared to 3 years was only 50.0%.

Conclusion

This study suggests serial lung function over 18 months cannot identify AATD patients who have rapidly declining lung function. There is an urgent need for different biomarkers to help identify these patients at the earliest opportunity.",,pdf:https://www.dovepress.com/getfile.php?fileID=68078; doi:https://doi.org/10.2147/COPD.S298585; html:https://europepmc.org/articles/PMC8018552; pdf:https://europepmc.org/articles/PMC8018552?pdf=render +37393610,https://doi.org/10.1016/j.xpro.2023.102392,Protocol for the automatic extraction of epidemiological information via a pre-trained language model.,"Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wang Z, Cao Y, Wong ZSY, Xu XK, Sun Y.",,STAR protocols,2023,2023-07-01,Y,Health Sciences; Clinical Protocol; Computer Sciences,,,"The lack of systems to automatically extract epidemiological fields from open-access COVID-19 cases restricts the timeliness of formulating prevention measures. Here we present a protocol for using CCIE, a COVID-19 Cases Information Extraction system based on the pre-trained language model.1 We describe steps for preparing supervised training data and executing python scripts for named entity recognition and text category classification. We then detail the use of machine evaluation and manual validation to illustrate the effectiveness of CCIE. For complete details on the use and execution of this protocol, please refer to Wang et al.2.",,doi:https://doi.org/10.1016/j.xpro.2023.102392; doi:https://doi.org/10.1016/j.xpro.2023.102392; html:https://europepmc.org/articles/PMC10328978; pdf:https://europepmc.org/articles/PMC10328978?pdf=render 35842920,https://doi.org/10.1002/ehf2.14073,Blood-based biomarkers for the prediction of hypertrophic cardiomyopathy prognosis: a systematic review and meta-analysis.,"Jansen M, Algül S, Bosman LP, Michels M, van der Velden J, de Boer RA, van Tintelen JP, Asselbergs FW, Baas AF.",,ESC heart failure,2022,2022-07-17,Y,Prognosis; Biomarker; hypertrophic cardiomyopathy; Systematic review; Heart Failure; Sudden Cardiac Death,,,"

Aims

Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disease. HCM is an important cause of sudden cardiac death and may also lead to outflow tract obstruction and heart failure. Disease severity is highly variable and risk stratification remains limited. Therefore, we aimed to review current knowledge of prognostic blood-based biomarkers in HCM.

Methods and results

A systematic literature search was performed on PubMed, Embase, and the Cochrane library to identify studies assessing plasma or serum biomarkers for outcomes involving malignant ventricular arrhythmia, outflow tract obstruction, and heart failure. Risk of bias was assessed using the QUIPS tool. Meta-analyses were performed using the random effects method. A total of 26 unique cohort studies assessing 42 biomarkers were identified. Overall risk of bias was moderate. Thirty-two biomarkers were significantly associated to an HCM outcome in at least one study (nine biomarkers in at least two studies). In pooled analyses, cardiovascular mortality was predicted by N-terminal prohormone of brain natriuretic peptide (hazard ratio [HR] 5.38 per log[pg/mL], 95% confidence interval [CI] 2.07-14.03, P < 0.001, I2  = 0%) and high-sensitivity C-reactive protein (HR 1.30 per μg/mL, 95% CI 1.00-1.68, P = 0.05, I2  = 78%), all-cause mortality by low-density lipoprotein cholesterol (HR 0.63 per μmol/mL, 95% CI 0.49-0.80, P < 0.001, I2  = 0%), and a combined congestive heart failure, malignant ventricular arrhythmia, and stroke outcome by high-sensitivity cardiac troponin T (pooled HR 4.19 for ≥0.014 ng/mL, 95% CI 2.22-7.88, P < 0.001, I2  = 0%). Quality of evidence was low-moderate.

Conclusions

Several blood-based biomarkers were identified as predictors of HCM outcomes. Additional studies are required to validate their prognostic utility within current risk stratification models.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14073; doi:https://doi.org/10.1002/ehf2.14073; html:https://europepmc.org/articles/PMC9715795; pdf:https://europepmc.org/articles/PMC9715795?pdf=render 34018481,https://doi.org/10.2807/1560-7917.es.2021.26.20.2100428,The potential for vaccination-induced herd immunity against the SARS-CoV-2 B.1.1.7 variant.,"Hodgson D, Flasche S, Jit M, Kucharski AJ, CMMID COVID-19 Working Group, Centre for Mathematical Modelling of Infectious Disease (CMMID) COVID-19 Working Group.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2021,2021-05-01,Y,Vaccination; Herd immunity; Seroprevalence; Sars-cov-2,,,"We assess the feasibility of reaching the herd immunity threshold against SARS-CoV-2 through vaccination, considering vaccine effectiveness (VE), transmissibility of the virus and the level of pre-existing immunity in populations, as well as their age structure. If highly transmissible variants of concern become dominant in areas with low levels of naturally-acquired immunity and/or in populations with large proportions of < 15 year-olds, control of infection without non-pharmaceutical interventions may only be possible with a VE ≥ 80%, and coverage extended to children.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/26/20/eurosurv-26-20-1.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2021.26.20.2100428&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2021.26.20.2100428; html:https://europepmc.org/articles/PMC8138959; pdf:https://europepmc.org/articles/PMC8138959?pdf=render 36273236,https://doi.org/10.1038/s41746-022-00705-7,"Automated clinical coding: what, why, and where we are?","Dong H, Falis M, Whiteley W, Alex B, Matterson J, Ji S, Chen J, Wu H.",,NPJ digital medicine,2022,2022-10-22,Y,,,,"Clinical coding is the task of transforming medical information in a patient's health records into structured codes so that they can be used for statistical analysis. This is a cognitive and time-consuming task that follows a standard process in order to achieve a high level of consistency. Clinical coding could potentially be supported by an automated system to improve the efficiency and accuracy of the process. We introduce the idea of automated clinical coding and summarise its challenges from the perspective of Artificial Intelligence (AI) and Natural Language Processing (NLP), based on the literature, our project experience over the past two and half years (late 2019-early 2022), and discussions with clinical coding experts in Scotland and the UK. Our research reveals the gaps between the current deep learning-based approach applied to clinical coding and the need for explainability and consistency in real-world practice. Knowledge-based methods that represent and reason the standard, explainable process of a task may need to be incorporated into deep learning-based methods for clinical coding. Automated clinical coding is a promising task for AI, despite the technical and organisational challenges. Coders are needed to be involved in the development process. There is much to achieve to develop and deploy an AI-based automated system to support coding in the next five years and beyond.",,pdf:https://www.nature.com/articles/s41746-022-00705-7.pdf; doi:https://doi.org/10.1038/s41746-022-00705-7; html:https://europepmc.org/articles/PMC9588058; pdf:https://europepmc.org/articles/PMC9588058?pdf=render 37670953,https://doi.org/10.23889/ijpds.v8i1.2113,Lessons learned from using linked administrative data to evaluate the Family Nurse Partnership in England and Scotland.,"Cavallaro FL, Cannings-John R, Lugg-Widger F, Gilbert R, Kennedy E, Kendall S, Robling M, Harron KL.",,International journal of population data science,2023,2023-05-11,Y,Evaluation; Early Years; Administrative Data; Adolescent Motherhood; Cross-Sectoral Linkage,,,"

Introduction

""Big data"" - including linked administrative data - can be exploited to evaluate interventions for maternal and child health, providing time- and cost-effective alternatives to randomised controlled trials. However, using these data to evaluate population-level interventions can be challenging.

Objectives

We aimed to inform future evaluations of complex interventions by describing sources of bias, lessons learned, and suggestions for improvements, based on two observational studies using linked administrative data from health, education and social care sectors to evaluate the Family Nurse Partnership (FNP) in England and Scotland.

Methods

We first considered how different sources of potential bias within the administrative data could affect results of the evaluations. We explored how each study design addressed these sources of bias using maternal confounders captured in the data. We then determined what additional information could be captured at each step of the complex intervention to enable analysts to minimise bias and maximise comparability between intervention and usual care groups, so that any observed differences can be attributed to the intervention.

Results

Lessons learned include the need for i) detailed data on intervention activity (dates/geography) and usual care; ii) improved information on data linkage quality to accurately characterise control groups; iii) more efficient provision of linked data to ensure timeliness of results; iv) better measurement of confounding characteristics affecting who is eligible, approached and enrolled.

Conclusions

Linked administrative data are a valuable resource for evaluations of the FNP national programme and other complex population-level interventions. However, information on local programme delivery and usual care are required to account for biases that characterise those who receive the intervention, and to inform understanding of mechanisms of effect. National, ongoing, robust evaluations of complex public health evaluations would be more achievable if programme implementation was integrated with improved national and local data collection, and robust quasi-experimental designs.",,pdf:https://ijpds.org/article/download/2113/4170; doi:https://doi.org/10.23889/ijpds.v8i1.2113; html:https://europepmc.org/articles/PMC10476150; pdf:https://europepmc.org/articles/PMC10476150?pdf=render 38663408,https://doi.org/10.1016/j.xgen.2024.100541,Characterization of the genetic determinants of context-specific DNA methylation in primary monocytes.,"Gilchrist JJ, Fang H, Danielli S, Tomkova M, Nassiri I, Ng E, Tong O, Taylor C, Muldoon D, Cohen LRZ, Al-Mossawi H, Lau E, Neville M, Schuster-Boeckler B, Knight JC, Fairfax BP.",,Cell genomics,2024,2024-04-24,Y,Genetics; Monocytes; Cancer; LPS; DNA methylation; Innate Immune Activation; Mqtl; Epigenetic Aging,,,"To better understand inter-individual variation in sensitivity of DNA methylation (DNAm) to immune activity, we characterized effects of inflammatory stimuli on primary monocyte DNAm (n = 190). We find that monocyte DNAm is site-dependently sensitive to lipopolysaccharide (LPS), with LPS-induced demethylation occurring following hydroxymethylation. We identify 7,359 high-confidence immune-modulated CpGs (imCpGs) that differ in genomic localization and transcription factor usage according to whether they represent a gain or loss in DNAm. Demethylated imCpGs are profoundly enriched for enhancers and colocalize to genes enriched for disease associations, especially cancer. DNAm is age associated, and we find that 24-h LPS exposure triggers approximately 6 months of gain in epigenetic age, directly linking epigenetic aging with innate immune activity. By integrating LPS-induced changes in DNAm with genetic variation, we identify 234 imCpGs under local genetic control. Exploring shared causal loci between LPS-induced DNAm responses and human disease traits highlights examples of disease-associated loci that modulate imCpG formation.",,doi:https://doi.org/10.1016/j.xgen.2024.100541; html:https://europepmc.org/articles/PMC11099345; pdf:https://europepmc.org/articles/PMC11099345?pdf=render -37563195,https://doi.org/10.1038/s41598-023-38880-6,Locational memory of macrovessel vascular cells is transcriptionally imprinted.,"Spanjersberg TCF, Oosterhoff LA, Kruitwagen HS, van den Dungen NAM, Vernooij JCM, Asselbergs FW, Mokry M, Spee B, Harakalova M, van Steenbeek FG.",,Scientific reports,2023,2023-08-10,Y,,,,"Vascular pathologies show locational predisposition throughout the body; further insights into the transcriptomics basis of this vascular heterogeneity are needed. We analyzed transcriptomes from cultured endothelial cells and vascular smooth muscle cells from nine adult canine macrovessels: the aorta, coronary artery, vena cava, portal vein, femoral artery, femoral vein, saphenous vein, pulmonary vein, and pulmonary artery. We observed that organ-specific expression patterns persist in vitro, indicating that these genes are not regulated by blood flow or surrounding cell types but are likely fixed in the epigenetic memory. We further demonstrated the preserved location-specific expression of GATA4 protein in cultured cells and in the primary adult vessel. On a functional level, arterial and venous endothelial cells differed in vascular network morphology as the arterial networks maintained a higher complexity. Our findings prompt the rethinking of the extrapolation of results from single-origin endothelial cell systems.",,pdf:https://www.nature.com/articles/s41598-023-38880-6.pdf; doi:https://doi.org/10.1038/s41598-023-38880-6; html:https://europepmc.org/articles/PMC10415317; pdf:https://europepmc.org/articles/PMC10415317?pdf=render 36828609,https://doi.org/10.1016/s2589-7500(22)00252-7,Embedding patient-reported outcomes at the heart of artificial intelligence health-care technologies.,"Cruz Rivera S, Liu X, Hughes SE, Dunster H, Manna E, Denniston AK, Calvert MJ.",,The Lancet. Digital health,2023,2023-03-01,N,,,,"Integration of patient-reported outcome measures (PROMs) in artificial intelligence (AI) studies is a critical part of the humanisation of AI for health. It allows AI technologies to incorporate patients' own views of their symptoms and predict outcomes, reflecting a more holistic picture of health and wellbeing and ultimately helping patients and clinicians to make the best health-care decisions together. By positioning patient-reported outcomes (PROs) as a model input or output we propose a framework to embed PROMs within the function and evaluation of AI health care. However, the integration of PROs in AI systems presents several challenges. These challenges include (1) fragmentation of PRO data collection; (2) validation of AI systems trained and validated against clinician performance, rather than outcome data; (3) scarcity of large-scale PRO datasets; (4) inadequate selection of PROMs for the target population and inadequate infrastructure for collecting PROs; and (5) clinicians might not recognise the value of PROs and therefore not prioritise their adoption; and (6) studies involving PRO or AI frequently present suboptimal design. Notwithstanding these challenges, we propose considerations for the inclusion of PROs in AI health-care technologies to avoid promoting survival at the expense of wellbeing.",,doi:https://doi.org/10.1016/s2589-7500(22)00252-7; doi:https://doi.org/10.1016/S2589-7500(22)00252-7 +37563195,https://doi.org/10.1038/s41598-023-38880-6,Locational memory of macrovessel vascular cells is transcriptionally imprinted.,"Spanjersberg TCF, Oosterhoff LA, Kruitwagen HS, van den Dungen NAM, Vernooij JCM, Asselbergs FW, Mokry M, Spee B, Harakalova M, van Steenbeek FG.",,Scientific reports,2023,2023-08-10,Y,,,,"Vascular pathologies show locational predisposition throughout the body; further insights into the transcriptomics basis of this vascular heterogeneity are needed. We analyzed transcriptomes from cultured endothelial cells and vascular smooth muscle cells from nine adult canine macrovessels: the aorta, coronary artery, vena cava, portal vein, femoral artery, femoral vein, saphenous vein, pulmonary vein, and pulmonary artery. We observed that organ-specific expression patterns persist in vitro, indicating that these genes are not regulated by blood flow or surrounding cell types but are likely fixed in the epigenetic memory. We further demonstrated the preserved location-specific expression of GATA4 protein in cultured cells and in the primary adult vessel. On a functional level, arterial and venous endothelial cells differed in vascular network morphology as the arterial networks maintained a higher complexity. Our findings prompt the rethinking of the extrapolation of results from single-origin endothelial cell systems.",,pdf:https://www.nature.com/articles/s41598-023-38880-6.pdf; doi:https://doi.org/10.1038/s41598-023-38880-6; html:https://europepmc.org/articles/PMC10415317; pdf:https://europepmc.org/articles/PMC10415317?pdf=render 35504525,https://doi.org/10.1016/j.jclinepi.2022.04.025,How traditional informed consent impairs inclusivity in a learning healthcare system: lessons learned from the Utrecht Cardiovascular Cohort.,"Groenhof TKJ, Mostert M, Lea NC, Haitjema S, de Vries MC, van Dijk WB, Grobbee DE, Asselbergs FW, Bots ML, van der Graaf R.",,Journal of clinical epidemiology,2022,2022-04-30,N,,,,,,pdf:https://discovery.ucl.ac.uk/10160730/1/JCEPI-D-21-01101_R2-2%2022-40.pdf; doi:https://doi.org/10.1016/j.jclinepi.2022.04.025 34364665,https://doi.org/10.1016/j.cardfail.2021.05.012,Empagliflozin in Heart Failure With Predicted Preserved Versus Reduced Ejection Fraction: Data From the EMPA-REG OUTCOME Trial.,"Savarese G, Uijl A, Lund LH, Anker SD, Asselbergs F, Fitchett D, Inzucchi SE, Koudstaal S, Ofstad AP, Schrage B, Vedin O, Wanner C, Zannad F, Zwiener I, Butler J.",,Journal of cardiac failure,2021,2021-08-01,N,Type 2 diabetes mellitus; Heart Failure With Preserved Ejection Fraction; Heart Failure With Reduced Ejection Fraction; Empagliflozin; Empa-reg Outcome; Heart Failure With Mid-range Ejection Fraction; Heart Failure With Mildly Reduced Ejection Fraction,,,"

Background

In the EMPA-REG OUTCOME trial, ejection fraction (EF) data were not collected. In the subpopulation with heart failure (HF), we applied a new predictive model for EF to determine the effects of empagliflozin in HF with predicted reduced (HFrEF) vs preserved (HFpEF) EF vs no HF.

Methods and results

We applied a validated EF predictive model based on patient baseline characteristics and treatments to categorize patients with HF as being likely to have HF with mid-range EF (HFmrEF)/HFrEF (EF <50%) or HFpEF (EF ≥50%). Cox regression was used to assess the effect of empagliflozin vs placebo on cardiovascular death/HF hospitalization (HHF), cardiovascular and all-cause mortality, and HHF in patients with predicted HFpEF, HFmrEF/HFrEF and no HF. Of 7001 EMPA-REG OUTCOME patients with data available for this analysis, 6314 (90%) had no history of HF. Of the 687 with history of HF, 479 (69.7%) were predicted to have HFmrEF/HFrEF and 208 (30.3%) to have HFpEF. Empagliflozin's treatment effect was consistent in predicted HFpEF, HFmrEF/HFrEF and no-HF for each outcome (HR [95% CI] for the primary outcome 0.60 [0.31-1.17], 0.79 [0.51-1.23], and 0.63 [0.50-0.78], respectively; P interaction = 0.62).

Conclusions

In EMPA-REG OUTCOME, one-third of the patients with HF had predicted HFpEF. The benefits of empagliflozin on HF and mortality outcomes were consistent in nonHF, predicted HFpEF and HFmrEF/HFrEF.",,pdf:https://hal.univ-lorraine.fr/hal-03320880/file/1-s2.0-S1071916421002025-main.pdf; doi:https://doi.org/10.1016/j.cardfail.2021.05.012 34769922,https://doi.org/10.3390/ijerph182111380,"Driver, Collision and Meteorological Characteristics of Motor Vehicle Collisions among Road Trauma Survivors.","Giummarra MJ, Xu R, Guo Y, Dipnall JF, Ponsford J, Cameron PA, Ameratunga S, Gabbe BJ.",,International journal of environmental research and public health,2021,2021-10-29,Y,Trauma; Prevention; Traffic; Motor Vehicle,,,"Road trauma remains a significant public health problem. We aimed to identify sub-groups of motor vehicle collisions in Victoria, Australia, and the association between collision characteristics and outcomes up to 24 months post-injury. Data were extracted from the Victorian State Trauma Registry for injured drivers aged ≥16 years, from 2010 to 2016, with a compensation claim who survived ≥12 months post-injury. People with intentional or severe head injury were excluded, resulting in 2735 cases. Latent class analysis was used to identify collision classes for driver fault and blood alcohol concentration (BAC), day and time of collision, weather conditions, single vs. multi-vehicle and regional vs. metropolitan injury location. Five classes were identified: (1) daytime multi-vehicle collisions, no other at fault; (2) daytime single-vehicle predominantly weekday collisions; (3) evening single-vehicle collisions, no other at fault, 36% with BAC ≥ 0.05; (4) sunrise or sunset weekday collisions; and (5) dusk and evening multi-vehicle in metropolitan areas with BAC < 0.05. Mixed linear and logistic regression analyses examined associations between collision class and return to work, health (EQ-5D-3L summary score) and independent function Glasgow Outcome Scale - Extended at 6, 12 and 24 months. After adjusting for demographic, health and injury characteristics, collision class was not associated with outcomes. Rather, risk of poor outcomes was associated with age, sex and socioeconomic disadvantage, education, pre-injury health and injury severity. People at risk of poor recovery may be identified from factors available during the hospital admission and may benefit from clinical assessment and targeted referrals and treatments.",,pdf:https://www.mdpi.com/1660-4601/18/21/11380/pdf?version=1635513758; doi:https://doi.org/10.3390/ijerph182111380; html:https://europepmc.org/articles/PMC8583338; pdf:https://europepmc.org/articles/PMC8583338?pdf=render @@ -1546,9 +1546,9 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 36298714,https://doi.org/10.3390/v14102159,Production and Characterisation of Stabilised PV-3 Virus-like Particles Using Pichia pastoris.,"Sherry L, Grehan K, Swanson JJ, Bahar MW, Porta C, Fry EE, Stuart DI, Rowlands DJ, Stonehouse NJ.",,Viruses,2022,2022-09-30,Y,Poliovirus; Vaccine; virus-like particle; Pichia pastoris,,,"Following the success of global vaccination programmes using the live-attenuated oral and inactivated poliovirus vaccines (OPV and IPV), wild poliovirus (PV) is now only endemic in Afghanistan and Pakistan. However, the continued use of these vaccines poses potential risks to the eradication of PV. The production of recombinant PV virus-like particles (VLPs), which lack the viral genome offer great potential as next-generation vaccines for the post-polio world. We have previously reported production of PV VLPs using Pichia pastoris, however, these VLPs were in the non-native conformation (C Ag), which would not produce effective protection against PV. Here, we build on this work and show that it is possible to produce wt PV-3 and thermally stabilised PV-3 (referred to as PV-3 SC8) VLPs in the native conformation (D Ag) using Pichia pastoris. We show that the PV-3 SC8 VLPs provide a much-improved D:C antigen ratio as compared to wt PV-3, whilst exhibiting greater thermostability than the current IPV vaccine. Finally, we determine the cryo-EM structure of the yeast-derived PV-3 SC8 VLPs and compare this to previously published PV-3 D Ag structures, highlighting the similarities between these recombinantly expressed VLPs and the infectious virus, further emphasising their potential as a next-generation vaccine candidate for PV.",,pdf:https://www.mdpi.com/1999-4915/14/10/2159/pdf?version=1665465973; doi:https://doi.org/10.3390/v14102159; html:https://europepmc.org/articles/PMC9611624; pdf:https://europepmc.org/articles/PMC9611624?pdf=render 36711167,https://doi.org/10.1093/ehjdh/ztaa016,Real-time imputation of missing predictor values in clinical practice.,"Nijman SWJ, Hoogland J, Groenhof TKJ, Brandjes M, Jacobs JJL, Bots ML, Asselbergs FW, Moons KGM, Debray TPA.",,European heart journal. Digital health,2021,2020-12-19,Y,Prediction; Missing Data; Electronic Health Records; Computerized Decision Support System; Real-time Imputation; Joint Modelling Imputation,,,"

Aims

Use of prediction models is widely recommended by clinical guidelines, but usually requires complete information on all predictors, which is not always available in daily practice. We aim to describe two methods for real-time handling of missing predictor values when using prediction models in practice.

Methods and results

We compare the widely used method of mean imputation (M-imp) to a method that personalizes the imputations by taking advantage of the observed patient characteristics. These characteristics may include both prediction model variables and other characteristics (auxiliary variables). The method was implemented using imputation from a joint multivariate normal model of the patient characteristics (joint modelling imputation; JMI). Data from two different cardiovascular cohorts with cardiovascular predictors and outcome were used to evaluate the real-time imputation methods. We quantified the prediction model's overall performance [mean squared error (MSE) of linear predictor], discrimination (c-index), calibration (intercept and slope), and net benefit (decision curve analysis). When compared with mean imputation, JMI substantially improved the MSE (0.10 vs. 0.13), c-index (0.70 vs. 0.68), and calibration (calibration-in-the-large: 0.04 vs. 0.06; calibration slope: 1.01 vs. 0.92), especially when incorporating auxiliary variables. When the imputation method was based on an external cohort, calibration deteriorated, but discrimination remained similar.

Conclusions

We recommend JMI with auxiliary variables for real-time imputation of missing values, and to update imputation models when implementing them in new settings or (sub)populations.",,pdf:https://academic.oup.com/ehjdh/article-pdf/2/1/154/37807088/ztaa016.pdf; doi:https://doi.org/10.1093/ehjdh/ztaa016; html:https://europepmc.org/articles/PMC9707891; pdf:https://europepmc.org/articles/PMC9707891?pdf=render 35089054,https://doi.org/10.1161/circep.121.010221,Integrating Exercise Into Personalized Ventricular Arrhythmia Risk Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy.,"Bosman LP, Wang W, Lie ØH, van Lint FHM, Rootwelt-Norberg C, Murray B, Tichnell C, Cadrin-Tourigny J, van Tintelen JP, Asselbergs FW, Calkins H, Te Riele ASJM, Haugaa KH, James CA.",,Circulation. Arrhythmia and electrophysiology,2022,2022-01-28,N,Prognosis; Exercise; Arrhythmogenic right ventricular dysplasia,,,"

Background

Exercise is associated with sustained ventricular arrhythmias (VA) in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) but is not included in the ARVC risk calculator (arvcrisk.com). The objective of this study is to quantify the influence of exercise at diagnosis on incident VA risk and evaluate whether the risk calculator needs adjustment for exercise.

Methods

We interviewed ARVC patients without sustained VA at diagnosis about their exercise history. The relationship between exercise dose 3 years preceding diagnosis (average METh/wk) and incident VA during follow-up was analyzed with time-to-event analysis. The incremental prognostic value of exercise to the risk calculator was evaluated by Cox models.

Results

We included 176 patients (male, 43.2%; age, 37.6±16.1 years) from 3 ARVC centers, of whom 53 (30.1%) developed sustained VA during 5.4 (2.7-9.7) years of follow-up. Exercise at diagnosis showed a dose-dependent nonlinear relationship with VA, with no significant risk increase <15 to 30 METh/wk. Athlete status, using 3 definitions from literature (>18, >24, and >36 METh/wk), was significantly associated with VA (hazard ratios, 2.53-2.91) but was also correlated with risk factors currently in the risk calculator model. Thus, adding athlete status to the model did not change the C index of 0.77 (0.71-0.84) and showed no significant improvement (Akaike information criterion change, <2).

Conclusions

Exercise at diagnosis was dose dependently associated with risk of sustained VA in ARVC patients but only above 15 to 30 METh/wk. Exercise does not appear to have incremental prognostic value over the risk calculator. The ARVC risk calculator can be used accurately in athletic patients without modification.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCEP.121.010221; doi:https://doi.org/10.1161/CIRCEP.121.010221 -35692035,https://doi.org/10.1186/s12916-022-02399-w,"Role of circulating polyunsaturated fatty acids on cardiovascular diseases risk: analysis using Mendelian randomization and fatty acid genetic association data from over 114,000 UK Biobank participants.","Borges MC, Haycock PC, Zheng J, Hemani G, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA.",,BMC medicine,2022,2022-06-13,Y,Fatty acids; Cardiovascular diseases; Mendelian Randomization,,,"

Background

Despite early interest in the health effects of polyunsaturated fatty acids (PUFA), there is still substantial controversy and uncertainty on the evidence linking PUFA to cardiovascular diseases (CVDs). We investigated the effect of plasma concentration of omega-3 PUFA (i.e. docosahexaenoic acid (DHA) and total omega-3 PUFA) and omega-6 PUFA (i.e. linoleic acid and total omega-6 PUFA) on the risk of CVDs using Mendelian randomization.

Methods

We conducted the largest genome-wide association study (GWAS) of circulating PUFA to date including a sample of 114,999 individuals and incorporated these data in a two-sample Mendelian randomization framework to investigate the involvement of circulating PUFA on a wide range of CVDs in up to 1,153,768 individuals of European ancestry (i.e. coronary artery disease, ischemic stroke, haemorrhagic stroke, heart failure, atrial fibrillation, peripheral arterial disease, aortic aneurysm, venous thromboembolism and aortic valve stenosis).

Results

GWAS identified between 46 and 64 SNPs for the four PUFA traits, explaining 4.8-7.9% of circulating PUFA variance and with mean F statistics >100. Higher genetically predicted DHA (and total omega-3 fatty acids) concentration was related to higher risk of some cardiovascular endpoints; however, these findings did not pass our criteria for multiple testing correction and were attenuated when accounting for LDL-cholesterol through multivariable Mendelian randomization or excluding SNPs in the vicinity of the FADS locus. Estimates for the relation between higher genetically predicted linoleic acid (and total omega-6) concentration were inconsistent across different cardiovascular endpoints and Mendelian randomization methods. There was weak evidence of higher genetically predicted linoleic acid being related to lower risk of ischemic stroke and peripheral artery disease when accounting by LDL-cholesterol.

Conclusions

We have conducted the largest GWAS of circulating PUFA to date and the most comprehensive Mendelian randomization analyses. Overall, our Mendelian randomization findings do not support a protective role of circulating PUFA concentration on the risk of CVDs. However, horizontal pleiotropy via lipoprotein-related traits could be a key source of bias in our analyses.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02399-w; doi:https://doi.org/10.1186/s12916-022-02399-w; html:https://europepmc.org/articles/PMC9190170; pdf:https://europepmc.org/articles/PMC9190170?pdf=render 33372069,https://doi.org/10.1136/bmjopen-2020-038360,Cardiovascular risk prediction using physical performance measures in COPD: results from a multicentre observational study.,"Fermont JM, Fisk M, Bolton CE, MacNee W, Cockcroft JR, Fuld J, Cheriyan J, Mohan D, Mäki-Petäjä KM, Al-Hadithi AB, Tal-Singer R, Müllerova H, Polkey MI, Wood AM, McEniery CM, Wilkinson IB, ERICA consortium.",,BMJ open,2020,2020-12-28,Y,epidemiology; Primary Care; Cardiac Epidemiology; Chronic Airways Disease; Respiratory Medicine (See Thoracic Medicine),,,"

Objectives

Although cardiovascular disease (CVD) is a common comorbidity associated with chronic obstructive pulmonary disease (COPD), it is unknown how to improve prediction of cardiovascular (CV) risk in individuals with COPD. Traditional CV risk scores have been tested in different populations but not uniquely in COPD. The potential of alternative markers to improve CV risk prediction in individuals with COPD is unknown. We aimed to determine the predictive value of conventional CVD risk factors in COPD and to determine if additional markers improve prediction beyond conventional factors.

Design

Data from the Evaluation of the Role of Inflammation in Chronic Airways disease cohort, which enrolled 729 individuals with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II-IV COPD were used. Linked hospital episode statistics and survival data were prospectively collected for a median 4.6 years of follow-up.

Setting

Five UK centres interested in COPD.

Participants

Population-based sample including 714 individuals with spirometry-defined COPD, smoked at least 10 pack years and who were clinically stable for >4 weeks.

Interventions

Baseline measurements included aortic pulse wave velocity (aPWV), carotid intima-media thickness (CIMT), C reactive protein (CRP), fibrinogen, spirometry and Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) Index, 6 min walk test (6MWT) and 4 m gait speed (4MGS) test.

Primary and secondary outcome measures

New occurrence (first event) of fatal or non-fatal hospitalised CVD, and all-cause and cause-specific mortality.

Results

Out of 714 participants, 192 (27%) had CV hospitalisation and 6 died due to CVD. The overall CV risk model C-statistic was 0.689 (95% CI 0.688 to 0.691). aPWV and CIMT neither had an association with study outcome nor improved model prediction. CRP, fibrinogen, GOLD stage, BODE Index, 4MGS and 6MWT were associated with the outcome, independently of conventional risk factors (p<0.05 for all). However, only 6MWT improved model discrimination (C=0.727, 95% CI 0.726 to 0.728).

Conclusion

Poor physical performance defined by the 6MWT improves prediction of CV hospitalisation in individuals with COPD.

Trial registration number

ID 11101.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/12/e038360.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-038360; html:https://europepmc.org/articles/PMC7772292; pdf:https://europepmc.org/articles/PMC7772292?pdf=render 33939952,https://doi.org/10.1016/s0140-6736(21)00949-1,COVID-19 and disparities affecting ethnic minorities.,"Morales DR, Ali SN.",,"Lancet (London, England)",2021,2021-04-30,Y,,,,,,pdf:http://www.thelancet.com/article/S0140673621009491/pdf; doi:https://doi.org/10.1016/S0140-6736(21)00949-1; html:https://europepmc.org/articles/PMC9755653; pdf:https://europepmc.org/articles/PMC9755653?pdf=render +35692035,https://doi.org/10.1186/s12916-022-02399-w,"Role of circulating polyunsaturated fatty acids on cardiovascular diseases risk: analysis using Mendelian randomization and fatty acid genetic association data from over 114,000 UK Biobank participants.","Borges MC, Haycock PC, Zheng J, Hemani G, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA.",,BMC medicine,2022,2022-06-13,Y,Fatty acids; Cardiovascular diseases; Mendelian Randomization,,,"

Background

Despite early interest in the health effects of polyunsaturated fatty acids (PUFA), there is still substantial controversy and uncertainty on the evidence linking PUFA to cardiovascular diseases (CVDs). We investigated the effect of plasma concentration of omega-3 PUFA (i.e. docosahexaenoic acid (DHA) and total omega-3 PUFA) and omega-6 PUFA (i.e. linoleic acid and total omega-6 PUFA) on the risk of CVDs using Mendelian randomization.

Methods

We conducted the largest genome-wide association study (GWAS) of circulating PUFA to date including a sample of 114,999 individuals and incorporated these data in a two-sample Mendelian randomization framework to investigate the involvement of circulating PUFA on a wide range of CVDs in up to 1,153,768 individuals of European ancestry (i.e. coronary artery disease, ischemic stroke, haemorrhagic stroke, heart failure, atrial fibrillation, peripheral arterial disease, aortic aneurysm, venous thromboembolism and aortic valve stenosis).

Results

GWAS identified between 46 and 64 SNPs for the four PUFA traits, explaining 4.8-7.9% of circulating PUFA variance and with mean F statistics >100. Higher genetically predicted DHA (and total omega-3 fatty acids) concentration was related to higher risk of some cardiovascular endpoints; however, these findings did not pass our criteria for multiple testing correction and were attenuated when accounting for LDL-cholesterol through multivariable Mendelian randomization or excluding SNPs in the vicinity of the FADS locus. Estimates for the relation between higher genetically predicted linoleic acid (and total omega-6) concentration were inconsistent across different cardiovascular endpoints and Mendelian randomization methods. There was weak evidence of higher genetically predicted linoleic acid being related to lower risk of ischemic stroke and peripheral artery disease when accounting by LDL-cholesterol.

Conclusions

We have conducted the largest GWAS of circulating PUFA to date and the most comprehensive Mendelian randomization analyses. Overall, our Mendelian randomization findings do not support a protective role of circulating PUFA concentration on the risk of CVDs. However, horizontal pleiotropy via lipoprotein-related traits could be a key source of bias in our analyses.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02399-w; doi:https://doi.org/10.1186/s12916-022-02399-w; html:https://europepmc.org/articles/PMC9190170; pdf:https://europepmc.org/articles/PMC9190170?pdf=render 35072885,https://doi.org/10.1007/s10439-022-02905-4,Modeling the His-Purkinje Effect in Non-invasive Estimation of Endocardial and Epicardial Ventricular Activation.,"Boonstra MJ, Roudijk RW, Brummel R, Kassenberg W, Blom LJ, Oostendorp TF, Te Riele ASJM, van der Heijden JF, Asselbergs FW, Loh P, van Dam PM.",,Annals of biomedical engineering,2022,2022-01-24,Y,Electrophysiology; Electrocardiography; Cardiovascular Imaging; Electrocardiographic Imaging; Electro-anatomical Mapping; His-purkinje System; Inverse Electrocardiography; Equivalent Dipole Layer; Non-invasive Cardiac Activation Mapping,,,"Inverse electrocardiography (iECG) estimates epi- and endocardial electrical activity from body surface potentials maps (BSPM). In individuals at risk for cardiomyopathy, non-invasive estimation of normal ventricular activation may provide valuable information to aid risk stratification to prevent sudden cardiac death. However, multiple simultaneous activation wavefronts initiated by the His-Purkinje system, severely complicate iECG. To improve the estimation of normal ventricular activation, the iECG method should accurately mimic the effect of the His-Purkinje system, which is not taken into account in the previously published multi-focal iECG. Therefore, we introduce the novel multi-wave iECG method and report on its performance. Multi-wave iECG and multi-focal iECG were tested in four patients undergoing invasive electro-anatomical mapping during normal ventricular activation. In each subject, 67-electrode BSPM were recorded and used as input for both iECG methods. The iECG and invasive local activation timing (LAT) maps were compared. Median epicardial inter-map correlation coefficient (CC) between invasive LAT maps and estimated multi-wave iECG versus multi-focal iECG was 0.61 versus 0.31. Endocardial inter-map CC was 0.54 respectively 0.22. Modeling the His-Purkinje system resulted in a physiologically realistic and robust non-invasive estimation of normal ventricular activation, which might enable the early detection of cardiac disease during normal sinus rhythm.",,pdf:https://link.springer.com/content/pdf/10.1007/s10439-022-02905-4.pdf; doi:https://doi.org/10.1007/s10439-022-02905-4; html:https://europepmc.org/articles/PMC8847268; pdf:https://europepmc.org/articles/PMC8847268?pdf=render 37198662,https://doi.org/10.1186/s13293-023-00516-9,Sex-based differences in cardiovascular proteomic profiles and their associations with adverse outcomes in patients with chronic heart failure.,"de Bakker M, Petersen TB, Akkerhuis KM, Harakalova M, Umans VA, Germans T, Caliskan K, Katsikis PD, van der Spek PJ, Suthahar N, de Boer RA, Rizopoulos D, Asselbergs FW, Boersma E, Kardys I.",,Biology of sex differences,2023,2023-05-17,Y,Proteomics; Sex differences; Heart Failure; Hfref,,,"

Background

Studies focusing on sex differences in circulating proteins in patients with heart failure with reduced ejection fraction (HFrEF) are scarce. Insight into sex-specific cardiovascular protein profiles and their associations with the risk of adverse outcomes may contribute to a better understanding of the pathophysiological processes involved in HFrEF. Moreover, it could provide a basis for the use of circulating protein measurements for prognostication in women and men, wherein the most relevant protein measurements are applied in each of the sexes.

Methods

In 382 patients with HFrEF, we performed tri-monthly blood sampling (median follow-up: 25 [13-31] months). We selected all baseline samples and two samples closest to the primary endpoint (PEP: composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization) or censoring. We then applied an aptamer-based multiplex proteomic assay identifying 1105 proteins previously associated with cardiovascular disease. We used linear regression models and gene-enrichment analysis to study sex-based differences in baseline levels. We used time-dependent Cox models to study differences in the prognostic value of serially measured proteins. All models were adjusted for the MAGGIC HF mortality risk score and p-values for multiple testing.

Results

In 104 women and 278 men (mean age 62 and 64 years, respectively) cumulative PEP incidence at 30 months was 25% and 35%, respectively. At baseline, 55 (5%) out of the 1105 proteins were significantly different between women and men. The female protein profile was most strongly associated with extracellular matrix organization, while the male profile was dominated by regulation of cell death. The association of endothelin-1 (Pinteraction < 0.001) and somatostatin (Pinteraction = 0.040) with the PEP was modified by sex, independent of clinical characteristics. Endothelin-1 was more strongly associated with the PEP in men (HR 2.62 [95%CI, 1.98, 3.46], p < 0.001) compared to women (1.14 [1.01, 1.29], p = 0.036). Somatostatin was positively associated with the PEP in men (1.23 [1.10, 1.38], p < 0.001), but inversely associated in women (0.33 [0.12, 0.93], p = 0.036).

Conclusion

Baseline cardiovascular protein levels differ between women and men. However, the predictive value of repeatedly measured circulating proteins does not seem to differ except for endothelin-1 and somatostatin.",,pdf:https://bsd.biomedcentral.com/counter/pdf/10.1186/s13293-023-00516-9; doi:https://doi.org/10.1186/s13293-023-00516-9; html:https://europepmc.org/articles/PMC10193800; pdf:https://europepmc.org/articles/PMC10193800?pdf=render 32345651,https://doi.org/10.2337/dc19-2116,"Obstructive Sleep Apnea, a Risk Factor for Cardiovascular and Microvascular Disease in Patients With Type 2 Diabetes: Findings From a Population-Based Cohort Study.","Adderley NJ, Subramanian A, Toulis K, Gokhale K, Taverner T, Hanif W, Haroon S, Thomas GN, Sainsbury C, Tahrani AA, Nirantharakumar K.",,Diabetes care,2020,2020-04-28,N,,,,"

Objective

To determine the risk of cardiovascular disease (CVD), microvascular complications, and mortality in patients with type 2 diabetes who subsequently develop obstructive sleep apnea (OSA) compared with patients with type 2 diabetes without a diagnosis of OSA.

Research design and methods

This age-, sex-, BMI-, and diabetes duration-matched cohort study used data from a U.K. primary care database from 1 January 2005 to 17 January 2018. Participants aged ≥16 years with type 2 diabetes were included. Exposed participants were those who developed OSA after their diabetes diagnosis; unexposed participants were those without diagnosed OSA. Outcomes were composite CVD (ischemic heart disease [IHD], stroke/transient ischemic attack [TIA], heart failure [HF]), peripheral vascular disease (PVD), atrial fibrillation (AF), peripheral neuropathy (PN), diabetes-related foot disease (DFD), referable retinopathy, chronic kidney disease (CKD), and all-cause mortality. The same outcomes were explored in patients with preexisting OSA before a diagnosis of type 2 diabetes versus diabetes without diagnosed OSA.

Results

A total of 3,667 exposed participants and 10,450 matched control participants were included. Adjusted hazard ratios for the outcomes were as follows: composite CVD 1.54 (95% CI 1.32, 1.79), IHD 1.55 (1.26, 1.90), HF 1.67 (1.35, 2.06), stroke/TIA 1.57 (1.27, 1.94), PVD 1.10 (0.91, 1.32), AF 1.53 (1.28, 1.83), PN 1.32 (1.14, 1.51), DFD 1.42 (1.16, 1.74), referable retinopathy 0.99 (0.82, 1.21), CKD (stage 3-5) 1.18 (1.02, 1.36), albuminuria 1.11 (1.01, 1.22), and all-cause mortality 1.24 (1.10, 1.40). In the prevalent OSA cohort, the results were similar, but some associations were not observed.

Conclusions

Patients with type 2 diabetes who develop OSA are at increased risk of CVD, AF, PN, DFD, CKD, and all-cause mortality compared with patients without diagnosed OSA. Patients with type 2 diabetes who develop OSA are a high-risk population, and strategies to detect OSA and prevent cardiovascular and microvascular complications should be implemented.",,pdf:https://care.diabetesjournals.org/content/diacare/43/8/1868.full.pdf; doi:https://doi.org/10.2337/dc19-2116 @@ -1556,8 +1556,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 36331190,https://doi.org/10.1056/nejmoa2204233,Empagliflozin in Patients with Chronic Kidney Disease.,"The EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, Preiss D, Judge P, Mayne KJ, Ng SYA, Sammons E, Zhu D, Hill M, Stevens W, Wallendszus K, Brenner S, Cheung AK, Liu ZH, Li J, Hooi LS, Liu W, Kadowaki T, Nangaku M, Levin A, Cherney D, Maggioni AP, Pontremoli R, Deo R, Goto S, Rossello X, Tuttle KR, Steubl D, Petrini M, Massey D, Eilbracht J, Brueckmann M, Landray MJ, Baigent C, Haynes R.",,The New England journal of medicine,2023,2022-11-04,Y,,,,"

Background

The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients.

Methods

We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to <10 ml per minute per 1.73 m2, a sustained decrease in eGFR of ≥40% from baseline, or death from renal causes) or death from cardiovascular causes.

Results

A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P<0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P = 0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups.

Conclusions

Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110; EudraCT number, 2017-002971-24.).",,pdf:https://ora.ox.ac.uk/objects/uuid:f91f9722-f207-4d97-aa64-58636b323acc/files/r6969z144v; doi:https://doi.org/10.1056/NEJMoa2204233; html:https://europepmc.org/articles/PMC7614055; pdf:https://europepmc.org/articles/PMC7614055?pdf=render 38190103,https://doi.org/10.1016/j.xgen.2023.100469,Genome-wide classification of epigenetic activity reveals regions of enriched heritability in immune-related traits.,"Stricker M, Zhang W, Cheng WY, Gazal S, Dendrou C, Nahkuri S, Palamara PF.",,Cell genomics,2024,2023-12-28,Y,Immune system; Heritability; Epigenetics; Machine Learning,,,"Epigenetics underpins the regulation of genes known to play a key role in the adaptive and innate immune system (AIIS). We developed a method, EpiNN, that leverages epigenetic data to detect AIIS-relevant genomic regions and used it to detect 2,765 putative AIIS loci. Experimental validation of one of these loci, DNMT1, provided evidence for a novel AIIS-specific transcription start site. We built a genome-wide AIIS annotation and used linkage disequilibrium (LD) score regression to test whether it predicts regional heritability using association statistics for 176 traits. We detected significant heritability effects (average |τ∗|=1.65) for 20 out of 26 immune-relevant traits. In a meta-analysis, immune-relevant traits and diseases were 4.45× more enriched for heritability than other traits. The EpiNN annotation was also depleted of trans-ancestry genetic correlation, indicating ancestry-specific effects. These results underscore the effectiveness of leveraging supervised learning algorithms and epigenetic data to detect loci implicated in specific classes of traits and diseases.",,doi:https://doi.org/10.1016/j.xgen.2023.100469; html:https://europepmc.org/articles/PMC10794845; pdf:https://europepmc.org/articles/PMC10794845?pdf=render 35275087,https://doi.org/10.2196/34898,Longitudinal Relationships Between Depressive Symptom Severity and Phone-Measured Mobility: Dynamic Structural Equation Modeling Study.,"Zhang Y, Folarin AA, Sun S, Cummins N, Vairavan S, Bendayan R, Ranjan Y, Rashid Z, Conde P, Stewart C, Laiou P, Sankesara H, Matcham F, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Vilella E, Simblett S, Rintala A, Bruce S, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BW, Narayan VA, Annas P, Hotopf M, Dobson RJ, RADAR-CNS consortium.",,JMIR mental health,2022,2022-03-11,Y,Modeling; Mobility; Depression; Mental health; Medical Informatics; Mhealth; Mobile Health; Dynamic Structural Equation Modeling; Location Data,,,"

Background

The mobility of an individual measured by phone-collected location data has been found to be associated with depression; however, the longitudinal relationships (the temporal direction of relationships) between depressive symptom severity and phone-measured mobility have yet to be fully explored.

Objective

We aimed to explore the relationships and the direction of the relationships between depressive symptom severity and phone-measured mobility over time.

Methods

Data used in this paper came from a major EU program, called the Remote Assessment of Disease and Relapse-Major Depressive Disorder, which was conducted in 3 European countries. Depressive symptom severity was measured with the 8-item Patient Health Questionnaire (PHQ-8) through mobile phones every 2 weeks. Participants' location data were recorded by GPS and network sensors in mobile phones every 10 minutes, and 11 mobility features were extracted from location data for the 2 weeks prior to the PHQ-8 assessment. Dynamic structural equation modeling was used to explore the longitudinal relationships between depressive symptom severity and phone-measured mobility.

Results

This study included 2341 PHQ-8 records and corresponding phone-collected location data from 290 participants (age: median 50.0 IQR 34.0, 59.0) years; of whom 215 (74.1%) were female, and 149 (51.4%) were employed. Significant negative correlations were found between depressive symptom severity and phone-measured mobility, and these correlations were more significant at the within-individual level than the between-individual level. For the direction of relationships over time, Homestay (time at home) (φ=0.09, P=.01), Location Entropy (time distribution on different locations) (φ=-0.04, P=.02), and Residential Location Count (reflecting traveling) (φ=0.05, P=.02) were significantly correlated with the subsequent changes in the PHQ-8 score, while changes in the PHQ-8 score significantly affected (φ=-0.07, P<.001) the subsequent periodicity of mobility.

Conclusions

Several phone-derived mobility features have the potential to predict future depression, which may provide support for future clinical applications, relapse prevention, and remote mental health monitoring practices in real-world settings.",,pdf:https://mental.jmir.org/2022/3/e34898/PDF; doi:https://doi.org/10.2196/34898; html:https://europepmc.org/articles/PMC8957008 -35355205,https://doi.org/10.1007/s11897-022-00544-3,LVEF by Multigated Acquisition Scan Compared to Other Imaging Modalities in Cardio-Oncology: a Systematic Review.,"Printezi MI, Yousif LIE, Kamphuis JAM, van Laake LW, Cramer MJ, Hobbelink MGG, Asselbergs FW, Teske AJ.",,Current heart failure reports,2022,2022-03-30,Y,Cardiotoxicity; Echocardiography; Left ventricular ejection fraction; Cardiac Magnetic Resonance Imaging; Cardio-oncology; Multigated Acquisition Scan,,,"

Purpose of review

The prevalence of cancer therapy-related cardiac dysfunction (CTRCD) is increasing due to improved cancer survival. Serial monitoring of cardiac function is essential to detect CTRCD, guiding timely intervention strategies. Multigated radionuclide angiography (MUGA) has been the main screening tool using left ventricular ejection fraction (LVEF) to monitor cardiac dysfunction. However, transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) may be more suitable for serial assessment. We aimed to assess the concordance between different non-radiating imaging modalities with MUGA to determine whether they can be used interchangeably.

Recent findings

In order to identify relevant studies, a PubMed search was performed. We included cross-sectional studies comparing MUGA LVEF to that of 2D TTE, 3D TTE, and CMR. From 470 articles, 22 were selected, comprising 1017 patients in total. Among others, this included three 3D TTE, seven 2D harmonic TTE + contrast (2DHC), and seven CMR comparisons. The correlations and Bland-Altman limits of agreement varied for CMR but were stronger for 3D TTE and 2DHC. Our findings suggest that MUGA and CMR should not be used interchangeably whereas 3D TTE and 2DHC are appropriate alternatives following an initial MUGA scan. We propose a multimodality diagnostic imaging strategy for LVEF monitoring in patients undergoing cancer treatment.",,pdf:https://link.springer.com/content/pdf/10.1007/s11897-022-00544-3.pdf; doi:https://doi.org/10.1007/s11897-022-00544-3; html:https://europepmc.org/articles/PMC9177497; pdf:https://europepmc.org/articles/PMC9177497?pdf=render 32017129,https://doi.org/10.5694/mja2.50485,Discharge destination and patient-reported outcomes after inpatient treatment for isolated lower limb fractures.,"Kimmel LA, Simpson PM, Holland AE, Edwards ER, Cameron PA, de Steiger RS, Page RS, Hau R, Bucknill A, Kasza J, Gabbe BJ.",,The Medical journal of Australia,2020,2020-02-04,N,"Rehabilitation; Treatment outcome; Orthopedic Procedures; Fractures, Bone; Trauma Surgery",,,"

Objectives

To examine the association between discharge destination (home or inpatient rehabilitation) for adult patients treated in hospital for isolated lower limb fractures and patient-reported outcomes.

Design

Review of prospectively collected Victorian Orthopaedic Trauma Outcomes Registry (VOTOR) data.

Setting, participants

Adults (18-64 years old) treated for isolated lower limb fractures at four Melbourne trauma hospitals that contribute data to the VOTOR, 1 March 2007 - 31 March 2016.

Main outcome measures

Return to work and functional recovery (assessed with the extended Glasgow Outcomes Scale, GOS-E); propensity score analysis of association between discharge destination and outcome.

Results

Of 7961 eligible patients, 1432 (18%) were discharged to inpatient rehabilitation, and 6775 (85%) were followed up 12 months after their injuries. After propensity score adjustment, the odds of better functional recovery were 56% lower for patients discharged to inpatient rehabilitation than for those discharged directly home (odds ratio, 0.44; 95% CI, 0.37-0.51); for the 5057 people working before their accident, the odds of return to work were reduced by 66% (odds ratio, 0.34; 95% CI, 0.26-0.46). Propensity score analysis improved matching of the discharge destination groups, but imbalances in funding source remained for both outcome analyses, and for also for site and cause of injury in the GOS-E analysis (standardised differences, 10-16%).

Conclusions

Discharge to inpatient rehabilitation after treatment for isolated lower limb fractures was associated with poorer outcomes than discharge home. Factors that remained unbalanced after propensity score analysis could be assessed in controlled trials.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.5694/mja2.50485; doi:https://doi.org/10.5694/mja2.50485 +35355205,https://doi.org/10.1007/s11897-022-00544-3,LVEF by Multigated Acquisition Scan Compared to Other Imaging Modalities in Cardio-Oncology: a Systematic Review.,"Printezi MI, Yousif LIE, Kamphuis JAM, van Laake LW, Cramer MJ, Hobbelink MGG, Asselbergs FW, Teske AJ.",,Current heart failure reports,2022,2022-03-30,Y,Cardiotoxicity; Echocardiography; Left ventricular ejection fraction; Cardiac Magnetic Resonance Imaging; Cardio-oncology; Multigated Acquisition Scan,,,"

Purpose of review

The prevalence of cancer therapy-related cardiac dysfunction (CTRCD) is increasing due to improved cancer survival. Serial monitoring of cardiac function is essential to detect CTRCD, guiding timely intervention strategies. Multigated radionuclide angiography (MUGA) has been the main screening tool using left ventricular ejection fraction (LVEF) to monitor cardiac dysfunction. However, transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) may be more suitable for serial assessment. We aimed to assess the concordance between different non-radiating imaging modalities with MUGA to determine whether they can be used interchangeably.

Recent findings

In order to identify relevant studies, a PubMed search was performed. We included cross-sectional studies comparing MUGA LVEF to that of 2D TTE, 3D TTE, and CMR. From 470 articles, 22 were selected, comprising 1017 patients in total. Among others, this included three 3D TTE, seven 2D harmonic TTE + contrast (2DHC), and seven CMR comparisons. The correlations and Bland-Altman limits of agreement varied for CMR but were stronger for 3D TTE and 2DHC. Our findings suggest that MUGA and CMR should not be used interchangeably whereas 3D TTE and 2DHC are appropriate alternatives following an initial MUGA scan. We propose a multimodality diagnostic imaging strategy for LVEF monitoring in patients undergoing cancer treatment.",,pdf:https://link.springer.com/content/pdf/10.1007/s11897-022-00544-3.pdf; doi:https://doi.org/10.1007/s11897-022-00544-3; html:https://europepmc.org/articles/PMC9177497; pdf:https://europepmc.org/articles/PMC9177497?pdf=render 34019073,https://doi.org/10.1093/ibd/izab059,Ultra-high Magnification Endocytoscopy and Molecular Markers for Defining Endoscopic and Histologic Remission in Ulcerative Colitis-An Exploratory Study to Define Deep Remission.,"Iacucci M, Jeffery L, Acharjee A, Nardone OM, Zardo D, Smith SCL, Bazarova A, Cannatelli R, Shivaji UN, Williams J, Gkoutos G, Ghosh S.",,Inflammatory bowel diseases,2021,2021-10-01,Y,Rna-sequencing; Mucosal Healing; Histological Healing; Noninvasive Markers; Endocytoscope,,,"

Background

Endoscopic and histological remission are both important treatment goals in patients with ulcerative colitis (UC). We aimed to define cellular architecture, expression of molecular markers, and their correlation with endoscopic scores assessed by ultra-high magnification endocytoscopy (ECS) and histological scores.

Methods

Patients with UC (n = 29) were prospectively recruited. The correlation among ECS score (ECSS), Mayo endoscopic score (MES), and histological scores were determined. Area under curve were plotted to determine the best thresholds for ECSS that predicted histological remission by Robarts (RHI) and Nancy Histological Index (NHI).Soluble analytes relevant to inflammation were measured in serum and mucosal culture supernatants using ProcartaPlex Luminex assays and studied by partial least square discriminant analysis and logistic model. Mucosal RNA sequencing and bioinformatics analysis were performed to define differentially expressed genes/pathways.

Results

Endocytoscope scoring system correlated strongly with RHI (r = 0.89; 95% CI, 0.51-0.98) and NHI (r = 0.86; 95% CI, 0.42-0.98) but correlated poorly with MES (r = 0.28; 95% CI, 0.27-0.70). We identified soluble brain-derived neurotrophic factors (BDNF), macrophage inflammatory proteins (MIP-1 α) and soluble vascular cell adhesion molecule 1 (sVCAM-1) predicted histological remission. Mucosal biopsy cultures also identified sVCAM-1 associated with healed mucosa. RNA-seq analysis identified gene expressions shared between ECSS, RHI, or NHI defined healing. A number of gene expressions and pathways were identified including inflammation and metabolic and tumor suppressors that discriminated healed from nonhealed mucosa.

Conclusions

Endocytoscopy represents an interesting tool that may sit between endoscopy and histology-but closer to the latter-identifying gene expression markers and pathways that are also identified by histology.",,pdf:https://academic.oup.com/ibdjournal/article-pdf/27/11/1719/40784408/izab059.pdf; doi:https://doi.org/10.1093/ibd/izab059; html:https://europepmc.org/articles/PMC8528147; pdf:https://europepmc.org/articles/PMC8528147?pdf=render 36240828,https://doi.org/10.1016/s2214-109x(22)00358-8,Prediction of upcoming global infection burden of influenza seasons after relaxation of public health and social measures during the COVID-19 pandemic: a modelling study.,"Ali ST, Lau YC, Shan S, Ryu S, Du Z, Wang L, Xu XK, Chen D, Xiong J, Tae J, Tsang TK, Wu P, Lau EHY, Cowling BJ.",,The Lancet. Global health,2022,2022-11-01,Y,,,,"

Background

The transmission dynamics of influenza were affected by public health and social measures (PHSMs) implemented globally since early 2020 to mitigate the COVID-19 pandemic. We aimed to assess the effect of COVID-19 PHSMs on the transmissibility of influenza viruses and to predict upcoming influenza epidemics.

Methods

For this modelling study, we used surveillance data on influenza virus activity for 11 different locations and countries in 2017-22. We implemented a data-driven mechanistic predictive modelling framework to predict future influenza seasons on the basis of pre-COVID-19 dynamics and the effect of PHSMs during the COVID-19 pandemic. We simulated the potential excess burden of upcoming influenza epidemics in terms of fold rise in peak magnitude and epidemic size compared with pre-COVID-19 levels. We also examined how a proactive influenza vaccination programme could mitigate this effect.

Findings

We estimated that COVID-19 PHSMs reduced influenza transmissibility by a maximum of 17·3% (95% CI 13·3-21·4) to 40·6% (35·2-45·9) and attack rate by 5·1% (1·5-7·2) to 24·8% (20·8-27·5) in the 2019-20 influenza season. We estimated a 10-60% increase in the population susceptibility for influenza, which might lead to a maximum of 1-5-fold rise in peak magnitude and 1-4-fold rise in epidemic size for the upcoming 2022-23 influenza season across locations, with a significantly higher fold rise in Singapore and Taiwan. The infection burden could be mitigated by additional proactive one-off influenza vaccination programmes.

Interpretation

Our results suggest the potential for substantial increases in infection burden in upcoming influenza seasons across the globe. Strengthening influenza vaccination programmes is the best preventive measure to reduce the effect of influenza virus infections in the community.

Funding

Health and Medical Research Fund, Hong Kong.",,pdf:https://www.repository.cam.ac.uk/bitstreams/bb5465bd-c08f-4c3d-ab0e-87fee39fc92b/download; doi:https://doi.org/10.1016/S2214-109X(22)00358-8; html:https://europepmc.org/articles/PMC9573849 37046260,https://doi.org/10.1186/s12913-023-09363-1,Associations between the stringency of COVID-19 containment policies and health service disruptions in 10 countries.,"Reddy T, Kapoor NR, Kubota S, Doubova SV, Asai D, Mariam DH, Ayele W, Mebratie AD, Thermidor R, Sapag JC, Bedregal P, Passi-Solar Á, Gordon-Strachan G, Dulal M, Gadeka DD, Mehata S, Margozzini P, Leerapan B, Rittiphairoj T, Kaewkamjornchai P, Nega A, Awoonor-Williams JK, Kruk ME, Arsenault C.",,BMC health services research,2023,2023-04-12,Y,Health Services; Health Systems; Pandemic Response; Health System Resilience; Covid-19 Restrictions; Health Care Disruptions,,,"

Background

Disruptions in essential health services during the COVID-19 pandemic have been reported in several countries. Yet, patterns in health service disruption according to country responses remain unclear. In this paper, we investigate associations between the stringency of COVID-19 containment policies and disruptions in 31 health services in 10 low- middle- and high-income countries in 2020.

Methods

Using routine health information systems and administrative data from 10 countries (Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, South Korea, and Thailand) we estimated health service disruptions for the period of April to December 2020 by dividing monthly service provision at national levels by the average service provision in the 15 months pre-COVID (January 2019-March 2020). We used the Oxford COVID-19 Government Response Tracker (OxCGRT) index and multi-level linear regression analyses to assess associations between the stringency of restrictions and health service disruptions over nine months. We extended the analysis by examining associations between 11 individual containment or closure policies and health service disruptions. Models were adjusted for COVID caseload, health service category and country GDP and included robust standard errors.

Findings

Chronic disease care was among the most affected services. Regression analyses revealed that a 10% increase in the mean stringency index was associated with a 3.3 percentage-point (95% CI -3.9, -2.7) reduction in relative service volumes. Among individual policies, curfews, and the presence of a state of emergency, had the largest coefficients and were associated with 14.1 (95% CI -19.6, 8.7) and 10.7 (95% CI -12.7, -8.7) percentage-point lower relative service volumes, respectively. In contrast, number of COVID-19 cases in 2020 was not associated with health service disruptions in any model.

Conclusions

Although containment policies were crucial in reducing COVID-19 mortality in many contexts, it is important to consider the indirect effects of these restrictions. Strategies to improve the resilience of health systems should be designed to ensure that populations can continue accessing essential health care despite the presence of containment policies during future infectious disease outbreaks.",,pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-023-09363-1; doi:https://doi.org/10.1186/s12913-023-09363-1; html:https://europepmc.org/articles/PMC10096103; pdf:https://europepmc.org/articles/PMC10096103?pdf=render @@ -1584,21 +1584,21 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 33905476,https://doi.org/10.1093/cid/ciab192,Model-Based Geostatistical Methods Enable Efficient Design and Analysis of Prevalence Surveys for Soil-Transmitted Helminth Infection and Other Neglected Tropical Diseases.,"Johnson O, Fronterre C, Amoah B, Montresor A, Giorgi E, Midzi N, Mutsaka-Makuvaza MJ, Kargbo-Labor I, Hodges MH, Zhang Y, Okoyo C, Mwandawiro C, Minnery M, Diggle PJ.",,Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,2021,2021-06-01,Y,Geospatial Analysis; Prevalence Survey; Soil-transmitted Helminth Infection; Model-based Geostatistics; Control Of Neglected Tropical Diseases; Impact Survey,,,"Maps of the geographical variation in prevalence play an important role in large-scale programs for the control of neglected tropical diseases. Precontrol mapping is needed to establish the appropriate control intervention in each area of the country in question. Mapping is also needed postintervention to measure the success of control efforts. In the absence of comprehensive disease registries, mapping efforts can be informed by 2 kinds of data: empirical estimates of local prevalence obtained by testing individuals from a sample of communities within the geographical region of interest, and digital images of environmental factors that are predictive of local prevalence. In this article, we focus on the design and analysis of impact surveys, that is, prevalence surveys that are conducted postintervention with the aim of informing decisions on what further intervention, if any, is needed to achieve elimination of the disease as a public health problem. We show that geospatial statistical methods enable prevalence surveys to be designed and analyzed as efficiently as possible so as to make best use of hard-won field data. We use 3 case studies based on data from soil-transmitted helminth impact surveys in Kenya, Sierra Leone, and Zimbabwe to compare the predictive performance of model-based geostatistics with methods described in current World Health Organization (WHO) guidelines. In all 3 cases, we find that model-based geostatistics substantially outperforms the current WHO guidelines, delivering improved precision for reduced field-sampling effort. We argue from experience that similar improvements will hold for prevalence mapping of other neglected tropical diseases.",,pdf:https://academic.oup.com/cid/article-pdf/72/Supplement_3/S172/38618862/ciab192.pdf; doi:https://doi.org/10.1093/cid/ciab192; html:https://europepmc.org/articles/PMC8201574; pdf:https://europepmc.org/articles/PMC8201574?pdf=render 36819459,https://doi.org/10.1210/jendso/bvad020,"Polygenic Risk of Prediabetes, Undiagnosed Diabetes, and Incident Type 2 Diabetes Stratified by Diabetes Risk Factors.","Liu X, Collister JA, Clifton L, Hunter DJ, Littlejohns TJ.",,Journal of the Endocrine Society,2023,2023-01-30,Y,BMI; Family History; Polygenic Risk And Diabetes,,,"

Context

Early diagnosis of type 2 diabetes is crucial to reduce severe comorbidities and complications. Current screening recommendations for type 2 diabetes include traditional risk factors, primarily body mass index (BMI) and family history, however genetics also plays a key role in type 2 diabetes risk. It is important to understand whether genetic predisposition to type 2 diabetes modifies the effect of these traditional factors on type 2 diabetes risk.

Objective

This work aimed to investigate whether genetic risk of type 2 diabetes modifies associations between BMI and first-degree family history of diabetes with 1) prevalent prediabetes or undiagnosed diabetes; and 2) incident confirmed type 2 diabetes.

Methods

We included 431 658 individuals aged 40 to 69 years at baseline of multiethnic ancestry from the UK Biobank. We used a multiethnic polygenic risk score for type 2 diabetes (PRST2D) developed by Genomics PLC. Prediabetes or undiagnosed diabetes was defined as baseline glycated hemoglobin greater than or equal to 42 mmol/mol (6.0%), and incident type 2 diabetes was derived from medical records.

Results

At baseline, 43 472 participants had prediabetes or undiagnosed diabetes, and 17 259 developed type 2 diabetes over 15 years follow-up. Dose-response associations were observed for PRST2D with each outcome in each category of BMI or first-degree family history of diabetes. Those in the highest quintile of PRST2D with a normal BMI were at a similar risk as those in the middle quintile who were overweight. Participants who were in the highest quintile of PRST2D and did not have a first-degree family history of diabetes were at a similar risk as those with a family history who were in the middle category of PRST2D.

Conclusion

Genetic risk of type 2 diabetes remains strongly associated with risk of prediabetes, undiagnosed diabetes, and future type 2 diabetes within categories of nongenetic risk factors. This could have important implications for identifying individuals at risk of type 2 diabetes for prevention and early diagnosis programs.",,pdf:https://academic.oup.com/jes/article-pdf/7/4/bvad020/49229172/bvad020.pdf; doi:https://doi.org/10.1210/jendso/bvad020; html:https://europepmc.org/articles/PMC9933896; pdf:https://europepmc.org/articles/PMC9933896?pdf=render 35922433,https://doi.org/10.1038/s41467-022-32219-x,Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities.,"Francis CM, Futschik ME, Huang J, Bai W, Sargurupremraj M, Teumer A, Breteler MMB, Petretto E, Ho ASR, Amouyel P, Engelter ST, Bülow R, Völker U, Völzke H, Dörr M, Imtiaz MA, Aziz NA, Lohner V, Ware JS, Debette S, Elliott P, Dehghan A, Matthews PM.",,Nature communications,2022,2022-08-03,Y,,,,"Aortic dimensions and distensibility are key risk factors for aortic aneurysms and dissections, as well as for other cardiovascular and cerebrovascular diseases. We present genome-wide associations of ascending and descending aortic distensibility and area derived from cardiac magnetic resonance imaging (MRI) data of up to 32,590 Caucasian individuals in UK Biobank. We identify 102 loci (including 27 novel associations) tagging genes related to cardiovascular development, extracellular matrix production, smooth muscle cell contraction and heritable aortic diseases. Functional analyses highlight four signalling pathways associated with aortic distensibility (TGF-β, IGF, VEGF and PDGF). We identify distinct sex-specific associations with aortic traits. We develop co-expression networks associated with aortic traits and apply phenome-wide Mendelian randomization (MR-PheWAS), generating evidence for a causal role for aortic distensibility in development of aortic aneurysms. Multivariable MR suggests a causal relationship between aortic distensibility and cerebral white matter hyperintensities, mechanistically linking aortic traits and brain small vessel disease.",,pdf:https://www.nature.com/articles/s41467-022-32219-x.pdf; doi:https://doi.org/10.1038/s41467-022-32219-x; html:https://europepmc.org/articles/PMC9349177; pdf:https://europepmc.org/articles/PMC9349177?pdf=render -35410933,https://doi.org/10.1136/bmjopen-2021-057885,"Non-pharmacological therapies for postviral syndromes, including Long COVID: a systematic review and meta-analysis protocol.","Chandan JS, Brown K, Simms-Williams N, Camaradou J, Bashir N, Heining D, Aiyegbusi OL, Turner G, Cruz Rivera S, Hotham R, Nirantharakumar K, Sivan M, Khunti K, Raindi D, Marwaha S, Hughes SE, McMullan C, Calvert M, Haroon S.",,BMJ open,2022,2022-04-11,Y,Infectious diseases; Rehabilitation Medicine; Covid-19,,,"

Introduction

Postviral syndromes (PVS) describe the sustained presence of symptoms following an acute viral infection, for months or even years. Exposure to the SARS-CoV-2 virus and subsequent development of COVID-19 has shown to have similar effects with individuals continuing to exhibit symptoms for greater than 12 weeks. The sustained presence of symptoms is variably referred to as 'post COVID-19 syndrome', 'post-COVID condition' or more commonly 'Long COVID'. Knowledge of the long-term health impacts and treatments for Long COVID are evolving. To minimise overlap with existing work in the field exploring treatments of Long COVID, we have only chosen to focus on non-pharmacological treatments.

Aims

This review aims to summarise the effectiveness of non-pharmacological treatments for PVS, including Long COVID. A secondary aim is to summarise the symptoms and health impacts associated with PVS in individuals recruited to treatment studies.

Methods and analysis

Primary electronic searches will be performed in bibliographic databases including: Embase, MEDLINE, PyscINFO, CINAHL and MedRxiv from 1 January 2001 to 29 October 2021. At least two independent reviewers will screen each study for inclusion and data will be extracted from all eligible studies onto a data extraction form. The quality of all included studies will be assessed using Cochrane risk of bias tools and the Newcastle-Ottawa grading system. Non-pharmacological treatments for PVS and Long COVID will be narratively summarised and effect estimates will be pooled using random effects meta-analysis where there is sufficient methodological homogeneity. The symptoms and health impacts reported in the included studies on non-pharmacological interventions will be extracted and narratively reported.

Ethics and dissemination

This systematic review does not require ethical approval. The findings from this study will be submitted for peer-reviewed publication, shared at conference presentations and disseminated to both clinical and patient groups.

Prospero registration number

The review will adhere to this protocol which has also been registered with PROSPERO (CRD42021282074).",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057885.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057885; html:https://europepmc.org/articles/PMC9002258; pdf:https://europepmc.org/articles/PMC9002258?pdf=render 34606520,https://doi.org/10.1371/journal.pmed.1003815,"COVID-19 vaccination in Sindh Province, Pakistan: A modelling study of health impact and cost-effectiveness.","Pearson CAB, Bozzani F, Procter SR, Davies NG, Huda M, Jensen HT, Keogh-Brown M, Khalid M, Sweeney S, Torres-Rueda S, CHiL COVID-19 Working Group, CMMID COVID-19 Working Group, Eggo RM, Vassall A, Jit M.",,PLoS medicine,2021,2021-10-04,Y,,,,"

Background

Multiple Coronavirus Disease 2019 (COVID-19) vaccines appear to be safe and efficacious, but only high-income countries have the resources to procure sufficient vaccine doses for most of their eligible populations. The World Health Organization has published guidelines for vaccine prioritisation, but most vaccine impact projections have focused on high-income countries, and few incorporate economic considerations. To address this evidence gap, we projected the health and economic impact of different vaccination scenarios in Sindh Province, Pakistan (population: 48 million).

Methods and findings

We fitted a compartmental transmission model to COVID-19 cases and deaths in Sindh from 30 April to 15 September 2020. We then projected cases, deaths, and hospitalisation outcomes over 10 years under different vaccine scenarios. Finally, we combined these projections with a detailed economic model to estimate incremental costs (from healthcare and partial societal perspectives), disability-adjusted life years (DALYs), and incremental cost-effectiveness ratio (ICER) for each scenario. We project that 1 year of vaccine distribution, at delivery rates consistent with COVAX projections, using an infection-blocking vaccine at $3/dose with 70% efficacy and 2.5-year duration of protection is likely to avert around 0.9 (95% credible interval (CrI): 0.9, 1.0) million cases, 10.1 (95% CrI: 10.1, 10.3) thousand deaths, and 70.1 (95% CrI: 69.9, 70.6) thousand DALYs, with an ICER of $27.9 per DALY averted from the health system perspective. Under a broad range of alternative scenarios, we find that initially prioritising the older (65+) population generally prevents more deaths. However, unprioritised distribution has almost the same cost-effectiveness when considering all outcomes, and both prioritised and unprioritised programmes can be cost-effective for low per-dose costs. High vaccine prices ($10/dose), however, may not be cost-effective, depending on the specifics of vaccine performance, distribution programme, and future pandemic trends. The principal drivers of the health outcomes are the fitted values for the overall transmission scaling parameter and disease natural history parameters from other studies, particularly age-specific probabilities of infection and symptomatic disease, as well as social contact rates. Other parameters are investigated in sensitivity analyses. This study is limited by model approximations, available data, and future uncertainty. Because the model is a single-population compartmental model, detailed impacts of nonpharmaceutical interventions (NPIs) such as household isolation cannot be practically represented or evaluated in combination with vaccine programmes. Similarly, the model cannot consider prioritising groups like healthcare or other essential workers. The model is only fitted to the reported case and death data, which are incomplete and not disaggregated by, e.g., age. Finally, because the future impact and implementation cost of NPIs are uncertain, how these would interact with vaccination remains an open question.

Conclusions

COVID-19 vaccination can have a considerable health impact and is likely to be cost-effective if more optimistic vaccine scenarios apply. Preventing severe disease is an important contributor to this impact. However, the advantage of prioritising older, high-risk populations is smaller in generally younger populations. This reduction is especially true in populations with more past transmission, and if the vaccine is likely to further impede transmission rather than just disease. Those conditions are typical of many low- and middle-income countries.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003815&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003815; html:https://europepmc.org/articles/PMC8523052; pdf:https://europepmc.org/articles/PMC8523052?pdf=render +35410933,https://doi.org/10.1136/bmjopen-2021-057885,"Non-pharmacological therapies for postviral syndromes, including Long COVID: a systematic review and meta-analysis protocol.","Chandan JS, Brown K, Simms-Williams N, Camaradou J, Bashir N, Heining D, Aiyegbusi OL, Turner G, Cruz Rivera S, Hotham R, Nirantharakumar K, Sivan M, Khunti K, Raindi D, Marwaha S, Hughes SE, McMullan C, Calvert M, Haroon S.",,BMJ open,2022,2022-04-11,Y,Infectious diseases; Rehabilitation Medicine; Covid-19,,,"

Introduction

Postviral syndromes (PVS) describe the sustained presence of symptoms following an acute viral infection, for months or even years. Exposure to the SARS-CoV-2 virus and subsequent development of COVID-19 has shown to have similar effects with individuals continuing to exhibit symptoms for greater than 12 weeks. The sustained presence of symptoms is variably referred to as 'post COVID-19 syndrome', 'post-COVID condition' or more commonly 'Long COVID'. Knowledge of the long-term health impacts and treatments for Long COVID are evolving. To minimise overlap with existing work in the field exploring treatments of Long COVID, we have only chosen to focus on non-pharmacological treatments.

Aims

This review aims to summarise the effectiveness of non-pharmacological treatments for PVS, including Long COVID. A secondary aim is to summarise the symptoms and health impacts associated with PVS in individuals recruited to treatment studies.

Methods and analysis

Primary electronic searches will be performed in bibliographic databases including: Embase, MEDLINE, PyscINFO, CINAHL and MedRxiv from 1 January 2001 to 29 October 2021. At least two independent reviewers will screen each study for inclusion and data will be extracted from all eligible studies onto a data extraction form. The quality of all included studies will be assessed using Cochrane risk of bias tools and the Newcastle-Ottawa grading system. Non-pharmacological treatments for PVS and Long COVID will be narratively summarised and effect estimates will be pooled using random effects meta-analysis where there is sufficient methodological homogeneity. The symptoms and health impacts reported in the included studies on non-pharmacological interventions will be extracted and narratively reported.

Ethics and dissemination

This systematic review does not require ethical approval. The findings from this study will be submitted for peer-reviewed publication, shared at conference presentations and disseminated to both clinical and patient groups.

Prospero registration number

The review will adhere to this protocol which has also been registered with PROSPERO (CRD42021282074).",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057885.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057885; html:https://europepmc.org/articles/PMC9002258; pdf:https://europepmc.org/articles/PMC9002258?pdf=render 38106559,https://doi.org/10.1016/j.eclinm.2023.102251,Long-term symptom profiles after COVID-19 vs other acute respiratory infections: an analysis of data from the COVIDENCE UK study.,"Vivaldi G, Pfeffer PE, Talaei M, Basera TJ, Shaheen SO, Martineau AR.",,EClinicalMedicine,2023,2023-10-06,Y,Acute respiratory infections; Sars-cov-2; Long Covid; Post-acute Sequelae,,,"

Background

Long COVID is a well recognised, if heterogeneous, entity. Acute respiratory infections (ARIs) due to other pathogens may cause long-term symptoms, but few studies compare post-acute sequelae between SARS-CoV-2 and other ARIs. We aimed to compare symptom profiles between people with previous SARS-CoV-2 infection, people with previous non-COVID-19 ARIs, and contemporaneous controls, and to identify clusters of long-term symptoms.

Methods

COVIDENCE UK is a prospective, population-based UK study of ARIs in adults. We analysed data for 16 potential long COVID symptoms and health-related quality of life (HRQoL), reported between January 21 and February 15, 2021, by participants unvaccinated against SARS-CoV-2. We classified participants as having previous SARS-CoV-2 infection or previous non-COVID-19 ARI (≥4 weeks prior) or no reported ARI. We compared symptoms by infection status using logistic and fractional regression, and identified symptom clusters using latent class analysis (LCA). This study is registered with ClinicalTrials.gov, NCT04330599.

Findings

We included 10,171 participants (1311 [12.9%] with SARS-CoV-2 infection, 472 [4.6%] with non-COVID-19 ARI). Both types of infection were associated with increased prevalence/severity of most symptoms and decreased HRQoL compared with no infection. Participants with SARS-CoV-2 infection had increased odds of problems with taste/smell (odds ratio 19.74, 95% CI 10.53-37.00) and lightheadedness or dizziness (1.74, 1.18-2.56) compared with participants with non-COVID-19 ARIs. Separate LCA models identified three symptom severity groups for each infection type. In the most severe groups (representing 22% of participants for both SARS-CoV-2 and non-COVID-19 ARI), SARS-CoV-2 infection presented with a higher probability of problems with taste/smell (probability 0.41 vs 0.04), hair loss (0.25 vs 0.16), unusual sweating (0.38 vs 0.25), unusual racing of the heart (0.43 vs 0.33), and memory problems (0.70 vs 0.55) than non-COVID-19 ARI.

Interpretation

Both SARS-CoV-2 and non-COVID-19 ARIs are associated with a wide range of symptoms more than 4 weeks after the acute infection. Research on post-acute sequelae of ARIs should extend from SARS-CoV-2 to include other pathogens.

Funding

Barts Charity.",,doi:https://doi.org/10.1016/j.eclinm.2023.102251; html:https://europepmc.org/articles/PMC10721552; pdf:https://europepmc.org/articles/PMC10721552?pdf=render -35585575,https://doi.org/10.1186/s12889-022-13219-4,The impact of COVID-19 vaccination in prisons in England and Wales: a metapopulation model.,"McCarthy CV, O'Mara O, van Leeuwen E, CMMID COVID-19 Working Group, Jit M, Sandmann F.",,BMC public health,2022,2022-05-18,Y,Vaccination; mathematical model; Public Health; Prisons; Covid-19,,,"

Background

High incidence of cases and deaths due to coronavirus disease 2019 (COVID-19) have been reported in prisons worldwide. This study aimed to evaluate the impact of different COVID-19 vaccination strategies in epidemiologically semi-enclosed settings such as prisons, where staff interact regularly with those incarcerated and the wider community.

Methods

We used a metapopulation transmission-dynamic model of a local prison in England and Wales. Two-dose vaccination strategies included no vaccination, vaccination of all individuals who are incarcerated and/or staff, and an age-based approach. Outcomes were quantified in terms of COVID-19-related symptomatic cases, losses in quality-adjusted life-years (QALYs), and deaths.

Results

Compared to no vaccination, vaccinating all people living and working in prison reduced cases, QALY loss and deaths over a one-year period by 41%, 32% and 36% respectively. However, if vaccine introduction was delayed until the start of an outbreak, the impact was negligible. Vaccinating individuals who are incarcerated and staff over 50 years old averted one death for every 104 vaccination courses administered. All-staff-only strategies reduced cases by up to 5%. Increasing coverage from 30 to 90% among those who are incarcerated reduced cases by around 30 percentage points.

Conclusions

The impact of vaccination in prison settings was highly dependent on early and rapid vaccine delivery. If administered to both those living and working in prison prior to an outbreak occurring, vaccines could substantially reduce COVID-19-related morbidity and mortality in prison settings.",,pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-022-13219-4; doi:https://doi.org/10.1186/s12889-022-13219-4; html:https://europepmc.org/articles/PMC9115545; pdf:https://europepmc.org/articles/PMC9115545?pdf=render 31671849,https://doi.org/10.3390/ijerph16214178,Associations between the Home Physical Environment and Children's Home-Based Physical Activity and Sitting.,"Sheldrick MP, Maitland C, Mackintosh KA, Rosenberg M, Griffiths LJ, Fry R, Stratton G.",,International journal of environmental research and public health,2019,2019-10-29,Y,Families; Youth; Objective; Standing; House; Moderate-to-vigorous Physical Activity; Screen-time,,,"It is important to understand the correlates of children's physical activity (PA) and sitting at home, where children spend significant time. The home social environment has an important influence; however, much less is known about the home physical environment. Therefore, the study aimed to assess relationships between the physical environment and children's sitting and PA at home. In total, 235 child-parent dyads were included in the analyses. Children spent 67% of their time at home sitting. Linear regression analyses examined associations between physical home environmental factors obtained via an audit and children's (55% girl, 10.2 ± 0.7) objective PA and sitting at home. Following adjustment for socio-demographics and social environmental factors, an open plan living area (OPLA), musical instrument accessibility and availability, and perceived house size were negatively and positively associated, whereas media equipment accessibility and availability was positively and negatively associated with sitting and standing, respectively. Additionally, an OPLA was positively associated with total and moderate-to-vigorous PA. Furthermore, sitting breaks were positively associated with objective garden size and negatively associated with digital TV. The physical home environment may have an important influence on children's sitting, standing and PA at home; therefore, interventions that target this environment are needed.",,pdf:https://www.mdpi.com/1660-4601/16/21/4178/pdf?version=1573119054; doi:https://doi.org/10.3390/ijerph16214178; html:https://europepmc.org/articles/PMC6862192; pdf:https://europepmc.org/articles/PMC6862192?pdf=render +35585575,https://doi.org/10.1186/s12889-022-13219-4,The impact of COVID-19 vaccination in prisons in England and Wales: a metapopulation model.,"McCarthy CV, O'Mara O, van Leeuwen E, CMMID COVID-19 Working Group, Jit M, Sandmann F.",,BMC public health,2022,2022-05-18,Y,Vaccination; mathematical model; Public Health; Prisons; Covid-19,,,"

Background

High incidence of cases and deaths due to coronavirus disease 2019 (COVID-19) have been reported in prisons worldwide. This study aimed to evaluate the impact of different COVID-19 vaccination strategies in epidemiologically semi-enclosed settings such as prisons, where staff interact regularly with those incarcerated and the wider community.

Methods

We used a metapopulation transmission-dynamic model of a local prison in England and Wales. Two-dose vaccination strategies included no vaccination, vaccination of all individuals who are incarcerated and/or staff, and an age-based approach. Outcomes were quantified in terms of COVID-19-related symptomatic cases, losses in quality-adjusted life-years (QALYs), and deaths.

Results

Compared to no vaccination, vaccinating all people living and working in prison reduced cases, QALY loss and deaths over a one-year period by 41%, 32% and 36% respectively. However, if vaccine introduction was delayed until the start of an outbreak, the impact was negligible. Vaccinating individuals who are incarcerated and staff over 50 years old averted one death for every 104 vaccination courses administered. All-staff-only strategies reduced cases by up to 5%. Increasing coverage from 30 to 90% among those who are incarcerated reduced cases by around 30 percentage points.

Conclusions

The impact of vaccination in prison settings was highly dependent on early and rapid vaccine delivery. If administered to both those living and working in prison prior to an outbreak occurring, vaccines could substantially reduce COVID-19-related morbidity and mortality in prison settings.",,pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-022-13219-4; doi:https://doi.org/10.1186/s12889-022-13219-4; html:https://europepmc.org/articles/PMC9115545; pdf:https://europepmc.org/articles/PMC9115545?pdf=render 33588321,https://doi.org/10.1016/j.retram.2021.103276,Biological responses to COVID-19: Insights from physiological and blood biomarker profiles.,"Zakeri R, Pickles A, Carr E, Bean DM, O'Gallagher K, Kraljewic Z, Searle T, Shek A, Galloway JB, Teo JTH, Shah AM, Dobson RJB, Bendayan R.",,Current research in translational medicine,2021,2021-02-03,Y,Inflammation; Biomarkers; Classes; Sars-cov-2,,,"

Background

Understanding the spectrum and course of biological responses to coronavirus disease 2019 (COVID-19) may have important therapeutic implications. We sought to characterise biological responses among patients hospitalised with severe COVID-19 based on serial, routinely collected, physiological and blood biomarker values.

Methods and findings

We performed a retrospective cohort study of 1335 patients hospitalised with laboratory-confirmed COVID-19 (median age 70 years, 56 % male), between 1st March and 30th April 2020. Latent profile analysis was performed on serial physiological and blood biomarkers. Patient characteristics, comorbidities and rates of death and admission to intensive care, were compared between the latent classes. A five class solution provided the best fit. Class 1 ""Typical response"" exhibited a moderately elevated and rising C-reactive protein (CRP), stable lymphopaenia, and the lowest rates of 14-day adverse outcomes. Class 2 ""Rapid hyperinflammatory response"" comprised older patients, with higher admission white cell and neutrophil counts, which declined over time, accompanied by a very high and rising CRP and platelet count, and exibited the highest mortality risk. Class 3 ""Progressive inflammatory response"" was similar to the typical response except for a higher and rising CRP, though similar mortality rate. Class 4 ""Inflammatory response with kidney injury"" had prominent lymphopaenia, moderately elevated (and rising) CRP, and severe renal failure. Class 5 ""Hyperinflammatory response with kidney injury"" comprised older patients, with a very high and rising CRP, and severe renal failure that attenuated over time. Physiological measures did not substantially vary between classes at baseline or early admission.

Conclusions and relevance

Our identification of five distinct classes of biomarker profiles provides empirical evidence for heterogeneous biological responses to COVID-19. Early hyperinflammatory responses and kidney injury may signify unique pathophysiology that requires targeted therapy.",,doi:https://doi.org/10.1016/j.retram.2021.103276; doi:https://doi.org/10.1016/j.retram.2021.103276; html:https://europepmc.org/articles/PMC7857048; pdf:https://europepmc.org/articles/PMC7857048?pdf=render -35381001,https://doi.org/10.1371/journal.pgen.1010093,Analyzing human knockouts to validate GPR151 as a therapeutic target for reduction of body mass index.,"Gurtan A, Dominy J, Khalid S, Vong L, Caplan S, Currie T, Richards S, Lamarche L, Denning D, Shpektor D, Gurinovich A, Rasheed A, Hameed S, Saeed S, Saleem I, Jalal A, Abbas S, Sultana R, Rasheed SZ, Memon FU, Shah N, Ishaq M, Khera AV, Danesh J, Frossard P, Saleheen D.",,PLoS genetics,2022,2022-04-05,Y,,,,"Novel drug targets for sustained reduction in body mass index (BMI) are needed to curb the epidemic of obesity, which affects 650 million individuals worldwide and is a causal driver of cardiovascular and metabolic disease and mortality. Previous studies reported that the Arg95Ter nonsense variant of GPR151, an orphan G protein-coupled receptor, is associated with reduced BMI and reduced risk of Type 2 Diabetes (T2D). Here, we further investigate GPR151 with the Pakistan Genome Resource (PGR), which is one of the largest exome biobanks of human homozygous loss-of-function carriers (knockouts) in the world. Among PGR participants, we identify eleven GPR151 putative loss-of-function (plof) variants, three of which are present at homozygosity (Arg95Ter, Tyr99Ter, and Phe175LeufsTer7), with a cumulative allele frequency of 2.2%. We confirm these alleles in vitro as loss-of-function. We test if GPR151 plof is associated with BMI, T2D, or other metabolic traits and find that GPR151 deficiency in complete human knockouts is not associated with clinically significant differences in these traits. Relative to Gpr151+/+ mice, Gpr151-/- animals exhibit no difference in body weight on normal chow and higher body weight on a high-fat diet. Together, our findings indicate that GPR151 antagonism is not a compelling therapeutic approach to treatment of obesity.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010093&type=printable; doi:https://doi.org/10.1371/journal.pgen.1010093; html:https://europepmc.org/articles/PMC9022822; pdf:https://europepmc.org/articles/PMC9022822?pdf=render 31409800,https://doi.org/10.1038/s41467-019-11451-y,GWAS for urinary sodium and potassium excretion highlights pathways shared with cardiovascular traits.,"Pazoki R, Evangelou E, Mosen-Ansorena D, Pinto RC, Karaman I, Blakeley P, Gill D, Zuber V, Elliott P, Tzoulaki I, Dehghan A.",,Nature communications,2019,2019-08-13,Y,,Understanding the Causes of Disease,,"Urinary sodium and potassium excretion are associated with blood pressure (BP) and cardiovascular disease (CVD). The exact biological link between these traits is yet to be elucidated. Here, we identify 50 loci for sodium and 13 for potassium excretion in a large-scale genome-wide association study (GWAS) on urinary sodium and potassium excretion using data from 446,237 individuals of European descent from the UK Biobank study. We extensively interrogate the results using multiple analyses such as Mendelian randomization, functional assessment, co localization, genetic risk score, and pathway analyses. We identify a shared genetic component between urinary sodium and potassium expression and cardiovascular traits. Ingenuity pathway analysis shows that urinary sodium and potassium excretion loci are over-represented in behavioural response to stimuli. Our study highlights pathways that are shared between urinary sodium and potassium excretion and cardiovascular traits.",,pdf:https://www.nature.com/articles/s41467-019-11451-y.pdf; doi:https://doi.org/10.1038/s41467-019-11451-y; html:https://europepmc.org/articles/PMC6692500; pdf:https://europepmc.org/articles/PMC6692500?pdf=render +35381001,https://doi.org/10.1371/journal.pgen.1010093,Analyzing human knockouts to validate GPR151 as a therapeutic target for reduction of body mass index.,"Gurtan A, Dominy J, Khalid S, Vong L, Caplan S, Currie T, Richards S, Lamarche L, Denning D, Shpektor D, Gurinovich A, Rasheed A, Hameed S, Saeed S, Saleem I, Jalal A, Abbas S, Sultana R, Rasheed SZ, Memon FU, Shah N, Ishaq M, Khera AV, Danesh J, Frossard P, Saleheen D.",,PLoS genetics,2022,2022-04-05,Y,,,,"Novel drug targets for sustained reduction in body mass index (BMI) are needed to curb the epidemic of obesity, which affects 650 million individuals worldwide and is a causal driver of cardiovascular and metabolic disease and mortality. Previous studies reported that the Arg95Ter nonsense variant of GPR151, an orphan G protein-coupled receptor, is associated with reduced BMI and reduced risk of Type 2 Diabetes (T2D). Here, we further investigate GPR151 with the Pakistan Genome Resource (PGR), which is one of the largest exome biobanks of human homozygous loss-of-function carriers (knockouts) in the world. Among PGR participants, we identify eleven GPR151 putative loss-of-function (plof) variants, three of which are present at homozygosity (Arg95Ter, Tyr99Ter, and Phe175LeufsTer7), with a cumulative allele frequency of 2.2%. We confirm these alleles in vitro as loss-of-function. We test if GPR151 plof is associated with BMI, T2D, or other metabolic traits and find that GPR151 deficiency in complete human knockouts is not associated with clinically significant differences in these traits. Relative to Gpr151+/+ mice, Gpr151-/- animals exhibit no difference in body weight on normal chow and higher body weight on a high-fat diet. Together, our findings indicate that GPR151 antagonism is not a compelling therapeutic approach to treatment of obesity.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010093&type=printable; doi:https://doi.org/10.1371/journal.pgen.1010093; html:https://europepmc.org/articles/PMC9022822; pdf:https://europepmc.org/articles/PMC9022822?pdf=render 36054463,https://doi.org/10.1111/ans.17985,Examining the patient profile and variance of management and in-hospital outcomes for Australian adult burns patients.,"Tracy LM, Darton A, Gabbe BJ, Heath K, Kurmis R, Lisec C, Lo C, Singer Y, Wood FM, Cleland HJ.",,ANZ journal of surgery,2022,2022-08-22,Y,Adult; Variation; Australia; Burn; Registry,,,"

Background

Burn injuries are a common subtype of trauma. Variation in models of care impacts clinical measures of interest, but a nation-wide examination of these measures has not been undertaken. Using data from the Burns Registry of Australia and New Zealand (BRANZ), we explored variation between Australian adult burn services with respect to treatment and clinical measures of interest.

Methods

Data for admissions July 2016 to June 2020 were extracted. Clinical measures of interest included intensive care admission, skin grafting, in-hospital death, unplanned readmissions, and length of stay (LOS). Estimated probabilities, means, and corresponding 95% confidence intervals (CI) were calculated for each service.

Results

The BRANZ recorded 8365 admissions during the study period. Variation between specialist burn services in admissions, demographics, management, and clinical measures of interest were observed. This variation remained after accounting for covariates. Specifically, the adjusted proportion (95% CI) of in-hospital mortality ranged from 0.15% (0.10-0.21%) to 1.22% (0.9-1.5%). The adjusted mean LOS ranged from 3.8 (3.3-4.3) to 8.2 (6.7-9.7) days.

Conclusions

A decade after its launch, BRANZ data displays variation between Australian specialist burn services. We suspect differences in models of care between services contributes to this variation. Ongoing research has begun to explore reasons underlying how this variation influences clinical measures of interest. Further engagement with services about models of care will enhance understanding of this variation and develop evidence-based guidelines for burn care in Australia.",,doi:https://doi.org/10.1111/ans.17985; doi:https://doi.org/10.1111/ans.17985; html:https://europepmc.org/articles/PMC9804322; pdf:https://europepmc.org/articles/PMC9804322?pdf=render -36224602,https://doi.org/10.1186/s12916-022-02544-5,Early onset of immune-mediated diseases in minority ethnic groups in the UK.,"Sharma-Oates A, Zemedikun DT, Kumar K, Reynolds JA, Jain A, Raza K, Williams JA, Bravo L, Cardoso VR, Gkoutos G, Nirantharakumar K, Lord JM.",,BMC medicine,2022,2022-10-13,Y,Ageing; Diagnosis; Ethnicity; Rheumatic Diseases; South Asian; African-caribbean; Immune-mediated Diseases; Autoimmune Inflammatory Diseases,,,"

Background

The prevalence of some immune-mediated diseases (IMDs) shows distinct differences between populations of different ethnicities. The aim of this study was to determine if the age at diagnosis of common IMDs also differed between different ethnic groups in the UK, suggestive of distinct influences of ethnicity on disease pathogenesis.

Methods

This was a population-based retrospective primary care study. Linear regression provided unadjusted and adjusted estimates of age at diagnosis for common IMDs within the following ethnic groups: White, South Asian, African-Caribbean and Mixed-race/Other. Potential disease risk confounders in the association between ethnicity and diagnosis age including sex, smoking, body mass index and social deprivation (Townsend quintiles) were adjusted for. The analysis was replicated using data from UK Biobank (UKB).

Results

After adjusting for risk confounders, we observed that individuals from South Asian, African-Caribbean and Mixed-race/Other ethnicities were diagnosed with IMDs at a significantly younger age than their White counterparts for almost all IMDs. The difference in the diagnosis age (ranging from 2 to 30 years earlier) varied for each disease and by ethnicity. For example, rheumatoid arthritis was diagnosed at age 49, 48 and 47 years in individuals of African-Caribbean, South Asian and Mixed-race/Other ethnicities respectively, compared to 56 years in White ethnicities. The earlier diagnosis of most IMDs observed was validated in UKB although with a smaller effect size.

Conclusion

Individuals from non-White ethnic groups in the UK had an earlier age at diagnosis for several IMDs than White adults.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02544-5; doi:https://doi.org/10.1186/s12916-022-02544-5; html:https://europepmc.org/articles/PMC9558944; pdf:https://europepmc.org/articles/PMC9558944?pdf=render 31446403,https://doi.org/10.1136/bmjopen-2018-026677,Diagnosis and treatment for hyperuricemia and gout: a systematic review of clinical practice guidelines and consensus statements.,"Li Q, Li X, Wang J, Liu H, Kwong JS, Chen H, Li L, Chung SC, Shah A, Chen Y, An Z, Sun X, Hemingway H, Tian H, Li S.",,BMJ open,2019,2019-08-24,Y,Gout; Hyperuricemia; Systematic review; Clinical Practice Guideline,,,"

Objectives

Despite the publication of hundreds of trials on gout and hyperuricemia, management of these conditions remains suboptimal. We aimed to assess the quality and consistency of guidance documents for gout and hyperuricemia.

Design

Systematic review and quality assessment using the appraisal of guidelines for research and evaluation (AGREE) II methodology.

Data sources

PubMed and EMBASE (27 October 2016), two Chinese academic databases, eight guideline databases, and Google and Google scholar (July 2017).

Eligibility criteria

We included the latest version of international and national/regional clinical practice guidelines and consensus statements for diagnosis and/or treatment of hyperuricemia and gout, published in English or Chinese.

Data extraction and synthesis

Two reviewers independently screened searched items and extracted data. Four reviewers independently scored documents using AGREE II. Recommendations from all documents were tabulated and visualised in a coloured grid.

Results

Twenty-four guidance documents (16 clinical practice guidelines and 8 consensus statements) published between 2003 and 2017 were included. Included documents performed well in the domains of scope and purpose (median 85.4%, range 66.7%-100.0%) and clarity of presentation (median 79.2%, range 48.6%-98.6%), but unsatisfactory in applicability (median 10.9%, range 0.0%-66.7%) and editorial independence (median 28.1%, range 0.0%-83.3%). The 2017 British Society of Rheumatology guideline received the highest scores. Recommendations were concordant on the target serum uric acid level for long-term control, on some indications for urate-lowering therapy (ULT), and on the first-line drugs for ULT and for acute attack. Substantially inconsistent recommendations were provided for many items, especially for the timing of initiation of ULT and for treatment for asymptomatic hyperuricemia.

Conclusions

Methodological quality needs improvement in guidance documents on gout and hyperuricemia. Evidence for certain clinical questions is lacking, despite numerous trials in this field. Promoting standard guidance development methods and synthesising high-quality clinical evidence are potential approaches to reduce recommendation inconsistencies.

Prospero registration number

CRD42016046104.",,pdf:https://bmjopen.bmj.com/content/bmjopen/9/8/e026677.full.pdf; doi:https://doi.org/10.1136/bmjopen-2018-026677; html:https://europepmc.org/articles/PMC6720466; pdf:https://europepmc.org/articles/PMC6720466?pdf=render +36224602,https://doi.org/10.1186/s12916-022-02544-5,Early onset of immune-mediated diseases in minority ethnic groups in the UK.,"Sharma-Oates A, Zemedikun DT, Kumar K, Reynolds JA, Jain A, Raza K, Williams JA, Bravo L, Cardoso VR, Gkoutos G, Nirantharakumar K, Lord JM.",,BMC medicine,2022,2022-10-13,Y,Ageing; Diagnosis; Ethnicity; Rheumatic Diseases; South Asian; African-caribbean; Immune-mediated Diseases; Autoimmune Inflammatory Diseases,,,"

Background

The prevalence of some immune-mediated diseases (IMDs) shows distinct differences between populations of different ethnicities. The aim of this study was to determine if the age at diagnosis of common IMDs also differed between different ethnic groups in the UK, suggestive of distinct influences of ethnicity on disease pathogenesis.

Methods

This was a population-based retrospective primary care study. Linear regression provided unadjusted and adjusted estimates of age at diagnosis for common IMDs within the following ethnic groups: White, South Asian, African-Caribbean and Mixed-race/Other. Potential disease risk confounders in the association between ethnicity and diagnosis age including sex, smoking, body mass index and social deprivation (Townsend quintiles) were adjusted for. The analysis was replicated using data from UK Biobank (UKB).

Results

After adjusting for risk confounders, we observed that individuals from South Asian, African-Caribbean and Mixed-race/Other ethnicities were diagnosed with IMDs at a significantly younger age than their White counterparts for almost all IMDs. The difference in the diagnosis age (ranging from 2 to 30 years earlier) varied for each disease and by ethnicity. For example, rheumatoid arthritis was diagnosed at age 49, 48 and 47 years in individuals of African-Caribbean, South Asian and Mixed-race/Other ethnicities respectively, compared to 56 years in White ethnicities. The earlier diagnosis of most IMDs observed was validated in UKB although with a smaller effect size.

Conclusion

Individuals from non-White ethnic groups in the UK had an earlier age at diagnosis for several IMDs than White adults.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02544-5; doi:https://doi.org/10.1186/s12916-022-02544-5; html:https://europepmc.org/articles/PMC9558944; pdf:https://europepmc.org/articles/PMC9558944?pdf=render 34950917,https://doi.org/10.1016/j.lanepe.2021.100248,"Late effects of cancer in children, teenagers and young adults: Population-based study on the burden of 183 conditions, in-patient and critical care admissions and years of life lost.","Chang WH, Katsoulis M, Tan YY, Mueller SH, Green K, Lai AG.",,The Lancet regional health. Europe,2022,2021-11-14,Y,"Primary Care; Hospitalisation; Cancer Treatment; Years Of Life Lost; Cancer Late Effects; Children, Teenagers And Young Adults",,,"

Background

Children, teenagers and young adults who survived cancer are prone to developing late effects. The burden of late effects across a large number of conditions, in-patient hospitalisation and critical care admissions have not been described using a population-based dataset. We aim to systematically quantify the cumulative burden of late effects across all cancer subtypes, treatment modalities and chemotherapy drug classes.

Methods

We employed primary care records linked to hospitals, the death registry and cancer registry from 1998-2020. CTYA survivors were 25 years or younger at the time of cancer diagnosis had survived ≥5 years post-diagnosis. Year-of-birth and sex-matched community controls were used for comparison. We considered nine treatment types, nine chemotherapy classes and 183 physical and mental health late effects. Cumulative burden was estimated using mean cumulative count, which considers recurring events. Multivariable logistic regression was used to investigate the association between treatment exposures and late effects. Excess years of life lost (YLL) attributable to late effects were estimated.

Findings

Among 4,063 patients diagnosed with cancer, 3,466 survived ≥ 5 years (85%); 13,517 matched controls were identified. The cumulative burden of late effects at age 35 was the highest in survivors of leukaemia (23.52 per individual [95% CI:19.85-29.33]) and lowest in survivors of germ cell tumours (CI:6.04 [5.32-6.91]). In controls, the cumulative burden was 3.99 (CI:3.93-4.08) at age 35 years. When survivors reach age 45, the cumulative burden for immunological conditions and infections was the highest (3.27 [CI:3.01-3.58]), followed by cardiovascular conditions (3.08 [CI:1.98-3.29]). Survivors who received chemotherapy and radiotherapy had the highest disease burden compared to those who received surgery only. These patients also had the highest burden of hospitalisation (by age 45: 10.43 [CI:8.27-11.95]). Survivors who received antimetabolite chemotherapy had the highest disease and hospitalisation burden, while the lowest burden is observed in those receiving antitumour antibiotics. Regression analyses revealed that survivors who received only surgery had lower odds of developing cardiovascular (adjusted odds ratio 0.73 [CI:0.56-0.94]), haematological (aOR 0.51 [CI:0.37-0.70]), immunology and infection (aOR 0.84 [CI:0.71-0.99]) and renal (aOR 0.51 [CI:0.39-0.66]) late effects. By contrast, the opposite trend was observed in survivors who received chemo-radiotherapy. High antimetabolite chemotherapy cumulative dose was associated with increased risks of subsequent cancer (aOR 2.32 [CI:1.06-4.84]), metastatic cancer (aOR 4.44 [CI:1.29-11.66]) and renal (aOR 3.48 [CI:1.36-7.86]) conditions. Patients who received radiation dose of ≥50 Gy experienced higher risks of developing metastatic cancer (aOR 5.51 [CI:2.21-11.86]), cancer (aOR 3.77 [CI:2.22-6.34]), haematological (aOR 3.43 [CI:1.54-6.83]) and neurological (aOR 3.24 [CI:1.78-5.66]) conditions. Similar trends were observed in survivors who received more than three teletherapy fields. Cumulative burden analyses on 183 conditions separately revealed varying dominance of different late effects across cancer types, socioeconomic deprivation and treatment modalities. Late effects are associated with excess YLL (i.e., the difference in YLL between survivors with or without late effects), which was the most pronounced among survivors with haematological comorbidities.

Interpretation

To our knowledge, this is the first study to dissect and quantify the importance of late morbidities on subsequent survival using linked electronic health records from multiple settings. The burden of late effects is heterogeneous, as is the risk of premature mortality associated with late effects. We provide an extensive knowledgebase to help inform treatment decisions at the point of diagnosis, future interventional trials and late-effects screening centred on the holistic needs of this vulnerable population.",,doi:https://doi.org/10.1016/j.lanepe.2021.100248; doi:https://doi.org/10.1016/j.lanepe.2021.100248; html:https://europepmc.org/articles/PMC8672041; pdf:https://europepmc.org/articles/PMC8672041?pdf=render 36228971,https://doi.org/10.1016/j.jclinepi.2022.10.011,"In simulated data and health records, latent class analysis was the optimum multimorbidity clustering algorithm.","Nichols L, Taverner T, Crowe F, Richardson S, Yau C, Kiddle S, Kirk P, Barrett J, Nirantharakumar K, Griffin S, Edwards D, Marshall T.",,Journal of clinical epidemiology,2022,2022-10-11,Y,Hierarchical cluster analysis; Clustering Methods; Latent Class Analysis; Electronic Medical Records; Multimorbidity; K-means; Multiple Correspondence Analysis,,,"

Background and objectives

To investigate the reproducibility and validity of latent class analysis (LCA) and hierarchical cluster analysis (HCA), multiple correspondence analysis followed by k-means (MCA-kmeans) and k-means (kmeans) for multimorbidity clustering.

Methods

We first investigated clustering algorithms in simulated datasets with 26 diseases of varying prevalence in predetermined clusters, comparing the derived clusters to known clusters using the adjusted Rand Index (aRI). We then them investigated the medical records of male patients, aged 65 to 84 years from 50 UK general practices, with 49 long-term health conditions. We compared within cluster morbidity profiles using the Pearson correlation coefficient and assessed cluster stability using in 400 bootstrap samples.

Results

In the simulated datasets, the closest agreement (largest aRI) to known clusters was with LCA and then MCA-kmeans algorithms. In the medical records dataset, all four algorithms identified one cluster of 20-25% of the dataset with about 82% of the same patients across all four algorithms. LCA and MCA-kmeans both found a second cluster of 7% of the dataset. Other clusters were found by only one algorithm. LCA and MCA-kmeans clustering gave the most similar partitioning (aRI 0.54).

Conclusion

LCA achieved higher aRI than other clustering algorithms.",,doi:https://doi.org/10.1016/j.jclinepi.2022.10.011; doi:https://doi.org/10.1016/j.jclinepi.2022.10.011; html:https://europepmc.org/articles/PMC7613854; pdf:https://europepmc.org/articles/PMC7613854?pdf=render -36752447,https://doi.org/10.1016/j.jcmg.2022.11.012,Prognostic Value of RV Abnormalities on CMR in Patients With Known or Suspected Cardiac Sarcoidosis.,"Wang J, Zhang J, Hosadurg N, Iwanaga Y, Chen Y, Liu W, Wan K, Patel AR, Wicks EC, Gkoutos GV, Han Y, Chen Y.",,JACC. Cardiovascular imaging,2023,2023-01-11,N,Right Ventricle; Sudden Cardiac Death; Cardiac Sarcoidosis; Cardiac Magnetic Resonance; Late Gadolinium Enhancement,,,"

Background

Left ventricular abnormalities in cardiac sarcoidosis (CS) are associated with adverse cardiovascular events, whereas the prognostic value of right ventricular (RV) involvement found on cardiac magnetic resonance is unclear.

Objectives

This study aimed to systematically assess the prognostic value of right ventricular ejection fraction (RVEF) and RV late gadolinium enhancement (LGE) in known or suspected CS.

Methods

This study was prospectively registered in PROSPERO (CRD42022302579). PubMed, Embase, and Web of Science were searched to identify studies that evaluated the association between RVEF or RV LGE on clinical outcomes in CS. A composite endpoint of all-cause death, cardiovascular events, or sudden cardiac death (SCD) was used. A meta-analysis was performed to determine the pooled risk ratio (RR) for these adverse events. The calculated sensitivity, specificity, and area under the curve with 95% CIs were weighted and summarized.

Results

Eight studies including a total of 899 patients with a mean follow-up duration of 3.2 ± 0.7 years were included. The pooled RR of RV systolic dysfunction was 3.1 (95% CI: 1.7-5.5; P < 0.01) for composite events and 3.0 (95% CI: 1.3-7.0; P < 0.01) for SCD events. In addition, CS patients with RV LGE had a significant risk for composite events (RR: 4.8 [95% CI: 2.4-9.6]; P < 0.01) and a higher risk for SCD (RR: 9.5 [95% CI: 4.4-20.5]; P < 0.01) than patients without RV LGE. Furthermore, the pooled area under the curve, sensitivity, and specificity of RV LGE for identifying patients with CS who were at highest SCD risk were 0.8 (95% CI: 0.8-0.9), 69% (95% CI: 50%-84%), and 90% (95% CI: 70%-97%), respectively.

Conclusions

In patients with known or suspected CS, RVEF and RV LGE were both associated with adverse events. Furthermore, RV LGE shows good discrimination in identifying CS patients at high risk of SCD.",,doi:https://doi.org/10.1016/j.jcmg.2022.11.012; doi:https://doi.org/10.1016/j.jcmg.2022.11.012 33779119,https://doi.org/10.1002/ejhf.2169,Identification of distinct phenotypic clusters in heart failure with preserved ejection fraction.,"Uijl A, Savarese G, Vaartjes I, Dahlström U, Brugts JJ, Linssen GCM, van Empel V, Brunner-La Rocca HP, Asselbergs FW, Lund LH, Hoes AW, Koudstaal S.",,European journal of heart failure,2021,2021-05-01,Y,Treatment; Phenotyping; Clusters; Latent Class Analysis; Comorbidities; Heart Failure With Preserved Ejection Fraction; External Validation,,,"

Aims

We aimed to derive and validate clinically useful clusters of patients with heart failure with preserved ejection fraction (HFpEF; left ventricular ejection fraction ≥50%).

Methods and results

We derived a cluster model from 6909 HFpEF patients from the Swedish Heart Failure Registry (SwedeHF) and externally validated this in 2153 patients from the Chronic Heart Failure ESC-guideline based Cardiology practice Quality project (CHECK-HF) registry. In SwedeHF, the median age was 80 [interquartile range 72-86] years, 52% of patients were female and most frequent comorbidities were hypertension (82%), atrial fibrillation (68%), and ischaemic heart disease (48%). Latent class analysis identified five distinct clusters: cluster 1 (10% of patients) were young patients with a low comorbidity burden and the highest proportion of implantable devices; cluster 2 (30%) patients had atrial fibrillation, hypertension without diabetes; cluster 3 (25%) patients were the oldest with many cardiovascular comorbidities and hypertension; cluster 4 (15%) patients had obesity, diabetes and hypertension; and cluster 5 (20%) patients were older with ischaemic heart disease, hypertension and renal failure and were most frequently prescribed diuretics. The clusters were reproduced in the CHECK-HF cohort. Patients in cluster 1 had the best prognosis, while patients in clusters 3 and 5 had the worst age- and sex-adjusted prognosis.

Conclusions

Five distinct clusters of HFpEF patients were identified that differed in clinical characteristics, heart failure drug therapy and prognosis. These results confirm the heterogeneity of HFpEF and form a basis for tailoring trial design to individualized drug therapy in HFpEF patients.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejhf.2169; doi:https://doi.org/10.1002/ejhf.2169; html:https://europepmc.org/articles/PMC8359985; pdf:https://europepmc.org/articles/PMC8359985?pdf=render +36752447,https://doi.org/10.1016/j.jcmg.2022.11.012,Prognostic Value of RV Abnormalities on CMR in Patients With Known or Suspected Cardiac Sarcoidosis.,"Wang J, Zhang J, Hosadurg N, Iwanaga Y, Chen Y, Liu W, Wan K, Patel AR, Wicks EC, Gkoutos GV, Han Y, Chen Y.",,JACC. Cardiovascular imaging,2023,2023-01-11,N,Right Ventricle; Sudden Cardiac Death; Cardiac Sarcoidosis; Cardiac Magnetic Resonance; Late Gadolinium Enhancement,,,"

Background

Left ventricular abnormalities in cardiac sarcoidosis (CS) are associated with adverse cardiovascular events, whereas the prognostic value of right ventricular (RV) involvement found on cardiac magnetic resonance is unclear.

Objectives

This study aimed to systematically assess the prognostic value of right ventricular ejection fraction (RVEF) and RV late gadolinium enhancement (LGE) in known or suspected CS.

Methods

This study was prospectively registered in PROSPERO (CRD42022302579). PubMed, Embase, and Web of Science were searched to identify studies that evaluated the association between RVEF or RV LGE on clinical outcomes in CS. A composite endpoint of all-cause death, cardiovascular events, or sudden cardiac death (SCD) was used. A meta-analysis was performed to determine the pooled risk ratio (RR) for these adverse events. The calculated sensitivity, specificity, and area under the curve with 95% CIs were weighted and summarized.

Results

Eight studies including a total of 899 patients with a mean follow-up duration of 3.2 ± 0.7 years were included. The pooled RR of RV systolic dysfunction was 3.1 (95% CI: 1.7-5.5; P < 0.01) for composite events and 3.0 (95% CI: 1.3-7.0; P < 0.01) for SCD events. In addition, CS patients with RV LGE had a significant risk for composite events (RR: 4.8 [95% CI: 2.4-9.6]; P < 0.01) and a higher risk for SCD (RR: 9.5 [95% CI: 4.4-20.5]; P < 0.01) than patients without RV LGE. Furthermore, the pooled area under the curve, sensitivity, and specificity of RV LGE for identifying patients with CS who were at highest SCD risk were 0.8 (95% CI: 0.8-0.9), 69% (95% CI: 50%-84%), and 90% (95% CI: 70%-97%), respectively.

Conclusions

In patients with known or suspected CS, RVEF and RV LGE were both associated with adverse events. Furthermore, RV LGE shows good discrimination in identifying CS patients at high risk of SCD.",,doi:https://doi.org/10.1016/j.jcmg.2022.11.012; doi:https://doi.org/10.1016/j.jcmg.2022.11.012 34535484,https://doi.org/10.1136/bmjopen-2021-050647,The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH): protocol for a prospective longitudinal cohort study of healthcare and ancillary workers in UK healthcare settings.,"Woolf K, Melbourne C, Bryant L, Guyatt AL, McManus IC, Gupta A, Free RC, Nellums L, Carr S, John C, Martin CA, Wain LV, Gray LJ, Garwood C, Modhwadia V, Abrams KR, Tobin MD, Khunti K, Pareek M, UK-REACH Study Collaborative Group+.",,BMJ open,2021,2021-09-17,Y,Mental health; Public Health; Covid-19,,,"

Introduction

The COVID-19 pandemic has resulted in significant morbidity and mortality and devastated economies globally. Among groups at increased risk are healthcare workers (HCWs) and ethnic minority groups. Emerging evidence suggests that HCWs from ethnic minority groups are at increased risk of adverse COVID-19-related outcomes. To date, there has been no large-scale analysis of these risks in UK HCWs or ancillary workers in healthcare settings, stratified by ethnicity or occupation, and adjusted for confounders. This paper reports the protocol for a prospective longitudinal questionnaire study of UK HCWs, as part of the UK-REACH programme (The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers).

Methods and analysis

A baseline questionnaire will be administered to a national cohort of UK HCWs and ancillary workers in healthcare settings, and those registered with UK healthcare regulators, with follow-up questionnaires administered at 4 and 8 months. With consent, questionnaire data will be linked to health records with 25-year follow-up. Univariate associations between ethnicity and clinical COVID-19 outcomes, physical and mental health, and key confounders/explanatory variables will be tested. Multivariable analyses will test for associations between ethnicity and key outcomes adjusted for the confounder/explanatory variables. We will model changes over time by ethnic group, facilitating understanding of absolute and relative risks in different ethnic groups, and generalisability of findings.

Ethics and dissemination

The study is approved by Health Research Authority (reference 20/HRA/4718), and carries minimal risk. We aim to manage the small risk of participant distress about questions on sensitive topics by clearly participant information that the questionnaire covers sensitive topics and there is no obligation to answer these or any other questions, and by providing support organisation links. Results will be disseminated with reports to Government and papers submitted to pre-print servers and peer reviewed journals.

Trial registration number

ISRCTN11811602; Pre-results.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/9/e050647.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-050647; html:https://europepmc.org/articles/PMC8450967; pdf:https://europepmc.org/articles/PMC8450967?pdf=render 34753797,https://doi.org/10.2337/db21-0320,An Expanded Genome-Wide Association Study of Fructosamine Levels Identifies RCN3 as a Replicating Locus and Implicates FCGRT as the Effector Transcript.,"Riveros-Mckay F, Roberts D, Di Angelantonio E, Yu B, Soranzo N, Danesh J, Selvin E, Butterworth AS, Barroso I.",,Diabetes,2022,2022-02-01,N,,,,"Fructosamine is a measure of short-term glycemic control, which has been suggested as a useful complement to glycated hemoglobin (HbA1c) for the diagnosis and monitoring of diabetes. To date, a single genome-wide association study (GWAS) including 8,951 U.S. White and 2,712 U.S. Black individuals without a diabetes diagnosis has been published. Results in Whites and Blacks yielded different association loci, near RCN3 and CNTN5, respectively. In this study, we performed a GWAS on 20,731 European-ancestry blood donors and meta-analyzed our results with previous data from U.S. White participants from the Atherosclerosis Risk in Communities (ARIC) study (Nmeta = 29,685). We identified a novel association near GCK (rs3757840, βmeta = 0.0062; minor allele frequency [MAF] = 0.49; Pmeta = 3.66 × 10-8) and confirmed the association near RCN3 (rs113886122, βmeta = 0.0134; MAF = 0.17; Pmeta = 5.71 × 10-18). Colocalization analysis with whole-blood expression quantitative trait loci data suggested FCGRT as the effector transcript at the RCN3 locus. We further showed that fructosamine has low heritability (h2 = 7.7%), has no significant genetic correlation with HbA1c and other glycemic traits in individuals without a diabetes diagnosis (P > 0.05), but has evidence of shared genetic etiology with some anthropometric traits (Bonferroni-corrected P < 0.0012). Our results broaden knowledge of the genetic architecture of fructosamine and prioritize FCGRT for downstream functional studies at the established RCN3 locus.",,pdf:https://diabetesjournals.org/diabetes/article-pdf/71/2/359/640867/db210320.pdf; doi:https://doi.org/10.2337/db21-0320; html:https://europepmc.org/articles/PMC8914280; pdf:https://europepmc.org/articles/PMC8914280?pdf=render; doi:https://doi.org/10.2337/db21-0320 31994239,https://doi.org/10.1002/bimj.201900041,Estimating treatment effects with partially observed covariates using outcome regression with missing indicators.,"Blake HA, Leyrat C, Mansfield KE, Tomlinson LA, Carpenter J, Williamson EJ.",,Biometrical journal. Biometrische Zeitschrift,2020,2020-01-29,N,Average Treatment Effect; Outcome Regression; Missing Covariate Data; Missing Indicator; Missing Confounder Data,,,"Missing data is a common issue in research using observational studies to investigate the effect of treatments on health outcomes. When missingness occurs only in the covariates, a simple approach is to use missing indicators to handle the partially observed covariates. The missing indicator approach has been criticized for giving biased results in outcome regression. However, recent papers have suggested that the missing indicator approach can provide unbiased results in propensity score analysis under certain assumptions. We consider assumptions under which the missing indicator approach can provide valid inferences, namely, (1) no unmeasured confounding within missingness patterns; either (2a) covariate values of patients with missing data were conditionally independent of treatment or (2b) these values were conditionally independent of outcome; and (3) the outcome model is correctly specified: specifically, the true outcome model does not include interactions between missing indicators and fully observed covariates. We prove that, under the assumptions above, the missing indicator approach with outcome regression can provide unbiased estimates of the average treatment effect. We use a simulation study to investigate the extent of bias in estimates of the treatment effect when the assumptions are violated and we illustrate our findings using data from electronic health records. In conclusion, the missing indicator approach can provide valid inferences for outcome regression, but the plausibility of its assumptions must first be considered carefully.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4655332/1/Estimating-treatment-effects-with-partially-observed-covariates-using-outcome-regression-with-missing-indicators.pdf; doi:https://doi.org/10.1002/bimj.201900041 @@ -1607,22 +1607,22 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 34032955,https://doi.org/10.1007/s11136-021-02876-4,"Health status after penetrating major trauma in Victoria, Australia: a registry-based cohort study.","Giummarra MJ, Dipnall JF, Gibson G, Beck B, Gabbe BJ.",,"Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation",2021,2021-05-25,N,Recovery; Health Status; Health-related Quality Of Life; Gunshot Wounds; Penetrating Trauma; Stab Wounds,,,"

Purpose

As few studies have examined long-term health after penetrating injury, this population-based registry study sought to assess health outcomes up to 24 months post-injury.

Methods

Major trauma patients with penetrating trauma (2009-2017) were included from the Victorian State Trauma Registry (N = 1,067; 102 died, 208 were lost to follow-up). The EQ-5D-3L was used to measure health status at 6, 12 and 24-months. Mixed linear and logistic regressions were used to examine predictors of summary scores, and problems versus no problems on each health dimension.

Results

Average health status summary scores were 0.70 (sd = 0.26) at 6 and 12 months, and 0.72 (sd = 0.26) at 24 months post-injury. Prevalence of problems was consistent over time: mobility (24-26%), self-care (17-20%), usual activities (47-50%), pain/discomfort (44-49%), and anxiety/depression (54-56%). Lower health status and reporting problems was associated with middle-older age, female sex, unemployment; pre-injury disability, comorbid conditions; and assault and firearm injury versus cutting/piercing.

Conclusion

Problems with usual activities, pain/discomfort and anxiety or depression are common after penetrating major trauma. Risk factor screening in hospital could be used to identify people at risk of poor health outcomes, and to link people at risk with services in hospital or early post-discharge to improve their longer-term health outcomes.",,doi:https://doi.org/10.1007/s11136-021-02876-4 33959646,https://doi.org/10.3389/fcvm.2021.658915,"Common Variants Associated With OSMR Expression Contribute to Carotid Plaque Vulnerability, but Not to Cardiovascular Disease in Humans.","van Keulen D, van Koeverden ID, Boltjes A, Princen HMG, van Gool AJ, de Borst GJ, Asselbergs FW, Tempel D, Pasterkamp G, van der Laan SW.",,Frontiers in cardiovascular medicine,2021,2021-04-20,Y,Genetics; Atherosclerosis; Cardiovascular disease; Plaque; Osm; Osmr; Lifr,,,"Background and Aims: Oncostatin M (OSM) signaling is implicated in atherosclerosis, however the mechanism remains unclear. We investigated the impact of common genetic variants in OSM and its receptors, OSMR and LIFR, on overall plaque vulnerability, plaque phenotype, intraplaque OSMR and LIFR expression, coronary artery calcification burden and cardiovascular disease susceptibility. Methods and Results: We queried Genotype-Tissue Expression data and found that rs13168867 (C allele) was associated with decreased OSMR expression and that rs10491509 (A allele) was associated with increased LIFR expression in arterial tissues. No variant was significantly associated with OSM expression. We associated these two variants with plaque characteristics from 1,443 genotyped carotid endarterectomy patients in the Athero-Express Biobank Study. After correction for multiple testing, rs13168867 was significantly associated with an increased overall plaque vulnerability (β = 0.118 ± s.e. = 0.040, p = 3.00 × 10-3, C allele). Looking at individual plaque characteristics, rs13168867 showed strongest associations with intraplaque fat (β = 0.248 ± s.e. = 0.088, p = 4.66 × 10-3, C allele) and collagen content (β = -0.259 ± s.e. = 0.095, p = 6.22 × 10-3, C allele), but these associations were not significant after correction for multiple testing. rs13168867 was not associated with intraplaque OSMR expression. Neither was intraplaque OSMR expression associated with plaque vulnerability and no known OSMR eQTLs were associated with coronary artery calcification burden, or cardiovascular disease susceptibility. No associations were found for rs10491509 in the LIFR locus. Conclusions: Our study suggests that rs1316887 in the OSMR locus is associated with increased plaque vulnerability, but not with coronary calcification or cardiovascular disease risk. It remains unclear through which precise biological mechanisms OSM signaling exerts its effects on plaque morphology. However, the OSM-OSMR/LIFR pathway is unlikely to be causally involved in lifetime cardiovascular disease susceptibility.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.658915/pdf; doi:https://doi.org/10.3389/fcvm.2021.658915; html:https://europepmc.org/articles/PMC8093786; pdf:https://europepmc.org/articles/PMC8093786?pdf=render 31408247,https://doi.org/10.1002/hpja.287,An assessment of program evaluation methods and quality in Australian prevention agencies.,"Schwarzman J, Nau T, Bauman A, Gabbe BJ, Rissel C, Shilton T, Smith BJ.",,Health promotion journal of Australia : official journal of Australian Association of Health Promotion Professionals,2020,2019-08-13,N,Program Evaluation; Government; Primary Prevention; Health Promotion; Evidence-based Practice; Health Equity; Non-government Organisations,,,"

Issue addressed

This study aimed to examine evaluation methods and quality in Australian health promotion agencies and the factors associated with this. The evidence base for prevention strategies is limited, with the evidence generated through program evaluation by health promotion and disease prevention agencies lacking rigour. Despite the need to improve the quality of evaluation, there is limited evidence of what influences evaluation quality in the prevention field.

Methods

Data were collected using the Evaluation Practice Analysis Survey and an audit and appraisal of evaluation reports. Descriptive analysis was used to examine evaluation characteristics and multivariable regression was used to explore the association between evaluation and organisational attributes and evaluation quality.

Results

In total, 392 evaluation reports were reviewed from 78 government and non-government agencies. Process evaluation was conducted most frequently, followed by impact evaluation. Overall evaluation quality was low (median 24.5%). In multivariable regression analysis, only two factors were associated with evaluation quality: health promotion budget (ratio of geometric means 1.53 [95% CI 1.02-2.29]); and, conducting statewide or national prevention programs (1.38 [95% CI 1.05-1.82]).

Conclusions

The findings show that the potential to improve evaluation quality is greatest in smaller organisations that deliver health promotion at a local or regional scale. SO WHAT?: By improving the rigour of existing evaluation, there is opportunity to build the evidence base for prevention strategies, which highlights the importance of embedding the enablers of program learning and evidence generation within health promotion and prevention organisations.",,doi:https://doi.org/10.1002/hpja.287 -38642613,https://doi.org/10.1016/j.clinme.2024.100209,Addressing ethnic disparities in neurological research in the United Kingdom: An example from the prospective multicentre COVID-19 Clinical Neuroscience Study.,"van Wamelen DJ, Rota S, Hartmann M, Martin NH, Alam AM, Thomas RH, Dodd KC, Jenkins T, Smith CJ, Zandi MS, Easton A, Carr G, Benjamin LA, Lilleker JB, Saucer D, Coles AJ, Wood N, Ray Chaudhuri K, Breen G, Michael BD, COVID-CNS consortium.",,"Clinical medicine (London, England)",2024,2024-04-19,Y,Diversity; Recruitment; Neurology; Ethnicity; Covid-19,,,"

Background

Minority ethnic groups have often been underrepresented in research, posing a problem in relation to external validity and extrapolation of findings. Here, we aimed to assess recruitment and retainment strategies in a large observational study assessing neurological complications following SARS-CoV-2 infection.

Methods

Participants were recruited following confirmed infection with SARS-CoV-2 and hospitalisation. Self-reported ethnicity was recorded alongside other demographic data to identify potential barriers to recruitment.

Results

807 participants were recruited to COVID-CNS, and ethnicity data were available for 93.2%. We identified a proportionate representation of self-reported ethnicity categories, and distribution of broad ethnicity categories mirrored individual centres' catchment areas. White ethnicity within individual centres ranged between 44.5% and 89.1%, with highest percentage of participants with non-White ethnicity in London-based centres. Examples are provided how to reach potentially underrepresented minority ethnic groups.

Conclusions

Recruitment barriers in relation to potentially underrepresented ethnic groups may be overcome with strategies identified here.",,doi:https://doi.org/10.1016/j.clinme.2024.100209; html:https://europepmc.org/articles/PMC11091497; pdf:https://europepmc.org/articles/PMC11091497?pdf=render -35115689,https://doi.org/10.1038/s41588-021-00991-z,Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort.,"Qin Y, Havulinna AS, Liu Y, Jousilahti P, Ritchie SC, Tokolyi A, Sanders JG, Valsta L, Brożyńska M, Zhu Q, Tripathi A, Vázquez-Baeza Y, Loomba R, Cheng S, Jain M, Niiranen T, Lahti L, Knight R, Salomaa V, Inouye M, Méric G.",,Nature genetics,2022,2022-02-03,N,,,,"Human genetic variation affects the gut microbiota through a complex combination of environmental and host factors. Here we characterize genetic variations associated with microbial abundances in a single large-scale population-based cohort of 5,959 genotyped individuals with matched gut microbial metagenomes, and dietary and health records (prevalent and follow-up). We identified 567 independent SNP-taxon associations. Variants at the LCT locus associated with Bifidobacterium and other taxa, but they differed according to dairy intake. Furthermore, levels of Faecalicatena lactaris associated with ABO, and suggested preferential utilization of secreted blood antigens as energy source in the gut. Enterococcus faecalis levels associated with variants in the MED13L locus, which has been linked to colorectal cancer. Mendelian randomization analysis indicated a potential causal effect of Morganella on major depressive disorder, consistent with observational incident disease analysis. Overall, we identify and characterize the intricate nature of host-microbiota interactions and their association with disease.",,pdf:https://www.nature.com/articles/s41588-021-00991-z.pdf; doi:https://doi.org/10.1038/s41588-021-00991-z; html:https://europepmc.org/articles/PMC9883041; pdf:https://europepmc.org/articles/PMC9883041?pdf=render; doi:https://doi.org/10.1038/s41588-021-00991-z 32685698,https://doi.org/10.12688/wellcomeopenres.15842.3,Estimating the overdispersion in COVID-19 transmission using outbreak sizes outside China.,"Endo A, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Abbott S, Kucharski AJ, Funk S.",,Wellcome open research,2020,2020-07-10,Y,Branching Process; Overdispersion; Novel Coronavirus; Superspreading; Covid-19; Sars-cov-2,,,"Background: A novel coronavirus disease (COVID-19) outbreak has now spread to a number of countries worldwide. While sustained transmission chains of human-to-human transmission suggest high basic reproduction number R 0, variation in the number of secondary transmissions (often characterised by so-called superspreading events) may be large as some countries have observed fewer local transmissions than others. Methods: We quantified individual-level variation in COVID-19 transmission by applying a mathematical model to observed outbreak sizes in affected countries. We extracted the number of imported and local cases in the affected countries from the World Health Organization situation report and applied a branching process model where the number of secondary transmissions was assumed to follow a negative-binomial distribution. Results: Our model suggested a high degree of individual-level variation in the transmission of COVID-19. Within the current consensus range of R 0 (2-3), the overdispersion parameter k of a negative-binomial distribution was estimated to be around 0.1 (median estimate 0.1; 95% CrI: 0.05-0.2 for R0 = 2.5), suggesting that 80% of secondary transmissions may have been caused by a small fraction of infectious individuals (~10%). A joint estimation yielded likely ranges for R 0 and k (95% CrIs: R 0 1.4-12; k 0.04-0.2); however, the upper bound of R 0 was not well informed by the model and data, which did not notably differ from that of the prior distribution. Conclusions: Our finding of a highly-overdispersed offspring distribution highlights a potential benefit to focusing intervention efforts on superspreading. As most infected individuals do not contribute to the expansion of an epidemic, the effective reproduction number could be drastically reduced by preventing relatively rare superspreading events.",,doi:https://doi.org/10.12688/wellcomeopenres.15842.3; html:https://europepmc.org/articles/PMC7338915; pdf:https://europepmc.org/articles/PMC7338915?pdf=render +35115689,https://doi.org/10.1038/s41588-021-00991-z,Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort.,"Qin Y, Havulinna AS, Liu Y, Jousilahti P, Ritchie SC, Tokolyi A, Sanders JG, Valsta L, Brożyńska M, Zhu Q, Tripathi A, Vázquez-Baeza Y, Loomba R, Cheng S, Jain M, Niiranen T, Lahti L, Knight R, Salomaa V, Inouye M, Méric G.",,Nature genetics,2022,2022-02-03,N,,,,"Human genetic variation affects the gut microbiota through a complex combination of environmental and host factors. Here we characterize genetic variations associated with microbial abundances in a single large-scale population-based cohort of 5,959 genotyped individuals with matched gut microbial metagenomes, and dietary and health records (prevalent and follow-up). We identified 567 independent SNP-taxon associations. Variants at the LCT locus associated with Bifidobacterium and other taxa, but they differed according to dairy intake. Furthermore, levels of Faecalicatena lactaris associated with ABO, and suggested preferential utilization of secreted blood antigens as energy source in the gut. Enterococcus faecalis levels associated with variants in the MED13L locus, which has been linked to colorectal cancer. Mendelian randomization analysis indicated a potential causal effect of Morganella on major depressive disorder, consistent with observational incident disease analysis. Overall, we identify and characterize the intricate nature of host-microbiota interactions and their association with disease.",,pdf:https://www.nature.com/articles/s41588-021-00991-z.pdf; doi:https://doi.org/10.1038/s41588-021-00991-z; html:https://europepmc.org/articles/PMC9883041; pdf:https://europepmc.org/articles/PMC9883041?pdf=render; doi:https://doi.org/10.1038/s41588-021-00991-z +38642613,https://doi.org/10.1016/j.clinme.2024.100209,Addressing ethnic disparities in neurological research in the United Kingdom: An example from the prospective multicentre COVID-19 Clinical Neuroscience Study.,"van Wamelen DJ, Rota S, Hartmann M, Martin NH, Alam AM, Thomas RH, Dodd KC, Jenkins T, Smith CJ, Zandi MS, Easton A, Carr G, Benjamin LA, Lilleker JB, Saucer D, Coles AJ, Wood N, Ray Chaudhuri K, Breen G, Michael BD, COVID-CNS consortium.",,"Clinical medicine (London, England)",2024,2024-04-19,Y,Diversity; Recruitment; Neurology; Ethnicity; Covid-19,,,"

Background

Minority ethnic groups have often been underrepresented in research, posing a problem in relation to external validity and extrapolation of findings. Here, we aimed to assess recruitment and retainment strategies in a large observational study assessing neurological complications following SARS-CoV-2 infection.

Methods

Participants were recruited following confirmed infection with SARS-CoV-2 and hospitalisation. Self-reported ethnicity was recorded alongside other demographic data to identify potential barriers to recruitment.

Results

807 participants were recruited to COVID-CNS, and ethnicity data were available for 93.2%. We identified a proportionate representation of self-reported ethnicity categories, and distribution of broad ethnicity categories mirrored individual centres' catchment areas. White ethnicity within individual centres ranged between 44.5% and 89.1%, with highest percentage of participants with non-White ethnicity in London-based centres. Examples are provided how to reach potentially underrepresented minority ethnic groups.

Conclusions

Recruitment barriers in relation to potentially underrepresented ethnic groups may be overcome with strategies identified here.",,doi:https://doi.org/10.1016/j.clinme.2024.100209; html:https://europepmc.org/articles/PMC11091497; pdf:https://europepmc.org/articles/PMC11091497?pdf=render 38180742,https://doi.org/10.1097/qai.0000000000003326,Estimation of Improvements in Mortality in Spectrum Among Adults With HIV Receiving Antiretroviral Therapy in High-Income Countries.,"Trickey A, Glaubius R, Pantazis N, Zangerle R, Wittkop L, Vehreschild J, Grabar S, Cavassini M, Teira R, d'Arminio Monforte A, Casabona J, van Sighem A, Jarrin I, Ingle SM, Sterne JAC, Imai-Eaton JW, Johnson LF.",,Journal of acquired immune deficiency syndromes (1999),2024,2024-01-04,Y,,,,"

Introduction

Mortality rates for people living with HIV (PLHIV) on antiretroviral therapy (ART) in high-income countries continue to decline. We compared mortality rates among PLHIV on ART in Europe for 2016-2020 with Spectrum's estimates.

Methods

The AIDS Impact Module in Spectrum is a compartmental HIV epidemic model coupled with a demographic population projection model. We used national Spectrum projections developed for the 2022 HIV estimates round to calculate mortality rates among PLHIV on ART, adjusting to the age/country distribution of PLHIV starting ART from 1996 to 2020 in the Antiretroviral Therapy Cohort Collaboration (ART-CC)'s European cohorts.

Results

In the ART-CC, 11,504 of 162,835 PLHIV died. Between 1996-1999 and 2016-2020, AIDS-related mortality in the ART-CC decreased from 8.8 (95% CI: 7.6 to 10.1) to 1.0 (0.9-1.2) and from 5.9 (4.4-8.1) to 1.1 (0.9-1.4) deaths per 1000 person-years among men and women, respectively. Non-AIDS-related mortality decreased from 9.1 (7.9-10.5) to 6.1 (5.8-6.5) and from 7.0 (5.2-9.3) to 4.8 (4.3-5.2) deaths per 1000 person-years among men and women, respectively. Adjusted all-cause mortality rates in Spectrum among men were near ART-CC estimates for 2016-2020 (Spectrum: 7.02-7.47 deaths per 1000 person-years) but approximately 20% lower in women (Spectrum: 4.66-4.70). Adjusted excess mortality rates in Spectrum were 2.5-fold higher in women and 3.1-3.4-fold higher in men in comparison to the ART-CC's AIDS-specific mortality rates.

Discussion

Spectrum's all-cause mortality estimates among PLHIV are consistent with age/country-controlled mortality observed in ART-CC, with some underestimation of mortality among women. Comparing results suggest that 60%-70% of excess deaths among PLHIV on ART in Spectrum are from non-AIDS causes.",,html:https://journals.lww.com/jaids/fulltext/2024/01011/estimation_of_improvements_in_mortality_in.10.aspx; doi:https://doi.org/10.1097/QAI.0000000000003326; html:https://europepmc.org/articles/PMC10769170; pdf:https://europepmc.org/articles/PMC10769170?pdf=render 35866236,https://doi.org/10.7189/jogh.12.05033,The road to recovery: an interrupted time series analysis of policy intervention to restore essential health services in Mexico during the COVID-19 pandemic.,"Doubova SV, Arsenault C, Contreras-Sánchez SE, Borrayo-Sánchez G, Leslie HH.",,Journal of global health,2022,2022-07-23,Y,,,,"

Background

Recovery of health services disrupted by the COVID-19 pandemic represents a significant challenge in low- and middle-income countries. In April 2021, the Mexican Institute of Social Security (IMSS), which provides health care to 68.5 million people, launched the National Strategy for Health Services Recovery (Recovery policy). The study objective was to evaluate whether the Recovery policy addressed COVID-related declines in maternal, child health, and non-communicable diseases (NCDs) services.

Methods

We analysed the data of 35 IMSS delegations from January 2019 to November 2021 on contraceptive visits, antenatal care consultations, deliveries, caesarean sections, sick children's consultations, child vaccination, breast and cervical cancer screening, diabetes and hypertension consultations, and control. We focused on the period before (April 2020 - March 2021) and during (April 2021 - November 2021) the Recovery policy and used an interrupted time series design and Poisson Generalized Estimating Equation models to estimate the association of this policy with service use and outcomes and change in their trends.

Results

Despite the third wave of the pandemic in 2021, service utilization increased in the Recovery period, reaching (at minimum) 49% of pre-pandemic levels for sick children's consultations and (at maximum) 106% of pre-pandemic levels for breast cancer screenings. Evidence for the Recovery policy role was mixed: the policy was associated with increased facility deliveries (IRR = 1.15, 95%CI = 1.11-1.19) with a growing trend over time (IRR = 1.04, 95%CI = 1.03-1.05); antenatal care and child health services saw strong level effects but decrease over time. Additionally, the Recovery policy was associated with diabetes and hypertension control. Services recovery varied across delegations.

Conclusions

Health service utilization and NCDs control demonstrated important gains in 2021, but evidence suggests the policy had inconsistent effects across services and decreasing impact over time. Further efforts to strengthen essential health services and ensure consistent recovery across delegations are warranted.",,pdf:https://jogh.org/wp-content/uploads/2022/07/jogh-12-05033.pdf; doi:https://doi.org/10.7189/jogh.12.05033; html:https://europepmc.org/articles/PMC9304921; pdf:https://europepmc.org/articles/PMC9304921?pdf=render -33372068,https://doi.org/10.1136/bmjopen-2020-038324,Risk factors for mental illness in adults with atopic eczema or psoriasis: protocol for a systematic review.,"Adesanya EI, Schonmann Y, Hayes JF, Mathur R, Mulick AR, Rayner L, Smeeth L, Smith CH, Langan SM, Mansfield KE.",,BMJ open,2020,2020-12-28,Y,Psoriasis; Mental health; Eczema; Anxiety Disorders; Schizophrenia & Psychotic Disorders; Depression & Mood Disorders,,,"

Introduction

Evidence indicates that people with the common inflammatory skin diseases atopic eczema or psoriasis are at increased risk of mental illness. However, the reasons for the relationship between skin disease and common mental disorders (ie, depression and anxiety) or severe mental illnesses (ie, schizophrenia, bipolar disorder and other psychoses) are unclear. Therefore, we aim to synthesise the available evidence regarding the risk factors for mental illness in adults with atopic eczema or psoriasis.

Methods and analysis

We will conduct a systematic review of randomised controlled trials, cohort, case-control and cross-sectional studies. We will search the following databases from inception to March 2020: Medline, Embase, Global Health, Scopus, the Cochrane Library, Web of Science, Base, PsycInfo, the Global Resource of Eczema Trials, and the grey literature databases Open Grey, PsycExtra and the New York Academy of Medicine Grey Literature Report. We will also search the bibliographies of eligible studies and relevant systematic reviews to identify additional relevant studies. Citation searching of large summary papers will be used to further identify relevant publications. Two reviewers will initially review study titles and abstracts for eligibility, followed by full text screening. We will extract data using a standardised data extraction form. We will assess the risk of bias of included studies using the Quality in Prognosis Studies tool. We will synthesise data narratively, and if studies are sufficiently homogenous, we will consider a meta-analysis. We will assess the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework.

Ethics and dissemination

Ethical approval is not required for a systematic review. Results of the review will be published in a peer-reviewed journal and disseminated through conferences.

Prospero registration number

CRD42020163941.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/12/e038324.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-038324; html:https://europepmc.org/articles/PMC7772326; pdf:https://europepmc.org/articles/PMC7772326?pdf=render 31282950,https://doi.org/10.1001/jamaneurol.2019.1812,Association Between Idiopathic Intracranial Hypertension and Risk of Cardiovascular Diseases in Women in the United Kingdom.,"Adderley NJ, Subramanian A, Nirantharakumar K, Yiangou A, Gokhale KM, Mollan SP, Sinclair AJ.",,JAMA neurology,2019,2019-09-01,Y,,Understanding the Causes of Disease,,"

Importance

Cardiovascular disease (CVD) risk has not been previously evaluated in a large matched cohort study in idiopathic intracranial hypertension (IIH).

Objectives

To estimate the risk of composite cardiovascular events, heart failure, ischemic heart disease, stroke/transient ischemic attack (TIA), type 2 diabetes, and hypertension in women with idiopathic intracranial hypertension and compare it with the risk in women, matched on body mass index (BMI) and age, without the condition; and to evaluate the prevalence and incidence of IIH.

Design, setting, and participants

This population-based matched controlled cohort study used 28 years of data, from January 1, 1990, to January 17, 2018, from The Health Improvement Network (THIN), an anonymized, nationally representative electronic medical records database in the United Kingdom. All female patients aged 16 years or older were eligible for inclusion. Female patients with IIH (n = 2760) were included and randomly matched with up to 10 control patients (n = 27 125) by BMI and age.

Main outcomes and measures

Adjusted hazard ratios (aHRs) of cardiovascular outcomes were calculated using Cox regression models. The primary outcome was a composite of any CVD (heart failure, ischemic heart disease, and stroke/TIA), and the secondary outcomes were each CVD outcome, type 2 diabetes, and hypertension.

Results

In total, 2760 women with IIH and 27 125 women without IIH were included. Age and BMI were similar between the 2 groups, with a median (interquartile range) age of 32.1 (25.6-42.0) years in the exposed group and 32.1 (25.7-42.1) years in the control group; in the exposed group 1728 women (62.6%) were obese, and in the control group 16514 women (60.9%) were obese. Higher absolute risks for all cardiovascular outcomes were observed in women with IIH compared with control patients. The aHRs were as follows: composite cardiovascular events, 2.10 (95% CI, 1.61-2.74; P < .001); heart failure, 1.97 (95% CI, 1.16-3.37; P = .01); ischemic heart disease, 1.94 (95% CI, 1.27-2.94; P = .002); stroke/TIA, 2.27 (95% CI, 1.61-3.21; P < .001); type 2 diabetes, 1.30 (95% CI, 1.07-1.57; P = .009); and hypertension, 1.55 (95% CI, 1.30-1.84; P < .001). The incidence of IIH in female patients more than tripled between 2005 and 2017, from 2.5 to 9.3 per 100 000 person-years. Similarly, IIH prevalence increased in the same period, from 26 to 79 per 100 000 women. Incidence increased markedly with BMI higher than 30.

Conclusions and relevance

Idiopathic intracranial hypertension in women appeared to be associated with a 2-fold increase in CVD risk; change in patient care to modify risk factors for CVD may reduce long-term morbidity for women with IIH and warrants further evaluation.",,pdf:https://jamanetwork.com/journals/jamaneurology/articlepdf/2737044/jamaneurology_adderley_2019_oi_190046.pdf; doi:https://doi.org/10.1001/jamaneurol.2019.1812; html:https://europepmc.org/articles/PMC6618853 +33372068,https://doi.org/10.1136/bmjopen-2020-038324,Risk factors for mental illness in adults with atopic eczema or psoriasis: protocol for a systematic review.,"Adesanya EI, Schonmann Y, Hayes JF, Mathur R, Mulick AR, Rayner L, Smeeth L, Smith CH, Langan SM, Mansfield KE.",,BMJ open,2020,2020-12-28,Y,Psoriasis; Mental health; Eczema; Anxiety Disorders; Schizophrenia & Psychotic Disorders; Depression & Mood Disorders,,,"

Introduction

Evidence indicates that people with the common inflammatory skin diseases atopic eczema or psoriasis are at increased risk of mental illness. However, the reasons for the relationship between skin disease and common mental disorders (ie, depression and anxiety) or severe mental illnesses (ie, schizophrenia, bipolar disorder and other psychoses) are unclear. Therefore, we aim to synthesise the available evidence regarding the risk factors for mental illness in adults with atopic eczema or psoriasis.

Methods and analysis

We will conduct a systematic review of randomised controlled trials, cohort, case-control and cross-sectional studies. We will search the following databases from inception to March 2020: Medline, Embase, Global Health, Scopus, the Cochrane Library, Web of Science, Base, PsycInfo, the Global Resource of Eczema Trials, and the grey literature databases Open Grey, PsycExtra and the New York Academy of Medicine Grey Literature Report. We will also search the bibliographies of eligible studies and relevant systematic reviews to identify additional relevant studies. Citation searching of large summary papers will be used to further identify relevant publications. Two reviewers will initially review study titles and abstracts for eligibility, followed by full text screening. We will extract data using a standardised data extraction form. We will assess the risk of bias of included studies using the Quality in Prognosis Studies tool. We will synthesise data narratively, and if studies are sufficiently homogenous, we will consider a meta-analysis. We will assess the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework.

Ethics and dissemination

Ethical approval is not required for a systematic review. Results of the review will be published in a peer-reviewed journal and disseminated through conferences.

Prospero registration number

CRD42020163941.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/12/e038324.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-038324; html:https://europepmc.org/articles/PMC7772326; pdf:https://europepmc.org/articles/PMC7772326?pdf=render 34348396,https://doi.org/10.1097/ede.0000000000001393,Weight Change and the Onset of Cardiovascular Diseases: Emulating Trials Using Electronic Health Records.,"Katsoulis M, Stavola BD, Diaz-Ordaz K, Gomes M, Lai A, Lagiou P, Wannamethee G, Tsilidis K, Lumbers RT, Denaxas S, Banerjee A, Parisinos CA, Batterham R, Patel R, Langenberg C, Hemingway H.",,"Epidemiology (Cambridge, Mass.)",2021,2021-09-01,Y,,,,"

Background

Cross-sectional measures of body mass index (BMI) are associated with cardiovascular disease (CVD) incidence, but less is known about whether weight change affects the risk of CVD.

Methods

We estimated the effect of 2-y weight change interventions on 7-y risk of CVD (CVD death, myocardial infarction, stroke, hospitalization from coronary heart disease, and heart failure) by emulating hypothetical interventions using electronic health records. We identified 138,567 individuals with 45-69 years of age without chronic disease in England from 1998 to 2016. We performed pooled logistic regression, using inverse-probability weighting to adjust for baseline and time-varying confounders. We categorized each individual into a weight loss, maintenance, or gain group.

Results

Among those of normal weight, both weight loss [risk difference (RD) vs. weight maintenance = 1.5% (0.3% to 3.0%)] and gain [RD = 1.3% (0.5% to 2.2%)] were associated with increased risk for CVD compared with weight maintenance. Among overweight individuals, we observed moderately higher risk of CVD in both the weight loss [RD = 0.7% (-0.2% to 1.7%)] and the weight gain group [RD = 0.7% (-0.1% to 1.7%)], compared with maintenance. In the obese, those losing weight showed lower risk of coronary heart disease [RD = -1.4% (-2.4% to -0.6%)] but not of stroke. When we assumed that chronic disease occurred 1-3 years before the recorded date, estimates for weight loss and gain were attenuated among overweight individuals; estimates for loss were lower among obese individuals.

Conclusion

Among individuals with obesity, the weight-loss group had a lower risk of coronary heart disease but not of stroke. Weight gain was associated with increased risk of CVD across BMI groups. See video abstract at, http://links.lww.com/EDE/B838.",,html:https://journals.lww.com/epidem/Fulltext/2021/09000/Weight_Change_and_the_Onset_of_Cardiovascular.19.aspx; doi:https://doi.org/10.1097/EDE.0000000000001393; html:https://europepmc.org/articles/PMC8318567; pdf:https://europepmc.org/articles/PMC8318567?pdf=render 33521535,https://doi.org/10.1136/bmjnph-2020-000107,Genetic risk of obesity as a modifier of associations between neighbourhood environment and body mass index: an observational study of 335 046 UK Biobank participants.,"Mason KE, Palla L, Pearce N, Phelan J, Cummins S.",,"BMJ nutrition, prevention & health",2020,2020-10-05,Y,Malnutrition; Dietary Patterns,,,"

Background

There is growing recognition that recent global increases in obesity are the product of a complex interplay between genetic and environmental factors. However, in gene-environment studies of obesity, 'environment' usually refers to individual behavioural factors that influence energy balance, whereas more upstream environmental factors are overlooked. We examined gene-environment interactions between genetic risk of obesity and two neighbourhood characteristics likely to be associated with obesity (proximity to takeaway/fast-food outlets and availability of physical activity facilities).

Methods

We used data from 335 046 adults aged 40-70 in the UK Biobank cohort to conduct a population-based cross-sectional study of interactions between neighbourhood characteristics and genetic risk of obesity, in relation to body mass index (BMI). Proximity to a fast-food outlet was defined as distance from home address to nearest takeaway/fast-food outlet, and availability of physical activity facilities as the number of formal physical activity facilities within 1 km of home address. Genetic risk of obesity was operationalised by weighted Genetic Risk Scores of 91 or 69 single nucleotide polymorphisms (SNP), and by six individual SNPs considered separately. Multivariable, mixed-effects models with product terms for the gene-environment interactions were estimated.

Results

After accounting for likely confounding, the association between proximity to takeaway/fast-food outlets and BMI was stronger among those at increased genetic risk of obesity, with evidence of an interaction with polygenic risk scores (p=0.018 and p=0.028 for 69-SNP and 91-SNP scores, respectively) and in particular with a SNP linked to MC4R (p=0.009), a gene known to regulate food intake. We found very little evidence of gene-environment interaction for the availability of physical activity facilities.

Conclusions

Individuals at an increased genetic risk of obesity may be more sensitive to exposure to the local fast-food environment. Ensuring that neighbourhood residential environments are designed to promote a healthy weight may be particularly important for those with greater genetic susceptibility to obesity.",,pdf:https://nutrition.bmj.com/content/bmjnph/3/2/247.full.pdf; doi:https://doi.org/10.1136/bmjnph-2020-000107; html:https://europepmc.org/articles/PMC7841812; pdf:https://europepmc.org/articles/PMC7841812?pdf=render 37777287,https://doi.org/10.1016/s2468-2667(23)00178-0,"All-cause hospitalisation among people living with HIV according to gender, mode of HIV acquisition, ethnicity, and geographical origin in Europe and North America: findings from the ART-CC cohort collaboration.","Rein SM, Lampe FC, Ingle SM, Sterne JAC, Trickey A, Gill MJ, Papastamopoulos V, Wittkop L, van der Valk M, Kitchen M, Guest JL, Satre DD, Wandeler G, Galindo P, Castilho J, Crane HM, Smith CJ.",,The Lancet. Public health,2023,2023-10-01,Y,,,,"

Background

Understanding demographic disparities in hospitalisation is crucial for the identification of vulnerable populations, interventions, and resource planning.

Methods

Data were from the Antiretroviral Therapy Cohort Collaboration (ART-CC) on people living with HIV in Europe and North America, followed up between January, 2007 and December, 2020. We investigated differences in all-cause hospitalisation according to gender and mode of HIV acquisition, ethnicity, and combined geographical origin and ethnicity, in people living with HIV on modern combination antiretroviral therapy (cART). Analyses were performed separately for European and North American cohorts. Hospitalisation rates were assessed using negative binomial multilevel regression, adjusted for age, time since cART intitiaion, and calendar year.

Findings

Among 23 594 people living with HIV in Europe and 9612 in North America, hospitalisation rates per 100 person-years were 16·2 (95% CI 16·0-16·4) and 13·1 (12·8-13·5). Compared with gay, bisexual, and other men who have sex with men, rates were higher for heterosexual men and women, and much higher for men and women who acquired HIV through injection drug use (adjusted incidence rate ratios ranged from 1·2 to 2·5 in Europe and from 1·2 to 3·3 in North America). In both regions, individuals with geographical origin other than the region of study generally had lower hospitalisation rates compared with those with geographical origin of the study country. In North America, Indigenous people and Black or African American individuals had higher rates than White individuals (adjusted incidence rate ratios 1·9 and 1·2), whereas Asian and Hispanic people living with HIV had somewhat lower rates. In Europe there was a lower rate in Asian individuals compared with White individuals.

Interpretation

Substantial disparities exist in all-cause hospitalisation between demographic groups of people living with HIV in the current cART era in high-income settings, highlighting the need for targeted support.

Funding

Royal Free Charity and the National Institute on Alcohol Abuse and Alcoholism.",,pdf:http://www.thelancet.com/article/S2468266723001780/pdf; doi:https://doi.org/10.1016/S2468-2667(23)00178-0; html:https://europepmc.org/articles/PMC10851157; pdf:https://europepmc.org/articles/PMC10851157?pdf=render 36689332,https://doi.org/10.1093/neuonc/noad021,GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data.,"Ajaib S, Lodha D, Pollock S, Hemmings G, Finetti MA, Gusnanto A, Chakrabarty A, Ismail A, Wilson E, Varn FS, Hunter B, Filby A, Brockman AA, McDonald D, Verhaak RGW, Ihrie RA, Stead LF.",,Neuro-oncology,2023,2023-07-01,Y,Immune; Deconvolution; Glioblastoma; Neoplastic; Transcriptomics,,,"

Background

Characterizing and quantifying cell types within glioblastoma (GBM) tumors at scale will facilitate a better understanding of the association between the cellular landscape and tumor phenotypes or clinical correlates. We aimed to develop a tool that deconvolutes immune and neoplastic cells within the GBM tumor microenvironment from bulk RNA sequencing data.

Methods

We developed an IDH wild-type (IDHwt) GBM-specific single immune cell reference consisting of B cells, T-cells, NK-cells, microglia, tumor associated macrophages, monocytes, mast and DC cells. We used this alongside an existing neoplastic single cell-type reference for astrocyte-like, oligodendrocyte- and neuronal progenitor-like and mesenchymal GBM cancer cells to create both marker and gene signature matrix-based deconvolution tools. We applied single-cell resolution imaging mass cytometry (IMC) to ten IDHwt GBM samples, five paired primary and recurrent tumors, to determine which deconvolution approach performed best.

Results

Marker-based deconvolution using GBM-tissue specific markers was most accurate for both immune cells and cancer cells, so we packaged this approach as GBMdeconvoluteR. We applied GBMdeconvoluteR to bulk GBM RNAseq data from The Cancer Genome Atlas and recapitulated recent findings from multi-omics single cell studies with regards associations between mesenchymal GBM cancer cells and both lymphoid and myeloid cells. Furthermore, we expanded upon this to show that these associations are stronger in patients with worse prognosis.

Conclusions

GBMdeconvoluteR accurately quantifies immune and neoplastic cell proportions in IDHwt GBM bulk RNA sequencing data and is accessible here: https://gbmdeconvoluter.leeds.ac.uk.",,pdf:https://academic.oup.com/neuro-oncology/advance-article-pdf/doi/10.1093/neuonc/noad021/49522012/noad021.pdf; doi:https://doi.org/10.1093/neuonc/noad021; html:https://europepmc.org/articles/PMC10326489; pdf:https://europepmc.org/articles/PMC10326489?pdf=render 37264679,https://doi.org/10.1093/eurjpc/zwad187,Improving 10-year cardiovascular risk prediction in apparently healthy people: flexible addition of risk modifiers on top of SCORE2.,"Hageman SHJ, Petitjaen C, Pennells L, Kaptoge S, Pajouheshnia R, Tillmann T, Blaha MJ, McClelland RL, Matsushita K, Nambi V, Klungel OH, Souverein PC, van der Schouw YT, Verschuren WMM, Lehmann N, Erbel R, Jöckel KH, Di Angelantonio E, Visseren FLJ, Dorresteijn JAN.",,European journal of preventive cardiology,2023,2023-10-01,Y,Biomarkers; Risk stratification; Risk Prediction; cardiovascular; Coronary Calcium Score; Score2,,,"

Aims

In clinical practice, factors associated with cardiovascular disease (CVD) like albuminuria, education level, or coronary artery calcium (CAC) are often known, but not incorporated in cardiovascular risk prediction models. The aims of the current study were to evaluate a methodology for the flexible addition of risk modifying characteristics on top of SCORE2 and to quantify the added value of several clinically relevant risk modifying characteristics.

Methods and results

Individuals without previous CVD or DM were included from the UK Biobank; Atherosclerosis Risk in Communities (ARIC); Multi-Ethnic Study of Atherosclerosis (MESA); European Prospective Investigation into Cancer, The Netherlands (EPIC-NL); and Heinz Nixdorf Recall (HNR) studies (n = 409 757) in whom 16 166 CVD events and 19 149 non-cardiovascular deaths were observed over exactly 10.0 years of follow-up. The effect of each possible risk modifying characteristic was derived using competing risk-adjusted Fine and Gray models. The risk modifying characteristics were applied to individual predictions with a flexible method using the population prevalence and the subdistribution hazard ratio (SHR) of the relevant predictor. Risk modifying characteristics that increased discrimination most were CAC percentile with 0.0198 [95% confidence interval (CI) 0.0115; 0.0281] and hs-Troponin-T with 0.0100 (95% CI 0.0063; 0.0137). External validation was performed in the Clinical Practice Research Datalink (CPRD) cohort (UK, n = 518 015, 12 675 CVD events). Adjustment of SCORE2-predicted risks with both single and multiple risk modifiers did not negatively affect calibration and led to a modest increase in discrimination [0.740 (95% CI 0.736-0.745) vs. unimproved SCORE2 risk C-index 0.737 (95% CI 0.732-0.741)].

Conclusion

The current paper presents a method on how to integrate possible risk modifying characteristics that are not included in existing CVD risk models for the prediction of CVD event risk in apparently healthy people. This flexible methodology improves the accuracy of predicted risks and increases applicability of prediction models for individuals with additional risk known modifiers.",,pdf:https://academic.oup.com/eurjpc/advance-article-pdf/doi/10.1093/eurjpc/zwad187/50506335/zwad187.pdf; doi:https://doi.org/10.1093/eurjpc/zwad187; html:https://europepmc.org/articles/PMC10600319; pdf:https://europepmc.org/articles/PMC10600319?pdf=render -37705296,https://doi.org/10.1002/sim.9898,Using temporal recalibration to improve the calibration of risk prediction models in competing risk settings when there are trends in survival over time.,"Booth S, Mozumder SI, Archer L, Ensor J, Riley RD, Lambert PC, Rutherford MJ.",,Statistics in medicine,2023,2023-09-13,Y,calibration; Risk Prediction; Competing Risks; Temporal Recalibration; Prognostic Models,,,"We have previously proposed temporal recalibration to account for trends in survival over time to improve the calibration of predictions from prognostic models for new patients. This involves first estimating the predictor effects using data from all individuals (full dataset) and then re-estimating the baseline using a subset of the most recent data whilst constraining the predictor effects to remain the same. In this article, we demonstrate how temporal recalibration can be applied in competing risk settings by recalibrating each cause-specific (or subdistribution) hazard model separately. We illustrate this using an example of colon cancer survival with data from the Surveillance Epidemiology and End Results (SEER) program. Data from patients diagnosed in 1995-2004 were used to fit two models for deaths due to colon cancer and other causes respectively. We discuss considerations that need to be made in order to apply temporal recalibration such as the choice of data used in the recalibration step. We also demonstrate how to assess the calibration of these models in new data for patients diagnosed subsequently in 2005. Comparison was made to a standard analysis (when improvements over time are not taken into account) and a period analysis which is similar to temporal recalibration but differs in the data used to estimate the predictor effects. The 10-year calibration plots demonstrated that using the standard approach over-estimated the risk of death due to colon cancer and the total risk of death and that calibration was improved using temporal recalibration or period analysis.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/sim.9898; doi:https://doi.org/10.1002/sim.9898; html:https://europepmc.org/articles/PMC10946485; pdf:https://europepmc.org/articles/PMC10946485?pdf=render 33591280,https://doi.org/10.2196/16348,A Social Media Campaign (#datasaveslives) to Promote the Benefits of Using Health Data for Research Purposes: Mixed Methods Analysis.,"Hassan L, Nenadic G, Tully MP.",,Journal of medical Internet research,2021,2021-02-16,Y,Medical research; Public Engagement; Social Network Analysis; Social Media,,,"

Background

Social media provides the potential to engage a wide audience about scientific research, including the public. However, little empirical research exists to guide health scientists regarding what works and how to optimize impact. We examined the social media campaign #datasaveslives established in 2014 to highlight positive examples of the use and reuse of health data in research.

Objective

This study aims to examine how the #datasaveslives hashtag was used on social media, how often, and by whom; thus, we aim to provide insights into the impact of a major social media campaign in the UK health informatics research community and further afield.

Methods

We analyzed all publicly available posts (tweets) that included the hashtag #datasaveslives (N=13,895) on the microblogging platform Twitter between September 1, 2016, and August 31, 2017. Using a combination of qualitative and quantitative analyses, we determined the frequency and purpose of tweets. Social network analysis was used to analyze and visualize tweet sharing (retweet) networks among hashtag users.

Results

Overall, we found 4175 original posts and 9720 retweets featuring #datasaveslives by 3649 unique Twitter users. In total, 66.01% (2756/4175) of the original posts were retweeted at least once. Higher frequencies of tweets were observed during the weeks of prominent policy publications, popular conferences, and public engagement events. Cluster analysis based on retweet relationships revealed an interconnected series of groups of #datasaveslives users in academia, health services and policy, and charities and patient networks. Thematic analysis of tweets showed that #datasaveslives was used for a broader range of purposes than indexing information, including event reporting, encouraging participation and action, and showing personal support for data sharing.

Conclusions

This study shows that a hashtag-based social media campaign was effective in encouraging a wide audience of stakeholders to disseminate positive examples of health research. Furthermore, the findings suggest that the campaign supported community building and bridging practices within and between the interdisciplinary sectors related to the field of health data science and encouraged individuals to demonstrate personal support for sharing health data.",,pdf:https://www.jmir.org/2021/2/e16348/PDF; doi:https://doi.org/10.2196/16348; html:https://europepmc.org/articles/PMC7925154 -37984978,https://doi.org/10.1136/bmj-2023-076754,ROB-ME: a tool for assessing risk of bias due to missing evidence in systematic reviews with meta-analysis.,"Page MJ, Sterne JAC, Boutron I, Hróbjartsson A, Kirkham JJ, Li T, Lundh A, Mayo-Wilson E, McKenzie JE, Stewart LA, Sutton AJ, Bero L, Dunn AG, Dwan K, Elbers RG, Kanukula R, Meerpohl JJ, Turner EH, Higgins JPT.",,BMJ (Clinical research ed.),2023,2023-11-20,N,,,,,,doi:https://doi.org/10.1136/bmj-2023-076754 +37705296,https://doi.org/10.1002/sim.9898,Using temporal recalibration to improve the calibration of risk prediction models in competing risk settings when there are trends in survival over time.,"Booth S, Mozumder SI, Archer L, Ensor J, Riley RD, Lambert PC, Rutherford MJ.",,Statistics in medicine,2023,2023-09-13,Y,calibration; Risk Prediction; Competing Risks; Temporal Recalibration; Prognostic Models,,,"We have previously proposed temporal recalibration to account for trends in survival over time to improve the calibration of predictions from prognostic models for new patients. This involves first estimating the predictor effects using data from all individuals (full dataset) and then re-estimating the baseline using a subset of the most recent data whilst constraining the predictor effects to remain the same. In this article, we demonstrate how temporal recalibration can be applied in competing risk settings by recalibrating each cause-specific (or subdistribution) hazard model separately. We illustrate this using an example of colon cancer survival with data from the Surveillance Epidemiology and End Results (SEER) program. Data from patients diagnosed in 1995-2004 were used to fit two models for deaths due to colon cancer and other causes respectively. We discuss considerations that need to be made in order to apply temporal recalibration such as the choice of data used in the recalibration step. We also demonstrate how to assess the calibration of these models in new data for patients diagnosed subsequently in 2005. Comparison was made to a standard analysis (when improvements over time are not taken into account) and a period analysis which is similar to temporal recalibration but differs in the data used to estimate the predictor effects. The 10-year calibration plots demonstrated that using the standard approach over-estimated the risk of death due to colon cancer and the total risk of death and that calibration was improved using temporal recalibration or period analysis.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/sim.9898; doi:https://doi.org/10.1002/sim.9898; html:https://europepmc.org/articles/PMC10946485; pdf:https://europepmc.org/articles/PMC10946485?pdf=render 32846977,https://doi.org/10.3390/ijerph17176139,Agreement between the International Physical Activity Questionnaire and Accelerometry in Adults with Orthopaedic Injury.,"Veitch WG, Climie RE, Gabbe BJ, Dunstan DW, Owen N, Ekegren CL.",,International journal of environmental research and public health,2020,2020-08-24,Y,Activity; Validation; Sitting; Accelerometer; Sedentary Behaviour; Ipaq,,,"Orthopaedic injury can lead to decreased physical activity. Valid measures for assessing physical activity are therefore needed in this population. The aim of this study was to determine the agreement and concordance between the International Physical Activity Questionnaire-Short Form (IPAQ) and device-measured physical activity and sitting time in orthopaedic injury patients. Adults with isolated upper or lower limb fracture (n = 46; mean age of 40.5 years) wore two activity monitors (ActiGraph wGT3X-BT and activPAL) for 10 days, from 2 weeks post-discharge. The IPAQ was also completed for a concurrent 7-day period. Lin's concordance correlation coefficients and Bland-Altman plots were calculated to compare walking/stepping time, total METmins, and sitting time. The IPAQ overestimated device-derived walking time (mean difference = 2.34 ± 7.33 h/week) and total METmins (mean difference = 767 ± 1659 METmins/week) and underestimated sitting time (mean difference = -2.26 ± 3.87 h/day). There was fair concordance between IPAQ-reported and device-measured walking (ρ = 0.34) and sitting time (ρ = 0.38) and moderate concordance between IPAQ-reported and device-measured METmins (ρ = 0.43). In patients with orthopaedic injury, the IPAQ overestimates physical activity and underestimates sitting time. Higher agreement was observed in the forms of activity (walking, total PA and sitting) commonly performed by this patient group.",,pdf:https://www.mdpi.com/1660-4601/17/17/6139/pdf?version=1598511551; doi:https://doi.org/10.3390/ijerph17176139; html:https://europepmc.org/articles/PMC7504024; pdf:https://europepmc.org/articles/PMC7504024?pdf=render +37984978,https://doi.org/10.1136/bmj-2023-076754,ROB-ME: a tool for assessing risk of bias due to missing evidence in systematic reviews with meta-analysis.,"Page MJ, Sterne JAC, Boutron I, Hróbjartsson A, Kirkham JJ, Li T, Lundh A, Mayo-Wilson E, McKenzie JE, Stewart LA, Sutton AJ, Bero L, Dunn AG, Dwan K, Elbers RG, Kanukula R, Meerpohl JJ, Turner EH, Higgins JPT.",,BMJ (Clinical research ed.),2023,2023-11-20,N,,,,,,doi:https://doi.org/10.1136/bmj-2023-076754 37994361,https://doi.org/10.12688/gatesopenres.13654.1,"Higher mortality associated with the SARS-CoV-2 Delta variant in the Western Cape, South Africa, using RdRp target delay as a proxy: a cross-sectional study.","Hussey H, Davies MA, Heekes A, Williamson C, Valley-Omar Z, Hardie D, Korsman S, Doolabh D, Preiser W, Maponga T, Iranzadeh A, Engelbrecht S, Wasserman S, Schrueder N, Boloko L, Symons G, Raubenheimer P, Viljoen A, Parker A, Cohen C, Jasat W, Lessells R, Wilkinson RJ, Boulle A, Hsiao M.",,Gates open research,2022,2022-08-31,Y,DELTA; South Africa; Clinical Severity; Sars-cov-2; B.1.617.2; Rdrp Target Delay,,,"Background: The SARS-CoV-2 Delta variant (B.1.617.2) has been associated with more severe disease, particularly when compared to the Alpha variant. Most of this data, however, is from high income countries and less is understood about the variant's disease severity in other settings, particularly in an African context, and when compared to the Beta variant. Methods: A novel proxy marker, RNA-dependent RNA polymerase (RdRp) target delay in the Seegene Allplex TM 2019-nCoV (polymerase chain reaction) PCR assay, was used to identify suspected Delta variant infection in routine laboratory data. All cases diagnosed on this assay in the public sector in the Western Cape, South Africa, from 1 April to 31 July 2021, were included in the dataset provided by the Western Cape Provincial Health Data Centre (PHDC). The PHDC collates information on all COVID-19 related laboratory tests, hospital admissions and deaths for the province. Odds ratios for the association between the proxy marker and death were calculated, adjusted for prior diagnosed infection and vaccination status. Results: A total of 11,355 cases with 700 deaths were included in this study. RdRp target delay (suspected Delta variant) was associated with higher mortality (adjusted odds ratio [aOR] 1.45; 95% confidence interval [CI]: 1.13-1.86), compared to presumptive Beta infection. Prior diagnosed infection during the previous COVID-19 wave, which was driven by the Beta variant, was protective (aOR 0.32; 95%CI: 0.11-0.92) as was vaccination (aOR [95%CI] 0.15 [0.03-0.62] for complete vaccination [≥28 days post a single dose of Ad26.COV2.S or ≥14 days post second BNT162b2 dose]). Conclusion: RdRp target delay, a proxy for infection with the Delta variant, is associated with an increased risk of mortality amongst those who were tested for COVID-19 in our setting.",,doi:https://doi.org/10.12688/gatesopenres.13654.1; html:https://europepmc.org/articles/PMC10663174; pdf:https://europepmc.org/articles/PMC10663174?pdf=render 36253349,https://doi.org/10.1038/s41467-022-33675-1,Systematic Mendelian randomization using the human plasma proteome to discover potential therapeutic targets for stroke.,"Chen L, Peters JE, Prins B, Persyn E, Traylor M, Surendran P, Karthikeyan S, Yonova-Doing E, Di Angelantonio E, Roberts DJ, Watkins NA, Ouwehand WH, Danesh J, Lewis CM, Bronson PG, Markus HS, Burgess S, Butterworth AS, Howson JMM.",,Nature communications,2022,2022-10-17,Y,,,,"Stroke is the second leading cause of death with substantial unmet therapeutic needs. To identify potential stroke therapeutic targets, we estimate the causal effects of 308 plasma proteins on stroke outcomes in a two-sample Mendelian randomization framework and assess mediation effects by stroke risk factors. We find associations between genetically predicted plasma levels of six proteins and stroke (P ≤ 1.62 × 10-4). The genetic associations with stroke colocalize (Posterior Probability >0.7) with the genetic associations of four proteins (TFPI, TMPRSS5, CD6, CD40). Mendelian randomization supports atrial fibrillation, body mass index, smoking, blood pressure, white matter hyperintensities and type 2 diabetes as stroke risk factors (P ≤ 0.0071). Body mass index, white matter hyperintensity and atrial fibrillation appear to mediate the TFPI, IL6RA, TMPRSS5 associations with stroke. Furthermore, thirty-six proteins are associated with one or more of these risk factors using Mendelian randomization. Our results highlight causal pathways and potential therapeutic targets for stroke.",,pdf:https://www.nature.com/articles/s41467-022-33675-1.pdf; doi:https://doi.org/10.1038/s41467-022-33675-1; html:https://europepmc.org/articles/PMC9576777; pdf:https://europepmc.org/articles/PMC9576777?pdf=render 36828655,https://doi.org/10.1136/bmjopen-2022-068718,Maternal and child outcomes for pregnant women with pre-existing multiple long-term conditions: protocol for an observational study in the UK.,"Lee SI, Hope H, O'Reilly D, Kent L, Santorelli G, Subramanian A, Moss N, Azcoaga-Lorenzo A, Fagbamigbe AF, Nelson-Piercy C, Yau C, McCowan C, Kennedy JI, Phillips K, Singh M, Mhereeg M, Cockburn N, Brocklehurst P, Plachcinski R, Riley RD, Thangaratinam S, Brophy S, Hemali Sudasinghe SPB, Agrawal U, Vowles Z, Abel KM, Nirantharakumar K, Black M, Eastwood KA, MuM-PreDiCT.",,BMJ open,2023,2023-02-24,Y,Obstetrics; epidemiology; Maternal Medicine,,,"

Introduction

One in five pregnant women has multiple pre-existing long-term conditions in the UK. Studies have shown that maternal multiple long-term conditions are associated with adverse outcomes. This observational study aims to compare maternal and child outcomes for pregnant women with multiple long-term conditions to those without multiple long-term conditions (0 or 1 long-term conditions).

Methods and analysis

Pregnant women aged 15-49 years old with a conception date between 2000 and 2019 in the UK will be included with follow-up till 2019. The data source will be routine health records from all four UK nations (Clinical Practice Research Datalink (England), Secure Anonymised Information Linkage (Wales), Scotland routine health records and Northern Ireland Maternity System) and the Born in Bradford birth cohort. The exposure of two or more pre-existing, long-term physical or mental health conditions will be defined from a list of health conditions predetermined by women and clinicians. The association of maternal multiple long-term conditions with (a) antenatal, (b) peripartum, (c) postnatal and long-term and (d) mental health outcomes, for both women and their children will be examined. Outcomes of interest will be guided by a core outcome set. Comparisons will be made between pregnant women with and without multiple long-term conditions using modified Poisson and Cox regression. Generalised estimating equation will account for the clustering effect of women who had more than one pregnancy episode. Where appropriate, multiple imputation with chained equation will be used for missing data. Federated analysis will be conducted for each dataset and results will be pooled using random-effects meta-analyses.

Ethics and dissemination

Approval has been obtained from the respective data sources in each UK nation. Study findings will be submitted for publications in peer-reviewed journals and presented at key conferences.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/2/e068718.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-068718; html:https://europepmc.org/articles/PMC9972454; pdf:https://europepmc.org/articles/PMC9972454?pdf=render @@ -1630,31 +1630,31 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 33788869,https://doi.org/10.1371/journal.pone.0249258,Using graphic modelling to identify modifiable mediators of the association between area-based deprivation at birth and offspring unemployment.,"Bogie J, Fleming M, Cullen B, Mackay D, Pell JP.",,PloS one,2021,2021-03-31,Y,,,,"

Background

Deprivation can perpetuate across generations; however, the causative pathways are not well understood. Directed acyclic graphs (DAG) with mediation analysis can help elucidate and quantify complex pathways in order to identify modifiable factors at which to target interventions.

Methods and findings

We linked ten Scotland-wide databases (six health and four education) to produce a cohort of 217,226 pupils who attended Scottish schools between 2009 and 2013. The DAG comprised 23 potential mediators of the association between area deprivation at birth and subsequent offspring 'not in education, employment or training' status, covering maternal, antenatal, perinatal and child health, school engagement, and educational factors. Analyses were performed using modified g-computation. Deprivation at birth was associated with a 7.3% increase in offspring 'not in education, employment or training'. The principal mediators of this association were smoking during pregnancy (natural indirect effect of 0·016, 95% CI 0·013, 0·019) and school absences (natural indirect effect of 0·021, 95% CI 0·018, 0·024), explaining 22% and 30% of the total effect respectively. The proportion of the association potentially eliminated by addressing these factors was 19% (controlled direct effect when set to non-smoker 0·058; 95% CI 0·053, 0·063) for smoking during pregnancy and 38% (controlled direct effect when set to no absences 0·043; 95% CI 0·037, 0·049) for school absences.

Conclusions

Combining a DAG with mediation analysis helped disentangle a complex public health problem and quantified the modifiable factors of maternal smoking and school absence that could be targeted for intervention. This study also demonstrates the general utility of DAGs in understanding complex public health problems.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0249258&type=printable; doi:https://doi.org/10.1371/journal.pone.0249258; html:https://europepmc.org/articles/PMC8011734; pdf:https://europepmc.org/articles/PMC8011734?pdf=render 36066609,https://doi.org/10.1007/s00392-022-02088-x,Towards automatic classification of cardiovascular magnetic resonance Task Force Criteria for diagnosis of arrhythmogenic right ventricular cardiomyopathy.,"Bourfiss M, Sander J, de Vos BD, Te Riele ASJM, Asselbergs FW, Išgum I, Velthuis BK.",,Clinical research in cardiology : official journal of the German Cardiac Society,2023,2022-09-06,Y,Cardiac Magnetic Resonance Imaging; Arrhythmogenic Right Ventricular Cardiomyopathy; Automatic Segmentation; Deep Learning,,,"

Background

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is diagnosed according to the Task Force Criteria (TFC) in which cardiovascular magnetic resonance (CMR) imaging plays an important role. Our study aims to apply an automatic deep learning-based segmentation for right and left ventricular CMR assessment and evaluate this approach for classification of the CMR TFC.

Methods

We included 227 subjects suspected of ARVC who underwent CMR. Subjects were classified into (1) ARVC patients fulfilling TFC; (2) at-risk family members; and (3) controls. To perform automatic segmentation, a Bayesian Dilated Residual Neural Network was trained and tested. Performance of automatic versus manual segmentation was assessed using Dice-coefficient and Hausdorff distance. Since automatic segmentation is most challenging in basal slices, manual correction of the automatic segmentation in the most basal slice was simulated (automatic-basal). CMR TFC calculated using manual and automatic-basal segmentation were compared using Cohen's Kappa (κ).

Results

Automatic segmentation was trained on CMRs of 70 subjects (39.6 ± 18.1 years, 47% female) and tested on 157 subjects (36.9 ± 17.6 years, 59% female). Dice-coefficient and Hausdorff distance showed good agreement between manual and automatic segmentations (≥ 0.89 and ≤ 10.6 mm, respectively) which further improved after simulated correction of the most basal slice (≥ 0.92 and ≤ 9.2 mm, p < 0.001). Pearson correlation of volumetric and functional CMR measurements was good to excellent (automatic (r = 0.78-0.99, p < 0.001) and automatic-basal (r = 0.88-0.99, p < 0.001) measurements). CMR TFC classification using automatic-basal segmentations was comparable to manual segmentations (κ 0.98 ± 0.02) with comparable diagnostic performance.

Conclusions

Combining automatic segmentation of CMRs with correction of the most basal slice results in accurate CMR TFC classification of subjects suspected of ARVC.",,pdf:https://link.springer.com/content/pdf/10.1007/s00392-022-02088-x.pdf; doi:https://doi.org/10.1007/s00392-022-02088-x; html:https://europepmc.org/articles/PMC9998324; pdf:https://europepmc.org/articles/PMC9998324?pdf=render 35241573,https://doi.org/10.1136/bmjqs-2020-012108,Comparing antibiotic prescribing between clinicians in UK primary care: an analysis in a cohort study of eight different measures of antibiotic prescribing.,"Van Staa T, Li Y, Gold N, Chadborn T, Welfare W, Palin V, Ashcroft DM, Bircher J.",,BMJ quality & safety,2022,2022-10-19,Y,General Practice; Antibiotic Management; Healthcare Quality Improvement,,,"

Background

There is a need to reduce antimicrobial uses in humans. Previous studies have found variations in antibiotic (AB) prescribing between practices in primary care. This study assessed variability of AB prescribing between clinicians.

Methods

Clinical Practice Research Datalink, which collects electronic health records in primary care, was used to select anonymised clinicians providing 500+ consultations during 2012-2017. Eight measures of AB prescribing were assessed, such as overall and incidental AB prescribing, repeat AB courses and extent of risk-based prescribing. Poisson regression models with random effect for clinicians were fitted.

Results

6111 clinicians from 466 general practices were included. Considerable variability between individual clinicians was found for most AB measures. For example, the rate of AB prescribing varied between 77.4 and 350.3 per 1000 consultations; percentage of repeat AB courses within 30 days ranged from 13.1% to 34.3%; predicted patient risk of hospital admission for infection-related complications in those prescribed AB ranged from 0.03% to 0.32% (5th and 95th percentiles). The adjusted relative rate between clinicians in rates of AB prescribing was 5.23. Weak correlation coefficients (<0.5) were found between most AB measures. There was considerable variability in case mix seen by clinicians. The largest potential impact to reduce AB prescribing could be around encouraging risk-based prescribing and addressing repeat issues of ABs. Reduction of repeat AB courses to prescribing habit of median clinician would save 21 813 AB prescriptions per 1000 clinicians per year.

Conclusions

The wide variation seen in all measures of AB prescribing and weak correlation between them suggests that a single AB measure, such as prescribing rate, is not sufficient to underpin the optimisation of AB prescribing.",,pdf:https://qualitysafety.bmj.com/content/qhc/early/2022/03/02/bmjqs-2020-012108.full.pdf; doi:https://doi.org/10.1136/bmjqs-2020-012108; html:https://europepmc.org/articles/PMC9606525; pdf:https://europepmc.org/articles/PMC9606525?pdf=render -37647652,https://doi.org/10.1182/blood.2023021100,A signature of platelet reactivity in CBC scattergrams reveals genetic predictors of thrombotic disease risk.,"Verdier H, Thomas P, Batista J, Kempster C, McKinney H, Gleadall N, Danesh J, Mumford A, Heemskerk JWM, Ouwehand WH, Downes K, Astle WJ, Turro E.",,Blood,2023,2023-11-01,Y,,,,"Genetic studies of platelet reactivity (PR) phenotypes may identify novel antiplatelet drug targets. However, such studies have been limited by small sample sizes (n < 5000) because of the complexity of measuring PR. We trained a model to predict PR from complete blood count (CBC) scattergrams. A genome-wide association study of this phenotype in 29 806 blood donors identified 21 distinct associations implicating 20 genes, of which 6 have been identified previously. The effect size estimates were significantly correlated with estimates from a study of flow cytometry-measured PR and a study of a phenotype of in vitro thrombus formation. A genetic score of PR built from the 21 variants was associated with the incidence rates of myocardial infarction and pulmonary embolism. Mendelian randomization analyses showed that PR was causally associated with the risks of coronary artery disease, stroke, and venous thromboembolism. Our approach provides a blueprint for using phenotype imputation to study the determinants of hard-to-measure but biologically important hematological traits.",,pdf:https://ashpublications.org/blood/article-pdf/doi/10.1182/blood.2023021100/2076169/blood.2023021100.pdf; doi:https://doi.org/10.1182/blood.2023021100; html:https://europepmc.org/articles/PMC10733829 33836256,https://doi.org/10.1016/j.jclinepi.2021.03.025,Internal-external cross-validation helped to evaluate the generalizability of prediction models in large clustered datasets.,"Takada T, Nijman S, Denaxas S, Snell KIE, Uijl A, Nguyen TL, Asselbergs FW, Debray TPA.",,Journal of clinical epidemiology,2021,2021-04-06,N,Heterogeneity; Discrimination; Validation; Prediction model; calibration; Model Comparison,,,"

Objective

To illustrate how to evaluate the need of complex strategies for developing generalizable prediction models in large clustered datasets.

Study design and setting

We developed eight Cox regression models to estimate the risk of heart failure using a large population-level dataset. These models differed in the number of predictors, the functional form of the predictor effects (non-linear effects and interaction) and the estimation method (maximum likelihood and penalization). Internal-external cross-validation was used to evaluate the models' generalizability across the included general practices.

Results

Among 871,687 individuals from 225 general practices, 43,987 (5.5%) developed heart failure during a median follow-up time of 5.8 years. For discrimination, the simplest prediction model yielded a good concordance statistic, which was not much improved by adopting complex strategies. Between-practice heterogeneity in discrimination was similar in all models. For calibration, the simplest model performed satisfactorily. Although accounting for non-linear effects and interaction slightly improved the calibration slope, it also led to more heterogeneity in the observed/expected ratio. Similar results were found in a second case study involving patients with stroke.

Conclusion

In large clustered datasets, prediction model studies may adopt internal-external cross-validation to evaluate the generalizability of competing models, and to identify promising modelling strategies.",,pdf:http://www.jclinepi.com/article/S0895435621001074/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.03.025 +37647652,https://doi.org/10.1182/blood.2023021100,A signature of platelet reactivity in CBC scattergrams reveals genetic predictors of thrombotic disease risk.,"Verdier H, Thomas P, Batista J, Kempster C, McKinney H, Gleadall N, Danesh J, Mumford A, Heemskerk JWM, Ouwehand WH, Downes K, Astle WJ, Turro E.",,Blood,2023,2023-11-01,Y,,,,"Genetic studies of platelet reactivity (PR) phenotypes may identify novel antiplatelet drug targets. However, such studies have been limited by small sample sizes (n < 5000) because of the complexity of measuring PR. We trained a model to predict PR from complete blood count (CBC) scattergrams. A genome-wide association study of this phenotype in 29 806 blood donors identified 21 distinct associations implicating 20 genes, of which 6 have been identified previously. The effect size estimates were significantly correlated with estimates from a study of flow cytometry-measured PR and a study of a phenotype of in vitro thrombus formation. A genetic score of PR built from the 21 variants was associated with the incidence rates of myocardial infarction and pulmonary embolism. Mendelian randomization analyses showed that PR was causally associated with the risks of coronary artery disease, stroke, and venous thromboembolism. Our approach provides a blueprint for using phenotype imputation to study the determinants of hard-to-measure but biologically important hematological traits.",,pdf:https://ashpublications.org/blood/article-pdf/doi/10.1182/blood.2023021100/2076169/blood.2023021100.pdf; doi:https://doi.org/10.1182/blood.2023021100; html:https://europepmc.org/articles/PMC10733829 34957541,https://doi.org/10.1111/bjh.18013,A novel algorithmic approach to generate consensus treatment guidelines in adult acute myeloid leukaemia.,"Coats T, Bean D, Basset A, Sirkis T, Brammeld J, Johnson S, Thomas I, Gilkes A, Raj K, Dennis M, Knapper S, Mehta P, Khwaja A, Hunter H, Tauro S, Bowen D, Jones G, Dobson R, Russell N, Dillon R.",,British journal of haematology,2022,2021-12-26,N,Myeloid Leukaemia; Classifications; Diagnostic Haematology; Clinical Haematology,,,"Induction therapy for acute myeloid leukaemia (AML) has changed with the approval of a number of new agents. Clinical guidelines can struggle to keep pace with an evolving treatment and evidence landscape and therefore identifying the most appropriate front-line treatment is challenging for clinicians. Here, we combined drug eligibility criteria and genetic risk stratification into a digital format, allowing the full range of possible treatment eligibility scenarios to be defined. Using exemplar cases representing each of the 22 identified scenarios, we sought to generate consensus on treatment choice from a panel of nine aUK AML experts. We then analysed >2500 real-world cases using the same algorithm, confirming the existence of 21/22 of these scenarios and demonstrating that our novel approach could generate a consensus AML induction treatment in 98% of cases. Our approach, driven by the use of decision trees, is an efficient way to develop consensus guidance rapidly and could be applied to other disease areas. It has the potential to be updated frequently to capture changes in eligibility criteria, novel therapies and emerging trial data. An interactive digital version of the consensus guideline is available.",,pdf:https://discovery.dundee.ac.uk/files/71382229/Br_J_Haematol_2022_Coats_A_novel_algorithmic_approach_to_generate_consensus_treatment_guidelines_in_adult_acute.pdf; doi:https://doi.org/10.1111/bjh.18013 36029662,https://doi.org/10.1016/j.bios.2022.114623,Triazole-derivatized near-infrared cyanine dyes enable local functional fluorescent imaging of ocular inflammation.,"Thomas CN, Alfahad N, Capewell N, Cowley J, Hickman E, Fernandez A, Harrison N, Qureshi OS, Bennett N, Barnes NM, Dick AD, Chu CJ, Liu X, Denniston AK, Vendrell M, Hill LJ.",,Biosensors & bioelectronics,2022,2022-08-13,N,Leukocytes; Uveitis; Cyanine; Near-infrared; optical coherence tomography; Fluorophores,,,"Near-infrared (NIR) chemical fluorophores are promising tools for in-vivo imaging in real time but often succumb to rapid photodegradation. Indocyanine green (ICG) is the only NIR dye with regulatory approval for ocular imaging in humans; however, ICG, when employed for applications such as labelling immune cells, has limited sensitivity and does not allow precise detection of specific inflammatory events, for example leukocyte recruitment during uveitic flare-ups. We investigated the potential use of photostable novel triazole NIR cyanine (TNC) dyes for detecting and characterising activated T-cell activity within the eye. Three TNC dyes were evaluated for ocular cytotoxicity in-vitro using a MTT assay and optimised concentrations for intraocular detection within ex-vivo porcine eyes after topical application or intracameral injections of the dyes. TNC labelled T-cell tracking experiments and mechanistic studies were also performed in-vitro. TNC-1 and TNC-2 dyes exhibited greater fluorescence intensity than ICG at 10 μM, whereas TNC-3 was only detectable at 100 μM within the porcine eye. TNC dyes did not demonstrate any ocular cell toxicity at working concentrations of 10 μM. CD4+T-cells labelled with TNC-1 or TNC-2 were detected within the porcine eye, with TNC-1 being brighter than TNC-2. Detection of TNC-1 and TNC-2 into CD4+T-cells was prevented by prior incubation with dynole 34-2 (50 μM), suggesting active uptake of these dyes via dynamin-dependent processes. The present study provides evidence that TNC dyes are suitable to detect activated CD4+T-cells within the eye with potential as a diagnostic marker for ocular inflammatory diseases.",,pdf:https://research-information.bris.ac.uk/files/338519213/1_s2.0_S0956566322006637_main.pdf; doi:https://doi.org/10.1016/j.bios.2022.114623 33692568,https://doi.org/10.1038/s41588-021-00783-5,The Polygenic Score Catalog as an open database for reproducibility and systematic evaluation.,"Lambert SA, Gil L, Jupp S, Ritchie SC, Xu Y, Buniello A, McMahon A, Abraham G, Chapman M, Parkinson H, Danesh J, MacArthur JAL, Inouye M.",,Nature genetics,2021,2021-04-01,N,,,,,,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/05/23/2020.05.20.20108217.full.pdf; doi:https://doi.org/10.1038/s41588-021-00783-5 32743489,https://doi.org/10.1016/j.eclinm.2020.100469,Gender differences in the presentation of fibromyalgia amongst children who have been maltreated.,"Chandan JS, Bandyopadhyay S, Taylor J, Nirantharakumar K.",,EClinicalMedicine,2020,2020-07-23,Y,,,,,,pdf:http://www.thelancet.com/article/S2589537020302133/pdf; doi:https://doi.org/10.1016/j.eclinm.2020.100469; html:https://europepmc.org/articles/PMC7385442; pdf:https://europepmc.org/articles/PMC7385442?pdf=render 37206266,https://doi.org/10.1002/jha2.698,Biallelic deleterious germline SH2B3 variants cause a novel syndrome of myeloproliferation and multi-organ autoimmunity.,"Blombery P, Pazhakh V, Albuquerque AS, Maimaris J, Tu L, Briones Miranda B, Evans F, Thompson ER, Carpenter B, Proctor I, Curtin JA, Lambert J, Burns SO, Lieschke GJ.",,EJHaem,2023,2023-04-30,Y,Genetics; Molecular diagnosis; Myeloid Function And Development,,,"SH2B3 is a negative regulator of multiple cytokine receptor signalling pathways in haematopoietic tissue. To date, a single kindred has been described with germline biallelic loss-of-function SH2B3 variants characterized by early onset developmental delay, hepatosplenomegaly and autoimmune thyroiditis/hepatitis. Herein, we described two further unrelated kindreds with germline biallelic loss-of-function SH2B3 variants that show striking phenotypic similarity to each other as well as to the previous kindred of myeloproliferation and multi-organ autoimmunity. One proband also suffered severe thrombotic complications. CRISPR-Cas9 gene editing of zebrafish sh2b3 created assorted deleterious variants in F0 crispants, which manifest significantly increased number of macrophages and thrombocytes, partially replicating the human phenotype. Treatment of the sh2b3 crispant fish with ruxolitinib intercepted this myeloproliferative phenotype. Skin-derived fibroblasts from one patient demonstrated increased phosphorylation of JAK2 and STAT5 after stimulation with IL-3, GH, GM-CSF and EPO compared to healthy controls. In conclusion, these additional probands and functional data in combination with the previous kindred provide sufficient evidence for biallelic homozygous deleterious variants in SH2B3 to be considered a valid gene-disease association for a clinical syndrome of bone marrow myeloproliferation and multi-organ autoimmune manifestations.",,doi:https://doi.org/10.1002/jha2.698; doi:https://doi.org/10.1002/jha2.698; html:https://europepmc.org/articles/PMC10188477; pdf:https://europepmc.org/articles/PMC10188477?pdf=render 35152298,https://doi.org/10.1093/ehjci/jeac030,Prognostic value of strain by feature-tracking cardiac magnetic resonance in arrhythmogenic right ventricular cardiomyopathy.,"Bourfiss M, Prakken NHJ, James CA, Planken RN, Boekholdt SM, Ahmetagic D, van den Berg MP, Tichnell C, Van der Heijden JF, Loh P, Murray B, Tandri H, Kamel I, Calkins H, Asselbergs FW, Zimmerman SL, Velthuis BK, Te Riele ASJM.",,European heart journal. Cardiovascular Imaging,2022,2022-12-01,Y,Strain; Arrhythmias; Cardiac Magnetic Resonance Imaging; Arrhythmogenic Right Ventricular Cardiomyopathy; Feature Tracking,,,"

Aims

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by ventricular dysfunction and ventricular arrhythmias (VA). Adequate arrhythmic risk assessment is important to prevent sudden cardiac death. We aimed to study the incremental value of strain by feature-tracking cardiac magnetic resonance imaging (FT-CMR) in predicting sustained VA in ARVC patients.

Methods and results

CMR images of 132 ARVC patients (43% male, 40.6 ± 16.0 years) without prior VA were analysed for global and regional right and left ventricular (RV, LV) strain. Primary outcome was sustained VA during follow-up. We performed multivariable regression assessing strain, in combination with (i) RV ejection fraction (EF); (ii) LVEF; and (iii) the ARVC risk calculator. False discovery rate adjusted P-values were given to correct for multiple comparisons and c-statistics were calculated for each model. During 4.3 (2.0-7.9) years of follow-up, 19% of patients experienced sustained VA. Compared to patients without VA, those with VA had significantly reduced RV longitudinal (P ≤ 0.03) and LV circumferential (P ≤ 0.04) strain. In addition, patients with VA had significantly reduced biventricular EF (P ≤ 0.02). After correcting for RVEF, LVEF, and the ARVC risk calculator separately in multivariable analysis, both RV and LV strain lost their significance [hazard ratio 1.03-1.18, P > 0.05]. Likewise, while strain improved the c-statistic in combination with RVEF, LVEF, and the ARVC risk calculator separately, this did not reach statistical significance (P ≥ 0.18).

Conclusion

Both RV longitudinal and LV circumferential strain are reduced in ARVC patients with sustained VA during follow-up. However, strain does not have incremental value over RVEF, LVEF, and the ARVC VA risk calculator.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeac030/42506545/jeac030.pdf; doi:https://doi.org/10.1093/ehjci/jeac030; html:https://europepmc.org/articles/PMC9762936; pdf:https://europepmc.org/articles/PMC9762936?pdf=render -36462729,https://doi.org/10.1016/j.neuroimage.2022.119779,Amplitudes of resting-state functional networks - investigation into their correlates and biophysical properties.,"Lee S, Bijsterbosch JD, Almagro FA, Elliott L, McCarthy P, Taschler B, Sala-Llonch R, Beckmann CF, Duff EP, Smith SM, Douaud G.",,NeuroImage,2023,2022-12-01,Y,Dual regression; Gwas; Resting-state Fmri; Uk Biobank; Temporal Synchrony; Network Amplitude,,,"Resting-state fMRI studies have shown that multiple functional networks, which consist of distributed brain regions that share synchronised spontaneous activity, co-exist in the brain. As these resting-state networks (RSNs) have been thought to reflect the brain's intrinsic functional organization, intersubject variability in the networks' spontaneous fluctuations may be associated with individuals' clinical, physiological, cognitive, and genetic traits. Here, we investigated resting-state fMRI data along with extensive clinical, lifestyle, and genetic data collected from 37,842 UK Biobank participants, with the object of elucidating intersubject variability in the fluctuation amplitudes of RSNs. Functional properties of the RSN amplitudes were first examined by analyzing correlations with the well-established between-network functional connectivity. It was found that a network amplitude is highly correlated with the mean strength of the functional connectivity that the network has with the other networks. Intersubject clustering analysis showed the amplitudes are most strongly correlated with age, cardiovascular factors, body composition, blood cell counts, lung function, and sex, with some differences in the correlation strengths between sensory and cognitive RSNs. Genome-wide association studies (GWASs) of RSN amplitudes identified several significant genetic variants reported in previous GWASs for their implications in sleep duration. We provide insight into key factors determining RSN amplitudes and demonstrate that intersubject variability of the amplitudes primarily originates from differences in temporal synchrony between functionally linked brain regions, rather than differences in the magnitude of raw voxelwise BOLD signal changes. This finding additionally revealed intriguing differences between sensory and cognitive RSNs with respect to sex effects on temporal synchrony and provided evidence suggesting that synchronous coactivations of functionally linked brain regions, and magnitudes of BOLD signal changes, may be related to different genetic mechanisms. These results underscore that intersubject variability of the amplitudes in health and disease need to be interpreted largely as a measure of the sum of within-network temporal synchrony and amplitudes of BOLD signals, with a dominant contribution from the former.",,doi:https://doi.org/10.1016/j.neuroimage.2022.119779; doi:https://doi.org/10.1016/j.neuroimage.2022.119779; html:https://europepmc.org/articles/PMC10933815; pdf:https://europepmc.org/articles/PMC10933815?pdf=render 33782427,https://doi.org/10.1038/s41598-021-86266-3,Analysis of temporal trends in potential COVID-19 cases reported through NHS Pathways England.,"Leclerc QJ, Nightingale ES, Abbott S, CMMID COVID-19 Working Group, Jombart T.",,Scientific reports,2021,2021-03-29,Y,,,,"The National Health Service (NHS) Pathways triage system collates data on enquiries to 111 and 999 services in England. Since the 18th of March 2020, these data have been made publically available for potential COVID-19 symptoms self-reported by members of the public. Trends in such reports over time are likely to reflect behaviour of the ongoing epidemic within the wider community, potentially capturing valuable information across a broader severity profile of cases than hospital admission data. We present a fully reproducible analysis of temporal trends in NHS Pathways reports until 14th May 2020, nationally and regionally, and demonstrate that rates of growth/decline and effective reproduction number estimated from these data may be useful in monitoring transmission. This is a particularly pressing issue as lockdown restrictions begin to be lifted and evidence of disease resurgence must be constantly reassessed. We further assess the correlation between NHS Pathways reports and a publicly available NHS dataset of COVID-19-associated deaths in England, finding that enquiries to 111/999 were strongly associated with daily deaths reported 16 days later. Our results highlight the potential of NHS Pathways as the basis of an early warning system. However, this dataset relies on self-reported symptoms, which are at risk of being severely biased. Further detailed work is therefore necessary to investigate potential behavioural issues which might otherwise explain our conclusions.",,pdf:https://www.nature.com/articles/s41598-021-86266-3.pdf; doi:https://doi.org/10.1038/s41598-021-86266-3; html:https://europepmc.org/articles/PMC8007605; pdf:https://europepmc.org/articles/PMC8007605?pdf=render 30742608,https://doi.org/10.1371/journal.pcbi.1006785,"Assessing the performance of real-time epidemic forecasts: A case study of Ebola in the Western Area region of Sierra Leone, 2014-15.","Funk S, Camacho A, Kucharski AJ, Lowe R, Eggo RM, Edmunds WJ.",,PLoS computational biology,2019,2019-02-11,Y,,Applied Analytics,,"Real-time forecasts based on mathematical models can inform critical decision-making during infectious disease outbreaks. Yet, epidemic forecasts are rarely evaluated during or after the event, and there is little guidance on the best metrics for assessment. Here, we propose an evaluation approach that disentangles different components of forecasting ability using metrics that separately assess the calibration, sharpness and bias of forecasts. This makes it possible to assess not just how close a forecast was to reality but also how well uncertainty has been quantified. We used this approach to analyse the performance of weekly forecasts we generated in real time for Western Area, Sierra Leone, during the 2013-16 Ebola epidemic in West Africa. We investigated a range of forecast model variants based on the model fits generated at the time with a semi-mechanistic model, and found that good probabilistic calibration was achievable at short time horizons of one or two weeks ahead but model predictions were increasingly unreliable at longer forecasting horizons. This suggests that forecasts may have been of good enough quality to inform decision making based on predictions a few weeks ahead of time but not longer, reflecting the high level of uncertainty in the processes driving the trajectory of the epidemic. Comparing forecasts based on the semi-mechanistic model to simpler null models showed that the best semi-mechanistic model variant performed better than the null models with respect to probabilistic calibration, and that this would have been identified from the earliest stages of the outbreak. As forecasts become a routine part of the toolkit in public health, standards for evaluation of performance will be important for assessing quality and improving credibility of mathematical models, and for elucidating difficulties and trade-offs when aiming to make the most useful and reliable forecasts.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1006785&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1006785; html:https://europepmc.org/articles/PMC6386417; pdf:https://europepmc.org/articles/PMC6386417?pdf=render +36462729,https://doi.org/10.1016/j.neuroimage.2022.119779,Amplitudes of resting-state functional networks - investigation into their correlates and biophysical properties.,"Lee S, Bijsterbosch JD, Almagro FA, Elliott L, McCarthy P, Taschler B, Sala-Llonch R, Beckmann CF, Duff EP, Smith SM, Douaud G.",,NeuroImage,2023,2022-12-01,Y,Dual regression; Gwas; Resting-state Fmri; Uk Biobank; Temporal Synchrony; Network Amplitude,,,"Resting-state fMRI studies have shown that multiple functional networks, which consist of distributed brain regions that share synchronised spontaneous activity, co-exist in the brain. As these resting-state networks (RSNs) have been thought to reflect the brain's intrinsic functional organization, intersubject variability in the networks' spontaneous fluctuations may be associated with individuals' clinical, physiological, cognitive, and genetic traits. Here, we investigated resting-state fMRI data along with extensive clinical, lifestyle, and genetic data collected from 37,842 UK Biobank participants, with the object of elucidating intersubject variability in the fluctuation amplitudes of RSNs. Functional properties of the RSN amplitudes were first examined by analyzing correlations with the well-established between-network functional connectivity. It was found that a network amplitude is highly correlated with the mean strength of the functional connectivity that the network has with the other networks. Intersubject clustering analysis showed the amplitudes are most strongly correlated with age, cardiovascular factors, body composition, blood cell counts, lung function, and sex, with some differences in the correlation strengths between sensory and cognitive RSNs. Genome-wide association studies (GWASs) of RSN amplitudes identified several significant genetic variants reported in previous GWASs for their implications in sleep duration. We provide insight into key factors determining RSN amplitudes and demonstrate that intersubject variability of the amplitudes primarily originates from differences in temporal synchrony between functionally linked brain regions, rather than differences in the magnitude of raw voxelwise BOLD signal changes. This finding additionally revealed intriguing differences between sensory and cognitive RSNs with respect to sex effects on temporal synchrony and provided evidence suggesting that synchronous coactivations of functionally linked brain regions, and magnitudes of BOLD signal changes, may be related to different genetic mechanisms. These results underscore that intersubject variability of the amplitudes in health and disease need to be interpreted largely as a measure of the sum of within-network temporal synchrony and amplitudes of BOLD signals, with a dominant contribution from the former.",,doi:https://doi.org/10.1016/j.neuroimage.2022.119779; doi:https://doi.org/10.1016/j.neuroimage.2022.119779; html:https://europepmc.org/articles/PMC10933815; pdf:https://europepmc.org/articles/PMC10933815?pdf=render 37722858,https://doi.org/10.3399/bjgp.2023.0077,Inequities in hypertension management: observational cross-sectional study in North East London using electronic health records.,"Rison S, Redfern O, Dostal I, Carvalho C, Mathur R, Raisi-Estabragh Z, Robson J.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2023,2023-10-26,Y,Hypertension; Cardiovascular diseases; Blood pressure; General Practice; Antihypertensives; Health Inequities,,,"

Background

Hypertension is a key modifiable risk factor for cardiovascular disease - the leading cause of death in the UK. Good blood pressure (BP) control reduces mortality. However, health inequities may lead to variability in hypertension monitoring and control.

Aim

To investigate health inequities related to ethnicity, sex, age, and socioeconomic status in the monitoring, treatment, and control of BP in a large cohort of adult patients with hypertension.

Design and setting

A cross-sectional cohort study of adults with hypertension registered with general practices in North East London on 1 April 2019.

Method

Multivariable logistic regression was used to estimate associations of demographics and treatment intensity for the following hypertension management indicators: a) BP recording in past 12 months; b) BP on age- adjusted target; and c) BP on age-adjusted target and BP recorded in past 12 months.

Results

In total, 156 296 adults were included. The Black ethnicity group was less likely to have controlled BP than the White ethnicity group (odds ratio [OR] 0.87, 95% [confidence interval] CI = 0.84 to 0.91). The Asian ethnicity group was more likely to have controlled BP (OR 1.28, 95% CI = 1.23 to 1.32). Ethnicity differences in control could not be explained by the likelihood of having a recent BP recording, nor by treatment intensity differences. Older adults (aged ≥50 years) were more likely to have controlled hypertension than younger patients.

Conclusion

Individuals of Black ethnicity and younger people are less likely to have controlled hypertension and may warrant targeted interventions. Possible explanations for these findings are presented but further research is needed about reasons for ethnic differences.",,doi:https://doi.org/10.3399/BJGP.2023.0077; html:https://europepmc.org/articles/PMC10523336; pdf:https://europepmc.org/articles/PMC10523336?pdf=render 32400358,https://doi.org/10.2807/1560-7917.es.2020.25.18.2000632,"Estimating number of cases and spread of coronavirus disease (COVID-19) using critical care admissions, United Kingdom, February to March 2020.","Jit M, Jombart T, Nightingale ES, Endo A, Abbott S, LSHTM Centre for Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Edmunds WJ.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2020,2020-05-01,Y,Surveillance; intensive care unit; mathematical model; Reproduction Number; Sars-cov-2; Coronavirus Disease 2019,,,"An exponential growth model was fitted to critical care admissions from two surveillance databases to determine likely coronavirus disease (COVID-19) case numbers, critical care admissions and epidemic growth in the United Kingdom before the national lockdown. We estimate, on 23 March, a median of 114,000 (95% credible interval (CrI): 78,000-173,000) new cases and 258 (95% CrI: 220-319) new critical care reports, with 527,000 (95% CrI: 362,000-797,000) cumulative cases since 16 February.","The authors of this paper estimate the number of cases and spread of COVID-19 using data on critical care admissions within the UK, from a period of February to March 2020. Their results suggest that the UK had hundreds of thousands of COVID-19 cases by the time the national lockdown was implemented. They highlight the usefulness of surveilling critical care data to better understand the dynamics of the epidemic and better inform the response measures.",pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/18/eurosurv-25-18-2.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.18.2000632&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2020.25.18.2000632; html:https://europepmc.org/articles/PMC7219029; pdf:https://europepmc.org/articles/PMC7219029?pdf=render 36060542,https://doi.org/10.3389/fdgth.2022.939292,Clinical deployment environments: Five pillars of translational machine learning for health.,"Harris S, Bonnici T, Keen T, Lilaonitkul W, White MJ, Swanepoel N.",,Frontiers in digital health,2022,2022-08-19,Y,Safety; Artificial intelligence; Machine Learning; Health Informatics; Translational Medicine; Ml-ops,,,"Machine Learning for Health (ML4H) has demonstrated efficacy in computer imaging and other self-contained digital workflows, but has failed to substantially impact routine clinical care. This is no longer because of poor adoption of Electronic Health Records Systems (EHRS), but because ML4H needs an infrastructure for development, deployment and evaluation within the healthcare institution. In this paper, we propose a design pattern called a Clinical Deployment Environment (CDE). We sketch the five pillars of the CDE: (1) real world development supported by live data where ML4H teams can iteratively build and test at the bedside (2) an ML-Ops platform that brings the rigour and standards of continuous deployment to ML4H (3) design and supervision by those with expertise in AI safety (4) the methods of implementation science that enable the algorithmic insights to influence the behaviour of clinicians and patients and (5) continuous evaluation that uses randomisation to avoid bias but in an agile manner. The CDE is intended to answer the same requirements that bio-medicine articulated in establishing the translational medicine domain. It envisions a transition from ""real-world"" data to ""real-world"" development.",,pdf:https://www.frontiersin.org/articles/10.3389/fdgth.2022.939292/pdf; doi:https://doi.org/10.3389/fdgth.2022.939292; html:https://europepmc.org/articles/PMC9437594; pdf:https://europepmc.org/articles/PMC9437594?pdf=render 34155917,https://doi.org/10.1161/jaha.120.020246,Antenatal Exposure to UV-B Radiation and Preeclampsia: A Retrospective Cohort Study.,"Hastie CE, Mackay DF, Clemens TL, Cherrie MPC, Megaw LJ, Smith GCS, Stock SJ, Dibben C, Pell JP.",,Journal of the American Heart Association,2021,2021-06-22,Y,UV light; Preeclampsia; Seasonal variations; Environmental Exposures,,,"Background Risk of preeclampsia varies by month of delivery. We tested whether this seasonal patterning may be mediated through maternal vitamin D concentration using antenatal exposure to UV-B radiation as an instrumental variable. Methods and Results Scottish maternity records were linked to antenatal UV-B exposure derived from satellites between 2000 and 2010. Logistic regression analyses were used to explore the association between UV-B and preeclampsia, adjusting for the potential confounding effects of month of conception, child's sex, gestation, parity, and mean monthly temperature. Of the 522 896 eligible singleton deliveries, 8689 (1.66%) mothers developed preeclampsia. Total antenatal UV-B exposure ranged from 43.18 to 101.11 kJ/m2 and was associated with reduced risk of preeclampsia with evidence of a dose-response relationship (highest quintile of exposure: adjusted odds ratio, 0.57; 95% CI, 0.44-0.72; P<0.001). Associations were demonstrated for UV-B exposure in all 3 trimesters. Conclusions The seasonal patterning of preeclampsia may be mediated through low maternal vitamin D concentration in winter resulting from low UV-B radiation. Interventional studies are required to determine whether vitamin D supplements or UV-B-emitting light boxes can reduce the seasonal patterning of preeclampsia.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.120.020246; doi:https://doi.org/10.1161/JAHA.120.020246; html:https://europepmc.org/articles/PMC8403301; pdf:https://europepmc.org/articles/PMC8403301?pdf=render 38597854,https://doi.org/10.1016/j.jcmg.2024.03.001,Noninvasive Techniques for Tracking Biological Aging of the Cardiovascular System: JACC Family Series.,"Raisi-Estabragh Z, Szabo L, Schuermans A, Salih AM, Chin CWL, Vágó H, Altmann A, Ng FS, Garg P, Pavanello S, Marwick TH, Petersen SE.",,JACC. Cardiovascular imaging,2024,2024-04-08,N,Molecular markers; Echocardiography; Cardiac Computed Tomography; Healthy Aging; Cardiac Magnetic Resonance; Multimodality Cardiovascular Imaging; Biological Heart Age,,,"Population aging is one of the most important demographic transformations of our time. Increasing the ""health span""-the proportion of life spent in good health-is a global priority. Biological aging comprises molecular and cellular modifications over many years, which culminate in gradual physiological decline across multiple organ systems and predispose to age-related illnesses. Cardiovascular disease is a major cause of ill health and premature death in older people. The rate at which biological aging occurs varies across individuals of the same age and is influenced by a wide range of genetic and environmental exposures. The authors review the hallmarks of biological cardiovascular aging and their capture using imaging and other noninvasive techniques and examine how this information may be used to understand aging trajectories, with the aim of guiding individual- and population-level interventions to promote healthy aging.",,doi:https://doi.org/10.1016/j.jcmg.2024.03.001 33559289,https://doi.org/10.1002/ejp.1750,The association between exposure to domestic abuse in women and the development of syndromes indicating central nervous system sensitization: A retrospective cohort study using UK primary care records.,"Chandan JS, Keerthy D, Gokhale KM, Bradbury-Jones C, Raza K, Bandyopadhyay S, Taylor J, Nirantharakumar K.",,"European journal of pain (London, England)",2021,2021-03-15,N,,,,"

Background

Domestic abuse is a global public health issue. The association between the development of central sensitivity syndromes (CSS) and previous exposure to domestic abuse has been poorly understood particularly within European populations.

Methods

A retrospective cohort study using the 'The Health Improvement Network,' (UK primary care medical records) between 1st January 1995-31st December 2018. 22,604 adult women exposed to domestic abuse were age matched to 44,671 unexposed women. The average age at cohort entry was 36 years and the median follow-up was 2.5 years. The outcomes of interest were the development of a variety of syndromes which demonstrate central nervous system sensitization. Fibromyalgia, chronic fatigue syndrome and temporomandibular joint disorder outcomes have been reported previously. Outcomes were adjusted for the presence of mental ill health.

Results

During the study period, women exposed to domestic abuse experienced an increased risk of developing chronic lower back pain (adjusted incidence rate ratio [aIRR] 2.28; 95% CI 1.85-2.80), chronic headaches (aIRR 3.15; 95% CI 1.07-9.23), irritable bowel syndrome (aIRR 1.41; 95% CI 1.25-1.60) and restless legs syndrome (aIRR 1.89; 95% CI 1.44-2.48). However, no positive association was seen with the development of interstitial cystitis (aIRR 0.52; 95% CI 0.14-1.93), vulvodynia (aIRR 0.42; 95% CI 0.14-1.25) and myofascial pain syndrome (aIRR 1.01; 95% CI 0.28-3.61).

Conclusion

This study demonstrates the need to consider a past history of domestic abuse in patients presenting with CSS; and also consider preventative approaches in mitigating the risk of developing CSS following exposure to domestic abuse.

Significance

Domestic abuse is a global public health issue, with a poorly understood relationship with the development of complex pain syndromes. Using a large UK primary care database, we were able to conduct the first global cohort study to explore this further. We found a strong pain morbidity burden associated with domestic abuse, suggesting the need for urgent public health intervention to not only prevent domestic abuse but also the associated negative pain consequences.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejp.1750; doi:https://doi.org/10.1002/ejp.1750 -37751444,https://doi.org/10.1371/journal.pone.0290583,Long Covid symptoms and diagnosis in primary care: A cohort study using structured and unstructured data in The Health Improvement Network primary care database.,"Shah AD, Subramanian A, Lewis J, Dhalla S, Ford E, Haroon S, Kuan V, Nirantharakumar K.",,PloS one,2023,2023-09-26,Y,,,,"

Background

Long Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes.

Aims

To compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis.

Methods

We used primary care electronic health record data until the end of December 2020 from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and 'Long Covid' diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis.

Results

We compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.46, 95% confidence interval (CI) 2.87, 4.17), shortness of breath (aHR 2.89, 95% CI 2.48, 3.36), palpitations (aHR 2.59, 95% CI 1.86, 3.60), and phlegm (aHR 2.43, 95% CI 1.65, 3.59). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression.

Conclusions

Numerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0290583&type=printable; doi:https://doi.org/10.1371/journal.pone.0290583; html:https://europepmc.org/articles/PMC10521988; pdf:https://europepmc.org/articles/PMC10521988?pdf=render 32570434,https://doi.org/10.3233/shti200210,Using Unsupervised Learning to Identify Clinical Subtypes of Alzheimer's Disease in Electronic Health Records.,"Alexander N, Alexander DC, Barkhof F, Denaxas S.",,Studies in health technology and informatics,2020,2020-06-01,N,Phenotyping; Alzheimer’s disease; Machine Learning; Electronic Health Records,,,"Identifying subtypes of Alzheimer's Disease (AD) can lead towards the creation of personalized interventions and potentially improve outcomes. In this study, we use UK primary care electronic health records (EHR) from the CALIBER resource to identify and characterize clinically-meaningful clusters patients using unsupervised learning approaches of MCA and K-means. We discovered and characterized five clusters with different profiles (mental health, non-typical AD, typical AD, CVD and men with cancer). The mental health cluster had faster rate of progression than all the other clusters making it a target for future research and intervention. Our results demonstrate that unsupervised learning approaches can be utilized on EHR to identify subtypes of heterogeneous conditions.",,doi:https://doi.org/10.3233/SHTI200210 +37751444,https://doi.org/10.1371/journal.pone.0290583,Long Covid symptoms and diagnosis in primary care: A cohort study using structured and unstructured data in The Health Improvement Network primary care database.,"Shah AD, Subramanian A, Lewis J, Dhalla S, Ford E, Haroon S, Kuan V, Nirantharakumar K.",,PloS one,2023,2023-09-26,Y,,,,"

Background

Long Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes.

Aims

To compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis.

Methods

We used primary care electronic health record data until the end of December 2020 from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and 'Long Covid' diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis.

Results

We compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.46, 95% confidence interval (CI) 2.87, 4.17), shortness of breath (aHR 2.89, 95% CI 2.48, 3.36), palpitations (aHR 2.59, 95% CI 1.86, 3.60), and phlegm (aHR 2.43, 95% CI 1.65, 3.59). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression.

Conclusions

Numerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0290583&type=printable; doi:https://doi.org/10.1371/journal.pone.0290583; html:https://europepmc.org/articles/PMC10521988; pdf:https://europepmc.org/articles/PMC10521988?pdf=render 36960327,https://doi.org/10.2147/clep.s384605,Severe Mental Illness Among Adults with Atopic Eczema or Psoriasis: Population-Based Matched Cohort Studies within UK Primary Care.,"Adesanya EI, Henderson AD, Matthewman J, Bhate K, Hayes JF, Mulick A, Mathur R, Smith C, Carreira H, Rathod SD, Langan SM, Mansfield KE.",,Clinical epidemiology,2023,2023-03-17,Y,Psychology; epidemiology; Dermatology,,,"

Background

Existing research exploring associations between atopic eczema (AE) or psoriasis, and severe mental illness (SMI - ie, schizophrenia, bipolar disorder, other psychoses) is limited, with longitudinal evidence particularly scarce. Therefore, temporal directions of associations are unclear. We aimed to investigate associations between AE or psoriasis and incident SMI among adults.

Methods

We conducted matched cohort studies using primary care electronic health records (January 1997 to January 2020) from the UK Clinical Practice Research Datalink GOLD. We identified two cohorts: 1) adults (≥18 years) with and without AE and 2) adults with and without psoriasis. We matched (on age, sex, general practice) adults with AE or psoriasis with up to five adults without. We used Cox regression, stratified by matched set, to estimate hazard ratios (HRs) comparing incident SMI among adults with and without AE or psoriasis.

Results

We identified 1,023,232 adults with AE and 4,908,059 without, and 363,210 with psoriasis and 1,801,875 without. After adjusting for matching variables (age, sex, general practice) and potential confounders (deprivation, calendar period) both AE and psoriasis were associated with at least a 17% increased hazard of SMI (AE: HR=1.17,95% CI=1.12-1.22; psoriasis: HR=1.26,95% CI=1.18-1.35). After additionally adjusting for potential mediators (comorbidity burden, harmful alcohol use, smoking status, body mass index, and, in AE only, sleep problems and high-dose glucocorticoids), associations with SMI did not persist for AE (HR=0.98,95% CI=0.93-1.04), and were attenuated for psoriasis (HR=1.14,95% CI=1.05-1.23).

Conclusion

Our findings suggest adults with AE or psoriasis are at increased risk of SMI compared to matched comparators. After adjusting for potential mediators, associations with SMI did not persist for AE, and were attenuated for psoriasis, suggesting that the increased risk may be explained by mediating factors (eg, sleep problems). Our research highlights the importance of monitoring mental health in adults with AE or psoriasis.",,pdf:https://www.dovepress.com/getfile.php?fileID=88236; doi:https://doi.org/10.2147/CLEP.S384605; html:https://europepmc.org/articles/PMC10030004; pdf:https://europepmc.org/articles/PMC10030004?pdf=render 33615277,https://doi.org/10.1016/j.xpro.2021.100334,Massive expansion and cryopreservation of functional human induced pluripotent stem cell-derived cardiomyocytes.,"Maas RGC, Lee S, Harakalova M, Snijders Blok CJB, Goodyer WR, Hjortnaes J, Doevendans PAFM, Van Laake LW, van der Velden J, Asselbergs FW, Wu JC, Sluijter JPG, Wu SM, Buikema JW.",,STAR protocols,2021,2021-02-09,Y,Cell differentiation; Cell culture; Stem Cells,,,"Since the discovery of human induced pluripotent stem cells (hiPSCs), numerous strategies have been established to efficiently derive cardiomyocytes from hiPSCs (hiPSC-CMs). Here, we describe a cost-effective strategy for the subsequent massive expansion (>250-fold) of high-purity hiPSC-CMs relying on two aspects: removal of cell-cell contacts and small-molecule inhibition with CHIR99021. The protocol maintains CM functionality, allows cryopreservation, and the cells can be used in downstream assays such as disease modeling, drug and toxicity screening, and cell therapy. For complete details on the use and execution of this protocol, please refer to Buikema (2020).",,doi:https://doi.org/10.1016/j.xpro.2021.100334; doi:https://doi.org/10.1016/j.xpro.2021.100334; html:https://europepmc.org/articles/PMC7881265; pdf:https://europepmc.org/articles/PMC7881265?pdf=render 32735830,https://doi.org/10.1016/s2352-3026(20)30228-3,Cardiovascular adverse events following treatment for non-Hodgkin lymphoma - Authors' reply.,"Linschoten M, Kamphuis JA, Asselbergs FW.",,The Lancet. Haematology,2020,2020-08-01,N,,,,,,doi:https://doi.org/10.1016/S2352-3026(20)30228-3 32023934,https://doi.org/10.3390/ijerph17030892,Identifying Homogeneous Patterns of Injury in Paediatric Trauma Patients to Improve Risk-Adjusted Models of Mortality and Functional Outcomes.,"Dipnall JF, Gabbe BJ, Teague WJ, Beck B.",,International journal of environmental research and public health,2020,2020-01-31,Y,"Trauma; Injury; Paediatric; Latent Class Analysis; Risk Adjustment; Mortality, Koschi, Classes",Improving Public Health,injuries and accidents,"Injury is a leading cause of morbidity and mortality in the paediatric population and exhibits complex injury patterns. This study aimed to identify homogeneous groups of paediatric major trauma patients based on their profile of injury for use in mortality and functional outcomes risk-adjusted models. Data were extracted from the population-based Victorian State Trauma Registry for patients aged 0-15 years, injured 2006-2016. Four Latent Class Analysis (LCA) models with/without covariates of age/sex tested up to six possible latent classes. Five risk-adjusted models of in-hospital mortality and 6-month functional outcomes incorporated a combination of Injury Severity Score (ISS), New ISS (NISS), and LCA classes. LCA models replicated the best log-likelihood and entropy > 0.8 for all models (N = 1281). Four latent injury classes were identified: isolated head; isolated abdominal organ; multi-trauma injuries, and other injuries. The best models, in terms of goodness of fit statistics and model diagnostics, included the LCA classes and NISS. The identification of isolated head, isolated abdominal, multi-trauma and other injuries as key latent paediatric injury classes highlights areas for emphasis in planning prevention initiatives and paediatric trauma system development. Future risk-adjusted paediatric injury models that include these injury classes with the NISS when evaluating mortality and functional outcomes is recommended.",,pdf:https://www.mdpi.com/1660-4601/17/3/892/pdf?version=1580475934; doi:https://doi.org/10.3390/ijerph17030892; html:https://europepmc.org/articles/PMC7037699; pdf:https://europepmc.org/articles/PMC7037699?pdf=render -37407123,https://doi.org/10.1016/j.jcmg.2023.01.016,Ischemic Heart Disease and Vascular Risk Factors Are Associated With Accelerated Brain Aging.,"Rauseo E, Salih A, Raisi-Estabragh Z, Aung N, Khanderia N, Slabaugh GG, Marshall CR, Neubauer S, Radeva P, Galazzo IB, Menegaz G, Petersen SE.",,JACC. Cardiovascular imaging,2023,2023-04-12,Y,brain aging; ischemic heart disease; Cognitive Decline; Vascular Risk Factors; Brain Health,,,"

Background

Ischemic heart disease (IHD) has been linked with poor brain outcomes. The brain magnetic resonance imaging-derived difference between predicted brain age and actual chronological age (brain-age delta in years, positive for accelerated brain aging) may serve as an effective means of communicating brain health to patients to promote healthier lifestyles.

Objectives

The authors investigated the impact of prevalent IHD on brain aging, potential underlying mechanisms, and its relationship with dementia risk, vascular risk factors, cardiovascular structure, and function.

Methods

Brain age was estimated in subjects with prevalent IHD (n = 1,341) using a Bayesian ridge regression model with 25 structural (volumetric) brain magnetic resonance imaging features and built using UK Biobank participants with no prevalent IHD (n = 35,237).

Results

Prevalent IHD was linked to significantly accelerated brain aging (P < 0.001) that was not fully mediated by microvascular injury. Brain aging (positive brain-age delta) was associated with increased risk of dementia (OR: 1.13 [95% CI: 1.04-1.22]; P = 0.002), vascular risk factors (such as diabetes), and high adiposity. In the absence of IHD, brain aging was also associated with cardiovascular structural and functional changes typically observed in aging hearts. However, such alterations were not linked with risk of dementia.

Conclusions

Prevalent IHD and coexisting vascular risk factors are associated with accelerated brain aging and risk of dementia. Positive brain-age delta representing accelerated brain aging may serve as an effective communication tool to show the impact of modifiable risk factors and disease supporting preventative strategies.",,doi:https://doi.org/10.1016/j.jcmg.2023.01.016; html:https://europepmc.org/articles/PMC10317841; pdf:https://europepmc.org/articles/PMC10317841?pdf=render 35115301,https://doi.org/10.1136/bjophthalmol-2021-319641,Metformin and risk of age-related macular degeneration in individuals with type 2 diabetes: a retrospective cohort study.,"Gokhale KM, Adderley NJ, Subramanian A, Lee WH, Han D, Coker J, Braithwaite T, Denniston AK, Keane PA, Nirantharakumar K.",,The British journal of ophthalmology,2023,2022-02-03,N,Degeneration; epidemiology; Macula,,,"

Background

Age-related macular degeneration (AMD) in its late stages is a leading cause of sight loss in developed countries. Some previous studies have suggested that metformin may be associated with a reduced risk of developing AMD, but the evidence is inconclusive.

Aims

To explore the relationship between metformin use and development of AMD among patients with type 2 diabetes in the UK.

Methods

A large, population-based retrospective open cohort study with a time-dependent exposure design was carried out using IQVIA Medical Research Data, 1995-2019. Patients aged ≥40 with diagnosed type 2 diabetes were included.The exposed group was those prescribed metformin (with or without any other antidiabetic medications); the comparator (unexposed) group was those prescribed other antidiabetic medications only. The exposure status was treated as time varying, collected at 3-monthly time intervals.Extended Cox proportional hazards regression was used to calculate the adjusted HRs for development of the outcome, newly diagnosed AMD.

Results

A total of 173 689 patients, 57% men, mean (SD) age 62.8 (11.6) years, with incident type 2 diabetes and a record of one or more antidiabetic medications were included in the study. Median follow-up was 4.8 (IQR 2.3-8.3, range 0.5-23.8) years. 3111 (1.8%) patients developed AMD. The adjusted HR for diagnosis of AMD was 1.02 (95% CI 0.92 to 1.12) in patients prescribed metformin (with or without other antidiabetic medications) compared with those prescribed any other antidiabetic medication only.

Conclusion

We found no evidence that metformin was associated with risk of AMD in primary care patients requiring treatment for type 2 diabetes.",,pdf:https://discovery.ucl.ac.uk/10143945/1/Keane_T2DM%20metformin%20and%20risk%20of%20AMD%20BJO%2020220111%20clean.pdf; doi:https://doi.org/10.1136/bjophthalmol-2021-319641 +37407123,https://doi.org/10.1016/j.jcmg.2023.01.016,Ischemic Heart Disease and Vascular Risk Factors Are Associated With Accelerated Brain Aging.,"Rauseo E, Salih A, Raisi-Estabragh Z, Aung N, Khanderia N, Slabaugh GG, Marshall CR, Neubauer S, Radeva P, Galazzo IB, Menegaz G, Petersen SE.",,JACC. Cardiovascular imaging,2023,2023-04-12,Y,brain aging; ischemic heart disease; Cognitive Decline; Vascular Risk Factors; Brain Health,,,"

Background

Ischemic heart disease (IHD) has been linked with poor brain outcomes. The brain magnetic resonance imaging-derived difference between predicted brain age and actual chronological age (brain-age delta in years, positive for accelerated brain aging) may serve as an effective means of communicating brain health to patients to promote healthier lifestyles.

Objectives

The authors investigated the impact of prevalent IHD on brain aging, potential underlying mechanisms, and its relationship with dementia risk, vascular risk factors, cardiovascular structure, and function.

Methods

Brain age was estimated in subjects with prevalent IHD (n = 1,341) using a Bayesian ridge regression model with 25 structural (volumetric) brain magnetic resonance imaging features and built using UK Biobank participants with no prevalent IHD (n = 35,237).

Results

Prevalent IHD was linked to significantly accelerated brain aging (P < 0.001) that was not fully mediated by microvascular injury. Brain aging (positive brain-age delta) was associated with increased risk of dementia (OR: 1.13 [95% CI: 1.04-1.22]; P = 0.002), vascular risk factors (such as diabetes), and high adiposity. In the absence of IHD, brain aging was also associated with cardiovascular structural and functional changes typically observed in aging hearts. However, such alterations were not linked with risk of dementia.

Conclusions

Prevalent IHD and coexisting vascular risk factors are associated with accelerated brain aging and risk of dementia. Positive brain-age delta representing accelerated brain aging may serve as an effective communication tool to show the impact of modifiable risk factors and disease supporting preventative strategies.",,doi:https://doi.org/10.1016/j.jcmg.2023.01.016; html:https://europepmc.org/articles/PMC10317841; pdf:https://europepmc.org/articles/PMC10317841?pdf=render 36456017,https://doi.org/10.1136/bmjopen-2022-066288,"Impact of the COVID-19 pandemic on timeliness and equity of measles, mumps and rubella vaccinations in North East London: a longitudinal study using electronic health records.","Firman N, Marszalek M, Gutierrez A, Homer K, Williams C, Harper G, Dostal I, Ahmed Z, Robson J, Dezateux C.",,BMJ open,2022,2022-12-01,Y,Public Health; Primary Care; Paediatric Infectious Disease & Immunisation; Covid-19,,,"

Objectives

To quantify the effect of the COVID-19 pandemic on the timeliness of, and geographical and sociodemographic inequalities in, receipt of first measles, mumps and rubella (MMR) vaccination.

Design

Longitudinal study using primary care electronic health records.

Setting

285 general practices in North East London.

Participants

Children born between 23 August 2017 and 22 September 2018 (pre-pandemic cohort) or between 23 March 2019 and 1 May 2020 (pandemic cohort).

Main outcome measure

Receipt of timely MMR vaccination between 12 and 18 months of age.

Methods

We used logistic regression to estimate the ORs (95% CIs) of receipt of a timely vaccination adjusting for sex, deprivation, ethnic background and Clinical Commissioning Group. We plotted choropleth maps of the proportion receiving timely vaccinations.

Results

Timely MMR receipt fell by 4.0% (95% CI: 3.4% to 4.6%) from 79.2% (78.8% to 79.6%) to 75.2% (74.7% to 75.7%) in the pre-pandemic (n=33 226; 51.3% boys) and pandemic (n=32 446; 51.4%) cohorts, respectively. After adjustment, timely vaccination was less likely in the pandemic cohort (0.79; 0.76 to 0.82), children from black (0.70; 0.65 to 0.76), mixed/other (0.77; 0.72 to 0.82) or with missing (0.77; 0.74 to 0.81) ethnic background, and more likely in girls (1.07; 1.03 to 1.11) and those from South Asian backgrounds (1.39; 1.30 to 1.48). Children living in the least deprived areas were more likely to receive a timely MMR (2.09; 1.78 to 2.46) but there was no interaction between cohorts and deprivation (Wald statistic: 3.44; p=0.49). The proportion of neighbourhoods where less than 60% of children received timely vaccination increased from 7.5% to 12.7% during the pandemic.

Conclusions

The COVID-19 pandemic was associated with a significant fall in timely MMR receipt and increased geographical clustering of measles susceptibility in an area of historically low and inequitable MMR coverage. Immediate action is needed to avert measles outbreaks and support primary care to deliver timely and equitable vaccinations.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e066288.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-066288; html:https://europepmc.org/articles/PMC9723415; pdf:https://europepmc.org/articles/PMC9723415?pdf=render 36609282,https://doi.org/10.1186/s13063-022-06967-6,A comparison of covariate adjustment approaches under model misspecification in individually randomized trials.,"Tackney MS, Morris T, White I, Leyrat C, Diaz-Ordaz K, Williamson E.",,Trials,2023,2023-01-06,Y,Randomized controlled trials; Iptw; G-computation; Tmle; Covariate Adjustment; Ancova; Misspecification; Aiptw,,,"Adjustment for baseline covariates in randomized trials has been shown to lead to gains in power and can protect against chance imbalances in covariates. For continuous covariates, there is a risk that the the form of the relationship between the covariate and outcome is misspecified when taking an adjusted approach. Using a simulation study focusing on individually randomized trials with small sample sizes, we explore whether a range of adjustment methods are robust to misspecification, either in the covariate-outcome relationship or through an omitted covariate-treatment interaction. Specifically, we aim to identify potential settings where G-computation, inverse probability of treatment weighting (IPTW), augmented inverse probability of treatment weighting (AIPTW) and targeted maximum likelihood estimation (TMLE) offer improvement over the commonly used analysis of covariance (ANCOVA). Our simulations show that all adjustment methods are generally robust to model misspecification if adjusting for a few covariates, sample size is 100 or larger, and there are no covariate-treatment interactions. When there is a non-linear interaction of treatment with a skewed covariate and sample size is small, all adjustment methods can suffer from bias; however, methods that allow for interactions (such as G-computation with interaction and IPTW) show improved results compared to ANCOVA. When there are a high number of covariates to adjust for, ANCOVA retains good properties while other methods suffer from under- or over-coverage. An outstanding issue for G-computation, IPTW and AIPTW in small samples is that standard errors are underestimated; they should be used with caution without the availability of small-sample corrections, development of which is needed. These findings are relevant for covariate adjustment in interim analyses of larger trials.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-022-06967-6; doi:https://doi.org/10.1186/s13063-022-06967-6; html:https://europepmc.org/articles/PMC9817411; pdf:https://europepmc.org/articles/PMC9817411?pdf=render 36457326,https://doi.org/10.3389/fpubh.2022.1017337,Seroepidemiology of SARS-CoV-2 on a partially vaccinated island in Brazil: Determinants of infection and vaccine response.,"Cerbino-Neto J, Peres IT, Varela MC, Brandão LGP, de Matos JA, Pinto LF, da Costa MD, Garcia MHO, Soranz D, Maia MLS, Krieger MA, da Cunha RV, Camacho LAB, Ranzani O, Hamacher S, Bozza FA, Penna GO.",,Frontiers in public health,2022,2022-11-14,Y,Vaccine; Antibody response; risk factors; Seroepidemiologic Studies; Seropositivity; Covid-19,,,"

Background

A vaccination campaign targeted adults in response to the pandemic in the City of Rio de Janeiro.

Objective

We aimed to evaluate the seroprevalence of SARS-CoV-2 antibodies and identify factors associated with seropositivity on vaccinated and unvaccinated residents.

Methods

We performed a seroepidemiologic survey in all residents of Paquetá Island, a neighborhood of Rio de Janeiro city, during the COVID-19 vaccine roll-out. Serological tests were performed from June 16 to June 19, 2021, and adjusted seropositivity rates were estimated by age and epidemiological variables. Logistic regression models were used to estimate adjusted ORs for risk factors to SARS-CoV-2 seropositivity in non-vaccinated individuals, and potential determinants of the magnitude of antibody responses in the seropositive population.

Results

We included in the study 3,016 residents of Paquetá (83.5% of the island population). The crude seroprevalence of COVID-19 antibodies in our sample was 53.6% (95% CI = 51.0, 56.3). The risk factors for SARS-CoV-2 seropositivity in non-vaccinated individuals were history of confirmed previous COVID-19 infection (OR = 4.74; 95% CI = 3.3, 7.0), being a household contact of a case (OR = 1.93; 95% CI = 1.5, 2.6) and in-person learning (OR = 2.01; 95% CI = 1.4, 3.0). Potential determinants of the magnitude of antibody responses among the seropositive were hybrid immunity, the type of vaccine received, and time since the last vaccine dose. Being vaccinated with Pfizer or AstraZeneca (Beta = 2.2; 95% CI = 1.8, 2.6) determined higher antibody titers than those observed with CoronaVac (Beta = 1.2; 95% CI = 0.9, 1.5).

Conclusions

Our study highlights the impact of vaccination on COVID-19 collective immunity even in a highly affected population, showing the difference in antibody titers achieved with different vaccines and how they wane with time, reinforcing how these factors should be considered when estimating effectiveness of a vaccination program at any given time. We also found that hybrid immunity was superior to both infection-induced and vaccine-induced immunity alone, and online learning protected students from COVID-19 exposure.",,pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.1017337/pdf; doi:https://doi.org/10.3389/fpubh.2022.1017337; html:https://europepmc.org/articles/PMC9706255; pdf:https://europepmc.org/articles/PMC9706255?pdf=render @@ -1662,10 +1662,10 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 36958365,https://doi.org/10.1016/s2352-3018(23)00028-0,Life expectancy after 2015 of adults with HIV on long-term antiretroviral therapy in Europe and North America: a collaborative analysis of cohort studies.,"Trickey A, Sabin CA, Burkholder G, Crane H, d'Arminio Monforte A, Egger M, Gill MJ, Grabar S, Guest JL, Jarrin I, Lampe FC, Obel N, Reyes JM, Stephan C, Sterling TR, Teira R, Touloumi G, Wasmuth JC, Wit F, Wittkop L, Zangerle R, Silverberg MJ, Justice A, Sterne JAC.",,The lancet. HIV,2023,2023-03-20,N,,,,"

Background

The life expectancy of people with HIV taking antiretroviral therapy (ART) has increased substantially over the past 25 years. Most previous studies of life expectancy were based on data from the first few years after starting ART, when mortality is highest. However, many people with HIV have been successfully treated with ART for many years, and up-to-date prognosis data are needed. We aimed to estimate life expectancy in adults with HIV on ART for at least 1 year in Europe and North America from 2015 onwards.

Methods

We used data for people with HIV taking ART from the Antiretroviral Therapy Cohort Collaboration and the UK Collaborative HIV Cohort Study. Included participants started ART between 1996 and 2014 and had been on ART for at least 1 year by 2015, or started ART between 2015 and 2019 and survived for at least 1 year; all participants were aged at least 16 years at ART initiation. We used Poisson models to estimate the associations between mortality and demographic and clinical characteristics, including CD4 cell count at the start of follow-up. We also estimated the remaining years of life left for people with HIV aged 40 years who were taking ART, and stratified these estimates by variables associated with mortality. These estimates were compared with estimates for years of life remaining in a corresponding multi-country general population.

Findings

Among 206 891 people with HIV included, 5780 deaths were recorded since 2015. We estimated that women with HIV at age 40 years had 35·8 years (95% CI 35·2-36·4) of life left if they started ART before 2015, and 39·0 years (38·5-39·5) left if they started ART after 2015. For men with HIV, the corresponding estimates were 34·5 years (33·8-35·2) and 37·0 (36·5-37·6). Women with CD4 counts of fewer than 49 cells per μL at the start of follow-up had an estimated 19·4 years (18·2-20·5) of life left at age 40 years if they started ART before 2015 and 24·9 years (23·9-25·9) left if they started ART after 2015. The corresponding estimates for men were 18·2 years (17·1-19·4) and 23·7 years (22·7-24·8). Women with CD4 counts of at least 500 cells per μL at the start of follow-up had an estimated 40·2 years (39·7-40·6) of life left at age 40 years if they started ART before 2015 and 42·0 years (41·7-42·3) left if they started ART after 2015. The corresponding estimates for men were 38·0 years (37·5-38·5) and 39·2 years (38·7-39·7).

Interpretation

For people with HIV on ART and with high CD4 cell counts who survived to 2015 or started ART after 2015, life expectancy was only a few years lower than that in the general population, irrespective of when ART was started. However, for people with low CD4 counts at the start of follow-up, life-expectancy estimates were substantially lower, emphasising the continuing importance of early diagnosis and sustained treatment of HIV.

Funding

US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council.",,doi:https://doi.org/10.1016/s2352-3018(23)00028-0; doi:https://doi.org/10.1016/S2352-3018(23)00028-0; html:https://europepmc.org/articles/PMC10288029; pdf:https://europepmc.org/articles/PMC10288029?pdf=render; doi:https://doi.org/10.1016/s2352-3018(23)00028-0 34931349,https://doi.org/10.1111/bcp.15191,Dissecting the IL-6 pathway in cardiometabolic disease: A Mendelian randomization study on both IL6 and IL6R.,"Cupido AJ, Asselbergs FW, Natarajan P, CHARGE Inflammation Working Group, Ridker PM, Hovingh GK, Schmidt AF.",,British journal of clinical pharmacology,2022,2022-01-28,Y,IL-6; Cardiovascular disease; Trans-signalling; Classical Signalling,,,"

Aims

Chronic inflammation is a risk factor for cardiovascular disease (CVD). IL-6 signalling perturbation through IL-6 or IL-6R blockade may have potential benefit on cardiovascular risk. It is unknown whether targeting either IL-6 or IL-6 receptor may result in similar effects on CVD and adverse events. We compared the anticipated effects of targeting IL-6 and IL-6 receptor on cardiometabolic risk and potential side effects.

Methods

We constructed four instruments: two main instruments with genetic variants in the IL6 and IL6R loci weighted for their association with CRP, and two after firstly filtering variants for their association with IL-6 or IL-6R expression. Analyses were performed for coronary artery disease (CAD), ischemic stroke, atrial fibrillation (AF), heart failure, type 2 diabetes (T2D), rheumatoid arthritis (RA), infection endpoints, and quantitative haematological, metabolic and anthropometric parameters.

Results

A 1 mg/L lower CRP by the IL6 instrument was associated with lower CAD (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.77;0.96), AF and T2D risk. A 1 mg/L lower CRP by the IL6R instrument was associated with lower CAD (OR 0.90, 95% CI 0.86;0.95), any stroke and ischemic stroke, AF, RA risk and higher pneumonia risk. The eQTL-filtered results were in concordance with the main results, but with wider confidence intervals.

Conclusions

IL-6 signalling perturbation by either IL6 or IL6R genetic instruments is associated with a similar risk reduction for multiple cardiometabolic diseases, suggesting that both IL-6 and IL-6R are potential therapeutic targets to lower CVD. Moreover, IL-6 rather than IL-6R inhibition might have a more favourable pneumonia risk.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bcp.15191; doi:https://doi.org/10.1111/bcp.15191; html:https://europepmc.org/articles/PMC9303316; pdf:https://europepmc.org/articles/PMC9303316?pdf=render 31756303,https://doi.org/10.1161/circgen.119.002711,Genetic Determinants of Lipids and Cardiovascular Disease Outcomes: A Wide-Angled Mendelian Randomization Investigation.,"Allara E, Morani G, Carter P, Gkatzionis A, Zuber V, Foley CN, Rees JMB, Mason AM, Bell S, Gill D, Lindström S, Butterworth AS, Di Angelantonio E, Peters J, Burgess S, INVENT consortium.",,Circulation. Genomic and precision medicine,2019,2019-11-22,Y,Lipids; Aortic valve stenosis; epidemiology; Venous Thromboembolism; Mendelian Randomization,,,"

Background

Evidence from randomized trials has shown that therapies that lower LDL (low-density lipoprotein)-cholesterol and triglycerides reduce coronary artery disease (CAD) risk. However, there is still uncertainty about their effects on other cardiovascular outcomes. We therefore performed a systematic investigation of causal relationships between circulating lipids and cardiovascular outcomes using a Mendelian randomization approach.

Methods

In the primary analysis, we performed 2-sample multivariable Mendelian randomization using data from participants of European ancestry. We also conducted univariable analyses using inverse-variance weighted and robust methods, and gene-specific analyses using variants that can be considered as proxies for specific lipid-lowering medications. We obtained associations with lipid fractions from the Global Lipids Genetics Consortium, a meta-analysis of 188 577 participants, and genetic associations with cardiovascular outcomes from 367 703 participants in UK Biobank.

Results

For LDL-cholesterol, in addition to the expected positive associations with CAD risk (odds ratio [OR] per 1 SD increase, 1.45 [95% CI, 1.35-1.57]) and other atheromatous outcomes (ischemic cerebrovascular disease and peripheral vascular disease), we found independent associations of genetically predicted LDL-cholesterol with abdominal aortic aneurysm (OR, 1.75 [95% CI, 1.40-2.17]) and aortic valve stenosis (OR, 1.46 [95% CI, 1.25-1.70]). Genetically predicted triglyceride levels were positively associated with CAD (OR, 1.25 [95% CI, 1.12-1.40]), aortic valve stenosis (OR, 1.29 [95% CI, 1.04-1.61]), and hypertension (OR, 1.17 [95% CI, 1.07-1.27]), but inversely associated with venous thromboembolism (OR, 0.79 [95% CI, 0.67-0.93]) and hemorrhagic stroke (OR, 0.78 [95% CI, 0.62-0.98]). We also found positive associations of genetically predicted LDL-cholesterol and triglycerides with heart failure that appeared to be mediated by CAD.

Conclusions

Lowering LDL-cholesterol is likely to prevent abdominal aortic aneurysm and aortic stenosis, in addition to CAD and other atheromatous cardiovascular outcomes. Lowering triglycerides is likely to prevent CAD and aortic valve stenosis but may increase thromboembolic risk.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.119.002711; doi:https://doi.org/10.1161/CIRCGEN.119.002711; html:https://europepmc.org/articles/PMC6922071; pdf:https://europepmc.org/articles/PMC6922071?pdf=render -38233595,https://doi.org/10.1038/s41588-023-01638-x,Inherited polygenic effects on common hematological traits influence clonal selection on JAK2V617F and the development of myeloproliferative neoplasms.,"Guo J, Walter K, Quiros PM, Gu M, Baxter EJ, Danesh J, Di Angelantonio E, Roberts D, Guglielmelli P, Harrison CN, Godfrey AL, Green AR, Vassiliou GS, Vuckovic D, Nangalia J, Soranzo N.",,Nature genetics,2024,2024-01-17,Y,,,,"Myeloproliferative neoplasms (MPNs) are chronic cancers characterized by overproduction of mature blood cells. Their causative somatic mutations, for example, JAK2V617F, are common in the population, yet only a minority of carriers develop MPN. Here we show that the inherited polygenic loci that underlie common hematological traits influence JAK2V617F clonal expansion. We identify polygenic risk scores (PGSs) for monocyte count and plateletcrit as new risk factors for JAK2V617F positivity. PGSs for several hematological traits influenced the risk of different MPN subtypes, with low PGSs for two platelet traits also showing protective effects in JAK2V617F carriers, making them two to three times less likely to have essential thrombocythemia than carriers with high PGSs. We observed that extreme hematological PGSs may contribute to an MPN diagnosis in the absence of somatic driver mutations. Our study showcases how polygenic backgrounds underlying common hematological traits influence both clonal selection on somatic mutations and the subsequent phenotype of cancer.",,pdf:https://www.nature.com/articles/s41588-023-01638-x.pdf; doi:https://doi.org/10.1038/s41588-023-01638-x; html:https://europepmc.org/articles/PMC10864174; pdf:https://europepmc.org/articles/PMC10864174?pdf=render -36732776,https://doi.org/10.1186/s13040-023-00321-5,LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes.,"Alasiri A, Karczewski KJ, Cole B, Loza BL, Moore JH, van der Laan SW, Asselbergs FW, Keating BJ, van Setten J.",,BioData mining,2023,2023-02-02,Y,Human Genetic; Loss-of-function Variants; Compound Heterozygotes; Knockout Genes,,,"

Background

Loss-of-Function (LoF) variants in human genes are important due to their impact on clinical phenotypes and frequent occurrence in the genomes of healthy individuals. The association of LoF variants with complex diseases and traits may lead to the discovery and validation of novel therapeutic targets. Current approaches predict high-confidence LoF variants without identifying the specific genes or the number of copies they affect. Moreover, there is a lack of methods for detecting knockout genes caused by compound heterozygous (CH) LoF variants.

Results

We have developed the Loss-of-Function ToolKit (LoFTK), which allows efficient and automated prediction of LoF variants from genotyped, imputed and sequenced genomes. LoFTK enables the identification of genes that are inactive in one or two copies and provides summary statistics for downstream analyses. LoFTK can identify CH LoF variants, which result in LoF genes with two copies lost. Using data from parents and offspring we show that 96% of CH LoF genes predicted by LoFTK in the offspring have the respective alleles donated by each parent.

Conclusions

LoFTK is a command-line based tool that provides a reliable computational workflow for predicting LoF variants from genotyped and sequenced genomes, identifying genes that are inactive in 1 or 2 copies. LoFTK is an open software and is freely available to non-commercial users at https://github.com/CirculatoryHealth/LoFTK .",,pdf:https://biodatamining.biomedcentral.com/counter/pdf/10.1186/s13040-023-00321-5; doi:https://doi.org/10.1186/s13040-023-00321-5; html:https://europepmc.org/articles/PMC9893534; pdf:https://europepmc.org/articles/PMC9893534?pdf=render 37671353,https://doi.org/10.23889/ijpds.v5i3.2133,Public Involvement & Engagement in health inequalities research on COVID-19 pandemic: a case study of CIDACS/FIOCRUZ BAHIA.,"Dos Anjos Fonseca A, Pimenta DM, de Almeida MRS, Lima RT, Barreto ML, Ichihara MYT.",,International journal of population data science,2020,2020-01-01,Y,Brazil; Pandemic; Policymakers; Social Inequalities; Public Engagement; Community Groups; Public Involvement,,,"

Introduction

Health inequalities in Brazil have deepened on Covid-19 pandemic, and the most vulnerable people were the more affected. A multidisciplinary team from Cidacs/Fiocruz Bahia developed a Social Disparities Index for Covid-19 (IDS-COVID-19) to support the evaluation of effects of health inequalities on the pandemic in Brazil. Public Involvement and Engagement were the pillars of this research because they allowed us to access first hand experiences about the social context in our country.

Objectives

This paper aims to describe our Public Involvement and Engagement experience by analysing our challenges, strategies, activities, results, and lessons learned during the construction of IDS-COVID-19.

Methods

The basis of the IDS-Covid-19 public engagement model was the participation of different social groups through methods and techniques that allow dialogue. Several activities and communication products supported the continuous interactions. Another guideline was the inclusion and the welcoming of participants from the beginning of the project to ensure that the participant's contributions could drive decision-making about the research.

Results

Participants made several contributions to the research as a new layer of information to the Index, and improvements were made to the interactive panel. They also compromised to support the dissemination and use of the product. Eight representatives of community groups and 29 policymakers participated in our engagement activities during the project. More than 500 people were in our open webinars. In addition, more than 140 news items about IDS-Covid-19 were published in national and international media.

Conclusions

We highlight as lessons learned the adaptation of some dissemination formats to the public, and the necessity of being flexible and accessible to participants. We strengthened the relationship with relevant stakeholders by exploring individual conversations by phone, WhatsApp, email, and interviews to produce a documentary that registered this whole experience. Cidacs/Fiocruz Bahia has also embedded public engagement and involvement in the study agenda.",,doi:https://doi.org/10.23889/ijpds.v5i3.2133; html:https://europepmc.org/articles/PMC10476697; pdf:https://europepmc.org/articles/PMC10476697?pdf=render +38233595,https://doi.org/10.1038/s41588-023-01638-x,Inherited polygenic effects on common hematological traits influence clonal selection on JAK2V617F and the development of myeloproliferative neoplasms.,"Guo J, Walter K, Quiros PM, Gu M, Baxter EJ, Danesh J, Di Angelantonio E, Roberts D, Guglielmelli P, Harrison CN, Godfrey AL, Green AR, Vassiliou GS, Vuckovic D, Nangalia J, Soranzo N.",,Nature genetics,2024,2024-01-17,Y,,,,"Myeloproliferative neoplasms (MPNs) are chronic cancers characterized by overproduction of mature blood cells. Their causative somatic mutations, for example, JAK2V617F, are common in the population, yet only a minority of carriers develop MPN. Here we show that the inherited polygenic loci that underlie common hematological traits influence JAK2V617F clonal expansion. We identify polygenic risk scores (PGSs) for monocyte count and plateletcrit as new risk factors for JAK2V617F positivity. PGSs for several hematological traits influenced the risk of different MPN subtypes, with low PGSs for two platelet traits also showing protective effects in JAK2V617F carriers, making them two to three times less likely to have essential thrombocythemia than carriers with high PGSs. We observed that extreme hematological PGSs may contribute to an MPN diagnosis in the absence of somatic driver mutations. Our study showcases how polygenic backgrounds underlying common hematological traits influence both clonal selection on somatic mutations and the subsequent phenotype of cancer.",,pdf:https://www.nature.com/articles/s41588-023-01638-x.pdf; doi:https://doi.org/10.1038/s41588-023-01638-x; html:https://europepmc.org/articles/PMC10864174; pdf:https://europepmc.org/articles/PMC10864174?pdf=render 33653287,https://doi.org/10.1186/s12875-021-01384-1,"A cross-sectional study reporting concussion exposure, assessment and management in Western Australian general practice.","Thomas E, Chih H, Gabbe B, Fitzgerald M, Cowen G.",,BMC family practice,2021,2021-03-02,Y,,,,"

Background

General Practitioners (GPs) may be called upon to assess patients who have sustained a concussion despite limited information being available at this assessment. Information relating to how concussion is actually being assessed and managed in General Practice is scarce. This study aimed to identify characteristics of current Western Australian (WA) GP exposure to patients with concussion, factors associated with GPs' knowledge of concussion, confidence of GPs in diagnosing and managing patients with concussion, typical referral practices and familiarity of GPs with guidelines.

Methods

In this cross-sectional study, GPs in WA were recruited via the RACGP WA newsletter and shareGP and the consented GPs completed an electronic survey. Associations were performed using Chi-squared tests or Fisher's Exact test.

Results

Sixty-six GPs in WA responded to the survey (response rate = 1.7%). Demographics, usual practice, knowledge, confidence, identification of prolonged recovery as well as guideline and resource awareness of GPs who practised in regional and metropolitan areas were comparable (p > 0.05). Characteristics of GPs were similar between those who identified all symptoms of concussion and distractors correctly and those who did not (p > 0.05). However, 84% of the respondents who had never heard of concussion guidelines were less likely to answer all symptoms and distractors correctly (p = 0.039). Whilst 78% of the GPs who were confident in their diagnoses had heard of guidelines (p = 0.029), confidence in managing concussion was not significantly associated with GPs exposure to guidelines. It should be noted that none of the respondents correctly identified signs of concussion and excluded the distractors.

Conclusions

Knowledge surrounding concussion guidelines, diagnosis and management varied across GPs in WA. Promotion of available concussion guidelines may assist GPs who lack confidence in making a diagnosis. The lack of association between GPs exposure to guidelines and confidence managing concussion highlights that concussion management may be an area where GPs could benefit from additional education and support.",,pdf:https://bmcfampract.biomedcentral.com/track/pdf/10.1186/s12875-021-01384-1; doi:https://doi.org/10.1186/s12875-021-01384-1; html:https://europepmc.org/articles/PMC7927406; pdf:https://europepmc.org/articles/PMC7927406?pdf=render +36732776,https://doi.org/10.1186/s13040-023-00321-5,LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes.,"Alasiri A, Karczewski KJ, Cole B, Loza BL, Moore JH, van der Laan SW, Asselbergs FW, Keating BJ, van Setten J.",,BioData mining,2023,2023-02-02,Y,Human Genetic; Loss-of-function Variants; Compound Heterozygotes; Knockout Genes,,,"

Background

Loss-of-Function (LoF) variants in human genes are important due to their impact on clinical phenotypes and frequent occurrence in the genomes of healthy individuals. The association of LoF variants with complex diseases and traits may lead to the discovery and validation of novel therapeutic targets. Current approaches predict high-confidence LoF variants without identifying the specific genes or the number of copies they affect. Moreover, there is a lack of methods for detecting knockout genes caused by compound heterozygous (CH) LoF variants.

Results

We have developed the Loss-of-Function ToolKit (LoFTK), which allows efficient and automated prediction of LoF variants from genotyped, imputed and sequenced genomes. LoFTK enables the identification of genes that are inactive in one or two copies and provides summary statistics for downstream analyses. LoFTK can identify CH LoF variants, which result in LoF genes with two copies lost. Using data from parents and offspring we show that 96% of CH LoF genes predicted by LoFTK in the offspring have the respective alleles donated by each parent.

Conclusions

LoFTK is a command-line based tool that provides a reliable computational workflow for predicting LoF variants from genotyped and sequenced genomes, identifying genes that are inactive in 1 or 2 copies. LoFTK is an open software and is freely available to non-commercial users at https://github.com/CirculatoryHealth/LoFTK .",,pdf:https://biodatamining.biomedcentral.com/counter/pdf/10.1186/s13040-023-00321-5; doi:https://doi.org/10.1186/s13040-023-00321-5; html:https://europepmc.org/articles/PMC9893534; pdf:https://europepmc.org/articles/PMC9893534?pdf=render 38115598,https://doi.org/10.1089/neu.2023.0461,"The Australian Traumatic Brain Injury Initiative: Systematic Review and Consensus Process to Determine the Predictive Value of Demographic, Injury Event, and Social Characteristics on Outcomes for People With Moderate-Severe Traumatic Brain Injury.","Gabbe BJ, Keeves J, McKimmie A, Gadowski AM, Holland AJ, Semple BD, Young JT, Crowe L, Ownsworth T, Bagg MK, Antonic-Baker A, Hicks AJ, Hill R, Curtis K, Romero L, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Fitzgerald M.",,Journal of neurotrauma,2024,2024-04-01,N,"Traumatic; Demography; Common Data Elements; Social Factors; Outcome Assessment, Health Care; Systematic Review [Publication Type]; Brain Injuries, Culture",,,"The objective of the Australian Traumatic Brain Injury (AUS-TBI) Initiative is to develop a data dictionary to inform data collection and facilitate prediction of outcomes of people who experience moderate-severe TBI in Australia. The aim of this systematic review was to summarize the evidence of the association between demographic, injury event, and social characteristics with outcomes, in people with moderate-severe TBI, to identify potentially predictive indicators. Standardized searches were implemented across bibliographic databases to March 31, 2022. English-language reports, excluding case series, which evaluated the association between demographic, injury event, and social characteristics, and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Abstracts and full text records were independently screened by at least two reviewers in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association. The review findings were discussed with an expert panel to determine the feasibility of incorporation of routine measurement into standard care. The search strategy retrieved 16,685 records; 867 full-length records were screened, and 111 studies included. Twenty-two predictors of 32 different outcomes were identified; 7 were classified as high-level (age, sex, ethnicity, employment, insurance, education, and living situation at the time of injury). After discussion with an expert consensus group, 15 were recommended for inclusion in the data dictionary. This review identified numerous predictors capable of enabling early identification of those at risk for poor outcomes and improved personalization of care through inclusion in routine data collection.",,doi:https://doi.org/10.1089/neu.2023.0461 34982094,https://doi.org/10.1167/tvst.11.1.3,OCT Assisted Quantification of Vitreous Inflammation in Uveitis.,"Liu X, Kale AU, Ometto G, Montesano G, Sitch AJ, Capewell N, Radovanovic C, Bucknall N, Beare NAV, Moore DJ, Keane PA, Crabb DP, Denniston AK.",,Translational vision science & technology,2022,2022-01-01,Y,,,,"

Purpose

Vitreous haze (VH) is a key marker of inflammation in uveitis but limited by its subjectivity. Optical coherence tomography (OCT) has potential as an objective, noninvasive method for quantifying VH. We test the hypotheses that OCT can reliably quantify VH and the measurement is associated with slit-lamp based grading of VH.

Methods

In this prospective study, participants underwent three repeated OCT macular scans to evaluate the within-eye reliability of the OCT vitreous intensity (VI). Association between OCT VI and clinical findings (including VH grade, phakic status, visual acuity [VA], anterior chamber cells, and macular thickness) were assessed.

Results

One hundred nineteen participants were included (41 healthy participants, 32 patients with uveitis without VH, and 46 patients with uveitis with VH). Within-eye test reliability of OCT VI was high in healthy eyes and in all grades of VH (intraclass correlation coefficient [ICC] > 0.79). Average OCT VI was significantly different between healthy eyes and uveitic eyes without and uveitic eyes with VH, and was associated with increasing clinical VH grade (P < 0.05). OCT VI was significantly associated with VA, whereas clinical VH grading was not. Cataract was also associated with higher OCT VI (P = 0.03).

Conclusions

OCT VI is a fast, noninvasive, objective, and automated method for measuring vitreous inflammation. It is associated with clinician grading of vitreous inflammation and VA, however, it can be affected by media opacities.

Translational relevance

OCT imaging for quantifying vitreous inflammation shows high within-eye repeatability and is associated with clinical grading of vitreous haze. OCT measurements are also associated with visual acuity but may be affected by structures anterior to the acquisition window, such as lens opacity and other anterior segment changes.",,doi:https://doi.org/10.1167/tvst.11.1.3; doi:https://doi.org/10.1167/tvst.11.1.3; html:https://europepmc.org/articles/PMC8742534; pdf:https://europepmc.org/articles/PMC8742534?pdf=render 35983770,https://doi.org/10.2807/1560-7917.es.2022.27.33.2100885,"Recording of 'COVID-19 vaccine declined': a cohort study on 57.9 million National Health Service patients' records in situ using OpenSAFELY, England, 8 December 2020 to 25 May 2021.","Curtis HJ, Inglesby P, MacKenna B, Croker R, Hulme WJ, Rentsch CT, Bhaskaran K, Mathur R, Morton CE, Bacon SC, Smith RM, Evans D, Mehrkar A, Tomlinson L, Walker AJ, Bates C, Hickman G, Ward T, Morley J, Cockburn J, Davy S, Williamson EJ, Eggo RM, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Evans SJ, Douglas IJ, Smeeth L, Goldacre B.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2022,2022-08-01,Y,Vaccination; Vaccine Hesitancy; Nhs England; Covid-19; Sars-cov-2,,,"BackgroundPriority patients in England were offered COVID-19 vaccination by mid-April 2021. Codes in clinical record systems can denote the vaccine being declined.AimWe describe records of COVID-19 vaccines being declined, according to clinical and demographic factors.MethodsWith the approval of NHS England, we conducted a retrospective cohort study between 8 December 2020 and 25 May 2021 with primary care records for 57.9 million patients using OpenSAFELY, a secure health analytics platform. COVID-19 vaccination priority patients were those aged ≥ 50 years or ≥ 16 years clinically extremely vulnerable (CEV) or 'at risk'. We describe the proportion recorded as declining vaccination for each group and stratified by clinical and demographic subgroups, subsequent vaccination and distribution of clinical code usage across general practices.ResultsOf 24.5 million priority patients, 663,033 (2.7%) had a decline recorded, while 2,155,076 (8.8%) had neither a vaccine nor decline recorded. Those recorded as declining, who were subsequently vaccinated (n = 125,587; 18.9%) were overrepresented in the South Asian population (32.3% vs 22.8% for other ethnicities aged ≥ 65 years). The proportion of declining unvaccinated patients was highest in CEV (3.3%), varied strongly with ethnicity (black 15.3%, South Asian 5.6%, white 1.5% for ≥ 80 years) and correlated positively with increasing deprivation.ConclusionsClinical codes indicative of COVID-19 vaccinations being declined are commonly used in England, but substantially more common among black and South Asian people, and in more deprived areas. Qualitative research is needed to determine typical reasons for recorded declines, including to what extent they reflect patients actively declining.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/27/33/eurosurv-27-33-5.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2022.27.33.2100885&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2022.27.33.2100885; html:https://europepmc.org/articles/PMC9389857 @@ -1674,25 +1674,25 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 34425897,https://doi.org/10.1186/s13326-021-00249-x,Linking common human diseases to their phenotypes; development of a resource for human phenomics.,"Kafkas Ş, Althubaiti S, Gkoutos GV, Hoehndorf R, Schofield PN.",,Journal of biomedical semantics,2021,2021-08-23,Y,Ontologies; Text Mining; Uk Biobank; Disease–phenotype Associations,,,"

Background

In recent years a large volume of clinical genomics data has become available due to rapid advances in sequencing technologies. Efficient exploitation of this genomics data requires linkage to patient phenotype profiles. Current resources providing disease-phenotype associations are not comprehensive, and they often do not have broad coverage of the disease terminologies, particularly ICD-10, which is still the primary terminology used in clinical settings.

Methods

We developed two approaches to gather disease-phenotype associations. First, we used a text mining method that utilizes semantic relations in phenotype ontologies, and applies statistical methods to extract associations between diseases in ICD-10 and phenotype ontology classes from the literature. Second, we developed a semi-automatic way to collect ICD-10-phenotype associations from existing resources containing known relationships.

Results

We generated four datasets. Two of them are independent datasets linking diseases to their phenotypes based on text mining and semi-automatic strategies. The remaining two datasets are generated from these datasets and cover a subset of ICD-10 classes of common diseases contained in UK Biobank. We extensively validated our text mined and semi-automatically curated datasets by: comparing them against an expert-curated validation dataset containing disease-phenotype associations, measuring their similarity to disease-phenotype associations found in public databases, and assessing how well they could be used to recover gene-disease associations using phenotype similarity.

Conclusion

We find that our text mining method can produce phenotype annotations of diseases that are correct but often too general to have significant information content, or too specific to accurately reflect the typical manifestations of the sporadic disease. On the other hand, the datasets generated from integrating multiple knowledgebases are more complete (i.e., cover more of the required phenotype annotations for a given disease). We make all data freely available at https://doi.org/10.5281/zenodo.4726713 .",,pdf:https://jbiomedsem.biomedcentral.com/track/pdf/10.1186/s13326-021-00249-x; doi:https://doi.org/10.1186/s13326-021-00249-x; html:https://europepmc.org/articles/PMC8383460; pdf:https://europepmc.org/articles/PMC8383460?pdf=render 37270201,https://doi.org/10.1136/heartjnl-2023-322616,Reliability of major bleeding events in UK routine data versus clinical trial adjudicated follow-up data.,"Harper C, Mafham M, Herrington W, Staplin N, Stevens W, Wallendszus K, Haynes R, Landray MJ, Parish S, Bowman L, Armitage J.",,Heart (British Cardiac Society),2023,2023-09-13,Y,"Atherosclerosis; Research Design; Electronic Health Records; Outcome Assessment, Health Care",,,"

Objective

To assess how reliable UK routine data are for ascertaining major bleeding events compared with adjudicated follow-up.

Methods

The ASCEND (A Study of Cardiovascular Events iN Diabetes) primary prevention trial randomised 15 480 UK people with diabetes to aspirin versus matching placebo. The primary safety outcome was major bleeding (including intracranial haemorrhage, sight-threatening eye bleeding, serious gastrointestinal bleeding and other major bleeding (epistaxis, haemoptysis, haematuria, vaginal and other bleeding)) ascertained by direct-participant mail-based follow-up, with >90% of outcomes undergoing adjudication. Nearly all participants were linked to routinely collected hospitalisation and death data (ie, routine data). An algorithm categorised bleeding events from routine data as major/minor. Kappa statistics were used to assess agreement between data sources, and randomised comparisons were re-run using routine data.

Results

When adjudicated follow-up and routine data were compared, there was agreement for 318 major bleeding events, with routine data identifying 281 additional-potential events, and not identifying 241 participant-reported events (kappa 0.53, 95% CI 0.49 to 0.57). Repeating ASCEND's randomised comparisons using routine data only found estimated relative and absolute effects of allocation to aspirin versus placebo on major bleeding similar to adjudicated follow-up (adjudicated follow-up: aspirin 314 (4.1%) vs placebo 245 (3.2%); rate ratio (RR) 1.29, 95% CI 1.09 to 1.52; absolute excess +6.3/5000 person-years (mean SE±2.1); vs routine data: 327 (4.2%) vs 272 (3.5%); RR 1.21, 95% CI 1.03 to 1.41; absolute excess +5.0/5000 (±2.2)).

Conclusions

Analyses of the ASCEND randomised trial found that major bleeding events ascertained via UK routine data sources provided relative and absolute treatment effects similar to adjudicated follow-up.

Trial registration number

ISRCTN60635500; NCT00135226.",,pdf:https://heart.bmj.com/content/heartjnl/early/2023/06/02/heartjnl-2023-322616.full.pdf; doi:https://doi.org/10.1136/heartjnl-2023-322616; html:https://europepmc.org/articles/PMC10511984; pdf:https://europepmc.org/articles/PMC10511984?pdf=render 34939832,https://doi.org/10.1308/rcsann.2021.0206,"Projections for primary hip and knee replacement surgery up to the year 2060: an analysis based on data from The National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.","Matharu GS, Culliford DJ, Blom AW, Judge A.",,Annals of the Royal College of Surgeons of England,2022,2021-12-23,N,Total hip replacement; Total Knee Replacement; Demand; Future Numbers,,,"

Introduction

We estimated the number of primary total hip and knee replacements (THR and TKR) that will need to be performed up to the year 2060.

Methods

We used data from The National Joint Registry for England, Wales, Northern Ireland and the Isle of Man on the volume of primary THRs (n=94,936) and TKRs (n=100,547) performed in 2018. We projected future numbers of THR and TKR using a static estimated rate from 2018 applied to population growth forecast data from the UK Office for National Statistics up to 2060.

Results

By 2060, THR and TKR volume would increase from 2018 levels by an estimated 37.7% (n=130,766) and 36.6% (n=137,341), respectively. For both males and females demand for surgery was also higher for patients aged 70 and over, with older patients having the biggest relative increase in volume over time: 70-79 years (44.6% males, 41.2% females); 80-89 years (112.4% males, 85.6% females); 90 years and older (348.0% males, 198.2% females).

Conclusion

By 2060 demand for hip and knee joint replacement is estimated to increase by almost 40%. Demand will be greatest in older patients (70+ years), which will have significant implications for the health service requiring forward planning given that morbidity and resource use is higher in this population. These issues, coupled with two waves of COVID-19, will impact the ability of health services to deliver timely joint replacement to many patients for a number of years, requiring urgent planning.",,doi:https://doi.org/10.1308/rcsann.2021.0206; html:https://europepmc.org/articles/PMC9157920; pdf:https://europepmc.org/articles/PMC9157920?pdf=render; doi:https://doi.org/10.1308/rcsann.2021.0206 -36814324,https://doi.org/10.1186/s13195-023-01184-y,"Investigating associations between blood metabolites, later life brain imaging measures, and genetic risk for Alzheimer's disease.","Green RE, Lord J, Scelsi MA, Xu J, Wong A, Naomi-James S, Handy A, Gilchrist L, Williams DM, Parker TD, Lane CA, Malone IB, Cash DM, Sudre CH, Coath W, Thomas DL, Keuss S, Dobson R, Legido-Quigley C, Fox NC, Schott JM, Richards M, Proitsi P, Insight 46 study team.",,Alzheimer's research & therapy,2023,2023-02-22,Y,Metabolites; Ageing; Brain imaging; Alzheimer’s disease; Dementia; Birth Cohort; Polygenic Scores; Weighted-gene Coexpression Network Analysis,,,"

Background

Identifying blood-based signatures of brain health and preclinical pathology may offer insights into early disease mechanisms and highlight avenues for intervention. Here, we systematically profiled associations between blood metabolites and whole-brain volume, hippocampal volume, and amyloid-β status among participants of Insight 46-the neuroscience sub-study of the National Survey of Health and Development (NSHD). We additionally explored whether key metabolites were associated with polygenic risk for Alzheimer's disease (AD).

Methods

Following quality control, levels of 1019 metabolites-detected with liquid chromatography-mass spectrometry-were available for 1740 participants at age 60-64. Metabolite data were subsequently clustered into modules of co-expressed metabolites using weighted coexpression network analysis. Accompanying MRI and amyloid-PET imaging data were present for 437 participants (age 69-71). Regression analyses tested relationships between metabolite measures-modules and hub metabolites-and imaging outcomes. Hub metabolites were defined as metabolites that were highly connected within significant (pFDR < 0.05) modules or were identified as a hub in a previous analysis on cognitive function in the same cohort. Regression models included adjustments for age, sex, APOE genotype, lipid medication use, childhood cognitive ability, and social factors. Finally, associations were tested between AD polygenic risk scores (PRS), including and excluding the APOE region, and metabolites and modules that significantly associated (pFDR < 0.05) with an imaging outcome (N = 1638).

Results

In the fully adjusted model, three lipid modules were associated with a brain volume measure (pFDR < 0.05): one enriched in sphingolipids (hippocampal volume: ß = 0.14, 95% CI = [0.055,0.23]), one in several fatty acid pathways (whole-brain volume: ß =  - 0.072, 95%CI = [- 0.12, - 0.026]), and another in diacylglycerols and phosphatidylethanolamines (whole-brain volume: ß =  - 0.066, 95% CI = [- 0.11, - 0.020]). Twenty-two hub metabolites were associated (pFDR < 0.05) with an imaging outcome (whole-brain volume: 22; hippocampal volume: 4). Some nominal associations were reported for amyloid-β, and with an AD PRS in our genetic analysis, but none survived multiple testing correction.

Conclusions

Our findings highlight key metabolites, with functions in membrane integrity and cell signalling, that associated with structural brain measures in later life. Future research should focus on replicating this work and interrogating causality.",,pdf:https://alzres.biomedcentral.com/counter/pdf/10.1186/s13195-023-01184-y; doi:https://doi.org/10.1186/s13195-023-01184-y; html:https://europepmc.org/articles/PMC9945600; pdf:https://europepmc.org/articles/PMC9945600?pdf=render 33174528,https://doi.org/10.3310/hta24570,Antimicrobial-impregnated central venous catheters for preventing neonatal bloodstream infection: the PREVAIL RCT.,"Gilbert R, Brown M, Faria R, Fraser C, Donohue C, Rainford N, Grosso A, Sinha AK, Dorling J, Gray J, Muller-Pebody B, Harron K, Moitt T, McGuire W, Bojke L, Gamble C, Oddie SJ.",,"Health technology assessment (Winchester, England)",2020,2020-11-01,Y,Infant; Newborn; Economic analysis; Central Venous Catheter; Bloodstream Infection; Randomised Controlled Trial; Generalisability; Antimicrobial-impregnated Catheter,,,"

Background

Clinical trials show that antimicrobial-impregnated central venous catheters reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is insufficient evidence for use in newborn babies.

Objectives

The objectives were (1) to determine clinical effectiveness by conducting a randomised controlled trial comparing antimicrobial-impregnated peripherally inserted central venous catheters with standard peripherally inserted central venous catheters for reducing bloodstream or cerebrospinal fluid infections (referred to as bloodstream infections); (2) to conduct an economic evaluation of the costs, cost-effectiveness and value of conducting additional research; and (3) to conduct a generalisability analysis of trial findings to neonatal care in the NHS.

Design

Three separate studies were undertaken, each addressing one of the three objectives. (1) This was a multicentre, open-label, pragmatic randomised controlled trial; (2) an analysis was undertaken of hospital care costs, lifetime cost-effectiveness and value of information from an NHS perspective; and (3) this was a retrospective cohort study of bloodstream infection rates in neonatal units in England.

Setting

The randomised controlled trial was conducted in 18 neonatal intensive care units in England.

Participants

Participants were babies who required a peripherally inserted central venous catheter (of 1 French gauge in size).

Interventions

The interventions were an antimicrobial-impregnated peripherally inserted central venous catheter (coated with rifampicin-miconazole) or a standard peripherally inserted central venous catheter, allocated randomly (1 : 1) using web randomisation.

Main outcome measure

Study 1 - time to first bloodstream infection, sampled between 24 hours after randomisation and 48 hours after peripherally inserted central venous catheter removal. Study 2 - cost-effectiveness of the antimicrobial-impregnated peripherally inserted central venous catheter compared with the standard peripherally inserted central venous catheters. Study 3 - risk-adjusted bloodstream rates in the trial compared with those in neonatal units in England. For study 3, the data used were as follows: (1) case report forms and linked death registrations; (2) case report forms and linked death registrations linked to administrative health records with 6-month follow-up; and (3) neonatal health records linked to infection surveillance data.

Results

Study 1, clinical effectiveness - 861 babies were randomised (antimicrobial-impregnated peripherally inserted central venous catheter, n = 430; standard peripherally inserted central venous catheter, n = 431). Bloodstream infections occurred in 46 babies (10.7%) randomised to antimicrobial-impregnated peripherally inserted central venous catheters and in 44 (10.2%) babies randomised to standard peripherally inserted central venous catheters. No difference in time to bloodstream infection was detected (hazard ratio 1.11, 95% confidence interval 0.73 to 1.67; p = 0.63). Secondary outcomes of rifampicin resistance in positive blood/cerebrospinal fluid cultures, mortality, clinical outcomes at neonatal unit discharge and time to peripherally inserted central venous catheter removal were similar in both groups. Rifampicin resistance in positive peripherally inserted central venous catheter tip cultures was higher in the antimicrobial-impregnated peripherally inserted central venous catheter group (relative risk 3.51, 95% confidence interval 1.16 to 10.57; p = 0.02) than in the standard peripherally inserted central venous catheter group. Adverse events were similar in both groups. Study 2, economic evaluation - the mean cost of babies' hospital care was £83,473. Antimicrobial-impregnated peripherally inserted central venous catheters were not cost-effective. Given the increased price, compared with standard peripherally inserted central venous catheters, the minimum reduction in risk of bloodstream infection for antimicrobial-impregnated peripherally inserted central venous catheters to be cost-effective was 3% and 15% for babies born at 23-27 and 28-32 weeks' gestation, respectively. Study 3, generalisability analysis - risk-adjusted bloodstream infection rates per 1000 peripherally inserted central venous catheter days were similar among babies in the trial and in all neonatal units. Of all bloodstream infections in babies receiving intensive or high-dependency care in neonatal units, 46% occurred during peripherally inserted central venous catheter days.

Limitations

The trial was open label as antimicrobial-impregnated and standard peripherally inserted central venous catheters are different colours. There was insufficient power to determine differences in rifampicin resistance.

Conclusions

No evidence of benefit or harm was found of peripherally inserted central venous catheters impregnated with rifampicin-miconazole during neonatal care. Interventions with small effects on bloodstream infections could be cost-effective over a child's life course. Findings were generalisable to neonatal units in England. Future research should focus on other types of antimicrobial impregnation of peripherally inserted central venous catheters and alternative approaches for preventing bloodstream infections in neonatal care.

Trial registration

Current Controlled Trials ISRCTN81931394.

Funding

This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 57. See the NIHR Journals Library website for further project information.",,pdf:https://njl-admin.nihr.ac.uk/document/download/2034745; html:http://europepmc.org/books/NBK563908; doi:https://doi.org/10.3310/hta24570 37814896,https://doi.org/10.1161/circgen.123.004181,Cardiovascular Disease Knowledge Portal: A Community Resource for Cardiovascular Disease Research.,"Costanzo MC, Roselli C, Brandes M, Duby M, Hoang Q, Jang D, Koesterer R, Kudtarkar P, Moriondo A, Nguyen T, Ruebenacker O, Smadbeck P, Sun Y, Butterworth AS, Aragam KG, Lumbers RT, Khera AV, Lubitz SA, Ellinor PT, Gaulton KJ, Flannick J, Burtt NP.",,Circulation. Genomic and precision medicine,2023,2023-10-10,N,Cardiovascular diseases; Database; Phenotype; Myocardial infarction; Biomarkers; epigenomics,,,,,doi:https://doi.org/10.1161/CIRCGEN.123.004181 +36814324,https://doi.org/10.1186/s13195-023-01184-y,"Investigating associations between blood metabolites, later life brain imaging measures, and genetic risk for Alzheimer's disease.","Green RE, Lord J, Scelsi MA, Xu J, Wong A, Naomi-James S, Handy A, Gilchrist L, Williams DM, Parker TD, Lane CA, Malone IB, Cash DM, Sudre CH, Coath W, Thomas DL, Keuss S, Dobson R, Legido-Quigley C, Fox NC, Schott JM, Richards M, Proitsi P, Insight 46 study team.",,Alzheimer's research & therapy,2023,2023-02-22,Y,Metabolites; Ageing; Brain imaging; Alzheimer’s disease; Dementia; Birth Cohort; Polygenic Scores; Weighted-gene Coexpression Network Analysis,,,"

Background

Identifying blood-based signatures of brain health and preclinical pathology may offer insights into early disease mechanisms and highlight avenues for intervention. Here, we systematically profiled associations between blood metabolites and whole-brain volume, hippocampal volume, and amyloid-β status among participants of Insight 46-the neuroscience sub-study of the National Survey of Health and Development (NSHD). We additionally explored whether key metabolites were associated with polygenic risk for Alzheimer's disease (AD).

Methods

Following quality control, levels of 1019 metabolites-detected with liquid chromatography-mass spectrometry-were available for 1740 participants at age 60-64. Metabolite data were subsequently clustered into modules of co-expressed metabolites using weighted coexpression network analysis. Accompanying MRI and amyloid-PET imaging data were present for 437 participants (age 69-71). Regression analyses tested relationships between metabolite measures-modules and hub metabolites-and imaging outcomes. Hub metabolites were defined as metabolites that were highly connected within significant (pFDR < 0.05) modules or were identified as a hub in a previous analysis on cognitive function in the same cohort. Regression models included adjustments for age, sex, APOE genotype, lipid medication use, childhood cognitive ability, and social factors. Finally, associations were tested between AD polygenic risk scores (PRS), including and excluding the APOE region, and metabolites and modules that significantly associated (pFDR < 0.05) with an imaging outcome (N = 1638).

Results

In the fully adjusted model, three lipid modules were associated with a brain volume measure (pFDR < 0.05): one enriched in sphingolipids (hippocampal volume: ß = 0.14, 95% CI = [0.055,0.23]), one in several fatty acid pathways (whole-brain volume: ß =  - 0.072, 95%CI = [- 0.12, - 0.026]), and another in diacylglycerols and phosphatidylethanolamines (whole-brain volume: ß =  - 0.066, 95% CI = [- 0.11, - 0.020]). Twenty-two hub metabolites were associated (pFDR < 0.05) with an imaging outcome (whole-brain volume: 22; hippocampal volume: 4). Some nominal associations were reported for amyloid-β, and with an AD PRS in our genetic analysis, but none survived multiple testing correction.

Conclusions

Our findings highlight key metabolites, with functions in membrane integrity and cell signalling, that associated with structural brain measures in later life. Future research should focus on replicating this work and interrogating causality.",,pdf:https://alzres.biomedcentral.com/counter/pdf/10.1186/s13195-023-01184-y; doi:https://doi.org/10.1186/s13195-023-01184-y; html:https://europepmc.org/articles/PMC9945600; pdf:https://europepmc.org/articles/PMC9945600?pdf=render 38198570,https://doi.org/10.1126/scitranslmed.adf4428,Prospective study design and data analysis in UK Biobank.,"Allen NE, Lacey B, Lawlor DA, Pell JP, Gallacher J, Smeeth L, Elliott P, Matthews PM, Lyons RA, Whetton AD, Lucassen A, Hurles ME, Chapman M, Roddam AW, Fitzpatrick NK, Hansell AL, Hardy R, Marioni RE, O'Donnell VB, Williams J, Lindgren CM, Effingham M, Sellors J, Danesh J, Collins R.",,Science translational medicine,2024,2024-01-10,N,,,,"Population-based prospective studies, such as UK Biobank, are valuable for generating and testing hypotheses about the potential causes of human disease. We describe how UK Biobank's study design, data access policies, and approaches to statistical analysis can help to minimize error and improve the interpretability of research findings, with implications for other population-based prospective studies being established worldwide.",,pdf:https://www.pure.ed.ac.uk/ws/files/405264227/scitranslmed.adf4428.pdf; doi:https://doi.org/10.1126/scitranslmed.adf4428; html:https://europepmc.org/articles/PMC11127744; pdf:https://europepmc.org/articles/PMC11127744?pdf=render; doi:https://doi.org/10.1126/scitranslmed.adf4428 -36774358,https://doi.org/10.1038/s41467-023-36439-7,Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer.,"Malagoli Tagliazucchi G, Wiecek AJ, Withnell E, Secrier M.",,Nature communications,2023,2023-02-11,Y,,,,"The epithelial to mesenchymal transition (EMT) is a key cellular process underlying cancer progression, with multiple intermediate states whose molecular hallmarks remain poorly characterised. To fill this gap, we present a method to robustly evaluate EMT transformation in individual tumours based on transcriptomic signals. We apply this approach to explore EMT trajectories in 7180 tumours of epithelial origin and identify three macro-states with prognostic and therapeutic value, attributable to epithelial, hybrid E/M and mesenchymal phenotypes. We show that the hybrid state is relatively stable and linked with increased aneuploidy. We further employ spatial transcriptomics and single cell datasets to explore the spatial heterogeneity of EMT transformation and distinct interaction patterns with cytotoxic, NK cells and fibroblasts in the tumour microenvironment. Additionally, we provide a catalogue of genomic events underlying distinct evolutionary constraints on EMT transformation. This study sheds light on the aetiology of distinct stages along the EMT trajectory, and highlights broader genomic and environmental hallmarks shaping the mesenchymal transformation of primary tumours.",,pdf:https://www.nature.com/articles/s41467-023-36439-7.pdf; doi:https://doi.org/10.1038/s41467-023-36439-7; html:https://europepmc.org/articles/PMC9922305; pdf:https://europepmc.org/articles/PMC9922305?pdf=render 34750571,https://doi.org/10.1038/s42255-021-00478-5,Integrative analysis of the plasma proteome and polygenic risk of cardiometabolic diseases.,"Ritchie SC, Lambert SA, Arnold M, Teo SM, Lim S, Scepanovic P, Marten J, Zahid S, Chaffin M, Liu Y, Abraham G, Ouwehand WH, Roberts DJ, Watkins NA, Drew BG, Calkin AC, Di Angelantonio E, Soranzo N, Burgess S, Chapman M, Kathiresan S, Khera AV, Danesh J, Butterworth AS, Inouye M.",,Nature metabolism,2021,2021-11-08,Y,,,,"Cardiometabolic diseases are frequently polygenic in architecture, comprising a large number of risk alleles with small effects spread across the genome1-3. Polygenic scores (PGS) aggregate these into a metric representing an individual's genetic predisposition to disease. PGS have shown promise for early risk prediction4-7 and there is an open question as to whether PGS can also be used to understand disease biology8. Here, we demonstrate that cardiometabolic disease PGS can be used to elucidate the proteins underlying disease pathogenesis. In 3,087 healthy individuals, we found that PGS for coronary artery disease, type 2 diabetes, chronic kidney disease and ischaemic stroke are associated with the levels of 49 plasma proteins. Associations were polygenic in architecture, largely independent of cis and trans protein quantitative trait loci and present for proteins without quantitative trait loci. Over a follow-up of 7.7 years, 28 of these proteins associated with future myocardial infarction or type 2 diabetes events, 16 of which were mediators between polygenic risk and incident disease. Twelve of these were druggable targets with therapeutic potential. Our results demonstrate the potential for PGS to uncover causal disease biology and targets with therapeutic potential, including those that may be missed by approaches utilizing information at a single locus.",,pdf:https://www.nature.com/articles/s42255-021-00478-5.pdf; doi:https://doi.org/10.1038/s42255-021-00478-5; html:https://europepmc.org/articles/PMC8574944; pdf:https://europepmc.org/articles/PMC8574944?pdf=render +36774358,https://doi.org/10.1038/s41467-023-36439-7,Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer.,"Malagoli Tagliazucchi G, Wiecek AJ, Withnell E, Secrier M.",,Nature communications,2023,2023-02-11,Y,,,,"The epithelial to mesenchymal transition (EMT) is a key cellular process underlying cancer progression, with multiple intermediate states whose molecular hallmarks remain poorly characterised. To fill this gap, we present a method to robustly evaluate EMT transformation in individual tumours based on transcriptomic signals. We apply this approach to explore EMT trajectories in 7180 tumours of epithelial origin and identify three macro-states with prognostic and therapeutic value, attributable to epithelial, hybrid E/M and mesenchymal phenotypes. We show that the hybrid state is relatively stable and linked with increased aneuploidy. We further employ spatial transcriptomics and single cell datasets to explore the spatial heterogeneity of EMT transformation and distinct interaction patterns with cytotoxic, NK cells and fibroblasts in the tumour microenvironment. Additionally, we provide a catalogue of genomic events underlying distinct evolutionary constraints on EMT transformation. This study sheds light on the aetiology of distinct stages along the EMT trajectory, and highlights broader genomic and environmental hallmarks shaping the mesenchymal transformation of primary tumours.",,pdf:https://www.nature.com/articles/s41467-023-36439-7.pdf; doi:https://doi.org/10.1038/s41467-023-36439-7; html:https://europepmc.org/articles/PMC9922305; pdf:https://europepmc.org/articles/PMC9922305?pdf=render 30554166,https://doi.org/10.1136/injuryprev-2018-043019,"Work absence due to compensable RTCs in Victoria, Australia.","Gray SE, Gabbe BJ, Collie A.",,Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention,2020,2018-12-15,N,Functional Outcome; Burden Of Disease; Descriptive Epidemiology; Occupational Injury; Motor Vehicle Occupant,,,"

Introduction

RTC burden is commonly measured using fatality or hospitalisation statistics. However, non-fatal and less severe injuries contribute substantial economic and human costs, including work absence. In Victoria, Australia, two major compensation systems provide income support to employed people injured in RTCs; workers' compensation (if RTC occurred during work) and an RTC-specific compensation system. This study aimed to describe the number and rate of episodes of work absence due to compensable RTC and determine factors associated with work-related RTC resulting in work absence.

Methods

Administrative data for working-age people (15-65 years) with accepted compensation claims between 1 July 2003 and 30 June 2013 were extracted from Victoria's Compensation Research Database and analysed. Injured people receiving at least one day of income support were retained. Rate calculations used Victoria's labour force as the denominator and negative binomial regression determined any time-based trend changes. Multivariable logistic regression was used to determine odds of the RTC being work-related.

Results

There were 40 677 claims made by workers with an RTC injury that consequently missed work, averaging 4068 claims per year at a rate of 12.9 per 100 000 working population. Work-related cases contributed 17.4% (N=7061). Males, older adults and RTCs involving heavy vehicles, buses, trains and trams had higher odds of a work-related RTC resulting in work absence. More severe injuries tended not to be work-related.

Conclusions

Work absence due to RTC injury constitutes a substantial burden, and this measure could provide a valuable addition to conventional RTC statistics.",,doi:https://doi.org/10.1136/injuryprev-2018-043019 +33654696,https://doi.org/10.1093/burnst/tkaa044,Venous thromboembolism prophylaxis practice and its association with outcomes in Australia and New Zealand burns patients.,"Tracy LM, Cameron PA, Singer Y, Earnest A, Wood F, Cleland H, Gabbe BJ.",,Burns & trauma,2021,2021-01-01,Y,Australia; New Zealand; Burn injury; Prophylaxis; Venous Thromboembolism,,,"

Background

Patients with burn injuries are considered to have an increased risk of venous thromboembolism (VTE). While untreated VTEs can be fatal, no studies have examined chemoprophylaxis effectiveness. This study aimed to quantify the variation in prevalence of VTE prophylaxis use in patients in Australian and New Zealand burns units and whether prophylaxis use is associated with in-hospital outcomes following burn injury.

Methods

Admission data for adult burns patients (aged ≥16 years) admitted between 1 July 2016 and 31 December 2018 were extracted from the Burns Registry of Australia and New Zealand. Mixed effects logistic regression modelling investigated whether VTE prophylaxis use was associated with the primary outcome of in-hospital mortality.

Results

There were 5066 admissions over the study period. Of these patients, 81% (n = 3799) with a valid response to the VTE prophylaxis data field received some form of VTE prophylaxis. Use of VTE prophylaxis ranged from 48.6% to 94.8% of patients between units. In-hospital death was recorded in <1% of patients (n = 33). After adjusting for confounders, receiving VTE prophylaxis was associated with a decrease in the adjusted odds of in-hospital mortality (adjusted odds ratio = 0.21; 95% CI, 0.07-0.63; p = 0.006).

Conclusions

Variation in the use of VTE prophylaxis was observed between the units, and prophylaxis use was associated with a decrease in the odds of mortality. These findings provide an opportunity to engage with units to further explore differences in prophylaxis use and develop future best practice guidelines.",,pdf:https://academic.oup.com/burnstrauma/article-pdf/doi/10.1093/burnst/tkaa044/37307900/tkaa044.pdf; doi:https://doi.org/10.1093/burnst/tkaa044; html:https://europepmc.org/articles/PMC7901708; pdf:https://europepmc.org/articles/PMC7901708?pdf=render 33837377,https://doi.org/10.1038/s41591-021-01310-z,Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19.,"Gaziano L, Giambartolomei C, Pereira AC, Gaulton A, Posner DC, Swanson SA, Ho YL, Iyengar SK, Kosik NM, Vujkovic M, Gagnon DR, Bento AP, Barrio-Hernandez I, Rönnblom L, Hagberg N, Lundtoft C, Langenberg C, Pietzner M, Valentine D, Gustincich S, Tartaglia GG, Allara E, Surendran P, Burgess S, Zhao JH, Peters JE, Prins BP, Angelantonio ED, Devineni P, Shi Y, Lynch KE, DuVall SL, Garcon H, Thomann LO, Zhou JJ, Gorman BR, Huffman JE, O'Donnell CJ, Tsao PS, Beckham JC, Pyarajan S, Muralidhar S, Huang GD, Ramoni R, Beltrao P, Danesh J, Hung AM, Chang KM, Sun YV, Joseph J, Leach AR, Edwards TL, Cho K, Gaziano JM, Butterworth AS, Casas JP, VA Million Veteran Program COVID-19 Science Initiative.",,Nature medicine,2021,2021-04-09,Y,,,,"Drug repurposing provides a rapid approach to meet the urgent need for therapeutics to address COVID-19. To identify therapeutic targets relevant to COVID-19, we conducted Mendelian randomization analyses, deriving genetic instruments based on transcriptomic and proteomic data for 1,263 actionable proteins that are targeted by approved drugs or in clinical phase of drug development. Using summary statistics from the Host Genetics Initiative and the Million Veteran Program, we studied 7,554 patients hospitalized with COVID-19 and >1 million controls. We found significant Mendelian randomization results for three proteins (ACE2, P = 1.6 × 10-6; IFNAR2, P = 9.8 × 10-11 and IL-10RB, P = 2.3 × 10-14) using cis-expression quantitative trait loci genetic instruments that also had strong evidence for colocalization with COVID-19 hospitalization. To disentangle the shared expression quantitative trait loci signal for IL10RB and IFNAR2, we conducted phenome-wide association scans and pathway enrichment analysis, which suggested that IFNAR2 is more likely to play a role in COVID-19 hospitalization. Our findings prioritize trials of drugs targeting IFNAR2 and ACE2 for early management of COVID-19.",,pdf:https://www.nature.com/articles/s41591-021-01310-z.pdf; doi:https://doi.org/10.1038/s41591-021-01310-z; html:https://europepmc.org/articles/PMC7612986; pdf:https://europepmc.org/articles/PMC7612986?pdf=render 36082306,https://doi.org/10.1016/j.xgen.2021.100004,Workshop proceedings: GWAS summary statistics standards and sharing.,"MacArthur JAL, Buniello A, Harris LW, Hayhurst J, McMahon A, Sollis E, Cerezo M, Hall P, Lewis E, Whetzel PL, Bahcall OG, Barroso I, Carroll RJ, Inouye M, Manolio TA, Rich SS, Hindorff LA, Wiley K, Parkinson H.",,Cell genomics,2021,2021-10-01,Y,,,,"Genome-wide association studies (GWASs) have enabled robust mapping of complex traits in humans. The open sharing of GWAS summary statistics (SumStats) is essential in facilitating the larger meta-analyses needed for increased power in resolving the genetic basis of disease. However, most GWAS SumStats are not readily accessible because of limited sharing and a lack of defined standards. With the aim of increasing the availability, quality, and utility of GWAS SumStats, the National Human Genome Research Institute-European Bioinformatics Institute (NHGRI-EBI) GWAS Catalog organized a community workshop to address the standards, infrastructure, and incentives required to promote and enable sharing. We evaluated the barriers to SumStats sharing, both technological and sociological, and developed an action plan to address those challenges and ensure that SumStats and study metadata are findable, accessible, interoperable, and reusable (FAIR). We encourage early deposition of datasets in the GWAS Catalog as the recognized central repository. We recommend standard requirements for reporting elements and formats for SumStats and accompanying metadata as guidelines for community standards and a basis for submission to the GWAS Catalog. Finally, we provide recommendations to enable, promote, and incentivize broader data sharing, standards and FAIRness in order to advance genomic medicine.",,doi:https://doi.org/10.1016/j.xgen.2021.100004; doi:https://doi.org/10.1016/j.xgen.2021.100004; html:https://europepmc.org/articles/PMC9451133; pdf:https://europepmc.org/articles/PMC9451133?pdf=render -33654696,https://doi.org/10.1093/burnst/tkaa044,Venous thromboembolism prophylaxis practice and its association with outcomes in Australia and New Zealand burns patients.,"Tracy LM, Cameron PA, Singer Y, Earnest A, Wood F, Cleland H, Gabbe BJ.",,Burns & trauma,2021,2021-01-01,Y,Australia; New Zealand; Burn injury; Prophylaxis; Venous Thromboembolism,,,"

Background

Patients with burn injuries are considered to have an increased risk of venous thromboembolism (VTE). While untreated VTEs can be fatal, no studies have examined chemoprophylaxis effectiveness. This study aimed to quantify the variation in prevalence of VTE prophylaxis use in patients in Australian and New Zealand burns units and whether prophylaxis use is associated with in-hospital outcomes following burn injury.

Methods

Admission data for adult burns patients (aged ≥16 years) admitted between 1 July 2016 and 31 December 2018 were extracted from the Burns Registry of Australia and New Zealand. Mixed effects logistic regression modelling investigated whether VTE prophylaxis use was associated with the primary outcome of in-hospital mortality.

Results

There were 5066 admissions over the study period. Of these patients, 81% (n = 3799) with a valid response to the VTE prophylaxis data field received some form of VTE prophylaxis. Use of VTE prophylaxis ranged from 48.6% to 94.8% of patients between units. In-hospital death was recorded in <1% of patients (n = 33). After adjusting for confounders, receiving VTE prophylaxis was associated with a decrease in the adjusted odds of in-hospital mortality (adjusted odds ratio = 0.21; 95% CI, 0.07-0.63; p = 0.006).

Conclusions

Variation in the use of VTE prophylaxis was observed between the units, and prophylaxis use was associated with a decrease in the odds of mortality. These findings provide an opportunity to engage with units to further explore differences in prophylaxis use and develop future best practice guidelines.",,pdf:https://academic.oup.com/burnstrauma/article-pdf/doi/10.1093/burnst/tkaa044/37307900/tkaa044.pdf; doi:https://doi.org/10.1093/burnst/tkaa044; html:https://europepmc.org/articles/PMC7901708; pdf:https://europepmc.org/articles/PMC7901708?pdf=render 37477760,https://doi.org/10.1007/s10875-023-01547-y,Immunologic and Genetic Contributors to CD46-Dependent Immune Dysregulation.,"Meyer BJ, Kunz N, Seki S, Higgins R, Ghosh A, Hupfer R, Baldrich A, Hirsiger JR, Jauch AJ, Burgener AV, Lötscher J, Aschwanden M, Dickenmann M, Stegert M, Berger CT, Daikeler T, Heijnen I, Navarini AA, Rudin C, Yamamoto H, Kemper C, Hess C, Recher M.",,Journal of clinical immunology,2023,2023-07-21,Y,SLE; systemic lupus erythematosus; Next-generation Sequencing; Penetrance; Atypical Hemolytic Uremic Syndrome; Cd46; Haploinsufficiency; Ahus; Inborn Errors Of Immunity; Primary Immunodeficiency Complement,,,"Mutations in CD46 predispose to atypical hemolytic uremic syndrome (aHUS) with low penetrance. Factors driving immune-dysregulatory disease in individual mutation carriers have remained ill-understood. In addition to its role as a negative regulator of the complement system, CD46 modifies T cell-intrinsic metabolic adaptation and cytokine production. Comparative immunologic analysis of diseased vs. healthy CD46 mutation carriers has not been performed in detail yet. In this study, we comprehensively analyzed clinical, molecular, immune-phenotypic, cytokine secretion, immune-metabolic, and genetic profiles in healthy vs. diseased individuals carrying a rare, heterozygous CD46 mutation identified within a large single family. Five out of six studied individuals carried a CD46 gene splice-site mutation causing an in-frame deletion of 21 base pairs. One child suffered from aHUS and his paternal uncle manifested with adult-onset systemic lupus erythematosus (SLE). Three mutation carriers had no clinical evidence of CD46-related disease to date. CD4+ T cell-intrinsic CD46 expression was uniformly 50%-reduced but was comparable in diseased vs. healthy mutation carriers. Reconstitution experiments defined the 21-base pair-deleted CD46 variant as intracellularly-but not surface-expressed and haploinsufficient. Both healthy and diseased mutation carriers displayed reduced CD46-dependent T cell mitochondrial adaptation. Diseased mutation carriers had lower peripheral regulatory T cell (Treg) frequencies and carried potentially epistatic, private rare variants in other inborn errors of immunity (IEI)-associated proinflammatory genes, not found in healthy mutation carriers. In conclusion, low Treg and rare non-CD46 immune-gene variants may contribute to clinically manifest CD46 haploinsufficiency-associated immune-dysregulation.",,pdf:https://link.springer.com/content/pdf/10.1007/s10875-023-01547-y.pdf; doi:https://doi.org/10.1007/s10875-023-01547-y; html:https://europepmc.org/articles/PMC10661731; pdf:https://europepmc.org/articles/PMC10661731?pdf=render 36944376,https://doi.org/10.1098/rsob.220373,"The lipid linked oligosaccharide polymerase Wzy and its regulating co-polymerase, Wzz, from enterobacterial common antigen biosynthesis form a complex.","Weckener M, Woodward LS, Clarke BR, Liu H, Ward PN, Le Bas A, Bhella D, Whitfield C, Naismith JH.",,Open biology,2023,2023-03-22,Y,Oligosaccharides; Lipid; Regulating; Polymerase; Wzy,,,"The enterobacterial common antigen (ECA) is a carbohydrate polymer that is associated with the cell envelope in the Enterobacteriaceae. ECA contains a repeating trisaccharide which is polymerized by WzyE, a member of the Wzy membrane protein polymerase superfamily. WzyE activity is regulated by a membrane protein polysaccharide co-polymerase, WzzE. Förster resonance energy transfer experiments demonstrate that WzyE and WzzE from Pectobacterium atrosepticum form a complex in vivo, and immunoblotting and cryo-electron microscopy (cryo-EM) analysis confirm a defined stoichiometry of approximately eight WzzE to one WzyE. Low-resolution cryo-EM reconstructions of the complex, aided by an antibody recognizing the C-terminus of WzyE, reveals WzyE sits in the central membrane lumen formed by the octameric arrangement of the transmembrane helices of WzzE. The pairing of Wzy and Wzz is found in polymerization systems for other bacterial polymers, including lipopolysaccharide O-antigens and capsular polysaccharides. The data provide new structural insight into a conserved mechanism for regulating polysaccharide chain length in bacteria.",,doi:https://doi.org/10.1098/rsob.220373; doi:https://doi.org/10.1098/rsob.220373; html:https://europepmc.org/articles/PMC10030265; pdf:https://europepmc.org/articles/PMC10030265?pdf=render 34396190,https://doi.org/10.1016/j.jaccao.2019.09.007,Cancer Therapy-Related Cardiac Dysfunction of Nonanthracycline Chemotherapeutics: What Is the Evidence?,"Kamphuis JAM, Linschoten M, Cramer MJ, Gort EH, van Rhenen A, Asselbergs FW, Doevendans PA, Teske AJ.",,JACC. CardioOncology,2019,2019-12-17,Y,"Cardiomyopathy; Heart Failure; Risk Prediction; Fda, Food And Drug Administration; Hf, Heart Failure; Mmc, Mitomycin C; Alkylating Therapy; Ctrcd, Cancer Therapy–Related Cardiac Dysfunction",,,"Cancer therapy-related cardiac dysfunction (CTRCD) is one of the most concerning cardiovascular side effects of cancer treatment. Important reviews within the field of cardio-oncology have described various agents to be associated with a high risk of CTRCD, including mitomycin C, ifosfamide, vincristine, cyclophosphamide, and clofarabine. The aim of this study was to provide insight into the data on which these incidence rates are based. We observed that the reported cardiotoxicity of mitomycin C and ifosfamide is based on studies in which most patients received anthracyclines, complicating the interpretation of their association with CTRCD. The high incidence of vincristine-induced cardiotoxicity is based on an incorrect interpretation of a single study. Incidence rates of clofarabine remain uncertain due to a lack of cardiac screening in clinical trials. The administration of high-dose cyclophosphamide (>1.5 g/m2/day) is associated with a high incidence of CTRCD. Based on our findings, a critical re-evaluation of the cardiotoxicity of these agents is warranted.",,doi:https://doi.org/10.1016/j.jaccao.2019.09.007; doi:https://doi.org/10.1016/j.jaccao.2019.09.007; html:https://europepmc.org/articles/PMC8352330; pdf:https://europepmc.org/articles/PMC8352330?pdf=render 33072403,https://doi.org/10.1186/s40959-020-00079-3,Early- and late anthracycline-induced cardiac dysfunction: echocardiographic characterization and response to heart failure therapy.,"Kamphuis JAM, Linschoten M, Cramer MJ, Doevendans PA, Asselbergs FW, Teske AJ.",,"Cardio-oncology (London, England)",2020,2020-10-13,Y,Heart Failure; Anthracyclines; Cardiac Dysfunction; Cardiac Effects Of Cancer Treatment,,,"

Background

Anthracycline-induced cardiac dysfunction (ACD) is a notorious side effect of anticancer treatment. It has been described as a phenomenon of a continuous progressive decline of cardiac function, eventually leading to dilated cardiomyopathy (DCM). This progressive nature suggests that patients with a delayed ACD diagnosis have greater compromise of cardiac function and more adverse remodeling, with a poor response to heart failure (HF) treatment. This study aimed to delineate the impact of a delayed ACD diagnosis on echocardiographic characteristics and response to HF treatment.

Methods and results

From the population of our cardio-oncology outpatient clinic, 92 ACD patients were included in this study (age 51.6 ± 16.2 years, median cumulative anthracycline dose 329 [200-329] mg/m2), and a median follow-up of 25.0 [9.6-37.2] months after ACD diagnosis. Median time to ACD diagnosis for patients diagnosed early (< 1 year) and late (> 1 year) was 4.0 vs. 47.7 months respectively. There were no echocardiographic differences between patients diagnosed early vs. late (LVEF 43.6 ± 4.9% vs. 43.0 ± 6.2% and iEDV 63.6 vs. 62.9 mL/m2). Eighty-three percent of patients presented with mild LV dysfunction and in 79% the LV was not dilated. Patients diagnosed early were more likely to have (partial) recovery of cardiac function upon HF treatment initiation (p = 0.015).

Conclusions

In the setting of a cardio-oncology outpatient clinic, patients with ACD presented with a hypokinetic non-dilated cardiomyopathy, rather than typical DCM. Timing of ACD diagnosis did not impact HF disease severity. However, in patients receiving an early diagnosis, cardiac function was more likely to recover upon HF treatment.",,pdf:https://cardiooncologyjournal.biomedcentral.com/track/pdf/10.1186/s40959-020-00079-3; doi:https://doi.org/10.1186/s40959-020-00079-3; html:https://europepmc.org/articles/PMC7557080; pdf:https://europepmc.org/articles/PMC7557080?pdf=render 32810544,https://doi.org/10.1016/j.ijcard.2020.08.030,The relation between VLDL-cholesterol and risk of cardiovascular events in patients with manifest cardiovascular disease.,"Heidemann BE, Koopal C, Bots ML, Asselbergs FW, Westerink J, Visseren FLJ.",,International journal of cardiology,2021,2020-08-15,N,Inflammation; Vascular disease; Major Adverse Cardiovascular Events; Non-hdl-c; Vldl-c; Triglyceride Rich Lipoproteins,,,"

Introduction

Apolipoprotein B containing lipoproteins are atherogenic. There is evidence that with low plasma low density lipoprotein cholesterol (LDL-C) levels residual vascular risk might be caused by triglyceride rich lipoproteins such as very-low density lipoproteins (VLDL), chylomicrons and their remnants. We investigated the relationship between VLDL-cholesterol (VLDL-C) and recurrent major adverse cardiovascular events (MACE), major adverse limb events (MALE) and all-cause mortality in a cohort of patients with cardiovascular disease.

Methods

Prospective cohort study in 8057 patients with cardiovascular disease from the UCC-SMART study. The relation between calculated VLDL-C levels and the occurrence of MACE, MALE and all-cause mortality was analyzed with Cox regression models.

Results

Patients mean age was 60 ± 10 years, 74% were male, 4894 (61%) had coronary artery disease, 2445 (30%) stroke, 1425 (18%) peripheral arterial disease and 684 (8%) patients had an abdominal aorta aneurysm at baseline. A total of 1535 MACE, 571 MALE and 1792 deaths were observed during a median follow up of 8.2 years (interquartile range 4.512.2). VLDL-C was not associated with risk of MACE or all-cause mortality. In the highest quartile of VLDL-C the risk was higher for major adverse limb events (MALE) (HR 1.49; 95%CI 1.16-1.93) compared to the lowest quartile, after adjustment for confounders including LDL-C and lipid lowering medication.

Conclusion

In patients with clinically manifest cardiovascular disease plasma VLDL-C confers an increased risk for MALE, but not for MACE and all-cause mortality, independent of established risk factors including LDL-C and lipid-lowering medication.",,pdf:http://www.internationaljournalofcardiology.com/article/S0167527320335579/pdf; doi:https://doi.org/10.1016/j.ijcard.2020.08.030 -34756707,https://doi.org/10.1016/j.evalprogplan.2021.102019,"How practitioner, organisational and system-level factors act to influence health promotion evaluation capacity: Validation of a conceptual framework.","Schwarzman J, Bauman A, Gabbe BJ, Rissel C, Shilton T, Smith BJ.",,Evaluation and program planning,2022,2021-10-20,N,Path analysis; Primary Prevention; Health Promotion; Confirmatory Factor Analysis; Evaluation Capacity,,,"The need to improve the practice and quality of evaluation in the health promotion and disease prevention field is widely recognised. In order to plan, implement and evaluate health promotion evaluation capacity building efforts, there is a need to better understand the practitioner, organisational and system-level determinants of evaluation capacity and practice. This study aimed to assess the validity Evaluation Practice Analysis Survey (EPAS) constructs using confirmatory factor analysis and validate a conceptual framework of health promotion evaluation capacity using path analysis. Experienced Australian health promotion practitioners completed the survey (n = 219). Twenty-one of the original 23 EPAS scales were assessed as reliable and valid. The final model was found to have good fit (χ214 = 18.72, p = 0.18, root mean square error of approximation = 0.04, 90% CI 0.00-0.82, Comparative Fit Index = 1.00, standardised root mean square residual = 0.04). This model supports the role of the organisation in facilitating evaluation practice through leadership, culture, systems, support and resources. It builds on existing frameworks from other fields to incorporate political, funding and administrative factors. This study provides an evidence-based model of evaluation capacity that organisations, funders and policy makers can use to plan and implement more effective evaluation capacity building strategies within organisations and the wider prevention field.",,doi:https://doi.org/10.1016/j.evalprogplan.2021.102019 31816119,https://doi.org/10.1002/sim.8443,Dynamic predictive probabilities to monitor rapid cystic fibrosis disease progression.,"Szczesniak RD, Su W, Brokamp C, Keogh RH, Pestian JP, Seid M, Diggle PJ, Clancy JP.",,Statistics in medicine,2020,2019-12-09,Y,Longitudinal Data Analysis; Medical Monitoring; Nonstationary Process; Nowcasting; Predictive Probability Distributions,Understanding the Causes of Disease,,"Cystic fibrosis (CF) is a progressive, genetic disease characterized by frequent, prolonged drops in lung function. Accurately predicting rapid underlying lung-function decline is essential for clinical decision support and timely intervention. Determining whether an individual is experiencing a period of rapid decline is complicated due to its heterogeneous timing and extent, and error component of the measured lung function. We construct individualized predictive probabilities for ""nowcasting"" rapid decline. We assume each patient's true longitudinal lung function, S(t), follows a nonlinear, nonstationary stochastic process, and accommodate between-patient heterogeneity through random effects. Corresponding lung-function decline at time t is defined as the rate of change, S'(t). We predict S'(t) conditional on observed covariate and measurement history by modeling a measured lung function as a noisy version of S(t). The method is applied to data on 30 879 US CF Registry patients. Results are contrasted with a currently employed decision rule using single-center data on 212 individuals. Rapid decline is identified earlier using predictive probabilities than the center's currently employed decision rule (mean difference: 0.65 years; 95% confidence interval (CI): 0.41, 0.89). We constructed a bootstrapping algorithm to obtain CIs for predictive probabilities. We illustrate real-time implementation with R Shiny. Predictive accuracy is investigated using empirical simulations, which suggest this approach more accurately detects peak decline, compared with a uniform threshold of rapid decline. Median area under the ROC curve estimates (Q1-Q3) were 0.817 (0.814-0.822) and 0.745 (0.741-0.747), respectively, implying reasonable accuracy for both. This article demonstrates how individualized rate of change estimates can be coupled with probabilistic predictive inference and implementation for a useful medical-monitoring approach.",The objective of this paper was to construct individualised dynamic predictive probabilities to monitor rapid Cystic Fibrosis (CF) disease progression. The results demonstrated how individualised rate of change estimates can be coupled with probabilitic predictive inference and implementation for a useful medical-monitoring approach.,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/sim.8443; doi:https://doi.org/10.1002/sim.8443; html:https://europepmc.org/articles/PMC7028099; pdf:https://europepmc.org/articles/PMC7028099?pdf=render -38609437,https://doi.org/10.1038/s41746-024-01062-3,"Self-supervised learning for human activity recognition using 700,000 person-days of wearable data.","Yuan H, Chan S, Creagh AP, Tong C, Acquah A, Clifton DA, Doherty A.",,NPJ digital medicine,2024,2024-04-12,Y,,,,"Accurate physical activity monitoring is essential to understand the impact of physical activity on one's physical health and overall well-being. However, advances in human activity recognition algorithms have been constrained by the limited availability of large labelled datasets. This study aims to leverage recent advances in self-supervised learning to exploit the large-scale UK Biobank accelerometer dataset-a 700,000 person-days unlabelled dataset-in order to build models with vastly improved generalisability and accuracy. Our resulting models consistently outperform strong baselines across eight benchmark datasets, with an F1 relative improvement of 2.5-130.9% (median 24.4%). More importantly, in contrast to previous reports, our results generalise across external datasets, cohorts, living environments, and sensor devices. Our open-sourced pre-trained models will be valuable in domains with limited labelled data or where good sampling coverage (across devices, populations, and activities) is hard to achieve.",,pdf:https://www.nature.com/articles/s41746-024-01062-3.pdf; doi:https://doi.org/10.1038/s41746-024-01062-3; html:https://europepmc.org/articles/PMC11015005; pdf:https://europepmc.org/articles/PMC11015005?pdf=render +34756707,https://doi.org/10.1016/j.evalprogplan.2021.102019,"How practitioner, organisational and system-level factors act to influence health promotion evaluation capacity: Validation of a conceptual framework.","Schwarzman J, Bauman A, Gabbe BJ, Rissel C, Shilton T, Smith BJ.",,Evaluation and program planning,2022,2021-10-20,N,Path analysis; Primary Prevention; Health Promotion; Confirmatory Factor Analysis; Evaluation Capacity,,,"The need to improve the practice and quality of evaluation in the health promotion and disease prevention field is widely recognised. In order to plan, implement and evaluate health promotion evaluation capacity building efforts, there is a need to better understand the practitioner, organisational and system-level determinants of evaluation capacity and practice. This study aimed to assess the validity Evaluation Practice Analysis Survey (EPAS) constructs using confirmatory factor analysis and validate a conceptual framework of health promotion evaluation capacity using path analysis. Experienced Australian health promotion practitioners completed the survey (n = 219). Twenty-one of the original 23 EPAS scales were assessed as reliable and valid. The final model was found to have good fit (χ214 = 18.72, p = 0.18, root mean square error of approximation = 0.04, 90% CI 0.00-0.82, Comparative Fit Index = 1.00, standardised root mean square residual = 0.04). This model supports the role of the organisation in facilitating evaluation practice through leadership, culture, systems, support and resources. It builds on existing frameworks from other fields to incorporate political, funding and administrative factors. This study provides an evidence-based model of evaluation capacity that organisations, funders and policy makers can use to plan and implement more effective evaluation capacity building strategies within organisations and the wider prevention field.",,doi:https://doi.org/10.1016/j.evalprogplan.2021.102019 37907686,https://doi.org/10.1038/s41397-023-00317-8,British South Asian ancestry participants views of pharmacogenomics clinical implementation and research: a thematic analysis.,"Magavern EF, Durrani F, Raza M, Lerner R, Islam MR, Genes & Health Research Team, Clinch M, Caulfield MJ.",,The pharmacogenomics journal,2023,2023-11-01,Y,,,,"

Background

South Asian ancestry populations are underrepresented in genomic studies and therapeutics trials. British South Asians suffer from multi-morbidity leading to polypharmacy. Our objective was to elucidate British South Asian ancestry community perspectives on pharmacogenomic implementation and sharing pharmacogenomic clinical data for research.

Methods

Four focus groups were conducted (9-12 participants in each). Two groups were mixed gender, while one group was male only and one was female only. Simultaneous interpretation was available to participants in Urdu and Bengali. Focus groups were recorded and abridged transcription and thematic analysis were undertaken.

Results

There were 42 participants, 64% female. 26% were born in the UK or Europe. 52% were born in Bangladesh and 17% in Pakistan. 36% reported university level education. Implementation of pharmacogenomics was perceived to be beneficial to individuals but pose a risk of overburdening resource limited systems. Pharmacogenomic research was perceived to be beneficial to the community, with concerns about data privacy and misuse. Data sharing was desirable if the researchers did not have a financial stake, and benefits would be shared. Trust was the key condition for the acceptability of both clinical implementation and research. Trust was linked with medication compliance. Education, outreach, and communication facilitate trust.

Conclusions (significance and impact of the study)

Pharmacogenomics implementation with appropriate education and communication has the potential to enhance trust and contribute to increased medication compliance. Trust drives data sharing, which would enable enhanced representation in research. Representation in scientific evidence base could cyclically enhance trust and compliance.",,doi:https://doi.org/10.1038/s41397-023-00317-8; html:https://europepmc.org/articles/PMC10661738; pdf:https://europepmc.org/articles/PMC10661738?pdf=render +38609437,https://doi.org/10.1038/s41746-024-01062-3,"Self-supervised learning for human activity recognition using 700,000 person-days of wearable data.","Yuan H, Chan S, Creagh AP, Tong C, Acquah A, Clifton DA, Doherty A.",,NPJ digital medicine,2024,2024-04-12,Y,,,,"Accurate physical activity monitoring is essential to understand the impact of physical activity on one's physical health and overall well-being. However, advances in human activity recognition algorithms have been constrained by the limited availability of large labelled datasets. This study aims to leverage recent advances in self-supervised learning to exploit the large-scale UK Biobank accelerometer dataset-a 700,000 person-days unlabelled dataset-in order to build models with vastly improved generalisability and accuracy. Our resulting models consistently outperform strong baselines across eight benchmark datasets, with an F1 relative improvement of 2.5-130.9% (median 24.4%). More importantly, in contrast to previous reports, our results generalise across external datasets, cohorts, living environments, and sensor devices. Our open-sourced pre-trained models will be valuable in domains with limited labelled data or where good sampling coverage (across devices, populations, and activities) is hard to achieve.",,pdf:https://www.nature.com/articles/s41746-024-01062-3.pdf; doi:https://doi.org/10.1038/s41746-024-01062-3; html:https://europepmc.org/articles/PMC11015005; pdf:https://europepmc.org/articles/PMC11015005?pdf=render 32247548,https://doi.org/10.1016/j.tips.2020.03.003,Electronic Health Records to Predict Gestational Diabetes Risk.,"Mateen BA, David AL, Denaxas S.",,Trends in pharmacological sciences,2020,2020-04-01,N,Artificial intelligence; Gestational Diabetes Mellitus; Machine Learning; Risk Prediction; Electronic Health Records,,,"Gestational diabetes mellitus is a common pregnancy complication associated with significant adverse health outcomes for both women and infants. Effective screening and early prediction tools as part of routine clinical care are needed to reduce the impact of the disease on the baby and mother. Using large-scale electronic health records, Artzi and colleagues developed and evaluated a machine learning driven tool to identify women at high and low risk of GDM. Their findings showcase how artificial intelligence approaches can potentially be embedded in clinical care to enable accurate and rapid risk stratification.",,pdf:https://discovery.ucl.ac.uk/10097090/3/Denaxas_Electronic%20Health%20Records%20to%20Predict%20Gestational%20Diabetes%20Risk_AAM.pdf; doi:https://doi.org/10.1016/j.tips.2020.03.003 31965568,https://doi.org/10.1002/bjs.11433,Impact of bariatric surgery on cardiovascular outcomes and mortality: a population-based cohort study.,"Singh P, Subramanian A, Adderley N, Gokhale K, Singhal R, Bellary S, Nirantharakumar K, Tahrani AA.",,The British journal of surgery,2020,2020-01-21,N,,,,"

Background

Cohort studies have shown that bariatric surgery may reduce the incidence of and mortality from cardiovascular disease (CVD), but studies using real-world data are limited. This study examined the impact of bariatric surgery on incident CVD, hypertension and atrial fibrillation, and all-cause mortality.

Methods

A retrospective, matched, controlled cohort study of The Health Improvement Network primary care database (from 1 January 1990 to 31 January 2018) was performed (approximately 6 per cent of the UK population). Adults with a BMI of 30 kg/m2 or above who did not have gastric cancer were included as the exposed group. Each exposed patient, who had undergone bariatric surgery, was matched for age, sex, BMI and presence of type 2 diabetes mellitus (T2DM) with two controls who had not had bariatric surgery.

Results

A total of 5170 exposed and 9995 control participants were included; their mean(s.d.) age was 45·3(10·5) years and 21·5 per cent (3265 of 15 165 participants) had T2DM. Median follow-up was 3·9 (i.q.r. 1·8- 6·4) years. Mean(s.d.) percentage weight loss was 20·0(13·2) and 0·8(9·5) per cent in exposed and control groups respectively. Overall, bariatric surgery was not associated with a significantly lower CVD risk (adjusted hazard ratio (HR) 0·80; 95 per cent c.i. 0·62 to 1·02; P = 0·074). Only in the gastric bypass group was a significant impact on CVD observed (HR 0·53, 0·34 to 0·81; P = 0·003). Bariatric surgery was associated with significant reduction in all-cause mortality (adjusted HR 0·70, 0·55 to 0·89; P = 0·004), hypertension (adjusted HR 0·41, 0·34 to 0·50; P < 0·001) and heart failure (adjusted HR 0·57, 0·34 to 0·96; P = 0·033). Outcomes were similar in patients with and those without T2DM (exposed versus controls), except for incident atrial fibrillation, which was reduced in the T2DM group.

Conclusion

Bariatric surgery is associated with a reduced risk of hypertension, heart failure and mortality, compared with routine care. Gastric bypass was associated with reduced risk of CVD compared to routine care.",,pdf:https://academic.oup.com/bjs/article-pdf/107/4/432/36117941/bjs11433.pdf; doi:https://doi.org/10.1002/bjs.11433 37280096,https://doi.org/10.1136/thorax-2023-220057,"Asthma symptoms, spirometry and air pollution exposure in schoolchildren in an informal settlement and an affluent area of Nairobi, Kenya.","Meme H, Amukoye E, Bowyer C, Chakaya J, Das D, Dobson R, Dragosits U, Fuld J, Gray C, Hahn M, Kiplimo R, Lesosky M, Loh MM, McKendree J, Mortimer K, Ndombi A, Netter L, Obasi A, Orina F, Pearson C, Price H, Quint JK, Semple S, Twigg M, Waelde C, Walnycki A, Warwick M, Wendler J, West SE, Wilson M, Zurba L, Devereux G.",,Thorax,2023,2023-06-06,Y,Asthma; Paediatric Asthma; Asthma Epidemiology,,,"

Background

Although 1 billion people live in informal (slum) settlements, the consequences for respiratory health of living in these settlements remain largely unknown. This study investigated whether children living in an informal settlement in Nairobi, Kenya are at increased risk of asthma symptoms.

Methods

Children attending schools in Mukuru (an informal settlement in Nairobi) and a more affluent area (Buruburu) were compared. Questionnaires quantified respiratory symptoms and environmental exposures; spirometry was performed; personal exposure to particulate matter (PM2.5) was estimated.

Results

2373 children participated, 1277 in Mukuru (median age, IQR 11, 9-13 years, 53% girls), and 1096 in Buruburu (10, 8-12 years, 52% girls). Mukuru schoolchildren were from less affluent homes, had greater exposure to pollution sources and PM2.5. When compared with Buruburu schoolchildren, Mukuru schoolchildren had a greater prevalence of symptoms, 'current wheeze' (9.5% vs 6.4%, p=0.007) and 'trouble breathing' (16.3% vs 12.6%, p=0.01), and these symptoms were more severe and problematic. Diagnosed asthma was more common in Buruburu (2.8% vs 1.2%, p=0.004). Spirometry did not differ between Mukuru and Buruburu. Regardless of community, significant adverse associations were observed with self-reported exposure to 'vapours, dusts, gases, fumes', mosquito coil burning, adult smoker(s) in the home, refuse burning near homes and residential proximity to roads.

Conclusion

Children living in informal settlements are more likely to develop wheezing symptoms consistent with asthma that are more severe but less likely to be diagnosed as asthma. Self-reported but not objectively measured air pollution exposure was associated with increased risk of asthma symptoms.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2023/05/24/thorax-2023-220057.full.pdf; doi:https://doi.org/10.1136/thorax-2023-220057; html:https://europepmc.org/articles/PMC10715514; pdf:https://europepmc.org/articles/PMC10715514?pdf=render @@ -1705,8 +1705,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 31168069,https://doi.org/10.1038/s41380-019-0439-8,"The genomic basis of mood instability: identification of 46 loci in 363,705 UK Biobank participants, genetic correlation with psychiatric disorders, and association with gene expression and function.","Ward J, Tunbridge EM, Sandor C, Lyall LM, Ferguson A, Strawbridge RJ, Lyall DM, Cullen B, Graham N, Johnston KJA, Webber C, Escott-Price V, O'Donovan M, Pell JP, Bailey MES, Harrison PJ, Smith DJ.",,Molecular psychiatry,2020,2019-06-05,Y,,,,"Genome-wide association studies (GWAS) of psychiatric phenotypes have tended to focus on categorical diagnoses, but to understand the biology of mental illness it may be more useful to study traits which cut across traditional boundaries. Here, we report the results of a GWAS of mood instability as a trait in a large population cohort (UK Biobank, n = 363,705). We also assess the clinical and biological relevance of the findings, including whether genetic associations show enrichment for nervous system pathways. Forty six unique loci associated with mood instability were identified with a SNP heritability estimate of 9%. Linkage Disequilibrium Score Regression (LDSR) analyses identified genetic correlations with Major Depressive Disorder (MDD), Bipolar Disorder (BD), Schizophrenia, anxiety, and Post Traumatic Stress Disorder (PTSD). Gene-level and gene set analyses identified 244 significant genes and 6 enriched gene sets. Tissue expression analysis of the SNP-level data found enrichment in multiple brain regions, and eQTL analyses highlighted an inversion on chromosome 17 plus two brain-specific eQTLs. In addition, we used a Phenotype Linkage Network (PLN) analysis and community analysis to assess for enrichment of nervous system gene sets using mouse orthologue databases. The PLN analysis found enrichment in nervous system PLNs for a community containing serotonin and melatonin receptors. In summary, this work has identified novel loci, tissues and gene sets contributing to mood instability. These findings may be relevant for the identification of novel trans-diagnostic drug targets and could help to inform future stratified medicine innovations in mental health.",,pdf:https://eprints.gla.ac.uk/185493/1/185493.pdf; doi:https://doi.org/10.1038/s41380-019-0439-8; html:https://europepmc.org/articles/PMC7116257; pdf:https://europepmc.org/articles/PMC7116257?pdf=render 32238333,https://doi.org/10.2196/16400,Low-Density Lipoprotein Cholesterol Target Attainment in Patients With Established Cardiovascular Disease: Analysis of Routine Care Data.,"Groenhof TKJ, Kofink D, Bots ML, Nathoe HM, Hoefer IE, Van Solinge WW, Lely AT, Asselbergs FW, Haitjema S.",,JMIR medical informatics,2020,2020-04-02,Y,LDL-C; Cardiovascular Risk Management; Learning Health Care System; Routine Clinical Data,Better Care,cardiovascular,"

Background

Direct feedback on quality of care is one of the key features of a learning health care system (LHS), enabling health care professionals to improve upon the routine clinical care of their patients during practice.

Objective

This study aimed to evaluate the potential of routine care data extracted from electronic health records (EHRs) in order to obtain reliable information on low-density lipoprotein cholesterol (LDL-c) management in cardiovascular disease (CVD) patients referred to a tertiary care center.

Methods

We extracted all LDL-c measurements from the EHRs of patients with a history of CVD referred to the University Medical Center Utrecht. We assessed LDL-c target attainment at the time of referral and per year. In patients with multiple measurements, we analyzed LDL-c trajectories, truncated at 6 follow-up measurements. Lastly, we performed a logistic regression analysis to investigate factors associated with improvement of LDL-c at the next measurement.

Results

Between February 2003 and December 2017, 250,749 LDL-c measurements were taken from 95,795 patients, of whom 23,932 had a history of CVD. At the time of referral, 51% of patients had not reached their LDL-c target. A large proportion of patients (55%) had no follow-up LDL-c measurements. Most of the patients with repeated measurements showed no change in LDL-c levels over time: the transition probability to remain in the same category was up to 0.84. Sequence clustering analysis showed more women (odds ratio 1.18, 95% CI 1.07-1.10) in the cluster with both most measurements off target and the most LDL-c measurements furthest from the target. Timing of drug prescription was difficult to determine from our data, limiting the interpretation of results regarding medication management.

Conclusions

Routine care data can be used to provide feedback on quality of care, such as LDL-c target attainment. These routine care data show high off-target prevalence and little change in LDL-c over time. Registrations of diagnosis; follow-up trajectory, including primary and secondary care; and medication use need to be improved in order to enhance usability of the EHR system for adequate feedback.",,pdf:https://medinform.jmir.org/2020/4/e16400/PDF; doi:https://doi.org/10.2196/16400; html:https://europepmc.org/articles/PMC7163416 35385889,https://doi.org/10.1515/dmpt-2021-0104,Prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.,"Al-Rubaish AM, Al-Muhanna FA, Alshehri AM, Alsulaiman AA, Alabdulali MM, Alkhamis F, Alamri AS, Alali RA, Akhtar MS, Cyrus C, Claassens DMF, Asselbergs FW, Al-Ali AK.",,Drug metabolism and personalized therapy,2021,2021-07-08,N,Genotyping; Stroke; aspirin; Clopidogrel; Cyp2c19*2,,,"

Objectives

To mitigate the incidence of recurrent stroke in patients, dual antiplatelet therapy comprising aspirin and clopidogrel is usually administered. Clopidogrel is a prodrug and its bioactivation is catalyzed by cytochrome P450 (CYP)2C19. The main objective of this work was to determine the prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and assess the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.

Methods

This prospective (2018-2019) study was conducted on 256 patients (age 61 ± 12.5) clinically diagnosed with ischemic stroke who were genotyped using Spartan RX CYP2C19 assay.

Results

From the total patient group (256), upon admission, 210 patients were prescribed either aspirin, clopidogrel or dual antiplatelet therapy. Of the 27 patients with the CYP2C19*2 allele who were prescribed clopidogrel (18) or dual antiplatelet therapy (9), only 21 patients could be followed up for a period of six months post stroke event, in addition to 21 age- and sex-matched patients with the normal allele. The CYP2C19*2 allele carriers had a statistically significant increased risk of recurrent stroke compared to patients carrying the normal allele.

Conclusions

This study shows the suitability of using genotyping to guide antiplatelet therapy in ischemic stroke patients in a clinical setting.",,pdf:https://discovery.ucl.ac.uk/10135735/1/Asselbergs_10.1515_dmdi-2021-0104.pdf; doi:https://doi.org/10.1515/dmpt-2021-0104 -38115587,https://doi.org/10.1089/neu.2023.0464,The Australian Traumatic Brain Injury Initiative: Systematic Review of Predictive Value of Biological Markers for People With Moderate-Severe Traumatic Brain Injury.,"Bagg MK, Hellewell SC, Keeves J, Antonic-Baker A, McKimmie A, Hicks AJ, Gadowski A, Newcombe VFJ, Barlow KM, Balogh ZJ, Ross JP, Law M, Caeyenberghs K, Parizel PM, Thorne J, Papini M, Gill G, Jefferson A, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Gabbe BJ, Fitzgerald M.",,Journal of neurotrauma,2024,2024-03-08,N,"Tomography, X-ray computed; Tissues; Biomarkers; Magnetic Resonance Imaging; Body Fluids; Common Data Elements; Brain Injuries, Traumatic; Systematic Review [Publication Type]",,,"The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to co-design a data resource to predict outcomes for people with moderate-severe traumatic brain injury (TBI) across Australia. Fundamental to this resource is the data dictionary, which is an ontology of data items. Here, we report the systematic review and consensus process for inclusion of biological markers in the data dictionary. Standardized database searches were implemented from inception through April 2022. English-language studies evaluating association between a fluid, tissue, or imaging marker and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Records were screened using a prioritization algorithm and saturation threshold in Research Screener. Full-length records were then screened in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association, and high-value predictors were discussed in a consensus process. Searches retrieved 106,593 records; 1,417 full-length records were screened, resulting in 546 included records. Two hundred thirty-nine individual markers were extracted, evaluated against 101 outcomes. Forty-one markers were judged to be high-value predictors of 15 outcomes. Fluid markers retained following the consensus process included ubiquitin C-terminal hydrolase L1 (UCH-L1), S100, and glial fibrillary acidic protein (GFAP). Imaging markers included computed tomography (CT) scores (e.g., Marshall scores), pathological observations (e.g., hemorrhage, midline shift), and magnetic resonance imaging (MRI) classification (e.g., diffuse axonal injury). Clinical context and time of sampling of potential predictive indicators are important considerations for utility. This systematic review and consensus process has identified fluid and imaging biomarkers with high predictive value of clinical and long-term outcomes following moderate-severe TBI.",,doi:https://doi.org/10.1089/neu.2023.0464 34237806,https://doi.org/10.1515/dmdi-2021-0104,Prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.,"Al-Rubaish AM, Al-Muhanna FA, Alshehri AM, Alsulaiman AA, Alabdulali MM, Alkhamis F, Alamri AS, Alali RA, Akhtar MS, Cyrus C, Claassens DMF, Asselbergs FW, Al-Ali AK.",,Drug metabolism and personalized therapy,2021,2021-07-08,N,Genotyping; Stroke; aspirin; Clopidogrel; Cyp2c19*2,,,"

Objectives

To mitigate the incidence of recurrent stroke in patients, dual antiplatelet therapy comprising aspirin and clopidogrel is usually administered. Clopidogrel is a prodrug and its bioactivation is catalyzed by cytochrome P450 (CYP)2C19. The main objective of this work was to determine the prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and assess the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.

Methods

This prospective (2018-2019) study was conducted on 256 patients (age 61 ± 12.5) clinically diagnosed with ischemic stroke who were genotyped using Spartan RX CYP2C19 assay.

Results

From the total patient group (256), upon admission, 210 patients were prescribed either aspirin, clopidogrel or dual antiplatelet therapy. Of the 27 patients with the CYP2C19*2 allele who were prescribed clopidogrel (18) or dual antiplatelet therapy (9), only 21 patients could be followed up for a period of six months post stroke event, in addition to 21 age- and sex-matched patients with the normal allele. The CYP2C19*2 allele carriers had a statistically significant increased risk of recurrent stroke compared to patients carrying the normal allele.

Conclusions

This study shows the suitability of using genotyping to guide antiplatelet therapy in ischemic stroke patients in a clinical setting.",,pdf:https://discovery.ucl.ac.uk/10135735/1/Asselbergs_10.1515_dmdi-2021-0104.pdf; doi:https://doi.org/10.1515/dmdi-2021-0104 +38115587,https://doi.org/10.1089/neu.2023.0464,The Australian Traumatic Brain Injury Initiative: Systematic Review of Predictive Value of Biological Markers for People With Moderate-Severe Traumatic Brain Injury.,"Bagg MK, Hellewell SC, Keeves J, Antonic-Baker A, McKimmie A, Hicks AJ, Gadowski A, Newcombe VFJ, Barlow KM, Balogh ZJ, Ross JP, Law M, Caeyenberghs K, Parizel PM, Thorne J, Papini M, Gill G, Jefferson A, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Gabbe BJ, Fitzgerald M.",,Journal of neurotrauma,2024,2024-03-08,N,"Tomography, X-ray computed; Tissues; Biomarkers; Magnetic Resonance Imaging; Body Fluids; Common Data Elements; Brain Injuries, Traumatic; Systematic Review [Publication Type]",,,"The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to co-design a data resource to predict outcomes for people with moderate-severe traumatic brain injury (TBI) across Australia. Fundamental to this resource is the data dictionary, which is an ontology of data items. Here, we report the systematic review and consensus process for inclusion of biological markers in the data dictionary. Standardized database searches were implemented from inception through April 2022. English-language studies evaluating association between a fluid, tissue, or imaging marker and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Records were screened using a prioritization algorithm and saturation threshold in Research Screener. Full-length records were then screened in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association, and high-value predictors were discussed in a consensus process. Searches retrieved 106,593 records; 1,417 full-length records were screened, resulting in 546 included records. Two hundred thirty-nine individual markers were extracted, evaluated against 101 outcomes. Forty-one markers were judged to be high-value predictors of 15 outcomes. Fluid markers retained following the consensus process included ubiquitin C-terminal hydrolase L1 (UCH-L1), S100, and glial fibrillary acidic protein (GFAP). Imaging markers included computed tomography (CT) scores (e.g., Marshall scores), pathological observations (e.g., hemorrhage, midline shift), and magnetic resonance imaging (MRI) classification (e.g., diffuse axonal injury). Clinical context and time of sampling of potential predictive indicators are important considerations for utility. This systematic review and consensus process has identified fluid and imaging biomarkers with high predictive value of clinical and long-term outcomes following moderate-severe TBI.",,doi:https://doi.org/10.1089/neu.2023.0464 32907797,https://doi.org/10.1136/bmj.m3210,Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI Extension.,"Rivera SC, Liu X, Chan AW, Denniston AK, Calvert MJ, SPIRIT-AI and CONSORT-AI Working Group.",,BMJ (Clinical research ed.),2020,2020-09-09,Y,,,,"The SPIRIT 2013 (The Standard Protocol Items: Recommendations for Interventional Trials) statement aims to improve the completeness of clinical trial protocol reporting, by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there is a growing recognition that interventions involving artificial intelligence need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes.The SPIRIT-AI extension is a new reporting guideline for clinical trials protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI. Both guidelines were developed using a staged consensus process, involving a literature review and expert consultation to generate 26 candidate items, which were consulted on by an international multi-stakeholder group in a 2-stage Delphi survey (103 stakeholders), agreed on in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants).The SPIRIT-AI extension includes 15 new items, which were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations around the handling of input and output data, the human-AI interaction and analysis of error cases.SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer-reviewers, as well as the general readership, to understand, interpret and critically appraise the design and risk of bias for a planned clinical trial.",,pdf:https://www.bmj.com/content/bmj/370/bmj.m3210.full.pdf; doi:https://doi.org/10.1136/bmj.m3210; html:https://europepmc.org/articles/PMC7490785 32900377,https://doi.org/10.1186/s12916-020-01754-z,Going on up to the SPIRIT in AI: will new reporting guidelines for clinical trials of AI interventions improve their rigour?,"Wicks P, Liu X, Denniston AK.",,BMC medicine,2020,2020-09-09,Y,Artificial intelligence; Checklist; Clinical Trial; Machine Learning; Reporting Guidelines,,,,,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-020-01754-z; doi:https://doi.org/10.1186/s12916-020-01754-z; html:https://europepmc.org/articles/PMC7487816; pdf:https://europepmc.org/articles/PMC7487816?pdf=render 34535985,https://doi.org/10.1002/hep4.1805,Genome-Wide Association Study of NAFLD Using Electronic Health Records.,"Fairfield CJ, Drake TM, Pius R, Bretherick AD, Campbell A, Clark DW, Fallowfield JA, Hayward C, Henderson NC, Joshi PK, Mills NL, Porteous DJ, Ramachandran P, Semple RK, Shaw CA, Sudlow CLM, Timmers PRHJ, Wilson JF, Wigmore SJ, Harrison EM, Spiliopoulou A.",,Hepatology communications,2022,2021-09-17,Y,,,,"Genome-wide association studies (GWAS) have identified several risk loci for nonalcoholic fatty liver disease (NAFLD). Previous studies have largely relied on small sample sizes and have assessed quantitative traits. We performed a case-control GWAS in the UK Biobank using recorded diagnosis of NAFLD based on diagnostic codes recommended in recent consensus guidelines. We performed a GWAS of 4,761 cases of NAFLD and 373,227 healthy controls without evidence of NAFLD. Sensitivity analyses were performed excluding other co-existing hepatic pathology, adjusting for body mass index (BMI) and adjusting for alcohol intake. A total of 9,723,654 variants were assessed by logistic regression adjusted for age, sex, genetic principal components, and genotyping batch. We performed a GWAS meta-analysis using available summary association statistics. Six risk loci were identified (P < 5*10-8 ) (apolipoprotein E [APOE], patatin-like phospholipase domain containing 3 [PNPLA3, transmembrane 6 superfamily member 2 [TM6SF2], glucokinase regulator [GCKR], mitochondrial amidoxime reducing component 1 [MARC1], and tribbles pseudokinase 1 [TRIB1]). All loci retained significance in sensitivity analyses without co-existent hepatic pathology and after adjustment for BMI. PNPLA3 and TM6SF2 remained significant after adjustment for alcohol (alcohol intake was known in only 158,388 individuals), with others demonstrating consistent direction and magnitude of effect. All six loci were significant on meta-analysis. Rs429358 (P = 2.17*10-11 ) is a missense variant within the APOE gene determining ϵ4 versus ϵ2/ϵ3 alleles. The ϵ4 allele of APOE offered protection against NAFLD (odds ratio for heterozygotes 0.84 [95% confidence interval 0.78-0.90] and homozygotes 0.64 [0.50-0.79]). Conclusion: This GWAS replicates six known NAFLD-susceptibility loci and confirms that the ϵ4 allele of APOE is associated with protection against NAFLD. The results are consistent with published GWAS using histological and radiological measures of NAFLD, confirming that NAFLD identified through diagnostic codes from consensus guidelines is a valid alternative to more invasive and costly approaches.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep4.1805; doi:https://doi.org/10.1002/hep4.1805; html:https://europepmc.org/articles/PMC8793997; pdf:https://europepmc.org/articles/PMC8793997?pdf=render @@ -1731,24 +1731,24 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 34980174,https://doi.org/10.1186/s12967-021-03210-9,"Increased burden of cardiovascular disease in people with liver disease: unequal geographical variations, risk factors and excess years of life lost.","Chang WH, Mueller SH, Chung SC, Foster GR, Lai AG.",,Journal of translational medicine,2022,2022-01-03,Y,liver disease; Geographical variations; incidence; Cardiovascular Risk; Electronic Health Records; Years Of Life Lost,,,"

Background

People with liver disease are at increased risk of developing cardiovascular disease (CVD), however, there has yet been an investigation of incidence burden, risk, and premature mortality across a wide range of liver conditions and cardiovascular outcomes.

Methods

We employed population-wide electronic health records (EHRs; from 1998 to 2020) consisting of almost 4 million adults to assess regional variations in disease burden of five liver conditions, alcoholic liver disease (ALD), autoimmune liver disease, chronic hepatitis B infection (HBV), chronic hepatitis C infection (HCV) and NAFLD, in England. We analysed regional differences in incidence rates for 17 manifestations of CVD in people with or without liver disease. The associations between biomarkers and comorbidities and risk of CVD in patients with liver disease were estimated using Cox models. For each liver condition, we estimated excess years of life lost (YLL) attributable to CVD (i.e., difference in YLL between people with or without CVD).

Results

The age-standardised incidence rate for any liver disease was 114.5 per 100,000 person years. The highest incidence was observed in NAFLD (85.5), followed by ALD (24.7), HCV (6.0), HBV (4.1) and autoimmune liver disease (3.7). Regionally, the North West and North East regions consistently exhibited high incidence burden. Age-specific incidence rate analyses revealed that the peak incidence for liver disease of non-viral aetiology is reached in individuals aged 50-59 years. Patients with liver disease had a two-fold higher incidence burden of CVD (2634.6 per 100,000 persons) compared to individuals without liver disease (1339.7 per 100,000 persons). When comparing across liver diseases, atrial fibrillation was the most common initial CVD presentation while hypertrophic cardiomyopathy was the least common. We noted strong positive associations between body mass index and current smoking and risk of CVD. Patients who also had diabetes, hypertension, proteinuric kidney disease, chronic kidney disease, diverticular disease and gastro-oesophageal reflex disorders had a higher risk of CVD, as do patients with low albumin, raised C-reactive protein and raised International Normalized Ratio levels. All types of CVD were associated with shorter life expectancies. When evaluating excess YLLs by age of CVD onset and by liver disease type, differences in YLLs, when comparing across CVD types, were more pronounced at younger ages.

Conclusions

We developed a public online app ( https://lailab.shinyapps.io/cvd_in_liver_disease/ ) to showcase results interactively. We provide a blueprint that revealed previously underappreciated clinical factors related to the risk of CVD, which differed in the magnitude of effects across liver diseases. We found significant geographical variations in the burden of liver disease and CVD, highlighting the need to devise local solutions. Targeted policies and regional initiatives addressing underserved communities might help improve equity of access to CVD screening and treatment.",,pdf:https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/s12967-021-03210-9; doi:https://doi.org/10.1186/s12967-021-03210-9; html:https://europepmc.org/articles/PMC8722174; pdf:https://europepmc.org/articles/PMC8722174?pdf=render 31312209,https://doi.org/10.3389/fgene.2019.00567,Use of Pharmacogenetic Drugs by the Dutch Population.,"Alshabeeb MA, Deneer VHM, Khan A, Asselbergs FW.",,Frontiers in genetics,2019,2019-07-02,Y,CYP2C19; CYP2D6; Pharmacogenetics; Adrs; Slco1b1; Preemptive Genetic Testing,Better Care,,"

Introduction

The Dutch Pharmacogenetics Working Group (DPWG) indicated a list of actionable genotypes that affect patients' response to more 50 drugs; these drugs which show variable effects based on patients' genetic traits were named as pharmacogenetics (PGX) drugs. Preemptive genetic testing before using these drugs may protect certain patients from serious adverse reactions and could help in avoiding treatment failures. The objectives of this study include identifying the rate of PGX drug usage among Dutch population, estimating the level of users who carry the actionable genotypes and determining the main genes involved in drug's effect variability.

Methods

Usage of PGX drugs over 2011-2017 by the insured population (an average of 11.4 million) in outpatient clinics in Netherlands was obtained from the publically available GIP databank. The data of 45 drugs were analyzed and their interactions with selected pharmacogenes were estimated. Frequency of actionable genotypes of 249 Dutch parents was obtained from the public database: Genome of Netherlands (GoNL), to identify the pattern of genetic characteristics of Dutch population.

Results

Over a 7 year period, 51.3 million exposures of patients to PGX drugs were reported with an average of 5.3 exposures per each drug user. One quarterof the exposures (12.4 million) are predicted to be experienced by individuals with actionable genotypes (risky exposures). Up to 60% of the risky exposures (around 7.5 million) were related to drugs metabolized by CYP2D6. SLCO1B1, and CYP2C19 were also identified among the top genes affecting response of drugs users (involved in about 22 and 12.4% of the risky exposures, respectively). Cardiovascular medications were the top prescribed PGX drug class (43%), followed by gastroenterology (29%) and psychiatry/neurology medications (15%). Women use more PGX drugs than men (55.8 vs. 44.2%, respectively) with the majority (84%) of users in both sexes are above 45 years.

Conclusion

PGX drugs are commonly used in Netherlands. Preemptive panel testing for CYP2D6, SLCO1B1, and CYP2C19 only could be useful to predict 95% of vulnerable patients' exposures to PGX drugs. Future studies to assess the economic impact of preemptive panel testing on patients of older age are suggested.",,pdf:https://www.frontiersin.org/articles/10.3389/fgene.2019.00567/pdf; doi:https://doi.org/10.3389/fgene.2019.00567; html:https://europepmc.org/articles/PMC6614185; pdf:https://europepmc.org/articles/PMC6614185?pdf=render 33933530,https://doi.org/10.1016/j.jinf.2021.04.027,Early observations on the impact of a healthcare worker COVID-19 vaccination programme at a major UK tertiary centre.,"Garvey MI, Wilkinson MAC, Holden E, Shields A, Robertson A, Richter A, Ball S.",,The Journal of infection,2021,2021-04-29,Y,Vaccination; Healthcare Workers; Lateral Flow; Covid-19,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081749; doi:https://doi.org/10.1016/j.jinf.2021.04.027; html:https://europepmc.org/articles/PMC8081749; pdf:https://europepmc.org/articles/PMC8081749?pdf=render -38082486,https://doi.org/10.1681/asn.0000000000000271,"Effects of Empagliflozin on Fluid Overload, Weight, and Blood Pressure in CKD.","Mayne KJ, Staplin N, Keane DF, Wanner C, Brenner S, Cejka V, Stegbauer J, Judge PK, Preiss D, Emberson J, Trinca D, Dayanandan R, Lee R, Nolan J, Omata A, Green JB, Cherney DZI, Hooi LS, Pontremoli R, Tuttle KR, Lees JS, Mark PB, Davies SJ, Hauske SJ, Steubl D, Brückmann M, Landray MJ, Baigent C, Haynes R, Herrington WG, EMPA-KIDNEY Collaborative Group.",,Journal of the American Society of Nephrology : JASN,2024,2023-12-12,Y,,,,"

Significance statement

SGLT2 inhibitors reduce risk of kidney progression, AKI, and cardiovascular disease, but the mechanisms of benefit are incompletely understood. Bioimpedance spectroscopy can estimate body water and fat mass. One quarter of the EMPA-KIDNEY bioimpedance substudy CKD population had clinically significant levels of bioimpedance-derived ""Fluid Overload"" at recruitment. Empagliflozin induced a prompt and sustained reduction in ""Fluid Overload,"" irrespective of sex, diabetes, and baseline N-terminal pro B-type natriuretic peptide or eGFR. No significant effect on bioimpedance-derived fat mass was observed. The effects of SGLT2 inhibitors on body water may be one of the contributing mechanisms by which they mediate effects on cardiovascular risk.

Background

CKD is associated with fluid excess that can be estimated by bioimpedance spectroscopy. We aimed to assess effects of sodium glucose co-transporter 2 inhibition on bioimpedance-derived ""Fluid Overload"" and adiposity in a CKD population.

Methods

EMPA-KIDNEY was a double-blind placebo-controlled trial of empagliflozin 10 mg once daily in patients with CKD at risk of progression. In a substudy, bioimpedance measurements were added to the main trial procedures at randomization and at 2- and 18-month follow-up visits. The substudy's primary outcome was the study-average difference in absolute ""Fluid Overload"" (an estimate of excess extracellular water) analyzed using a mixed model repeated measures approach.

Results

The 660 substudy participants were broadly representative of the 6609-participant trial population. Substudy mean baseline absolute ""Fluid Overload"" was 0.4±1.7 L. Compared with placebo, the overall mean absolute ""Fluid Overload"" difference among those allocated empagliflozin was -0.24 L (95% confidence interval [CI], -0.38 to -0.11), with similar sized differences at 2 and 18 months, and in prespecified subgroups. Total body water differences comprised between-group differences in extracellular water of -0.49 L (95% CI, -0.69 to -0.30, including the -0.24 L ""Fluid Overload"" difference) and a -0.30 L (95% CI, -0.57 to -0.03) difference in intracellular water. There was no significant effect of empagliflozin on bioimpedance-derived adipose tissue mass (-0.28 kg [95% CI, -1.41 to 0.85]). The between-group difference in weight was -0.7 kg (95% CI, -1.3 to -0.1).

Conclusions

In a broad range of patients with CKD, empagliflozin resulted in a sustained reduction in a bioimpedance-derived estimate of fluid overload, with no statistically significant effect on fat mass.

Trial registration

Clinicaltrials.gov: NCT03594110 ; EuDRACT: 2017-002971-24 ( https://eudract.ema.europa.eu/ ).",,doi:https://doi.org/10.1681/ASN.0000000000000271; html:https://europepmc.org/articles/PMC7615589; pdf:https://europepmc.org/articles/PMC7615589?pdf=render 34040552,https://doi.org/10.3389/fpsyt.2021.627996,Optimising a Simple Fully Convolutional Network for Accurate Brain Age Prediction in the PAC 2019 Challenge.,"Gong W, Beckmann CF, Vedaldi A, Smith SM, Peng H.",,Frontiers in psychiatry,2021,2021-05-10,Y,Brain imaging; Predictive Analysis; Big Data; Deep Learning; Convolution Neural Network; Brain Age Prediction,,,"Brain age prediction from brain MRI scans not only helps improve brain ageing modelling generally, but also provides benchmarks for predictive analysis methods. Brain-age delta, which is the difference between a subject's predicted age and true age, has become a meaningful biomarker for the health of the brain. Here, we report the details of our brain age prediction models and results in the Predictive Analysis Challenge 2019. The aim of the challenge was to use T1-weighted brain MRIs to predict a subject's age in multicentre datasets. We apply a lightweight deep convolutional neural network architecture, Simple Fully Convolutional Neural Network (SFCN), and combined several techniques including data augmentation, transfer learning, model ensemble, and bias correction for brain age prediction. The model achieved first place in both of the two objectives in the PAC 2019 brain age prediction challenge: Mean absolute error (MAE) = 2.90 years without bias removal (Second Place = 3.09 yrs; Third Place = 3.33 yrs), and MAE = 2.95 years with bias removal, leading by a large margin (Second Place = 3.80 yrs; Third Place = 3.92 yrs).",,pdf:https://www.frontiersin.org/articles/10.3389/fpsyt.2021.627996/pdf; doi:https://doi.org/10.3389/fpsyt.2021.627996; html:https://europepmc.org/articles/PMC8141616; pdf:https://europepmc.org/articles/PMC8141616?pdf=render 33824163,https://doi.org/10.3399/bjgp20x714161,Post-bariatric surgery nutritional follow-up in primary care: a population-based cohort study.,"Parretti HM, Subramanian A, Adderley NJ, Abbott S, Tahrani AA, Nirantharakumar K.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2021,2021-05-27,Y,Nutrition; Followup; Cohort studies; General Practice; Bariatric Surgery; The Health Improvement Network,,,"

Background

Bariatric surgery is the most effective treatment for severe obesity. However, without recommended follow-up it has long-term risks.

Aim

To investigate whether nutritional and weight monitoring in primary care meets current clinical guidance, after patients are discharged from specialist bariatric care.

Design and setting

Retrospective cohort study in primary care practices contributing to IQVIA Medical Research Data in the UK (1 January 2000 to 17 January 2018).

Method

Participants were adults who had had bariatric surgery with a minimum of 3 years' follow-up post-surgery, as this study focused on patients discharged from specialist care (at 2 years post-surgery). Outcomes were the annual proportion of patients from 2 years post-surgery with a record of recommended nutritional screening blood tests, weight measurement, and prescription of nutritional supplements, and the proportions with nutritional deficiencies based on blood tests.

Results

A total of 3137 participants were included in the study, and median follow-up post-surgery was 5.7 (4.2-7.6) years. Between 45% and 59% of these patients had an annual weight measurement. The greatest proportions of patients with a record of annual nutritional blood tests were for tests routinely conducted in primary care, for example, recorded haemoglobin measurement varied between 44.9% (n = 629/1400) and 61.2% (n = 653/1067). Annual proportions of blood tests specific to bariatric surgery were low, for example, recorded copper measurement varied between 1.2% (n = 10/818) and 1.5% (n = 16/1067) where recommended. Results indicated that the most common deficiency was anaemia. Annual proportions of patients with prescriptions for recommended nutritional supplements were low.

Conclusion

This study suggests that patients who have bariatric surgery are not receiving the recommended nutritional monitoring after discharge from specialist care. GPs and patients should be supported to engage with follow-up care. Future research should aim to understand the reasons underpinning these findings.",,pdf:https://bjgp.org/content/bjgp/71/707/e441.full.pdf; doi:https://doi.org/10.3399/bjgp20X714161; html:https://europepmc.org/articles/PMC8041293; pdf:https://europepmc.org/articles/PMC8041293?pdf=render 30444743,https://doi.org/10.1097/ccm.0000000000003424,"Risk Factors for 1-Year Mortality and Hospital Utilization Patterns in Critical Care Survivors: A Retrospective, Observational, Population-Based Data Linkage Study.","Szakmany T, Walters AM, Pugh R, Battle C, Berridge DM, Lyons RA.",,Critical care medicine,2019,2019-01-01,N,,,,"

Objectives

Clear understanding of the long-term consequences of critical care survivorship is essential. We investigated the care process and individual factors associated with long-term mortality among ICU survivors and explored hospital use in this group.

Design

Population-based data linkage study using the Secure Anonymised Information Linkage databank.

Setting

All ICUs between 2006 and 2013 in Wales, United Kingdom.

Patients

We identified 40,631 patients discharged alive from Welsh adult ICUs.

Interventions

None.

Measurements and main results

Primary outcome was 365-day survival. The secondary outcomes were 30- and 90-day survival and hospital utilization in the 365 days following ICU discharge. Kaplan-Meier curves were plotted to compare survival rates. Cox proportional hazards regression models were used to determine risk factors of mortality. Seven-thousand eight-hundred eighty-three patients (19.4%) died during the 1-year follow-up period. In the multivariable Cox regression analysis, advanced age and comorbidities were significant determinants of long-term mortality. Expedited discharge due to ICU bed shortage was associated with higher risk. The rate of hospitalization in the year prior to the critical care admission was 28 hospitalized days/1,000 d; post critical care was 88 hospitalized days/1,000 d for those who were still alive; and 57 hospitalized days/1,000 d and 412 hospitalized days/1,000 d for those who died by the end of the study, respectively.

Conclusions

One in five ICU survivors die within 1 year, with advanced age and comorbidity being significant predictors of outcome, leading to high resource use. Care process factors indicating high system stress were associated with increased risk. More detailed understanding is needed on the effects of the potentially modifiable factors to optimize service delivery and improve long-term outcomes of the critically ill.",,pdf:https://europepmc.org/articles/pmc6330072?pdf=render; doi:https://doi.org/10.1097/CCM.0000000000003424; html:https://europepmc.org/articles/PMC6330072; pdf:https://europepmc.org/articles/PMC6330072?pdf=render; doi:https://doi.org/10.1097/ccm.0000000000003424 +38082486,https://doi.org/10.1681/asn.0000000000000271,"Effects of Empagliflozin on Fluid Overload, Weight, and Blood Pressure in CKD.","Mayne KJ, Staplin N, Keane DF, Wanner C, Brenner S, Cejka V, Stegbauer J, Judge PK, Preiss D, Emberson J, Trinca D, Dayanandan R, Lee R, Nolan J, Omata A, Green JB, Cherney DZI, Hooi LS, Pontremoli R, Tuttle KR, Lees JS, Mark PB, Davies SJ, Hauske SJ, Steubl D, Brückmann M, Landray MJ, Baigent C, Haynes R, Herrington WG, EMPA-KIDNEY Collaborative Group.",,Journal of the American Society of Nephrology : JASN,2024,2023-12-12,Y,,,,"

Significance statement

SGLT2 inhibitors reduce risk of kidney progression, AKI, and cardiovascular disease, but the mechanisms of benefit are incompletely understood. Bioimpedance spectroscopy can estimate body water and fat mass. One quarter of the EMPA-KIDNEY bioimpedance substudy CKD population had clinically significant levels of bioimpedance-derived ""Fluid Overload"" at recruitment. Empagliflozin induced a prompt and sustained reduction in ""Fluid Overload,"" irrespective of sex, diabetes, and baseline N-terminal pro B-type natriuretic peptide or eGFR. No significant effect on bioimpedance-derived fat mass was observed. The effects of SGLT2 inhibitors on body water may be one of the contributing mechanisms by which they mediate effects on cardiovascular risk.

Background

CKD is associated with fluid excess that can be estimated by bioimpedance spectroscopy. We aimed to assess effects of sodium glucose co-transporter 2 inhibition on bioimpedance-derived ""Fluid Overload"" and adiposity in a CKD population.

Methods

EMPA-KIDNEY was a double-blind placebo-controlled trial of empagliflozin 10 mg once daily in patients with CKD at risk of progression. In a substudy, bioimpedance measurements were added to the main trial procedures at randomization and at 2- and 18-month follow-up visits. The substudy's primary outcome was the study-average difference in absolute ""Fluid Overload"" (an estimate of excess extracellular water) analyzed using a mixed model repeated measures approach.

Results

The 660 substudy participants were broadly representative of the 6609-participant trial population. Substudy mean baseline absolute ""Fluid Overload"" was 0.4±1.7 L. Compared with placebo, the overall mean absolute ""Fluid Overload"" difference among those allocated empagliflozin was -0.24 L (95% confidence interval [CI], -0.38 to -0.11), with similar sized differences at 2 and 18 months, and in prespecified subgroups. Total body water differences comprised between-group differences in extracellular water of -0.49 L (95% CI, -0.69 to -0.30, including the -0.24 L ""Fluid Overload"" difference) and a -0.30 L (95% CI, -0.57 to -0.03) difference in intracellular water. There was no significant effect of empagliflozin on bioimpedance-derived adipose tissue mass (-0.28 kg [95% CI, -1.41 to 0.85]). The between-group difference in weight was -0.7 kg (95% CI, -1.3 to -0.1).

Conclusions

In a broad range of patients with CKD, empagliflozin resulted in a sustained reduction in a bioimpedance-derived estimate of fluid overload, with no statistically significant effect on fat mass.

Trial registration

Clinicaltrials.gov: NCT03594110 ; EuDRACT: 2017-002971-24 ( https://eudract.ema.europa.eu/ ).",,doi:https://doi.org/10.1681/ASN.0000000000000271; html:https://europepmc.org/articles/PMC7615589; pdf:https://europepmc.org/articles/PMC7615589?pdf=render 33036417,https://doi.org/10.3390/ijerph17197320,"Prognostic Role of Demographic, Injury and Claim Factors in Disabling Pain and Mental Health Conditions 12 Months after Compensable Injury.","Nguyen TL, Baker KS, Ioannou L, Hassani-Mahmooei B, Gibson SJ, Collie A, Ponsford J, Cameron PA, Gabbe BJ, Giummarra MJ.",,International journal of environmental research and public health,2020,2020-10-07,Y,Injury; Pain; Compensation; Mental health; Insurance; Disability; Traumatic Injury,,,"Identifying who might develop disabling pain or poor mental health after injury is a high priority so that healthcare providers can provide targeted preventive interventions. This retrospective cohort study aimed to identify predictors of disabling pain or probable mental health conditions at 12 months post-injury. Participants were recruited 12-months after admission to a major trauma service for a compensable transport or workplace injury (n = 157). Injury, compensation claim, health services and medication information were obtained from the Victorian Orthopaedic Trauma Outcome Registry, Victorian State Trauma Registry and Compensation Research Database. Participants completed questionnaires about pain, and mental health (anxiety, depression, posttraumatic stress disorder) at 12 months post-injury. One third had disabling pain, one third had at least one probable mental health condition and more than one in five had both disabling pain and a mental health condition at 12 months post-injury. Multivariable logistic regression found mental health treatment 3-6 months post-injury, persistent work disability and opioid use at 6-12 months predicted disabling pain at 12 months post-injury. The presence of opioid use at 3-6 months, work disability and psychotropic medications at 6-12 months predicted a mental health condition at 12 months post-injury. These factors could be used to identify at risk of developing disabling pain who could benefit from timely interventions to better manage both pain and mental health post-injury. Implications for healthcare and compensation system are discussed.",,pdf:https://www.mdpi.com/1660-4601/17/19/7320/pdf?version=1602228180; doi:https://doi.org/10.3390/ijerph17197320; html:https://europepmc.org/articles/PMC7579145; pdf:https://europepmc.org/articles/PMC7579145?pdf=render 34906385,https://doi.org/10.1016/j.burns.2021.07.025,Re: Re: Driving improved burns care and patient outcomes through clinical registry data: A review of quality indicators in the burns registry of Australia and New Zealand.,"Cleland H, Tracy LM, Singer Y, Wood F, Gong J, Cameron P, Gabbe BJ.",,Burns : journal of the International Society for Burn Injuries,2022,2021-08-12,N,,,,,,doi:https://doi.org/10.1016/j.burns.2021.07.025 33605084,https://doi.org/10.1111/jcmm.16388,P62-positive aggregates are homogenously distributed in the myocardium and associated with the type of mutation in genetic cardiomyopathy.,"van der Klooster ZJ, Sepehrkhouy S, Dooijes D, Te Rijdt WP, Schuiringa FSAM, Lingeman J, van Tintelen JP, Harakalova M, Goldschmeding R, Suurmeijer AJH, Asselbergs FW, Vink A.",,Journal of cellular and molecular medicine,2021,2021-02-18,Y,Histology; Pathology; Senescence; Genetic; Cardiomyopathy; Autophagy; P62; Phospholamban; Desminopathy; Sequestosome-1,,,"Genetic cardiomyopathy is caused by mutations in various genes. The accumulation of potentially proteotoxic mutant protein aggregates due to insufficient autophagy is a possible mechanism of disease development. The objective of this study was to investigate the distribution in the myocardium of such aggregates in relation to specific pathogenic genetic mutations in cardiomyopathy hearts. Hearts from 32 genetic cardiomyopathy patients, 4 non-genetic cardiomyopathy patients and 5 controls were studied. Microscopic slices from an entire midventricular heart slice were stained for p62 (sequestosome-1, marker for aggregated proteins destined for autophagy). The percentage of cardiomyocytes with p62 accumulation was higher in cardiomyopathy hearts (median 3.3%) than in healthy controls (0.3%; P < .0001). p62 accumulation was highest in the desmin (15.6%) and phospholamban (7.2%) groups. P62 accumulation was homogeneously distributed in the myocardium. Fibrosis was not associated with p62 accumulation in subgroup analysis of phospholamban hearts. In conclusion, accumulation of p62-positive protein aggregates is homogeneously distributed in the myocardium independently of fibrosis distribution and associated with desmin and phospholamban cardiomyopathy. Proteotoxic protein accumulation is a diffuse process in the myocardium while a more localized second hit, such as local strain during exercise, might determine whether this leads to regional myocyte decay.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jcmm.16388; doi:https://doi.org/10.1111/jcmm.16388; html:https://europepmc.org/articles/PMC7957157; pdf:https://europepmc.org/articles/PMC7957157?pdf=render 37817277,https://doi.org/10.1186/s13063-023-07656-8,"e-Consent in UK academic-led clinical trials: current practice, challenges and the need for more evidence.","Mitchell EJ, Appelbe D, Bravery A, Culliford L, Evans H, Farrin AJ, Gillies K, Hood K, Love SB, Sydes MR, Williamson PR, Wakefield N, as part of the e-Consent collaborative group.",,Trials,2023,2023-10-10,Y,Consent; Clinical Trial; E-consent,,,"

Background

During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent.

Methods

A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April-June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research.

Results

Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions.

Conclusion

e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent.",,doi:https://doi.org/10.1186/s13063-023-07656-8; html:https://europepmc.org/articles/PMC10565982; pdf:https://europepmc.org/articles/PMC10565982?pdf=render 31481394,https://doi.org/10.1136/bmj.l4892,"Thyroid replacement therapy, thyroid stimulating hormone concentrations, and long term health outcomes in patients with hypothyroidism: longitudinal study.","Thayakaran R, Adderley NJ, Sainsbury C, Torlinska B, Boelaert K, Šumilo D, Price M, Thomas GN, Toulis KA, Nirantharakumar K.",,BMJ (Clinical research ed.),2019,2019-09-03,Y,,Understanding the Causes of Disease,,"

Objective

To explore whether thyroid stimulating hormone (TSH) concentration in patients with a diagnosis of hypothyroidism is associated with increased all cause mortality and a higher risk of cardiovascular disease and fractures.

Design

Retrospective cohort study.

Setting

The Health Improvement Network (THIN), a database of electronic patient records from UK primary care.

Participants

Adult patients with incident hypothyroidism from 1 January 1995 to 31 December 2017.

Exposure

TSH concentration in patients with hypothyroidism.

Main outcome measures

Ischaemic heart disease, heart failure, stroke/transient ischaemic attack, atrial fibrillation, any fractures, fragility fractures, and mortality. Longitudinal TSH measurements from diagnosis to outcomes, study end, or loss to follow-up were collected. An extended Cox proportional hazards model with TSH considered as a time varying covariate was fitted for each outcome.

Results

162 369 patients with hypothyroidism and 863 072 TSH measurements were included in the analysis. Compared with the reference TSH category (2-2.5 mIU/L), risk of ischaemic heart disease and heart failure increased at high TSH concentrations (>10 mIU/L) (hazard ratio 1.18 (95% confidence interval 1.02 to 1.38; P=0.03) and 1.42 (1.21 to 1.67; P<0.001), respectively). A protective effect for heart failure was seen at low TSH concentrations (hazard ratio 0.79 (0.64 to 0.99; P=0.04) for TSH <0.1 mIU/L and 0.76 (0.62 to 0.92; P=0.006) for 0.1-0.4 mIU/L). Increased mortality was observed in both the lowest and highest TSH categories (hazard ratio 1.18 (1.08 to 1.28; P<0.001), 1.29 (1.22 to 1.36; P<0.001), and 2.21 (2.07 to 2.36; P<0.001) for TSH <0.1 mIU/L, 4-10 mIU/L, and >10 mIU/L. An increase in the risk of fragility fractures was observed in patients in the highest TSH category (>10 mIU/L) (hazard ratio 1.15 (1.01 to 1.31; P=0.03)).

Conclusions

In patients with a diagnosis of hypothyroidism, no evidence was found to suggest a clinically meaningful difference in the pattern of long term health outcomes (all cause mortality, atrial fibrillation, ischaemic heart disease, heart failure, stroke/transient ischaemic attack, fractures) when TSH concentrations were within recommended normal limits. Evidence was found for adverse health outcomes when TSH concentration is outside this range, particularly above the upper reference value.",,pdf:https://www.bmj.com/content/bmj/366/bmj.l4892.full.pdf; doi:https://doi.org/10.1136/bmj.l4892; html:https://europepmc.org/articles/PMC6719286 36330526,https://doi.org/10.3389/fimmu.2022.1032331,Levels of soluble complement regulators predict severity of COVID-19 symptoms.,"Tierney AL, Alali WM, Scott T, Rees-Unwin KS, CITIID-NIHR BioResource COVID-19 Collaboration, Clark SJ, Unwin RD.",,Frontiers in immunology,2022,2022-10-18,Y,Complement; Mass spectrometry; Biomarkers; Factor H; Factor H-related Proteins; Covid-19; Sars-cov-2,,,"The SARS-CoV-2 virus continues to cause significant morbidity and mortality worldwide from COVID-19. One of the major challenges of patient management is the broad range of symptoms observed. While the majority of individuals experience relatively mild disease, a significant minority of patients require hospitalisation, with COVID-19 still proving fatal for some. As such, there remains a desperate need to better understand what drives this severe disease, both in terms of the underlying biology, but also to potentially predict at diagnosis which patients are likely to require further interventions, thus enabling better outcomes for both patients and healthcare systems. Several lines of evidence have pointed to dysregulation of the complement cascade as a major factor in severe COVID-19 outcomes. How this is underpinned mechanistically is not known. Here, we have focussed on the role of the soluble complement regulators Complement Factor H (FH), its splice variant Factor H-like 1 (FHL-1) and five Factor H-Related proteins (FHR1-5). Using a targeted mass spectrometry approach, we quantified these proteins in a cohort of 188 plasma samples from controls and SARS-CoV-2 patients taken at diagnosis. This analysis revealed significant elevations in all FHR proteins, but not FH, in patients with more severe disease, particularly FHR2 and FHR5 (FHR2: 1.97-fold, p<0.0001; FHR5: 2.4-fold, p<0.0001). Furthermore, for a subset of 77 SARS-CoV-2 +ve patients we also analysed time course samples taken approximately 28 days post-diagnosis. Here, we see complement regulator levels drop in all individuals with asymptomatic or mild disease, but regulators remain high in those with more severe outcomes, with elevations in FHR2 over baseline levels in this group. These data support the hypothesis that elevation of circulating levels of the FHR family of proteins could predict disease severity in COVID-19 patients, and that the duration of elevation (or lack of immune activation resolution) may be partly responsible for driving poor outcomes in COVID-19.",,pdf:https://www.frontiersin.org/articles/10.3389/fimmu.2022.1032331/pdf; doi:https://doi.org/10.3389/fimmu.2022.1032331; html:https://europepmc.org/articles/PMC9624227; pdf:https://europepmc.org/articles/PMC9624227?pdf=render -37339333,https://doi.org/10.1002/jia2.26104,"COVID-19 among adults living with HIV: correlates of mortality among public sector healthcare users in Western Cape, South Africa.","Kassanjee R, Davies MA, Ngwenya O, Osei-Yeboah R, Jacobs T, Morden E, Timmerman V, Britz S, Mendelson M, Taljaard J, Riou J, Boulle A, Tiffin N, Zinyakatira N.",,Journal of the International AIDS Society,2023,2023-06-01,Y,Mortality; HIV; South Africa; Cd4 Count; Covid-19; Sars-cov-2,,,"

Introduction

While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty about the role of HIV disease severity on COVID-19 outcomes, especially in lower-income settings. We studied the association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH.

Methods

We analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS-CoV-2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID-19 vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period.

Results

Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17,831 first-diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults.

Conclusions

Mortality was strongly associated with suboptimal HIV control, and the prevalence of these risk factors increased in later COVID-19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimized.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jia2.26104; doi:https://doi.org/10.1002/jia2.26104; html:https://europepmc.org/articles/PMC10281639; pdf:https://europepmc.org/articles/PMC10281639?pdf=render 31964672,https://doi.org/10.1136/bmjopen-2019-033318,"Educational differentials in key domains of physical activity by ethnicity, age and sex: a cross-sectional study of over 40 000 participants in the UK household longitudinal study (2013-2015).","Fluharty ME, Pinto Pereira SM, Benzeval M, Hamer M, Jefferis B, Griffiths LJ, Cooper R, Bann D.",,BMJ open,2020,2020-01-20,Y,epidemiology; Physical Activity; Health Disparities,Improving Public Health,,"

Objectives

To assess whether educational differentials in three key physical activity (PA) domains vary by age, sex and ethnicity.

Design

National cross-sectional survey.

Setting

UK.

Participants

Altogether 40 270 participants, aged 20 years and over, from the UK Household Longitudinal Study with information on education, PA and demographics collected in 2013-2015.

Outcome measures

Participation in active travel (AT), occupational activity (OA) and leisure time physical activity (LTPA) at the time of assessment.

Results

Lower educational attainment was associated with higher AT and OA, but lower weekly LTPA activity; these associations were modified by sex, ethnicity and age. Education-related differences in AT were larger for women-the difference in predicted probability of activity between the highest and the lowest education groups was -10% in women (95% CI: -11.9% to 7.9%) and -3% in men (-4.8% to -0.4%). Education-related differences in OA were larger among men -35% (-36.9% to -32.4%) than women -17% (-19.4% to -15.0%). Finally, education-related differences in moderate-to-vigorous LTPA varied by ethnicity; for example, differences were 17% (16.2% to 18.7%) for white individuals compared with 6% (0.6% to 11.6%) for black individuals.

Conclusions

Educational differences in PA vary by domain and are modified by age, sex and ethnicity. A better understanding of physically inactive subgroups may aid development of interventions to both increase activity levels and reduce health inequalities.","This study which includes over 40 thousant adults in the UK, aims to assess whether there are links between different levels of physical activity and educational achievements. It found that lower educational achievement was associated with higher travel and work related physical activity, but not leisure time activity. They found this difference to be larger in men than in women, and also in white compared to black individuals.",pdf:https://bmjopen.bmj.com/content/bmjopen/10/1/e033318.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-033318; html:https://europepmc.org/articles/PMC7045199; pdf:https://europepmc.org/articles/PMC7045199?pdf=render +37339333,https://doi.org/10.1002/jia2.26104,"COVID-19 among adults living with HIV: correlates of mortality among public sector healthcare users in Western Cape, South Africa.","Kassanjee R, Davies MA, Ngwenya O, Osei-Yeboah R, Jacobs T, Morden E, Timmerman V, Britz S, Mendelson M, Taljaard J, Riou J, Boulle A, Tiffin N, Zinyakatira N.",,Journal of the International AIDS Society,2023,2023-06-01,Y,Mortality; HIV; South Africa; Cd4 Count; Covid-19; Sars-cov-2,,,"

Introduction

While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty about the role of HIV disease severity on COVID-19 outcomes, especially in lower-income settings. We studied the association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH.

Methods

We analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS-CoV-2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID-19 vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period.

Results

Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17,831 first-diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults.

Conclusions

Mortality was strongly associated with suboptimal HIV control, and the prevalence of these risk factors increased in later COVID-19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimized.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jia2.26104; doi:https://doi.org/10.1002/jia2.26104; html:https://europepmc.org/articles/PMC10281639; pdf:https://europepmc.org/articles/PMC10281639?pdf=render 36482104,https://doi.org/10.1038/s41591-022-02100-x,Association of wearable device-measured vigorous intermittent lifestyle physical activity with mortality.,"Stamatakis E, Ahmadi MN, Gill JMR, Thøgersen-Ntoumani C, Gibala MJ, Doherty A, Hamer M.",,Nature medicine,2022,2022-12-08,Y,,,,"Wearable devices can capture unexplored movement patterns such as brief bursts of vigorous intermittent lifestyle physical activity (VILPA) that is embedded into everyday life, rather than being done as leisure time exercise. Here, we examined the association of VILPA with all-cause, cardiovascular disease (CVD) and cancer mortality in 25,241 nonexercisers (mean age 61.8 years, 14,178 women/11,063 men) in the UK Biobank. Over an average follow-up of 6.9 years, during which 852 deaths occurred, VILPA was inversely associated with all three of these outcomes in a near-linear fashion. Compared with participants who engaged in no VILPA, participants who engaged in VILPA at the sample median VILPA frequency of 3 length-standardized bouts per day (lasting 1 or 2 min each) showed a 38%-40% reduction in all-cause and cancer mortality risk and a 48%-49% reduction in CVD mortality risk. Moreover, the sample median VILPA duration of 4.4 min per day was associated with a 26%-30% reduction in all-cause and cancer mortality risk and a 32%-34% reduction in CVD mortality risk. We obtained similar results when repeating the above analyses for vigorous physical activity (VPA) in 62,344 UK Biobank participants who exercised (1,552 deaths, 35,290 women/27,054 men). These results indicate that small amounts of vigorous nonexercise physical activity are associated with substantially lower mortality. VILPA in nonexercisers appears to elicit similar effects to VPA in exercisers, suggesting that VILPA may be a suitable physical activity target, especially in people not able or willing to exercise.",,pdf:https://www.nature.com/articles/s41591-022-02100-x.pdf; doi:https://doi.org/10.1038/s41591-022-02100-x; html:https://europepmc.org/articles/PMC9800274; pdf:https://europepmc.org/articles/PMC9800274?pdf=render -37348789,https://doi.org/10.1016/j.jhep.2023.05.046,Liver disease is a significant risk factor for cardiovascular outcomes - A UK Biobank study.,"Roca-Fernandez A, Banerjee R, Thomaides-Brears H, Telford A, Sanyal A, Neubauer S, Nichols TE, Raman B, McCracken C, Petersen SE, Ntusi NA, Cuthbertson DJ, Lai M, Dennis A, Banerjee A.",,Journal of hepatology,2023,2023-06-20,N,Cardiac; MRI; Imaging; Hepatic; Heart Failure; liver disease; Cvd; Nafld; Atrial Fibrilliation,,,"

Background & aims

Chronic liver disease (CLD) is associated with increased cardiovascular disease (CVD) risk. We investigated whether early signs of liver disease (measured by iron-corrected T1-mapping [cT1]) were associated with an increased risk of major CVD events.

Methods

Liver disease activity (cT1) and fat (proton density fat fraction [PDFF]) were measured using LiverMultiScan® between January 2016 and February 2020 in the UK Biobank imaging sub-study. Using multivariable Cox regression, we explored associations between liver cT1 (MRI) and primary CVD (coronary artery disease, atrial fibrillation [AF], embolism/vascular events, heart failure [HF] and stroke), and CVD hospitalisation and all-cause mortality. Liver blood biomarkers, general metabolism biomarkers, and demographics were also included. Subgroup analysis was conducted in those without metabolic syndrome (defined as at least three of: a large waist, high triglycerides, low high-density lipoprotein cholesterol, increased systolic blood pressure, or elevated haemoglobin A1c).

Results

A total of 33,616 participants (mean age 65 years, mean BMI 26 kg/m2, mean haemoglobin A1c 35 mmol/mol) had complete MRI liver data with linked clinical outcomes (median time to major CVD event onset: 1.4 years [range: 0.002-5.1]; follow-up: 2.5 years [range: 1.1-5.2]). Liver disease activity (cT1), but not liver fat (PDFF), was associated with higher risk of any major CVD event (hazard ratio 1.14; 95% CI 1.03-1.26; p = 0.008), AF (1.30; 1.12-1.51; p <0.001); HF (1.30; 1.09-1.56; p= 0.004); CVD hospitalisation (1.27; 1.18-1.37; p <0.001) and all-cause mortality (1.19; 1.02-1.38; p = 0.026). FIB-4 index was associated with HF (1.06; 1.01-1.10; p = 0.007). Risk of CVD hospitalisation was independently associated with cT1 in individuals without metabolic syndrome (1.26; 1.13-1.4; p <0.001).

Conclusion

Liver disease activity, by cT1, was independently associated with a higher risk of incident CVD and all-cause mortality, independent of pre-existing metabolic syndrome, liver fibrosis or fat.

Impact and implications

Chronic liver disease (CLD) is associated with a twofold greater incidence of cardiovascular disease. Our work shows that early liver disease on iron-corrected T1 mapping was associated with a higher risk of major cardiovascular disease (14%), cardiovascular disease hospitalisation (27%) and all-cause mortality (19%). These findings highlight the prognostic relevance of a comprehensive evaluation of liver health in populations at risk of CVD and/or CLD, even in the absence of clinical manifestations or metabolic syndrome, when there is an opportunity to modify/address risk factors and prevent disease progression. As such, they are relevant to patients, carers, clinicians, and policymakers.",,pdf:http://www.journal-of-hepatology.eu/article/S0168827823004208/pdf; doi:https://doi.org/10.1016/j.jhep.2023.05.046 32401709,https://doi.org/10.1016/s2468-2667(20)30112-2,COVID-19: a public health approach to manage domestic violence is needed.,"Chandan JS, Taylor J, Bradbury-Jones C, Nirantharakumar K, Kane E, Bandyopadhyay S.",,The Lancet. Public health,2020,2020-05-10,Y,,,,,Chandan et al. comment on the effect the covid pandemic may have on domestic violence and propose surveillance for domestic violence is needed. ,pdf:http://www.thelancet.com/article/S2468266720301122/pdf; doi:https://doi.org/10.1016/S2468-2667(20)30112-2; html:https://europepmc.org/articles/PMC7252171; pdf:https://europepmc.org/articles/PMC7252171?pdf=render +37348789,https://doi.org/10.1016/j.jhep.2023.05.046,Liver disease is a significant risk factor for cardiovascular outcomes - A UK Biobank study.,"Roca-Fernandez A, Banerjee R, Thomaides-Brears H, Telford A, Sanyal A, Neubauer S, Nichols TE, Raman B, McCracken C, Petersen SE, Ntusi NA, Cuthbertson DJ, Lai M, Dennis A, Banerjee A.",,Journal of hepatology,2023,2023-06-20,N,Cardiac; MRI; Imaging; Hepatic; Heart Failure; liver disease; Cvd; Nafld; Atrial Fibrilliation,,,"

Background & aims

Chronic liver disease (CLD) is associated with increased cardiovascular disease (CVD) risk. We investigated whether early signs of liver disease (measured by iron-corrected T1-mapping [cT1]) were associated with an increased risk of major CVD events.

Methods

Liver disease activity (cT1) and fat (proton density fat fraction [PDFF]) were measured using LiverMultiScan® between January 2016 and February 2020 in the UK Biobank imaging sub-study. Using multivariable Cox regression, we explored associations between liver cT1 (MRI) and primary CVD (coronary artery disease, atrial fibrillation [AF], embolism/vascular events, heart failure [HF] and stroke), and CVD hospitalisation and all-cause mortality. Liver blood biomarkers, general metabolism biomarkers, and demographics were also included. Subgroup analysis was conducted in those without metabolic syndrome (defined as at least three of: a large waist, high triglycerides, low high-density lipoprotein cholesterol, increased systolic blood pressure, or elevated haemoglobin A1c).

Results

A total of 33,616 participants (mean age 65 years, mean BMI 26 kg/m2, mean haemoglobin A1c 35 mmol/mol) had complete MRI liver data with linked clinical outcomes (median time to major CVD event onset: 1.4 years [range: 0.002-5.1]; follow-up: 2.5 years [range: 1.1-5.2]). Liver disease activity (cT1), but not liver fat (PDFF), was associated with higher risk of any major CVD event (hazard ratio 1.14; 95% CI 1.03-1.26; p = 0.008), AF (1.30; 1.12-1.51; p <0.001); HF (1.30; 1.09-1.56; p= 0.004); CVD hospitalisation (1.27; 1.18-1.37; p <0.001) and all-cause mortality (1.19; 1.02-1.38; p = 0.026). FIB-4 index was associated with HF (1.06; 1.01-1.10; p = 0.007). Risk of CVD hospitalisation was independently associated with cT1 in individuals without metabolic syndrome (1.26; 1.13-1.4; p <0.001).

Conclusion

Liver disease activity, by cT1, was independently associated with a higher risk of incident CVD and all-cause mortality, independent of pre-existing metabolic syndrome, liver fibrosis or fat.

Impact and implications

Chronic liver disease (CLD) is associated with a twofold greater incidence of cardiovascular disease. Our work shows that early liver disease on iron-corrected T1 mapping was associated with a higher risk of major cardiovascular disease (14%), cardiovascular disease hospitalisation (27%) and all-cause mortality (19%). These findings highlight the prognostic relevance of a comprehensive evaluation of liver health in populations at risk of CVD and/or CLD, even in the absence of clinical manifestations or metabolic syndrome, when there is an opportunity to modify/address risk factors and prevent disease progression. As such, they are relevant to patients, carers, clinicians, and policymakers.",,pdf:http://www.journal-of-hepatology.eu/article/S0168827823004208/pdf; doi:https://doi.org/10.1016/j.jhep.2023.05.046 35244709,https://doi.org/10.1093/europace/euac022,Impact of oral anticoagulation on the association between frailty and clinical outcomes in people with atrial fibrillation: nationwide primary care records on treatment analysis.,"Wilkinson C, Wu J, Clegg A, Nadarajah R, Rockwood K, Todd O, Gale CP.",,"Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology",2022,2022-07-01,Y,Bleeding; Atrial fibrillation; Stroke; Frailty; Outcome; Oral Anticoagulation; Oral Anticoagulation Prescription,,,"

Aims

People with atrial fibrillation (AF) frequently live with frailty, which increases the risk of mortality and stroke. This study reports the association between oral anticoagulation (OAC) and outcomes for people with frailty, and whether there is overall net benefit from treatment in people with AF.

Methods and results

Retrospective open cohort electronic records study. Frailty was identified using the electronic frailty index. Primary care electronic health records of 89 996 adults with AF and CHA2DS2-Vasc score of ≥2 were linked with secondary care and mortality data in the Clinical Practice Research Database (CPRD) from 1 January 1998 to 30 November 2018. The primary outcome was a composite of death, stroke, systemic embolism, or major bleeding. Secondary outcomes were stroke, major bleeding, all-cause mortality, transient ischaemic attack, and falls. Of 89 996 participants, 71 256 (79.2%) were living with frailty. The prescription of OAC increased with degree of frailty. For patients not prescribed OAC, rates of the primary outcome increased alongside frailty category. Prescription of OAC was associated with a reduction in the primary outcome for each frailty category [adjusted hazard ratio, 95% confidence interval, no OAC as reference; fit: vitamin K antagonist (VKA) 0.69, 0.64-0.75, direct oral anticoagulant (DOAC) 0.42, 0.33-0.53; mild frailty: VKA 0.52, 0.50-0.54, DOAC 0.57, 0.52-0.63; moderate: VKA 0.54, 0.52-0.56, DOAC 0.57, 0.52-0.63; severe: VKA 0.48, 0.45-0.51, DOAC 0.58, 0.52-0.65], with cumulative incidence function effects greater for DOAC than VKA.

Conclusion

Frailty among people with AF is common. The OAC was associated with a reduction in the primary endpoint across all degrees of frailty.",,doi:https://doi.org/10.1093/europace/euac022; doi:https://doi.org/10.1093/europace/euac022; html:https://europepmc.org/articles/PMC9326851; pdf:https://europepmc.org/articles/PMC9326851?pdf=render -36869930,https://doi.org/10.1007/s00520-023-07633-6,Cost consequences of unscheduled emergency admissions in cancer patients in the last year of life.,"McFerran E, Cairnduff V, Elder R, Gavin A, Lawler M.",,Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer,2023,2023-03-04,Y,Neoplasms; Death; Palliative care; Emergency Care; Cost Consequences,,,"

Objectives

Cancer is a leading cause of death. This paper examines the utilisation of unscheduled emergency end-of-life healthcare and estimates expenditure in this domain. We explore care patterns and quantify the likely benefits from service reconfigurations which may influence rates of hospital admission and deaths.

Methods

Using prevalence-based retrospective data from the Northern Ireland General Registrar's Office linked by cancer diagnosis to Patient Administration episode data for unscheduled emergency care (1st January 2014 to 31st December 2015), we estimate unscheduled-emergency-care costs in the last year of life. We model potential resources released by reductions in length-of-stay for cancer patients. Linear regression examined patient characteristics affecting length of stay.

Results

A total of 3134 cancer patients used 60,746 days of unscheduled emergency care (average 19.5 days). Of these, 48.9% had ≥1 admission during their last 28 days of life. Total estimated cost was £28,684,261, averaging £9200 per person. Lung cancer patients had the highest proportion of admissions (23.2%, mean length of stay = 17.9 days, mean cost=£7224). The highest service use and total cost was in those diagnosed at stage IV (38.4%), who required 22,099 days of care, costing £9,629,014. Palliative care support, identified in 25.5% of patients, contributed £1,322,328. A 3-day reduction in the mean length of stay with a 10% reduction in admissions, could reduce costs by £7.37 million. Regression analyses explained 41% of length-of-stay variability.

Conclusions

The cost burden from unscheduled care use in the last year of life of cancer patients is significant. Opportunities to prioritise service reconfiguration for high-costing users emphasized lung and colorectal cancers as offering the greatest potential to influence outcomes.",,pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07633-6.pdf; doi:https://doi.org/10.1007/s00520-023-07633-6; html:https://europepmc.org/articles/PMC9985568; pdf:https://europepmc.org/articles/PMC9985568?pdf=render 34173614,https://doi.org/10.1016/s2666-7568(20)30012-x,Evolution and effects of COVID-19 outbreaks in care homes: a population analysis in 189 care homes in one geographical region of the UK.,"Burton JK, Bayne G, Evans C, Garbe F, Gorman D, Honhold N, McCormick D, Othieno R, Stevenson JE, Swietlik S, Templeton KE, Tranter M, Willocks L, Guthrie B.",,The lancet. Healthy longevity,2020,2020-10-20,Y,,,,"

Background

COVID-19 has affected care home residents internationally, but detailed information on outbreaks is scarce. We aimed to describe the evolution of outbreaks of COVID-19 in all care homes in one large health region in Scotland.

Methods

We did a population analysis of testing, cases, and deaths in care homes in the National Health Service (NHS) Lothian health region of the UK. We obtained data for COVID-19 testing (PCR testing of nasopharyngeal swabs for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) and deaths (COVID-19-related and non-COVID-19-related), and we analysed data by several variables including type of care home, number of beds, and locality. Outcome measures were timing of outbreaks, number of confirmed cases of COVID-19 in care home residents, care home characteristics associated with the presence of an outbreak, and deaths of residents in both care homes and hospitals. We calculated excess deaths (both COVID-19-related and non-COVID-19-related), which we defined as the sum of deaths over and above the historical average in the same period over the past 5 years.

Findings

Between March 10 and Aug 2, 2020, residents at 189 care homes (5843 beds) were tested for COVID-19 when symptomatic. A COVID-19 outbreak was confirmed at 69 (37%) care homes, of which 66 (96%) were care homes for older people. The size of care homes for older people was strongly associated with a COVID-19 outbreak (odds ratio per 20-bed increase 3·35, 95% CI 1·99-5·63). 907 confirmed cases of SARS-CoV-2 infection were recorded during the study period, and 432 COVID-19-related deaths. 229 (25%) COVID-19-related cases and 99 (24%) COVID-related deaths occurred in five (3%) of 189 care homes, and 441 (49%) cases and 207 (50%) deaths were in 13 (7%) care homes. 411 (95%) COVID-19-related deaths occurred in the 69 care homes with a confirmed COVID-19 outbreak, 19 (4%) deaths were in hospital, and two (<1%) were in one of the 120 care homes without a confirmed COVID-19 outbreak. At the 69 care homes with a confirmed COVID-19 outbreak, 74 excess non-COVID-19-related deaths were reported, whereas ten non-COVID-19-related excess deaths were observed in the 120 care homes without a confirmed COVID-19 outbreak. 32 fewer non-COVID-19-related deaths than expected were reported among care home residents in hospital.

Interpretation

The effect of COVID-19 on care homes has been substantial but concentrated in care homes with known outbreaks. A key implication from our findings is that, if community incidence of COVID-19 increases again, many care home residents will be susceptible. Shielding care home residents from potential sources of SARS-CoV-2 infection, and ensuring rapid action to minimise outbreak size if infection is introduced, will be important for any second wave.

Funding

None.",,doi:https://doi.org/10.1016/s2666-7568(20)30012-x; doi:https://doi.org/10.1016/S2666-7568(20)30012-X; html:https://europepmc.org/articles/PMC7574931; pdf:https://europepmc.org/articles/PMC7574931?pdf=render +36869930,https://doi.org/10.1007/s00520-023-07633-6,Cost consequences of unscheduled emergency admissions in cancer patients in the last year of life.,"McFerran E, Cairnduff V, Elder R, Gavin A, Lawler M.",,Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer,2023,2023-03-04,Y,Neoplasms; Death; Palliative care; Emergency Care; Cost Consequences,,,"

Objectives

Cancer is a leading cause of death. This paper examines the utilisation of unscheduled emergency end-of-life healthcare and estimates expenditure in this domain. We explore care patterns and quantify the likely benefits from service reconfigurations which may influence rates of hospital admission and deaths.

Methods

Using prevalence-based retrospective data from the Northern Ireland General Registrar's Office linked by cancer diagnosis to Patient Administration episode data for unscheduled emergency care (1st January 2014 to 31st December 2015), we estimate unscheduled-emergency-care costs in the last year of life. We model potential resources released by reductions in length-of-stay for cancer patients. Linear regression examined patient characteristics affecting length of stay.

Results

A total of 3134 cancer patients used 60,746 days of unscheduled emergency care (average 19.5 days). Of these, 48.9% had ≥1 admission during their last 28 days of life. Total estimated cost was £28,684,261, averaging £9200 per person. Lung cancer patients had the highest proportion of admissions (23.2%, mean length of stay = 17.9 days, mean cost=£7224). The highest service use and total cost was in those diagnosed at stage IV (38.4%), who required 22,099 days of care, costing £9,629,014. Palliative care support, identified in 25.5% of patients, contributed £1,322,328. A 3-day reduction in the mean length of stay with a 10% reduction in admissions, could reduce costs by £7.37 million. Regression analyses explained 41% of length-of-stay variability.

Conclusions

The cost burden from unscheduled care use in the last year of life of cancer patients is significant. Opportunities to prioritise service reconfiguration for high-costing users emphasized lung and colorectal cancers as offering the greatest potential to influence outcomes.",,pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07633-6.pdf; doi:https://doi.org/10.1007/s00520-023-07633-6; html:https://europepmc.org/articles/PMC9985568; pdf:https://europepmc.org/articles/PMC9985568?pdf=render 34930919,https://doi.org/10.1038/s41467-021-26280-1,Finding genetically-supported drug targets for Parkinson's disease using Mendelian randomization of the druggable genome.,"Storm CS, Kia DA, Almramhi MM, Bandres-Ciga S, Finan C, International Parkinson’s Disease Genomics Consortium (IPDGC), Hingorani AD, Wood NW.",,Nature communications,2021,2021-12-20,Y,,,,"Parkinson's disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization to investigate over 3,000 genes that encode druggable proteins and predict their efficacy as drug targets for Parkinson's disease. We use expression and protein quantitative trait loci to mimic exposure to medications, and we examine the causal effect on Parkinson's disease risk (in two large cohorts), age at onset and progression. We propose 23 drug-targeting mechanisms for Parkinson's disease, including four possible drug repurposing opportunities and two drugs which may increase Parkinson's disease risk. Of these, we put forward six drug targets with the strongest Mendelian randomization evidence. There is remarkably little overlap between our drug targets to reduce Parkinson's disease risk versus progression, suggesting different molecular mechanisms. Drugs with genetic support are considerably more likely to succeed in clinical trials, and we provide compelling genetic evidence and an analysis pipeline to prioritise Parkinson's disease drug development.",,pdf:https://www.nature.com/articles/s41467-021-26280-1.pdf; doi:https://doi.org/10.1038/s41467-021-26280-1; html:https://europepmc.org/articles/PMC8688480; pdf:https://europepmc.org/articles/PMC8688480?pdf=render 38429458,https://doi.org/10.1038/s41590-024-01754-8,Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19.,"Hanson AL, Mulè MP, Ruffieux H, Mescia F, Bergamaschi L, Pelly VS, Turner L, Kotagiri P, Cambridge Institute of Therapeutic Immunology and Infectious Disease–National Institute for Health Research (CITIID–NIHR) COVID BioResource Collaboration, Göttgens B, Hess C, Gleadall N, Bradley JR, Nathan JA, Lyons PA, Drakesmith H, Smith KGC.",,Nature immunology,2024,2024-03-01,Y,,,,"Persistent symptoms following SARS-CoV-2 infection are increasingly reported, although the drivers of post-acute sequelae (PASC) of COVID-19 are unclear. Here we assessed 214 individuals infected with SARS-CoV-2, with varying disease severity, for one year from COVID-19 symptom onset to determine the early correlates of PASC. A multivariate signature detected beyond two weeks of disease, encompassing unresolving inflammation, anemia, low serum iron, altered iron-homeostasis gene expression and emerging stress erythropoiesis; differentiated those who reported PASC months later, irrespective of COVID-19 severity. A whole-blood heme-metabolism signature, enriched in hospitalized patients at month 1-3 post onset, coincided with pronounced iron-deficient reticulocytosis. Lymphopenia and low numbers of dendritic cells persisted in those with PASC, and single-cell analysis reported iron maldistribution, suggesting monocyte iron loading and increased iron demand in proliferating lymphocytes. Thus, defects in iron homeostasis, dysregulated erythropoiesis and immune dysfunction due to COVID-19 possibly contribute to inefficient oxygen transport, inflammatory disequilibrium and persisting symptomatology, and may be therapeutically tractable.",,doi:https://doi.org/10.1038/s41590-024-01754-8; doi:https://doi.org/10.1038/s41590-024-01754-8; html:https://europepmc.org/articles/PMC10907301; pdf:https://europepmc.org/articles/PMC10907301?pdf=render 35967893,https://doi.org/10.1080/20008066.2022.2105577,Factors influencing the mental health of an ethnically diverse healthcare workforce during COVID-19: a qualitative study in the United Kingdom.,"Qureshi I, Gogoi M, Al-Oraibi A, Wobi F, Chaloner J, Gray L, Guyatt AL, Hassan O, Nellums LB, Pareek M, UK-REACH Collaborative Group.",,European journal of psychotraumatology,2022,2022-08-09,Y,Stress; Trauma; Anxiety; Mental health; Workforce; Healthcare; Ethnic Minority; Covid-19,,,"Background: Healthcare workers (HCWs) have been reported to be experiencing a deterioration in their mental health due to COVID-19. In addition, ethnic minority populations in the United Kingdom are disproportionately affected by COVID-19. It is imperative that HCWs are appropriately supported and protected from mental harm during the pandemic. Our research aims to add to the evidence base by providing greater insight into the lived experience of HCWs from diverse ethnic backgrounds during the pandemic that had an impact on their mental health. Methods: We undertook a qualitative work package as part of the United Kingdom Research study into Ethnicity And COVID-19 outcomes among Healthcare workers (UK-REACH). As part of the qualitative research, we carried out 16 focus groups with a total of 61 HCWs between December 2020 and July 2021. The aim of the study was to explore topics such as their experiences, fears and concerns, while working during the pandemic. The purposive sample included ancillary healthcare workers, doctors, nurses, midwives and allied health professionals from diverse ethnic backgrounds to ensure inclusion of underrepresented and disproportionately impacted individuals. We conducted discussions using Microsoft Teams. Recordings were transcribed and thematically analysed. Results: Several factors were identified which impacted on the mental health of HCWs during this period including anxiety (due to inconsistent protocols and policy); fear (of infection); trauma (due to increased exposure to severe illness and death); guilt (of potentially infecting loved ones); and stress (due to longer working hours and increased workload). Conclusion: COVID-19 has affected the mental health of HCWs. We identified a number of factors which may be contributing to a deterioration in mental health for participants from diverse ethnic backgrounds. Healthcare organisations should consider developing strategies to counter the negative impact of these factors, including recommendations made by HCWs themselves.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9364733; doi:https://doi.org/10.1080/20008066.2022.2105577; html:https://europepmc.org/articles/PMC9364733; pdf:https://europepmc.org/articles/PMC9364733?pdf=render @@ -1769,8 +1769,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 32679111,https://doi.org/10.1016/s0140-6736(20)31356-8,COVID-19 pandemic and admission rates for and management of acute coronary syndromes in England.,"Mafham MM, Spata E, Goldacre R, Gair D, Curnow P, Bray M, Hollings S, Roebuck C, Gale CP, Mamas MA, Deanfield JE, de Belder MA, Luescher TF, Denwood T, Landray MJ, Emberson JR, Collins R, Morris EJA, Casadei B, Baigent C.",,"Lancet (London, England)",2020,2020-07-14,Y,,,,"

Background

Several countries affected by the COVID-19 pandemic have reported a substantial drop in the number of patients attending the emergency department with acute coronary syndromes and a reduced number of cardiac procedures. We aimed to understand the scale, nature, and duration of changes to admissions for different types of acute coronary syndrome in England and to evaluate whether in-hospital management of patients has been affected as a result of the COVID-19 pandemic.

Methods

We analysed data on hospital admissions in England for types of acute coronary syndrome from Jan 1, 2019, to May 24, 2020, that were recorded in the Secondary Uses Service Admitted Patient Care database. Admissions were classified as ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), myocardial infarction of unknown type, or other acute coronary syndromes (including unstable angina). We identified revascularisation procedures undertaken during these admissions (ie, coronary angiography without percutaneous coronary intervention [PCI], PCI, and coronary artery bypass graft surgery). We calculated the numbers of weekly admissions and procedures undertaken; percentage reductions in weekly admissions and across subgroups were also calculated, with 95% CIs.

Findings

Hospital admissions for acute coronary syndrome declined from mid-February, 2020, falling from a 2019 baseline rate of 3017 admissions per week to 1813 per week by the end of March, 2020, a reduction of 40% (95% CI 37-43). This decline was partly reversed during April and May, 2020, such that by the last week of May, 2020, there were 2522 admissions, representing a 16% (95% CI 13-20) reduction from baseline. During the period of declining admissions, there were reductions in the numbers of admissions for all types of acute coronary syndrome, including both STEMI and NSTEMI, but relative and absolute reductions were larger for NSTEMI, with 1267 admissions per week in 2019 and 733 per week by the end of March, 2020, a percent reduction of 42% (95% CI 38-46). In parallel, reductions were recorded in the number of PCI procedures for patients with both STEMI (438 PCI procedures per week in 2019 vs 346 by the end of March, 2020; percent reduction 21%, 95% CI 12-29) and NSTEMI (383 PCI procedures per week in 2019 vs 240 by the end of March, 2020; percent reduction 37%, 29-45). The median length of stay among patients with acute coronary syndrome fell from 4 days (IQR 2-9) in 2019 to 3 days (1-5) by the end of March, 2020.

Interpretation

Compared with the weekly average in 2019, there was a substantial reduction in the weekly numbers of patients with acute coronary syndrome who were admitted to hospital in England by the end of March, 2020, which had been partly reversed by the end of May, 2020. The reduced number of admissions during this period is likely to have resulted in increases in out-of-hospital deaths and long-term complications of myocardial infarction and missed opportunities to offer secondary prevention treatment for patients with coronary heart disease. The full extent of the effect of COVID-19 on the management of patients with acute coronary syndrome will continue to be assessed by updating these analyses.

Funding

UK Medical Research Council, British Heart Foundation, Public Health England, Health Data Research UK, and the National Institute for Health Research Oxford Biomedical Research Centre.",,doi:https://doi.org/10.1016/s0140-6736(20)31356-8; doi:https://doi.org/10.1016/S0140-6736(20)31356-8; html:https://europepmc.org/articles/PMC7429983; pdf:https://europepmc.org/articles/PMC7429983?pdf=render 35047183,https://doi.org/10.7189/jogh.11.01011,The COVID-19 pandemic in children and young people during 2020-2021: A complex discussion on vaccination.,"Rudan I, Adeloye D, Katikireddi V, Murray J, Simpson C, Shah SA, Robertson C, Sheikh A, EAVE II collaboration.",,Journal of global health,2021,2021-12-25,Y,,,,,,doi:https://doi.org/10.7189/jogh.11.01011; doi:https://doi.org/10.7189/jogh.11.01011; html:https://europepmc.org/articles/PMC8763337; pdf:https://europepmc.org/articles/PMC8763337?pdf=render 35047182,https://doi.org/10.7189/jogh.11.01010,"The COVID-19 pandemic in children and young people during 2020-2021: Learning about clinical presentation, patterns of spread, viral load, diagnosis and treatment.","Rudan I, Adeloye D, Katikireddi SV, Murray J, Simpson C, Shah SA, Robertson C, Sheikh A, EAVE II collaboration.",,Journal of global health,2021,2021-12-25,Y,,,,,,doi:https://doi.org/10.7189/jogh.11.01010; doi:https://doi.org/10.7189/jogh.11.01010; html:https://europepmc.org/articles/PMC8763336; pdf:https://europepmc.org/articles/PMC8763336?pdf=render -38280393,https://doi.org/10.1016/s2352-3018(23)00272-2,Longitudinal trends in causes of death among adults with HIV on antiretroviral therapy in Europe and North America from 1996 to 2020: a collaboration of cohort studies.,"Trickey A, McGinnis K, Gill MJ, Abgrall S, Berenguer J, Wyen C, Hessamfar M, Reiss P, Kusejko K, Silverberg MJ, Imaz A, Teira R, d'Arminio Monforte A, Zangerle R, Guest JL, Papastamopoulos V, Crane H, Sterling TR, Grabar S, Ingle SM, Sterne JAC.",,The lancet. HIV,2024,2024-01-24,N,,,,"

Background

Mortality rates among people with HIV have fallen since 1996 following the widespread availability of effective antiretroviral therapy (ART). Patterns of cause-specific mortality are evolving as the population with HIV ages. We aimed to investigate longitudinal trends in cause-specific mortality among people with HIV starting ART in Europe and North America.

Methods

In this collaborative observational cohort study, we used data from 17 European and North American HIV cohorts contributing data to the Antiretroviral Therapy Cohort Collaboration. We included data for people with HIV who started ART between 1996 and 2020 at the age of 16 years or older. Causes of death were classified into a single cause by both a clinician and an algorithm if International Classification of Diseases, Ninth Revision or Tenth Revision data were available, or independently by two clinicians. Disagreements were resolved through panel discussion. We used Poisson models to compare cause-specific mortality rates during the calendar periods 1996-99, 2000-03, 2004-07, 2008-11, 2012-15, and 2016-20, adjusted for time-updated age, CD4 count, and whether the individual was ART-naive at the start of each period.

Findings

Among 189 301 people with HIV included in this study, 16 832 (8·9%) deaths were recorded during 1 519 200 person-years of follow-up. 13 180 (78·3%) deaths were classified by cause: the most common causes were AIDS (4203 deaths; 25·0%), non-AIDS non-hepatitis malignancy (2311; 13·7%), and cardiovascular or heart-related (1403; 8·3%) mortality. The proportion of deaths due to AIDS declined from 49% during 1996-99 to 16% during 2016-20. Rates of all-cause mortality per 1000 person-years decreased from 16·8 deaths (95% CI 15·4-18·4) during 1996-99 to 7·9 deaths (7·6-8·2) during 2016-20. Rates of all-cause mortality declined with time: the average adjusted mortality rate ratio per calendar period was 0·85 (95% CI 0·84-0·86). Rates of cause-specific mortality also declined: the most pronounced reduction was for AIDS-related mortality (0·81; 0·79-0·83). There were also reductions in rates of cardiovascular-related (0·83, 0·79-0·87), liver-related (0·88, 0·84-0·93), non-AIDS infection-related (0·91, 0·86-0·96), non-AIDS-non-hepatocellular carcinoma malignancy-related (0·94, 0·90-0·97), and suicide or accident-related mortality (0·89, 0·82-0·95). Mortality rates among people who acquired HIV through injecting drug use increased in women (1·07, 1·00-1·14) and decreased slightly in men (0·96, 0·93-0·99).

Interpretation

Reductions of most major causes of death, particularly AIDS-related deaths among people with HIV on ART, were not seen for all subgroups. Interventions targeted at high-risk groups, substance use, and comorbidities might further increase life expectancy in people with HIV towards that in the general population.

Funding

US National Institute on Alcohol Abuse and Alcoholism.",,doi:https://doi.org/10.1016/S2352-3018(23)00272-2 32935062,https://doi.org/10.23889/ijpds.v5i2.1383,Prospective data linkage to facilitate COVID-19 trials - A call to action.,"Paprica PA, Sydes MR, McGrail KM, Morris AD, Schull MJ, Walker R.",,International journal of population data science,2020,2020-08-11,Y,,,,,,pdf:https://ijpds.org/article/download/1383/2566; doi:https://doi.org/10.23889/ijpds.v5i2.1383; html:https://europepmc.org/articles/PMC7473253; pdf:https://europepmc.org/articles/PMC7473253?pdf=render +38280393,https://doi.org/10.1016/s2352-3018(23)00272-2,Longitudinal trends in causes of death among adults with HIV on antiretroviral therapy in Europe and North America from 1996 to 2020: a collaboration of cohort studies.,"Trickey A, McGinnis K, Gill MJ, Abgrall S, Berenguer J, Wyen C, Hessamfar M, Reiss P, Kusejko K, Silverberg MJ, Imaz A, Teira R, d'Arminio Monforte A, Zangerle R, Guest JL, Papastamopoulos V, Crane H, Sterling TR, Grabar S, Ingle SM, Sterne JAC.",,The lancet. HIV,2024,2024-01-24,N,,,,"

Background

Mortality rates among people with HIV have fallen since 1996 following the widespread availability of effective antiretroviral therapy (ART). Patterns of cause-specific mortality are evolving as the population with HIV ages. We aimed to investigate longitudinal trends in cause-specific mortality among people with HIV starting ART in Europe and North America.

Methods

In this collaborative observational cohort study, we used data from 17 European and North American HIV cohorts contributing data to the Antiretroviral Therapy Cohort Collaboration. We included data for people with HIV who started ART between 1996 and 2020 at the age of 16 years or older. Causes of death were classified into a single cause by both a clinician and an algorithm if International Classification of Diseases, Ninth Revision or Tenth Revision data were available, or independently by two clinicians. Disagreements were resolved through panel discussion. We used Poisson models to compare cause-specific mortality rates during the calendar periods 1996-99, 2000-03, 2004-07, 2008-11, 2012-15, and 2016-20, adjusted for time-updated age, CD4 count, and whether the individual was ART-naive at the start of each period.

Findings

Among 189 301 people with HIV included in this study, 16 832 (8·9%) deaths were recorded during 1 519 200 person-years of follow-up. 13 180 (78·3%) deaths were classified by cause: the most common causes were AIDS (4203 deaths; 25·0%), non-AIDS non-hepatitis malignancy (2311; 13·7%), and cardiovascular or heart-related (1403; 8·3%) mortality. The proportion of deaths due to AIDS declined from 49% during 1996-99 to 16% during 2016-20. Rates of all-cause mortality per 1000 person-years decreased from 16·8 deaths (95% CI 15·4-18·4) during 1996-99 to 7·9 deaths (7·6-8·2) during 2016-20. Rates of all-cause mortality declined with time: the average adjusted mortality rate ratio per calendar period was 0·85 (95% CI 0·84-0·86). Rates of cause-specific mortality also declined: the most pronounced reduction was for AIDS-related mortality (0·81; 0·79-0·83). There were also reductions in rates of cardiovascular-related (0·83, 0·79-0·87), liver-related (0·88, 0·84-0·93), non-AIDS infection-related (0·91, 0·86-0·96), non-AIDS-non-hepatocellular carcinoma malignancy-related (0·94, 0·90-0·97), and suicide or accident-related mortality (0·89, 0·82-0·95). Mortality rates among people who acquired HIV through injecting drug use increased in women (1·07, 1·00-1·14) and decreased slightly in men (0·96, 0·93-0·99).

Interpretation

Reductions of most major causes of death, particularly AIDS-related deaths among people with HIV on ART, were not seen for all subgroups. Interventions targeted at high-risk groups, substance use, and comorbidities might further increase life expectancy in people with HIV towards that in the general population.

Funding

US National Institute on Alcohol Abuse and Alcoholism.",,doi:https://doi.org/10.1016/S2352-3018(23)00272-2 36343994,https://doi.org/10.1136/bmjopen-2022-063159,"Demographic, behavioural and occupational risk factors associated with SARS-CoV-2 infection in UK healthcare workers: a retrospective observational study.","Cooper DJ, Lear S, Sithole N, Shaw A, Stark H, Ferris M, CITIID-NIHR BioResource COVID-19 collaboration consortium, Bradley J, Maxwell P, Goodfellow I, Weekes MP, Seaman S, Baker S.",,BMJ open,2022,2022-11-07,Y,Infection control; epidemiology; Public Health; Covid-19,,,"

Objective

Healthcare workers (HCWs) are at higher risk of SARS-CoV-2 infection than the general population. This group is pivotal to healthcare system resilience during the COVID-19, and future, pandemics. We investigated demographic, social, behavioural and occupational risk factors for SARS-CoV-2 infection among HCWs.

Design/setting/participants

HCWs enrolled in a large-scale sero-epidemiological study at a UK university teaching hospital were sent questionnaires spanning a 5-month period from March to July 2020. In a retrospective observational cohort study, univariate logistic regression was used to assess factors associated with SARS-CoV-2 infection. A Least Absolute Shrinkage Selection Operator regression model was used to identify variables to include in a multivariate logistic regression model.

Results

Among 2258 HCWs, highest ORs associated with SARS-CoV-2 antibody seropositivity on multivariate analysis were having a household member previously testing positive for SARS-CoV-2 antibodies (OR 6.94 (95% CI 4.15 to 11.6); p<0.0001) and being of black ethnicity (6.21 (95% CI 2.69 to 14.3); p<0.0001). Occupational factors associated with a higher risk of seropositivity included working as a physiotherapist (OR 2.78 (95% CI 1.21 to 6.36); p=0.015) and working predominantly in acute medicine (OR 2.72 (95% CI 1.57 to 4.69); p<0.0001) or medical subspecialties (not including infectious diseases) (OR 2.33 (95% CI 1.4 to 3.88); p=0.001). Reporting that adequate personal protective equipment (PPE) was 'rarely' available had an OR of 2.83 (95% CI 1.29 to 6.25; p=0.01). Reporting attending a handover where social distancing was not possible had an OR of 1.39 (95% CI 1.02 to 1.9; p=0.038).

Conclusions

The emergence of SARS-CoV-2 variants and potential vaccine escape continue to threaten stability of healthcare systems worldwide, and sustained vigilance against HCW infection remains a priority. Enhanced risk assessments should be considered for HCWs of black ethnicity, physiotherapists and those working in acute medicine or medical subspecialties. Workplace risk reduction measures include ongoing access to high-quality PPE and effective social distancing measures.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e063159.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-063159; html:https://europepmc.org/articles/PMC9644078; pdf:https://europepmc.org/articles/PMC9644078?pdf=render 32909959,https://doi.org/10.1136/bmj.m3164,Reporting guidelines for clinical trial reports for interventions involving artificial intelligence: the CONSORT-AI Extension.,"Liu X, Rivera SC, Moher D, Calvert MJ, Denniston AK, SPIRIT-AI and CONSORT-AI Working Group.",,BMJ (Clinical research ed.),2020,2020-09-09,Y,,,,"The CONSORT 2010 (Consolidated Standards of Reporting Trials) statement provides minimum guidelines for reporting randomised trials. Its widespread use has been instrumental in ensuring transparency when evaluating new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate impact on health outcomes.The CONSORT-AI extension is a new reporting guideline for clinical trials evaluating interventions with an AI component. It was developed in parallel with its companion statement for clinical trial protocols: SPIRIT-AI. Both guidelines were developed through a staged consensus process, involving a literature review and expert consultation to generate 29 candidate items, which were assessed by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed on in a two-day consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants).The CONSORT-AI extension includes 14 new items, which were considered sufficiently important for AI interventions, that they should be routinely reported in addition to the core CONSORT 2010 items. CONSORT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention is integrated, the handling of inputs and outputs of the AI intervention, the human-AI interaction and providing analysis of error cases.CONSORT-AI will help promote transparency and completeness in reporting clinical trials for AI interventions. It will assist editors and peer-reviewers, as well as the general readership, to understand, interpret and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.",,pdf:https://www.bmj.com/content/bmj/370/bmj.m3164.full.pdf; doi:https://doi.org/10.1136/bmj.m3164; html:https://europepmc.org/articles/PMC7490784 32371477,https://doi.org/10.1126/science.abc0473,Rapid implementation of mobile technology for real-time epidemiology of COVID-19.,"Drew DA, Nguyen LH, Steves CJ, Menni C, Freydin M, Varsavsky T, Sudre CH, Cardoso MJ, Ourselin S, Wolf J, Spector TD, Chan AT, COPE Consortium.",,"Science (New York, N.Y.)",2020,2020-05-05,Y,,,,"The rapid pace of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents challenges to the robust collection of population-scale data to address this global health crisis. We established the COronavirus Pandemic Epidemiology (COPE) Consortium to unite scientists with expertise in big data research and epidemiology to develop the COVID Symptom Study, previously known as the COVID Symptom Tracker, mobile application. This application-which offers data on risk factors, predictive symptoms, clinical outcomes, and geographical hotspots-was launched in the United Kingdom on 24 March 2020 and the United States on 29 March 2020 and has garnered more than 2.8 million users as of 2 May 2020. Our initiative offers a proof of concept for the repurposing of existing approaches to enable rapidly scalable epidemiologic data collection and analysis, which is critical for a data-driven response to this public health challenge.","Drew et al. decribe the use of a smart-phone App to track Covid-19 symptoms reported by users to track, in real time, information on newly infected individuals. It has been launched in the UK and US and has 2.8 million users and is used to rapidly identify emerging hot spots for infection.",pdf:https://www.science.org/cms/asset/fb31d61b-4be3-483a-b040-2ee970dfb432/pap.pdf; doi:https://doi.org/10.1126/science.abc0473; html:https://europepmc.org/articles/PMC7200009; pdf:https://europepmc.org/articles/PMC7200009?pdf=render @@ -1779,8 +1779,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 35410184,https://doi.org/10.1186/s12889-022-13069-0,The local burden of disease during the first wave of the COVID-19 epidemic in England: estimation using different data sources from changing surveillance practices.,"Nightingale ES, Abbott S, Russell TW, CMMID Covid-19 Working Group, Lowe R, Medley GF, Brady OJ.",,BMC public health,2022,2022-04-11,Y,,,,"

Background

The COVID-19 epidemic has differentially impacted communities across England, with regional variation in rates of confirmed cases, hospitalisations and deaths. Measurement of this burden changed substantially over the first months, as surveillance was expanded to accommodate the escalating epidemic. Laboratory confirmation was initially restricted to clinical need (""pillar 1"") before expanding to community-wide symptomatics (""pillar 2""). This study aimed to ascertain whether inconsistent measurement of case data resulting from varying testing coverage could be reconciled by drawing inference from COVID-19-related deaths.

Methods

We fit a Bayesian spatio-temporal model to weekly COVID-19-related deaths per local authority (LTLA) throughout the first wave (1 January 2020-30 June 2020), adjusting for the local epidemic timing and the age, deprivation and ethnic composition of its population. We combined predictions from this model with case data under community-wide, symptomatic testing and infection prevalence estimates from the ONS infection survey, to infer the likely trajectory of infections implied by the deaths in each LTLA.

Results

A model including temporally- and spatially-correlated random effects was found to best accommodate the observed variation in COVID-19-related deaths, after accounting for local population characteristics. Predicted case counts under community-wide symptomatic testing suggest a total of 275,000-420,000 cases over the first wave - a median of over 100,000 additional to the total confirmed in practice under varying testing coverage. This translates to a peak incidence of around 200,000 total infections per week across England. The extent to which estimated total infections are reflected in confirmed case counts was found to vary substantially across LTLAs, ranging from 7% in Leicester to 96% in Gloucester with a median of 23%.

Conclusions

Limitations in testing capacity biased the observed trajectory of COVID-19 infections throughout the first wave. Basing inference on COVID-19-related mortality and higher-coverage testing later in the time period, we could explore the extent of this bias more explicitly. Evidence points towards substantial under-representation of initial growth and peak magnitude of infections nationally, to which different parts of the country contribute unequally.",,pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-022-13069-0; doi:https://doi.org/10.1186/s12889-022-13069-0; html:https://europepmc.org/articles/PMC8996221; pdf:https://europepmc.org/articles/PMC8996221?pdf=render 33048945,https://doi.org/10.1371/journal.pmed.1003290,Neurodevelopmental multimorbidity and educational outcomes of Scottish schoolchildren: A population-based record linkage cohort study.,"Fleming M, Salim EE, Mackay DF, Henderson A, Kinnear D, Clark D, King A, McLay JS, Cooper SA, Pell JP.",,PLoS medicine,2020,2020-10-13,Y,,,,"

Background

Neurodevelopmental conditions commonly coexist in children, but compared to adults, childhood multimorbidity attracts less attention in research and clinical practice. We previously reported that children treated for attention deficit hyperactivity disorder (ADHD) and depression have more school absences and exclusions, additional support needs, poorer attainment, and increased unemployment. They are also more likely to have coexisting conditions, including autism and intellectual disability. We investigated prevalence of neurodevelopmental multimorbidity (≥2 conditions) among Scottish schoolchildren and their educational outcomes compared to peers.

Methods and findings

We retrospectively linked 6 Scotland-wide databases to analyse 766,244 children (390,290 [50.9%] boys; 375,954 [49.1%] girls) aged 4 to 19 years (mean = 10.9) attending Scottish schools between 2009 and 2013. Children were distributed across all deprivation quintiles (most to least deprived: 22.7%, 20.1%, 19.3%, 19.5%, 18.4%). The majority (96.2%) were white ethnicity. We ascertained autism spectrum disorder (ASD) and intellectual disabilities from records of additional support needs and ADHD and depression through relevant encashed prescriptions. We identified neurodevelopmental multimorbidity (≥2 of these conditions) in 4,789 (0.6%) children, with ASD and intellectual disability the most common combination. On adjusting for sociodemographic (sex, age, ethnicity, deprivation) and maternity (maternal age, maternal smoking, sex-gestation-specific birth weight centile, gestational age, 5-minute Apgar score, mode of delivery, parity) factors, multimorbidity was associated with increased school absenteeism and exclusion, unemployment, and poorer exam attainment. Significant dose relationships were evident between number of conditions (0, 1, ≥2) and the last 3 outcomes. Compared to children with no conditions, children with 1 condition, and children with 2 or more conditions, had more absenteeism (1 condition adjusted incidence rate ratio [IRR] 1.28, 95% CI 1.27-1.30, p < 0.001 and 2 or more conditions adjusted IRR 1.23, 95% CI 1.20-1.28, p < 0.001), greater exclusion (adjusted IRR 2.37, 95% CI 2.25-2.48, p < 0.001 and adjusted IRR 3.04, 95% CI 2.74-3.38, p < 0.001), poorer attainment (adjusted odds ratio [OR] 3.92, 95% CI 3.63-4.23, p < 0.001 and adjusted OR 12.07, 95% CI 9.15-15.94, p < 0.001), and increased unemployment (adjusted OR 1.57, 95% CI 1.49-1.66, p < 0.001 and adjusted OR 2.11, 95% CI 1.83-2.45, p < 0.001). Associations remained after further adjustment for comorbid physical conditions and additional support needs. Coexisting depression was the strongest driver of absenteeism and coexisting ADHD the strongest driver of exclusion. Absence of formal primary care diagnoses was a limitation since ascertaining depression and ADHD from prescriptions omitted affected children receiving alternative or no treatment and some antidepressants can be prescribed for other indications.

Conclusions

Structuring clinical practice and training around single conditions may disadvantage children with neurodevelopmental multimorbidity, who we observed had significantly poorer educational outcomes compared to children with 1 condition and no conditions.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003290&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003290; html:https://europepmc.org/articles/PMC7553326; pdf:https://europepmc.org/articles/PMC7553326?pdf=render 30993728,https://doi.org/10.1111/cen.13990,Risk of incident circulatory disease in patients treated for differentiated thyroid carcinoma with no history of cardiovascular disease.,"Toulis KA, Viola D, Gkoutos G, Keerthy D, Boelaert K, Nirantharakumar K.",,Clinical endocrinology,2019,2019-05-17,N,Atrial fibrillation; Cardiovascular events; Thyroid cancer; Differentiated Thyroid Carcinoma,,,"

Context

The incidence of differentiated thyroid cancer (DTC) is increasing, yet the prognosis is favourable and long-term survival is expected. Exogenous TSH suppression has been used for many years to prevent DTC recurrence and may be associated with increased risks of circulatory diseases.

Design

Risks of circulatory disease in patients treated for DTC were compared to randomly matched patients without DTC (controls) up to a 1:5 ratio using age, sex, body mass index (BMI) and smoking as the matching parameters in a population-based, open cohort study using The Health Improvement Network.

Patients

A total of 3009 patients treated for DTC with no pre-existing cardiovascular disease were identified and matched to 11 303 controls, followed up to median of 5 years.

Results

A total of 1259 incident circulatory events were recorded during the observation period. No difference in the risk of ischaemic heart disease (IHD) (adjusted hazards ratio [aHR]: 1.04, 95% CI: 0.80-1.36) or heart failure (HF) (aHR: 1.27, 95% CI: 0.89-1.81) was detected. The risk of atrial fibrillation (AF) and stroke was significantly higher in patients with DTC (aHR: 1.71, 95% CI: 1.36-2.15 and aHR: 1.34, 95% CI: 1.05-1.72, respectively). In a sensitivity analysis limited to newly diagnosed patients with DTC, only the risk of AF was consistently elevated (aHR: 1.86, 95% CI: 1.33-2.60).

Conclusions

The increased risk of AF in patients who have undergone treatment for DTC but without pre-existing CVD may warrant periodic screening for this arrhythmia. Whereas no evidence of increased risk of IHD or HF was observed, the increased risk of stroke/TIA warrants further investigation.",,doi:https://doi.org/10.1111/cen.13990 -36093379,https://doi.org/10.1016/j.isci.2022.105079,Epidemiologic information discovery from open-access COVID-19 case reports via pretrained language model.,"Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wong ZSY, Xu XK, Sun Y.",,iScience,2022,2022-09-05,Y,Artificial intelligence; Virology; Machine Learning; Health Sciences,,,"Although open-access data are increasingly common and useful to epidemiological research, the curation of such datasets is resource-intensive and time-consuming. Despite the existence of a major source of COVID-19 data, the regularly disclosed case reports were often written in natural language with an unstructured format. Here, we propose a computational framework that can automatically extract epidemiological information from open-access COVID-19 case reports. We develop this framework by coupling a language model developed using deep neural networks with training samples compiled using an optimized data annotation strategy. When applied to the COVID-19 case reports collected from mainland China, our framework outperforms all other state-of-the-art deep learning models. The information extracted from our approach is highly consistent with that obtained from the gold-standard manual coding, with a matching rate of 80%. To disseminate our algorithm, we provide an open-access online platform that is able to estimate key epidemiological statistics in real time, with much less effort for data curation.",,pdf:http://www.cell.com/article/S2589004222013517/pdf; doi:https://doi.org/10.1016/j.isci.2022.105079; html:https://europepmc.org/articles/PMC9441477; pdf:https://europepmc.org/articles/PMC9441477?pdf=render 33306713,https://doi.org/10.1371/journal.pone.0243383,"Health, educational and employment outcomes among children treated for a skin disorder: Scotland-wide retrospective record linkage cohort study of 766,244 children.","Fleming M, McLay JS, Clark D, King A, Mackay DF, Pell JP.",,PloS one,2020,2020-12-11,Y,,,,"

Background

To compare health, educational and employment outcomes of schoolchildren receiving medication for a skin disorder with peers.

Methods

This retrospective population cohort study linked eight Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, school examinations, school absences/exclusions and unemployment to investigate educational (absence, exclusion, special educational need, academic attainment), employment, and health (admissions and mortality) outcomes of 766,244 children attending local authority run primary, secondary and special schools in Scotland between 2009 and 2013.

Results

After adjusting for sociodemographic and maternity confounders the 130,087 (17.0%) children treated for a skin disorder had increased hospitalisation, particularly within one year of commencing treatment (IRR 1.38, 95% CI 1.35-1.41, p<0.001) and mortality (HR 1.50, 95% CI 1.18-1.90, p<0.001). They had greater special educational need (OR 1.19, 95% CI 1.17-1.21, p<0.001) and more frequent absences from school (IRR 1.07, 95% CI 1.06-1.08, p<0.001) but did not exhibit poorer exam attainment or increased post-school unemployment. The associations remained after further adjustment for comorbid chronic conditions.

Conclusions

Despite increased hospitalisation, school absenteeism, and special educational need, children treated for a skin disorder did not have poorer exam attainment or employment outcomes. Whilst findings relating to educational and employment outcomes are reassuring, the association with increased risk of mortality is alarming and merits further investigation.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0243383&type=printable; doi:https://doi.org/10.1371/journal.pone.0243383; html:https://europepmc.org/articles/PMC7732076; pdf:https://europepmc.org/articles/PMC7732076?pdf=render +36093379,https://doi.org/10.1016/j.isci.2022.105079,Epidemiologic information discovery from open-access COVID-19 case reports via pretrained language model.,"Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wong ZSY, Xu XK, Sun Y.",,iScience,2022,2022-09-05,Y,Artificial intelligence; Virology; Machine Learning; Health Sciences,,,"Although open-access data are increasingly common and useful to epidemiological research, the curation of such datasets is resource-intensive and time-consuming. Despite the existence of a major source of COVID-19 data, the regularly disclosed case reports were often written in natural language with an unstructured format. Here, we propose a computational framework that can automatically extract epidemiological information from open-access COVID-19 case reports. We develop this framework by coupling a language model developed using deep neural networks with training samples compiled using an optimized data annotation strategy. When applied to the COVID-19 case reports collected from mainland China, our framework outperforms all other state-of-the-art deep learning models. The information extracted from our approach is highly consistent with that obtained from the gold-standard manual coding, with a matching rate of 80%. To disseminate our algorithm, we provide an open-access online platform that is able to estimate key epidemiological statistics in real time, with much less effort for data curation.",,pdf:http://www.cell.com/article/S2589004222013517/pdf; doi:https://doi.org/10.1016/j.isci.2022.105079; html:https://europepmc.org/articles/PMC9441477; pdf:https://europepmc.org/articles/PMC9441477?pdf=render 37719788,https://doi.org/10.1093/noajnl/vdad096,Development of a core outcome set for use in adult primary glioma phase III interventional trials: A mixed methods study.,"Retzer A, Baddeley E, Sivell S, Scott H, Nelson A, Bulbeck H, Seddon K, Grant R, Adams R, Watts C, Aiyegbusi OL, Kearns P, Rivera SC, Dirven L, Calvert M, Byrne A.",,Neuro-oncology advances,2023,2023-01-01,Y,trials; Outcomes; Neuro-oncology; Delphi; Primary Glioma,,,"

Background

Glioma interventional studies should collect data aligned with patient priorities, enabling treatment benefit assessment and informed decision-making. This requires effective data synthesis and meta-analyses, underpinned by consistent trial outcome measurement, analysis, and reporting. Development of a core outcome set (COS) may contribute to a solution.

Methods

A 5-stage process was used to develop a COS for glioma trials from the UK perspective. Outcome lists were generated in stages 1: a trial registry review and systematic review of qualitative studies and 2: interviews with glioma patients and caregivers. In stage 3, the outcome lists were de-duplicated with accessible terminology, in stage 4 outcomes were rated via a 2-round Delphi process, and stage 5 comprised a consensus meeting to finalize the COS. Patient-reportable COS outcomes were identified.

Results

In Delphi round 1, 96 participants rated 35 outcomes identified in stages 1 and 2, to which a further 10 were added. Participants (77/96) rated the resulting 45 outcomes in round 2. Of these, 22 outcomes met a priori threshold for inclusion in the COS. After further review, a COS consisting of 19 outcomes grouped into 7 outcome domains (survival, adverse events, activities of daily living, health-related quality of life, seizure activity, cognitive function, and physical function) was finalized by 13 participants at the consensus meeting.

Conclusions

A COS for glioma trials was developed, comprising 7 outcome domains. Additional research will identify appropriate measurement tools and further validate this COS.",,pdf:https://academic.oup.com/noa/advance-article-pdf/doi/10.1093/noajnl/vdad096/51026152/vdad096.pdf; doi:https://doi.org/10.1093/noajnl/vdad096; html:https://europepmc.org/articles/PMC10503650; pdf:https://europepmc.org/articles/PMC10503650?pdf=render 35210596,https://doi.org/10.1038/s41591-022-01736-z,Modeling comparative cost-effectiveness of SARS-CoV-2 vaccine dose fractionation in India.,"Du Z, Wang L, Pandey A, Lim WW, Chinazzi M, Piontti APY, Lau EHY, Wu P, Malani A, Cobey S, Cowling BJ.",,Nature medicine,2022,2022-02-24,Y,,,,"Given global Coronavirus Disease 2019 (COVID-19) vaccine shortages and inequity of vaccine distributions, fractionation of vaccine doses might be an effective strategy for reducing public health and economic burden, notwithstanding the emergence of new variants of concern. In this study, we developed a multi-scale model incorporating population-level transmission and individual-level vaccination to estimate the costs of hospitalization and vaccination and the economic benefits of reducing COVID-19 deaths due to dose-fractionation strategies in India. We used large-scale survey data of the willingness to pay together with data of vaccine and hospital admission costs to build the model. We found that fractional doses of vaccines could be an economically viable vaccination strategy compared to alternatives of either full-dose vaccination or no vaccination. Dose-sparing strategies could save a large number of lives, even with the emergence of new variants with higher transmissibility.",,pdf:https://www.nature.com/articles/s41591-022-01736-z.pdf; doi:https://doi.org/10.1038/s41591-022-01736-z; html:https://europepmc.org/articles/PMC9117137; pdf:https://europepmc.org/articles/PMC9117137?pdf=render 34112101,https://doi.org/10.1186/s12872-021-02020-7,Routine clinical care data from thirteen cardiac outpatient clinics: design of the Cardiology Centers of the Netherlands (CCN) database.,"Bots SH, Siegersma KR, Onland-Moret NC, Asselbergs FW, Somsen GA, Tulevski II, den Ruijter HM, Hofstra L.",,BMC cardiovascular disorders,2021,2021-06-10,Y,Prevention; Big Data; Cardiovascular Care; Clinical Care Data,,,"

Background

Despite the increasing availability of clinical data due to the digitalisation of healthcare systems, data often remain inaccessible due to the diversity of data collection systems. In the Netherlands, Cardiology Centers of the Netherlands (CCN) introduced ""one-stop shop"" diagnostic clinics for patients suspected of cardiac disease by their general practitioner. All CCN clinics use the same data collection system and standardised protocol, creating a large regular care database. This database can be used to describe referral practices, evaluate risk factors for cardiovascular disease (CVD) in important patient subgroups, and develop prediction models for use in daily care.

Construction and content

The current database contains data on all patients who underwent a cardiac workup in one of the 13 CCN clinics between 2007 and February 2018 (n = 109,151, 51.9% women). Data were pseudonymised and contain information on anthropometrics, cardiac symptoms, risk factors, comorbidities, cardiovascular and family history, standard blood laboratory measurements, transthoracic echocardiography, electrocardiography in rest and during exercise, and medication use. Clinical follow-up is based on medical need and consisted of either a repeat visit at CCN (43.8%) or referral for an external procedure in a hospital (16.5%). Passive follow-up via linkage to national mortality registers is available for 95% of the database.

Utility and discussion

The CCN database provides a strong base for research into historically underrepresented patient groups due to the large number of patients and the lack of in- and exclusion criteria. It also enables the development of artificial intelligence-based decision support tools. Its contemporary nature allows for comparison of daily care with the current guidelines and protocols. Missing data is an inherent limitation, as the cardiologist could deviate from standardised protocols when clinically indicated.

Conclusion

The CCN database offers the opportunity to conduct research in a unique population referred from the general practitioner to the cardiologist for diagnostic workup. This, in combination with its large size, the representation of historically underrepresented patient groups and contemporary nature makes it a valuable tool for expanding our knowledge of cardiovascular diseases.

Trial registration

Not applicable.",,pdf:https://bmccardiovascdisord.biomedcentral.com/counter/pdf/10.1186/s12872-021-02020-7; doi:https://doi.org/10.1186/s12872-021-02020-7; html:https://europepmc.org/articles/PMC8191101; pdf:https://europepmc.org/articles/PMC8191101?pdf=render @@ -1789,23 +1789,23 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 38555664,https://doi.org/10.1016/j.envint.2024.108602,A tool to assess risk of bias in non-randomized follow-up studies of exposure effects (ROBINS-E).,"Higgins JPT, Morgan RL, Rooney AA, Taylor KW, Thayer KA, Silva RA, Lemeris C, Akl EA, Bateson TF, Berkman ND, Glenn BS, Hróbjartsson A, LaKind JS, McAleenan A, Meerpohl JJ, Nachman RM, Obbagy JE, O'Connor A, Radke EG, Savović J, Schünemann HJ, Shea B, Tilling K, Verbeek J, Viswanathan M, Sterne JAC.",,Environment international,2024,2024-03-24,N,Exposure; Environmental; epidemiology; Selection Bias; Confounding; Risk Of Bias; Misclassification/measurement Bias,,,"

Background

Observational epidemiologic studies provide critical data for the evaluation of the potential effects of environmental, occupational and behavioural exposures on human health. Systematic reviews of these studies play a key role in informing policy and practice. Systematic reviews should incorporate assessments of the risk of bias in results of the included studies.

Objective

To develop a new tool, Risk Of Bias In Non-randomized Studies - of Exposures (ROBINS-E) to assess risk of bias in estimates from cohort studies of the causal effect of an exposure on an outcome.

Methods and results

ROBINS-E was developed by a large group of researchers from diverse research and public health disciplines through a series of working groups, in-person meetings and pilot testing phases. The tool aims to assess the risk of bias in a specific result (exposure effect estimate) from an individual observational study that examines the effect of an exposure on an outcome. A series of preliminary considerations informs the core ROBINS-E assessment, including details of the result being assessed and the causal effect being estimated. The assessment addresses bias within seven domains, through a series of 'signalling questions'. Domain-level judgements about risk of bias are derived from the answers to these questions, then combined to produce an overall risk of bias judgement for the result, together with judgements about the direction of bias.

Conclusion

ROBINS-E provides a standardized framework for examining potential biases in results from cohort studies. Future work will produce variants of the tool for other epidemiologic study designs (e.g. case-control studies). We believe that ROBINS-E represents an important development in the integration of exposure assessment, evidence synthesis and causal inference.",,doi:https://doi.org/10.1016/j.envint.2024.108602 30551632,https://doi.org/10.3390/ijerph15122845,"Incidence, Costs and Predictors of Non-Union, Delayed Union and Mal-Union Following Long Bone Fracture.","Ekegren CL, Edwards ER, de Steiger R, Gabbe BJ.",,International journal of environmental research and public health,2018,2018-12-13,Y,Costs; Bone; Fracture; Data Linkage; Non-union; Mal-union; Delayed Union,Improving Public Health,,"Fracture healing complications are common and result in significant healthcare burden. The aim of this study was to determine the rate, costs and predictors of two-year readmission for surgical management of healing complications (delayed, mal, non-union) following fracture of the humerus, tibia or femur. Humeral, tibial and femoral (excluding proximal) fractures registered by the Victorian Orthopaedic Trauma Outcomes Registry over five years (n = 3962) were linked with population-level hospital admissions data to identify two-year readmissions for delayed, mal or non-union. Study outcomes included hospital length-of-stay (LOS) and inpatient costs. Multivariable logistic regression was used to determine demographic and injury-related factors associated with admission for fracture healing complications. Of the 3886 patients linked, 8.1% were readmitted for healing complications within two years post-fracture, with non-union the most common complication and higher rates for femoral and tibial shaft fractures. Admissions for fracture healing complications incurred total costs of $4.9 million AUD, with a median LOS of two days. After adjusting for confounders, patients had higher odds of developing complications if they were older, receiving compensation or had tibial or femoral shaft fractures. Patients who are older, with tibial and femoral shaft fractures should be targeted for future research aimed at preventing complications.",,pdf:https://www.mdpi.com/1660-4601/15/12/2845/pdf?version=1544701398; doi:https://doi.org/10.3390/ijerph15122845; html:https://europepmc.org/articles/PMC6313538; pdf:https://europepmc.org/articles/PMC6313538?pdf=render 33659712,https://doi.org/10.12688/wellcomeopenres.16431.2,Healthcare use by people who use illicit opioids (HUPIO): development of a cohort based on electronic primary care records in England.,"Lewer D, Padmanathan P, Qummer Ul Arfeen M, Denaxas S, Forbes H, Gonzalez-Izquierdo A, Hickman M.",,Wellcome open research,2020,2020-01-01,Y,Drug dependence; Illicit Drugs; Substance Use Disorders; Electronic Health Records; Opioid Agonist Therapy,,,"Background: People who use illicit opioids such as heroin have substantial health needs, but there are few longitudinal studies of general health and healthcare in this population. Most research to date has focused on a narrow set of outcomes, including overdoses and HIV or hepatitis infections. We developed and validated a cohort using UK primary care electronic health records (Clinical Practice Research Datalink GOLD and AURUM databases) to facilitate research into healthcare use by people who use illicit opioid use (HUPIO). Methods: Participants are patients in England with primary care records indicating a history of illicit opioid use. We identified codes including prescriptions of opioid agonist therapies (methadone and buprenorphine) and clinical observations such as 'heroin dependence'. We constructed a cohort of patients with at least one of these codes and aged 18-64 at cohort entry, with follow-up between January 1997 and March 2020. We validated the cohort by comparing patient characteristics and mortality rates to other cohorts of people who use illicit opioids, with different recruitment methods. Results: Up to March 2020, the HUPIO cohort included 138,761 patients with a history of illicit opioid use. Demographic characteristics and all-cause mortality were similar to existing cohorts: 69% were male; the median age at index for patients in CPRD AURUM (the database with more included participants) was 35.3 (interquartile range 29.1-42.6); the average age of new cohort entrants increased over time; 76% had records indicating current tobacco smoking; patients disproportionately lived in deprived neighbourhoods; and all-cause mortality risk was 6.6 (95% CI 6.5-6.7) times the general population of England. Conclusions: Primary care data offer new opportunities to study holistic health outcomes and healthcare of this population. The large sample enables investigation of rare outcomes, whilst the availability of linkage to external datasets allows investigation of hospital use, cancer treatment, and mortality.",,doi:https://doi.org/10.12688/wellcomeopenres.16431.2; html:https://europepmc.org/articles/PMC7901498; pdf:https://europepmc.org/articles/PMC7901498?pdf=render -38438269,https://doi.org/10.3399/bjgp.2023.0214,Post-hospitalisation asthma management in primary care: a retrospective cohort study.,"Punyadasa D, Simms-Williams N, Adderley NJ, Thayakaran R, Mansur AH, Nirantharakumar K, Nagakumar P, Haroon S.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2024,2024-05-30,Y,Management; Asthma; Cohort studies; Primary Health Care; Ethnic And Racial Minorities; Post-hospitalisation,,,"

Background

Clinical guidelines recommend that patients admitted to hospital for asthma attacks are reviewed in primary care following hospital discharge.

Aim

To evaluate asthma management in primary care following a hospital admission for asthma and its associations with patient characteristics.

Design and setting

A retrospective cohort study using English primary care data from the Clinical Practice Research Datalink Aurum database and linked Hospital Episode Statistics Admitted Patient Care data.

Method

Patients with asthma aged ≥5 years who had at least one asthma-related hospital admission from 1 January 2017 to 31 December 2019 were included. The primary outcome was a composite of any of the following delivered in primary care within 28 days from hospital discharge: asthma review, asthma management plan, asthma medication prescriptions, demonstration of inhaler technique, or smoking cessation counselling. The association between patient characteristics and delivery of clinical care was assessed using logistic regression.

Results

The study included 17 457 patients. A total of 10 515 (60.2%) patients received the primary outcome within 28 days of hospital discharge. There were 2311 (13.2%) who received an asthma review, 1459 (8.4%) an asthma management plan, 9996 (57.3%) an asthma medication, 1500 (8.6%) a demonstration of inhaler technique, and 52 (1.2% of smokers) had smoking cessation counselling. Patients from Black ethnic minority groups received less of this care (27%-54% lower odds, depending on age). However, short-acting bronchodilator prescriptions in the previous year were associated with an increased likelihood of the primary outcome.

Conclusion

A significant proportion of patients do not receive timely follow-up in primary care following asthma-related admissions to hospital, particularly among Black ethnic minority groups.",,doi:https://doi.org/10.3399/BJGP.2023.0214; html:https://europepmc.org/articles/PMC10947362; pdf:https://europepmc.org/articles/PMC10947362?pdf=render 32807724,https://doi.org/10.1016/j.auec.2020.07.007,Pain assessment following burn injury in Australia and New Zealand: Variation in practice and its association on in-hospital outcomes.,"Tracy LM, Cleland H, Cameron PA, Gabbe BJ.",,Australasian emergency care,2021,2020-08-15,N,Australia; Burn; Pain; New Zealand; Registry; Pain Assessment,,,"

Background

Pain is common following burn injury. Pain assessments are required to ensure appropriate pain management is provided. This study aimed to describe the prevalence and potential variation in practice of validated and documented pain assessment following burn injury in Australian and New Zealand burn units, identify clinical characteristics of patients who receive a pain assessment, and explore the associations between receiving a pain assessment and in-hospital outcomes.

Methods

Burns Registry of Australia and New Zealand (BRANZ) admissions data were extracted. Responses to the pain assessment field were presented by contributing burns unit using frequencies and percentages. Demographic, injury severity and event, and in-hospital outcomes data were assessed.

Results

There were 3009 admissions over the study period; 2481 of these received an assessment. The rate of pain assessment varied considerably between units. Women and adult patients more commonly received a pain assessment. Receiving a pain assessment was associated with a 53% adjusted increase in LOS.

Conclusions

There are differences in the profile of patients who receive a pain assessment after burn injury. The findings of this study will be reported back to designated burns units to improve pain assessment rates and patient care.",,doi:https://doi.org/10.1016/j.auec.2020.07.007 31053412,https://doi.org/10.1016/j.burns.2019.04.006,Severe burns in Australian and New Zealand adults: Epidemiology and burn centre care.,"Toppi J, Cleland H, Gabbe B.",,Burns : journal of the International Society for Burn Injuries,2019,2019-04-30,N,Mortality; Burn; Severe burns; epidemiology,,,"

Introduction

Studies describing the epidemiology of severe burns (>20% total body surface area) in adults are limited despite the extensive associated morbidity and mortality. This study aimed to describe the epidemiology of severe burn injuries admitted to burn centres in Australia and New Zealand.

Materials and methods

Data from the Burns Registry of Australia and New Zealand (BRANZ) were used in this study. Patients were eligible for inclusion if they were admitted between August 2009 and June 2013, were adults (18-years or older), and had burns of 20% total body surface area (TBSA) or greater. Demographics, burn characteristics and in-hospital mortality risk factors were investigated using multivariable Cox proportional hazards analysis.

Results

There were 496 BRANZ registered patients who met the inclusion criteria. Over half of the patients were aged 18-40 years and most were male. The median (IQR) TBSA was 31 (25-47). Most (75%) patients had burns involving <50% TBSA, 58% sustained their burn injury at home, and 86% had sustained flame burns. Leisure activities, working for income and preparing food together accounted for over 48% of the activities undertaken at the time of injury. The in-hospital mortality rate was 17% and the median (IQR) length of stay was 24 (12-44) days. Seventy-two percent were admitted to an intensive care unit (ICU) and 40% of patients had an associated inhalation injury. Alcohol and/or drug involvement was suspected in 25% of cases.

Conclusion

This study describes the demographics, burn injury characteristics and in-hospital outcomes of severe burn injuries in adults whilst also identifying key predictors of inpatient mortality. Key findings included the over-representation of young males, intentional self-harm injuries and flame as a cause of burns and highlights high risk groups to help aid in the development of targeted prevention strategies.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa50368/Download/0050368-25062019091637.pdf; doi:https://doi.org/10.1016/j.burns.2019.04.006 +38438269,https://doi.org/10.3399/bjgp.2023.0214,Post-hospitalisation asthma management in primary care: a retrospective cohort study.,"Punyadasa D, Simms-Williams N, Adderley NJ, Thayakaran R, Mansur AH, Nirantharakumar K, Nagakumar P, Haroon S.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2024,2024-05-30,Y,Management; Asthma; Cohort studies; Primary Health Care; Ethnic And Racial Minorities; Post-hospitalisation,,,"

Background

Clinical guidelines recommend that patients admitted to hospital for asthma attacks are reviewed in primary care following hospital discharge.

Aim

To evaluate asthma management in primary care following a hospital admission for asthma and its associations with patient characteristics.

Design and setting

A retrospective cohort study using English primary care data from the Clinical Practice Research Datalink Aurum database and linked Hospital Episode Statistics Admitted Patient Care data.

Method

Patients with asthma aged ≥5 years who had at least one asthma-related hospital admission from 1 January 2017 to 31 December 2019 were included. The primary outcome was a composite of any of the following delivered in primary care within 28 days from hospital discharge: asthma review, asthma management plan, asthma medication prescriptions, demonstration of inhaler technique, or smoking cessation counselling. The association between patient characteristics and delivery of clinical care was assessed using logistic regression.

Results

The study included 17 457 patients. A total of 10 515 (60.2%) patients received the primary outcome within 28 days of hospital discharge. There were 2311 (13.2%) who received an asthma review, 1459 (8.4%) an asthma management plan, 9996 (57.3%) an asthma medication, 1500 (8.6%) a demonstration of inhaler technique, and 52 (1.2% of smokers) had smoking cessation counselling. Patients from Black ethnic minority groups received less of this care (27%-54% lower odds, depending on age). However, short-acting bronchodilator prescriptions in the previous year were associated with an increased likelihood of the primary outcome.

Conclusion

A significant proportion of patients do not receive timely follow-up in primary care following asthma-related admissions to hospital, particularly among Black ethnic minority groups.",,doi:https://doi.org/10.3399/BJGP.2023.0214; html:https://europepmc.org/articles/PMC10947362; pdf:https://europepmc.org/articles/PMC10947362?pdf=render 35513530,https://doi.org/10.1038/s41591-022-01781-8,Patient reported outcome assessment must be inclusive and equitable.,"Calvert MJ, Cruz Rivera S, Retzer A, Hughes SE, Campbell L, Molony-Oates B, Aiyegbusi OL, Stover AM, Wilson R, McMullan C, Anderson NE, Turner GM, Davies EH, Verdi R, Velikova G, Kamudoni P, Muslim S, Gheorghe A, O'Connor D, Liu X, Wu AW, Denniston AK.",,Nature medicine,2022,2022-06-01,N,,,,,,pdf:https://www.nature.com/articles/s41591-022-01781-8.pdf; doi:https://doi.org/10.1038/s41591-022-01781-8 32346541,https://doi.org/10.1093/burnst/tkz004,Predictors of itch and pain in the 12 months following burn injury: results from the Burns Registry of Australia and New Zealand (BRANZ) Long-Term Outcomes Project.,"Tracy LM, Edgar DW, Schrale R, Cleland H, Gabbe BJ, BRANZ Adult Long-Term Outcomes Pilot Project participating sites and working party.",,Burns & trauma,2020,2020-02-27,Y,Australia; Pain; New Zealand; Cohort study; Outcomes; Predictor; Itch; Burn Registry,Better Care,injuries and accidents,"

Background

Itch and pain are common complaints of patients with burn injuries. This study aimed to describe the prevalence and predictors of itch and moderate to severe pain in the first 12 months following a burn injury, and determine the association between itch, moderate to severe pain, work-related outcomes, and health-related quality of life following a burn injury.

Methods

Burn patients aged 18 years and older were recruited from five Australian specialist burn units. Patients completed the 36-item Short Form Health Survey Version 2 (SF-36 V2), the Sickness Impact Profile (SIP) work scale, and a specially developed questionnaire relating to itch at 1, 6, and 12 months post-injury. Moderate to severe pain was defined as a score less than 40 on the bodily pain domain of the SF-36 V2. Multivariate mixed-effects regression models were used to identify patient and burn injury predictors of itch and moderate to severe pain.

Results

Three hundred and twenty-eight patients were included. The prevalence of itch decreased from 50% at 1 month to 27% at 12 months. Similarly, the prevalence of moderate to severe pain decreased from 23% at 1 month to 13% at 12 months. Compared to patients aged 18-34, the adjusted odds of experiencing any itch were 59% (95% CI: 0.20, 0.82) and 55% (95% CI: 0.22, 0.91) lower for patients aged between 35 and 49 and ≥ 50 years, respectively. Compared to patients aged 18-34, the adjusted odds of experiencing moderate to severe pain were 3.12 (95% CI: 1.35, 7.20) and 3.42 (95% CI: 1.47, 7.93) times higher for patients aged 35-49 and ≥ 50 years, respectively.

Conclusions

Less than 15% of patients reported moderate or severe pain at 12 months, while approximately one-quarter of the patients reported itch at the same period. The presence of moderate to severe pain was associated with a greater negative impact on health-related quality of life and work outcomes compared to itch. Further research is needed to improve our ability to identify patients at higher risk of persistent itch and pain who would benefit from targeted review and intervention studies.",,pdf:https://academic.oup.com/burnstrauma/article-pdf/doi/10.1093/burnst/tkz004/33423529/tkz004.pdf; doi:https://doi.org/10.1093/burnst/tkz004; html:https://europepmc.org/articles/PMC7175773; pdf:https://europepmc.org/articles/PMC7175773?pdf=render 37748493,https://doi.org/10.1016/s2213-2600(23)00262-x,"Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study.",C-MORE/PHOSP-COVID Collaborative Group.,,The Lancet. Respiratory medicine,2023,2023-09-22,Y,,,,"

Introduction

The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures.

Methods

In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025.

Findings

Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2-6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5-5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4-10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32-4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23-11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation.

Interpretation

After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification.

Funding

UK Research and Innovation and National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S221326002300262X/pdf; doi:https://doi.org/10.1016/S2213-2600(23)00262-X; html:https://europepmc.org/articles/PMC7615263; pdf:https://europepmc.org/articles/PMC7615263?pdf=render -34611362,https://doi.org/10.1038/s41588-021-00944-6,Polygenic basis and biomedical consequences of telomere length variation.,"Codd V, Wang Q, Allara E, Musicha C, Kaptoge S, Stoma S, Jiang T, Hamby SE, Braund PS, Bountziouka V, Budgeon CA, Denniff M, Swinfield C, Papakonstantinou M, Sheth S, Nanus DE, Warner SC, Wang M, Khera AV, Eales J, Ouwehand WH, Thompson JR, Di Angelantonio E, Wood AM, Butterworth AS, Danesh JN, Nelson CP, Samani NJ.",,Nature genetics,2021,2021-10-05,Y,,,,"Telomeres, the end fragments of chromosomes, play key roles in cellular proliferation and senescence. Here we characterize the genetic architecture of naturally occurring variation in leukocyte telomere length (LTL) and identify causal links between LTL and biomedical phenotypes in 472,174 well-characterized UK Biobank participants. We identified 197 independent sentinel variants associated with LTL at 138 genomic loci (108 new). Genetically determined differences in LTL were associated with multiple biological traits, ranging from height to bone marrow function, as well as several diseases spanning neoplastic, vascular and inflammatory pathologies. Finally, we estimated that, at the age of 40 years, people with an LTL >1 s.d. shorter than the population mean had a 2.5-year-lower life expectancy compared with the group with ≥1 s.d. longer LDL. Overall, we furnish new insights into the genetic regulation of LTL, reveal wide-ranging influences of LTL on physiological traits, diseases and longevity, and provide a powerful resource available to the global research community.",,pdf:https://www.nature.com/articles/s41588-021-00944-6.pdf; doi:https://doi.org/10.1038/s41588-021-00944-6; html:https://europepmc.org/articles/PMC8492471; pdf:https://europepmc.org/articles/PMC8492471?pdf=render 33472714,https://doi.org/10.1017/s1368980021000197,Diet and risk of gastro-oesophageal reflux disease in the Melbourne Collaborative Cohort Study.,"Wang SE, Hodge AM, Dashti SG, Dixon-Suen SC, Mitchell H, Thomas RJ, Williamson EM, Makalic E, Boussioutas A, Haydon AM, Giles GG, Milne RL, Kendall BJ, English DR.",,Public health nutrition,2021,2021-01-21,N,Fat; Diet; Prospective Cohort Study; Gastro-oesophageal Reflux Disease; Carbonated Beverages,,,"

Objective

To examine associations between diet and risk of developing gastro-oesophageal reflux disease (GERD).

Design

Prospective cohort with a median follow-up of 15·8 years. Baseline diet was measured using a FFQ. GERD was defined as self-reported current or history of daily heartburn or acid regurgitation beginning at least 2 years after baseline. Sex-specific logistic regressions were performed to estimate OR for GERD associated with diet quality scores and intakes of nutrients, food groups and individual foods and beverages. The effect of substituting saturated fat for monounsaturated or polyunsaturated fat on GERD risk was examined.

Setting

Melbourne, Australia.

Participants

A cohort of 20 926 participants (62 % women) aged 40-59 years at recruitment between 1990 and 1994.

Results

For men, total fat intake was associated with increased risk of GERD (OR 1·05 per 5 g/d; 95 % CI 1·01, 1·09; P = 0·016), whereas total carbohydrate (OR 0·89 per 30 g/d; 95 % CI 0·82, 0·98; P = 0·010) and starch intakes (OR 0·84 per 30 g/d; 95 % CI 0·75, 0·94; P = 0·005) were associated with reduced risk. Nutrients were not associated with risk for women. For both sexes, substituting saturated fat for polyunsaturated or monounsaturated fat did not change risk. For both sexes, fish, chicken, cruciferous vegetables and carbonated beverages were associated with increased risk, whereas total fruit and citrus were associated with reduced risk. No association was observed with diet quality scores.

Conclusions

Diet is a possible risk factor for GERD, but food considered as triggers of GERD symptoms might not necessarily contribute to disease development. Potential differential associations for men and women warrant further investigation.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/274F1A424FA99A10625C3447D256A318/S1368980021000197a.pdf/div-class-title-diet-and-risk-of-gastro-oesophageal-reflux-disease-in-the-melbourne-collaborative-cohort-study-div.pdf; doi:https://doi.org/10.1017/S1368980021000197; html:https://europepmc.org/articles/PMC11082811; pdf:https://europepmc.org/articles/PMC11082811?pdf=render; doi:https://doi.org/10.1017/s1368980021000197 +34611362,https://doi.org/10.1038/s41588-021-00944-6,Polygenic basis and biomedical consequences of telomere length variation.,"Codd V, Wang Q, Allara E, Musicha C, Kaptoge S, Stoma S, Jiang T, Hamby SE, Braund PS, Bountziouka V, Budgeon CA, Denniff M, Swinfield C, Papakonstantinou M, Sheth S, Nanus DE, Warner SC, Wang M, Khera AV, Eales J, Ouwehand WH, Thompson JR, Di Angelantonio E, Wood AM, Butterworth AS, Danesh JN, Nelson CP, Samani NJ.",,Nature genetics,2021,2021-10-05,Y,,,,"Telomeres, the end fragments of chromosomes, play key roles in cellular proliferation and senescence. Here we characterize the genetic architecture of naturally occurring variation in leukocyte telomere length (LTL) and identify causal links between LTL and biomedical phenotypes in 472,174 well-characterized UK Biobank participants. We identified 197 independent sentinel variants associated with LTL at 138 genomic loci (108 new). Genetically determined differences in LTL were associated with multiple biological traits, ranging from height to bone marrow function, as well as several diseases spanning neoplastic, vascular and inflammatory pathologies. Finally, we estimated that, at the age of 40 years, people with an LTL >1 s.d. shorter than the population mean had a 2.5-year-lower life expectancy compared with the group with ≥1 s.d. longer LDL. Overall, we furnish new insights into the genetic regulation of LTL, reveal wide-ranging influences of LTL on physiological traits, diseases and longevity, and provide a powerful resource available to the global research community.",,pdf:https://www.nature.com/articles/s41588-021-00944-6.pdf; doi:https://doi.org/10.1038/s41588-021-00944-6; html:https://europepmc.org/articles/PMC8492471; pdf:https://europepmc.org/articles/PMC8492471?pdf=render 33986429,https://doi.org/10.1038/s41598-021-89743-x,Predicting sex from retinal fundus photographs using automated deep learning.,"Korot E, Pontikos N, Liu X, Wagner SK, Faes L, Huemer J, Balaskas K, Denniston AK, Khawaja A, Keane PA.",,Scientific reports,2021,2021-05-13,Y,,,,"Deep learning may transform health care, but model development has largely been dependent on availability of advanced technical expertise. Herein we present the development of a deep learning model by clinicians without coding, which predicts reported sex from retinal fundus photographs. A model was trained on 84,743 retinal fundus photos from the UK Biobank dataset. External validation was performed on 252 fundus photos from a tertiary ophthalmic referral center. For internal validation, the area under the receiver operating characteristic curve (AUROC) of the code free deep learning (CFDL) model was 0.93. Sensitivity, specificity, positive predictive value (PPV) and accuracy (ACC) were 88.8%, 83.6%, 87.3% and 86.5%, and for external validation were 83.9%, 72.2%, 78.2% and 78.6% respectively. Clinicians are currently unaware of distinct retinal feature variations between males and females, highlighting the importance of model explainability for this task. The model performed significantly worse when foveal pathology was present in the external validation dataset, ACC: 69.4%, compared to 85.4% in healthy eyes, suggesting the fovea is a salient region for model performance OR (95% CI): 0.36 (0.19, 0.70) p = 0.0022. Automated machine learning (AutoML) may enable clinician-driven automated discovery of novel insights and disease biomarkers.",,pdf:https://www.nature.com/articles/s41598-021-89743-x.pdf; doi:https://doi.org/10.1038/s41598-021-89743-x; html:https://europepmc.org/articles/PMC8119673; pdf:https://europepmc.org/articles/PMC8119673?pdf=render 38371671,https://doi.org/10.1016/j.jdin.2023.09.007,Fasting blood glucose and insulin are not associated with atopic dermatitis in a pediatric population: A longitudinal cohort study from the Avon Longitudinal Study of Parents and Children.,"Shan J, Ye M, Ku E, McCulloch CE, Langan SM, Abuabara K.",,JAAD international,2024,2023-10-23,N,Diabetes mellitus; Biomarkers; Clinical research; epidemiology; endocrinology; Atopic Dermatitis; Alspac; Pediatric Dermatology,,,,,doi:https://doi.org/10.1016/j.jdin.2023.09.007; html:https://europepmc.org/articles/PMC10869312; pdf:https://europepmc.org/articles/PMC10869312?pdf=render; doi:https://doi.org/10.1016/j.jdin.2023.09.007 35681241,https://doi.org/10.1186/s12933-022-01525-5,Elevated plasma triglyceride concentration and risk of adverse clinical outcomes in 1.5 million people: a CALIBER linked electronic health record study.,"Patel RS, Pasea L, Soran H, Downie P, Jones R, Hingorani AD, Neely D, Denaxas S, Hemingway H.",,Cardiovascular diabetology,2022,2022-06-09,Y,Lipids; Triglycerides; Myocardial infarction; Diabetes; Pancreatitis,,,"

Background

Assessing the spectrum of disease risk associated with hypertriglyceridemia is needed to inform potential benefits from emerging triglyceride lowering treatments. We sought to examine the associations between a full range of plasma triglyceride concentration with five clinical outcomes.

Methods

We used linked data from primary and secondary care for 15 M people, to explore the association between triglyceride concentration and risk of acute pancreatitis, chronic pancreatitis, new onset diabetes, myocardial infarction and all-cause mortality, over a median of 6-7 years follow up.

Results

Triglyceride concentration was available for 1,530,411 individuals (mean age 56·6 ± 15·6 years, 51·4% female), with a median of 1·3 mmol/L (IQR: 0.9.to 1.9). Severe hypertriglyceridemia, defined as > 10 mmol/L, was identified in 3289 (0·21%) individuals including 620 with > 20 mmol/L. In multivariable analyses, a triglyceride concentration > 20 mmol/L was associated with very high risk for acute pancreatitis (Hazard ratio (HR) 13·55 (95% CI 9·15-20·06)); chronic pancreatitis (HR 25·19 (14·91-42·55)); and high risk for diabetes (HR 5·28 (4·51-6·18)) and all-cause mortality (HR 3·62 (2·82-4·65)) when compared to the reference category of ≤ 1·7 mmol/L. An association with myocardial infarction, however, was only observed for more moderate hypertriglyceridaemia between 1.7 and 10 mmol/L. We found a risk interaction with age, with higher risks for all outcomes including mortality among those ≤ 40 years compared to > 40 years.

Conclusions

We highlight an exponential association between severe hypertriglyceridaemia and risk of incident acute and chronic pancreatitis, new diabetes, and mortality, especially at younger ages, but not for myocardial infarction for which only moderate hypertriglyceridemia conferred risk.",,pdf:https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-022-01525-5; doi:https://doi.org/10.1186/s12933-022-01525-5; html:https://europepmc.org/articles/PMC9185961; pdf:https://europepmc.org/articles/PMC9185961?pdf=render 34226637,https://doi.org/10.1038/s41366-021-00896-1,Effects of adiposity on the human plasma proteome: observational and Mendelian randomisation estimates.,"Goudswaard LJ, Bell JA, Hughes DA, Corbin LJ, Walter K, Davey Smith G, Soranzo N, Danesh J, Di Angelantonio E, Ouwehand WH, Watkins NA, Roberts DJ, Butterworth AS, Hers I, Timpson NJ.",,International journal of obesity (2005),2021,2021-07-05,Y,,,,"

Background

Variation in adiposity is associated with cardiometabolic disease outcomes, but mechanisms leading from this exposure to disease are unclear. This study aimed to estimate effects of body mass index (BMI) on an extensive set of circulating proteins.

Methods

We used SomaLogic proteomic data from up to 2737 healthy participants from the INTERVAL study. Associations between self-reported BMI and 3622 unique plasma proteins were explored using linear regression. These were complemented by Mendelian randomisation (MR) analyses using a genetic risk score (GRS) comprised of 654 BMI-associated polymorphisms from a recent genome-wide association study (GWAS) of adult BMI. A disease enrichment analysis was performed using DAVID Bioinformatics 6.8 for proteins which were altered by BMI.

Results

Observationally, BMI was associated with 1576 proteins (P < 1.4 × 10-5), with particularly strong evidence for a positive association with leptin and fatty acid-binding protein-4 (FABP4), and a negative association with sex hormone-binding globulin (SHBG). Observational estimates were likely confounded, but the GRS for BMI did not associate with measured confounders. MR analyses provided evidence for a causal relationship between BMI and eight proteins including leptin (0.63 standard deviation (SD) per SD BMI, 95% CI 0.48-0.79, P = 1.6 × 10-15), FABP4 (0.64 SD per SD BMI, 95% CI 0.46-0.83, P = 6.7 × 10-12) and SHBG (-0.45 SD per SD BMI, 95% CI -0.65 to -0.25, P = 1.4 × 10-5). There was agreement in the magnitude of observational and MR estimates (R2 = 0.33) and evidence that proteins most strongly altered by BMI were enriched for genes involved in cardiovascular disease.

Conclusions

This study provides evidence for a broad impact of adiposity on the human proteome. Proteins strongly altered by BMI include those involved in regulating appetite, sex hormones and inflammation; such proteins are also enriched for cardiovascular disease-related genes. Altogether, results help focus attention onto new proteomic signatures of obesity-related disease.",,pdf:https://www.nature.com/articles/s41366-021-00896-1.pdf; doi:https://doi.org/10.1038/s41366-021-00896-1; html:https://europepmc.org/articles/PMC8455324; pdf:https://europepmc.org/articles/PMC8455324?pdf=render -36215124,https://doi.org/10.1161/circgen.121.003598,Gene Sequencing Identifies Perturbation in Nitric Oxide Signaling as a Nonlipid Molecular Subtype of Coronary Artery Disease.,"Khera AV, Wang M, Chaffin M, Emdin CA, Samani NJ, Schunkert H, Watkins H, McPherson R, Erdmann J, Elosua R, Boerwinkle E, Ardissino D, Butterworth AS, Di Angelantonio E, Naheed A, Danesh J, Chowdhury R, Krumholz HM, Sheu WH, Rich SS, Rotter JI, Chen YI, Gabriel S, Lander ES, Saleheen D, Kathiresan S.",,Circulation. Genomic and precision medicine,2022,2022-10-10,N,Atherosclerosis; coronary artery disease; Genetic Association Studies; Nitric Oxide Synthase Type Iii; Precision Medicine,,,"

Background

A key goal of precision medicine is to disaggregate common, complex diseases into discrete molecular subtypes. Rare coding variants in the low-density lipoprotein receptor gene (LDLR) are identified in 1% to 2% of coronary artery disease (CAD) patients, defining a molecular subtype with risk driven by hypercholesterolemia.

Methods

To search for additional subtypes, we compared the frequency of rare, predicted loss-of-function and damaging missense variants aggregated within a given gene in 41 081 CAD cases versus 217 115 controls.

Results

Rare variants in LDLR were most strongly associated with CAD, present in 1% of cases and associated with 4.4-fold increased CAD risk. A second subtype was characterized by variants in endothelial nitric oxide synthase gene (NOS3), a key enzyme regulating vascular tone, endothelial function, and platelet aggregation. A rare predicted loss-of-function or damaging missense variants in NOS3 was present in 0.6% of cases and associated with 2.42-fold increased risk of CAD (95% CI, 1.80-3.26; P=5.50×10-9). These variants were associated with higher systolic blood pressure (+3.25 mm Hg; [95% CI, 1.86-4.65]; P=5.00×10-6) and increased risk of hypertension (adjusted odds ratio 1.31; [95% CI, 1.14-1.51]; P=2.00×10-4) but not circulating cholesterol concentrations, suggesting that, beyond lipid pathways, nitric oxide synthesis is a key nonlipid driver of CAD risk.

Conclusions

Beyond LDLR, we identified an additional nonlipid molecular subtype of CAD characterized by rare variants in the NOS3 gene.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.121.003598; doi:https://doi.org/10.1161/CIRCGEN.121.003598; html:https://europepmc.org/articles/PMC9771961; pdf:https://europepmc.org/articles/PMC9771961?pdf=render; doi:https://doi.org/10.1161/circgen.121.003598 32704413,https://doi.org/10.1167/tvst.9.2.7,A Clinician's Guide to Artificial Intelligence: How to Critically Appraise Machine Learning Studies.,"Faes L, Liu X, Wagner SK, Fu DJ, Balaskas K, Sim DA, Bachmann LM, Keane PA, Denniston AK.",,Translational vision science & technology,2020,2020-02-12,Y,Artificial intelligence; Critical Appraisal; Machine Learning,,,"In recent years, there has been considerable interest in the prospect of machine learning models demonstrating expert-level diagnosis in multiple disease contexts. However, there is concern that the excitement around this field may be associated with inadequate scrutiny of methodology and insufficient adoption of scientific good practice in the studies involving artificial intelligence in health care. This article aims to empower clinicians and researchers to critically appraise studies of clinical applications of machine learning, through: (1) introducing basic machine learning concepts and nomenclature; (2) outlining key applicable principles of evidence-based medicine; and (3) highlighting some of the potential pitfalls in the design and reporting of these studies.",,pdf:https://tvst.arvojournals.org/arvo/content_public/journal/tvst/938366/i2164-2591-9-2-7_1597165820.03912.pdf; doi:https://doi.org/10.1167/tvst.9.2.7; html:https://europepmc.org/articles/PMC7346877; pdf:https://europepmc.org/articles/PMC7346877?pdf=render -37865101,https://doi.org/10.1016/s2213-8587(23)00253-x,"Empagliflozin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,The lancet. Diabetes & endocrinology,2023,2023-10-18,Y,,,,"

Background

Empagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic, and haemodynamic effects. The RECOVERY trial aimed to assess its safety and efficacy in patients admitted to hospital with COVID-19.

Methods

In the randomised, controlled, open-label RECOVERY trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. In this analysis, we assess eligible and consenting adults who were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus oral empagliflozin 10 mg once daily for 28 days or until discharge (whichever came first) using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. On March 3, 2023 the independent data monitoring committee recommended that the investigators review the data and recruitment was consequently stopped on March 7, 2023. The ongoing RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between July 28, 2021 and March 6, 2023, 4271 patients were randomly allocated to receive either empagliflozin (2113 patients) or usual care alone (2158 patients). Primary and secondary outcome data were known for greater than 99% of randomly assigned patients. Overall, 289 (14%) of 2113 patients allocated to empagliflozin and 307 (14%) of 2158 patients allocated to usual care died within 28 days (rate ratio 0·96 [95% CI 0·82-1·13]; p=0·64). There was no evidence of significant differences in duration of hospitalisation (median 8 days for both groups) or the proportion of patients discharged from hospital alive within 28 days (1678 [79%] in the empagliflozin group vs 1677 [78%] in the usual care group; rate ratio 1·03 [95% CI 0·96-1·10]; p=0·44). Among those not on invasive mechanical ventilation at baseline, there was no evidence of a significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (338 [16%] of 2084 vs 371 [17%] of 2143; risk ratio 0·95 [95% CI 0·84-1·08]; p=0·44). Two serious adverse events believed to be related to empagliflozin were reported: both were ketosis without acidosis.

Interpretation

In adults hospitalised with COVID-19, empagliflozin was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death so is not indicated for the treatment of such patients unless there is an established indication due to a different condition such as diabetes.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (MC_PC_19056), and Wellcome Trust (222406/Z/20/Z).

Translations

For the Nepali, Hindi, Indonesian (Bahasa) and Vietnamese translations of the abstract see Supplementary Materials section.",,doi:https://doi.org/10.1016/S2213-8587(23)00253-X; html:https://europepmc.org/articles/PMC10957483; pdf:https://europepmc.org/articles/PMC10957483?pdf=render +36215124,https://doi.org/10.1161/circgen.121.003598,Gene Sequencing Identifies Perturbation in Nitric Oxide Signaling as a Nonlipid Molecular Subtype of Coronary Artery Disease.,"Khera AV, Wang M, Chaffin M, Emdin CA, Samani NJ, Schunkert H, Watkins H, McPherson R, Erdmann J, Elosua R, Boerwinkle E, Ardissino D, Butterworth AS, Di Angelantonio E, Naheed A, Danesh J, Chowdhury R, Krumholz HM, Sheu WH, Rich SS, Rotter JI, Chen YI, Gabriel S, Lander ES, Saleheen D, Kathiresan S.",,Circulation. Genomic and precision medicine,2022,2022-10-10,N,Atherosclerosis; coronary artery disease; Genetic Association Studies; Nitric Oxide Synthase Type Iii; Precision Medicine,,,"

Background

A key goal of precision medicine is to disaggregate common, complex diseases into discrete molecular subtypes. Rare coding variants in the low-density lipoprotein receptor gene (LDLR) are identified in 1% to 2% of coronary artery disease (CAD) patients, defining a molecular subtype with risk driven by hypercholesterolemia.

Methods

To search for additional subtypes, we compared the frequency of rare, predicted loss-of-function and damaging missense variants aggregated within a given gene in 41 081 CAD cases versus 217 115 controls.

Results

Rare variants in LDLR were most strongly associated with CAD, present in 1% of cases and associated with 4.4-fold increased CAD risk. A second subtype was characterized by variants in endothelial nitric oxide synthase gene (NOS3), a key enzyme regulating vascular tone, endothelial function, and platelet aggregation. A rare predicted loss-of-function or damaging missense variants in NOS3 was present in 0.6% of cases and associated with 2.42-fold increased risk of CAD (95% CI, 1.80-3.26; P=5.50×10-9). These variants were associated with higher systolic blood pressure (+3.25 mm Hg; [95% CI, 1.86-4.65]; P=5.00×10-6) and increased risk of hypertension (adjusted odds ratio 1.31; [95% CI, 1.14-1.51]; P=2.00×10-4) but not circulating cholesterol concentrations, suggesting that, beyond lipid pathways, nitric oxide synthesis is a key nonlipid driver of CAD risk.

Conclusions

Beyond LDLR, we identified an additional nonlipid molecular subtype of CAD characterized by rare variants in the NOS3 gene.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.121.003598; doi:https://doi.org/10.1161/CIRCGEN.121.003598; html:https://europepmc.org/articles/PMC9771961; pdf:https://europepmc.org/articles/PMC9771961?pdf=render; doi:https://doi.org/10.1161/circgen.121.003598 32781946,https://doi.org/10.1098/rspb.2020.1405,Key questions for modelling COVID-19 exit strategies.,"Thompson RN, Hollingsworth TD, Isham V, Arribas-Bel D, Ashby B, Britton T, Challenor P, Chappell LHK, Clapham H, Cunniffe NJ, Dawid AP, Donnelly CA, Eggo RM, Funk S, Gilbert N, Glendinning P, Gog JR, Hart WS, Heesterbeek H, House T, Keeling M, Kiss IZ, Kretzschmar ME, Lloyd AL, McBryde ES, McCaw JM, McKinley TJ, Miller JC, Morris M, O'Neill PD, Parag KV, Pearson CAB, Pellis L, Pulliam JRC, Ross JV, Tomba GS, Silverman BW, Struchiner CJ, Tildesley MJ, Trapman P, Webb CR, Mollison D, Restif O.",,Proceedings. Biological sciences,2020,2020-08-12,Y,Uncertainty; Mathematical Modelling; Epidemic Control; Exit Strategy; Covid-19; Sars-cov-2,,,"Combinations of intense non-pharmaceutical interventions (lockdowns) were introduced worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement exit strategies that relax restrictions while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute 'Models for an exit strategy' workshop (11-15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, would allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. This roadmap requires a global collaborative effort from the scientific community and policymakers, and has three parts: (i) improve estimation of key epidemiological parameters; (ii) understand sources of heterogeneity in populations; and (iii) focus on requirements for data collection, particularly in low-to-middle-income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health.",,doi:https://doi.org/10.1098/rspb.2020.1405; doi:https://doi.org/10.1098/rspb.2020.1405; html:https://europepmc.org/articles/PMC7575516; pdf:https://europepmc.org/articles/PMC7575516?pdf=render 37025302,https://doi.org/10.1093/jacamr/dlad039,Inclusion of minor alleles improves catalogue-based prediction of fluoroquinolone resistance in Mycobacterium tuberculosis.,"Brankin AE, Fowler PW.",,JAC-antimicrobial resistance,2023,2023-04-04,Y,,,,"

Objectives

Fluoroquinolone resistance poses a threat to the successful treatment of tuberculosis. WGS, and the subsequent detection of catalogued resistance-associated mutations, offers an attractive solution to fluoroquinolone susceptibility testing but sensitivities are often less than 90%. We hypothesize that this is partly because the bioinformatic pipelines used usually mask the recognition of minor alleles that have been implicated in fluoroquinolone resistance.

Methods

We analysed the Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC) dataset of globally diverse WGS Mycobacterium tuberculosis isolates, with matched MICs for two fluoroquinolone drugs and allowed putative minor alleles to contribute to resistance prediction.

Results

Detecting minor alleles increased the sensitivity of WGS for moxifloxacin resistance prediction from 85.4% to 94.0%, without significantly reducing specificity. We also found no correlation between the proportion of an M. tuberculosis population containing a resistance-conferring allele and the magnitude of resistance.

Conclusions

Together our results highlight the importance of detecting minor resistance-conferring alleles when using WGS, or indeed any sequencing-based approach, to diagnose fluoroquinolone resistance.",,pdf:https://academic.oup.com/jacamr/article-pdf/5/2/dlad039/49747584/dlad039.pdf; doi:https://doi.org/10.1093/jacamr/dlad039; html:https://europepmc.org/articles/PMC10072237; pdf:https://europepmc.org/articles/PMC10072237?pdf=render +37865101,https://doi.org/10.1016/s2213-8587(23)00253-x,"Empagliflozin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,The lancet. Diabetes & endocrinology,2023,2023-10-18,Y,,,,"

Background

Empagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic, and haemodynamic effects. The RECOVERY trial aimed to assess its safety and efficacy in patients admitted to hospital with COVID-19.

Methods

In the randomised, controlled, open-label RECOVERY trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. In this analysis, we assess eligible and consenting adults who were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus oral empagliflozin 10 mg once daily for 28 days or until discharge (whichever came first) using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. On March 3, 2023 the independent data monitoring committee recommended that the investigators review the data and recruitment was consequently stopped on March 7, 2023. The ongoing RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between July 28, 2021 and March 6, 2023, 4271 patients were randomly allocated to receive either empagliflozin (2113 patients) or usual care alone (2158 patients). Primary and secondary outcome data were known for greater than 99% of randomly assigned patients. Overall, 289 (14%) of 2113 patients allocated to empagliflozin and 307 (14%) of 2158 patients allocated to usual care died within 28 days (rate ratio 0·96 [95% CI 0·82-1·13]; p=0·64). There was no evidence of significant differences in duration of hospitalisation (median 8 days for both groups) or the proportion of patients discharged from hospital alive within 28 days (1678 [79%] in the empagliflozin group vs 1677 [78%] in the usual care group; rate ratio 1·03 [95% CI 0·96-1·10]; p=0·44). Among those not on invasive mechanical ventilation at baseline, there was no evidence of a significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (338 [16%] of 2084 vs 371 [17%] of 2143; risk ratio 0·95 [95% CI 0·84-1·08]; p=0·44). Two serious adverse events believed to be related to empagliflozin were reported: both were ketosis without acidosis.

Interpretation

In adults hospitalised with COVID-19, empagliflozin was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death so is not indicated for the treatment of such patients unless there is an established indication due to a different condition such as diabetes.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (MC_PC_19056), and Wellcome Trust (222406/Z/20/Z).

Translations

For the Nepali, Hindi, Indonesian (Bahasa) and Vietnamese translations of the abstract see Supplementary Materials section.",,doi:https://doi.org/10.1016/S2213-8587(23)00253-X; html:https://europepmc.org/articles/PMC10957483; pdf:https://europepmc.org/articles/PMC10957483?pdf=render 36423925,https://doi.org/10.1136/thorax-2022-219591,Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK).,"Tydeman F, Pfeffer PE, Vivaldi G, Holt H, Talaei M, Jolliffe D, Davies G, Lyons RA, Griffiths C, Kee F, Sheikh A, Shaheen SO, Martineau AR.",,Thorax,2023,2022-11-23,Y,Asthma; Covid-19,,,"

Background

The imposition of restrictions on social mixing early in the COVID-19 pandemic was followed by a reduction in asthma exacerbations in multiple settings internationally. Temporal trends in social mixing, incident acute respiratory infections (ARI) and asthma exacerbations following relaxation of COVID-19 restrictions have not yet been described.

Methods

We conducted a population-based longitudinal study in 2312 UK adults with asthma between November 2020 and April 2022. Details of face covering use, social mixing, incident ARI and severe asthma exacerbations were collected via monthly online questionnaires. Temporal changes in these parameters were visualised using Poisson generalised additive models. Multilevel logistic regression was used to test for associations between incident ARI and risk of asthma exacerbations, adjusting for potential confounders.

Results

Relaxation of COVID-19 restrictions from April 2021 coincided with reduced face covering use (p<0.001), increased frequency of indoor visits to public places and other households (p<0.001) and rising incidence of COVID-19 (p<0.001), non-COVID-19 ARI (p<0.001) and severe asthma exacerbations (p=0.007). Incident non-COVID-19 ARI associated independently with increased risk of asthma exacerbation (adjusted OR 5.75, 95% CI 4.75 to 6.97) as did incident COVID-19, both prior to emergence of the omicron variant of SARS-CoV-2 (5.89, 3.45 to 10.04) and subsequently (5.69, 3.89 to 8.31).

Conclusions

Relaxation of COVID-19 restrictions coincided with decreased face covering use, increased social mixing and a rebound in ARI and asthma exacerbations. Associations between incident ARI and risk of severe asthma exacerbation were similar for non-COVID-19 ARI and COVID-19, both before and after emergence of the SARS-CoV-2 omicron variant.

Study registration number

NCT04330599.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/12/29/thorax-2022-219591.full.pdf; doi:https://doi.org/10.1136/thorax-2022-219591; html:https://europepmc.org/articles/PMC10359556; pdf:https://europepmc.org/articles/PMC10359556?pdf=render 35165324,https://doi.org/10.1038/s41598-022-06315-3,Improving robustness of automatic cardiac function quantification from cine magnetic resonance imaging using synthetic image data.,"Gheorghiță BA, Itu LM, Sharma P, Suciu C, Wetzl J, Geppert C, Ali MAA, Lee AM, Piechnik SK, Neubauer S, Petersen SE, Schulz-Menger J, Chițiboi T.",,Scientific reports,2022,2022-02-14,Y,,,,"Although having been the subject of intense research over the years, cardiac function quantification from MRI is still not a fully automatic process in the clinical practice. This is partly due to the shortage of training data covering all relevant cardiovascular disease phenotypes. We propose to synthetically generate short axis CINE MRI using a generative adversarial model to expand the available data sets that consist of predominantly healthy subjects to include more cases with reduced ejection fraction. We introduce a deep learning convolutional neural network (CNN) to predict the end-diastolic volume, end-systolic volume, and implicitly the ejection fraction from cardiac MRI without explicit segmentation. The left ventricle volume predictions were compared to the ground truth values, showing superior accuracy compared to state-of-the-art segmentation methods. We show that using synthetic data generated for pre-training a CNN significantly improves the prediction compared to only using the limited amount of available data, when the training set is imbalanced.",,pdf:https://www.nature.com/articles/s41598-022-06315-3.pdf; doi:https://doi.org/10.1038/s41598-022-06315-3; html:https://europepmc.org/articles/PMC8844403; pdf:https://europepmc.org/articles/PMC8844403?pdf=render 32637892,https://doi.org/10.1016/j.eclinm.2020.100392,The association between exposure to childhood maltreatment and the subsequent development of functional somatic and visceral pain syndromes.,"Chandan JS, Keerthy D, Zemedikun DT, Okoth K, Gokhale KM, Raza K, Bandyopadhyay S, Taylor J, Nirantharakumar K.",,EClinicalMedicine,2020,2020-06-06,Y,epidemiology; Primary Care; Childhood Maltreatment; Central Sensitivity Syndromes,,,"

Background

Childhood maltreatment is a global public health issue linked to a vast mortality and morbidity burden. This study builds on current literature to explore the risk of developing central sensitivity syndromes (CSS) (consisting of somatic and visceral pain syndromes) subsequent to childhood maltreatment exposure.

Methods

A retrospective population based open cohort study using the UK primary care database, 'The Health Improvement Network,' between 1st January 1995-31st December 2018. 80,657 adult patients who had experienced childhood maltreatment or maltreatment related concerns (exposed patients) were matched to 161,314 unexposed patients by age and sex. Outcomes of interest were the development of CSS: either somatic (Fibromyalgia, chronic fatigue syndrome, temporomandibular joint disorder, chronic lower back pain, chronic headache, myofascial pain syndrome and restless leg syndrome) or visceral (Interstitial cystitis, vulvodynia, chronic prostatitis and irritable bowel syndrome) in nature. Effect sizes are presented as adjusted incidence rate ratios (aIRR) with confidence intervals (CI). Models were adjusted for the following covariates at cohort entry: age, sex, deprivation, anxiety, depression and serious mental ill health.

Results

The average age at cohort entry was 23.4 years and the median follow was 2.2 years. There was an increased risk of developing fibromyalgia (aIRR 2.06; 95% CI 1.71-2.48), chronic fatigue syndrome (1.47; 1.08-2.00), chronic lower back pain (1.99; 1.68-2.35), restless leg syndrome (1.82; 1.41-2.35) and irritable bowel syndrome (1.15; 1.08-1.22) when compared to the unexposed group, whereas no statistical association was seen with the development of temporomandibular joint disorder (1.00; 0.88-1.13), chronic headache (1.04; 0.59-1.86), interstitial cystitis (1.19; 0.51-2.74), vulvodynia (0.65; 0.34-1.26), chronic prostatitis (0.34; 0.07-1.77) and myofascial pain syndrome (0.88; 0.36-2.14). Outcome numbers were low, most likely, due to the rarity of visceral conditions (aside from irritable bowel syndrome). The association between a history of childhood maltreatment and CSS were mainly observed in somatic CSS.

Interpretation

The debilitating effects of CSS carry a substantial physical, psychological and economic burden to both the individuals who are diagnosed with them and the health services who serve them. Primary prevention approaches targeting childhood maltreatment as well as secondary preventative approaches should be considered to minimise the associated burden of CSS.",,pdf:http://www.thelancet.com/article/S258953702030136X/pdf; doi:https://doi.org/10.1016/j.eclinm.2020.100392; html:https://europepmc.org/articles/PMC7329705; pdf:https://europepmc.org/articles/PMC7329705?pdf=render @@ -1828,8 +1828,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 31443926,https://doi.org/10.1016/s0140-6736(19)31674-5,Medium and long-term risks of specific cardiovascular diseases in survivors of 20 adult cancers: a population-based cohort study using multiple linked UK electronic health records databases.,"Strongman H, Gadd S, Matthews A, Mansfield KE, Stanway S, Lyon AR, Dos-Santos-Silva I, Smeeth L, Bhaskaran K.",,"Lancet (London, England)",2019,2019-08-20,Y,,Understanding the Causes of Disease,,"

Background

The past few decades have seen substantial improvements in cancer survival, but concerns exist about long-term cardiovascular disease risk in survivors. Evidence is scarce on the risks of specific cardiovascular diseases in survivors of a wide range of cancers to inform prevention and management. In this study, we used large-scale electronic health records data from multiple linked UK databases to address these evidence gaps.

Methods

For this population-based cohort study, we used linked primary care, hospital, and cancer registry data from the UK Clinical Practice Research Datalink to identify cohorts of survivors of the 20 most common cancers who were 18 years or older and alive 12 months after diagnosis and controls without history of cancer, matched for age, sex, and general practice. We compared risks for a range of cardiovascular disease outcomes using crude and adjusted Cox models. We fitted interactions to investigate effect modification, and flexible parametric survival models to estimate absolute excess risks over time.

Findings

Between Jan 1, 1990, and Dec 31, 2015, 126 120 individuals with a diagnosis of a cancer of interest still being followed up at least 1 year later were identified and matched to 630 144 controls. After exclusions, 108 215 cancer survivors and 523 541 controls were included in the main analyses. Venous thromboembolism risk was elevated in survivors of 18 of 20 site-specific cancers compared with that of controls; adjusted hazard ratios (HRs) ranged from 1·72 (95% CI 1·57-1·89) in patients after prostate cancer to 9·72 (5·50-17·18) after pancreatic cancer. HRs decreased over time, but remained elevated more than 5 years after diagnosis. We observed increased risks of heart failure or cardiomyopathy in patients after ten of 20 cancers, including haematological (adjusted HR 1·94, 1·66-2·25, with non-Hodgkin lymphoma; 1·77, 1·50-2·09, with leukaemia; and 3·29, 2·59-4·18, with multiple myeloma), oesophageal (1·96, 1·46-2·64), lung (1·82, 1·52-2·17) kidney (1·73, 1·38-2·17) and ovarian (1·59, 1·19-2·12). Elevated risks of arrhythmia, pericarditis, coronary artery disease, stroke, and valvular heart disease were also observed for multiple cancers, including haematological malignancies. HRs for heart failure or cardiomyopathy and venous thromboembolism were greater in patients without previous cardiovascular disease and in younger patients. However, absolute excess risks were generally greater with increasing age. Increased risks of these outcomes seemed most pronounced in patients who had received chemotherapy.

Interpretation

Survivors of most site-specific cancers had increased medium-term to long-term risk for one or more cardiovascular diseases compared with that for the general population, with substantial variations between cancer sites.

Funding

Wellcome Trust and Royal Society.",,pdf:http://www.thelancet.com/article/S0140673619316745/pdf; doi:https://doi.org/10.1016/S0140-6736(19)31674-5; html:https://europepmc.org/articles/PMC6857444; pdf:https://europepmc.org/articles/PMC6857444?pdf=render 37278928,https://doi.org/10.1007/s12265-023-10398-2,Circulating Acylcarnitines Associated with Hypertrophic Cardiomyopathy Severity: an Exploratory Cross-Sectional Study in MYBPC3 Founder Variant Carriers.,"Jansen M, Schmidt AF, Jans JJM, Christiaans I, van der Crabben SN, Hoedemaekers YM, Dooijes D, Jongbloed JDH, Boven LG, Lekanne Deprez RH, Wilde AAM, van der Velden J, de Boer RA, van Tintelen JP, Asselbergs FW, Baas AF.",,Journal of cardiovascular translational research,2023,2023-06-06,Y,Metabolism; Biomarker; hypertrophic cardiomyopathy; Acylcarnitine; Mybpc3,,,"Hypertrophic cardiomyopathy (HCM) is a relatively common genetic heart disease characterised by myocardial hypertrophy. HCM can cause outflow tract obstruction, sudden cardiac death and heart failure, but severity is highly variable. In this exploratory cross-sectional study, circulating acylcarnitines were assessed as potential biomarkers in 124 MYBPC3 founder variant carriers (59 with severe HCM, 26 with mild HCM and 39 phenotype-negative [G + P-]). Elastic net logistic regression identified eight acylcarnitines associated with HCM severity. C3, C4, C6-DC, C8:1, C16, C18 and C18:2 were significantly increased in severe HCM compared to G + P-, and C3, C6-DC, C8:1 and C18 in mild HCM compared to G + P-. In multivariable linear regression, C6-DC and C8:1 correlated to log-transformed maximum wall thickness (coefficient 5.01, p = 0.005 and coefficient 0.803, p = 0.007, respectively), and C6-DC to log-transformed ejection fraction (coefficient -2.50, p = 0.004). Acylcarnitines seem promising biomarkers for HCM severity, however prospective studies are required to determine their prognostic value.",,pdf:https://link.springer.com/content/pdf/10.1007/s12265-023-10398-2.pdf; doi:https://doi.org/10.1007/s12265-023-10398-2; html:https://europepmc.org/articles/PMC10721678; pdf:https://europepmc.org/articles/PMC10721678?pdf=render 35045937,https://doi.org/10.1016/j.amjcard.2021.12.022,Relation of Iron Status to Prognosis After Acute Coronary Syndrome.,"Gürgöze MT, Kardys I, Akkerhuis KM, Oemrawsingh RM, Groot HE, van der Harst P, Umans VA, Kietselaer B, Ronner E, Lenderink T, Asselbergs FW, Manintveld OC, Boersma E.",,The American journal of cardiology,2022,2022-01-16,N,,,,"Iron deficiency has been extensively researched and is associated with adverse outcomes in heart failure. However, to our knowledge, the temporal evolution of iron status has not been previously investigated in patients with acute coronary syndrome (ACS). Therefore, we aimed to explore the temporal pattern of repeatedly measured iron, ferritin, transferrin, and transferrin saturation (TSAT) in relation to prognosis post-ACS. BIOMArCS (BIOMarker study to identify the Acute risk of a Coronary Syndrome) is a prospective, multicenter, observational cohort study conducted in The Netherlands between 2008 and 2015. A total of 844 patients with post-ACS were enrolled and underwent high-frequency (median 17) blood sampling during 1 year follow-up. Biomarkers of iron status were measured batchwise in a central laboratory. We analyzed 3 patient subsets, including the case-cohort (n = 187). The primary endpoint (PE) was a composite of cardiovascular mortality and repeat nonfatal ACS, including unstable angina pectoris requiring revascularization. The association between iron status and the PE was analyzed using multivariable joint models. Mean age was 63 years; 78% were men, and >50% had iron deficiency at first sample in the case-cohort. After adjustment for a broad range of clinical variables, 1 SD decrease in log-iron was associated with a 2.2-fold greater risk of the PE (hazard ratio 2.19, 95% confidence interval 1.34 to 3.54, p = 0.002). Similarly, 1 SD decrease in log-TSAT was associated with a 78% increased risk of the PE (hazard ratio 1.78, 95% confidence interval 1.17 to 2.65, p = 0.006). Ferritin and transferrin were not associated with the PE. Repeated measurements of iron and TSAT predict risk of adverse outcomes in patients with post-ACS during 1 year follow-up. Trial Registration: The Netherlands Trial Register. Unique identifiers: NTR1698 and NTR1106. Registered at https://www.trialregister.nl/trial/1614 and https://www.trialregister.nl/trial/1073.",,pdf:http://www.ajconline.org/article/S0002914921012418/pdf; doi:https://doi.org/10.1016/j.amjcard.2021.12.022 -33017023,https://doi.org/10.1001/jamaneurol.2020.3502,Trends in Optic Neuritis Incidence and Prevalence in the UK and Association With Systemic and Neurologic Disease.,"Braithwaite T, Subramanian A, Petzold A, Galloway J, Adderley NJ, Mollan SP, Plant GT, Nirantharakumar K, Denniston AK.",,JAMA neurology,2020,2020-12-01,N,,,,"

Importance

Epidemiologic data on optic neuritis (ON) incidence and associations with immune-mediated inflammatory diseases (IMIDs) are sparse.

Objective

To estimate 22-year trends in ON prevalence and incidence and association with IMIDs in the United Kingdom.

Design, setting, and participants

This cohort study analyzed data from The Health Improvement Network from January 1, 1995, to September 1, 2019. The study included 10 937 511 patients 1 year or older with 75.2 million person-years' follow-up. Annual ON incidence rates were estimated yearly (January 1, 1997, to December 31, 2018), and annual ON prevalence was estimated by performing sequential cross-sectional studies on data collected on January 1 each year for the same period. Data for 1995, 1996, and 2019 were excluded as incomplete. Risk factors for ON were explored in a cohort analysis from January 1, 1997, to December 31, 2018. Matched case-control and retrospective cohort studies were performed using data from January 1, 1995, to September 1, 2019, to explore the odds of antecedent diagnosis and hazard of incident diagnosis of 66 IMIDs in patients compared with controls.

Exposures

Optic neuritis.

Main outcomes and measures

Annual point prevalence and incidence rates of ON, adjusted incident rate ratios (IRRs) for risk factors, and adjusted odds ratios (ORs) and adjusted hazard ratios (HRs) for 66 IMIDs.

Results

A total of 10 937 511 patients (median [IQR] age at cohort entry, 32.6 [18.0-50.4] years; 5 571 282 [50.9%] female) were studied. A total of 1962 of 2826 patients (69.4%) with incident ON were female and 1192 of 1290 92.4%) were White, with a mean (SD) age of 35.6 (15.6) years. Overall incidence across 22 years was stable at 3.7 (95% CI, 3.6-3.9) per 100 000 person-years. Annual point prevalence (per 100 000 population) increased with database maturity, from 69.3 (95% CI, 57.2-81.3) in 1997 to 114.8 (95% CI, 111.0-118.6) in 2018. The highest risk of incident ON was associated with female sex, obesity, reproductive age, smoking, and residence at higher latitude, with significantly lower risk in South Asian or mixed race/ethnicity compared with White people. Patients with ON had significantly higher odds of prior multiple sclerosis (MS) (OR, 98.22; 95% CI, 65.40-147.52), syphilis (OR, 5.76; 95% CI, 1.39-23.96), Mycoplasma (OR, 3.90; 95% CI, 1.09-13.93), vasculitis (OR, 3.70; 95% CI, 1.68-8.15), sarcoidosis (OR, 2.50; 95% CI, 1.21-5.18), Epstein-Barr virus (OR, 2.29; 95% CI, 1.80-2.92), Crohn disease (OR, 1.97; 95% CI, 1.13-3.43), and psoriasis (OR, 1.28; 95% CI, 1.03-1.58). Patients with ON had a significantly higher hazard of incident MS (HR, 284.97; 95% CI, 167.85-483.81), Behçet disease (HR, 17.39; 95% CI, 1.55-195.53), sarcoidosis (HR, 14.80; 95% CI, 4.86-45.08), vasculitis (HR, 4.89; 95% CI, 1.82-13.10), Sjögren syndrome (HR, 3.48; 95% CI, 1.38-8.76), and herpetic infection (HR, 1.68; 95% CI, 1.24-2.28).

Conclusions and relevance

The UK incidence of ON is stable. Even though predominantly associated with MS, ON has numerous other associations with IMIDs. Although individually rare, together these associations outnumber MS-associated ON and typically require urgent management to preserve sight.",,pdf:http://pure-oai.bham.ac.uk/ws/files/100688542/NEU20_1602R_Merged_PDF.pdf; doi:https://doi.org/10.1001/jamaneurol.2020.3502; html:https://europepmc.org/articles/PMC7536630; doi:https://doi.org/10.1001/jamaneurol.2020.3502 32702311,https://doi.org/10.1016/s1470-2045(20)30392-2,Effect of delays in the 2-week-wait cancer referral pathway during the COVID-19 pandemic on cancer survival in the UK: a modelling study.,"Sud A, Torr B, Jones ME, Broggio J, Scott S, Loveday C, Garrett A, Gronthoud F, Nicol DL, Jhanji S, Boyce SA, Williams M, Riboli E, Muller DC, Kipps E, Larkin J, Navani N, Swanton C, Lyratzopoulos G, McFerran E, Lawler M, Houlston R, Turnbull C.",,The Lancet. Oncology,2020,2020-07-20,Y,,,,"

Background

During the COVID-19 lockdown, referrals via the 2-week-wait urgent pathway for suspected cancer in England, UK, are reported to have decreased by up to 84%. We aimed to examine the impact of different scenarios of lockdown-accumulated backlog in cancer referrals on cancer survival, and the impact on survival per referred patient due to delayed referral versus risk of death from nosocomial infection with severe acute respiratory syndrome coronavirus 2.

Methods

In this modelling study, we used age-stratified and stage-stratified 10-year cancer survival estimates for patients in England, UK, for 20 common tumour types diagnosed in 2008-17 at age 30 years and older from Public Health England. We also used data for cancer diagnoses made via the 2-week-wait referral pathway in 2013-16 from the Cancer Waiting Times system from NHS Digital. We applied per-day hazard ratios (HRs) for cancer progression that we generated from observational studies of delay to treatment. We quantified the annual numbers of cancers at stage I-III diagnosed via the 2-week-wait pathway using 2-week-wait age-specific and stage-specific breakdowns. From these numbers, we estimated the aggregate number of lives and life-years lost in England for per-patient delays of 1-6 months in presentation, diagnosis, or cancer treatment, or a combination of these. We assessed three scenarios of a 3-month period of lockdown during which 25%, 50%, and 75% of the normal monthly volumes of symptomatic patients delayed their presentation until after lockdown. Using referral-to-diagnosis conversion rates and COVID-19 case-fatality rates, we also estimated the survival increment per patient referred.

Findings

Across England in 2013-16, an average of 6281 patients with stage I-III cancer were diagnosed via the 2-week-wait pathway per month, of whom 1691 (27%) would be predicted to die within 10 years from their disease. Delays in presentation via the 2-week-wait pathway over a 3-month lockdown period (with an average presentational delay of 2 months per patient) would result in 181 additional lives and 3316 life-years lost as a result of a backlog of referrals of 25%, 361 additional lives and 6632 life-years lost for a 50% backlog of referrals, and 542 additional lives and 9948 life-years lost for a 75% backlog in referrals. Compared with all diagnostics for the backlog being done in month 1 after lockdown, additional capacity across months 1-3 would result in 90 additional lives and 1662 live-years lost due to diagnostic delays for the 25% backlog scenario, 183 additional lives and 3362 life-years lost under the 50% backlog scenario, and 276 additional lives and 5075 life-years lost under the 75% backlog scenario. However, a delay in additional diagnostic capacity with provision spread across months 3-8 after lockdown would result in 401 additional lives and 7332 life-years lost due to diagnostic delays under the 25% backlog scenario, 811 additional lives and 14 873 life-years lost under the 50% backlog scenario, and 1231 additional lives and 22 635 life-years lost under the 75% backlog scenario. A 2-month delay in 2-week-wait investigatory referrals results in an estimated loss of between 0·0 and 0·7 life-years per referred patient, depending on age and tumour type.

Interpretation

Prompt provision of additional capacity to address the backlog of diagnostics will minimise deaths as a result of diagnostic delays that could add to those predicted due to expected presentational delays. Prioritisation of patient groups for whom delay would result in most life-years lost warrants consideration as an option for mitigating the aggregate burden of mortality in patients with cancer.

Funding

None.",,pdf:http://www.thelancet.com/article/S1470204520303922/pdf; doi:https://doi.org/10.1016/S1470-2045(20)30392-2; html:https://europepmc.org/articles/PMC7116538; pdf:https://europepmc.org/articles/PMC7116538?pdf=render +33017023,https://doi.org/10.1001/jamaneurol.2020.3502,Trends in Optic Neuritis Incidence and Prevalence in the UK and Association With Systemic and Neurologic Disease.,"Braithwaite T, Subramanian A, Petzold A, Galloway J, Adderley NJ, Mollan SP, Plant GT, Nirantharakumar K, Denniston AK.",,JAMA neurology,2020,2020-12-01,N,,,,"

Importance

Epidemiologic data on optic neuritis (ON) incidence and associations with immune-mediated inflammatory diseases (IMIDs) are sparse.

Objective

To estimate 22-year trends in ON prevalence and incidence and association with IMIDs in the United Kingdom.

Design, setting, and participants

This cohort study analyzed data from The Health Improvement Network from January 1, 1995, to September 1, 2019. The study included 10 937 511 patients 1 year or older with 75.2 million person-years' follow-up. Annual ON incidence rates were estimated yearly (January 1, 1997, to December 31, 2018), and annual ON prevalence was estimated by performing sequential cross-sectional studies on data collected on January 1 each year for the same period. Data for 1995, 1996, and 2019 were excluded as incomplete. Risk factors for ON were explored in a cohort analysis from January 1, 1997, to December 31, 2018. Matched case-control and retrospective cohort studies were performed using data from January 1, 1995, to September 1, 2019, to explore the odds of antecedent diagnosis and hazard of incident diagnosis of 66 IMIDs in patients compared with controls.

Exposures

Optic neuritis.

Main outcomes and measures

Annual point prevalence and incidence rates of ON, adjusted incident rate ratios (IRRs) for risk factors, and adjusted odds ratios (ORs) and adjusted hazard ratios (HRs) for 66 IMIDs.

Results

A total of 10 937 511 patients (median [IQR] age at cohort entry, 32.6 [18.0-50.4] years; 5 571 282 [50.9%] female) were studied. A total of 1962 of 2826 patients (69.4%) with incident ON were female and 1192 of 1290 92.4%) were White, with a mean (SD) age of 35.6 (15.6) years. Overall incidence across 22 years was stable at 3.7 (95% CI, 3.6-3.9) per 100 000 person-years. Annual point prevalence (per 100 000 population) increased with database maturity, from 69.3 (95% CI, 57.2-81.3) in 1997 to 114.8 (95% CI, 111.0-118.6) in 2018. The highest risk of incident ON was associated with female sex, obesity, reproductive age, smoking, and residence at higher latitude, with significantly lower risk in South Asian or mixed race/ethnicity compared with White people. Patients with ON had significantly higher odds of prior multiple sclerosis (MS) (OR, 98.22; 95% CI, 65.40-147.52), syphilis (OR, 5.76; 95% CI, 1.39-23.96), Mycoplasma (OR, 3.90; 95% CI, 1.09-13.93), vasculitis (OR, 3.70; 95% CI, 1.68-8.15), sarcoidosis (OR, 2.50; 95% CI, 1.21-5.18), Epstein-Barr virus (OR, 2.29; 95% CI, 1.80-2.92), Crohn disease (OR, 1.97; 95% CI, 1.13-3.43), and psoriasis (OR, 1.28; 95% CI, 1.03-1.58). Patients with ON had a significantly higher hazard of incident MS (HR, 284.97; 95% CI, 167.85-483.81), Behçet disease (HR, 17.39; 95% CI, 1.55-195.53), sarcoidosis (HR, 14.80; 95% CI, 4.86-45.08), vasculitis (HR, 4.89; 95% CI, 1.82-13.10), Sjögren syndrome (HR, 3.48; 95% CI, 1.38-8.76), and herpetic infection (HR, 1.68; 95% CI, 1.24-2.28).

Conclusions and relevance

The UK incidence of ON is stable. Even though predominantly associated with MS, ON has numerous other associations with IMIDs. Although individually rare, together these associations outnumber MS-associated ON and typically require urgent management to preserve sight.",,pdf:http://pure-oai.bham.ac.uk/ws/files/100688542/NEU20_1602R_Merged_PDF.pdf; doi:https://doi.org/10.1001/jamaneurol.2020.3502; html:https://europepmc.org/articles/PMC7536630; doi:https://doi.org/10.1001/jamaneurol.2020.3502 34347787,https://doi.org/10.1371/journal.pone.0253809,Developing a Natural Language Processing tool to identify perinatal self-harm in electronic healthcare records.,"Ayre K, Bittar A, Kam J, Verma S, Howard LM, Dutta R.",,PloS one,2021,2021-08-04,Y,,,,"

Background

Self-harm occurring within pregnancy and the postnatal year (""perinatal self-harm"") is a clinically important yet under-researched topic. Current research likely under-estimates prevalence due to methodological limitations. Electronic healthcare records (EHRs) provide a source of clinically rich data on perinatal self-harm.

Aims

(1) To create a Natural Language Processing (NLP) tool that can, with acceptable precision and recall, identify mentions of acts of perinatal self-harm within EHRs. (2) To use this tool to identify service-users who have self-harmed perinatally, based on their EHRs.

Methods

We used the Clinical Record Interactive Search system to extract de-identified EHRs of secondary mental healthcare service-users at South London and Maudsley NHS Foundation Trust. We developed a tool that applied several layers of linguistic processing based on the spaCy NLP library for Python. We evaluated mention-level performance in the following domains: span, status, temporality and polarity. Evaluation was done against a manually coded reference standard. Mention-level performance was reported as precision, recall, F-score and Cohen's kappa for each domain. Performance was also assessed at 'service-user' level and explored whether a heuristic rule improved this. We report per-class statistics for service-user performance, as well as likelihood ratios and post-test probabilities.

Results

Mention-level performance: micro-averaged F-score, precision and recall for span, polarity and temporality >0.8. Kappa for status 0.68, temporality 0.62, polarity 0.91. Service-user level performance with heuristic: F-score, precision, recall of minority class 0.69, macro-averaged F-score 0.81, positive LR 9.4 (4.8-19), post-test probability 69.0% (53-82%). Considering the task difficulty, the tool performs well, although temporality was the attribute with the lowest level of annotator agreement.

Conclusions

It is feasible to develop an NLP tool that identifies, with acceptable validity, mentions of perinatal self-harm within EHRs, although with limitations regarding temporality. Using a heuristic rule, it can also function at a service-user-level.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0253809&type=printable; doi:https://doi.org/10.1371/journal.pone.0253809; html:https://europepmc.org/articles/PMC8336818; pdf:https://europepmc.org/articles/PMC8336818?pdf=render 31234639,https://doi.org/10.1161/circulationaha.118.038814,Use of Genetic Variants Related to Antihypertensive Drugs to Inform on Efficacy and Side Effects.,"Gill D, Georgakis MK, Koskeridis F, Jiang L, Feng Q, Wei WQ, Theodoratou E, Elliott P, Denny JC, Malik R, Evangelou E, Dehghan A, Dichgans M, Tzoulaki I.",,Circulation,2019,2019-06-25,Y,Antihypertensive drugs; Mendelian Randomization Analysis,"Better Care, The Human Phenome",,"

Background

Drug effects can be investigated through natural variation in the genes for their protein targets. The present study aimed to use this approach to explore the potential side effects and repurposing potential of antihypertensive drugs, which are among the most commonly used medications worldwide.

Methods

Genetic proxies for the effect of antihypertensive drug classes were identified as variants in the genes for the corresponding targets that associated with systolic blood pressure at genome-wide significance. Mendelian randomization estimates for drug effects on coronary heart disease and stroke risk were compared with randomized, controlled trial results. A phenome-wide association study in the UK Biobank was performed to identify potential side effects and repurposing opportunities, with findings investigated in the Vanderbilt University biobank (BioVU) and in observational analysis of the UK Biobank.

Results

Suitable genetic proxies for angiotensin-converting enzyme inhibitors, β-blockers, and calcium channel blockers (CCBs) were identified. Mendelian randomization estimates for their effect on coronary heart disease and stroke risk, respectively, were comparable to results from randomized, controlled trials against placebo. A phenome-wide association study in the UK Biobank identified an association of the CCB standardized genetic risk score with increased risk of diverticulosis (odds ratio, 1.02 per standard deviation increase; 95% CI, 1.01-1.04), with a consistent estimate found in BioVU (odds ratio, 1.01; 95% CI, 1.00-1.02). Cox regression analysis of drug use in the UK Biobank suggested that this association was specific to nondihydropyridine CCBs (hazard ratio 1.49 considering thiazide diuretic agents as a comparator; 95% CI, 1.04-2.14) but not dihydropyridine CCBs (hazard ratio, 1.04; 95% CI, 0.83-1.32).

Conclusions

Genetic variants can be used to explore the efficacy and side effects of antihypertensive medications. The identified potential effect of nondihydropyridine CCBs on diverticulosis risk could have clinical implications and warrants further investigation.",,doi:https://doi.org/10.1161/circulationaha.118.038814; doi:https://doi.org/10.1161/CIRCULATIONAHA.118.038814; html:https://europepmc.org/articles/PMC6687408; pdf:https://europepmc.org/articles/PMC6687408?pdf=render 37538810,https://doi.org/10.1016/j.ekir.2023.05.008,Impact of outcome adjudication in kidney disease trials: observations from the Study of Heart and Renal Protection (SHARP).,"Herrington WG, Harper C, Staplin N, Haynes R, Emberson J, Reith C, Hooi LS, Levin A, Wanner C, Baigent C, Landray M, SHARP Collaborative Group.",,Kidney international reports,2023,2023-08-01,Y,Transplantation; Dialysis; Chronic Kidney Disease; Clinical Trials; Adjudication,,,"

Introduction

We aimed to assess opportunities for trial streamlining and the scientific impact of adjudication on kidney and cardiovascular outcomes in CKD.

Methods

We analysed the effects of adjudication of ~2100 maintenance kidney replacement therapy (KRT) and ~1300 major atherosclerotic events (MAEs) recorded in SHARP. We first compared outcome classification before versus after adjudication, and then re-ran randomised comparisons using pre-adjudicated follow-up data.

Results

For maintenance KRT, adjudication had little impact with only 1% of events being refuted (28/2115). Consequently, randomised comparisons using pre-adjudication reports found almost identical results (pre-adjudication: simvastatin/ezetimibe 1038 vs placebo 1077; risk ratio [RR] 0.95, 95%CI 0.88-1.04; post-adjudicated: 1057 vs 1084; RR=0.97, 95%CI 0.89-1.05). For MAEs, about one-quarter of patient reports were refuted (324/1275 [25%]), and reviewing 3538 other potential vascular events and death reports identified only 194 additional MAEs. Nevertheless, randomised analyses using SHARP's pre-adjudicated data alone found similar results to analyses based on adjudicated outcomes (pre-adjudication: 573 vs 702; RR=0.80, 95%CI 0.72-0.89; adjudicated: 526 vs 619; RR=0.83, 95%CI 0.74- 0.94), and also suggested refuted MAEs were likely to represent atherosclerotic disease (RR for refuted MAEs=0.80, 95%CI 0.65-1.00).

Conclusions

These analyses provide three key insights. First, they provide a rationale for nephrology trials not to adjudicate maintenance KRT. Secondly, when an event that mimics an atherosclerotic outcome is not expected to be influenced by the treatment under study (e.g. heart failure), the aim of adjudicating atherosclerotic outcomes should be to remove such events. Lastly, restrictive definitions for the remaining suspected atherosclerotic outcomes may reduce statistical power.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7614871; doi:https://doi.org/10.1016/j.ekir.2023.05.008; html:https://europepmc.org/articles/PMC7614871; pdf:https://europepmc.org/articles/PMC7614871?pdf=render @@ -1837,37 +1837,37 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 36936592,https://doi.org/10.1136/bmjmed-2022-000151,Covid-19 variants of concern and pregnancy.,"Stock SJ, Harmer C, Calvert C.",,BMJ medicine,2022,2022-03-02,Y,Pregnancy complications; Covid-19,,,,,pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000151.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000151; html:https://europepmc.org/articles/PMC9951363; pdf:https://europepmc.org/articles/PMC9951363?pdf=render 36058413,https://doi.org/10.1016/j.jinf.2022.08.030,A prospective study of risk factors associated with seroprevalence of SARS-CoV-2 antibodies in healthcare workers at a large UK teaching hospital.,"Cooper DJ, Lear S, Watson L, Shaw A, Ferris M, Doffinger R, Bousfield R, Sharrocks K, Weekes MP, Warne B, Sparkes D, Jones NK, Rivett L, Routledge M, Chaudhry A, Dempsey K, Matson M, Lakha A, Gathercole G, O'Connor O, Wilson E, Shahzad O, Toms K, Thompson R, Halsall I, Halsall D, Houghton S, Papadia S, Kingston N, Stirrups KE, Graves B, Townsend P, Walker N, Stark H, CITIID-NIHR BioResource COVID-19 Collaboration, De Angelis D, Seaman S, Dougan G, Bradley JR, Török ME, Goodfellow I, Baker S.",,The Journal of infection,2022,2022-09-02,Y,Healthcare Workers; Sero-epidemiology; Risk Factor Analysis; Covid-19; Sars-cov-2,,,"

Objectives

To describe the risk factors for SARS-CoV-2 infection in UK healthcare workers (HCWs).

Methods

We conducted a prospective sero-epidemiological study of HCWs at a major UK teaching hospital using a SARS-CoV-2 immunoassay. Risk factors for seropositivity were analysed using multivariate logistic regression.

Results

410/5,698 (7·2%) staff tested positive for SARS-CoV-2 antibodies. Seroprevalence was higher in those working in designated COVID-19 areas compared with other areas (9·47% versus 6·16%) Healthcare assistants (aOR 2·06 [95%CI 1·14-3·71]; p=0·016) and domestic and portering staff (aOR 3·45 [95% CI 1·07-11·42]; p=0·039) had significantly higher seroprevalence than other staff groups after adjusting for age, sex, ethnicity and COVID-19 working location. Staff working in acute medicine and medical sub-specialities were also at higher risk (aOR 2·07 [95% CI 1·31-3·25]; p<0·002). Staff from Black, Asian and minority ethnic (BAME) backgrounds had an aOR of 1·65 (95% CI 1·32 - 2·07; p<0·001) compared to white staff; this increased risk was independent of COVID-19 area working. The only symptoms significantly associated with seropositivity in a multivariable model were loss of sense of taste or smell, fever, and myalgia; 31% of staff testing positive reported no prior symptoms.

Conclusions

Risk of SARS-CoV-2 infection amongst HCWs is highly heterogeneous and influenced by COVID-19 working location, role, age and ethnicity. Increased risk amongst BAME staff cannot be accounted for solely by occupational factors.",,pdf:https://www.repository.cam.ac.uk/bitstream/1810/341240/2/1-s2.0-S016344532200514X-main.pdf; doi:https://doi.org/10.1016/j.jinf.2022.08.030; html:https://europepmc.org/articles/PMC9436870; pdf:https://europepmc.org/articles/PMC9436870?pdf=render 35803473,https://doi.org/10.1016/j.neuroimage.2022.119452,Identifying microstructural changes in diffusion MRI; How to circumvent parameter degeneracy.,"Rafipoor H, Zheng YQ, Griffanti L, Jbabdi S, Cottaar M.",,NeuroImage,2022,2022-07-05,Y,,,,"Biophysical models that attempt to infer real-world quantities from data usually have many free parameters. This over-parameterisation can result in degeneracies in model inversion and render parameter estimation ill-posed. However, in many applications, we are not interested in quantifying the parameters per se, but rather in identifying changes in parameters between experimental conditions (e.g. patients vs controls). Here we present a Bayesian framework to make inference on changes in the parameters of biophysical models even when model inversion is degenerate, which we refer to as Bayesian EstimatioN of CHange (BENCH). We infer the parameter changes in two steps; First, we train models that can estimate the pattern of change in the measurements given any hypothetical direction of change in the parameters using simulations. Next, for any pair of real data sets, we use these pre-trained models to estimate the probability that an observed difference in the data can be explained by each model of change. BENCH is applicable to any type of data and models and particularly useful for biophysical models with parameter degeneracies, where we can assume the change is sparse. In this paper, we apply the approach in the context of microstructural modelling of diffusion MRI data, where the models are usually over-parameterised and not invertible without injecting strong assumptions. Using simulations, we show that in the context of the standard model of white matter our approach is able to identify changes in microstructural parameters from conventional multi-shell diffusion MRI data. We also apply our approach to a subset of subjects from the UK-Biobank Imaging to identify the dominant standard model parameter change in areas of white matter hyperintensities under the assumption that the standard model holds in white matter hyperintensities.",,doi:https://doi.org/10.1016/j.neuroimage.2022.119452; doi:https://doi.org/10.1016/j.neuroimage.2022.119452; html:https://europepmc.org/articles/PMC10933779; pdf:https://europepmc.org/articles/PMC10933779?pdf=render +34345870,https://doi.org/10.1016/j.bbih.2021.100286,The effects of genotype on inflammatory response in hippocampal progenitor cells: A computational approach.,"Lee H, Metz A, McDiarmid A, Palmos A, Lee SH, Curtis CJ, Patel H, Newhouse SJ, Thuret S.",,"Brain, behavior, & immunity - health",2021,2021-08-01,Y,Hippocampus; Neurogenesis; Inflammation; Neural stem cells; in vitro model; single nucleotide polymorphisms SNP; Eqtl; Gene Variants,,,"Cell culture models are valuable tools to study biological mechanisms underlying health and disease in a controlled environment. Although their genotype influences their phenotype, subtle genetic variations in cell lines are rarely characterised and taken into account for in vitro studies. To investigate how the genetic makeup of a cell line might affect the cellular response to inflammation, we characterised the single nucleotide variants (SNPs) relevant to inflammation-related genes in an established hippocampal progenitor cell line (HPC0A07/03C) that is frequently used as an in vitro model for hippocampal neurogenesis (HN). SNPs were identified using a genotyping array, and genes associated with chronic inflammatory and neuroinflammatory response gene ontology terms were retrieved using the AmiGO application. SNPs associated with these genes were then extracted from the genotyping dataset, for which a literature search was conducted, yielding relevant research articles for a total of 17 SNPs. Of these variants, 10 were found to potentially affect hippocampal neurogenesis whereby a majority (n=7) is likely to reduce neurogenesis under inflammatory conditions. Taken together, the existing literature seems to suggest that all stages of hippocampal neurogenesis could be negatively affected due to the genetic makeup in HPC0A07/03C cells under inflammation. Additional experiments will be needed to validate these specific findings in a laboratory setting. However, this computational approach already confirms that in vitro studies in general should control for cell lines subtle genetic variations which could mask or exacerbate findings.",,doi:https://doi.org/10.1016/j.bbih.2021.100286; doi:https://doi.org/10.1016/j.bbih.2021.100286; html:https://europepmc.org/articles/PMC8261829; pdf:https://europepmc.org/articles/PMC8261829?pdf=render 37981722,https://doi.org/10.1093/aje/kwad232,Inconsistency in UK Biobank Event Definitions From Different Data Sources and Its Impact on Bias and Generalizability: A Case Study of Venous Thromboembolism.,"Bassett E, Broadbent J, Gill D, Burgess S, Mason AM.",,American journal of epidemiology,2024,2024-05-01,Y,Pulmonary embolism; Bias; Deep vein thrombosis; Venous Thromboembolism; Generalizability; Uk Biobank; Sociodemographic Characteristics; Representativeness; Event Definition,,,"The UK Biobank study contains several sources of diagnostic data, including hospital inpatient data and data on self-reported conditions for approximately 500,000 participants and primary-care data for approximately 177,000 participants (35%). Epidemiologic investigations require a primary disease definition, but whether to combine data sources to maximize statistical power or focus on only 1 source to ensure a consistent outcome is not clear. The consistency of disease definitions was investigated for venous thromboembolism (VTE) by evaluating overlap when defining cases from 3 sources: hospital inpatient data, primary-care reports, and self-reported questionnaires. VTE cases showed little overlap between data sources, with only 6% of reported events for persons with primary-care data being identified by all 3 sources (hospital, primary-care, and self-reports), while 71% appeared in only 1 source. Deep vein thrombosis-only events represented 68% of self-reported VTE cases and 36% of hospital-reported VTE cases, while pulmonary embolism-only events represented 20% of self-reported VTE cases and 50% of hospital-reported VTE cases. Additionally, different distributions of sociodemographic characteristics were observed; for example, patients in 46% of hospital-reported VTE cases were female, compared with 58% of self-reported VTE cases. These results illustrate how seemingly neutral decisions taken to improve data quality can affect the representativeness of a data set.",,pdf:https://academic.oup.com/aje/advance-article-pdf/doi/10.1093/aje/kwad232/53485177/kwad232.pdf; doi:https://doi.org/10.1093/aje/kwad232; html:https://europepmc.org/articles/PMC11074710; pdf:https://europepmc.org/articles/PMC11074710?pdf=render 36335192,https://doi.org/10.1038/s41598-022-22218-9,"Genetic insights into smoking behaviours in 10,558 men of African ancestry from continental Africa and the UK.","Piga NN, Boua PR, Soremekun C, Shrine N, Coley K, Brandenburg JT, Tobin MD, Ramsay M, Fatumo S, Choudhury A, Batini C.",,Scientific reports,2022,2022-11-05,Y,,,,"Smoking is a leading risk factor for many of the top ten causes of death worldwide. Of the 1.3 billion smokers globally, 80% live in low- and middle-income countries, where the number of deaths due to tobacco use is expected to double in the next decade according to the World Health Organization. Genetic studies have helped to identify biological pathways for smoking behaviours, but have mostly focussed on individuals of European ancestry or living in either North America or Europe. We performed a genome-wide association study of two smoking behaviour traits in 10,558 men of African ancestry living in five African countries and the UK. Eight independent variants were associated with either smoking initiation or cessation at P-value < 5 × 10-6, four being monomorphic or rare in European populations. Gene prioritisation strategy highlighted five genes, including SEMA6D, previously described as associated with several smoking behaviour traits. These results confirm the importance of analysing underrepresented populations in genetic epidemiology, and the urgent need for larger genomic studies to boost discovery power to better understand smoking behaviours, as well as many other traits.",,pdf:https://www.nature.com/articles/s41598-022-22218-9.pdf; doi:https://doi.org/10.1038/s41598-022-22218-9; html:https://europepmc.org/articles/PMC9637114; pdf:https://europepmc.org/articles/PMC9637114?pdf=render -34345870,https://doi.org/10.1016/j.bbih.2021.100286,The effects of genotype on inflammatory response in hippocampal progenitor cells: A computational approach.,"Lee H, Metz A, McDiarmid A, Palmos A, Lee SH, Curtis CJ, Patel H, Newhouse SJ, Thuret S.",,"Brain, behavior, & immunity - health",2021,2021-08-01,Y,Hippocampus; Neurogenesis; Inflammation; Neural stem cells; in vitro model; single nucleotide polymorphisms SNP; Eqtl; Gene Variants,,,"Cell culture models are valuable tools to study biological mechanisms underlying health and disease in a controlled environment. Although their genotype influences their phenotype, subtle genetic variations in cell lines are rarely characterised and taken into account for in vitro studies. To investigate how the genetic makeup of a cell line might affect the cellular response to inflammation, we characterised the single nucleotide variants (SNPs) relevant to inflammation-related genes in an established hippocampal progenitor cell line (HPC0A07/03C) that is frequently used as an in vitro model for hippocampal neurogenesis (HN). SNPs were identified using a genotyping array, and genes associated with chronic inflammatory and neuroinflammatory response gene ontology terms were retrieved using the AmiGO application. SNPs associated with these genes were then extracted from the genotyping dataset, for which a literature search was conducted, yielding relevant research articles for a total of 17 SNPs. Of these variants, 10 were found to potentially affect hippocampal neurogenesis whereby a majority (n=7) is likely to reduce neurogenesis under inflammatory conditions. Taken together, the existing literature seems to suggest that all stages of hippocampal neurogenesis could be negatively affected due to the genetic makeup in HPC0A07/03C cells under inflammation. Additional experiments will be needed to validate these specific findings in a laboratory setting. However, this computational approach already confirms that in vitro studies in general should control for cell lines subtle genetic variations which could mask or exacerbate findings.",,doi:https://doi.org/10.1016/j.bbih.2021.100286; doi:https://doi.org/10.1016/j.bbih.2021.100286; html:https://europepmc.org/articles/PMC8261829; pdf:https://europepmc.org/articles/PMC8261829?pdf=render 35212847,https://doi.org/10.1007/s00455-022-10425-5,Identifying Dysphagia and Demographic Associations in Older Adults Using Electronic Health Records: A National Longitudinal Observational Study in Wales (United Kingdom) 2008-2018.,"Hollinghurst J, Smithard DG.",,Dysphagia,2022,2022-02-25,Y,Prevalence; Frailty; epidemiology; Old Age; Dysphagia; Deprivation,,,"Dysphagia is increasingly being recognised as a geriatric syndrome (giant). There is limited research on the prevalence of dysphagia using electronic health records. To investigate associations between dysphagia, as recorded in electronic health records and age, frailty using the electronic frailty index, gender and deprivation (Welsh index of multiple deprivation). A Cross-sectional longitudinal cohort study in over 400,000 older adults was undertaken (65 +) in Wales (United Kingdom) per year from 2008 to 2018. We used the secure anonymised information linkage databank to identify dysphagia diagnoses in primary and secondary care. We used chi-squared tests and multivariate logistic regression to investigate associations between dysphagia diagnosis and age, frailty (using the electronic Frailty index), gender and deprivation. Data indicated < 1% of individuals were recorded as having a dysphagia diagnosis per year. We found dysphagia to be statistically significantly associated with older age, more severe frailty and individuals from more deprived areas. Multivariate analyses indicated increased odds ratios [OR (95% confidence intervals)] for a dysphagia diagnosis with increased age [reference 65-74: aged 75-84 OR 1.09 (1.07, 1.12), 85 + OR 1.23 (1.20, 1.27)], frailty (reference fit: mild frailty 2.45 (2.38, 2.53), moderate frailty 4.64 (4.49, 4.79) and severe frailty 7.87 (7.55, 8.21)] and individuals from most deprived areas [reference 5. Least deprived, 1. Most deprived: 1.10 (1.06, 1.14)]. The study has identified that prevalence of diagnosed dysphagia is lower than previously reported. This study has confirmed the association of dysphagia with increasing age and frailty. A previously unreported association with deprivation has been identified. Deprivation is a multifactorial problem that is known to affect health outcomes, and the association with dysphagia should not be a surprise. Research in to this relationship is indicated.",,pdf:https://link.springer.com/content/pdf/10.1007/s00455-022-10425-5.pdf; doi:https://doi.org/10.1007/s00455-022-10425-5; html:https://europepmc.org/articles/PMC9643178; pdf:https://europepmc.org/articles/PMC9643178?pdf=render 34791170,https://doi.org/10.1093/eurheartj/ehab759,A sex-specific prediction model is not enough to achieve equality for women in preventative cardiovascular medicine.,"Kimenai DM, Shah ASV, Mills NL.",,European heart journal,2022,2022-01-01,Y,,,,,,pdf:https://academic.oup.com/eurheartj/article-pdf/43/3/239/42296399/ehab759.pdf; doi:https://doi.org/10.1093/eurheartj/ehab759; html:https://europepmc.org/articles/PMC8790764; pdf:https://europepmc.org/articles/PMC8790764?pdf=render 37474660,https://doi.org/10.1038/s41591-023-02445-x,Considerations for patient and public involvement and engagement in health research.,"Aiyegbusi OL, McMullan C, Hughes SE, Turner GM, Subramanian A, Hotham R, Davies EH, Frost C, Alder Y, Agyen L, Buckland L, Camaradou J, Chong A, Jeyes F, Kumar S, Matthews KL, Moore P, Ormerod J, Price G, Saint-Cricq M, Stanton D, Walker A, Haroon S, Denniston AK, Calvert MJ, TLC Study Group.",,Nature medicine,2023,2023-07-20,N,,,,"Patient and public involvement and engagement (PPIE) can provide valuable insights into the experiences of those living with and affected by a disease or health condition. Inclusive collaboration between patients, the public and researchers can lead to productive relationships, ensuring that health research addresses patient needs. Guidelines are available to support effective PPIE; however, evaluation of the impact of PPIE strategies in health research is limited. In this Review, we evaluate the impact of PPIE in the 'Therapies for Long COVID in non-hospitalised individuals' (TLC) Study, using a combination of group discussions and interviews with patient partners and researchers. We identify areas of good practice and reflect on areas for improvement. Using these insights and the results of a survey, we synthesize two checklists of considerations for PPIE, and we propose that research teams use these checklists to optimize the impact of PPIE for both patients and researchers in future studies.",,doi:https://doi.org/10.1038/s41591-023-02445-x 34062542,https://doi.org/10.1159/000517521,Structural Endpoints and Outcome Measures in Uveitis.,"Wintergerst MWM, Liu X, Terheyden JH, Pohlmann D, Li JQ, Montesano G, Ometto G, Holz FG, Crabb DP, Pleyer U, Heinz C, Denniston AK, Finger RP.",,Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde,2021,2021-06-01,N,Biomarker; Uveitis; Outcome; Outcome Measure; Endpoint; Imaging Biomarker; Inflammatory Eye Diseases; Instrument-based Measure,,,"Most uveitis entities are rare diseases but, taken together, are responsible for 5-10% of worldwide visual impairment which largely affects persons of working age. As with many rare diseases, there is a lack of high-level evidence regarding its clinical management, partly due to a dearth of reliable and objective quantitative endpoints for clinical trials. This review provides an overview of available structural outcome measures for uveitis disease activity and damage in an anatomical order from the anterior to the posterior segment of the eye. While there is a multitude of available structural outcome measures, not all might qualify as endpoints for clinical uveitis trials, and thorough testing of applicability is warranted. Furthermore, a consensus on endpoint definition, standardization, and ""core outcomes"" is required. As stipulated by regulatory agencies, endpoints should be precisely defined, clinically important, internally consistent, reliable, responsive to treatment, and relevant for the respective subtype of uveitis. Out of all modalities used for assessment of the reviewed structural outcome measures, optical coherence tomography, color fundus photography, fundus autofluorescence, and fluorescein/indocyanine green angiography represent current ""core modalities"" for reliable and objective quantification of uveitis outcome measures, based on their practical availability and the evidence provided so far.",,pdf:https://www.karger.com/Article/Pdf/517521; doi:https://doi.org/10.1159/000517521 -37730620,https://doi.org/10.1186/s13643-023-02333-y,What is known about what works in community-involved decision-making relating to urban green and blue spaces? A realist review protocol.,"Rahtz E, Bell SL, Nurse A, Wheeler BW, Guell C, Elliott LR, Thompson CW, McDougall CW, Lovell R.",,Systematic reviews,2023,2023-09-20,Y,,,,"

Background

There is now a relatively well-established evidence base suggesting that greener living environments and time spent in urban green and blue spaces (UGBS) can be beneficial for human health and wellbeing. However, benefits are not universal and there remain widespread social inequalities in access to such resources and experiences, particularly along axes of class, race, ethnicity, age and disability, and in relation to efforts to increase the availability and accessibility of such spaces. These injustices often relate to distributive, procedural and recognition-based processes. There is growing interest in how to ensure that efforts to increase access to or use of UGBS (whether through infrastructural or social programmes) result in equitable outcomes whilst minimising potential for exacerbating existing inequalities and injustices. Community engagement is considered an important step towards more inclusive UGBS decision-making, from planning and design to management and maintenance processes. It is thought to contribute to better and more widely trusted decisions, enhanced democracy, community satisfaction, civic interest and feelings of green space ownership, and greater longevity of UGBS projects. However, uneven representation and barriers to participation can create imbalances and undermine these benefits.

Methods

An iterative, multi-stage realist-inspired review will be conducted to ask what works, in what context and in what ways relating to the meaningful involvement of communities in UGBS decision-making, focusing on the skills, capacities and capabilities of different stakeholders and the role of contexts and processes. 'Effectiveness' (or what works) will be understood as a multifaceted outcome, encompassing both the processes and results of community engagement efforts. Following a scoping stage to identify initial programme theory, inclusion/exclusion criteria and derive search terms, relevant databases and grey literature will be searched to identify interdisciplinary literature in two phases. The first phase will be used to further develop programme theories, which will be articulated as 'if then' statements. The second phase searches will be used to identify sources to further explore and evidence the programme and formal theory. We will assess all includable evidence for conceptual richness, prioritising more conceptually rich sources if needed.

Discussion

The realist synthesis will explore the key context, mechanism and outcome configurations that appear to explain if and how different approaches to community-involved UGBS decision-making are or are not effective. We will consider factors such as different conceptualisations of community, and if and how they have been involved in UGBS decision-making; the types of tools and approaches used; and the socio-cultural and political or governance structures within which decision-making takes place.",,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02333-y; doi:https://doi.org/10.1186/s13643-023-02333-y; html:https://europepmc.org/articles/PMC10512649; pdf:https://europepmc.org/articles/PMC10512649?pdf=render 35434685,https://doi.org/10.1016/j.lanepe.2022.100381,Dosing interval strategies for two-dose COVID-19 vaccination in 13 middle-income countries of Europe: Health impact modelling and benefit-risk analysis.,"Liu Y, Pearson CAB, Sandmann FG, Barnard RC, Kim JH, CMMID COVID-19 Working Group, Flasche S, Jit M, Abbas K.",,The Lancet regional health. Europe,2022,2022-04-11,Y,"Quantitative Methods; Mathematical Modelling; Public Health Intervention; Vaccine Policy; Ve, Vaccine Efficacy; Covid-19; Sars-cov-2; Voc, Variant Of Concern; Mic, Middle Income Country; Aefi, Adverse Events Following Immunisation",,,"

Background

In settings where the COVID-19 vaccine supply is constrained, extending the intervals between the first and second doses of the COVID-19 vaccine may allow more people receive their first doses earlier. Our aim is to estimate the health impact of COVID-19 vaccination alongside benefit-risk assessment of different dosing intervals in 13 middle-income countries (MICs) of Europe.

Methods

We fitted a dynamic transmission model to country-level daily reported COVID-19 mortality in 13 MICs in Europe (Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Bulgaria, Georgia, Republic of Moldova, Russian Federation, Serbia, North Macedonia, Turkey, and Ukraine). A vaccine product with characteristics similar to those of the Oxford/AstraZeneca COVID-19 (AZD1222) vaccine was used in the base case scenario and was complemented by sensitivity analyses around efficacies similar to other COVID-19 vaccines. Both fixed dosing intervals at 4, 8, 12, 16, and 20 weeks and dose-specific intervals that prioritise specific doses for certain age groups were tested. Optimal intervals minimise COVID-19 mortality between March 2021 and December 2022. We incorporated the emergence of variants of concern (VOCs) into the model and conducted a benefit-risk assessment to quantify the tradeoff between health benefits versus adverse events following immunisation.

Findings

In all countries modelled, optimal strategies are those that prioritise the first doses among older adults (60+ years) or adults (20+ years), which lead to dosing intervals longer than six months. In comparison, a four-week fixed dosing interval may incur 10.1% [range: 4.3% - 19.0%; n = 13 (countries)] more deaths. The rapid waning of the immunity induced by the first dose (i.e. with means ranging 60-120 days as opposed to 360 days in the base case) resulted in shorter optimal dosing intervals of 8-20 weeks. Benefit-risk ratios were the highest for fixed dosing intervals of 8-12 weeks.

Interpretation

We infer that longer dosing intervals of over six months could reduce COVID-19 mortality in MICs of Europe. Certain parameters, such as rapid waning of first-dose induced immunity and increased immune escape through the emergence of VOCs, could significantly shorten the optimal dosing intervals.

Funding

World Health Organization.",,doi:https://doi.org/10.1016/j.lanepe.2022.100381; doi:https://doi.org/10.1016/j.lanepe.2022.100381; html:https://europepmc.org/articles/PMC8996067; pdf:https://europepmc.org/articles/PMC8996067?pdf=render +37730620,https://doi.org/10.1186/s13643-023-02333-y,What is known about what works in community-involved decision-making relating to urban green and blue spaces? A realist review protocol.,"Rahtz E, Bell SL, Nurse A, Wheeler BW, Guell C, Elliott LR, Thompson CW, McDougall CW, Lovell R.",,Systematic reviews,2023,2023-09-20,Y,,,,"

Background

There is now a relatively well-established evidence base suggesting that greener living environments and time spent in urban green and blue spaces (UGBS) can be beneficial for human health and wellbeing. However, benefits are not universal and there remain widespread social inequalities in access to such resources and experiences, particularly along axes of class, race, ethnicity, age and disability, and in relation to efforts to increase the availability and accessibility of such spaces. These injustices often relate to distributive, procedural and recognition-based processes. There is growing interest in how to ensure that efforts to increase access to or use of UGBS (whether through infrastructural or social programmes) result in equitable outcomes whilst minimising potential for exacerbating existing inequalities and injustices. Community engagement is considered an important step towards more inclusive UGBS decision-making, from planning and design to management and maintenance processes. It is thought to contribute to better and more widely trusted decisions, enhanced democracy, community satisfaction, civic interest and feelings of green space ownership, and greater longevity of UGBS projects. However, uneven representation and barriers to participation can create imbalances and undermine these benefits.

Methods

An iterative, multi-stage realist-inspired review will be conducted to ask what works, in what context and in what ways relating to the meaningful involvement of communities in UGBS decision-making, focusing on the skills, capacities and capabilities of different stakeholders and the role of contexts and processes. 'Effectiveness' (or what works) will be understood as a multifaceted outcome, encompassing both the processes and results of community engagement efforts. Following a scoping stage to identify initial programme theory, inclusion/exclusion criteria and derive search terms, relevant databases and grey literature will be searched to identify interdisciplinary literature in two phases. The first phase will be used to further develop programme theories, which will be articulated as 'if then' statements. The second phase searches will be used to identify sources to further explore and evidence the programme and formal theory. We will assess all includable evidence for conceptual richness, prioritising more conceptually rich sources if needed.

Discussion

The realist synthesis will explore the key context, mechanism and outcome configurations that appear to explain if and how different approaches to community-involved UGBS decision-making are or are not effective. We will consider factors such as different conceptualisations of community, and if and how they have been involved in UGBS decision-making; the types of tools and approaches used; and the socio-cultural and political or governance structures within which decision-making takes place.",,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02333-y; doi:https://doi.org/10.1186/s13643-023-02333-y; html:https://europepmc.org/articles/PMC10512649; pdf:https://europepmc.org/articles/PMC10512649?pdf=render 33453763,https://doi.org/10.1016/s2468-1253(21)00005-4,Impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England: a population-based study.,"Morris EJA, Goldacre R, Spata E, Mafham M, Finan PJ, Shelton J, Richards M, Spencer K, Emberson J, Hollings S, Curnow P, Gair D, Sebag-Montefiore D, Cunningham C, Rutter MD, Nicholson BD, Rashbass J, Landray M, Collins R, Casadei B, Baigent C.",,The lancet. Gastroenterology & hepatology,2021,2021-01-15,Y,,,,"

Background

There are concerns that the COVID-19 pandemic has had a negative effect on cancer care but there is little direct evidence to quantify any effect. This study aims to investigate the impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England.

Methods

Data were extracted from four population-based datasets spanning NHS England (the National Cancer Cancer Waiting Time Monitoring, Monthly Diagnostic, Secondary Uses Service Admitted Patient Care and the National Radiotherapy datasets) for all referrals, colonoscopies, surgical procedures, and courses of rectal radiotherapy from Jan 1, 2019, to Oct 31, 2020, related to colorectal cancer in England. Differences in patterns of care were investigated between 2019 and 2020. Percentage reductions in monthly numbers and proportions were calculated.

Findings

As compared to the monthly average in 2019, in April, 2020, there was a 63% (95% CI 53-71) reduction (from 36 274 to 13 440) in the monthly number of 2-week referrals for suspected cancer and a 92% (95% CI 89-95) reduction in the number of colonoscopies (from 46 441 to 3484). Numbers had just recovered by October, 2020. This resulted in a 22% (95% CI 8-34) relative reduction in the number of cases referred for treatment (from a monthly average of 2781 in 2019 to 2158 referrals in April, 2020). By October, 2020, the monthly rate had returned to 2019 levels but did not exceed it, suggesting that, from April to October, 2020, over 3500 fewer people had been diagnosed and treated for colorectal cancer in England than would have been expected. There was also a 31% (95% CI 19-42) relative reduction in the numbers receiving surgery in April, 2020, and a lower proportion of laparoscopic and a greater proportion of stoma-forming procedures, relative to the monthly average in 2019. By October, 2020, laparoscopic surgery and stoma rates were similar to 2019 levels. For rectal cancer, there was a 44% (95% CI 17-76) relative increase in the use of neoadjuvant radiotherapy in April, 2020, relative to the monthly average in 2019, due to greater use of short-course regimens. Although in June, 2020, there was a drop in the use of short-course regimens, rates remained above 2019 levels until October, 2020.

Interpretation

The COVID-19 pandemic has led to a sustained reduction in the number of people referred, diagnosed, and treated for colorectal cancer. By October, 2020, achievement of care pathway targets had returned to 2019 levels, albeit with smaller volumes of patients and with modifications to usual practice. As pressure grows in the NHS due to the second wave of COVID-19, urgent action is needed to address the growing burden of undetected and untreated colorectal cancer in England.

Funding

Cancer Research UK, the Medical Research Council, Public Health England, Health Data Research UK, NHS Digital, and the National Institute for Health Research Oxford Biomedical Research Centre.",,pdf:http://www.thelancet.com/article/S2468125321000054/pdf; doi:https://doi.org/10.1016/S2468-1253(21)00005-4; html:https://europepmc.org/articles/PMC7808901; pdf:https://europepmc.org/articles/PMC7808901?pdf=render -37872160,https://doi.org/10.1038/s41467-023-42284-5,"Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease.","Williams AT, Chen J, Coley K, Batini C, Izquierdo A, Packer R, Abner E, Kanoni S, Shepherd DJ, Free RC, Hollox EJ, Brunskill NJ, Ntalla I, Reeve N, Brightling CE, Venn L, Adams E, Bee C, Wallace SE, Pareek M, Hansell AL, Esko T, Estonian Biobank Research Team, Stow D, Jacobs BM, van Heel DA, Genes & Health Research Team, Hennah W, Rao BS, Dudbridge F, Wain LV, Shrine N, Tobin MD, John C.",,Nature communications,2023,2023-10-23,Y,,,,"Thyroid hormones play a critical role in regulation of multiple physiological functions and thyroid dysfunction is associated with substantial morbidity. Here, we use electronic health records to undertake a genome-wide association study of thyroid-stimulating hormone (TSH) levels, with a total sample size of 247,107. We identify 158 novel genetic associations, more than doubling the number of known associations with TSH, and implicate 112 putative causal genes, of which 76 are not previously implicated. A polygenic score for TSH is associated with TSH levels in African, South Asian, East Asian, Middle Eastern and admixed American ancestries, and associated with hypothyroidism and other thyroid disease in South Asians. In Europeans, the TSH polygenic score is associated with thyroid disease, including thyroid cancer and age-of-onset of hypothyroidism and hyperthyroidism. We develop pathway-specific genetic risk scores for TSH levels and use these in phenome-wide association studies to identify potential consequences of pathway perturbation. Together, these findings demonstrate the potential utility of genetic associations to inform future therapeutics and risk prediction for thyroid diseases.",,pdf:https://www.nature.com/articles/s41467-023-42284-5.pdf; doi:https://doi.org/10.1038/s41467-023-42284-5; html:https://europepmc.org/articles/PMC10593800; pdf:https://europepmc.org/articles/PMC10593800?pdf=render 30102210,https://doi.org/10.1016/s1470-2045(18)30425-x,A roadmap for restoring trust in Big Data.,"Lawler M, Morris AD, Sullivan R, Birney E, Middleton A, Makaroff L, Knoppers BM, Horgan D, Eggermont A.",,The Lancet. Oncology,2018,2018-08-01,N,,,,,,doi:https://doi.org/10.1016/S1470-2045(18)30425-X -33928785,https://doi.org/10.1161/circulationaha.120.049844,Unfolded Protein Response as a Compensatory Mechanism and Potential Therapeutic Target in PLN R14del Cardiomyopathy.,"Feyen DAM, Perea-Gil I, Maas RGC, Harakalova M, Gavidia AA, Arthur Ataam J, Wu TH, Vink A, Pei J, Vadgama N, Suurmeijer AJ, Te Rijdt WP, Vu M, Amatya PL, Prado M, Zhang Y, Dunkenberger L, Sluijter JPG, Sallam K, Asselbergs FW, Mercola M, Karakikes I.",,Circulation,2021,2021-04-30,N,"Unfolded protein response; Models, Biological; Induced Pluripotent Stem Cells; Phospholamban; Cardiomyopathy, Dilated; Sequence Analysis, Rna",,,"

Background

Phospholamban (PLN) is a critical regulator of calcium cycling and contractility in the heart. The loss of arginine at position 14 in PLN (R14del) is associated with dilated cardiomyopathy with a high prevalence of ventricular arrhythmias. How the R14 deletion causes dilated cardiomyopathy is poorly understood, and there are no disease-specific therapies.

Methods

We used single-cell RNA sequencing to uncover PLN R14del disease mechanisms in human induced pluripotent stem cells (hiPSC-CMs). We used both 2-dimensional and 3-dimensional functional contractility assays to evaluate the impact of modulating disease-relevant pathways in PLN R14del hiPSC-CMs.

Results

Modeling of the PLN R14del cardiomyopathy with isogenic pairs of hiPSC-CMs recapitulated the contractile deficit associated with the disease in vitro. Single-cell RNA sequencing revealed the induction of the unfolded protein response (UPR) pathway in PLN R14del compared with isogenic control hiPSC-CMs. The activation of UPR was also evident in the hearts from PLN R14del patients. Silencing of each of the 3 main UPR signaling branches (IRE1, ATF6, or PERK) by siRNA exacerbated the contractile dysfunction of PLN R14del hiPSC-CMs. We explored the therapeutic potential of activating the UPR with a small molecule activator, BiP (binding immunoglobulin protein) inducer X. PLN R14del hiPSC-CMs treated with BiP protein inducer X showed a dose-dependent amelioration of the contractility deficit in both 2-dimensional cultures and 3-dimensional engineered heart tissues without affecting calcium homeostasis.

Conclusions

Together, these findings suggest that the UPR exerts a protective effect in the setting of PLN R14del cardiomyopathy and that modulation of the UPR might be exploited therapeutically.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.049844; doi:https://doi.org/10.1161/CIRCULATIONAHA.120.049844; html:https://europepmc.org/articles/PMC8667423; pdf:https://europepmc.org/articles/PMC8667423?pdf=render; doi:https://doi.org/10.1161/circulationaha.120.049844 +37872160,https://doi.org/10.1038/s41467-023-42284-5,"Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease.","Williams AT, Chen J, Coley K, Batini C, Izquierdo A, Packer R, Abner E, Kanoni S, Shepherd DJ, Free RC, Hollox EJ, Brunskill NJ, Ntalla I, Reeve N, Brightling CE, Venn L, Adams E, Bee C, Wallace SE, Pareek M, Hansell AL, Esko T, Estonian Biobank Research Team, Stow D, Jacobs BM, van Heel DA, Genes & Health Research Team, Hennah W, Rao BS, Dudbridge F, Wain LV, Shrine N, Tobin MD, John C.",,Nature communications,2023,2023-10-23,Y,,,,"Thyroid hormones play a critical role in regulation of multiple physiological functions and thyroid dysfunction is associated with substantial morbidity. Here, we use electronic health records to undertake a genome-wide association study of thyroid-stimulating hormone (TSH) levels, with a total sample size of 247,107. We identify 158 novel genetic associations, more than doubling the number of known associations with TSH, and implicate 112 putative causal genes, of which 76 are not previously implicated. A polygenic score for TSH is associated with TSH levels in African, South Asian, East Asian, Middle Eastern and admixed American ancestries, and associated with hypothyroidism and other thyroid disease in South Asians. In Europeans, the TSH polygenic score is associated with thyroid disease, including thyroid cancer and age-of-onset of hypothyroidism and hyperthyroidism. We develop pathway-specific genetic risk scores for TSH levels and use these in phenome-wide association studies to identify potential consequences of pathway perturbation. Together, these findings demonstrate the potential utility of genetic associations to inform future therapeutics and risk prediction for thyroid diseases.",,pdf:https://www.nature.com/articles/s41467-023-42284-5.pdf; doi:https://doi.org/10.1038/s41467-023-42284-5; html:https://europepmc.org/articles/PMC10593800; pdf:https://europepmc.org/articles/PMC10593800?pdf=render 32619549,https://doi.org/10.1016/j.cels.2020.05.012,Ultra-High-Throughput Clinical Proteomics Reveals Classifiers of COVID-19 Infection.,"Messner CB, Demichev V, Wendisch D, Michalick L, White M, Freiwald A, Textoris-Taube K, Vernardis SI, Egger AS, Kreidl M, Ludwig D, Kilian C, Agostini F, Zelezniak A, Thibeault C, Pfeiffer M, Hippenstiel S, Hocke A, von Kalle C, Campbell A, Hayward C, Porteous DJ, Marioni RE, Langenberg C, Lilley KS, Kuebler WM, Mülleder M, Drosten C, Suttorp N, Witzenrath M, Kurth F, Sander LE, Ralser M.",,Cell systems,2020,2020-06-02,Y,Mass spectrometry; High-throughput Proteomics; Swath-ms; Antiviral Immune Response; Clinical Classifiers; Covid-19 Infection,,,"The COVID-19 pandemic is an unprecedented global challenge, and point-of-care diagnostic classifiers are urgently required. Here, we present a platform for ultra-high-throughput serum and plasma proteomics that builds on ISO13485 standardization to facilitate simple implementation in regulated clinical laboratories. Our low-cost workflow handles up to 180 samples per day, enables high precision quantification, and reduces batch effects for large-scale and longitudinal studies. We use our platform on samples collected from a cohort of early hospitalized cases of the SARS-CoV-2 pandemic and identify 27 potential biomarkers that are differentially expressed depending on the WHO severity grade of COVID-19. They include complement factors, the coagulation system, inflammation modulators, and pro-inflammatory factors upstream and downstream of interleukin 6. All protocols and software for implementing our approach are freely available. In total, this work supports the development of routine proteomic assays to aid clinical decision making and generate hypotheses about potential COVID-19 therapeutic targets.",,pdf:http://www.cell.com/article/S2405471220301976/pdf; doi:https://doi.org/10.1016/j.cels.2020.05.012; html:https://europepmc.org/articles/PMC7264033 32212911,https://doi.org/10.1161/jaha.119.013684,Prognostic significance of troponin level in 3121 patients presenting with atrial fibrillation (The NIHR Health Informatics Collaborative TROP-AF study).,"Kaura A, Arnold AD, Panoulas V, Glampson B, Davies J, Mulla A, Woods K, Omigie J, Shah AD, Channon KM, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs FW, O'Sullivan M, Lord GM, Melikian N, Lefroy DC, Francis DP, Shah AM, Kharbanda R, Perera D, Patel RS, Mayet J.",,Journal of the American Heart Association,2020,2020-03-26,Y,Troponin; Mortality; Atrial fibrillation; coronary artery disease; angiography,,,"Background Patients presenting with atrial fibrillation (AF) often undergo a blood test to measure troponin, but interpretation of the result is impeded by uncertainty about its clinical importance. We investigated the relationship between troponin level, coronary angiography, and all-cause mortality in real-world patients presenting with AF. Methods and Results We used National Institute of Health Research Health Informatics Collaborative data to identify patients admitted between 2010 and 2017 at 5 tertiary centers in the United Kingdom with a primary diagnosis of AF. Peak troponin results were scaled as multiples of the upper limit of normal. A total of 3121 patients were included in the analysis. Over a median follow-up of 1462 (interquartile range, 929-1975) days, there were 586 deaths (18.8%). The adjusted hazard ratio for mortality associated with a positive troponin (value above upper limit of normal) was 1.20 (95% CI, 1.01-1.43; P<0.05). Higher troponin levels were associated with higher risk of mortality, reaching a maximum hazard ratio of 2.6 (95% CI, 1.9-3.4) at ≈250 multiples of the upper limit of normal. There was an exponential relationship between higher troponin levels and increased odds of coronary angiography. The mortality risk was 36% lower in patients undergoing coronary angiography than in those who did not (adjusted hazard ratio, 0.61; 95% CI, 0.42-0.89; P=0.01). Conclusions Increased troponin was associated with increased risk of mortality in patients presenting with AF. The lower hazard ratio in patients undergoing invasive management raises the possibility that the clinical importance of troponin release in AF may be mediated by coronary artery disease, which may be responsive to revascularization.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.119.013684; doi:https://doi.org/10.1161/JAHA.119.013684; html:https://europepmc.org/articles/PMC7428631; pdf:https://europepmc.org/articles/PMC7428631?pdf=render -35568032,https://doi.org/10.1016/j.ajhg.2022.04.009,Whole-exome sequencing identifies rare genetic variants associated with human plasma metabolites.,"Bomba L, Walter K, Guo Q, Surendran P, Kundu K, Nongmaithem S, Karim MA, Stewart ID, Langenberg C, Danesh J, Di Angelantonio E, Roberts DJ, Ouwehand WH, INTERVAL study, Dunham I, Butterworth AS, Soranzo N.",,American journal of human genetics,2022,2022-05-13,Y,Sequencing; Proteomics; drug targets; Metabolomics; Endophenotypes; Loss-of-function; Metabolon; Wgs; Wes; Rare Genetic Variant,,,"Metabolite levels measured in the human population are endophenotypes for biological processes. We combined sequencing data for 3,924 (whole-exome sequencing, WES, discovery) and 2,805 (whole-genome sequencing, WGS, replication) donors from a prospective cohort of blood donors in England. We used multiple approaches to select and aggregate rare genetic variants (minor allele frequency [MAF] < 0.1%) in protein-coding regions and tested their associations with 995 metabolites measured in plasma by using ultra-high-performance liquid chromatography-tandem mass spectrometry. We identified 40 novel associations implicating rare coding variants (27 genes and 38 metabolites), of which 28 (15 genes and 28 metabolites) were replicated. We developed algorithms to prioritize putative driver variants at each locus and used mediation and Mendelian randomization analyses to test directionality at associations of metabolite and protein levels at the ACY1 locus. Overall, 66% of reported associations implicate gene targets of approved drugs or bioactive drug-like compounds, contributing to drug targets' validating efforts.",,pdf:https://www.repository.cam.ac.uk/bitstream/1810/337646/3/1-s2.0-S0002929722001574-main.pdf; doi:https://doi.org/10.1016/j.ajhg.2022.04.009; html:https://europepmc.org/articles/PMC9247822; pdf:https://europepmc.org/articles/PMC9247822?pdf=render +33928785,https://doi.org/10.1161/circulationaha.120.049844,Unfolded Protein Response as a Compensatory Mechanism and Potential Therapeutic Target in PLN R14del Cardiomyopathy.,"Feyen DAM, Perea-Gil I, Maas RGC, Harakalova M, Gavidia AA, Arthur Ataam J, Wu TH, Vink A, Pei J, Vadgama N, Suurmeijer AJ, Te Rijdt WP, Vu M, Amatya PL, Prado M, Zhang Y, Dunkenberger L, Sluijter JPG, Sallam K, Asselbergs FW, Mercola M, Karakikes I.",,Circulation,2021,2021-04-30,N,"Unfolded protein response; Models, Biological; Induced Pluripotent Stem Cells; Phospholamban; Cardiomyopathy, Dilated; Sequence Analysis, Rna",,,"

Background

Phospholamban (PLN) is a critical regulator of calcium cycling and contractility in the heart. The loss of arginine at position 14 in PLN (R14del) is associated with dilated cardiomyopathy with a high prevalence of ventricular arrhythmias. How the R14 deletion causes dilated cardiomyopathy is poorly understood, and there are no disease-specific therapies.

Methods

We used single-cell RNA sequencing to uncover PLN R14del disease mechanisms in human induced pluripotent stem cells (hiPSC-CMs). We used both 2-dimensional and 3-dimensional functional contractility assays to evaluate the impact of modulating disease-relevant pathways in PLN R14del hiPSC-CMs.

Results

Modeling of the PLN R14del cardiomyopathy with isogenic pairs of hiPSC-CMs recapitulated the contractile deficit associated with the disease in vitro. Single-cell RNA sequencing revealed the induction of the unfolded protein response (UPR) pathway in PLN R14del compared with isogenic control hiPSC-CMs. The activation of UPR was also evident in the hearts from PLN R14del patients. Silencing of each of the 3 main UPR signaling branches (IRE1, ATF6, or PERK) by siRNA exacerbated the contractile dysfunction of PLN R14del hiPSC-CMs. We explored the therapeutic potential of activating the UPR with a small molecule activator, BiP (binding immunoglobulin protein) inducer X. PLN R14del hiPSC-CMs treated with BiP protein inducer X showed a dose-dependent amelioration of the contractility deficit in both 2-dimensional cultures and 3-dimensional engineered heart tissues without affecting calcium homeostasis.

Conclusions

Together, these findings suggest that the UPR exerts a protective effect in the setting of PLN R14del cardiomyopathy and that modulation of the UPR might be exploited therapeutically.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.049844; doi:https://doi.org/10.1161/CIRCULATIONAHA.120.049844; html:https://europepmc.org/articles/PMC8667423; pdf:https://europepmc.org/articles/PMC8667423?pdf=render; doi:https://doi.org/10.1161/circulationaha.120.049844 31657946,https://doi.org/10.1164/rccm.201903-0673oc,Long-Term Outcomes after Severe Traumatic Brain Injury in Older Adults. A Registry-based Cohort Study.,"Maiden MJ, Cameron PA, Rosenfeld JV, Cooper DJ, McLellan S, Gabbe BJ.",,American journal of respiratory and critical care medicine,2020,2020-01-01,N,Elderly; Brain trauma; Functional Performance; Critical Care Outcomes,,,"Rationale: Older adults (≥65 yr old) account for an increasing proportion of patients with severe traumatic brain injury (TBI), yet clinical trials and outcome studies contain relatively few of these patients.Objectives: To determine functional status 6 months after severe TBI in older adults, changes in this status over 2 years, and outcome covariates.Methods: This was a registry-based cohort study of older adults who were admitted to hospitals in Victoria, Australia, between 2007 and 2016 with severe TBI. Functional status was assessed with Glasgow Outcome Scale Extended (GOSE) 6, 12, and 24 months after injury. Cohort subgroups were defined by admission to an ICU. Features associated with functional outcome were assessed from the ICU subgroup.Measurements and Main Results: The study included 540 older adults who had been hospitalized with severe TBI over the 10-year period; 428 (79%) patients died in hospital, and 456 (84%) died 6 months after injury. There were 277 patients who had not been admitted to an ICU; at 6 months, 268 (97%) had died, 8 (3%) were dependent (GOSE 2-4), and 1 (0.4%) was functionally independent (GOSE 5-8). There were 263 patients who had been admitted to an ICU; at 6 months, 188 (73%) had died, 39 (15%) were dependent, and 32 (12%) were functionally independent. These proportions did not change over longer follow-up. The only clinical features associated with a lower rate of functional independence were Injury Severity Score ≥25 (adjusted odds ratio, 0.24 [95% confidence interval, 0.09-0.67]; P = 0.007) and older age groups (P = 0.017).Conclusions: Severe TBI in older adults is a condition with very high mortality, and few recover to functional independence.",,doi:https://doi.org/10.1164/rccm.201903-0673OC +35568032,https://doi.org/10.1016/j.ajhg.2022.04.009,Whole-exome sequencing identifies rare genetic variants associated with human plasma metabolites.,"Bomba L, Walter K, Guo Q, Surendran P, Kundu K, Nongmaithem S, Karim MA, Stewart ID, Langenberg C, Danesh J, Di Angelantonio E, Roberts DJ, Ouwehand WH, INTERVAL study, Dunham I, Butterworth AS, Soranzo N.",,American journal of human genetics,2022,2022-05-13,Y,Sequencing; Proteomics; drug targets; Metabolomics; Endophenotypes; Loss-of-function; Metabolon; Wgs; Wes; Rare Genetic Variant,,,"Metabolite levels measured in the human population are endophenotypes for biological processes. We combined sequencing data for 3,924 (whole-exome sequencing, WES, discovery) and 2,805 (whole-genome sequencing, WGS, replication) donors from a prospective cohort of blood donors in England. We used multiple approaches to select and aggregate rare genetic variants (minor allele frequency [MAF] < 0.1%) in protein-coding regions and tested their associations with 995 metabolites measured in plasma by using ultra-high-performance liquid chromatography-tandem mass spectrometry. We identified 40 novel associations implicating rare coding variants (27 genes and 38 metabolites), of which 28 (15 genes and 28 metabolites) were replicated. We developed algorithms to prioritize putative driver variants at each locus and used mediation and Mendelian randomization analyses to test directionality at associations of metabolite and protein levels at the ACY1 locus. Overall, 66% of reported associations implicate gene targets of approved drugs or bioactive drug-like compounds, contributing to drug targets' validating efforts.",,pdf:https://www.repository.cam.ac.uk/bitstream/1810/337646/3/1-s2.0-S0002929722001574-main.pdf; doi:https://doi.org/10.1016/j.ajhg.2022.04.009; html:https://europepmc.org/articles/PMC9247822; pdf:https://europepmc.org/articles/PMC9247822?pdf=render 36962407,https://doi.org/10.1371/journal.pgph.0000292,Health worker experiences of implementing TB infection prevention and control: A qualitative evidence synthesis to inform implementation recommendations.,"van der Westhuizen HM, Dorward J, Roberts N, Greenhalgh T, Ehrlich R, Butler CC, Tonkin-Crine S.",,PLOS global public health,2022,2022-07-07,Y,,,,"Implementation of TB infection prevention and control (IPC) measures in health facilities is frequently inadequate, despite nosocomial TB transmission to patients and health workers causing harm. We aimed to review qualitative evidence of the complexity associated with implementing TB IPC, to help guide the development of TB IPC implementation plans. We undertook a qualitative evidence synthesis of studies that used qualitative methods to explore the experiences of health workers implementing TB IPC in health facilities. We searched eight databases in November 2021, complemented by citation tracking. Two reviewers screened titles and abstracts and reviewed full texts of potentially eligible papers. We used the Critical Appraisals Skills Programme checklist for quality appraisal, thematic synthesis to identify key findings and the GRADE-CERQual method to appraise the certainty of review findings. The review protocol was pre-registered on PROSPERO, ID CRD42020165314. We screened 1062 titles and abstracts and reviewed 102 full texts, with 37 studies included in the synthesis. We developed 10 key findings, five of which we had high confidence in. We describe several components of TB IPC as a complex intervention. Health workers were influenced by their personal occupational TB risk perceptions when deciding whether to implement TB IPC and neglected the contribution of TB IPC to patient safety. Health workers and researchers expressed multiple uncertainties (for example the duration of infectiousness of people with TB), assumptions and misconceptions about what constitutes effective TB IPC, including focussing TB IPC on patients known with TB on treatment who pose a small risk of transmission. Instead, TB IPC resources should target high risk areas for transmission (crowded, poorly ventilated spaces). Furthermore, TB IPC implementation plans should support health workers to translate TB IPC guidelines to local contexts, including how to navigate unintended stigma caused by IPC, and using limited IPC resources effectively.",,pdf:https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0000292&type=printable; doi:https://doi.org/10.1371/journal.pgph.0000292; html:https://europepmc.org/articles/PMC10021216; pdf:https://europepmc.org/articles/PMC10021216?pdf=render -37210036,https://doi.org/10.1016/j.jacc.2023.05.005,Individualized Family Screening for Arrhythmogenic Right Ventricular Cardiomyopathy.,"Muller SA, Gasperetti A, Bosman LP, Schmidt AF, Baas AF, Amin AS, Houweling AC, Wilde AAM, Compagnucci P, Targetti M, Casella M, Calò L, Tondo C, van der Harst P, Asselbergs FW, van Tintelen JP, Oerlemans MIFJ, Te Riele ASJM.",,Journal of the American College of Cardiology,2023,2023-05-18,N,ventricular arrhythmia; Predictors; Screening Interval; Arvc; Family Screening,,,"

Background

Clinical guidelines recommend regular screening for arrhythmogenic right ventricular cardiomyopathy (ARVC) to monitor at-risk relatives, resulting in a significant burden on clinical resources. Prioritizing relatives on their probability of developing definite ARVC may provide more efficient patient care.

Objectives

The aim of this study was to determine the predictors and probability of ARVC development over time among at-risk relatives.

Methods

A total of 136 relatives (46% men, median age 25.5 years [IQR: 15.8-44.4 years]) from the Netherlands Arrhythmogenic Cardiomyopathy Registry without definite ARVC by 2010 task force criteria were included. Phenotype was ascertained using electrocardiography, Holter monitoring, and cardiac imaging. Subjects were divided into groups with ""possible ARVC"" (only genetic or familial predisposition) and ""borderline ARVC"" (1 minor task force criterion plus genetic or familial predisposition). Cox regression was performed to determine predictors and multistate modeling to assess the probability of ARVC development. Results were replicated in an unrelated Italian cohort (57% men, median age 37.0 years [IQR: 25.4-50.4 years]).

Results

At baseline, 93 subjects (68%) had possible ARVC, and 43 (32%) had borderline ARVC. Follow-up was available for 123 relatives (90%). After 8.1 years (IQR: 4.2-11.4 years), 41 (33%) had developed definite ARVC. Independent of baseline phenotype, symptomatic subjects (P = 0.014) and those 20 to 30 years of age (P = 0.002) had a higher hazard of developing definite ARVC. Furthermore, patients with borderline ARVC had a higher probability of developing definite ARVC compared with those with possible ARVC (1-year probability 13% vs 0.6%, 3-year probability 35% vs 5%; P < 0.01). External replication showed comparable results (P > 0.05).

Conclusions

Symptomatic relatives, those 20 to 30 years of age, and those with borderline ARVC have a higher probability of developing definite ARVC. These patients may benefit from more frequent follow-up, while others may be monitored less often.",,doi:https://doi.org/10.1016/j.jacc.2023.05.005 31650125,https://doi.org/10.1016/s2589-7500(19)30012-3,A chronological map of 308 physical and mental health conditions from 4 million individuals in the English National Health Service.,"Kuan V, Denaxas S, Gonzalez-Izquierdo A, Direk K, Bhatti O, Husain S, Sutaria S, Hingorani M, Nitsch D, Parisinos CA, Lumbers RT, Mathur R, Sofat R, Casas JP, Wong ICK, Hemingway H, Hingorani AD.",,The Lancet. Digital health,2019,2019-05-20,Y,,The Human Phenome,,"

Background

To effectively prevent, detect, and treat health conditions that affect people during their lifecourse, health-care professionals and researchers need to know which sections of the population are susceptible to which health conditions and at which ages. Hence, we aimed to map the course of human health by identifying the 50 most common health conditions in each decade of life and estimating the median age at first diagnosis.

Methods

We developed phenotyping algorithms and codelists for physical and mental health conditions that involve intensive use of health-care resources. Individuals older than 1 year were included in the study if their primary-care and hospital-admission records met research standards set by the Clinical Practice Research Datalink and they had been registered in a general practice in England contributing up-to-standard data for at least 1 year during the study period. We used linked records of individuals from the CALIBER platform to calculate the sex-standardised cumulative incidence for these conditions by 10-year age groups between April 1, 2010, and March 31, 2015. We also derived the median age at diagnosis and prevalence estimates stratified by age, sex, and ethnicity (black, white, south Asian) over the study period from the primary-care and secondary-care records of patients.

Findings

We developed case definitions for 308 disease phenotypes. We used records of 2 784 138 patients for the calculation of cumulative incidence and of 3 872 451 patients for the calculation of period prevalence and median age at diagnosis of these conditions. Conditions that first gained prominence at key stages of life were: atopic conditions and infections that led to hospital admission in children (<10 years); acne and menstrual disorders in the teenage years (10-19 years); mental health conditions, obesity, and migraine in individuals aged 20-29 years; soft-tissue disorders and gastro-oesophageal reflux disease in individuals aged 30-39 years; dyslipidaemia, hypertension, and erectile dysfunction in individuals aged 40-59 years; cancer, osteoarthritis, benign prostatic hyperplasia, cataract, diverticular disease, type 2 diabetes, and deafness in individuals aged 60-79 years; and atrial fibrillation, dementia, acute and chronic kidney disease, heart failure, ischaemic heart disease, anaemia, and osteoporosis in individuals aged 80 years or older. Black or south-Asian individuals were diagnosed earlier than white individuals for 258 (84%) of the 308 conditions. Bone fractures and atopic conditions were recorded earlier in male individuals, whereas female individuals were diagnosed at younger ages with nutritional anaemias, tubulointerstitial nephritis, and urinary disorders.

Interpretation

We have produced the first chronological map of human health with cumulative-incidence and period-prevalence estimates for multiple morbidities in parallel from birth to advanced age. This can guide clinicians, policy makers, and researchers on how to formulate differential diagnoses, allocate resources, and target research priorities on the basis of the knowledge of who gets which diseases when. We have published our phenotyping algorithms on the CALIBER open-access Portal which will facilitate future research by providing a curated list of reusable case definitions.

Funding

Wellcome Trust, National Institute for Health Research, Medical Research Council, Arthritis Research UK, British Heart Foundation, Cancer Research UK, Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Department of Health and Social Care (England), Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), Economic and Social Research Council, Engineering and Physical Sciences Research Council, National Institute for Social Care and Health Research, and The Alan Turing Institute.",,doi:https://doi.org/10.1016/s2589-7500(19)30012-3; doi:https://doi.org/10.1016/S2589-7500(19)30012-3; html:https://europepmc.org/articles/PMC6798263; pdf:https://europepmc.org/articles/PMC6798263?pdf=render +37210036,https://doi.org/10.1016/j.jacc.2023.05.005,Individualized Family Screening for Arrhythmogenic Right Ventricular Cardiomyopathy.,"Muller SA, Gasperetti A, Bosman LP, Schmidt AF, Baas AF, Amin AS, Houweling AC, Wilde AAM, Compagnucci P, Targetti M, Casella M, Calò L, Tondo C, van der Harst P, Asselbergs FW, van Tintelen JP, Oerlemans MIFJ, Te Riele ASJM.",,Journal of the American College of Cardiology,2023,2023-05-18,N,ventricular arrhythmia; Predictors; Screening Interval; Arvc; Family Screening,,,"

Background

Clinical guidelines recommend regular screening for arrhythmogenic right ventricular cardiomyopathy (ARVC) to monitor at-risk relatives, resulting in a significant burden on clinical resources. Prioritizing relatives on their probability of developing definite ARVC may provide more efficient patient care.

Objectives

The aim of this study was to determine the predictors and probability of ARVC development over time among at-risk relatives.

Methods

A total of 136 relatives (46% men, median age 25.5 years [IQR: 15.8-44.4 years]) from the Netherlands Arrhythmogenic Cardiomyopathy Registry without definite ARVC by 2010 task force criteria were included. Phenotype was ascertained using electrocardiography, Holter monitoring, and cardiac imaging. Subjects were divided into groups with ""possible ARVC"" (only genetic or familial predisposition) and ""borderline ARVC"" (1 minor task force criterion plus genetic or familial predisposition). Cox regression was performed to determine predictors and multistate modeling to assess the probability of ARVC development. Results were replicated in an unrelated Italian cohort (57% men, median age 37.0 years [IQR: 25.4-50.4 years]).

Results

At baseline, 93 subjects (68%) had possible ARVC, and 43 (32%) had borderline ARVC. Follow-up was available for 123 relatives (90%). After 8.1 years (IQR: 4.2-11.4 years), 41 (33%) had developed definite ARVC. Independent of baseline phenotype, symptomatic subjects (P = 0.014) and those 20 to 30 years of age (P = 0.002) had a higher hazard of developing definite ARVC. Furthermore, patients with borderline ARVC had a higher probability of developing definite ARVC compared with those with possible ARVC (1-year probability 13% vs 0.6%, 3-year probability 35% vs 5%; P < 0.01). External replication showed comparable results (P > 0.05).

Conclusions

Symptomatic relatives, those 20 to 30 years of age, and those with borderline ARVC have a higher probability of developing definite ARVC. These patients may benefit from more frequent follow-up, while others may be monitored less often.",,doi:https://doi.org/10.1016/j.jacc.2023.05.005 30862657,https://doi.org/10.2337/dc18-2004,Risk of Incident Obstructive Sleep Apnea Among Patients With Type 2 Diabetes.,"Subramanian A, Adderley NJ, Tracy A, Taverner T, Hanif W, Toulis KA, Thomas GN, Tahrani AA, Nirantharakumar K.",,Diabetes care,2019,2019-03-12,N,,,,"

Objective

This study compared the incidence of obstructive sleep apnea (OSA) in patients with and without type 2 diabetes and investigated risk factors for OSA in patients with type 2 diabetes.

Research design and methods

A retrospective cohort study was performed to compare OSA incidence between adult patients with and without type 2 diabetes matched for age, sex, and BMI. Patients with a prevalent OSA diagnosis were excluded. The study cohort was derived from The Health Improvement Network (THIN), a U.K. primary care database, from 1 January 2005 to 31 December 2017.

Results

There were 3,110 (0.88%) and 5,968 (0.46%) incident OSA cases identified in the 360,250 exposed and 1,296,489 unexposed patient cohorts, respectively. Adjusted incidence rate ratio (aIRR) of OSA in patients with type 2 diabetes compared with those without was 1.48 (95% CI 1.42-1.55; P < 0.001). In a multivariate regression analysis of patients with type 2 diabetes, significant predictors of OSA were diabetes-related foot disease (1.23 [1.06-1.42]; P = 0.005), being prescribed insulin in the last 60 days (1.58 [1.42-1.75]; P < 0.001), male sex (2.27 [2.09-2.46]; P < 0.001), being overweight (2.02 [1.54-2.64]; P < 0.001) or obese (8.29 [6.42-10.69]; P < 0.001), heart failure (1.41 [1.18-1.70]; P < 0.001), ischemic heart disease (1.22 [1.11-1.34]; P < 0.001), atrial fibrillation (1.23 [1.04-1.46]; P = 0.015), hypertension (1.32 [1.23-1.43]; P < 0.001), and depression (1.75 [1.61-1.91]; P < 0.001).

Conclusions

When considered alongside previous evidence, this study indicates that the association between type 2 diabetes and OSA is bidirectional. In addition to known predictors of OSA, diabetes-related foot disease and insulin treatment were identified as risk factors in patients with type 2 diabetes.",,pdf:https://care.diabetesjournals.org/content/diacare/42/5/954.full.pdf; doi:https://doi.org/10.2337/dc18-2004 34337345,https://doi.org/10.1123/jmpb.2020-0038,Validation of Wearable Camera Still Images to Assess Posture in Free-Living Conditions.,"Martinez J, Decker A, Cho CC, Doherty A, Swartz AM, Staudenmayer JW, Strath SJ.",,Journal for the measurement of physical behaviour,2021,2021-02-24,N,Activpal; Autographer; Objective Measuring,,,"

Purpose

To assess the convergent validity of body worn wearable camera (WC) still-images (IMGs) for determining posture compared with activPAL (AP) classifications.

Methods

Participants (n=16, mean age 46.7±23.8yrs, 9F) wore an Autographer WC above the xyphoid process and an AP during three, 2hr free-living visits. IMGs were captured on average 8.47 seconds apart and were annotated with output consisting of events, transitory states, unknown and gaps. Events were annotations that matched AP classifications (sit, stand and move) consisting of at least 3 IMGs, transitory states were posture annotations fewer than 3 IMGs, unknown were IMGs that could not be accurately classified, and gaps were time between annotations. For analyses, annotation and AP output were converted to one-sec epochs and matched second-by-second. Total and average length of visits and events are reported in minutes. Bias and 95% CIs for event posture times from IMGs to AP posture times were calculated to determine accuracy and precision. Confusion matrices using total AP posture times were computed to determine misclassification.

Results

43 visits were analyzed with a total visit and event time of 5027.73 and 4237.23 minutes and average visit and event lengths being 116.92 and 98.54 minutes, respectively. Bias was not statistically significant for sitting but significant for standing and movement (0.84, -6.87 and 6.04 minutes). From confusion matrices, IMGs correctly classified sitting, standing and movement 85.69%, 54.87%, and 69.41% of total AP time, respectively.

Conclusion

WC IMGs provide a good estimation of overall sitting time but underestimate standing and overestimate movement time. Future work is warranted to improve posture classifications and examine IMG accuracy and precision in assessing activity type behaviors.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320753; doi:https://doi.org/10.1123/jmpb.2020-0038; html:https://europepmc.org/articles/PMC8320753; pdf:https://europepmc.org/articles/PMC8320753?pdf=render; doi:https://doi.org/10.1123/jmpb.2020-0038 34903266,https://doi.org/10.1186/s13059-021-02561-2,CIDER: an interpretable meta-clustering framework for single-cell RNA-seq data integration and evaluation.,"Hu Z, Ahmed AA, Yau C.",,Genome biology,2021,2021-12-13,Y,Clustering; Confounding Factors; Single-cell Rna-seq,,,"Clustering of joint single-cell RNA-Seq (scRNA-Seq) data is often challenged by confounding factors, such as batch effects and biologically relevant variability. Existing batch effect removal methods typically require strong assumptions on the composition of cell populations being near identical across samples. Here, we present CIDER, a meta-clustering workflow based on inter-group similarity measures. We demonstrate that CIDER outperforms other scRNA-Seq clustering methods and integration approaches in both simulated and real datasets. Moreover, we show that CIDER can be used to assess the biological correctness of integration in real datasets, while it does not require the existence of prior cellular annotations.",,pdf:https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-021-02561-2; doi:https://doi.org/10.1186/s13059-021-02561-2; html:https://europepmc.org/articles/PMC8667531; pdf:https://europepmc.org/articles/PMC8667531?pdf=render -35193912,https://doi.org/10.1136/bmjopen-2021-053884,"Variation in health visiting contacts for children in England: cross-sectional analysis of the 2-2½ year review using administrative data (Community Services Dataset, CSDS).","Fraser C, Harron K, Barlow J, Bennett S, Woods G, Shand J, Kendall S, Woodman J.",,BMJ open,2022,2022-02-22,Y,Public Health; Community Child Health; Child Protection; Organisation Of Health Services,,,"

Objective

The 2-2½ year universal health visiting review in England is a key time point for assessing child development and promoting school readiness. We aimed to ascertain which children were least likely to receive their 2-2½ year review and whether there were additional non-mandated contacts for children who missed this review.

Design, setting, participants

Cross-sectional analysis of the 2-2½ year review and additional health visiting contacts for 181 130 children aged 2 in England 2018/2019, stratified by ethnicity, deprivation, safeguarding vulnerability indicator and Looked After Child status.

Analysis

We used data from 33 local authorities submitting highly complete data on health visiting contacts to the Community Services Dataset. We calculated the percentage of children with a recorded 2-2½ year review and/or any additional health visiting contacts and average number of contacts, by child characteristic.

Results

The most deprived children were slightly less likely to receive a 2-2½ year review than the least deprived children (72% vs 78%) and Looked After Children much less likely, compared with other children (44% vs 69%). When all additional contacts were included, the pattern was reversed (deprivation) or disappeared (Looked After children). A substantial proportion of all children (24%), children with a 'safeguarding vulnerability' (22%) and Looked After children (29%) did not have a record of either a 2-2½ year review or any other face-to-face contact in the year.

Conclusions

A substantial minority of children aged 2 with known vulnerabilities did not see the health visiting team at all in the year. Some higher need children (eg, deprived and Looked After) appeared to be seeing the health visiting team but not receiving their mandated health review. Further work is needed to establish the reasons for this, and potential solutions. There is an urgent need to improve the quality of national health visiting data.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e053884.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-053884; html:https://europepmc.org/articles/PMC8867374; pdf:https://europepmc.org/articles/PMC8867374?pdf=render 31863937,https://doi.org/10.1016/j.aap.2019.105333,A systematic review of the association between fault or blame-related attributions and procedures after transport injury and health and work-related outcomes.,"Giummarra MJ, Lau G, Grant G, Gabbe BJ.",,Accident; analysis and prevention,2020,2019-12-19,N,Depression; Recovery; Pain; Anxiety; Mental health; Ptsd; Fault; Road Trauma; Transport Injury,,,"Attributions of fault are often associated with worse injury outcomes; however, the consistency and magnitude of these impacts is not known. This review examined the prognostic role of fault on health, mental health, pain and work outcomes after transport injury. A systematic search of five electronic databases (Medline, Embase, CINAHL, PsycINFO, Cochrane Library) yielded 16,324 records published between 2000 and January 2018. Eligibility criteria were: adult transport injury survivors; prospective design; multivariable analysis; fault-related factor analysed; pain, mental health, general health or work-related outcome. Citations (n = 10,558, excluding duplicates) and full text articles (n = 555) were screened manually (Reviewer 1), and using concurrent machine learning and text mining (Reviewer 2; using Abstrackr, WordStat and QDA miner). Data from 55 papers that met all inclusion criteria were extracted, papers were evaluated for risk of bias using the QUIPS tool, and overall level of evidence was assessed using the GRADE tool. There were six main fault-related factors classified as: fault or responsibility, fault-based compensation, lawyer involvement or litigation, blame or guilt, road user or position in vehicle, and impact direction. Overall there were inconsistent associations between fault and transport injury outcomes, and 60% of papers had high risk of bias. There was moderate evidence that fault-based compensation claims were associated with poorer health-related outcomes, and that lawyer involvement was associated with poorer work outcomes beyond 12 months post-injury. However, the evidence of negative associations between fault-based compensation claims and work-related outcomes was limited. Lawyer involvement and fault-based compensation claims were associated with adverse mental health outcomes six months post-injury, but not beyond 12 months. The most consistent associations between fault and negative outcomes were not for fault attributions, per se, but were related to fault-related procedures (e.g., lawyer engagement, fault-based compensation claims).",,doi:https://doi.org/10.1016/j.aap.2019.105333 +35193912,https://doi.org/10.1136/bmjopen-2021-053884,"Variation in health visiting contacts for children in England: cross-sectional analysis of the 2-2½ year review using administrative data (Community Services Dataset, CSDS).","Fraser C, Harron K, Barlow J, Bennett S, Woods G, Shand J, Kendall S, Woodman J.",,BMJ open,2022,2022-02-22,Y,Public Health; Community Child Health; Child Protection; Organisation Of Health Services,,,"

Objective

The 2-2½ year universal health visiting review in England is a key time point for assessing child development and promoting school readiness. We aimed to ascertain which children were least likely to receive their 2-2½ year review and whether there were additional non-mandated contacts for children who missed this review.

Design, setting, participants

Cross-sectional analysis of the 2-2½ year review and additional health visiting contacts for 181 130 children aged 2 in England 2018/2019, stratified by ethnicity, deprivation, safeguarding vulnerability indicator and Looked After Child status.

Analysis

We used data from 33 local authorities submitting highly complete data on health visiting contacts to the Community Services Dataset. We calculated the percentage of children with a recorded 2-2½ year review and/or any additional health visiting contacts and average number of contacts, by child characteristic.

Results

The most deprived children were slightly less likely to receive a 2-2½ year review than the least deprived children (72% vs 78%) and Looked After Children much less likely, compared with other children (44% vs 69%). When all additional contacts were included, the pattern was reversed (deprivation) or disappeared (Looked After children). A substantial proportion of all children (24%), children with a 'safeguarding vulnerability' (22%) and Looked After children (29%) did not have a record of either a 2-2½ year review or any other face-to-face contact in the year.

Conclusions

A substantial minority of children aged 2 with known vulnerabilities did not see the health visiting team at all in the year. Some higher need children (eg, deprived and Looked After) appeared to be seeing the health visiting team but not receiving their mandated health review. Further work is needed to establish the reasons for this, and potential solutions. There is an urgent need to improve the quality of national health visiting data.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e053884.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-053884; html:https://europepmc.org/articles/PMC8867374; pdf:https://europepmc.org/articles/PMC8867374?pdf=render 35386996,https://doi.org/10.3389/falgy.2021.677677,Purinergic Receptors in the Airways: Potential Therapeutic Targets for Asthma?,"Thompson RJ, Sayers I, Kuokkanen K, Hall IP.",,Frontiers in allergy,2021,2021-05-31,Y,Lung; Bioinformatics; Asthma; airway; Gene Expression; purinergic receptor; Purinergic Signaling,,,"Extracellular ATP functions as a signaling messenger through its actions on purinergic receptors, and is known to be involved in numerous physiological and pathophysiological processes throughout the body, including in the lungs and airways. Consequently, purinergic receptors are considered to be promising therapeutic targets for many respiratory diseases, including asthma. This review explores how online bioinformatics resources combined with recently generated datasets can be utilized to investigate purinergic receptor gene expression in tissues and cell types of interest in respiratory disease to identify potential therapeutic targets, which can then be investigated further. These approaches show that different purinergic receptors are expressed at different levels in lung tissue, and that purinergic receptors tend to be expressed at higher levels in immune cells and at more moderate levels in airway structural cells. Notably, P2RX1, P2RX4, P2RX7, P2RY1, P2RY11, and P2RY14 were revealed as the most highly expressed purinergic receptors in lung tissue, therefore suggesting that these receptors have good potential as therapeutic targets for asthma and other respiratory diseases.",,pdf:https://www.frontiersin.org/articles/10.3389/falgy.2021.677677/pdf; doi:https://doi.org/10.3389/falgy.2021.677677; html:https://europepmc.org/articles/PMC8974712; pdf:https://europepmc.org/articles/PMC8974712?pdf=render 35099396,https://doi.org/10.2196/21341,"Collaborative Research and Development of a Novel, Patient-Centered Digital Platform (MyEyeSite) for Rare Inherited Retinal Disease Data: Acceptability and Feasibility Study.","Gilbert RM, Sumodhee D, Pontikos N, Hollyhead C, Patrick A, Scarles S, Van Der Smissen S, Young RM, Nettleton N, Webster AR, Cammack J.",,JMIR formative research,2022,2022-01-31,Y,Genetics; Mobile phone; Ophthalmology; Rare Diseases; Digital Health; Gdpr; Eye Data; Inherited Retinal Diseases (Ird); Myeyesite; Subject Access Request (Sar),,,"

Background

Inherited retinal diseases (IRDs) are a leading cause of blindness in children and working age adults in the United Kingdom and other countries, with an appreciable socioeconomic impact. However, by definition, IRD data are individually rare, and as a result, this patient group has been underserved by research. Researchers need larger amounts of these rare data to make progress in this field, for example, through the development of gene therapies. The challenge has been how to find and make these data available to researchers in the most productive way. MyEyeSite is a research collaboration aiming to design and develop a digital platform (the MyEyeSite platform) for people with rare IRDs that will enable patients, doctors, and researchers to aggregate and share specialist eye health data. A crucial component of this platform is the MyEyeSite patient application, which will provide the means for patients with IRD to interact with the system and, in particular, to collate, manage, and share their personal specialist IRD data both for research and their own health care.

Objective

This study aims to test the acceptability and feasibility of the MyEyeSite platform in the target IRD population through a collaborative patient-centered study.

Methods

Qualitative data were generated through focus groups and workshops, and quantitative data were obtained through a survey of patients with IRD. Participants were recruited through clinics at Moorfields Eye Hospital National Health Service (NHS) Foundation Trust and the National Institute for Health Research (NIHR) Moorfields Biomedical Research Centre through their patient and public involvement databases.

Results

Our IRD focus group sample (n=50) highlighted the following themes: frustration with the current system regarding data sharing within the United Kingdom's NHS; positive expectations of the potential benefits of the MyEyeSite patient application, resulting from increased access to this specialized data; and concerns regarding data security, including potentially unethical use of the data outside the NHS. Of the surveyed 80 participants, 68 (85%) were motivated to have a more active role in their eye care and share their data for research purposes using a secure technology, such as a web application or mobile app.

Conclusions

This study demonstrates that patients with IRD are highly motivated to be actively involved in managing their own data for research and their own eye care. It demonstrates the feasibility of involving patients with IRD in the detailed design of the MyEyeSite platform exemplar, with input from the patient with IRD workshops playing a key role in determining both the functionality and accessibility of the designs and prototypes. The development of a user-centered technological solution to the problem of rare health data has the potential to benefit not only the patient with IRD community but also others with rare diseases.",,pdf:https://formative.jmir.org/2022/1/e21341/PDF; doi:https://doi.org/10.2196/21341; html:https://europepmc.org/articles/PMC8845013; pdf:https://europepmc.org/articles/PMC8845013?pdf=render 33043790,https://doi.org/10.1177/0141076820961776,Advancing UK regulatory science and innovation in healthcare.,"Calvert MJ, Marston E, Samuels M, Rivera SC, Torlinska B, Oliver K, Denniston AK, Hoare S.",,Journal of the Royal Society of Medicine,2021,2020-10-12,Y,,,,,,pdf:https://journals.sagepub.com/doi/pdf/10.1177/0141076820961776; doi:https://doi.org/10.1177/0141076820961776; html:https://europepmc.org/articles/PMC7809339; pdf:https://europepmc.org/articles/PMC7809339?pdf=render 36688706,https://doi.org/10.1093/rheumatology/kead038,Classification of patients with osteoarthritis through clusters of comorbidities using 633 330 individuals from Spain.,"Pineda-Moncusí M, Dernie F, Dell'Isola A, Kamps A, Runhaar J, Swain S, Zhang W, Englund M, Pitsillidou I, Strauss VY, Robinson DE, Prieto-Alhambra D, Khalid S.",,"Rheumatology (Oxford, England)",2023,2023-11-01,Y,Clustering; epidemiology; Comorbidities; Oa,,,"

Objectives

To explore clustering of comorbidities among patients with a new diagnosis of OA and estimate the 10-year mortality risk for each identified cluster.

Methods

This is a population-based cohort study of individuals with first incident diagnosis of OA of the hip, knee, ankle/foot, wrist/hand or 'unspecified' site between 2006 and 2020, using SIDIAP (a primary care database representative of Catalonia, Spain). At the time of OA diagnosis, conditions associated with OA in the literature that were found in ≥1% of the individuals (n = 35) were fitted into two cluster algorithms, k-means and latent class analysis. Models were assessed using a range of internal and external evaluation procedures. Mortality risk of the obtained clusters was assessed by survival analysis using Cox proportional hazards.

Results

We identified 633 330 patients with a diagnosis of OA. Our proposed best solution used latent class analysis to identify four clusters: 'low-morbidity' (relatively low number of comorbidities), 'back/neck pain plus mental health', 'metabolic syndrome' and 'multimorbidity' (higher prevalence of all studied comorbidities). Compared with the 'low-morbidity' cluster, the 'multimorbidity' cluster had the highest risk of 10-year mortality (adjusted hazard ratio [HR]: 2.19 [95% CI: 2.15, 2.23]), followed by the 'metabolic syndrome' cluster (adjusted HR: 1.24 [95% CI: 1.22, 1.27]) and the 'back/neck pain plus mental health' cluster (adjusted HR: 1.12 [95% CI: 1.09, 1.15]).

Conclusion

Patients with a new diagnosis of OA can be clustered into groups based on their comorbidity profile, with significant differences in 10-year mortality risk. Further research is required to understand the interplay between OA and particular comorbidity groups, and the clinical significance of such results.",,pdf:https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/kead038/49101708/kead038.pdf; doi:https://doi.org/10.1093/rheumatology/kead038; html:https://europepmc.org/articles/PMC10629784; pdf:https://europepmc.org/articles/PMC10629784?pdf=render -38296965,https://doi.org/10.1038/s41467-023-43644-x,"Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.","RECOVERY Collaborative Group, Horby PW, Peto L, Staplin N, Campbell M, Pessoa-Amorim G, Mafham M, Emberson JR, Stewart R, Prudon B, Uriel A, Green CA, Dhasmana DJ, Malein F, Majumdar J, Collini P, Shurmer J, Yates B, Baillie JK, Buch MH, Day J, Faust SN, Jaki T, Jeffery K, Juszczak E, Knight M, Lim WS, Montgomery A, Mumford A, Rowan K, Thwaites G, Haynes R, Landray MJ.",,Nature communications,2024,2024-01-31,Y,,,,"Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome.",,pdf:https://www.nature.com/articles/s41467-023-43644-x.pdf; doi:https://doi.org/10.1038/s41467-023-43644-x; html:https://europepmc.org/articles/PMC10831058; pdf:https://europepmc.org/articles/PMC10831058?pdf=render 35861818,https://doi.org/10.1161/jaha.121.025473,Interatrial Block Predicts Life-Threatening Arrhythmias in Dilated Cardiomyopathy.,"Henkens MTHM, López Martínez H, Weerts J, Sammani A, Raafs AG, Verdonschot JAJ, van de Leur RR, Sikking MA, Stroeks S, van Empel VPM, Brunner-La Rocca HP, van Stipdonk AMW, Farmakis D, Hazebroek MR, Vernooy K, Bayés-de-Luna A, Asselbergs FW, Bayés-Genís A, Heymans SRB.",,Journal of the American Heart Association,2022,2022-07-15,Y,Electrocardiography; Dilated cardiomyopathy; Sudden Cardiac Death; Interatrial Block; Non‐ischemic Cardiomyopathy; Life‐threatening Arrhythmias,,,"Background Interatrial block (IAB) has been associated with supraventricular arrhythmias and stroke, and even with sudden cardiac death in the general population. Whether IAB is associated with life-threatening arrhythmias (LTA) and sudden cardiac death in dilated cardiomyopathy (DCM) remains unknown. This study aimed to determine the association between IAB and LTA in ambulant patients with DCM. Methods and Results A derivation cohort (Maastricht Dilated Cardiomyopathy Registry; N=469) and an external validation cohort (Utrecht Cardiomyopathy Cohort; N=321) were used for this study. The presence of IAB (P-wave duration>120 milliseconds) or atrial fibrillation (AF) was determined using digital calipers by physicians blinded to the study data. In the derivation cohort, IAB and AF were present in 291 (62%) and 70 (15%) patients with DCM, respectively. LTA (defined as sudden cardiac death, justified shock from implantable cardioverter-defibrillator or anti-tachypacing, or hemodynamic unstable ventricular fibrillation/tachycardia) occurred in 49 patients (3 with no IAB, 35 with IAB, and 11 patients with AF, respectively; median follow-up, 4.4 years [2.1; 7.4]). The LTA-free survival distribution significantly differed between IAB or AF versus no IAB (both P<0.01), but not between IAB versus AF (P=0.999). This association remained statistically significant in the multivariable model (IAB: HR, 4.8 (1.4-16.1), P=0.013; AF: HR, 6.4 (1.7-24.0), P=0.007). In the external validation cohort, the survival distribution was also significantly worse for IAB or AF versus no IAB (P=0.037; P=0.005), but not for IAB versus AF (P=0.836). Conclusions IAB is an easy to assess, widely applicable marker associated with LTA in DCM. IAB and AF seem to confer similar risk of LTA. Further research on IAB in DCM, and on the management of IAB in DCM is warranted.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.025473; doi:https://doi.org/10.1161/JAHA.121.025473; html:https://europepmc.org/articles/PMC9707810; pdf:https://europepmc.org/articles/PMC9707810?pdf=render +38296965,https://doi.org/10.1038/s41467-023-43644-x,"Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.","RECOVERY Collaborative Group, Horby PW, Peto L, Staplin N, Campbell M, Pessoa-Amorim G, Mafham M, Emberson JR, Stewart R, Prudon B, Uriel A, Green CA, Dhasmana DJ, Malein F, Majumdar J, Collini P, Shurmer J, Yates B, Baillie JK, Buch MH, Day J, Faust SN, Jaki T, Jeffery K, Juszczak E, Knight M, Lim WS, Montgomery A, Mumford A, Rowan K, Thwaites G, Haynes R, Landray MJ.",,Nature communications,2024,2024-01-31,Y,,,,"Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome.",,pdf:https://www.nature.com/articles/s41467-023-43644-x.pdf; doi:https://doi.org/10.1038/s41467-023-43644-x; html:https://europepmc.org/articles/PMC10831058; pdf:https://europepmc.org/articles/PMC10831058?pdf=render 33184391,https://doi.org/10.1038/s41598-020-76816-6,Prediction of vascular aging based on smartphone acquired PPG signals.,"Dall'Olio L, Curti N, Remondini D, Safi Harb Y, Asselbergs FW, Castellani G, Uh HW.",,Scientific reports,2020,2020-11-12,Y,,,,"Photoplethysmography (PPG) measured by smartphone has the potential for a large scale, non-invasive, and easy-to-use screening tool. Vascular aging is linked to increased arterial stiffness, which can be measured by PPG. We investigate the feasibility of using PPG to predict healthy vascular aging (HVA) based on two approaches: machine learning (ML) and deep learning (DL). We performed data preprocessing, including detrending, demodulating, and denoising on the raw PPG signals. For ML, ridge penalized regression has been applied to 38 features extracted from PPG, whereas for DL several convolutional neural networks (CNNs) have been applied to the whole PPG signals as input. The analysis has been conducted using the crowd-sourced Heart for Heart data. The prediction performance of ML using two features (AUC of 94.7%) - the a wave of the second derivative PPG and tpr, including four covariates, sex, height, weight, and smoking - was similar to that of the best performing CNN, 12-layer ResNet (AUC of 95.3%). Without having the heavy computational cost of DL, ML might be advantageous in finding potential biomarkers for HVA prediction. The whole workflow of the procedure is clearly described, and open software has been made available to facilitate replication of the results.",,pdf:https://www.nature.com/articles/s41598-020-76816-6.pdf; doi:https://doi.org/10.1038/s41598-020-76816-6; html:https://europepmc.org/articles/PMC7661535; pdf:https://europepmc.org/articles/PMC7661535?pdf=render 33724919,https://doi.org/10.2196/26627,Artificial Intelligence-Enabled Analysis of Public Attitudes on Facebook and Twitter Toward COVID-19 Vaccines in the United Kingdom and the United States: Observational Study.,"Hussain A, Tahir A, Hussain Z, Sheikh Z, Gogate M, Dashtipour K, Ali A, Sheikh A.",,Journal of medical Internet research,2021,2021-04-05,Y,Artificial intelligence; Vaccination; Public Health; Health Informatics; Natural Language Processing; Facebook; Social Media; Twitter; Sentiment Analysis; Infodemiology; Deep Learning; Covid-19,,,"

Background

Global efforts toward the development and deployment of a vaccine for COVID-19 are rapidly advancing. To achieve herd immunity, widespread administration of vaccines is required, which necessitates significant cooperation from the general public. As such, it is crucial that governments and public health agencies understand public sentiments toward vaccines, which can help guide educational campaigns and other targeted policy interventions.

Objective

The aim of this study was to develop and apply an artificial intelligence-based approach to analyze public sentiments on social media in the United Kingdom and the United States toward COVID-19 vaccines to better understand the public attitude and concerns regarding COVID-19 vaccines.

Methods

Over 300,000 social media posts related to COVID-19 vaccines were extracted, including 23,571 Facebook posts from the United Kingdom and 144,864 from the United States, along with 40,268 tweets from the United Kingdom and 98,385 from the United States from March 1 to November 22, 2020. We used natural language processing and deep learning-based techniques to predict average sentiments, sentiment trends, and topics of discussion. These factors were analyzed longitudinally and geospatially, and manual reading of randomly selected posts on points of interest helped identify underlying themes and validated insights from the analysis.

Results

Overall averaged positive, negative, and neutral sentiments were at 58%, 22%, and 17% in the United Kingdom, compared to 56%, 24%, and 18% in the United States, respectively. Public optimism over vaccine development, effectiveness, and trials as well as concerns over their safety, economic viability, and corporation control were identified. We compared our findings to those of nationwide surveys in both countries and found them to correlate broadly.

Conclusions

Artificial intelligence-enabled social media analysis should be considered for adoption by institutions and governments alongside surveys and other conventional methods of assessing public attitude. Such analyses could enable real-time assessment, at scale, of public confidence and trust in COVID-19 vaccines, help address the concerns of vaccine sceptics, and help develop more effective policies and communication strategies to maximize uptake.",,pdf:https://www.jmir.org/2021/4/e26627/PDF; doi:https://doi.org/10.2196/26627; html:https://europepmc.org/articles/PMC8023383 37391266,https://doi.org/10.1016/s2589-7500(23)00087-0,Wearable technology and the cardiovascular system: the future of patient assessment.,"Williams GJ, Al-Baraikan A, Rademakers FE, Ciravegna F, van de Vosse FN, Lawrie A, Rothman A, Ashley EA, Wilkins MR, Lawford PV, Omholt SW, Wisløff U, Hose DR, Chico TJA, Gunn JP, Morris PD.",,The Lancet. Digital health,2023,2023-07-01,N,,,,"The past decade has seen a dramatic rise in consumer technologies able to monitor a variety of cardiovascular parameters. Such devices initially recorded markers of exercise, but now include physiological and health-care focused measurements. The public are keen to adopt these devices in the belief that they are useful to identify and monitor cardiovascular disease. Clinicians are therefore often presented with health app data accompanied by a diverse range of concerns and queries. Herein, we assess whether these devices are accurate, their outputs validated, and whether they are suitable for professionals to make management decisions. We review underpinning methods and technologies and explore the evidence supporting the use of these devices as diagnostic and monitoring tools in hypertension, arrhythmia, heart failure, coronary artery disease, pulmonary hypertension, and valvular heart disease. Used correctly, they might improve health care and support research.",,pdf:http://www.thelancet.com/article/S2589750023000870/pdf; doi:https://doi.org/10.1016/S2589-7500(23)00087-0 @@ -1876,24 +1876,24 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 32685697,https://doi.org/10.12688/wellcomeopenres.15788.1,The contribution of pre-symptomatic infection to the transmission dynamics of COVID-2019.,"Liu Y, Centre for Mathematical Modelling of Infectious Diseases nCoV Working Group, Funk S, Flasche S.",,Wellcome open research,2020,2020-04-01,Y,Incubation period; Serial Interval; Covid-19; Pre-symptomatic Transmission,,,"Background: Pre-symptomatic transmission can be a key determinant of the effectiveness of containment and mitigation strategies for infectious diseases, particularly if interventions rely on syndromic case finding. For COVID-19, infections in the absence of apparent symptoms have been reported frequently alongside circumstantial evidence for asymptomatic or pre-symptomatic transmission. We estimated the potential contribution of pre-symptomatic cases to COVID-19 transmission. Methods: Using the probability for symptom onset on a given day inferred from the incubation period, we attributed the serial interval reported from Shenzen, China, into likely pre-symptomatic and symptomatic transmission. We used the serial interval derived for cases isolated more than 6 days after symptom onset as the no active case finding scenario and the unrestricted serial interval as the active case finding scenario. We reported the estimate assuming no correlation between the incubation period and the serial interval alongside a range indicating alternative assumptions of positive and negative correlation. Results: We estimated that 23% (range accounting for correlation: 12 - 28%) of transmissions in Shenzen may have originated from pre-symptomatic infections. Through accelerated case isolation following symptom onset, this percentage increased to 46% (21 - 46%), implying that about 35% of secondary infections among symptomatic cases have been prevented. These results were robust to using reported incubation periods and serial intervals from other settings. Conclusions: Pre-symptomatic transmission may be essential to consider for containment and mitigation strategies for COVID-19.",,pdf:https://wellcomeopenresearch.org/articles/5-58/v1/pdf; doi:https://doi.org/10.12688/wellcomeopenres.15788.1; html:https://europepmc.org/articles/PMC7324944; pdf:https://europepmc.org/articles/PMC7324944?pdf=render 32255392,https://doi.org/10.1080/09273948.2019.1709650,Non-invasive Instrument-Based Tests for Quantifying Anterior Chamber Flare in Uveitis: A Systematic Review.,"Liu X, McNally TW, Beese S, Downie LE, Solebo AL, Faes L, Husain S, Keane PA, Moore DJ, Denniston AK.",,Ocular immunology and inflammation,2021,2020-04-07,N,"Diagnostic test; Systematic review; Uveitis; optical coherence tomography; Laser Flare Photometry; Anterior Chamber Flare; Tyndall Effect; Aqueous Humor, Aqueous Humour; Aqueous Protein Concentration",,,"Purpose: Anterior chamber (AC) flare is a key sign for anterior uveitis. New instrument-based techniques for measuring AC flare can offer automation and objectivity. This review aims to identify objective instrument-based measures for AC flare.Methods: In this systematic review, we identified studies reporting correlation between instrument-based tests versus clinician AC flare grading, and/or aqueous protein concentration, as well as test reliability.Results: Four index tests were identified in 11 studies: laser-flare photometry (LFP), optical coherence tomography, ocular flare analysis meter (OFAM) and the double-pass technique. The correlation between LFP and clinician grading was 0.40-0.93 and 0.87-0.94 for LFP and protein concentration. The double-pass technique showed no correlation with clinician grading and insufficient information was available for OFAM.Conclusion: LFP shows moderate to strong correlation with clinician grading and aqueous protein concentration. LFP could be a superior reference test compared to clinician AC flare grading for validating new index tests.",,pdf:https://discovery.ucl.ac.uk/10097154/3/Solebo_Liu%20AC%20Flare%20SR%20290919.pdf; doi:https://doi.org/10.1080/09273948.2019.1709650 33782080,https://doi.org/10.1136/thoraxjnl-2020-216512,Impact of COVID-19 national lockdown on asthma exacerbations: interrupted time-series analysis of English primary care data.,"Shah SA, Quint JK, Nwaru BI, Sheikh A.",,Thorax,2021,2021-03-29,Y,Asthma; Asthma Epidemiology; Covid-19,,,"

Background

The impact of COVID-19 and ensuing national lockdown on asthma exacerbations is unclear.

Methods

We conducted an interrupted time-series (lockdown on 23 March 2020 as point of interruption) analysis in asthma cohort identified using a validated algorithm from a national-level primary care database, the Optimum Patient Care Database. We derived asthma exacerbation rates for every week and compared exacerbation rates in the period: January to August 2020 with a pre-COVID-19 period and January to August 2016-2019. Exacerbations were defined as asthma-related hospital attendance/admission (including accident and emergency visit), or an acute course of oral corticosteroids with evidence of respiratory review, as recorded in primary care. We used a generalised least squares modelling approach and stratified the analyses by age, sex, English region and healthcare setting.

Results

From a database of 9 949 387 patients, there were 100 165 patients with asthma who experienced at least one exacerbation during 2016-2020. Of 278 996 exacerbation episodes, 49 938 (17.9%) required hospital visit. Comparing pre-lockdown to post-lockdown period, we observed a statistically significant reduction in the level (-0.196 episodes per person-year; p<0.001; almost 20 episodes for every 100 patients with asthma per year) of exacerbation rates across all patients. The reductions in level in stratified analyses were: 0.005-0.244 (healthcare setting, only those without hospital attendance/admission were significant), 0.210-0.277 (sex), 0.159-0.367 (age), 0.068-0.590 (region).

Conclusions

There has been a significant reduction in attendance to primary care for asthma exacerbations during the pandemic. This reduction was observed in all age groups, both sexes and across most regions in England.",,pdf:https://thorax.bmj.com/content/thoraxjnl/76/9/860.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2020-216512; html:https://europepmc.org/articles/PMC8011425; pdf:https://europepmc.org/articles/PMC8011425?pdf=render -36357634,https://doi.org/10.1007/s00467-022-05789-7,Shared genetic risk across different presentations of gene test-negative idiopathic nephrotic syndrome.,"Downie ML, Gupta S, Chan MMY, Sadeghi-Alavijeh O, Cao J, Parekh RS, Diz CB, Bierzynska A, Levine AP, Pepper RJ, Stanescu H, Saleem MA, Kleta R, Bockenhauer D, Koziell AB, Gale DP.",,"Pediatric nephrology (Berlin, Germany)",2023,2022-11-10,Y,Paediatrics; Minimal Change Disease; Focal Segmental Glomerulosclerosis; Monogenic; Genetic Risk Score; Steroid-resistant Nephrotic Syndrome; Steroid-sensitive Nephrotic Syndrome,,,"

Background

Idiop athic nephrotic syndrome (INS) is classified in children according to response to initial corticosteroid therapy into steroid-sensitive (SSNS) and steroid-resistant nephrotic syndrome (SRNS), and in adults according to histology into minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). However, there is well-recognised phenotypic overlap between these entities. Genome-wide association studies (GWAS) have shown a strong association between SSNS and variation at HLA, suggesting an underlying immunological basis. We sought to determine whether a risk score generated from genetic variants associated with SSNS could be used to gain insight into the pathophysiology of INS presenting in other ways.

Methods

We developed an SSNS genetic risk score (SSNS-GRS) from the five variants independently associated with childhood SSNS in a previous European GWAS. We quantified SSNS-GRS in independent cohorts of European individuals with childhood SSNS, non-monogenic SRNS, MCD, and FSGS, and contrasted them with SSNS-GRS quantified in individuals with monogenic SRNS, membranous nephropathy (a different immune-mediated disease-causing nephrotic syndrome), and healthy controls.

Results

The SSNS-GRS was significantly elevated in cohorts with SSNS, non-monogenic SRNS, MCD, and FSGS compared to healthy participants and those with membranous nephropathy. The SSNS-GRS in all cohorts with non-monogenic INS were also significantly elevated compared to those with monogenic SRNS.

Conclusions

The shared genetic risk factors among patients with different presentations of INS strongly suggests a shared autoimmune pathogenesis when monogenic causes are excluded. Use of the SSNS-GRS, in addition to testing for monogenic causes, may help to classify patients presenting with INS. A higher resolution version of the Graphical abstract is available as Supplementary information.",,pdf:https://link.springer.com/content/pdf/10.1007/s00467-022-05789-7.pdf; doi:https://doi.org/10.1007/s00467-022-05789-7; html:https://europepmc.org/articles/PMC10154254; pdf:https://europepmc.org/articles/PMC10154254?pdf=render 31145509,https://doi.org/10.1002/gepi.22215,A comparison of two workflows for regulome and transcriptome-based prioritization of genetic variants associated with myocardial mass.,"Manduchi E, Hemerich D, van Setten J, Tragante V, Harakalova M, Pei J, Williams SM, van der Harst P, Asselbergs FW, Moore JH.",,Genetic epidemiology,2019,2019-05-30,N,Functional genomics; Gwas; left ventricular mass; Snp Preselection,,,"A typical task arising from main effect analyses in a Genome Wide Association Study (GWAS) is to identify single nucleotide polymorphisms (SNPs), in linkage disequilibrium with the observed signals, that are likely causal variants and the affected genes. The affected genes may not be those closest to associating SNPs. Functional genomics data from relevant tissues are believed to be helpful in selecting likely causal SNPs and interpreting implicated biological mechanisms, ultimately facilitating prevention and treatment in the case of a disease trait. These data are typically used post GWAS analyses to fine-map the statistically significant signals identified agnostically by testing all SNPs and applying a multiple testing correction. The number of tested SNPs is typically in the millions, so the multiple testing burden is high. Motivated by this, in this study we investigated an alternative workflow, which consists in utilizing the available functional genomics data as a first step to reduce the number of SNPs tested for association. We analyzed GWAS on electrocardiographic QRS duration using these two workflows. The alternative workflow identified more SNPs, including some residing in loci not discovered with the typical workflow. Moreover, the latter are corroborated by other reports on QRS duration. This indicates the potential value of incorporating functional genomics information at the onset in GWAS analyses.",,pdf:https://pure.rug.nl/ws/files/89611268/Manduchi_et_al_2019_Genetic_Epidemiology.pdf; doi:https://doi.org/10.1002/gepi.22215; html:https://europepmc.org/articles/PMC6687530; pdf:https://europepmc.org/articles/PMC6687530?pdf=render; doi:https://doi.org/10.1002/gepi.22215 +36357634,https://doi.org/10.1007/s00467-022-05789-7,Shared genetic risk across different presentations of gene test-negative idiopathic nephrotic syndrome.,"Downie ML, Gupta S, Chan MMY, Sadeghi-Alavijeh O, Cao J, Parekh RS, Diz CB, Bierzynska A, Levine AP, Pepper RJ, Stanescu H, Saleem MA, Kleta R, Bockenhauer D, Koziell AB, Gale DP.",,"Pediatric nephrology (Berlin, Germany)",2023,2022-11-10,Y,Paediatrics; Minimal Change Disease; Focal Segmental Glomerulosclerosis; Monogenic; Genetic Risk Score; Steroid-resistant Nephrotic Syndrome; Steroid-sensitive Nephrotic Syndrome,,,"

Background

Idiop athic nephrotic syndrome (INS) is classified in children according to response to initial corticosteroid therapy into steroid-sensitive (SSNS) and steroid-resistant nephrotic syndrome (SRNS), and in adults according to histology into minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). However, there is well-recognised phenotypic overlap between these entities. Genome-wide association studies (GWAS) have shown a strong association between SSNS and variation at HLA, suggesting an underlying immunological basis. We sought to determine whether a risk score generated from genetic variants associated with SSNS could be used to gain insight into the pathophysiology of INS presenting in other ways.

Methods

We developed an SSNS genetic risk score (SSNS-GRS) from the five variants independently associated with childhood SSNS in a previous European GWAS. We quantified SSNS-GRS in independent cohorts of European individuals with childhood SSNS, non-monogenic SRNS, MCD, and FSGS, and contrasted them with SSNS-GRS quantified in individuals with monogenic SRNS, membranous nephropathy (a different immune-mediated disease-causing nephrotic syndrome), and healthy controls.

Results

The SSNS-GRS was significantly elevated in cohorts with SSNS, non-monogenic SRNS, MCD, and FSGS compared to healthy participants and those with membranous nephropathy. The SSNS-GRS in all cohorts with non-monogenic INS were also significantly elevated compared to those with monogenic SRNS.

Conclusions

The shared genetic risk factors among patients with different presentations of INS strongly suggests a shared autoimmune pathogenesis when monogenic causes are excluded. Use of the SSNS-GRS, in addition to testing for monogenic causes, may help to classify patients presenting with INS. A higher resolution version of the Graphical abstract is available as Supplementary information.",,pdf:https://link.springer.com/content/pdf/10.1007/s00467-022-05789-7.pdf; doi:https://doi.org/10.1007/s00467-022-05789-7; html:https://europepmc.org/articles/PMC10154254; pdf:https://europepmc.org/articles/PMC10154254?pdf=render 36210800,https://doi.org/10.1038/s43856-022-00189-2,Feasibility and ethics of using data from the Scottish newborn blood spot archive for research.,"Cunningham-Burley S, McCartney DL, Campbell A, Flaig R, Orange CEL, Porteous C, Aitken M, Mulholland C, Davidson S, McCafferty SM, Murphy L, Wrobel N, McCafferty S, Wallace K, StClair D, Kerr S, Hayward C, McIntosh AM, Sudlow C, Marioni RE, Pell J, Miedzybrodzka Z, Porteous DJ.",,Communications medicine,2022,2022-10-06,Y,epigenomics; epidemiology,,,"

Background

Newborn heel prick blood spots are routinely used to screen for inborn errors of metabolism and life-limiting inherited disorders. The potential value of secondary data from newborn blood spot archives merits ethical consideration and assessment of feasibility for public benefit. Early life exposures and behaviours set health trajectories in childhood and later life. The newborn blood spot is potentially well placed to create an unbiased and cost-effective population-level retrospective birth cohort study. Scotland has retained newborn blood spots for all children born since 1965, around 3 million in total. However, a moratorium on research access is currently in place, pending public consultation.

Methods

We conducted a Citizens' Jury as a first step to explore whether research use of newborn blood spots was in the public interest. We also assessed the feasibility and value of extracting research data from dried blood spots for predictive medicine.

Results

Jurors delivered an agreed verdict that conditional research access to the newborn blood spots was in the public interest. The Chief Medical Officer for Scotland authorised restricted lifting of the current research moratorium to allow a feasibility study. Newborn blood spots from consented Generation Scotland volunteers were retrieved and their potential for both epidemiological and biological research demonstrated.

Conclusions

Through the Citizens' Jury, we have begun to identify under what conditions, if any, should researchers in Scotland be granted access to the archive. Through the feasibility study, we have demonstrated the potential value of research access for health data science and predictive medicine.",,pdf:https://www.nature.com/articles/s43856-022-00189-2.pdf; doi:https://doi.org/10.1038/s43856-022-00189-2; html:https://europepmc.org/articles/PMC9537278; pdf:https://europepmc.org/articles/PMC9537278?pdf=render 33560344,https://doi.org/10.1210/clinem/dgab067,Association of Metformin with Susceptibility to COVID-19 in People with Type 2 Diabetes.,"Wang J, Cooper JM, Gokhale K, Acosta-Mena D, Dhalla S, Byne N, Chandan JS, Anand A, Okoth K, Subramanian A, Bangash MN, Jackson T, Zemedikun D, Taverner T, Hanif W, Ghosh S, Narendran P, Toulis KA, Tahrani AA, Surenthirakumaran R, Adderley NJ, Haroon S, Khunti K, Sainsbury C, Thomas GN, Nirantharakumar K.",,The Journal of clinical endocrinology and metabolism,2021,2021-04-01,Y,Type 2 diabetes mellitus; Metformin; Covid-19; Sars-cov-2 Infection,,,"

Objective

Diabetes has emerged as an important risk factor for mortality from COVID-19. Metformin, the most commonly prescribed glucose-lowering agent, has been proposed to influence susceptibility to and outcomes of COVID-19 via multiple mechanisms. We investigated whether, in patients with diabetes, metformin is associated with susceptibility to COVID-19 and its outcomes.

Research design and methods

We performed a propensity score-matched cohort study with active comparators using a large UK primary care dataset. Adults with type 2 diabetes patients and a current prescription for metformin and other glucose-lowering agents (MF+) were compared to those with a current prescription for glucose-lowering agents that did not include metformin (MF-). Outcomes were confirmed COVID-19, suspected/confirmed COVID-19, and associated mortality. A negative control outcome analysis (back pain) was also performed.

Results

There were 29 558 and 10 271 patients in the MF+ and MF- groups, respectively, who met the inclusion criteria. In the propensity score-matched analysis, the adjusted hazard ratios for suspected/confirmed COVID-19, confirmed COVID-19, and COVID-19-related mortality were 0.85 (95% CI 0.67, 1.08), 0.80 (95% CI 0.49, 1.30), and 0.87 (95% CI 0.34, 2.20) respectively. The negative outcome control analysis did not suggest unobserved confounding.

Conclusion

Current prescription of metformin was not associated with the risk of COVID-19 or COVID-19-related mortality. It is safe to continue prescribing metformin to improve glycemic control in patients with.",,pdf:https://academic.oup.com/jcem/article-pdf/106/5/1255/41848481/dgab067.pdf; doi:https://doi.org/10.1210/clinem/dgab067; html:https://europepmc.org/articles/PMC7928949 +31055854,https://doi.org/10.5694/mja2.50143,"Traumatic spinal cord injury in Victoria, 2007-2016.","Beck B, Cameron PA, Braaf S, Nunn A, Fitzgerald MC, Judson RT, Teague WJ, Lennox A, Middleton JW, Harrison JE, Gabbe BJ.",,The Medical journal of Australia,2019,2019-05-01,N,"Spinal cord injuries; epidemiology; Traumatology; Trauma, Nervous System",,,"

Objective

To investigate trends in the incidence and causes of traumatic spinal cord injury (TSCI) in Victoria over a 10-year period.

Design, setting, participants

Retrospective cohort study: analysis of Victorian State Trauma Registry (VSTR) data for people who sustained TSCIs during 2007-2016.

Main outcomes and measures

Temporal trends in population-based incidence rates of TSCI (injury to the spinal cord with an Abbreviated Injury Scale [AIS] score of 4 or more).

Results

There were 706 cases of TSCI, most the result of transport events (269 cases, 38%) or low falls (197 cases, 28%). The overall crude incidence of TSCI was 1.26 cases per 100 000 population (95% CI, 1.17-1.36 per 100 000 population), and did not change over the study period (incidence rate ratio [IRR], 1.01; 95% CI, 0.99-1.04). However, the incidence of TSCI resulting from low falls increased by 9% per year (95% CI, 4-15%). The proportion of TSCI cases classified as incomplete tetraplegia increased from 41% in 2007 to 55% in 2016 (P < 0.001). Overall in-hospital mortality was 15% (104 deaths), and was highest among people aged 65 years or more (31%, 70 deaths).

Conclusions

Given the devastating consequences of TSCI, improved primary prevention strategies are needed, particularly as the incidence of TSCI did not decline over the study period. The epidemiologic profile of TSCI has shifted, with an increasing number of TSCI events in older adults. This change has implications for prevention, acute and post-discharge care, and support.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.5694/mja2.50143; doi:https://doi.org/10.5694/mja2.50143 35238940,https://doi.org/10.1093/ndt/gfac040,"Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial.",EMPA-KIDNEY Collaborative Group.,,"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",2022,2022-06-01,Y,"Cardiovascular disease; Empagliflozin; Sodium-glucose Co-transporter 2 Inhibitor; Ckd, Clinical Trial",,,"

Background

The effects of the sodium-glucose co-transporter 2 inhibitor empagliflozin on renal and cardiovascular disease have not been tested in a dedicated population of people with chronic kidney disease (CKD).

Methods

The EMPA-KIDNEY trial is an international randomized, double-blind, placebo-controlled trial assessing whether empagliflozin 10 mg daily decreases the risk of kidney disease progression or cardiovascular death in people with CKD. People with or without diabetes mellitus (DM) were eligible provided they had an estimated glomerular filtration rate (eGFR) ≥20 but <45 mL/min/1.73 m2 or an eGFR ≥45 but <90 mL/min/1.73 m2 with a urinary albumin:creatinine ratio (uACR) ≥200 mg/g. The trial design is streamlined, as extra work for collaborating sites is kept to a minimum and only essential information is collected.

Results

Between 15 May 2019 and 16 April 2021, 6609 people from eight countries in Europe, North America and East Asia were randomized. The mean age at randomization was 63.8 years [standard deviation (SD) 13.9)], 2192 (33%) were female and 3570 (54%) had no prior history of DM. The mean eGFR was 37.5 mL/min/1.73 m2 (SD 14.8), including 5185 (78%) with an eGFR <45 mL/min/1.73 m2. The median uACR was 412 mg/g) (quartile 1-quartile 3 94-1190), with a uACR <300 mg/g in 3194 (48%). The causes of kidney disease included diabetic kidney disease [n = 2057 (31%)], glomerular disease [n = 1669 (25%)], hypertensive/renovascular disease [n = 1445 (22%)], other [n = 808 (12%)] and unknown causes [n = 630 (10%)].

Conclusions

EMPA-KIDNEY will evaluate the efficacy and safety of empagliflozin in a widely generalizable population of people with CKD at risk of kidney disease progression. Results are anticipated in 2022.",,pdf:https://academic.oup.com/ndt/article-pdf/37/7/1317/44138360/gfac040.pdf; doi:https://doi.org/10.1093/ndt/gfac040; html:https://europepmc.org/articles/PMC9217655; pdf:https://europepmc.org/articles/PMC9217655?pdf=render 37338017,https://doi.org/10.1111/jvh.13863,Contribution of alcohol use in HIV/hepatitis C virus co-infection to all-cause and cause-specific mortality: A collaboration of cohort studies.,"Trickey A, Ingle SM, Boyd A, Gill MJ, Grabar S, Jarrin I, Obel N, Touloumi G, Zangerle R, Rauch A, Rentsch CT, Satre DD, Silverberg MJ, Bonnet F, Guest J, Burkholder G, Crane H, Teira R, Berenguer J, Wyen C, Abgrall S, Hessamfar M, Reiss P, d'Arminio Monforte A, McGinnis KA, Sterne JAC, Wittkop L, Antiretroviral Therapy Cohort Collaboration.",,Journal of viral hepatitis,2023,2023-06-20,Y,Mortality; Alcohol; Hepatitis C virus; HIV; Cohort; Cause-specific,,,"Among persons with HIV (PWH), higher alcohol use and having hepatitis C virus (HCV) are separately associated with increased morbidity and mortality. We investigated whether the association between alcohol use and mortality among PWH is modified by HCV. Data were combined from European and North American cohorts of adult PWH who started antiretroviral therapy (ART). Self-reported alcohol use data, collected in diverse ways between cohorts, were converted to grams/day. Eligible PWH started ART during 2001-2017 and were followed from ART initiation for mortality. Interactions between the associations of baseline alcohol use (0, 0.1-20.0, >20.0 g/day) and HCV status were assessed using multivariable Cox models. Of 58,769 PWH, 29,711 (51%), 23,974 (41%) and 5084 (9%) self-reported alcohol use of 0 g/day, 0.1-20.0 g/day, and > 20.0 g/day, respectively, and 4799 (8%) had HCV at baseline. There were 844 deaths in 37,729 person-years and 2755 deaths in 443,121 person-years among those with and without HCV, respectively. Among PWH without HCV, adjusted hazard ratios (aHRs) for mortality were 1.18 (95% CI: 1.08-1.29) for 0.0 g/day and 1.84 (1.62-2.09) for >20.0 g/day compared with 0.1-20.0 g/day. This J-shaped pattern was absent among those with HCV: aHRs were 1.00 (0.86-1.17) for 0.0 g/day and 1.64 (1.33-2.02) for >20.0 g/day compared with 0.1-20.0 g/day (interaction p < .001). Among PWH without HCV, mortality was higher in both non-drinkers and heavy drinkers compared with moderate alcohol drinkers. Among those with HCV, mortality was higher in heavy drinkers but not non-drinkers, potentially due to differing reasons for not drinking (e.g. illness) between those with and without HCV.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jvh.13863; doi:https://doi.org/10.1111/jvh.13863; html:https://europepmc.org/articles/PMC10526649; pdf:https://europepmc.org/articles/PMC10526649?pdf=render -31055854,https://doi.org/10.5694/mja2.50143,"Traumatic spinal cord injury in Victoria, 2007-2016.","Beck B, Cameron PA, Braaf S, Nunn A, Fitzgerald MC, Judson RT, Teague WJ, Lennox A, Middleton JW, Harrison JE, Gabbe BJ.",,The Medical journal of Australia,2019,2019-05-01,N,"Spinal cord injuries; epidemiology; Traumatology; Trauma, Nervous System",,,"

Objective

To investigate trends in the incidence and causes of traumatic spinal cord injury (TSCI) in Victoria over a 10-year period.

Design, setting, participants

Retrospective cohort study: analysis of Victorian State Trauma Registry (VSTR) data for people who sustained TSCIs during 2007-2016.

Main outcomes and measures

Temporal trends in population-based incidence rates of TSCI (injury to the spinal cord with an Abbreviated Injury Scale [AIS] score of 4 or more).

Results

There were 706 cases of TSCI, most the result of transport events (269 cases, 38%) or low falls (197 cases, 28%). The overall crude incidence of TSCI was 1.26 cases per 100 000 population (95% CI, 1.17-1.36 per 100 000 population), and did not change over the study period (incidence rate ratio [IRR], 1.01; 95% CI, 0.99-1.04). However, the incidence of TSCI resulting from low falls increased by 9% per year (95% CI, 4-15%). The proportion of TSCI cases classified as incomplete tetraplegia increased from 41% in 2007 to 55% in 2016 (P < 0.001). Overall in-hospital mortality was 15% (104 deaths), and was highest among people aged 65 years or more (31%, 70 deaths).

Conclusions

Given the devastating consequences of TSCI, improved primary prevention strategies are needed, particularly as the incidence of TSCI did not decline over the study period. The epidemiologic profile of TSCI has shifted, with an increasing number of TSCI events in older adults. This change has implications for prevention, acute and post-discharge care, and support.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.5694/mja2.50143; doi:https://doi.org/10.5694/mja2.50143 36256701,https://doi.org/10.1093/eurjcn/zvac098,Bed rest duration and complications after transfemoral cardiac catheterization: a network meta-analysis.,"Busca E, Airoldi C, Bertoncini F, Buratti G, Casarotto R, Gaboardi S, Faggiano F, Barisone M, White IR, Allara E, Dal Molin A.",,European journal of cardiovascular nursing,2023,2023-07-01,Y,Cardiac catheterization; Percutaneous coronary intervention; Systematic review; Network Meta-analysis; Femoral Access,,,"

Aims

To assess the effects of bed rest duration on short-term complications following transfemoral catheterization.

Methods and results

A systematic search was carried out in MEDLINE, Embase, CINAHL, Cochrane Database of Systematic Reviews, Scopus, SciELO and in five registries of grey literature. Randomized controlled trials and quasi-experimental studies comparing different durations of bed rest after transfemoral catheterization were included. Primary outcomes were haematoma and bleeding near the access site. Secondary outcomes were arteriovenous fistula, pseudoaneurysm, back pain, general patient discomfort and urinary discomfort. Study findings were summarized using a network meta-analysis (NMA). Twenty-eight studies and 9217 participants were included (mean age 60.4 years). In NMA, bed rest duration was not consistently associated with either primary outcome, and this was confirmed in sensitivity analyses. There was no evidence of associations with secondary outcomes, except for two effects related to back pain. A bed rest duration of 2-2.9 h was associated with lower risk of back pain [risk ratio (RR) 0.33, 95% confidence interval (CI) 0.17-0.62] and a duration over 12 h with greater risk of back pain (RR 1.94, 95% CI 1.16-3.24), when compared with the 4-5.9 h interval. Post hoc analysis revealed an increased risk of back pain per hour of bed rest (RR 1.08, 95% CI 1.04-1.11).

Conclusion

A short bed rest was not associated with complications in patients undergoing transfemoral catheterization; the greater the duration of bed rest, the more likely the patients were to experience back pain. Ambulation as early as 2 h after transfemoral catheterization can be safely implemented.

Registration

PROSPERO: CRD42014014222.",,pdf:https://academic.oup.com/eurjcn/advance-article-pdf/doi/10.1093/eurjcn/zvac098/47022353/zvac098.pdf; doi:https://doi.org/10.1093/eurjcn/zvac098; html:https://europepmc.org/articles/PMC10353909; pdf:https://europepmc.org/articles/PMC10353909?pdf=render 33323251,https://doi.org/10.1016/s2589-7500(19)30123-2,A comparison of deep learning performance against health-care professionals in detecting diseases from medical imaging: a systematic review and meta-analysis.,"Liu X, Faes L, Kale AU, Wagner SK, Fu DJ, Bruynseels A, Mahendiran T, Moraes G, Shamdas M, Kern C, Ledsam JR, Schmid MK, Balaskas K, Topol EJ, Bachmann LM, Keane PA, Denniston AK.",,The Lancet. Digital health,2019,2019-09-25,N,,,,"

Background

Deep learning offers considerable promise for medical diagnostics. We aimed to evaluate the diagnostic accuracy of deep learning algorithms versus health-care professionals in classifying diseases using medical imaging.

Methods

In this systematic review and meta-analysis, we searched Ovid-MEDLINE, Embase, Science Citation Index, and Conference Proceedings Citation Index for studies published from Jan 1, 2012, to June 6, 2019. Studies comparing the diagnostic performance of deep learning models and health-care professionals based on medical imaging, for any disease, were included. We excluded studies that used medical waveform data graphics material or investigated the accuracy of image segmentation rather than disease classification. We extracted binary diagnostic accuracy data and constructed contingency tables to derive the outcomes of interest: sensitivity and specificity. Studies undertaking an out-of-sample external validation were included in a meta-analysis, using a unified hierarchical model. This study is registered with PROSPERO, CRD42018091176.

Findings

Our search identified 31 587 studies, of which 82 (describing 147 patient cohorts) were included. 69 studies provided enough data to construct contingency tables, enabling calculation of test accuracy, with sensitivity ranging from 9·7% to 100·0% (mean 79·1%, SD 0·2) and specificity ranging from 38·9% to 100·0% (mean 88·3%, SD 0·1). An out-of-sample external validation was done in 25 studies, of which 14 made the comparison between deep learning models and health-care professionals in the same sample. Comparison of the performance between health-care professionals in these 14 studies, when restricting the analysis to the contingency table for each study reporting the highest accuracy, found a pooled sensitivity of 87·0% (95% CI 83·0-90·2) for deep learning models and 86·4% (79·9-91·0) for health-care professionals, and a pooled specificity of 92·5% (95% CI 85·1-96·4) for deep learning models and 90·5% (80·6-95·7) for health-care professionals.

Interpretation

Our review found the diagnostic performance of deep learning models to be equivalent to that of health-care professionals. However, a major finding of the review is that few studies presented externally validated results or compared the performance of deep learning models and health-care professionals using the same sample. Additionally, poor reporting is prevalent in deep learning studies, which limits reliable interpretation of the reported diagnostic accuracy. New reporting standards that address specific challenges of deep learning could improve future studies, enabling greater confidence in the results of future evaluations of this promising technology.

Funding

None.",,pdf:http://www.thelancet.com/article/S2589750019301232/pdf; doi:https://doi.org/10.1016/S2589-7500(19)30123-2 36048760,https://doi.org/10.1371/journal.pgen.1010294,Neurocognitive trajectory and proteomic signature of inherited risk for Alzheimer's disease.,"Paranjpe MD, Chaffin M, Zahid S, Ritchie S, Rotter JI, Rich SS, Gerszten R, Guo X, Heckbert S, Tracy R, Danesh J, Lander ES, Inouye M, Kathiresan S, Butterworth AS, Khera AV.",,PLoS genetics,2022,2022-09-01,Y,,,,"For Alzheimer's disease-a leading cause of dementia and global morbidity-improved identification of presymptomatic high-risk individuals and identification of new circulating biomarkers are key public health needs. Here, we tested the hypothesis that a polygenic predictor of risk for Alzheimer's disease would identify a subset of the population with increased risk of clinically diagnosed dementia, subclinical neurocognitive dysfunction, and a differing circulating proteomic profile. Using summary association statistics from a recent genome-wide association study, we first developed a polygenic predictor of Alzheimer's disease comprised of 7.1 million common DNA variants. We noted a 7.3-fold (95% CI 4.8 to 11.0; p < 0.001) gradient in risk across deciles of the score among 288,289 middle-aged participants of the UK Biobank study. In cross-sectional analyses stratified by age, minimal differences in risk of Alzheimer's disease and performance on a digit recall test were present according to polygenic score decile at age 50 years, but significant gradients emerged by age 65. Similarly, among 30,541 participants of the Mass General Brigham Biobank, we again noted no significant differences in Alzheimer's disease diagnosis at younger ages across deciles of the score, but for those over 65 years we noted an odds ratio of 2.0 (95% CI 1.3 to 3.2; p = 0.002) in the top versus bottom decile of the polygenic score. To understand the proteomic signature of inherited risk, we performed aptamer-based profiling in 636 blood donors (mean age 43 years) with very high or low polygenic scores. In addition to the well-known apolipoprotein E biomarker, this analysis identified 27 additional proteins, several of which have known roles related to disease pathogenesis. Differences in protein concentrations were consistent even among the youngest subset of blood donors (mean age 33 years). Of these 28 proteins, 7 of the 8 proteins with concentrations available were similarly associated with the polygenic score in participants of the Multi-Ethnic Study of Atherosclerosis. These data highlight the potential for a DNA-based score to identify high-risk individuals during the prolonged presymptomatic phase of Alzheimer's disease and to enable biomarker discovery based on profiling of young individuals in the extremes of the score distribution.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010294&type=printable; doi:https://doi.org/10.1371/journal.pgen.1010294; html:https://europepmc.org/articles/PMC9436054; pdf:https://europepmc.org/articles/PMC9436054?pdf=render 35184736,https://doi.org/10.1186/s12916-022-02271-x,Comparative assessment of methods for short-term forecasts of COVID-19 hospital admissions in England at the local level.,"Meakin S, Abbott S, Bosse N, Munday J, Gruson H, Hellewell J, Sherratt K, CMMID COVID-19 Working Group, Funk S.",,BMC medicine,2022,2022-02-21,Y,Forecasting; Infectious disease; outbreak; Real-time; Ensemble; Healthcare Demand; Covid-19,,,"

Background

Forecasting healthcare demand is essential in epidemic settings, both to inform situational awareness and facilitate resource planning. Ideally, forecasts should be robust across time and locations. During the COVID-19 pandemic in England, it is an ongoing concern that demand for hospital care for COVID-19 patients in England will exceed available resources.

Methods

We made weekly forecasts of daily COVID-19 hospital admissions for National Health Service (NHS) Trusts in England between August 2020 and April 2021 using three disease-agnostic forecasting models: a mean ensemble of autoregressive time series models, a linear regression model with 7-day-lagged local cases as a predictor, and a scaled convolution of local cases and a delay distribution. We compared their point and probabilistic accuracy to a mean-ensemble of them all and to a simple baseline model of no change from the last day of admissions. We measured predictive performance using the weighted interval score (WIS) and considered how this changed in different scenarios (the length of the predictive horizon, the date on which the forecast was made, and by location), as well as how much admissions forecasts improved when future cases were known.

Results

All models outperformed the baseline in the majority of scenarios. Forecasting accuracy varied by forecast date and location, depending on the trajectory of the outbreak, and all individual models had instances where they were the top- or bottom-ranked model. Forecasts produced by the mean-ensemble were both the most accurate and most consistently accurate forecasts amongst all the models considered. Forecasting accuracy was improved when using future observed, rather than forecast, cases, especially at longer forecast horizons.

Conclusions

Assuming no change in current admissions is rarely better than including at least a trend. Using confirmed COVID-19 cases as a predictor can improve admissions forecasts in some scenarios, but this is variable and depends on the ability to make consistently good case forecasts. However, ensemble forecasts can make forecasts that make consistently more accurate forecasts across time and locations. Given minimal requirements on data and computation, our admissions forecasting ensemble could be used to anticipate healthcare needs in future epidemic or pandemic settings.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-022-02271-x; doi:https://doi.org/10.1186/s12916-022-02271-x; html:https://europepmc.org/articles/PMC8858706; pdf:https://europepmc.org/articles/PMC8858706?pdf=render 32623924,https://doi.org/10.1161/hypertensionaha.119.14302,Estimated 24-Hour Urinary Sodium Excretion and Incident Cardiovascular Disease and Mortality Among 398 628 Individuals in UK Biobank.,"Elliott P, Muller DC, Schneider-Luftman D, Pazoki R, Evangelou E, Dehghan A, Neal B, Tzoulaki I.",,"Hypertension (Dallas, Tex. : 1979)",2020,2020-07-06,N,Cardiovascular diseases; Mortality; Blood pressure; risk,,,"We report on an analysis to explore the association between estimated 24-hour urinary sodium excretion (surrogate for sodium intake) and incident cardiovascular disease (CVD) and mortality. Data were obtained from 398 628 UK Biobank prospective cohort study participants (40-69 years) recruited between 2006 and 2010, with no history of CVD, renal disease, diabetes mellitus or cancer, and cardiovascular events and mortality recorded during follow-up. Hazard ratios between 24-hour sodium excretion were estimated from spot urinary sodium concentrations across incident CVD and its components and all-cause and cause-specific mortality. In restricted cubic splines analyses, there was little evidence for an association between estimated 24-hour sodium excretion and CVD, coronary heart disease, or stroke; hazard ratios for CVD (95% CIs) for the 15th and 85th percentiles (2.5 and 4.2 g/day, respectively) compared with the 50th percentile of estimated sodium excretion (3.2 g/day) were 1.05 (1.01-1.10) and 0.96 (0.92-1.00), respectively. An inverse association was observed with heart failure, but that was no longer apparent in sensitivity analysis. A J-shaped association was observed between estimated sodium excretion and mortality. Our findings do not support a J-shaped association of estimated sodium excretion with CVD, although such an association was apparent for all-cause and cause-specific mortality across a wide range of diseases. Reasons for these differences are unclear; methodological limitations, including the use of estimating equations based on spot urinary data, need to be considered in interpreting our findings.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/HYPERTENSIONAHA.119.14302; doi:https://doi.org/10.1161/HYPERTENSIONAHA.119.14302 35835762,https://doi.org/10.1038/s41467-022-31626-4,"Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity.","Gilchrist JJ, Makino S, Naranbhai V, Sharma PK, Koturan S, Tong O, Taylor CA, Watson RA, de Los Aires AV, Cooper R, Lau E, Danielli S, Hameiri-Bowen D, Lee W, Ng E, Whalley J, Knight JC, Fairfax BP.",,Nature communications,2022,2022-07-14,Y,,,,"Natural Killer cells are innate lymphocytes with central roles in immunosurveillance and are implicated in autoimmune pathogenesis. The degree to which regulatory variants affect Natural Killer cell gene expression is poorly understood. Here we perform expression quantitative trait locus mapping of negatively selected Natural Killer cells from a population of healthy Europeans (n = 245). We find a significant subset of genes demonstrate expression quantitative trait loci specific to Natural Killer cells and these are highly informative of human disease, in particular autoimmunity. A Natural Killer cell transcriptome-wide association study across five common autoimmune diseases identifies further novel associations at 27 genes. In addition to these cis observations, we find novel master-regulatory regions impacting expression of trans gene networks at regions including 19q13.4, the Killer cell Immunoglobulin-like Receptor region, GNLY, MC1R and UVSSA. Our findings provide new insights into the unique biology of Natural Killer cells, demonstrating markedly different expression quantitative trait loci from other immune cells, with implications for disease mechanisms.",,pdf:https://www.nature.com/articles/s41467-022-31626-4.pdf; doi:https://doi.org/10.1038/s41467-022-31626-4; html:https://europepmc.org/articles/PMC9283523; pdf:https://europepmc.org/articles/PMC9283523?pdf=render +33021418,https://doi.org/10.1080/09273948.2020.1799038,Noninvasive Instrument-based Tests for Detecting and Measuring Vitreous Inflammation in Uveitis: A Systematic Review.,"Liu X, Hui BT, Way C, Beese S, Adriano A, Keane PA, Moore DJ, Denniston AK.",,Ocular immunology and inflammation,2022,2020-10-06,Y,Imaging; Diagnostic test; Systematic review; Vitreous; ultrasound; Uveitis; optical coherence tomography; Vitritis; Retinal Photography; Vitreous Inflammation,,,"

Purpose

This systematic review aims to identify instrument-based tests for quantifying vitreous inflammation in uveitis, report the test reliability and the level of correlation with clinician grading.

Methods

Studies describing instrument-based tests for detecting vitreous inflammation were identified by searching bibliographic databases and trials registers. Test reliability measures and level of correlation with clinician vitreous haze grading are extracted.

Results

Twelve studies describing ultrasound, optical coherence tomography (OCT), and retinal photography for detecting vitreous inflammation were included: Ultrasound was used for detection of disease features, whereas OCT and retinal photography provided quantifiable measurements. Correlation with clinician grading for OCT was 0.53-0.60 (three studies) and for retinal photography was 0.51 (1 study). Both instruments showed high inter- and intra-observer reliability (>0.70 intraclass correlation and Cohen's kappa), where reported in four studies.

Conclusion

Retinal photography and OCT are able to detect and measure vitreous inflammation. Both techniques are reliable, automatable, and warrant further evaluation.",,pdf:https://www.tandfonline.com/doi/pdf/10.1080/09273948.2020.1799038?needAccess=true; doi:https://doi.org/10.1080/09273948.2020.1799038; html:https://europepmc.org/articles/PMC8935946; pdf:https://europepmc.org/articles/PMC8935946?pdf=render 35279265,https://doi.org/10.1016/s2213-2600(21)00511-7,"Global, regional, and national prevalence of, and risk factors for, chronic obstructive pulmonary disease (COPD) in 2019: a systematic review and modelling analysis.","Adeloye D, Song P, Zhu Y, Campbell H, Sheikh A, Rudan I, NIHR RESPIRE Global Respiratory Health Unit.",,The Lancet. Respiratory medicine,2022,2022-03-10,Y,,,,"

Background

Chronic obstructive pulmonary disease (COPD) is an increasingly important cause of morbidity, disability, and mortality worldwide. We aimed to estimate global, regional, and national COPD prevalence and risk factors to guide policy and population interventions.

Methods

For this systematic review and modelling study, we searched MEDLINE, Embase, Global Health, and CINAHL, for population-based studies on COPD prevalence published between Jan 1, 1990, and Dec 31, 2019. We included data reported using the two main case definitions: the Global Initiative for Chronic Obstructive Lung Disease fixed ratio (GOLD; FEV1/FVC<0·7) and the lower limit of normal (LLN; FEV1/FVCFindingsWe identified 162 articles reporting population-based studies conducted across 260 sites in 65 countries. In 2019, the global prevalence of COPD among people aged 30-79 years was 10·3% (95% CI 8·2-12·8) using the GOLD case definition, which translates to 391·9 million people (95% CI 312·6-487·9), and 7·6% (5·8-10·1) using the LLN definition, which translates to 292·0 million people (219·8-385·6). Using the GOLD definition, we estimated that 391·9 million (95% CI 312·6-487·9) people aged 30-79 years had COPD worldwide in 2019, with most (315·5 million [246·7-399·6]; 80·5%) living in LMICs. The overall prevalence of GOLD-COPD among people aged 30-79 years was the highest in the Western Pacific region (11·7% [95% CI 9·3-14·6]) and lowest in the region of the Americas (6·8% [95% CI 5·6-8·2]). Globally, male sex (OR 2·1 [95% CI 1·8-2·3]), smoking (current smoker 3·2 [2·5-4·0]; ever smoker 2·3 [2·0-2·5]), body-mass index of less than 18·5 kg/m2 (2·2 [1·7-2·7]), biomass exposure (1·4 [1·2-1·7]), and occupational exposure to dust or smoke (1·4 [1·3-1·6]) were all substantial risk factors for COPD.

Interpretation

With more than three-quarters of global COPD cases in LMICs, tackling this chronic condition is a major and increasing challenge for health systems in these settings. In the absence of targeted population-wide efforts and health system reforms in these settings, many of which are under-resourced, achieving a substantial reduction in the burden of COPD globally might remain a difficult task.

Funding

National Institute for Health Research and Health Data Research UK.",,doi:https://doi.org/10.1016/s2213-2600(21)00511-7; doi:https://doi.org/10.1016/S2213-2600(21)00511-7; html:https://europepmc.org/articles/PMC9050565 35728939,https://doi.org/10.1136/archdischild-2021-323681,Reductions in hospital care among clinically vulnerable children aged 0-4 years during the COVID-19 pandemic.,"Etoori D, Harron KL, Mc Grath-Lone L, Verfürden ML, Gilbert R, Blackburn R.",,Archives of disease in childhood,2022,2022-09-20,Y,Child Health; Health Services Research; Healthcare Disparities; Covid-19,,,"

Objective

To quantify reductions in hospital care for clinically vulnerable children during the COVID-19 pandemic.

Design

Birth cohort.

Setting

National Health Service hospitals in England.

Study population

All children aged <5 years with a birth recorded in hospital administrative data (January 2010-March 2021).

Main exposure

Clinical vulnerability defined by a chronic health condition, preterm birth (<37 weeks' gestation) or low birth weight (<2500 g).

Main outcomes

Reductions in care defined by predicted hospital contact rates for 2020, estimated from 2015 to 2019, minus observed rates per 1000 child years during the first year of the pandemic (March 2020-2021).

Results

Of 3 813 465 children, 17.7% (one in six) were clinically vulnerable (9.5% born preterm or low birth weight, 10.3% had a chronic condition). Reductions in hospital care during the pandemic were much higher for clinically vulnerable children than peers: respectively, outpatient attendances (314 vs 73 per 1000 child years), planned admissions (55 vs 10) and unplanned admissions (105 vs 79). Clinically vulnerable children accounted for 50.1% of the reduction in outpatient attendances, 55.0% in planned admissions and 32.8% in unplanned hospital admissions. During the pandemic, weekly rates of planned care returned to prepandemic levels for infants with chronic conditions but not older children. Reductions in care differed by ethnic group and level of deprivation. Virtual outpatient attendances increased from 3.2% to 24.8% during the pandemic.

Conclusion

One in six clinically vulnerable children accounted for one-third to one half of the reduction in hospital care during the pandemic.",,pdf:https://adc.bmj.com/content/archdischild/107/10/e31.full.pdf; doi:https://doi.org/10.1136/archdischild-2021-323681; html:https://europepmc.org/articles/PMC9271837; pdf:https://europepmc.org/articles/PMC9271837?pdf=render -33021418,https://doi.org/10.1080/09273948.2020.1799038,Noninvasive Instrument-based Tests for Detecting and Measuring Vitreous Inflammation in Uveitis: A Systematic Review.,"Liu X, Hui BT, Way C, Beese S, Adriano A, Keane PA, Moore DJ, Denniston AK.",,Ocular immunology and inflammation,2022,2020-10-06,Y,Imaging; Diagnostic test; Systematic review; Vitreous; ultrasound; Uveitis; optical coherence tomography; Vitritis; Retinal Photography; Vitreous Inflammation,,,"

Purpose

This systematic review aims to identify instrument-based tests for quantifying vitreous inflammation in uveitis, report the test reliability and the level of correlation with clinician grading.

Methods

Studies describing instrument-based tests for detecting vitreous inflammation were identified by searching bibliographic databases and trials registers. Test reliability measures and level of correlation with clinician vitreous haze grading are extracted.

Results

Twelve studies describing ultrasound, optical coherence tomography (OCT), and retinal photography for detecting vitreous inflammation were included: Ultrasound was used for detection of disease features, whereas OCT and retinal photography provided quantifiable measurements. Correlation with clinician grading for OCT was 0.53-0.60 (three studies) and for retinal photography was 0.51 (1 study). Both instruments showed high inter- and intra-observer reliability (>0.70 intraclass correlation and Cohen's kappa), where reported in four studies.

Conclusion

Retinal photography and OCT are able to detect and measure vitreous inflammation. Both techniques are reliable, automatable, and warrant further evaluation.",,pdf:https://www.tandfonline.com/doi/pdf/10.1080/09273948.2020.1799038?needAccess=true; doi:https://doi.org/10.1080/09273948.2020.1799038; html:https://europepmc.org/articles/PMC8935946; pdf:https://europepmc.org/articles/PMC8935946?pdf=render -38040695,https://doi.org/10.1038/s41467-023-43522-6,Haplotype-based inference of recent effective population size in modern and ancient DNA samples.,"Fournier R, Tsangalidou Z, Reich D, Palamara PF.",,Nature communications,2023,2023-12-01,Y,,,,"Individuals sharing recent ancestors are likely to co-inherit large identical-by-descent (IBD) genomic regions. The distribution of these IBD segments in a population may be used to reconstruct past demographic events such as effective population size variation, but accurate IBD detection is difficult in ancient DNA data and in underrepresented populations with limited reference data. In this work, we introduce an accurate method for inferring effective population size variation during the past ~2000 years in both modern and ancient DNA data, called HapNe. HapNe infers recent population size fluctuations using either IBD sharing (HapNe-IBD) or linkage disequilibrium (HapNe-LD), which does not require phasing and can be computed in low coverage data, including data sets with heterogeneous sampling times. HapNe shows improved accuracy in a range of simulated demographic scenarios compared to currently available methods for IBD-based and LD-based inference of recent effective population size, while requiring fewer computational resources. We apply HapNe to several modern populations from the 1,000 Genomes Project, the UK Biobank, the Allen Ancient DNA Resource, and recently published samples from Iron Age Britain, detecting multiple instances of recent effective population size variation across these groups.",,pdf:https://www.nature.com/articles/s41467-023-43522-6.pdf; doi:https://doi.org/10.1038/s41467-023-43522-6; html:https://europepmc.org/articles/PMC10692198; pdf:https://europepmc.org/articles/PMC10692198?pdf=render 31702773,https://doi.org/10.1093/bioinformatics/btz796,Model selection for metabolomics: predicting diagnosis of coronary artery disease using automated machine learning.,"Orlenko A, Kofink D, Lyytikäinen LP, Nikus K, Mishra P, Kuukasjärvi P, Karhunen PJ, Kähönen M, Laurikka JO, Lehtimäki T, Asselbergs FW, Moore JH.",,"Bioinformatics (Oxford, England)",2020,2020-03-01,Y,,,,"

Motivation

Selecting the optimal machine learning (ML) model for a given dataset is often challenging. Automated ML (AutoML) has emerged as a powerful tool for enabling the automatic selection of ML methods and parameter settings for the prediction of biomedical endpoints. Here, we apply the tree-based pipeline optimization tool (TPOT) to predict angiographic diagnoses of coronary artery disease (CAD). With TPOT, ML models are represented as expression trees and optimal pipelines discovered using a stochastic search method called genetic programing. We provide some guidelines for TPOT-based ML pipeline selection and optimization-based on various clinical phenotypes and high-throughput metabolic profiles in the Angiography and Genes Study (ANGES).

Results

We analyzed nuclear magnetic resonance-derived lipoprotein and metabolite profiles in the ANGES cohort with a goal to identify the role of non-obstructive CAD patients in CAD diagnostics. We performed a comparative analysis of TPOT-generated ML pipelines with selected ML classifiers, optimized with a grid search approach, applied to two phenotypic CAD profiles. As a result, TPOT-generated ML pipelines that outperformed grid search optimized models across multiple performance metrics including balanced accuracy and area under the precision-recall curve. With the selected models, we demonstrated that the phenotypic profile that distinguishes non-obstructive CAD patients from no CAD patients is associated with higher precision, suggesting a discrepancy in the underlying processes between these phenotypes.

Availability and implementation

TPOT is freely available via http://epistasislab.github.io/tpot/.

Supplementary information

Supplementary data are available at Bioinformatics online.",,pdf:https://academic.oup.com/bioinformatics/article-pdf/36/6/1772/36089203/btz796.pdf; doi:https://doi.org/10.1093/bioinformatics/btz796; html:https://europepmc.org/articles/PMC7703753; pdf:https://europepmc.org/articles/PMC7703753?pdf=render +38040695,https://doi.org/10.1038/s41467-023-43522-6,Haplotype-based inference of recent effective population size in modern and ancient DNA samples.,"Fournier R, Tsangalidou Z, Reich D, Palamara PF.",,Nature communications,2023,2023-12-01,Y,,,,"Individuals sharing recent ancestors are likely to co-inherit large identical-by-descent (IBD) genomic regions. The distribution of these IBD segments in a population may be used to reconstruct past demographic events such as effective population size variation, but accurate IBD detection is difficult in ancient DNA data and in underrepresented populations with limited reference data. In this work, we introduce an accurate method for inferring effective population size variation during the past ~2000 years in both modern and ancient DNA data, called HapNe. HapNe infers recent population size fluctuations using either IBD sharing (HapNe-IBD) or linkage disequilibrium (HapNe-LD), which does not require phasing and can be computed in low coverage data, including data sets with heterogeneous sampling times. HapNe shows improved accuracy in a range of simulated demographic scenarios compared to currently available methods for IBD-based and LD-based inference of recent effective population size, while requiring fewer computational resources. We apply HapNe to several modern populations from the 1,000 Genomes Project, the UK Biobank, the Allen Ancient DNA Resource, and recently published samples from Iron Age Britain, detecting multiple instances of recent effective population size variation across these groups.",,pdf:https://www.nature.com/articles/s41467-023-43522-6.pdf; doi:https://doi.org/10.1038/s41467-023-43522-6; html:https://europepmc.org/articles/PMC10692198; pdf:https://europepmc.org/articles/PMC10692198?pdf=render 35762393,https://doi.org/10.1093/oncolo/oyac117,Using Patient-Reported Outcomes in Dose-Finding Oncology Trials: Surveys of Key Stakeholders and the National Cancer Research Institute Consumer Forum.,"Lai-Kwon J, Vanderbeek AM, Minchom A, Lee Aiyegbusi O, Ogunleye D, Stephens R, Calvert M, Yap C.",,The oncologist,2022,2022-09-01,Y,Cancer; Quality of life; Clinical Trials; Drug Development; Adverse Events; Patient-reported Outcomes,,,"

Background

Patient-reported adverse events may be a useful adjunct for assessing a drug's tolerability in dose-finding oncology trials (DFOT). We conducted surveys of international stakeholders and the National Cancer Research Institute (NCRI) Consumer Forum to understand attitudes about patient-reported outcome (PRO) use in DFOT.

Methods

A 35-question survey of clinicians, trial managers, statisticians, funders, and regulators of DFOT was distributed via professional bodies examining experience using PROs, benefits/barriers, and their potential role in defining tolerable doses. An 8-question survey of the NCRI Consumer Forum explored similar themes.

Results

International survey: 112 responses from 15 September-30 November 2020; 103 trialists [48 clinicians (42.9%), 38 statisticians (34.0%), 17 trial managers (15.2%)], 7 regulators (6.3%), 2 funders (1.8%)]. Most trialists had no experience designing (73, 70.9%), conducting (52, 50.5%), or reporting (88, 85.4%) PROs in DFOT. Most agreed that PROs could identify new toxicities (75, 67.0%) and provide data on the frequency (86, 76.8%) and duration (81, 72.3%) of toxicities. The top 3 barriers were lack of guidance regarding PRO selection (73/103, 70.9%), missing PRO data (71/103, 68.9%), and overburdening staff (68/103, 66.0%). NCRI survey: 57 responses on 21 March 2021. A total of 28 (49.1%) were willing to spend <15 min/day completing PROs. Most (55, 96.5%) preferred to complete PROs online. 61 (54.5%) trialists and 57 (100%) consumers agreed that patient-reported adverse events should be used to inform dose-escalation decisions.

Conclusion

Stakeholders reported minimal experience using PROs in DFOT but broadly supported their use. Guidelines are needed to standardize PRO selection, analysis, and reporting in DFOT.",,pdf:https://academic.oup.com/oncolo/article-pdf/27/9/768/45667678/oyac117.pdf; doi:https://doi.org/10.1093/oncolo/oyac117; html:https://europepmc.org/articles/PMC9438918; pdf:https://europepmc.org/articles/PMC9438918?pdf=render 35538704,https://doi.org/10.1177/1357633x221093434,"The development, validation and application of remote blood sample collection in telehealth programmes.","Koulman A, Rennie KL, Parkington D, Tyrrell CS, Catt M, Gkrania-Klotsas E, Wareham NJ.",,Journal of telemedicine and telecare,2024,2022-05-10,Y,Pathology; Self-care; Telehealth; Blood Sampling; Home Telecare,,,"

Introduction

The ability to collect blood samples remotely without the involvement of healthcare professionals is a key element of future telehealth applications. We developed and validated the application of the Drawbridge OneDraw device for use at home for blood sample collection. The device was then applied in a large population-based remote monitoring study to assess changes in SARS-CoV-2 IgG antibody levels.

Methods

We tested: (1) feasibility of participants using the device at home without a healthcare professional on the upper arm and thigh sites (2) stability of the dried blood sample collected remotely (3) participant acceptability of the device compared with finger-prick and venous blood samples and the validity of SARS-CoV-2 virus antibody measurement versus venous blood sample (4) application to the Fenland COVID-19 study in which 4023 participants at 3 timepoints across 6 months.

Results

Participant acceptability was high, with a significantly lower median perceived pain score and 76% of participants preferring the OneDraw device over the other blood collection methods. There was high level of agreement in SARS-CoV-2 virus antibody results with venous blood samples in 120 participants (Cohen's kappa 0.68 (95% CI 0.56, 0.83). In the Fenland COVID-19 study, 92% of participants returned a sample at baseline (3702/4023), 89% at 3 months (3492/3918) and 93% at 6 months (3453/3731), with almost all samples received successfully processed (99.9%).

Discussion

The OneDraw device enables a standardised blood sample collection at home by participants themselves. Due to its ease-of-use and acceptability the OneDraw device is particularly useful in telehealth approaches where multiple samples need to be collected.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/1357633X221093434; doi:https://doi.org/10.1177/1357633X221093434; html:https://europepmc.org/articles/PMC11027437; pdf:https://europepmc.org/articles/PMC11027437?pdf=render 35880304,https://doi.org/10.1002/jbmr.4664,Telomere Length and Risk of Incident Fracture and Arthroplasty: Findings From UK Biobank.,"Curtis EM, Codd V, Nelson C, D'Angelo S, Wang Q, Allara E, Kaptoge S, Matthews PM, Tobias JH, Danesh J, Cooper C, Samani NJ, Harvey NC.",,Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research,2022,2022-09-13,Y,Aging; Osteoporosis; Osteoarthritis; epidemiology; Leucocyte Telomere Length,,,"We investigated independent associations between telomere length and risk of fracture and arthroplasty in UK Biobank participants. Leukocyte telomere length (LTL) was measured in baseline samples using a validated polymerase chain reaction (PCR) method. We used, in men and women separately, Cox proportional hazards models to calculate the hazard ratio (HR) for incident fracture (any, osteoporotic) or arthroplasty (hip or knee) over 1,186,410 person-years of follow-up. Covariates included age, white cell count, ethnicity, smoking, alcohol, physical activity, and menopause (women). In further analyses we adjusted for either estimated bone mineral density (eBMD) from heel quantitative ultrasound, handgrip strength, gait speed, total fat mass (bioimpedance), or blood biomarkers, all measured at baseline (2006-2010). We studied 59,500 women and 51,895 men, mean ± standard deviation (SD) age 56.4 ± 8.0 and 57.0 ± 8.3 years, respectively. During follow-up there were 5619 fractures; 5285 hip and 4261 knee arthroplasties. In confounder-adjusted models, longer LTL was associated with reduced risk of incident knee arthroplasty in both men (HR/SD 0.93; 95% confidence interval [CI], 0.88-0.97) and women (0.92; 95% CI, 0.88-0.96), and hip arthroplasty in men (0.91; 95% CI, 0.87-0.95), but not women (0.98; 95% CI, 0.94-1.01). Longer LTL was weakly associated with reduced risk of any incident fracture in women (HR/SD 0.96; 95% CI, 0.93-1.00) with less evidence in men (0.98; 95% CI, 0.93-1.02). Associations with incident outcomes were not materially altered by adjustment for heel eBMD, grip strength, gait speed, fat mass, or blood biomarker measures. In this, the largest study to date, longer LTL was associated with lower risk of incident knee or hip arthroplasty, but only weakly associated with lower risk of fracture. The relative risks were low at a population level, but our findings suggest that common factors acting on the myeloid and musculoskeletal systems might influence later life musculoskeletal outcomes. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).",,pdf:https://research-information.bris.ac.uk/files/341783442/J_of_Bone_Mineral_Res_2022_Curtis_Telomere_Length_and_Risk_of_Incident_Fracture_and_Arthroplasty_Findings_From_UK_1_.pdf; doi:https://doi.org/10.1002/jbmr.4664; html:https://europepmc.org/articles/PMC9826022; pdf:https://europepmc.org/articles/PMC9826022?pdf=render @@ -1905,18 +1905,18 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 34632432,https://doi.org/10.1016/s2666-5247(21)00128-2,Epidemiology of Mycobacterium abscessus in England: an observational study.,"Lipworth S, Hough N, Weston N, Muller-Pebody B, Phin N, Myers R, Chapman S, Flight W, Alexander E, Smith EG, Robinson E, Peto TEA, Crook DW, Walker AS, Hopkins S, Eyre DW, Walker TM.",,The Lancet. Microbe,2021,2021-10-01,Y,,,,"

Background

Mycobacterium abscessus has emerged as a significant clinical concern following reports that it is readily transmissible in health-care settings between patients with cystic fibrosis. We linked routinely collected whole-genome sequencing and health-care usage data with the aim of investigating the extent to which such transmission explains acquisition in patients with and without cystic fibrosis in England.

Methods

In this retrospective observational study, we analysed consecutive M abscessus whole-genome sequencing data from England (beginning of February, 2015, to Nov 14, 2019) to identify genomically similar isolates. Linkage to a national health-care usage database was used to investigate possible contacts between patients. Multivariable regression analysis was done to investigate factors associated with acquisition of a genomically clustered strain (genomic distance <25 single nucleotide polymorphisms [SNPs]).

Findings

2297 isolates from 906 patients underwent whole-genome sequencing as part of the routine Public Health England diagnostic service. Of 14 genomic clusters containing isolates from ten or more patients, all but one contained patients with cystic fibrosis and patients without cystic fibrosis. Patients with cystic fibrosis were equally likely to have clustered isolates (258 [60%] of 431 patients) as those without cystic fibrosis (322 [63%] of 513 patients; p=0·38). High-density phylogenetic clusters were randomly distributed over a wide geographical area. Most isolates with a closest genetic neighbour consistent with potential transmission had no identifiable relevant epidemiological contacts. Having a clustered isolate was independently associated with increasing age (adjusted odds ratio 1·14 per 10 years, 95% CI 1·04-1·26), but not time spent as an hospital inpatient or outpatient. We identified two sibling pairs with cystic fibrosis with genetically highly divergent isolates and one pair with closely related isolates, and 25 uninfected presumed household contacts with cystic fibrosis.

Interpretation

Previously identified widely disseminated dominant clones of M abscessus are not restricted to patients with cystic fibrosis and occur in other chronic respiratory diseases. Although our analysis showed a small number of cases where person-to-person transmission could not be excluded, it did not support this being a major mechanism for M abscessus dissemination at a national level in England. Overall, these data should reassure patients and clinicians that the risk of acquisition from other patients in health-care settings is relatively low and motivate future research efforts to focus on identifying routes of acquisition outside of the cystic fibrosis health-care-associated niche.

Funding

The National Institute for Health Research, Health Data Research UK, The Wellcome Trust, The Medical Research Council, and Public Health England.",,pdf:http://www.thelancet.com/article/S2666524721001282/pdf; doi:https://doi.org/10.1016/S2666-5247(21)00128-2; html:https://europepmc.org/articles/PMC8481905 32294163,https://doi.org/10.1093/europace/euaa039,Diagnosing arrhythmogenic right ventricular cardiomyopathy by 2010 Task Force Criteria: clinical performance and simplified practical implementation.,"Bosman LP, Cadrin-Tourigny J, Bourfiss M, Aliyari Ghasabeh M, Sharma A, Tichnell C, Roudijk RW, Murray B, Tandri H, Khairy P, Kamel IR, Zimmerman SL, Reitsma JB, Asselbergs FW, van Tintelen JP, van der Heijden JF, Hauer RNW, Calkins H, James CA, Te Riele ASJM.",,"Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology",2020,2020-05-01,Y,Diagnosis; Cardiomyopathy; ventricular arrhythmia; Arrhythmogenic Right Ventricular Cardiomyopathy,,,"

Aims

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is diagnosed by a complex set of clinical tests as per 2010 Task Force Criteria (TFC). Avoiding misdiagnosis is crucial to prevent sudden cardiac death as well as unnecessary implantable cardioverter-defibrillator implantations. This study aims to validate the overall performance of the TFC in a real-world cohort of patients referred for ARVC evaluation.

Methods and results

We included patients consecutively referred to our centres for ARVC evaluation. Patients were diagnosed by consensus of three independent clinical experts. Using this as a reference standard, diagnostic performance was measured for each individual criterion as well as the overall TFC classification. Of 407 evaluated patients (age 38 ± 17 years, 51% male), the expert panel diagnosed 66 (16%) with ARVC. The clinically observed TFC was false negative in 7/66 (11%) patients and false positive in 10/69 (14%) patients. Idiopathic outflow tract ventricular tachycardia was the most common alternative diagnosis. While the TFC performed well overall (sensitivity and specificity 92%), signal-averaged electrocardiogram (SAECG, P = 0.43), and several family history criteria (P ≥ 0.17) failed to discriminate. Eliminating these criteria reduced false positives without increasing false negatives (net reclassification improvement 4.3%, P = 0.019). Furthermore, all ARVC patients met at least one electrocardiogram (ECG) or arrhythmia criterion (sensitivity 100%).

Conclusion

The TFC perform well but are complex and can lead to misdiagnosis. Simplification by eliminating SAECG and several family history criteria improves diagnostic accuracy. Arrhythmogenic right ventricular cardiomyopathy can be ruled out using ECG and arrhythmia criteria alone, hence these tests may serve as a first-line screening strategy among at-risk individuals.",,pdf:https://academic.oup.com/europace/article-pdf/22/5/787/33178222/euaa039.pdf; doi:https://doi.org/10.1093/europace/euaa039; html:https://europepmc.org/articles/PMC7203633; pdf:https://europepmc.org/articles/PMC7203633?pdf=render 35189884,https://doi.org/10.1186/s12913-022-07607-0,Factors influencing follow-up care post-TIA and minor stroke: a qualitative study using the theoretical domains framework.,"Turner GM, Aquino MRJV, Atkins L, Foy R, Mant J, Calvert M.",,BMC health services research,2022,2022-02-21,Y,Follow-up; Transient Ischaemic Attack; Tia; Minor Stroke; Theoretical Domains Framework,,,"

Background

Follow-up care after transient ischaemic attack (TIA) and minor stroke has been found to be sub-optimal, with individuals often feeling abandoned. We aimed to explore factors influencing holistic follow-up care after TIA and minor stroke.

Methods

Qualitative semi-structured interviews with 24 healthcare providers (HCPs): 5 stroke doctors, 4 nurses, 9 allied health professionals and 6 general practitioners. Participants were recruited from three TIA clinics, seven general practices and one community care trust in the West Midlands, England. Interview transcripts were deductively coded using the Theoretical Domains Framework and themes were generated from coded data.

Results

There was no clear pathway for supporting people with TIA or minor stroke after rapid specialist review in hospital; consequently, these patients had limited access to HCPs from all settings ('Environmental context and resources'). There was lack of understanding of potential needs post-TIA/minor stroke, in particular residual problems such as anxiety/fatigue ('Knowledge'). Identification and management of needs was largely influenced by HCPs' perceived role, professional training ('Social professional role and identity') and time constraints ('Environmental context and resources'). Follow-up was often passive - with onerous on patients to seek support - and predominantly focused on acute medical management ('Intentions'/'Goal').

Conclusions

Follow-up care post-TIA/minor stroke is currently sub-optimal. Through identifying factors which influence follow-up, we can inform guidelines and practical strategies to improve holistic healthcare.",,pdf:https://bmchealthservres.biomedcentral.com/track/pdf/10.1186/s12913-022-07607-0; doi:https://doi.org/10.1186/s12913-022-07607-0; html:https://europepmc.org/articles/PMC8859903; pdf:https://europepmc.org/articles/PMC8859903?pdf=render -36408685,https://doi.org/10.1161/circheartfailure.122.009526,"Multimarker Analysis of Serially Measured GDF-15, NT-proBNP, ST2, GAL-3, cTnI, Creatinine, and Prognosis in Acute Heart Failure.","Gürgöze MT, van Vark LC, Baart SJ, Kardys I, Akkerhuis KM, Manintveld OC, Postmus D, Hillege HL, Lesman-Leegte I, Asselbergs FW, Brunner-la-Rocca HP, van den Bos EJ, Orsel JG, de Ridder SPJ, Pinto YM, Boersma E.",,Circulation. Heart failure,2023,2022-11-21,Y,Prognosis; Biomarkers; Heart Failure; Growth Differentiation Factor 15,,,"

Background

Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk.

Methods

TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling.

Results

Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78-2.57) unadjusted, 1.96 (1.49-2.53) after adjustment for clinical confounders and 1.44 (1.05-1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78-3.33) and 1.52 (1.15-2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785).

Conclusions

Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates. Multiple biomarkers should be considered for stratification in clinical practice.

Registration

URL: https://www.trialregister.nl/trial/1783; Unique Identifier: NTR1893. (The trial can be found temporarily at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR1893.).",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCHEARTFAILURE.122.009526; doi:https://doi.org/10.1161/CIRCHEARTFAILURE.122.009526; html:https://europepmc.org/articles/PMC9833118; pdf:https://europepmc.org/articles/PMC9833118?pdf=render 35193920,https://doi.org/10.1136/bmjopen-2021-055773,Investigating the optimal handling of uncertain pregnancy episodes in the CPRD GOLD Pregnancy Register: a methodological study using UK primary care data.,"Campbell J, Bhaskaran K, Thomas S, Williams R, McDonald HI, Minassian C.",,BMJ open,2022,2022-02-22,Y,epidemiology; Public Health; Maternal Medicine,,,"

Objectives

To investigate why episodes of pregnancy identified from electronic health records may be incomplete or conflicting (overlapping), and provide guidance on how to handle them.

Setting

Pregnancy Register generated from the Clinical Practice Research Datalink (CPRD) GOLD UK primary care database.

Participants

Female patients with at least one pregnancy episode in the Register (01 January 1937-31 December 2017) which had no recorded outcome or conflicted with another episode.

Design

We identified multiple scenarios potentially explaining why uncertain episodes occur. Criteria were established and systematically applied to determine whether episodes had evidence of each scenario. Linked Hospital Episode Statistics were used to identify pregnancy events not captured in primary care.

Results

Of 5.8 million pregnancy episodes in the Register, 932 604 (16%) had no recorded outcome, and 478 341 (8.5%) conflicted with another episode (251 026 distinct conflicting pairs of episodes among 210 593 women). 826 146 (89%) of the episodes without outcome recorded in primary care and 215 577 (86%) of the conflicting pairs were consistent with one or more of our proposed scenarios. For 689 737 (74%) episodes with recorded outcome missing and 215 544 (86%) of the conflicting pairs (at least one episode), supportive evidence (eg, antenatal records, linked hospital records) suggested they were true and current pregnancies. Furthermore, 516 818 (55 %) and 160 936 (64%), respectively, were during research quality follow-up time. For a sizeable proportion of uncertain episode, there is evidence to suggest that historical outcomes being recorded by the general practitioner during an ongoing pregnancy may offer explanation (73 208 (29.2%) and 349 874 (37.5%)).

Conclusions

This work provides insight to users of the CPRD Pregnancy Register on why uncertain pregnancy episodes exist and indicates that most of these episodes are likely to be real pregnancies. Guidance is given to help researchers consider whether to include/exclude uncertain pregnancies from their studies, and how to tailor approaches to minimise underestimation and bias.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e055773.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055773; html:https://europepmc.org/articles/PMC8867343; pdf:https://europepmc.org/articles/PMC8867343?pdf=render +36408685,https://doi.org/10.1161/circheartfailure.122.009526,"Multimarker Analysis of Serially Measured GDF-15, NT-proBNP, ST2, GAL-3, cTnI, Creatinine, and Prognosis in Acute Heart Failure.","Gürgöze MT, van Vark LC, Baart SJ, Kardys I, Akkerhuis KM, Manintveld OC, Postmus D, Hillege HL, Lesman-Leegte I, Asselbergs FW, Brunner-la-Rocca HP, van den Bos EJ, Orsel JG, de Ridder SPJ, Pinto YM, Boersma E.",,Circulation. Heart failure,2023,2022-11-21,Y,Prognosis; Biomarkers; Heart Failure; Growth Differentiation Factor 15,,,"

Background

Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk.

Methods

TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling.

Results

Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78-2.57) unadjusted, 1.96 (1.49-2.53) after adjustment for clinical confounders and 1.44 (1.05-1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78-3.33) and 1.52 (1.15-2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785).

Conclusions

Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates. Multiple biomarkers should be considered for stratification in clinical practice.

Registration

URL: https://www.trialregister.nl/trial/1783; Unique Identifier: NTR1893. (The trial can be found temporarily at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR1893.).",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCHEARTFAILURE.122.009526; doi:https://doi.org/10.1161/CIRCHEARTFAILURE.122.009526; html:https://europepmc.org/articles/PMC9833118; pdf:https://europepmc.org/articles/PMC9833118?pdf=render 35251129,https://doi.org/10.3389/fgene.2022.818574,Calculating Polygenic Risk Scores (PRS) in UK Biobank: A Practical Guide for Epidemiologists.,"Collister JA, Liu X, Clifton L.",,Frontiers in genetics,2022,2022-02-18,Y,Polygenic Score; Genetic Risk Score; Uk Biobank; Polygenic Risk Score; Worked Example,,,"A polygenic risk score estimates the genetic risk of an individual for some disease or trait, calculated by aggregating the effect of many common variants associated with the condition. With the increasing availability of genetic data in large cohort studies such as the UK Biobank, inclusion of this genetic risk as a covariate in statistical analyses is becoming more widespread. Previously this required specialist knowledge, but as tooling and data availability have improved it has become more feasible for statisticians and epidemiologists to calculate existing scores themselves for use in analyses. While tutorial resources exist for conducting genome-wide association studies and generating of new polygenic risk scores, fewer guides exist for the simple calculation and application of existing genetic scores. This guide outlines the key steps of this process: selection of suitable polygenic risk scores from the literature, extraction of relevant genetic variants and verification of their quality, calculation of the risk score and key considerations of its inclusion in statistical models, using the UK Biobank imputed data as a model data set. Many of the techniques in this guide will generalize to other datasets, however we also focus on some of the specific techniques required for using data in the formats UK Biobank have selected. This includes some of the challenges faced when working with large numbers of variants, where the computation time required by some tools is impractical. While we have focused on only a couple of tools, which may not be the best ones for every given aspect of the process, one barrier to working with genetic data is the sheer volume of tools available, and the difficulty for a novice to assess their viability. By discussing in depth a couple of tools that are adequate for the calculation even at large scale, we hope to make polygenic risk scores more accessible to a wider range of researchers.",,pdf:https://www.frontiersin.org/articles/10.3389/fgene.2022.818574/pdf; doi:https://doi.org/10.3389/fgene.2022.818574; html:https://europepmc.org/articles/PMC8894758; pdf:https://europepmc.org/articles/PMC8894758?pdf=render 33434193,https://doi.org/10.1371/journal.pmed.1003487,Accelerometer measured physical activity and the incidence of cardiovascular disease: Evidence from the UK Biobank cohort study.,"Ramakrishnan R, Doherty A, Smith-Byrne K, Rahimi K, Bennett D, Woodward M, Walmsley R, Dwyer T.",,PLoS medicine,2021,2021-01-12,Y,,,,"

Background

Higher levels of physical activity (PA) are associated with a lower risk of cardiovascular disease (CVD). However, uncertainty exists on whether the inverse relationship between PA and incidence of CVD is greater at the highest levels of PA. Past studies have mostly relied on self-reported evidence from questionnaire-based PA, which is crude and cannot capture all PA undertaken. We investigated the association between accelerometer-measured moderate, vigorous, and total PA and incident CVD.

Methods and findings

We obtained accelerometer-measured moderate-intensity and vigorous-intensity physical activities and total volume of PA, over a 7-day period in 2013-2015, for 90,211 participants without prior or concurrent CVD in the UK Biobank cohort. Participants in the lowest category of total PA smoked more, had higher body mass index and C-reactive protein, and were diagnosed with hypertension. PA was associated with 3,617 incident CVD cases during 440,004 person-years of follow-up (median (interquartile range [IQR]): 5.2 (1.2) years) using Cox regression models. We found a linear dose-response relationship for PA, whether measured as moderate-intensity, vigorous-intensity, or as total volume, with risk of incident of CVD. Hazard ratios (HRs) and 95% confidence intervals for increasing quarters of the PA distribution relative to the lowest fourth were for moderate-intensity PA: 0.71 (0.65, 0.77), 0.59 (0.54, 0.65), and 0.46 (0.41, 0.51); for vigorous-intensity PA: 0.70 (0.64, 0.77), 0.54 (0.49,0.59), and 0.41 (0.37,0.46); and for total volume of PA: 0.73 (0.67, 0.79), 0.63 (0.57, 0.69), and 0.47 (0.43, 0.52). We took account of potential confounders but unmeasured confounding remains a possibility, and while removal of early deaths did not affect the estimated HRs, we cannot completely dismiss the likelihood that reverse causality has contributed to the findings. Another possible limitation of this work is the quantification of PA intensity-levels based on methods validated in relatively small studies.

Conclusions

In this study, we found no evidence of a threshold for the inverse association between objectively measured moderate, vigorous, and total PA with CVD. Our findings suggest that PA is not only associated with lower risk for of CVD, but the greatest benefit is seen for those who are active at the highest level.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003487&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003487; html:https://europepmc.org/articles/PMC7802951; pdf:https://europepmc.org/articles/PMC7802951?pdf=render 34737870,https://doi.org/10.7189/jogh.11.15003,Research priorities to address the global burden of chronic obstructive pulmonary disease (COPD) in the next decade.,"Adeloye D, Agarwal D, Barnes PJ, Bonay M, van Boven JF, Bryant J, Caramori G, Dockrell D, D'Urzo A, Ekström M, Erhabor G, Esteban C, Greene CM, Hurst J, Juvekar S, Khoo EM, Ko FW, Lipworth B, López-Campos JL, Maddocks M, Mannino DM, Martinez FJ, Martinez-Garcia MA, McNamara RJ, Miravitlles M, Pinnock H, Pooler A, Quint JK, Schwarz P, Slavich GM, Song P, Tai A, Watz H, Wedzicha JA, Williams MC, Campbell H, Sheikh A, Rudan I.",,Journal of global health,2021,2021-10-09,Y,,,,"

Background

The global prevalence of chronic obstructive pulmonary disease (COPD) has increased markedly in recent decades. Given the scarcity of resources available to address global health challenges and respiratory medicine being relatively under-invested in, it is important to define research priorities for COPD globally. In this paper, we aim to identify a ranked set of COPD research priorities that need to be addressed in the next 10 years to substantially reduce the global impact of COPD.

Methods

We adapted the Child Health and Nutrition Research Initiative (CHNRI) methodology to identify global COPD research priorities.

Results

62 experts contributed 230 research ideas, which were scored by 34 researchers according to six pre-defined criteria: answerability, effectiveness, feasibility, deliverability, burden reduction, and equity. The top-ranked research priority was the need for new effective strategies to support smoking cessation. Of the top 20 overall research priorities, six were focused on feasible and cost-effective pulmonary rehabilitation delivery and access, particularly in primary/community care and low-resource settings. Three of the top 10 overall priorities called for research on improved screening and accurate diagnostic methods for COPD in low-resource primary care settings. Further ideas that drew support involved a better understanding of risk factors for COPD, development of effective training programmes for health workers and physicians in low resource settings, and evaluation of novel interventions to encourage physical activity.

Conclusions

The experts agreed that the most pressing feasible research questions to address in the next decade for COPD reduction were on prevention, diagnosis and rehabilitation of COPD, especially in low resource settings. The largest gains should be expected in low- and middle-income countries (LMIC) settings, as the large majority of COPD deaths occur in those settings. Research priorities identified by this systematic international process should inform and motivate policymakers, funders, and researchers to support and conduct research to reduce the global burden of COPD.",,doi:https://doi.org/10.7189/jogh.11.15003; doi:https://doi.org/10.7189/jogh.11.15003; html:https://europepmc.org/articles/PMC8542376; pdf:https://europepmc.org/articles/PMC8542376?pdf=render 33635119,https://doi.org/10.1161/circgen.120.002963,Life-Time Covariation of Major Cardiovascular Diseases: A 40-Year Longitudinal Study and Genetic Studies.,"Lind L, Sundström J, Ärnlöv J, Ingelsson M, Henry A, Lumbers RT, Lampa E.",,Circulation. Genomic and precision medicine,2021,2021-02-26,N,Adult; Myocardial infarction; Atrial fibrillation; Stroke; Heart Failure,,,"

Background

It is known that certain cardiovascular diseases (CVD) are associated, like atrial fibrillation and stroke. However, for other CVDs, the links and temporal trends are less studied. In this longitudinal study, we have investigated temporal epidemiological and genetic associations between different CVDs.

Methods

The ULSAM (Uppsala Longitudinal Study of Adult Men; 2322 men aged 50 years) has been followed for 40 years regarding 4 major CVDs (incident myocardial infarction, ischemic stroke, heart failure, and atrial fibrillation). For the genetic analyses, publicly available data were used.

Results

Using multistate modeling, significant relationships were seen between pairs of all of the 4 investigated CVDs. However, the risk of obtaining one additional CVD differed substantially both between different CVDs and between their temporal order. The relationship between heart failure and atrial fibrillation showed a high risk ratio (risk ratios, 24-26) regardless of the temporal order. A consistent association was seen also for myocardial infarction and atrial fibrillation but with a lower relative risk (risk ratios, 4-5). In contrast, the risk of receiving a diagnosis of heart failure following a myocardial infarction was almost twice as high as for the reverse temporal order (risk ratios, 16 versus 9). Genetic loci linked to traditional risk factors could partly explain the observed associations between the CVDs, but pathway analyses disclosed also other pathophysiological links.

Conclusions

During 40 years, all of the 4 investigated CVDs were pairwise associated with each other regardless of the temporal order of occurrence, but the risk magnitude differed between different CVDs and their temporal order. Genetic analyses disclosed new pathophysiological links between CVDs.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.120.002963; doi:https://doi.org/10.1161/CIRCGEN.120.002963; html:https://europepmc.org/articles/PMC8284356; pdf:https://europepmc.org/articles/PMC8284356?pdf=render; doi:https://doi.org/10.1161/circgen.120.002963 -33090454,https://doi.org/10.1111/bjd.19597,Atopic eczema and obesity: a population-based study.,"Ascott A, Mansfield KE, Schonmann Y, Mulick A, Abuabara K, Roberts A, Smeeth L, Langan SM.",,The British journal of dermatology,2021,2020-12-01,N,,,,"

Background

Atopic eczema is a common chronic inflammatory skin disease. Research suggests an association between atopic eczema and obesity, with inconsistent evidence from European populations.

Objectives

To explore the association between diagnosed atopic eczema and being overweight or obese, and whether increased atopic eczema severity was associated with higher body mass index.

Methods

We undertook a cross-sectional analysis within a cohort of adults (matched by age, sex and general practice) with and without a diagnosis of atopic eczema. We used primary care (Clinical Practice Research Datalink Gold) and linked hospital admissions data (1998-2016). We used conditional logistic regression to compare the odds of being overweight or obese (adjusting for confounders and potential mediators) in those with atopic eczema (mild, moderate and severe, and all eczema) vs. those without.

Results

We identified 441 746 people with atopic eczema, matched to 1 849 722 without. People with atopic eczema had slightly higher odds of being overweight or obese vs. those without [odds ratio (OR) 1·08, 95% confidence interval (CI) 1·07-1·09] after adjusting for age, asthma and socioeconomic deprivation. Adjusting for potential mediators (high-dose glucocorticoids, harmful alcohol use, anxiety, depression, smoking) had a minimal impact on effect estimates (OR 1·07, 95% CI 1·06-1·08). We saw no evidence that odds of being overweight or obese increased with increasing atopic eczema severity, and there was no association in people with severe eczema.

Conclusions

We found evidence of a small overall association between atopic eczema and being overweight or obese. However, there was no association with obesity among those with the most severe eczema. Our findings are largely reassuring for this prevalent patient group who may already have an increased risk of cardiovascular disease.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4658151/1/Ascott-etal-2020_Atopic_eczema_and-obesity.pdf; doi:https://doi.org/10.1111/bjd.19597 32222069,https://doi.org/10.1111/bjd.19052,Risk of hospitalization and death due to infection in people with psoriasis: a population-based cohort study using the Clinical Practice Research Datalink.,"Yiu ZZN, Parisi R, Lunt M, Warren RB, Griffiths CEM, Langan SM, Ashcroft DM.",,The British journal of dermatology,2021,2020-05-12,N,,,,"

Background

Psoriasis is associated with risk factors for serious infections, but the independent relationship between psoriasis and serious infection is as yet unclear.

Objectives

To determine whether people with psoriasis have a higher risk of hospitalization due to any infection, respiratory infections, soft-tissue and skin infections, or a higher risk of death due to infection.

Methods

We conducted a cohort study of people (≥ 18 years) with psoriasis using the UK Clinical Practice Research Datalink (CPRD GOLD) linked to Hospital Episode Statistics (HES) and Office for National Statistics (ONS) mortality records between 1 April 2003 and 31 December 2016, and matched with up to six comparators on age, sex and general practice. Hospitalization was ascertained from HES records; death was ascertained from ONS mortality records. Stratified Cox proportional hazard models were estimated, with stepwise adjustment in different models for potential confounders or mediators between psoriasis and serious infection.

Results

There were 69 315 people with psoriasis and 338 620 comparators who were followed up for a median (interquartile range) of 4·9 (5·9) and 5·1 (6·3) years, respectively. People with psoriasis had a higher incidence rate of serious infection [20·5 per 1000 person-years, 95% confidence interval (CI) 20·0-21·0, n = 7631] compared with those without psoriasis (16·1 per 1000 person-years, 95% CI 15·9-16·3, n = 30 761). The fully adjusted hazard ratio for the association between psoriasis and serious infection was 1·36 (95% CI 1·31-1·40), with similar results across the other outcomes.

Conclusions

Psoriasis is associated with a small increase in the risk of serious infection. Further research is needed to understand how psoriasis predisposes to a higher risk of infection.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.19052; doi:https://doi.org/10.1111/bjd.19052 +33090454,https://doi.org/10.1111/bjd.19597,Atopic eczema and obesity: a population-based study.,"Ascott A, Mansfield KE, Schonmann Y, Mulick A, Abuabara K, Roberts A, Smeeth L, Langan SM.",,The British journal of dermatology,2021,2020-12-01,N,,,,"

Background

Atopic eczema is a common chronic inflammatory skin disease. Research suggests an association between atopic eczema and obesity, with inconsistent evidence from European populations.

Objectives

To explore the association between diagnosed atopic eczema and being overweight or obese, and whether increased atopic eczema severity was associated with higher body mass index.

Methods

We undertook a cross-sectional analysis within a cohort of adults (matched by age, sex and general practice) with and without a diagnosis of atopic eczema. We used primary care (Clinical Practice Research Datalink Gold) and linked hospital admissions data (1998-2016). We used conditional logistic regression to compare the odds of being overweight or obese (adjusting for confounders and potential mediators) in those with atopic eczema (mild, moderate and severe, and all eczema) vs. those without.

Results

We identified 441 746 people with atopic eczema, matched to 1 849 722 without. People with atopic eczema had slightly higher odds of being overweight or obese vs. those without [odds ratio (OR) 1·08, 95% confidence interval (CI) 1·07-1·09] after adjusting for age, asthma and socioeconomic deprivation. Adjusting for potential mediators (high-dose glucocorticoids, harmful alcohol use, anxiety, depression, smoking) had a minimal impact on effect estimates (OR 1·07, 95% CI 1·06-1·08). We saw no evidence that odds of being overweight or obese increased with increasing atopic eczema severity, and there was no association in people with severe eczema.

Conclusions

We found evidence of a small overall association between atopic eczema and being overweight or obese. However, there was no association with obesity among those with the most severe eczema. Our findings are largely reassuring for this prevalent patient group who may already have an increased risk of cardiovascular disease.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4658151/1/Ascott-etal-2020_Atopic_eczema_and-obesity.pdf; doi:https://doi.org/10.1111/bjd.19597 33637859,https://doi.org/10.1038/s41746-021-00404-9,Automatic multilabel detection of ICD10 codes in Dutch cardiology discharge letters using neural networks.,"Sammani A, Bagheri A, van der Heijden PGM, Te Riele ASJM, Baas AF, Oosters CAJ, Oberski D, Asselbergs FW.",,NPJ digital medicine,2021,2021-02-26,Y,,,,"Standard reference terminology of diagnoses and risk factors is crucial for billing, epidemiological studies, and inter/intranational comparisons of diseases. The International Classification of Disease (ICD) is a standardized and widely used method, but the manual classification is an enormously time-consuming endeavor. Natural language processing together with machine learning allows automated structuring of diagnoses using ICD-10 codes, but the limited performance of machine learning models, the necessity of gigantic datasets, and poor reliability of terminal parts of these codes restricted clinical usability. We aimed to create a high performing pipeline for automated classification of reliable ICD-10 codes in the free medical text in cardiology. We focussed on frequently used and well-defined three- and four-digit ICD-10 codes that still have enough granularity to be clinically relevant such as atrial fibrillation (I48), acute myocardial infarction (I21), or dilated cardiomyopathy (I42.0). Our pipeline uses a deep neural network known as a Bidirectional Gated Recurrent Unit Neural Network and was trained and tested with 5548 discharge letters and validated in 5089 discharge and procedural letters. As in clinical practice discharge letters may be labeled with more than one code, we assessed the single- and multilabel performance of main diagnoses and cardiovascular risk factors. We investigated using both the entire body of text and only the summary paragraph, supplemented by age and sex. Given the privacy-sensitive information included in discharge letters, we added a de-identification step. The performance was high, with F1 scores of 0.76-0.99 for three-character and 0.87-0.98 for four-character ICD-10 codes, and was best when using complete discharge letters. Adding variables age/sex did not affect results. For model interpretability, word coefficients were provided and qualitative assessment of classification was manually performed. Because of its high performance, this pipeline can be useful to decrease the administrative burden of classifying discharge diagnoses and may serve as a scaffold for reimbursement and research applications.",,pdf:https://www.nature.com/articles/s41746-021-00404-9.pdf; doi:https://doi.org/10.1038/s41746-021-00404-9; html:https://europepmc.org/articles/PMC7910461; pdf:https://europepmc.org/articles/PMC7910461?pdf=render 33941991,https://doi.org/10.1016/j.rse.2021.112339,"Multimodal deep learning from satellite and street-level imagery for measuring income, overcrowding, and environmental deprivation in urban areas.","Suel E, Bhatt S, Brauer M, Flaxman S, Ezzati M.",,Remote sensing of environment,2021,2021-05-01,Y,Segmentation; Satellite Images; Convolutional Neural Networks; Street-Level Images; Urban Measurements,,,"Data collected at large scale and low cost (e.g. satellite and street level imagery) have the potential to substantially improve resolution, spatial coverage, and temporal frequency of measurement of urban inequalities. Multiple types of data from different sources are often available for a given geographic area. Yet, most studies utilize a single type of input data when making measurements due to methodological difficulties in their joint use. We propose two deep learning-based methods for jointly utilizing satellite and street level imagery for measuring urban inequalities. We use London as a case study for three selected outputs, each measured in decile classes: income, overcrowding, and environmental deprivation. We compare the performances of our proposed multimodal models to corresponding unimodal ones using mean absolute error (MAE). First, satellite tiles are appended to street level imagery to enhance predictions at locations where street images are available leading to improvements in accuracy by 20, 10, and 9% in units of decile classes for income, overcrowding, and living environment. The second approach, novel to the best of our knowledge, uses a U-Net architecture to make predictions for all grid cells in a city at high spatial resolution (e.g. for 3 m × 3 m pixels in London in our experiments). It can utilize city wide availability of satellite images as well as more sparse information from street-level images where they are available leading to improvements in accuracy by 6, 10, and 11%. We also show examples of prediction maps from both approaches to visually highlight performance differences.",,doi:https://doi.org/10.1016/j.rse.2021.112339; doi:https://doi.org/10.1016/j.rse.2021.112339; html:https://europepmc.org/articles/PMC7985619; pdf:https://europepmc.org/articles/PMC7985619?pdf=render -35144751,https://doi.org/10.1016/j.jacc.2021.11.045,Echocardiographic Deformation Imaging for Early Detection of Genetic Cardiomyopathies: JACC Review Topic of the Week.,"Taha K, Kirkels FP, Teske AJ, Asselbergs FW, van Tintelen JP, Doevendans PA, Kutty S, Haugaa KH, Cramer MJ.",,Journal of the American College of Cardiology,2022,2022-02-01,N,Early Detection; Speckle Tracking; Family Screening; Deformation Imaging; Genetic Cardiomyopathy,,,"Clinical screening of the relatives of patients with genetic cardiomyopathies is challenging, as they often lack detectable cardiac abnormalities at presentation. Life-threatening adverse events can already occur in these early stages of disease, so sensitive tools to reveal the earliest signs of disease are needed. The utility of echocardiographic deformation imaging for early detection has been explored for this population in multiple studies but has not been broadly implemented in clinical practice. The authors discuss contemporary evidence on the utility of deformation imaging in relatives of patients with genetic cardiomyopathies. The available body of data shows that deformation imaging reveals early disease-specific abnormalities in dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic cardiomyopathy. Deformation imaging seems promising to enhance the screening and follow-up protocols in relatives, and the authors propose measures to accelerate its implementation in clinical care.",,doi:https://doi.org/10.1016/j.jacc.2021.11.045; doi:https://doi.org/10.1016/j.jacc.2021.11.045 33493433,https://doi.org/10.1016/s1470-2045(20)30743-9,"The impact of the COVID-19 pandemic on radiotherapy services in England, UK: a population-based study.","Spencer K, Jones CM, Girdler R, Roe C, Sharpe M, Lawton S, Miller L, Lewis P, Evans M, Sebag-Montefiore D, Roques T, Smittenaar R, Morris E.",,The Lancet. Oncology,2021,2021-01-22,Y,,,,"

Background

The indirect impact of the COVID-19 pandemic on cancer outcomes is of increasing concern. However, the extent to which key treatment modalities have been affected is unclear. We aimed to assess the impact of the pandemic on radiotherapy activity in England.

Methods

In this population-based study, data relating to all radiotherapy delivered for cancer in the English NHS, between Feb 4, 2019, and June 28, 2020, were extracted from the National Radiotherapy Dataset. Changes in mean weekly radiotherapy courses, attendances (reflecting fractions), and fractionation patterns following the start of the UK lockdown were compared with corresponding months in 2019 overall, for specific diagnoses, and across age groups. The significance of changes in radiotherapy activity during lockdown was examined using interrupted time-series (ITS) analysis.

Findings

In 2020, mean weekly radiotherapy courses fell by 19·9% in April, 6·2% in May, and 11·6% in June compared with corresponding months in 2019. A relatively greater fall was observed for attendances (29·1% in April, 31·4% in May, and 31·5% in June). These changes were significant on ITS analysis (p<0·0001). A greater reduction in treatment courses between 2019 and 2020 was seen for patients aged 70 years or older compared with those aged younger than 70 years (34·4% vs 7·3% in April). By diagnosis, the largest reduction from 2019 to 2020 in treatment courses was for prostate cancer (77·0% in April) and non-melanoma skin cancer (72·4% in April). Conversely, radiotherapy courses in April, 2020, compared with April, 2019, increased by 41·2% in oesophageal cancer, 64·2% in bladder cancer, and 36·3% in rectal cancer. Increased use of ultra-hypofractionated (26 Gy in five fractions) breast radiotherapy as a percentage of all courses (0·2% in April, 2019, to 60·6% in April, 2020; ITS p<0·0001) contributed to the substantial reduction in attendances.

Interpretation

Radiotherapy activity fell significantly, but use of hypofractionated regimens rapidly increased in the English NHS during the first peak of the COVID-19 pandemic. An increase in treatments for some cancers suggests that radiotherapy compensated for reduced surgical activity. These data will assist health-care providers in understanding the indirect consequences of the pandemic and the role of radiotherapy services in minimising these consequences.

Funding

None.",,pdf:http://www.thelancet.com/article/S1470204520307439/pdf; doi:https://doi.org/10.1016/S1470-2045(20)30743-9; html:https://europepmc.org/articles/PMC7825861; pdf:https://europepmc.org/articles/PMC7825861?pdf=render +35144751,https://doi.org/10.1016/j.jacc.2021.11.045,Echocardiographic Deformation Imaging for Early Detection of Genetic Cardiomyopathies: JACC Review Topic of the Week.,"Taha K, Kirkels FP, Teske AJ, Asselbergs FW, van Tintelen JP, Doevendans PA, Kutty S, Haugaa KH, Cramer MJ.",,Journal of the American College of Cardiology,2022,2022-02-01,N,Early Detection; Speckle Tracking; Family Screening; Deformation Imaging; Genetic Cardiomyopathy,,,"Clinical screening of the relatives of patients with genetic cardiomyopathies is challenging, as they often lack detectable cardiac abnormalities at presentation. Life-threatening adverse events can already occur in these early stages of disease, so sensitive tools to reveal the earliest signs of disease are needed. The utility of echocardiographic deformation imaging for early detection has been explored for this population in multiple studies but has not been broadly implemented in clinical practice. The authors discuss contemporary evidence on the utility of deformation imaging in relatives of patients with genetic cardiomyopathies. The available body of data shows that deformation imaging reveals early disease-specific abnormalities in dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic cardiomyopathy. Deformation imaging seems promising to enhance the screening and follow-up protocols in relatives, and the authors propose measures to accelerate its implementation in clinical care.",,doi:https://doi.org/10.1016/j.jacc.2021.11.045; doi:https://doi.org/10.1016/j.jacc.2021.11.045 34468736,https://doi.org/10.1093/europace/euab162,Comparing clinical performance of current implantable cardioverter-defibrillator implantation recommendations in arrhythmogenic right ventricular cardiomyopathy.,"Bosman LP, Bosman LP, Nielsen Gerlach CL, Cadrin-Tourigny J, Orgeron G, Tichnell C, Murray B, Bourfiss M, van der Heijden JF, Yap SC, Zeppenfeld K, van den Berg MP, Wilde AAM, Asselbergs FW, Tandri H, Calkins H, van Tintelen JP, James CA, Te Riele ASJM.",,"Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology",2022,2022-02-01,Y,Prognosis; Risk stratification; Ventricular Arrhythmias; Implantable Cardioverter-defibrillator; Arrhythmogenic Right Ventricular Cardiomyopathy,,,"

Aims

Arrhythmogenic right ventricular cardiomyopathy (ARVC) patients have an increased risk of ventricular arrhythmias (VA). Four implantable cardioverter-defibrillator (ICD) recommendation algorithms are available The International Task Force Consensus ('ITFC'), an ITFC modification by Orgeron et al. ('mITFC'), the AHA/HRS/ACC guideline for VA management ('AHA'), and the HRS expert consensus statement ('HRS'). This study aims to validate and compare the performance of these algorithms in ARVC.

Methods and results

We classified 617 definite ARVC patients (38.5 ± 15.1 years, 52.4% male, 39.2% prior sustained VA) according to four algorithms. Clinical performance was evaluated by sensitivity, specificity, ROC-analysis, and decision curve analysis for any sustained VA and for fast VA (>250 b.p.m.). During 6.4 [2.8-11.5] years follow-up, 282 (45.7%) patients experienced any sustained VA, and 63 (10.2%) fast VA. For any sustained VA, ITFC and mITFC provide higher sensitivity than AHA and HRS (94.0-97.8% vs. 76.7-83.5%), but lower specificity (15.9-32.0% vs. 42.7%-60.1%). Similarly, for fast VA, ITFC and mITFC provide higher sensitivity than AHA and HRS (95.2-97.1% vs. 76.7-78.4%) but lower specificity (42.7-43.1 vs. 76.7-78.4%). Decision curve analysis showed ITFC and mITFC to be superior for a 5-year sustained VA risk ICD indication threshold between 5-25% or 2-9% for fast VA.

Conclusion

The ITFC and mITFC provide the highest protection rates, whereas AHA and HRS decrease unnecessary ICD placements. ITFC or mITFC should be used if we consider the 5-year threshold for ICD indication to lie within 5-25% for sustained VA or 2-9% for fast VA. These data will inform decision-making for ICD placement in ARVC.",,pdf:https://academic.oup.com/europace/article-pdf/24/2/296/42370389/euab162.pdf; doi:https://doi.org/10.1093/europace/euab162; html:https://europepmc.org/articles/PMC8824519; pdf:https://europepmc.org/articles/PMC8824519?pdf=render 33246414,https://doi.org/10.1186/s12874-020-01163-z,Patient-specific record linkage between emergency department and hospital admission data for a cohort of people who inject drugs: methodological considerations for frequent presenters.,"Di Rico R, Nambiar D, Gabbe B, Stoové M, Dietze P.",,BMC medical research methodology,2020,2020-11-27,Y,Methods; Australia; Data Linkage; Record Linkage; Administrative Data; People Who Inject Drugs; Patient Pathways; Frequent Presenters; Vaed; Vemd,,,"

Background

People who inject drugs (PWID) have been identified as frequent users of emergency department (ED) and hospital inpatient services. The specific challenges of record linkage in cohorts with numerous administrative health records occurring in close proximity are not well understood. Here, we present a method for patient-specific record linkage of ED and hospital admission data for a cohort of PWID.

Methods

Data from 688 PWID were linked to two state-wide administrative health databases identifying all ED visits and hospital admissions for the cohort between January 2008 and June 2013. We linked patient-specific ED and hospital admissions data, using administrative date-time timestamps and pre-specified linkage criteria, to identify hospital admissions stemming from ED presentations for a given individual. The ability of standalone databases to identify linked ED visits or hospital admissions was examined.

Results

There were 3459 ED visits and 1877 hospital admissions identified during the study period. Thirty-four percent of ED visits were linked to hospital admissions. Most links had hospital admission timestamps in-between or identical to their ED visit timestamps (n = 1035, 87%). Allowing 24-h between ED visits and hospital admissions captured more linked records, but increased manual inspection requirements. In linked records (n = 1190), the ED 'departure status' variable correctly reflected subsequent hospital admission in only 68% of cases. The hospital 'admission type' variable was non-specific in identifying if a preceding ED visit had occurred.

Conclusions

Linking ED visits with subsequent hospital admissions in PWID requires access to date and time variables for accurate temporal sorting, especially for same-day presentations. Selecting time-windows to capture linked records requires discretion. Researchers risk under-ascertainment of hospital admissions if using ED data alone.",,pdf:https://bmcmedresmethodol.biomedcentral.com/track/pdf/10.1186/s12874-020-01163-z; doi:https://doi.org/10.1186/s12874-020-01163-z; html:https://europepmc.org/articles/PMC7694355; pdf:https://europepmc.org/articles/PMC7694355?pdf=render 38686701,https://doi.org/10.1210/clinem/dgae119,"The association of cardiometabolic, diet and lifestyle parameters with plasma glucagon-like peptide-1: An IMI DIRECT study.","Eriksen R, White MC, Dawed AY, Perez IG, Posma JM, Haid M, Sharma S, Prehn C, Thomas LE, Koivula RW, Bizzotto R, Mari A, Giordano GN, Pavo I, Schwenk JM, De Masi F, Tsirigos KD, Brunak S, Viñuela A, Mahajan A, McDonald TJ, Kokkola T, Rutters F, Beulens J, Muilwijk M, Blom M, Elders P, Hansen TH, Fernandez-Tajes J, Jones A, Jennison C, Walker M, McCarthy MI, Pedersen O, Ruetten H, Forgie I, Holst JJ, Thomsen HS, Ridderstråle M, Bell JD, Adamski J, Franks PW, Hansen T, Holmes E, Frost G, Pearson ER.",,The Journal of clinical endocrinology and metabolism,2024,2024-04-30,N,,,,"

Context

The role of glucagon-like peptide-1(GLP-1) in Type 2 diabetes (T2D) and obesity is not fully understood.

Objective

We investigate the association of cardiometabolic, diet and lifestyle parameters on fasting and postprandial GLP-1 in people at risk of, or living with, T2D.

Method

We analysed cross-sectional data from the two Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohorts, cohort 1(n=2127) individuals at risk of diabetes; cohort 2 (n=789) individuals with new-onset of T2D.

Results

Our multiple regression analysis reveals that fasting total GLP-1 is associated with an insulin resistant phenotype and observe a strong independent relationship with male sex, increased adiposity and liver fat particularly in the prediabetes population. In contrast, we showed that incremental GLP-1 decreases with worsening glycaemia, higher adiposity, liver fat, male sex and reduced insulin sensitivity in the prediabetes cohort. Higher fasting total GLP-1 was associated with a low intake of wholegrain, fruit and vegetables inpeople with prediabetes, and with a high intake of red meat and alcohol in people with diabetes.

Conclusion

These studies provide novel insights into the association between fasting and incremental GLP-1, metabolic traits of diabetes and obesity, and dietary intake and raise intriguing questions regarding the relevance of fasting GLP-1 in the pathophysiology T2D.",,doi:https://doi.org/10.1210/clinem/dgae119 @@ -1927,13 +1927,13 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 38135686,https://doi.org/10.1038/s41467-023-42320-4,Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses.,"Michael BD, Dunai C, Needham EJ, Tharmaratnam K, Williams R, Huang Y, Boardman SA, Clark JJ, Sharma P, Subramaniam K, Wood GK, Collie C, Digby R, Ren A, Norton E, Leibowitz M, Ebrahimi S, Fower A, Fox H, Tato E, Ellul MA, Sunderland G, Held M, Hetherington C, Egbe FN, Palmos A, Stirrups K, Grundmann A, Chiollaz AC, Sanchez JC, Stewart JP, Griffiths M, Solomon T, Breen G, Coles AJ, Kingston N, Bradley JR, Chinnery PF, Cavanagh J, Irani SR, Vincent A, Baillie JK, Openshaw PJ, Semple MG, ISARIC4C Investigators, COVID-CNS Consortium, Taams LS, Menon DK.",,Nature communications,2023,2023-12-22,Y,,,,"To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1-11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely.",,pdf:https://www.nature.com/articles/s41467-023-42320-4.pdf; doi:https://doi.org/10.1038/s41467-023-42320-4; html:https://europepmc.org/articles/PMC10746705; pdf:https://europepmc.org/articles/PMC10746705?pdf=render 37178708,https://doi.org/10.1016/s1470-2045(23)00156-0,Utility of polygenic risk scores in UK cancer screening: a modelling analysis.,"Huntley C, Torr B, Sud A, Rowlands CF, Way R, Snape K, Hanson H, Swanton C, Broggio J, Lucassen A, McCartney M, Houlston RS, Hingorani AD, Jones ME, Turnbull C.",,The Lancet. Oncology,2023,2023-05-10,N,,,,"

Background

It is proposed that, through restriction to individuals delineated as high risk, polygenic risk scores (PRSs) might enable more efficient targeting of existing cancer screening programmes and enable extension into new age ranges and disease types. To address this proposition, we present an overview of the performance of PRS tools (ie, models and sets of single nucleotide polymorphisms) alongside harms and benefits of PRS-stratified cancer screening for eight example cancers (breast, prostate, colorectal, pancreas, ovary, kidney, lung, and testicular cancer).

Methods

For this modelling analysis, we used age-stratified cancer incidences for the UK population from the National Cancer Registration Dataset (2016-18) and published estimates of the area under the receiver operating characteristic curve for current, future, and optimised PRS for each of the eight cancer types. For each of five PRS-defined high-risk quantiles (ie, the top 50%, 20%, 10%, 5%, and 1%) and according to each of the three PRS tools (ie, current, future, and optimised) for the eight cancers, we calculated the relative proportion of cancers arising, the odds ratios of a cancer arising compared with the UK population average, and the lifetime cancer risk. We examined maximal attainable rates of cancer detection by age stratum from combining PRS-based stratification with cancer screening tools and modelled the maximal impact on cancer-specific survival of hypothetical new UK programmes of PRS-stratified screening.

Findings

The PRS-defined high-risk quintile (20%) of the population was estimated to capture 37% of breast cancer cases, 46% of prostate cancer cases, 34% of colorectal cancer cases, 29% of pancreatic cancer cases, 26% of ovarian cancer cases, 22% of renal cancer cases, 26% of lung cancer cases, and 47% of testicular cancer cases. Extending UK screening programmes to a PRS-defined high-risk quintile including people aged 40-49 years for breast cancer, 50-59 years for colorectal cancer, and 60-69 years for prostate cancer has the potential to avert, respectively, a maximum of 102, 188, and 158 deaths annually. Unstratified screening of the full population aged 48-49 years for breast cancer, 58-59 years for colorectal cancer, and 68-69 years for prostate cancer would use equivalent resources and avert, respectively, an estimated maximum of 80, 155, and 95 deaths annually. These maximal modelled numbers will be substantially attenuated by incomplete population uptake of PRS profiling and cancer screening, interval cancers, non-European ancestry, and other factors.

Interpretation

Under favourable assumptions, our modelling suggests modest potential efficiency gain in cancer case detection and deaths averted for hypothetical new PRS-stratified screening programmes for breast, prostate, and colorectal cancer. Restriction of screening to high-risk quantiles means many or most incident cancers will arise in those assigned as being low-risk. To quantify real-world clinical impact, costs, and harms, UK-specific cluster-randomised trials are required.

Funding

The Wellcome Trust.",,pdf:http://www.thelancet.com/article/S1470204523001560/pdf; doi:https://doi.org/10.1016/S1470-2045(23)00156-0 32150548,https://doi.org/10.1371/journal.pgen.1008605,The influence of rare variants in circulating metabolic biomarkers.,"Riveros-Mckay F, Oliver-Williams C, Karthikeyan S, Walter K, Kundu K, Ouwehand WH, Roberts D, Di Angelantonio E, Soranzo N, Danesh J, INTERVAL Study, Wheeler E, Zeggini E, Butterworth AS, Barroso I.",,PLoS genetics,2020,2020-03-09,Y,,Understanding the Causes of Disease,cardiovascular,"Circulating metabolite levels are biomarkers for cardiovascular disease (CVD). Here we studied, association of rare variants and 226 serum lipoproteins, lipids and amino acids in 7,142 (discovery plus follow-up) healthy participants. We leveraged the information from multiple metabolite measurements on the same participants to improve discovery in rare variant association analyses for gene-based and gene-set tests by incorporating correlated metabolites as covariates in the validation stage. Gene-based analysis corrected for the effective number of tests performed, confirmed established associations at APOB, APOC3, PAH, HAL and PCSK (p<1.32x10-7) and identified novel gene-trait associations at a lower stringency threshold with ACSL1, MYCN, FBXO36 and B4GALNT3 (p<2.5x10-6). Regulation of the pyruvate dehydrogenase (PDH) complex was associated for the first time, in gene-set analyses also corrected for effective number of tests, with IDL and LDL parameters, as well as circulating cholesterol (pMETASKAT<2.41x10-6). In conclusion, using an approach that leverages metabolite measurements obtained in the same participants, we identified novel loci and pathways involved in the regulation of these important metabolic biomarkers. As large-scale biobanks continue to amass sequencing and phenotypic information, analytical approaches such as ours will be useful to fully exploit the copious amounts of biological data generated in these efforts.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1008605&type=printable; doi:https://doi.org/10.1371/journal.pgen.1008605; html:https://europepmc.org/articles/PMC7108731; pdf:https://europepmc.org/articles/PMC7108731?pdf=render -37075078,https://doi.org/10.1371/journal.pmed.1004223,The association between antihypertensive treatment and serious adverse events by age and frailty: A cohort study.,"Sheppard JP, Koshiaris C, Stevens R, Lay-Flurrie S, Banerjee A, Bellows BK, Clegg A, Hobbs FDR, Payne RA, Swain S, Usher-Smith JA, McManus RJ.",,PLoS medicine,2023,2023-04-19,Y,,,,"

Background

Antihypertensives are effective at reducing the risk of cardiovascular disease, but limited data exist quantifying their association with serious adverse events, particularly in older people with frailty. This study aimed to examine this association using nationally representative electronic health record data.

Methods and findings

This was a retrospective cohort study utilising linked data from 1,256 general practices across England held within the Clinical Practice Research Datalink between 1998 and 2018. Included patients were aged 40+ years, with a systolic blood pressure reading between 130 and 179 mm Hg, and not previously prescribed antihypertensive treatment. The main exposure was defined as a first prescription of antihypertensive treatment. The primary outcome was hospitalisation or death within 10 years from falls. Secondary outcomes were hypotension, syncope, fractures, acute kidney injury, electrolyte abnormalities, and primary care attendance with gout. The association between treatment and these serious adverse events was examined by Cox regression adjusted for propensity score. This propensity score was generated from a multivariable logistic regression model with patient characteristics, medical history and medication prescriptions as covariates, and new antihypertensive treatment as the outcome. Subgroup analyses were undertaken by age and frailty. Of 3,834,056 patients followed for a median of 7.1 years, 484,187 (12.6%) were prescribed new antihypertensive treatment in the 12 months before the index date (baseline). Antihypertensives were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.23, 95% confidence interval (CI) 1.21 to 1.26), hypotension (aHR 1.32, 95% CI 1.29 to 1.35), syncope (aHR 1.20, 95% CI 1.17 to 1.22), acute kidney injury (aHR 1.44, 95% CI 1.41 to 1.47), electrolyte abnormalities (aHR 1.45, 95% CI 1.43 to 1.48), and primary care attendance with gout (aHR 1.35, 95% CI 1.32 to 1.37). The absolute risk of serious adverse events with treatment was very low, with 6 fall events per 10,000 patients treated per year. In older patients (80 to 89 years) and those with severe frailty, this absolute risk was increased, with 61 and 84 fall events per 10,000 patients treated per year (respectively). Findings were consistent in sensitivity analyses using different approaches to address confounding and taking into account the competing risk of death. A strength of this analysis is that it provides evidence regarding the association between antihypertensive treatment and serious adverse events, in a population of patients more representative than those enrolled in previous randomised controlled trials. Although treatment effect estimates fell within the 95% CIs of those from such trials, these analyses were observational in nature and so bias from unmeasured confounding cannot be ruled out.

Conclusions

Antihypertensive treatment was associated with serious adverse events. Overall, the absolute risk of this harm was low, with the exception of older patients and those with moderate to severe frailty, where the risks were similar to the likelihood of benefit from treatment. In these populations, physicians may want to consider alternative approaches to management of blood pressure and refrain from prescribing new treatment.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004223&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004223; html:https://europepmc.org/articles/PMC10155987; pdf:https://europepmc.org/articles/PMC10155987?pdf=render 31699727,https://doi.org/10.1136/bmjopen-2019-030882,Optical coherence tomography (OCT) in unconscious and systemically unwell patients using a mobile OCT device: a pilot study.,"Liu X, Kale AU, Capewell N, Talbot N, Ahmed S, Keane PA, Mollan S, Belli A, Blanch RJ, Veenith T, Denniston AK.",,BMJ open,2019,2019-11-07,Y,optical coherence tomography; Optical Coherence Tomography Angiography; Adult Intensive & Critical Care,,,"

Objective

This study aims to evaluate the feasibility of retinal imaging in critical care using a novel mobile optical coherence tomography (OCT) device. The Heidelberg SPECTRALIS FLEX module (Heidelberg Engineering, Heidelberg, Germany) is an OCT unit with a boom arm, enabling ocular OCT assessment in less mobile patients.

Design

We undertook an evaluation of the feasibility of using the SPECTRALIS FLEX for undertaking ocular OCT images in unconscious and critically ill patients.

Setting

This study was conducted in the critical care unit of a large tertiary referral unit in the United Kingdom.

Participants

13 systemically unwell patients admitted to the critical care unit were purposively sampled to enable evaluation in patients with a range of clinical states.

Outcome measures

The primary outcome was the feasibility of acquiring clinically interpretable OCT scans on a consecutive series of patients. The standardised scanning protocol included macula-focused OCT, OCT optic nerve head (ONH), OCT angiography (OCTA) of the macula and ONH OCTA.

Results

OCT images from 13 patients were attempted. The success rates of each scan type are 84% for OCT macula, 76% for OCT ONH, 56% for OCTA macula and 36% for OCTA ONH. The overall mean success rate of scans per patient was 64% (95% CI 46% to 81%). Clinicians reported clinical value in 100% scans which were successfully obtained, including both ruling in and ruling out relevant ocular complications such as corneal thinning, macular oedema and optic disc swelling. The most common causes of failure to achieve clinically interpretable scans were inadequately sustained OCT alignment in delirious patients and a compromised ocular surface due to corneal exposure.

Conclusions

This prospective evaluation indicates the feasibility and potential clinical value of the SPECTRALIS FLEX OCT system on the critical care unit. Portable OCT systems have the potential to bring instrument-based ophthalmic assessment to critically ill patients, enabling detection and micron-level monitoring of ocular complications.",,pdf:https://bmjopen.bmj.com/content/bmjopen/9/11/e030882.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-030882; html:https://europepmc.org/articles/PMC6858135; pdf:https://europepmc.org/articles/PMC6858135?pdf=render +37075078,https://doi.org/10.1371/journal.pmed.1004223,The association between antihypertensive treatment and serious adverse events by age and frailty: A cohort study.,"Sheppard JP, Koshiaris C, Stevens R, Lay-Flurrie S, Banerjee A, Bellows BK, Clegg A, Hobbs FDR, Payne RA, Swain S, Usher-Smith JA, McManus RJ.",,PLoS medicine,2023,2023-04-19,Y,,,,"

Background

Antihypertensives are effective at reducing the risk of cardiovascular disease, but limited data exist quantifying their association with serious adverse events, particularly in older people with frailty. This study aimed to examine this association using nationally representative electronic health record data.

Methods and findings

This was a retrospective cohort study utilising linked data from 1,256 general practices across England held within the Clinical Practice Research Datalink between 1998 and 2018. Included patients were aged 40+ years, with a systolic blood pressure reading between 130 and 179 mm Hg, and not previously prescribed antihypertensive treatment. The main exposure was defined as a first prescription of antihypertensive treatment. The primary outcome was hospitalisation or death within 10 years from falls. Secondary outcomes were hypotension, syncope, fractures, acute kidney injury, electrolyte abnormalities, and primary care attendance with gout. The association between treatment and these serious adverse events was examined by Cox regression adjusted for propensity score. This propensity score was generated from a multivariable logistic regression model with patient characteristics, medical history and medication prescriptions as covariates, and new antihypertensive treatment as the outcome. Subgroup analyses were undertaken by age and frailty. Of 3,834,056 patients followed for a median of 7.1 years, 484,187 (12.6%) were prescribed new antihypertensive treatment in the 12 months before the index date (baseline). Antihypertensives were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.23, 95% confidence interval (CI) 1.21 to 1.26), hypotension (aHR 1.32, 95% CI 1.29 to 1.35), syncope (aHR 1.20, 95% CI 1.17 to 1.22), acute kidney injury (aHR 1.44, 95% CI 1.41 to 1.47), electrolyte abnormalities (aHR 1.45, 95% CI 1.43 to 1.48), and primary care attendance with gout (aHR 1.35, 95% CI 1.32 to 1.37). The absolute risk of serious adverse events with treatment was very low, with 6 fall events per 10,000 patients treated per year. In older patients (80 to 89 years) and those with severe frailty, this absolute risk was increased, with 61 and 84 fall events per 10,000 patients treated per year (respectively). Findings were consistent in sensitivity analyses using different approaches to address confounding and taking into account the competing risk of death. A strength of this analysis is that it provides evidence regarding the association between antihypertensive treatment and serious adverse events, in a population of patients more representative than those enrolled in previous randomised controlled trials. Although treatment effect estimates fell within the 95% CIs of those from such trials, these analyses were observational in nature and so bias from unmeasured confounding cannot be ruled out.

Conclusions

Antihypertensive treatment was associated with serious adverse events. Overall, the absolute risk of this harm was low, with the exception of older patients and those with moderate to severe frailty, where the risks were similar to the likelihood of benefit from treatment. In these populations, physicians may want to consider alternative approaches to management of blood pressure and refrain from prescribing new treatment.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004223&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004223; html:https://europepmc.org/articles/PMC10155987; pdf:https://europepmc.org/articles/PMC10155987?pdf=render 29966429,https://doi.org/10.1177/2047487318785228,"Clinically recorded heart rate and incidence of 12 coronary, cardiac, cerebrovascular and peripheral arterial diseases in 233,970 men and women: A linked electronic health record study.","Archangelidi O, Pujades-Rodriguez M, Timmis A, Jouven X, Denaxas S, Hemingway H.",,European journal of preventive cardiology,2018,2018-07-02,N,Heart rate; Sudden death; Heart Failure; cardiovascular; Linked Electronic Health Records,,,"Background In healthy population cohorts, resting heart rate above 90 bpm is associated with mortality from coronary heart disease, but it is not clear whether associations are present at lower heart rates or whether these associations differ between women. Methods The CALIBER resource of linked electronic health records from primary care, hospitalisations, myocardial infarction registry and cause-specific mortality in the UK was used to assess associations between resting heart rate and 12 fatal and non-fatal coronary, cardiac, cerebral and peripheral vascular cardiovascular diseases and death using Cox proportional hazard models. Results Among 233,970 patients, 29,690 fatal and non-fatal events occurred. Fully adjusted models showed that resting heart rate was not associated in men or women with cerebrovascular events. In men a resting heart rate of 70-79 bpm (29.1% of all men) versus less than 60 bpm was associated with an increased risk of heart failure (hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.26-2.16), unheralded coronary death (HR 1.65, 95% CI 1.13-2.41), total cardiovascular events (HR 1.22, 95% CI 1.15-1.28) and all-cause mortality (HR 1.39, 95% CI 1.22-1.58). Women with a higher resting heart rate level of 80-89 bpm versus 60 bpm had a higher risk of total cardiovascular disease events (HR 1.17, 95% CI 1.07-1.24) and all-cause mortality (HR 1.21, 95% CI 1.07-1.35) compared to a resting heart rate less than 60 bpm. The risk was also present at higher heart rates (>90 bpm) for heart failure and sudden cardiac death. Conclusions A resting heart rate that clinicians currently consider as 'normal' in the general population is specifically associated with the incidence of certain major cardiovascular diseases and death, with the risk starting at lower resting heart rate levels in men compared to women. Further research is required to evaluate whether interventions to lower resting heart rate are warranted to prevent disease. The study is registered at: clinicaltrials.gov (ID: NCT01947361).",,pdf:http://eprints.whiterose.ac.uk/134568/7/OArchangelidi_EJPC_accepted.pdf; doi:https://doi.org/10.1177/2047487318785228 34563860,https://doi.org/10.1016/j.media.2021.102228,Shape registration with learned deformations for 3D shape reconstruction from sparse and incomplete point clouds.,"Chen X, Ravikumar N, Xia Y, Attar R, Diaz-Pinto A, Piechnik SK, Neubauer S, Petersen SE, Frangi AF.",,Medical image analysis,2021,2021-09-09,N,Deep Learning; Graph Convolutional Network; Cardiac Mesh Reconstruction; Cardiac Surface Reconstruction; Contours To Mesh Reconstruction,,,"Shape reconstruction from sparse point clouds/images is a challenging and relevant task required for a variety of applications in computer vision and medical image analysis (e.g. surgical navigation, cardiac motion analysis, augmented/virtual reality systems). A subset of such methods, viz. 3D shape reconstruction from 2D contours, is especially relevant for computer-aided diagnosis and intervention applications involving meshes derived from multiple 2D image slices, views or projections. We propose a deep learning architecture, coined Mesh Reconstruction Network (MR-Net), which tackles this problem. MR-Net enables accurate 3D mesh reconstruction in real-time despite missing data and with sparse annotations. Using 3D cardiac shape reconstruction from 2D contours defined on short-axis cardiac magnetic resonance image slices as an exemplar, we demonstrate that our approach consistently outperforms state-of-the-art techniques for shape reconstruction from unstructured point clouds. Our approach can reconstruct 3D cardiac meshes to within 2.5-mm point-to-point error, concerning the ground-truth data (the original image spatial resolution is ∼1.8×1.8×10mm3). We further evaluate the robustness of the proposed approach to incomplete data, and contours estimated using an automatic segmentation algorithm. MR-Net is generic and could reconstruct shapes of other organs, making it compelling as a tool for various applications in medical image analysis.",,doi:https://doi.org/10.1016/j.media.2021.102228; doi:https://doi.org/10.1016/j.media.2021.102228 32564639,https://doi.org/10.1177/0300060520931298,Mortality statistics in England and Wales: the SARS-CoV-2 paradox.,"Harrison G, Newport D, Robbins T, Arvanitis TN, Stein A.",,The Journal of international medical research,2020,2020-06-01,Y,Respiratory disease; United Kingdom; Mortality Rate; Paradox; Covid-19; Sars-cov-2,,,"

Objective

To analyse mortality statistics in the United Kingdom during the initial phases of the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic and to understand the impact of the pandemic on national mortality.

Methods

Retrospective review of weekly national mortality statistics in the United Kingdom over the past 5 years, including subgroup analysis of respiratory mortality rates.

Results

During the early phases of the SARS-CoV-2 pandemic in the first months of 2020, there were consistently fewer deaths per week compared with the preceding 5 years. This pattern was not observed at any other time within the past 5 years. We have termed this phenomenon the ""SARS-CoV-2 paradox."" We postulate potential explanations for this seeming paradox and explore the implications of these data.

Conclusions

Paradoxically, but potentially importantly, lower rather than higher weekly mortality rates were observed during the early stages of the SARS-CoV-2 pandemic. This paradox may have implications for current and future healthcare utilisation. A rebound increase in non-SARS-CoV-2 mortality later this year might coincide with the peak of SARS-CoV-2 admissions and mortality.",,doi:https://doi.org/10.1177/0300060520931298; doi:https://doi.org/10.1177/0300060520931298; html:https://europepmc.org/articles/PMC7307394; pdf:https://europepmc.org/articles/PMC7307394?pdf=render -38388497,https://doi.org/10.1038/s41467-024-45355-3,Concordance of randomised controlled trials for artificial intelligence interventions with the CONSORT-AI reporting guidelines.,"Martindale APL, Ng B, Ngai V, Kale AU, Ferrante di Ruffano L, Golub RM, Collins GS, Moher D, McCradden MD, Oakden-Rayner L, Rivera SC, Calvert M, Kelly CJ, Lee CS, Yau C, Chan AW, Keane PA, Beam AL, Denniston AK, Liu X.",,Nature communications,2024,2024-02-22,Y,,,,"The Consolidated Standards of Reporting Trials extension for Artificial Intelligence interventions (CONSORT-AI) was published in September 2020. Since its publication, several randomised controlled trials (RCTs) of AI interventions have been published but their completeness and transparency of reporting is unknown. This systematic review assesses the completeness of reporting of AI RCTs following publication of CONSORT-AI and provides a comprehensive summary of RCTs published in recent years. 65 RCTs were identified, mostly conducted in China (37%) and USA (18%). Median concordance with CONSORT-AI reporting was 90% (IQR 77-94%), although only 10 RCTs explicitly reported its use. Several items were consistently under-reported, including algorithm version, accessibility of the AI intervention or code, and references to a study protocol. Only 3 of 52 included journals explicitly endorsed or mandated CONSORT-AI. Despite a generally high concordance amongst recent AI RCTs, some AI-specific considerations remain systematically poorly reported. Further encouragement of CONSORT-AI adoption by journals and funders may enable more complete adoption of the full CONSORT-AI guidelines.",,pdf:https://www.nature.com/articles/s41467-024-45355-3.pdf; doi:https://doi.org/10.1038/s41467-024-45355-3; html:https://europepmc.org/articles/PMC10883966; pdf:https://europepmc.org/articles/PMC10883966?pdf=render 33414548,https://doi.org/10.1038/s41588-020-00751-5,A cross-platform approach identifies genetic regulators of human metabolism and health.,"Lotta LA, Pietzner M, Stewart ID, Wittemans LBL, Li C, Bonelli R, Raffler J, Biggs EK, Oliver-Williams C, Auyeung VPW, Luan J, Wheeler E, Paige E, Surendran P, Michelotti GA, Scott RA, Burgess S, Zuber V, Sanderson E, Koulman A, Imamura F, Forouhi NG, Khaw KT, MacTel Consortium, Griffin JL, Wood AM, Kastenmüller G, Danesh J, Butterworth AS, Gribble FM, Reimann F, Bahlo M, Fauman E, Wareham NJ, Langenberg C.",,Nature genetics,2021,2021-01-07,N,,,,"In cross-platform analyses of 174 metabolites, we identify 499 associations (P < 4.9 × 10-10) characterized by pleiotropy, allelic heterogeneity, large and nonlinear effects and enrichment for nonsynonymous variation. We identify a signal at GLP2R (p.Asp470Asn) shared among higher citrulline levels, body mass index, fasting glucose-dependent insulinotropic peptide and type 2 diabetes, with β-arrestin signaling as the underlying mechanism. Genetically higher serine levels are shown to reduce the likelihood (by 95%) and predict development of macular telangiectasia type 2, a rare degenerative retinal disease. Integration of genomic and small molecule data across platforms enables the discovery of regulators of human metabolism and translation into clinical insights.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612925; doi:https://doi.org/10.1038/s41588-020-00751-5; html:https://europepmc.org/articles/PMC7612925; pdf:https://europepmc.org/articles/PMC7612925?pdf=render; doi:https://doi.org/10.1038/s41588-020-00751-5 +38388497,https://doi.org/10.1038/s41467-024-45355-3,Concordance of randomised controlled trials for artificial intelligence interventions with the CONSORT-AI reporting guidelines.,"Martindale APL, Ng B, Ngai V, Kale AU, Ferrante di Ruffano L, Golub RM, Collins GS, Moher D, McCradden MD, Oakden-Rayner L, Rivera SC, Calvert M, Kelly CJ, Lee CS, Yau C, Chan AW, Keane PA, Beam AL, Denniston AK, Liu X.",,Nature communications,2024,2024-02-22,Y,,,,"The Consolidated Standards of Reporting Trials extension for Artificial Intelligence interventions (CONSORT-AI) was published in September 2020. Since its publication, several randomised controlled trials (RCTs) of AI interventions have been published but their completeness and transparency of reporting is unknown. This systematic review assesses the completeness of reporting of AI RCTs following publication of CONSORT-AI and provides a comprehensive summary of RCTs published in recent years. 65 RCTs were identified, mostly conducted in China (37%) and USA (18%). Median concordance with CONSORT-AI reporting was 90% (IQR 77-94%), although only 10 RCTs explicitly reported its use. Several items were consistently under-reported, including algorithm version, accessibility of the AI intervention or code, and references to a study protocol. Only 3 of 52 included journals explicitly endorsed or mandated CONSORT-AI. Despite a generally high concordance amongst recent AI RCTs, some AI-specific considerations remain systematically poorly reported. Further encouragement of CONSORT-AI adoption by journals and funders may enable more complete adoption of the full CONSORT-AI guidelines.",,pdf:https://www.nature.com/articles/s41467-024-45355-3.pdf; doi:https://doi.org/10.1038/s41467-024-45355-3; html:https://europepmc.org/articles/PMC10883966; pdf:https://europepmc.org/articles/PMC10883966?pdf=render 33391794,https://doi.org/10.1098/rsos.200958,"ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 gene expression, and plasma ACE2 levels: a Mendelian randomization study.","Gill D, Arvanitis M, Carter P, Hernández Cordero AI, Jo B, Karhunen V, Larsson SC, Li X, Lockhart SM, Mason A, Pashos E, Saha A, Tan VY, Zuber V, Bossé Y, Fahle S, Hao K, Jiang T, Joubert P, Lunt AC, Ouwehand WH, Roberts DJ, Timens W, van den Berge M, Watkins NA, Battle A, Butterworth AS, Danesh J, Di Angelantonio E, Engelhardt BE, Peters JE, Sin DD, Burgess S.",,Royal Society open science,2020,2020-11-18,Y,Genetic epidemiology; Angiotensin-converting enzyme inhibitors; Mendelian Randomization; Covid-19,,,"Angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 have been implicated in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). The expression of ACE2 and TMPRSS2 in the lung epithelium might have implications for the risk of SARS-CoV-2 infection and severity of COVID-19. We use human genetic variants that proxy angiotensin-converting enzyme (ACE) inhibitor drug effects and cardiovascular risk factors to investigate whether these exposures affect lung ACE2 and TMPRSS2 gene expression and circulating ACE2 levels. We observed no consistent evidence of an association of genetically predicted serum ACE levels with any of our outcomes. There was weak evidence for an association of genetically predicted serum ACE levels with ACE2 gene expression in the Lung eQTL Consortium (p = 0.014), but this finding did not replicate. There was evidence of a positive association of genetic liability to type 2 diabetes mellitus with lung ACE2 gene expression in the Gene-Tissue Expression (GTEx) study (p = 4 × 10-4) and with circulating plasma ACE2 levels in the INTERVAL study (p = 0.03), but not with lung ACE2 expression in the Lung eQTL Consortium study (p = 0.68). There were no associations of genetically proxied liability to the other cardiometabolic traits with any outcome. This study does not provide consistent evidence to support an effect of serum ACE levels (as a proxy for ACE inhibitors) or cardiometabolic risk factors on lung ACE2 and TMPRSS2 expression or plasma ACE2 levels.",,pdf:https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.200958; doi:https://doi.org/10.1098/rsos.200958; html:https://europepmc.org/articles/PMC7735342; pdf:https://europepmc.org/articles/PMC7735342?pdf=render 32040531,https://doi.org/10.1371/journal.pone.0228940,Risk assessment for hospital admission in patients with COPD; a multi-centre UK prospective observational study.,"Fermont JM, Bolton CE, Fisk M, Mohan D, Macnee W, Cockcroft JR, McEniery C, Fuld J, Cheriyan J, Tal-Singer R, Wilkinson IB, Wood AM, Polkey MI, Müllerova H.",,PloS one,2020,2020-02-10,Y,,Better Care,,"In chronic obstructive pulmonary disease (COPD), acute exacerbation of COPD requiring hospital admission is associated with mortality and healthcare costs. The ERICA study assessed multiple clinical measures in people with COPD, including the short physical performance battery (SPPB), a simple test of physical function with 3 components (gait speed, balance and sit-to-stand). We tested the hypothesis that SPPB score would relate to risk of hospital admissions and length of hospital stay. Data were analysed from 714 of the total 729 participants (434 men and 280 women) with COPD. Data from this prospective observational longitudinal study were obtained from 4 secondary and 1 tertiary centres from England, Scotland, and Wales. The main outcome measures were to estimate the risk of hospitalisation with acute exacerbation of COPD (AECOPD and length of hospital stay derived from hospital episode statistics (HES). In total, 291 of 714 individuals experienced 762 hospitalised AECOPD during five-year follow up. Poorer performance of SPPB was associated with both higher rate (IRR 1.08 per 1 point decrease, 95% CI 1.01 to 1.14) and increased length of stay (IRR 1.18 per 1 point decrease, 95% CI 1.10 to 1.27) for hospitalised AECOPD. For the individual sit-to-stand component of the SPPB, the association was even stronger (IRR 1.14, 95% CI 1.02 to 1.26 for rate and IRR 1.32, 95% CI 1.16 to 1.49 for length of stay for hospitalised AECOPD). The SPPB, and in particular the sit-to-stand component can both evaluate the risk of H-AECOPD and length of hospital stay in COPD. The SPPB can aid in clinical decision making and when prioritising healthcare resources.","This article looks at risk assessment for hospital admission in patients with Chronic Obstructive Pulmonary Disease (COPD), which is a group of lung conditions that make it difficult to empty air out of the lungs. The objective of the risk assessment was to eventually aid in clinical decision making and prioritising healthcare resources.",pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0228940&type=printable; doi:https://doi.org/10.1371/journal.pone.0228940; html:https://europepmc.org/articles/PMC7010290; pdf:https://europepmc.org/articles/PMC7010290?pdf=render 34459239,https://doi.org/10.1161/jaha.120.021115,Factor V Leiden and the Risk of Bleeding in Patients With Acute Coronary Syndromes Treated With Antiplatelet Therapy: Pooled Analysis of 3 Randomized Clinical Trials.,"Mahmoodi BK, Eriksson N, Ross S, Claassens DMF, Asselbergs FW, Meijer K, Siegbahn A, James S, Pare G, Wallentin L, Ten Berg JM.",,Journal of the American Heart Association,2021,2021-08-28,Y,Bleeding; acute coronary syndrome; Factor V Leiden; Antiplatelet Therapy,,,"Background Whether factor V Leiden is associated with lower bleeding risk in patients with acute coronary syndromes using (dual) antiplatelet therapy has yet to be investigated. Methods and Results We pooled data from 3 randomized clinical trials, conducted in patients with acute coronary syndromes, with adjudicated bleeding outcomes. Cox regression models were used to obtain overall and cause-specific hazard ratios (HRs) to account for competing risk of atherothrombotic outcomes (ie, composite of ischemic stroke, myocardial infarction, and cardiovascular death) in each study. Estimates from the individual studies were pooled using fixed effect meta-analysis. The 3 studies combined included 17 623 patients of whom 969 (5.5%) were either heterozygous or homozygous (n=23) carriers of factor V Leiden. During 1 year of follow-up, a total of 1289 (7.3%) patients developed major (n=559) or minor bleeding. Factor V Leiden was associated with a lower risk of combined major and minor bleeding (adjusted cause-specific HR, 0.75; 95% CI, 0.56-1.00; P=0.046; I2=0%) but a comparable risk of major bleeding (adjusted cause-specific HR, 0.93; 95% CI, 0.62-1.39; P=0.73; I2=0%). Adjusted pooled cause-specific HRs for the association of factor V Leiden with atherothrombotic events alone and in combination with bleeding events were 0.75 (95% CI, 0.55-1.02; P=0.06; I2=0%) and 0.75 (95% CI, 0.61-0.92; P=0.007; I2=0%), respectively. Conclusions Given that the lower risk of bleeding conferred by factor V Leiden was not counterbalanced by a higher risk of atherothrombotic events, these findings warrant future assessment for personalized medicine such as selecting patients for extended or intensive antiplatelet therapy.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.120.021115; doi:https://doi.org/10.1161/JAHA.120.021115; html:https://europepmc.org/articles/PMC8649290; pdf:https://europepmc.org/articles/PMC8649290?pdf=render @@ -1949,26 +1949,26 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 34870142,https://doi.org/10.1016/j.infpip.2021.100192,"Effectiveness of infection prevention and control interventions, excluding personal protective equipment, to prevent nosocomial transmission of SARS-CoV-2: a systematic review and call for action.","Jafari Y, Yin M, Lim C, Pople D, Evans S, Stimson J, Pham TM, LSHTM CMMID COVID-19 working group, Read JM, Robotham JV, Cooper BS, Knight GM.",,Infection prevention in practice,2022,2021-11-29,Y,,,,"Many infection prevention and control (IPC) interventions have been adopted by hospitals to limit nosocomial transmission of SARS-CoV-2. The aim of this systematic review is to identify evidence on the effectiveness of these interventions. We conducted a literature search of five databases (OVID MEDLINE, Embase, CENTRAL, COVID-19 Portfolio (pre-print), Web of Science). SWIFT ActiveScreener software was used to screen English titles and abstracts published between 1st January 2020 and 6th April 2021. Intervention studies, defined by Cochrane Effective Practice and Organisation of Care, that evaluated IPC interventions with an outcome of SARS-CoV-2 infection in either patients or healthcare workers were included. Personal protective equipment (PPE) was excluded as this intervention had been previously reviewed. Risks of bias were assessed using the Cochrane tool for randomised trials (RoB2) and non-randomized studies of interventions (ROBINS-I). From 23,156 screened articles, we identified seven articles that met the inclusion criteria, all of which evaluated interventions to prevent infections in healthcare workers and the majority of which were focused on effectiveness of prophylaxes. Due to heterogeneity in interventions, we did not conduct a meta-analysis. All agents used for prophylaxes have little to no evidence of effectiveness against SARS-CoV-2 infections. We did not find any studies evaluating the effectiveness of interventions including but not limited to screening, isolation and improved ventilation. There is limited evidence from interventional studies, excluding PPE, evaluating IPC measures for SARS-CoV-2. This review calls for urgent action to implement such studies to inform policies to protect our most vulnerable populations and healthcare workers.",,doi:https://doi.org/10.1016/j.infpip.2021.100192; doi:https://doi.org/10.1016/j.infpip.2021.100192; html:https://europepmc.org/articles/PMC8628369; pdf:https://europepmc.org/articles/PMC8628369?pdf=render 33713332,https://doi.org/10.1007/s40620-021-00996-1,End-stage kidney disease in patients with clinically manifest vascular disease; incidence and risk factors: results from the UCC-SMART cohort study.,"Østergaard HB, Westerink J, Verhaar MC, Bots ML, Asselbergs FW, de Borst GJ, Kappelle LJ, Visseren FLJ, van der Leeuw J, UCC-SMART studygroup.",,Journal of nephrology,2021,2021-03-13,Y,Cardiovascular disease; incidence; End-stage Kidney Disease; Modifiable Risk Factors,,,"

Background

Patients with cardiovascular disease (CVD) are at increased risk of end-stage kidney disease (ESKD). Insights into the incidence and role of modifiable risk factors for end-stage kidney disease may provide means for prevention in patients with cardiovascular disease.

Methods

We included 8402 patients with stable cardiovascular disease. Incidence rates (IRs) for end-stage kidney disease were determined stratified according to vascular disease location. Cox proportional hazard models were used to assess the risk of end-stage kidney disease for the different determinants.

Results

Sixty-five events were observed with a median follow-up of 8.6 years. The overall incidence rate of end-stage kidney disease was 0.9/1000 person-years. Patients with polyvascular disease had the highest incidence rate (1.8/1000 person-years). Smoking (Hazard ratio (HR) 1.87; 95% CI 1.10-3.19), type 2 diabetes (HR 1.81; 95% CI 1.05-3.14), higher systolic blood pressure (HR 1.37; 95% CI 1.24-1.52/10 mmHg), lower estimated glomerular filtration rate (eGFR) (HR 2.86; 95% CI 2.44-3.23/10 mL/min/1.73 m2) and higher urine albumin/creatinine ratio (uACR) (HR 1.19; 95% CI 1.15-1.23/10 mg/mmol) were independently associated with elevated risk of end-stage kidney disease. Body mass index (BMI), waist circumference, non-HDL-cholesterol and exercise were not independently associated with risk of end-stage kidney disease.

Conclusions

Incidence of end-stage kidney disease in patients with cardiovascular disease varies according to vascular disease location. Several modifiable risk factors for end-stage kidney disease were identified in patients with cardiovascular disease. These findings highlight the potential of risk factor management in patients with manifest cardiovascular disease.",,pdf:https://link.springer.com/content/pdf/10.1007/s40620-021-00996-1.pdf; doi:https://doi.org/10.1007/s40620-021-00996-1; html:https://europepmc.org/articles/PMC8494654; pdf:https://europepmc.org/articles/PMC8494654?pdf=render 34863512,https://doi.org/10.1016/j.bja.2021.10.038,Review of the requirements for effective mass casualty preparedness for trauma systems. A disaster waiting to happen?,"Gabbe BJ, Veitch W, Mather A, Curtis K, Holland AJA, Gomez D, Civil I, Nathens A, Fitzgerald M, Martin K, Teague WJ, Joseph A.",,British journal of anaesthesia,2022,2021-12-02,N,Disaster Preparedness; Mass Casualty Incidents; Trauma Systems; Narrative Review; Trauma Centres,,,"Mass casualty incidents (MCIs) are diverse, unpredictable, and increasing in frequency, but preparation is possible and necessary. The nature of MCIs requires a trauma response but also requires effective and tested disaster preparedness planning. From an international perspective, the aims of this narrative review are to describe the key components necessary for optimisation of trauma system preparedness for MCIs, whether trauma systems and centres meet these components and areas for improvement of trauma system response. Many of the principles necessary for response to MCIs are embedded in trauma system design and trauma centre function. These include robust communication networks, established triage systems, and capacity to secure centres from threats to safety and quality of care. However, evidence from the current literature indicates the need to strengthen trauma system preparedness for MCIs through greater trauma leader representation at all levels of disaster preparedness planning, enhanced training of staff and simulated disaster training, expanded surge capacity planning, improved staff management and support during the MCI and in the post-disaster recovery phase, clear provision for the treatment of paediatric patients in disaster plans, and diversified and pre-agreed systems for essential supplies and services continuity. Mass casualty preparedness is a complex, iterative process that requires an integrated, multidisciplinary, and tiered approach. Through effective preparedness planning, trauma systems should be well-placed to deliver an optimal response when faced with MCIs.",,doi:https://doi.org/10.1016/j.bja.2021.10.038; doi:https://doi.org/10.1016/j.bja.2021.10.038 -34648354,https://doi.org/10.1126/science.abj1541,Mapping the proteo-genomic convergence of human diseases.,"Pietzner M, Wheeler E, Carrasco-Zanini J, Cortes A, Koprulu M, Wörheide MA, Oerton E, Cook J, Stewart ID, Kerrison ND, Luan J, Raffler J, Arnold M, Arlt W, O'Rahilly S, Kastenmüller G, Gamazon ER, Hingorani AD, Scott RA, Wareham NJ, Langenberg C.",,"Science (New York, N.Y.)",2021,2021-11-12,N,,,,"Characterization of the genetic regulation of proteins is essential for understanding disease etiology and developing therapies. We identified 10,674 genetic associations for 3892 plasma proteins to create a cis-anchored gene-protein-disease map of 1859 connections that highlights strong cross-disease biological convergence. This proteo-genomic map provides a framework to connect etiologically related diseases, to provide biological context for new or emerging disorders, and to integrate different biological domains to establish mechanisms for known gene-disease links. Our results identify proteo-genomic connections within and between diseases and establish the value of cis-protein variants for annotation of likely causal disease genes at loci identified in genome-wide association studies, thereby addressing a major barrier to experimental validation and clinical translation of genetic discoveries.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9904207; doi:https://doi.org/10.1126/science.abj1541; html:https://europepmc.org/articles/PMC9904207; pdf:https://europepmc.org/articles/PMC9904207?pdf=render; doi:https://doi.org/10.1126/science.abj1541 31820220,https://doi.org/10.1007/s10926-019-09867-w,The Association Between Fault Attribution and Work Participation After Road Traffic Injury: A Registry-Based Observational Study.,"Lau G, Gabbe BJ, Collie A, Ponsford J, Ameratunga S, Cameron PA, Harrison JE, Giummarra MJ.",,Journal of occupational rehabilitation,2020,2020-06-01,N,Trauma; Injury; Recovery; Traffic; Accidents; Return To Work,,,"Purpose To characterise associations between fault attribution and work participation and capacity after road traffic injury. Methods People aged 15-65 years, working pre-injury, without serious brain injury, who survived to 12 months after road traffic injury were included from two Victorian trauma registries (n = 2942). Fault profiles from linked compensation claims were defined as no other at fault, another at fault, denied another at fault, claimed another at fault, and unknown. Claimant reports in the denied and claimed another at fault groups contradicted police reports. Patients reported work capacity (Glasgow outcome scale-extended) and return to work (RTW) at 6, 12 and 24 months post-injury (early and sustained RTW, delayed RTW (≥ 12 months), failed RTW attempts, no RTW attempts). Analyses adjusted for demographic, clinical and injury covariates. Results The risk of not returning to work was higher if another was at fault [adjusted relative risk ratio (aRRR) = 1.67, 95% confidence interval (CI) 1.29, 2.17] or was claimed to be at fault (aRRR = 1.58, 95% CI 1.04, 2.41), and lower for those who denied that another was at fault (aRRR = 0.51, 95% CI 0.29, 0.91), compared to cases with no other at fault. Similarly, people had higher odds of work capacity limitations if another was at fault (12m: AOR = 1.49, 95% CI 1.24, 1.80; 24m: 1.63, 95% CI 1.35, 1.97) or was claimed to be at fault (12m: AOR = 1.54, 95% CI 1.16, 2.05; 24m: AOR = 1.80, 95% CI 1.34, 2.41), and lower odds if they denied another was at fault (6m: AOR = 0.67, 95% CI 0.48, 0.95), compared to cases with no other at fault. Conclusion Targeted interventions are needed to support work participation in people at risk of poor RTW post-injury. While interventions targeting fault and justice-related attributions are currently lacking, these may be beneficial for people who believe that another caused their injury.",,doi:https://doi.org/10.1007/s10926-019-09867-w 31815634,https://doi.org/10.1186/s12933-019-0972-4,Metformin use and cardiovascular outcomes after acute myocardial infarction in patients with type 2 diabetes: a cohort study.,"Bromage DI, Godec TR, Pujades-Rodriguez M, Gonzalez-Izquierdo A, Denaxas S, Hemingway H, Yellon DM.",,Cardiovascular diabetology,2019,2019-12-09,Y,Acute myocardial infarction; Type 2 diabetes; Cohort studies; Metformin; cardioprotection; Outcomes,,,"

Background

The use of metformin after acute myocardial infarction (AMI) has been associated with reduced mortality in people with type 2 diabetes mellitus (T2DM). However, it is not known if it is acutely cardioprotective in patients taking metformin at the time of AMI. We compared patient outcomes according to metformin status at the time of admission for fatal and non-fatal AMI in a large cohort of patients in England.

Methods

This study used linked data from primary care, hospital admissions and death registry from 4.7 million inhabitants in England, as part of the CALIBER resource. The primary endpoint was a composite of acute myocardial infarction requiring hospitalisation, stroke and cardiovascular death. The secondary endpoints were heart failure (HF) hospitalisation and all-cause mortality.

Results

4,030 patients with T2DM and incident AMI recorded between January 1998 and October 2010 were included. At AMI admission, 63.9% of patients were receiving metformin and 36.1% another oral hypoglycaemic drug. Median follow-up was 343 (IQR: 1-1436) days. Adjusted analyses showed an increased hazard of the composite endpoint in metformin users compared to non-users (HR 1.09 [1.01-1.19]), but not of the secondary endpoints. The higher risk of the composite endpoint in metformin users was only observed in people taking metformin at AMI admission, whereas metformin use post-AMI was associated with a reduction in risk of all-cause mortality (0.76 [0.62-0.93], P = 0.009).

Conclusions

Our study suggests that metformin use at the time of first AMI is associated with increased risk of cardiovascular disease and death in patients with T2DM, while its use post-AMI might be beneficial. Further investigation in well-designed randomised controlled trials is indicated, especially in view of emerging evidence of cardioprotection from sodium-glucose co-transporter-2 (SGLT2) inhibitors.",,pdf:https://cardiab.biomedcentral.com/track/pdf/10.1186/s12933-019-0972-4; doi:https://doi.org/10.1186/s12933-019-0972-4; html:https://europepmc.org/articles/PMC6900858; pdf:https://europepmc.org/articles/PMC6900858?pdf=render -37060915,https://doi.org/10.1016/s0140-6736(23)00510-x,"Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial.","RECOVERY Collaborative Group. Electronic address: recoverytrial@ndph.ox.ac.uk, RECOVERY Collaborative Group.",,"Lancet (London, England)",2023,2023-04-13,Y,,,,"

Background

Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group.

Methods

This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation <92% on room air) were randomly allocated (1:1) to either usual care with higher dose corticosteroids (dexamethasone 20 mg once daily for 5 days followed by 10 mg dexamethasone once daily for 5 days or until discharge if sooner) or usual standard of care alone (which included dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality among all randomised participants. On May 11, 2022, the independent data monitoring committee recommended stopping recruitment of patients receiving no oxygen or simple oxygen only due to safety concerns. We report the results for these participants only. Recruitment of patients receiving ventilatory support is ongoing. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1·59 [95% CI 1·20-2·10]; p=0·0012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3·7% [95% CI 0·7-6·6]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7·4% [95% CI 3·2-11·5]).

Interpretation

In patients hospitalised for COVID-19 with clinical hypoxia who required either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared with usual care, which included low-dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation.

Funding

UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust.",,doi:https://doi.org/10.1016/s0140-6736(23)00510-x; doi:https://doi.org/10.1016/S0140-6736(23)00510-X; html:https://europepmc.org/articles/PMC10156147; pdf:https://europepmc.org/articles/PMC10156147?pdf=render +34648354,https://doi.org/10.1126/science.abj1541,Mapping the proteo-genomic convergence of human diseases.,"Pietzner M, Wheeler E, Carrasco-Zanini J, Cortes A, Koprulu M, Wörheide MA, Oerton E, Cook J, Stewart ID, Kerrison ND, Luan J, Raffler J, Arnold M, Arlt W, O'Rahilly S, Kastenmüller G, Gamazon ER, Hingorani AD, Scott RA, Wareham NJ, Langenberg C.",,"Science (New York, N.Y.)",2021,2021-11-12,N,,,,"Characterization of the genetic regulation of proteins is essential for understanding disease etiology and developing therapies. We identified 10,674 genetic associations for 3892 plasma proteins to create a cis-anchored gene-protein-disease map of 1859 connections that highlights strong cross-disease biological convergence. This proteo-genomic map provides a framework to connect etiologically related diseases, to provide biological context for new or emerging disorders, and to integrate different biological domains to establish mechanisms for known gene-disease links. Our results identify proteo-genomic connections within and between diseases and establish the value of cis-protein variants for annotation of likely causal disease genes at loci identified in genome-wide association studies, thereby addressing a major barrier to experimental validation and clinical translation of genetic discoveries.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9904207; doi:https://doi.org/10.1126/science.abj1541; html:https://europepmc.org/articles/PMC9904207; pdf:https://europepmc.org/articles/PMC9904207?pdf=render; doi:https://doi.org/10.1126/science.abj1541 37117689,https://doi.org/10.1038/s43016-021-00309-6,Author Correction: Nutriome-metabolome relationships provide insights into dietary intake and metabolism.,"Posma JM, Garcia-Perez I, Frost G, Aljuraiban GS, Chan Q, Van Horn L, Daviglus M, Stamler J, Holmes E, Elliott P, Nicholson JK.",,Nature food,2021,2021-07-01,N,,,,,,pdf:https://www.nature.com/articles/s43016-021-00309-6.pdf; doi:https://doi.org/10.1038/s43016-021-00309-6 +37060915,https://doi.org/10.1016/s0140-6736(23)00510-x,"Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial.","RECOVERY Collaborative Group. Electronic address: recoverytrial@ndph.ox.ac.uk, RECOVERY Collaborative Group.",,"Lancet (London, England)",2023,2023-04-13,Y,,,,"

Background

Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group.

Methods

This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation <92% on room air) were randomly allocated (1:1) to either usual care with higher dose corticosteroids (dexamethasone 20 mg once daily for 5 days followed by 10 mg dexamethasone once daily for 5 days or until discharge if sooner) or usual standard of care alone (which included dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality among all randomised participants. On May 11, 2022, the independent data monitoring committee recommended stopping recruitment of patients receiving no oxygen or simple oxygen only due to safety concerns. We report the results for these participants only. Recruitment of patients receiving ventilatory support is ongoing. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1·59 [95% CI 1·20-2·10]; p=0·0012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3·7% [95% CI 0·7-6·6]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7·4% [95% CI 3·2-11·5]).

Interpretation

In patients hospitalised for COVID-19 with clinical hypoxia who required either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared with usual care, which included low-dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation.

Funding

UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust.",,doi:https://doi.org/10.1016/s0140-6736(23)00510-x; doi:https://doi.org/10.1016/S0140-6736(23)00510-X; html:https://europepmc.org/articles/PMC10156147; pdf:https://europepmc.org/articles/PMC10156147?pdf=render 35907789,https://doi.org/10.1186/s12859-022-04838-0,fcfdr: an R package to leverage continuous and binary functional genomic data in GWAS.,"Hutchinson A, Liley J, Wallace C.",,BMC bioinformatics,2022,2022-07-30,Y,Functional genomics; Power; FDR; Gwas; Multiple Testing,,,"

Background

Genome-wide association studies (GWAS) are limited in power to detect associations that exceed the stringent genome-wide significance threshold. This limitation can be alleviated by leveraging relevant auxiliary data, such as functional genomic data. Frameworks utilising the conditional false discovery rate have been developed for this purpose, and have been shown to increase power for GWAS discovery whilst controlling the false discovery rate. However, the methods are currently only applicable for continuous auxiliary data and cannot be used to leverage auxiliary data with a binary representation, such as whether SNPs are synonymous or non-synonymous, or whether they reside in regions of the genome with specific activity states.

Results

We describe an extension to the cFDR framework for binary auxiliary data, called ""Binary cFDR"". We demonstrate FDR control of our method using detailed simulations, and show that Binary cFDR performs better than a comparator method in terms of sensitivity and FDR control. We introduce an all-encompassing user-oriented CRAN R package ( https://annahutch.github.io/fcfdr/ ; https://cran.r-project.org/web/packages/fcfdr/index.html ) and demonstrate its utility in an application to type 1 diabetes, where we identify additional genetic associations.

Conclusions

Our all-encompassing R package, fcfdr, serves as a comprehensive toolkit to unite GWAS and functional genomic data in order to increase statistical power to detect genetic associations.",,pdf:https://bmcbioinformatics.biomedcentral.com/counter/pdf/10.1186/s12859-022-04838-0; doi:https://doi.org/10.1186/s12859-022-04838-0; html:https://europepmc.org/articles/PMC9338519; pdf:https://europepmc.org/articles/PMC9338519?pdf=render 33062309,https://doi.org/10.1177/2059513120952336,Epidemiology of burn injury in older adults: An Australian and New Zealand perspective.,"Tracy LM, Singer Y, Schrale R, Gong J, Darton A, Wood F, Kurmis R, Edgar D, Cleland H, Gabbe BJ.",,"Scars, burns & healing",2020,2020-01-01,Y,Burns; Australia; New Zealand; Older Adults; scald; Burn Database,,,"

Introduction

The ageing global population presents a novel set of challenges for trauma systems. Less research has focused on the older adult population with burns and how they differ compared to younger patients. This study aimed to describe, and compare with younger peers, the number, causes and surgical management of older adults with burn injuries in Australia and New Zealand.

Methods

The Burns Registry of Australia and New Zealand was used to identify patients with burn injuries between 1 July 2009 and 31 December 2018. Temporal trends in incidence rates were evaluated and categorised by age at injury. Patient demographics, injury severity and event characteristics, surgical intervention and in-hospital outcomes were investigated.

Results

There were 2394 burn-injured older adults admitted during the study period, accounting for 13.4% of adult admissions. Scalds were the most common cause of burn injury in older adults. The incidence of older adult burns increased by 2.96% each year (incidence rate ratio = 1.030, 95% confidence interval = 1.013-1.046, P < 0.001). Compared to their younger peers, a smaller proportion of older adult patients were taken to theatre for a surgical procedure, though a larger proportion of older adults received a skin graft.

Discussion

Differences in patient and injury characteristics, surgical management and in-hospital outcomes were observed for older adults. These findings provide the Australian and New Zealand burn care community with a greater understanding of burn injury and their treatments in a unique group of patients who are at risk of poorer outcomes than younger people.

Lay summary

The number and proportion of older persons in every country of the world is growing. This may create challenges for healthcare systems. While burn injuries are a unique subset of trauma that affect individuals of all ages, less is known about burns in older adults and how they differ from younger patients.We wanted to look at the number, type, management, and outcomes of burns in older adults in Australia and New Zealand. To do this, we used data from the Burns Registry of Australia and New Zealand, or BRANZ. The BRANZ is a database that collects information on patients that present to Australian and New Zealand hospitals that have a specialist burns unit.Our research found that one in eight adult burns patients was over the age of 65, and that the rate of burn injuries in older adults has increased over the last decade. Older adult burns patients were most commonly affected by scalds after coming in contact with wet heat such as boiling liquids or steam. Fewer older adults went to theatre for an operation or surgical procedure compared to their younger counterparts. However, a larger proportion of older adults that went to theatre had a skin graft (where skin is removed from an uninjured part of the body and placed over the injured part).This research provides important information about a unique and growing group of patients to the local burn care community. It also highlights potential avenues for injury prevention initiatives.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/2059513120952336; doi:https://doi.org/10.1177/2059513120952336; html:https://europepmc.org/articles/PMC7534068; pdf:https://europepmc.org/articles/PMC7534068?pdf=render 34888366,https://doi.org/10.3389/fcvm.2021.768245,MOCOnet: Robust Motion Correction of Cardiovascular Magnetic Resonance T1 Mapping Using Convolutional Neural Networks.,"Gonzales RA, Zhang Q, Papież BW, Werys K, Lukaschuk E, Popescu IA, Burrage MK, Shanmuganathan M, Ferreira VM, Piechnik SK.",,Frontiers in cardiovascular medicine,2021,2021-11-23,Y,image registration; Cardiovascular Magnetic Resonance; T1 Mapping; Deep Learning; Shmolli,,,"Background: Quantitative cardiovascular magnetic resonance (CMR) T1 mapping has shown promise for advanced tissue characterisation in routine clinical practise. However, T1 mapping is prone to motion artefacts, which affects its robustness and clinical interpretation. Current methods for motion correction on T1 mapping are model-driven with no guarantee on generalisability, limiting its widespread use. In contrast, emerging data-driven deep learning approaches have shown good performance in general image registration tasks. We propose MOCOnet, a convolutional neural network solution, for generalisable motion artefact correction in T1 maps. Methods: The network architecture employs U-Net for producing distance vector fields and utilises warping layers to apply deformation to the feature maps in a coarse-to-fine manner. Using the UK Biobank imaging dataset scanned at 1.5T, MOCOnet was trained on 1,536 mid-ventricular T1 maps (acquired using the ShMOLLI method) with motion artefacts, generated by a customised deformation procedure, and tested on a different set of 200 samples with a diverse range of motion. MOCOnet was compared to a well-validated baseline multi-modal image registration method. Motion reduction was visually assessed by 3 human experts, with motion scores ranging from 0% (strictly no motion) to 100% (very severe motion). Results: MOCOnet achieved fast image registration (<1 second per T1 map) and successfully suppressed a wide range of motion artefacts. MOCOnet significantly reduced motion scores from 37.1±21.5 to 13.3±10.5 (p < 0.001), whereas the baseline method reduced it to 15.8±15.6 (p < 0.001). MOCOnet was significantly better than the baseline method in suppressing motion artefacts and more consistently (p = 0.007). Conclusion: MOCOnet demonstrated significantly better motion correction performance compared to a traditional image registration approach. Salvaging data affected by motion with robustness and in a time-efficient manner may enable better image quality and reliable images for immediate clinical interpretation.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.768245/pdf; doi:https://doi.org/10.3389/fcvm.2021.768245; html:https://europepmc.org/articles/PMC8649951; pdf:https://europepmc.org/articles/PMC8649951?pdf=render -38613554,https://doi.org/10.1016/j.jcmg.2024.01.009,Cardiovascular Magnetic Resonance Reference Ranges From the Healthy Hearts Consortium.,"Raisi-Estabragh Z, Szabo L, McCracken C, Bülow R, Aquaro GD, Andre F, Le TT, Suchá D, Condurache DG, Salih AM, Chadalavada S, Aung N, Lee AM, Harvey NC, Leiner T, Chin CWL, Friedrich MG, Barison A, Dörr M, Petersen SE.",,JACC. Cardiovascular imaging,2024,2024-03-26,N,Artificial intelligence; Automated analysis; Sex differences; Ethnicity; Cardiovascular Magnetic Resonance; Healthy Reference Ranges,,,"

Background

The absence of population-stratified cardiovascular magnetic resonance (CMR) reference ranges from large cohorts is a major shortcoming for clinical care.

Objectives

This paper provides age-, sex-, and ethnicity-specific CMR reference ranges for atrial and ventricular metrics from the Healthy Hearts Consortium, an international collaborative comprising 9,088 CMR studies from verified healthy individuals, covering the complete adult age spectrum across both sexes, and with the highest ethnic diversity reported to date.

Methods

CMR studies were analyzed using certified software with batch processing capability (cvi42, version 5.14 prototype, Circle Cardiovascular Imaging) by 2 expert readers. Three segmentation methods (smooth, papillary, anatomic) were used to contour the endocardial and epicardial borders of the ventricles and atria from long- and short-axis cine series. Clinically established ventricular and atrial metrics were extracted and stratified by age, sex, and ethnicity. Variations by segmentation method, scanner vendor, and magnet strength were examined. Reference ranges are reported as 95% prediction intervals.

Results

The sample included 4,452 (49.0%) men and 4,636 (51.0%) women with average age of 61.1 ± 12.9 years (range: 18-83 years). Among these, 7,424 (81.7%) were from White, 510 (5.6%) South Asian, 478 (5.3%) mixed/other, 341 (3.7%) Black, and 335 (3.7%) Chinese ethnicities. Images were acquired using 1.5-T (n = 8,779; 96.6%) and 3.0-T (n = 309; 3.4%) scanners from Siemens (n = 8,299; 91.3%), Philips (n = 498; 5.5%), and GE (n = 291, 3.2%).

Conclusions

This work represents a resource with healthy CMR-derived volumetric reference ranges ready for clinical implementation.",,doi:https://doi.org/10.1016/j.jcmg.2024.01.009 31564467,https://doi.org/10.1016/s2215-0366(19)30369-4,"The burden of mental ill health associated with childhood maltreatment in the UK, using The Health Improvement Network database: a population-based retrospective cohort study.","Chandan JS, Thomas T, Gokhale KM, Bandyopadhyay S, Taylor J, Nirantharakumar K.",,The lancet. Psychiatry,2019,2019-09-26,N,,,,"

Background

Childhood maltreatment is a global public health, human rights, and moral issue that is associated with a substantial mental health burden. We aimed to assess the association between childhood maltreatment and the development of mental ill health and the initiation of new prescriptions for mental ill health.

Methods

In this population-based, retrospective, open cohort study, we used a dataset from individuals in The Health Improvement Network (THIN) database. THIN database comprises UK electronic medical records taken from 787 general practices throughout the UK. We used read codes in these records to identify exposed patients (those with a read code identifying officially confirmed childhood maltreatment or a maltreatment-related concern) and up to two unexposed patients (those without such read codes) from the same general practice, who were matched by age and sex. We evaluated the risk of developing depression, anxiety, or serious mental illness (a composite mental ill health outcome) or initiation of a prescription drug used to treat mental ill health, and the odds ratio of these events at baseline, in the exposed versus unexposed patients.

Findings

The first possible date for cohort entry (the study start date) was Jan 1, 1995, and patients could enter the cohort until the study end date, Dec 31, 2018. During the study period, 11 831 850 patients were eligible to participate. Of these patients, we identified 217 758 (1·8%) patients with any recorded childhood maltreatment. These patients were matched to 423 410 unexposed control patients with no recorded exposure to childhood maltreatment. The exposed group were followed up for a median of 1·8 years (IQR 0·6-4·3) versus 3·2 years (1·3-6·1) in the unexposed group. During the study period, 11 665 (5·9%) new diagnoses of mental ill health were made in the exposed group, giving an incidence rate of 16·8 events per 1000 person-years versus 15 301 (3·7%) new recorded diagnoses at an incidence rate of 8·3 events per 1000 person-years in the unexposed cohort, giving an adjusted IRR of 2·14 (95% CI 2·08-2·19). 30 911 (14·8%) patients in the exposed group received a new prescription for any type of mental ill health (incidence rate 46·5 events per 1000 person-years) versus 36 390 (8·9%) patients in the unexposed group (20·5 per 1000 person-years) resulting in an adjusted IRR of 2·44 (95% CI 2·40-2·48).

Interpretation

Childhood maltreatment is thought to affect one in three children globally; therefore, a doubled risk of developing mental ill health among these individuals represents a substantial contribution to the mental ill health burden in the UK. It is imperative that public health approaches, including those aimed at preventing and detecting childhood maltreatment and its associated negative consequences, are implemented to prevent mental ill health.

Funding

None.",,pdf:http://pure-oai.bham.ac.uk/ws/files/77236664/Chandan_et_al_The_burden_of_mental_ill_health_associated_with_childhood_maltreatment_in_the_UK_using_The_Health_Improvement_Network_database_The_Lancet_Psychiatry_2019.pdf; doi:https://doi.org/10.1016/S2215-0366(19)30369-4 +38613554,https://doi.org/10.1016/j.jcmg.2024.01.009,Cardiovascular Magnetic Resonance Reference Ranges From the Healthy Hearts Consortium.,"Raisi-Estabragh Z, Szabo L, McCracken C, Bülow R, Aquaro GD, Andre F, Le TT, Suchá D, Condurache DG, Salih AM, Chadalavada S, Aung N, Lee AM, Harvey NC, Leiner T, Chin CWL, Friedrich MG, Barison A, Dörr M, Petersen SE.",,JACC. Cardiovascular imaging,2024,2024-03-26,N,Artificial intelligence; Automated analysis; Sex differences; Ethnicity; Cardiovascular Magnetic Resonance; Healthy Reference Ranges,,,"

Background

The absence of population-stratified cardiovascular magnetic resonance (CMR) reference ranges from large cohorts is a major shortcoming for clinical care.

Objectives

This paper provides age-, sex-, and ethnicity-specific CMR reference ranges for atrial and ventricular metrics from the Healthy Hearts Consortium, an international collaborative comprising 9,088 CMR studies from verified healthy individuals, covering the complete adult age spectrum across both sexes, and with the highest ethnic diversity reported to date.

Methods

CMR studies were analyzed using certified software with batch processing capability (cvi42, version 5.14 prototype, Circle Cardiovascular Imaging) by 2 expert readers. Three segmentation methods (smooth, papillary, anatomic) were used to contour the endocardial and epicardial borders of the ventricles and atria from long- and short-axis cine series. Clinically established ventricular and atrial metrics were extracted and stratified by age, sex, and ethnicity. Variations by segmentation method, scanner vendor, and magnet strength were examined. Reference ranges are reported as 95% prediction intervals.

Results

The sample included 4,452 (49.0%) men and 4,636 (51.0%) women with average age of 61.1 ± 12.9 years (range: 18-83 years). Among these, 7,424 (81.7%) were from White, 510 (5.6%) South Asian, 478 (5.3%) mixed/other, 341 (3.7%) Black, and 335 (3.7%) Chinese ethnicities. Images were acquired using 1.5-T (n = 8,779; 96.6%) and 3.0-T (n = 309; 3.4%) scanners from Siemens (n = 8,299; 91.3%), Philips (n = 498; 5.5%), and GE (n = 291, 3.2%).

Conclusions

This work represents a resource with healthy CMR-derived volumetric reference ranges ready for clinical implementation.",,doi:https://doi.org/10.1016/j.jcmg.2024.01.009 35247983,https://doi.org/10.1186/s12877-021-02673-1,"Age is the main determinant of COVID-19 related in-hospital mortality with minimal impact of pre-existing comorbidities, a retrospective cohort study.","Henkens MTHM, Raafs AG, Verdonschot JAJ, Linschoten M, van Smeden M, Wang P, van der Hooft BHM, Tieleman R, Janssen MLF, Ter Bekke RMA, Hazebroek MR, van der Horst ICC, Asselbergs FW, Magdelijns FJH, Heymans SRB, CAPACITY-COVID collaborative consortium.",,BMC geriatrics,2022,2022-03-05,Y,Mortality; Hospitalization; Netherlands; Mediation Analysis; Covid-19,,,"

Background

Age and comorbidities increase COVID-19 related in-hospital mortality risk, but the extent by which comorbidities mediate the impact of age remains unknown.

Methods

In this multicenter retrospective cohort study with data from 45 Dutch hospitals, 4806 proven COVID-19 patients hospitalized in Dutch hospitals (between February and July 2020) from the CAPACITY-COVID registry were included (age 69[58-77]years, 64% men). The primary outcome was defined as a combination of in-hospital mortality or discharge with palliative care. Logistic regression analysis was performed to analyze the associations between sex, age, and comorbidities with the primary outcome. The effect of comorbidities on the relation of age with the primary outcome was evaluated using mediation analysis.

Results

In-hospital COVID-19 related mortality occurred in 1108 (23%) patients, 836 (76%) were aged ≥70 years (70+). Both age 70+ and female sex were univariably associated with outcome (odds ratio [OR]4.68, 95%confidence interval [4.02-5.45], OR0.68[0.59-0.79], respectively;both p<  0.001). All comorbidities were univariably associated with outcome (p<0.001), and all but dyslipidemia remained significant after adjustment for age70+ and sex. The impact of comorbidities was attenuated after age-spline adjustment, only leaving female sex, diabetes mellitus (DM), chronic kidney disease (CKD), and chronic pulmonary obstructive disease (COPD) significantly associated (female OR0.65[0.55-0.75], DM OR1.47[1.26-1.72], CKD OR1.61[1.32-1.97], COPD OR1.30[1.07-1.59]). Pre-existing comorbidities in older patients negligibly (<6% in all comorbidities) mediated the association between higher age and outcome.

Conclusions

Age is the main determinant of COVID-19 related in-hospital mortality, with negligible mediation effect of pre-existing comorbidities.

Trial registration

CAPACITY-COVID ( NCT04325412 ).",,doi:https://doi.org/10.1186/s12877-021-02673-1; doi:https://doi.org/10.1186/s12877-021-02673-1; html:https://europepmc.org/articles/PMC8897728; pdf:https://europepmc.org/articles/PMC8897728?pdf=render 32811694,https://doi.org/10.1016/j.burns.2020.01.005,Driving improved burns care and patient outcomes through clinical registry data: A review of quality indicators in the Burns Registry of Australia and New Zealand.,"Gong J, Singer Y, Cleland H, Wood F, Cameron P, Tracy LM, Gabbe BJ.",,Burns : journal of the International Society for Burn Injuries,2021,2020-08-15,N,Burns; Quality Indicators; Clinical Quality Registry,,,"

Background

In 2009, the Burns Registry of Australia and New Zealand (BRANZ) published a set of clinical quality indicators (QIs) to monitor performance, improve quality of care, and inform and change policy. With several years of data collected since the initial development of the indicators for burns, the BRANZ QI Working Party reviewed the clinical QIs for relevance and meaning, and considered new QIs that had not been collected previously.

Method

Using published literature and expert opinion, the QI Working Party, consisting of multidisciplinary burn clinicians, reviewed the QIs for burn care to be included as routine data items in the BRANZ.

Results

In July 2016, the list of clinical QIs in the BRANZ was updated to 23 QIs/data items, covering structure, process, and outcome measures. Four QIs were removed as they were not found to be useful, nine QIs/data items were revised, and eight new QIs/data items were added as they were considered to be clinically useful.

Conclusion

This review outlines the changes made to the QIs collected by the BRANZ four years since their development and implementation. Ongoing refinement of the BRANZ QIs will ensure that high quality data is collected to drive improvements in clinical and patient outcomes.",,doi:https://doi.org/10.1016/j.burns.2020.01.005 34470746,https://doi.org/10.1136/bmjgh-2021-006204,Disruption in essential health services in Mexico during COVID-19: an interrupted time series analysis of health information system data.,"Doubova SV, Leslie HH, Kruk ME, Pérez-Cuevas R, Arsenault C.",,BMJ global health,2021,2021-09-01,Y,Hypertension; Cancer; Diabetes; Maternal Health; Health Systems Evaluation,,,"

Introduction

The COVID-19 pandemic has disrupted health systems around the world. The objectives of this study are to estimate the overall effect of the pandemic on essential health service use and outcomes in Mexico, describe observed and predicted trends in services over 24 months, and to estimate the number of visits lost through December 2020.

Methods

We used health information system data for January 2019 to December 2020 from the Mexican Institute of Social Security (IMSS), which provides health services for more than half of Mexico's population-65 million people. Our analysis includes nine indicators of service use and three outcome indicators for reproductive, maternal and child health and non-communicable disease services. We used an interrupted time series design and linear generalised estimating equation models to estimate the change in service use and outcomes from April to December 2020. Estimates were expressed using average marginal effects on the risk ratio scale.

Results

The study found that across nine health services, an estimated 8.74 million patient visits were lost in Mexico. This included a decline of over two thirds for breast and cervical cancer screenings (79% and 68%, respectively), over half for sick child visits and female contraceptive services, approximately one-third for childhood vaccinations, diabetes, hypertension and antenatal care consultations, and a decline of 10% for deliveries performed at IMSS. In terms of patient outcomes, the proportion of patients with diabetes and hypertension with controlled conditions declined by 22% and 17%, respectively. Caesarean section rate did not change.

Conclusion

Significant disruptions in health services show that the pandemic has strained the resilience of the Mexican health system and calls for urgent efforts to resume essential services and plan for catching up on missed preventive care even as the COVID-19 crisis continues in Mexico.",,pdf:https://gh.bmj.com/content/bmjgh/6/9/e006204.full.pdf; doi:https://doi.org/10.1136/bmjgh-2021-006204; html:https://europepmc.org/articles/PMC8413469; pdf:https://europepmc.org/articles/PMC8413469?pdf=render +31233103,https://doi.org/10.1093/bioinformatics/btz469,PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations.,"Kamat MA, Blackshaw JA, Young R, Surendran P, Burgess S, Danesh J, Butterworth AS, Staley JR.",,"Bioinformatics (Oxford, England)",2019,2019-11-01,Y,,Applied Analytics,,"

Summary

PhenoScanner is a curated database of publicly available results from large-scale genetic association studies in humans. This online tool facilitates 'phenome scans', where genetic variants are cross-referenced for association with many phenotypes of different types. Here we present a major update of PhenoScanner ('PhenoScanner V2'), including over 150 million genetic variants and more than 65 billion associations (compared to 350 million associations in PhenoScanner V1) with diseases and traits, gene expression, metabolite and protein levels, and epigenetic markers. The query options have been extended to include searches by genes, genomic regions and phenotypes, as well as for genetic variants. All variants are positionally annotated using the Variant Effect Predictor and the phenotypes are mapped to Experimental Factor Ontology terms. Linkage disequilibrium statistics from the 1000 Genomes project can be used to search for phenotype associations with proxy variants.

Availability and implementation

PhenoScanner V2 is available at www.phenoscanner.medschl.cam.ac.uk.",Kamat et al. developed an improved version of phenoscanner which is a publicly available large-scale genetic dataset for evaluation of genetic associations.,pdf:https://academic.oup.com/bioinformatics/article-pdf/35/22/4851/30706861/btz469.pdf; doi:https://doi.org/10.1093/bioinformatics/btz469; html:https://europepmc.org/articles/PMC6853652; pdf:https://europepmc.org/articles/PMC6853652?pdf=render 35365070,https://doi.org/10.1186/s12879-022-07268-8,Impact of non-pharmaceutical interventions on SARS-CoV-2 outbreaks in English care homes: a modelling study.,"Rosello A, Barnard RC, Smith DRM, Evans S, Grimm F, Davies NG, Centre for Mathematical Modelling of Infectious Diseases COVID-19 Modelling Working Group, Deeny SR, Knight GM, Edmunds WJ.",,BMC infectious diseases,2022,2022-04-01,Y,PCR; Testing; mathematical model; Long-term Care Facility; Care Home; Non-pharmaceutical Interventions; Covid-19; Sars-cov-2,,,"

Background

COVID-19 outbreaks still occur in English care homes despite the interventions in place.

Methods

We developed a stochastic compartmental model to simulate the spread of SARS-CoV-2 within an English care home. We quantified the outbreak risk with baseline non-pharmaceutical interventions (NPIs) already in place, the role of community prevalence in driving outbreaks, and the relative contribution of all importation routes into a fully susceptible care home. We also considered the potential impact of additional control measures in care homes with and without immunity, namely: increasing staff and resident testing frequency, using lateral flow antigen testing (LFD) tests instead of polymerase chain reaction (PCR), enhancing infection prevention and control (IPC), increasing the proportion of residents isolated, shortening the delay to isolation, improving the effectiveness of isolation, restricting visitors and limiting staff to working in one care home. We additionally present a Shiny application for users to apply this model to their facility of interest, specifying care home, outbreak and intervention characteristics.

Results

The model suggests that importation of SARS-CoV-2 by staff, from the community, is the main driver of outbreaks, that importation by visitors or from hospitals is rare, and that the past testing strategy (monthly testing of residents and daily testing of staff by PCR) likely provides negligible benefit in preventing outbreaks. Daily staff testing by LFD was 39% (95% 18-55%) effective in preventing outbreaks at 30 days compared to no testing.

Conclusions

Increasing the frequency of testing in staff and enhancing IPC are important to preventing importations to the care home. Further work is needed to understand the impact of vaccination in this population, which is likely to be very effective in preventing outbreaks.",,pdf:https://bmcinfectdis.biomedcentral.com/track/pdf/10.1186/s12879-022-07268-8; doi:https://doi.org/10.1186/s12879-022-07268-8; html:https://europepmc.org/articles/PMC8972713; pdf:https://europepmc.org/articles/PMC8972713?pdf=render 33888728,https://doi.org/10.1038/s41598-021-86331-x,A multidimensional measure of polypharmacy for older adults using the Health and Retirement Study.,"Carr E, Federman A, Dzahini O, Dobson RJ, Bendayan R.",,Scientific reports,2021,2021-04-22,Y,,,,"Polypharmacy is commonly defined based on the number of medications taken concurrently using standard cut-offs, but several studies have highlighted the need for a multidimensional assessment. We developed a multidimensional measure of polypharmacy and compared with standard cut-offs. Data were extracted for 2141 respondents of the 2007 Prescription Drug Survey, a sub-study of the Health Retirement Study. Latent classes were identified based on multiple indicators of polypharmacy, including quantity, temporality and risk profile. A four-class model was selected based on fit statistics and clinical interpretability: 'High risk, long-term' (Class 1), 'Low risk, long-term' (Class 2), 'High risk, short-term' (Class 3), and 'High risk for drug interactions, medium-term, regular' (Class 4). Classes differed regarding sex, cohabitation, disability and multimorbidity. Participants in the 'low risk' class tended to be male, cohabitating, and reported fewer health conditions, compared to 'high risk' classes. Polypharmacy classes were compared to standard cut-offs (5+ or 9+ medications) in terms of overlap and mortality risk. The three 'high risk' classes overlapped with the groups concurrently taking 5+ and 9+ medications per month. However, the multidimensional measure further differentiated individuals in terms of risk profile and temporality of medication taking, thus offering a richer assessment of polypharmacy.",,pdf:https://www.nature.com/articles/s41598-021-86331-x.pdf; doi:https://doi.org/10.1038/s41598-021-86331-x; html:https://europepmc.org/articles/PMC8062687; pdf:https://europepmc.org/articles/PMC8062687?pdf=render -31233103,https://doi.org/10.1093/bioinformatics/btz469,PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations.,"Kamat MA, Blackshaw JA, Young R, Surendran P, Burgess S, Danesh J, Butterworth AS, Staley JR.",,"Bioinformatics (Oxford, England)",2019,2019-11-01,Y,,Applied Analytics,,"

Summary

PhenoScanner is a curated database of publicly available results from large-scale genetic association studies in humans. This online tool facilitates 'phenome scans', where genetic variants are cross-referenced for association with many phenotypes of different types. Here we present a major update of PhenoScanner ('PhenoScanner V2'), including over 150 million genetic variants and more than 65 billion associations (compared to 350 million associations in PhenoScanner V1) with diseases and traits, gene expression, metabolite and protein levels, and epigenetic markers. The query options have been extended to include searches by genes, genomic regions and phenotypes, as well as for genetic variants. All variants are positionally annotated using the Variant Effect Predictor and the phenotypes are mapped to Experimental Factor Ontology terms. Linkage disequilibrium statistics from the 1000 Genomes project can be used to search for phenotype associations with proxy variants.

Availability and implementation

PhenoScanner V2 is available at www.phenoscanner.medschl.cam.ac.uk.",Kamat et al. developed an improved version of phenoscanner which is a publicly available large-scale genetic dataset for evaluation of genetic associations.,pdf:https://academic.oup.com/bioinformatics/article-pdf/35/22/4851/30706861/btz469.pdf; doi:https://doi.org/10.1093/bioinformatics/btz469; html:https://europepmc.org/articles/PMC6853652; pdf:https://europepmc.org/articles/PMC6853652?pdf=render 34503513,https://doi.org/10.1186/s12916-021-02087-1,Genome-wide analysis of blood lipid metabolites in over 5000 South Asians reveals biological insights at cardiometabolic disease loci.,"Harshfield EL, Fauman EB, Stacey D, Paul DS, Ziemek D, Ong RMY, Danesh J, Butterworth AS, Rasheed A, Sattar T, Zameer-Ul-Asar, Saleem I, Hina Z, Ishtiaq U, Qamar N, Mallick NH, Yaqub Z, Saghir T, Rizvi SNH, Memon A, Ishaq M, Rasheed SZ, Memon FU, Jalal A, Abbas S, Frossard P, Saleheen D, Wood AM, Griffin JL, Koulman A.",,BMC medicine,2021,2021-09-10,Y,Genetics; Lipidomics; Network Analysis; South Asian; Gaussian Graphical Modelling,,,"

Background

Genetic, lifestyle, and environmental factors can lead to perturbations in circulating lipid levels and increase the risk of cardiovascular and metabolic diseases. However, how changes in individual lipid species contribute to disease risk is often unclear. Moreover, little is known about the role of lipids on cardiovascular disease in Pakistan, a population historically underrepresented in cardiovascular studies.

Methods

We characterised the genetic architecture of the human blood lipidome in 5662 hospital controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS) and 13,814 healthy British blood donors from the INTERVAL study. We applied a candidate causal gene prioritisation tool to link the genetic variants associated with each lipid to the most likely causal genes, and Gaussian Graphical Modelling network analysis to identify and illustrate relationships between lipids and genetic loci.

Results

We identified 253 genetic associations with 181 lipids measured using direct infusion high-resolution mass spectrometry in PROMIS, and 502 genetic associations with 244 lipids in INTERVAL. Our analyses revealed new biological insights at genetic loci associated with cardiometabolic diseases, including novel lipid associations at the LPL, MBOAT7, LIPC, APOE-C1-C2-C4, SGPP1, and SPTLC3 loci.

Conclusions

Our findings, generated using a distinctive lipidomics platform in an understudied South Asian population, strengthen and expand the knowledge base of the genetic determinants of lipids and their association with cardiometabolic disease-related loci.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-021-02087-1; doi:https://doi.org/10.1186/s12916-021-02087-1; html:https://europepmc.org/articles/PMC8431908; pdf:https://europepmc.org/articles/PMC8431908?pdf=render -37605204,https://doi.org/10.1186/s12916-023-03013-3,The development of a core outcome set for studies of pregnant women with multimorbidity.,"Lee SI, Hanley S, Vowles Z, Plachcinski R, Moss N, Singh M, Gale C, Fagbamigbe AF, Azcoaga-Lorenzo A, Subramanian A, Taylor B, Nelson-Piercy C, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Dolk H, Hope H, Phillips K, Abel KM, Eastwood KA, Kent L, Locock L, Loane M, Mhereeg M, Brocklehurst P, McCann S, Brophy S, Wambua S, Hemali Sudasinghe SPB, Thangaratinam S, Nirantharakumar K, Black M, MuM-PreDiCT Group.",,BMC medicine,2023,2023-08-21,Y,Pregnancy; Maternity; Outcome; Multimorbidity; Multiple Chronic Conditions; Core Outcome Set; Multiple Long-term Conditions,,,"

Background

Heterogeneity in reported outcomes can limit the synthesis of research evidence. A core outcome set informs what outcomes are important and should be measured as a minimum in all future studies. We report the development of a core outcome set applicable to observational and interventional studies of pregnant women with multimorbidity.

Methods

We developed the core outcome set in four stages: (i) a systematic literature search, (ii) three focus groups with UK stakeholders, (iii) two rounds of Delphi surveys with international stakeholders and (iv) two international virtual consensus meetings. Stakeholders included women with multimorbidity and experience of pregnancy in the last 5 years, or are planning a pregnancy, their partners, health or social care professionals and researchers. Study adverts were shared through stakeholder charities and organisations.

Results

Twenty-six studies were included in the systematic literature search (2017 to 2021) reporting 185 outcomes. Thematic analysis of the focus groups added a further 28 outcomes. Two hundred and nine stakeholders completed the first Delphi survey. One hundred and sixteen stakeholders completed the second Delphi survey where 45 outcomes reached Consensus In (≥70% of all participants rating an outcome as Critically Important). Thirteen stakeholders reviewed 15 Borderline outcomes in the first consensus meeting and included seven additional outcomes. Seventeen stakeholders reviewed these 52 outcomes in a second consensus meeting, the threshold was ≥80% of all participants voting for inclusion. The final core outcome set included 11 outcomes. The five maternal outcomes were as follows: maternal death, severe maternal morbidity, change in existing long-term conditions (physical and mental), quality and experience of care and development of new mental health conditions. The six child outcomes were as follows: survival of baby, gestational age at birth, neurodevelopmental conditions/impairment, quality of life, birth weight and separation of baby from mother for health care needs.

Conclusions

Multimorbidity in pregnancy is a new and complex clinical research area. Following a rigorous process, this complexity was meaningfully reduced to a core outcome set that balances the views of a diverse stakeholder group.",,doi:https://doi.org/10.1186/s12916-023-03013-3; html:https://europepmc.org/articles/PMC10441728; pdf:https://europepmc.org/articles/PMC10441728?pdf=render 31912232,https://doi.org/10.1007/s00394-019-02170-7,Adherence to the Dutch dietary guidelines and 15-year incidence of heart failure in the EPIC-NL cohort.,"Harbers MC, de Kroon AM, Boer JMA, Asselbergs FW, Geleijnse JM, Verschuren WMM, van der Schouw YT, Sluijs I.",,European journal of nutrition,2020,2020-01-07,N,Heart Failure; Dietary Patterns; Dutch Healthy Diet 2015 Index; Dutch Dietary Guidelines,,,"

Purpose

A healthy diet may contribute to the primary prevention of heart failure (HF), but evidence is still inconclusive. We aimed to study the association between adherence to the Dutch dietary guidelines and incidence of HF.

Methods

We studied 37,468 participants aged 20-70 years and free of HF at baseline from the EPIC-NL cohort. At baseline (1993-1997), data were collected on demographics, lifestyle, and presence of chronic diseases. Dietary intake was assessed using a 178-item validated food frequency questionnaire. Dietary intake data were used to calculate scores on the Dutch Healthy Diet 2015 Index (DHD15-index) measuring adherence to the Dutch dietary guidelines. The DHD15-index is based on the average daily intake of 14 food groups resulting in a total score ranging between 0 and 140, with higher scores indicating better adherence. HF morbidity and mortality during follow-up were ascertained through linkage with national registries. Cox proportional hazards analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between DHD15 adherence and HF risk, adjusting for sociodemographic and lifestyle characteristics.

Results

The average score on the DHD15-index was 71 (SD = 15). During a median follow-up of 15.2 years (IQR 14.1-16.5), 674 HF events occurred. After adjustment for demographic and lifestyle characteristics, higher scores on the DHD15-index were associated with lower risk of HF (HRQ4vsQ1 0.73; 95% CI 0.58-0.93; Ptrend 0.001).

Conclusion

In a large Dutch population of middle-aged adults, higher adherence to the Dutch dietary guidelines was associated with lower risk of HF.",,pdf:https://discovery.ucl.ac.uk/id/eprint/10104999/1/Harbers%20et%20al.%202019%20Adh%20do%20Dutch%20dietary%20guidelines%20and%20HF.pdf; doi:https://doi.org/10.1007/s00394-019-02170-7 33367483,https://doi.org/10.1093/bioinformatics/btaa1079,A non-linear regression method for estimation of gene-environment heritability.,"Kerin M, Marchini J.",,"Bioinformatics (Oxford, England)",2021,2021-04-01,Y,,,,"

Motivation

Gene-environment (GxE) interactions are one of the least studied aspects of the genetic architecture of human traits and diseases. The environment of an individual is inherently high dimensional, evolves through time and can be expensive and time consuming to measure. The UK Biobank study, with all 500 000 participants having undergone an extensive baseline questionnaire, represents a unique opportunity to assess GxE heritability for many traits and diseases in a well powered setting.

Results

We have developed a randomized Haseman-Elston non-linear regression method applicable when many environmental variables have been measured on each individual. The method (GPLEMMA) simultaneously estimates a linear environmental score (ES) and its GxE heritability. We compare the method via simulation to a whole-genome regression approach (LEMMA) for estimating GxE heritability. We show that GPLEMMA is more computationally efficient than LEMMA on large datasets, and produces results highly correlated with those from LEMMA when applied to simulated data and real data from the UK Biobank.

Availability and implementation

Software implementing the GPLEMMA method is available from https://jmarchini.org/gplemma/.

Supplementary information

Supplementary data are available at Bioinformatics online.",,pdf:https://academic.oup.com/bioinformatics/article-pdf/36/24/5632/36899551/btaa1079.pdf; doi:https://doi.org/10.1093/bioinformatics/btaa1079; html:https://europepmc.org/articles/PMC8023682; pdf:https://europepmc.org/articles/PMC8023682?pdf=render +37605204,https://doi.org/10.1186/s12916-023-03013-3,The development of a core outcome set for studies of pregnant women with multimorbidity.,"Lee SI, Hanley S, Vowles Z, Plachcinski R, Moss N, Singh M, Gale C, Fagbamigbe AF, Azcoaga-Lorenzo A, Subramanian A, Taylor B, Nelson-Piercy C, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Dolk H, Hope H, Phillips K, Abel KM, Eastwood KA, Kent L, Locock L, Loane M, Mhereeg M, Brocklehurst P, McCann S, Brophy S, Wambua S, Hemali Sudasinghe SPB, Thangaratinam S, Nirantharakumar K, Black M, MuM-PreDiCT Group.",,BMC medicine,2023,2023-08-21,Y,Pregnancy; Maternity; Outcome; Multimorbidity; Multiple Chronic Conditions; Core Outcome Set; Multiple Long-term Conditions,,,"

Background

Heterogeneity in reported outcomes can limit the synthesis of research evidence. A core outcome set informs what outcomes are important and should be measured as a minimum in all future studies. We report the development of a core outcome set applicable to observational and interventional studies of pregnant women with multimorbidity.

Methods

We developed the core outcome set in four stages: (i) a systematic literature search, (ii) three focus groups with UK stakeholders, (iii) two rounds of Delphi surveys with international stakeholders and (iv) two international virtual consensus meetings. Stakeholders included women with multimorbidity and experience of pregnancy in the last 5 years, or are planning a pregnancy, their partners, health or social care professionals and researchers. Study adverts were shared through stakeholder charities and organisations.

Results

Twenty-six studies were included in the systematic literature search (2017 to 2021) reporting 185 outcomes. Thematic analysis of the focus groups added a further 28 outcomes. Two hundred and nine stakeholders completed the first Delphi survey. One hundred and sixteen stakeholders completed the second Delphi survey where 45 outcomes reached Consensus In (≥70% of all participants rating an outcome as Critically Important). Thirteen stakeholders reviewed 15 Borderline outcomes in the first consensus meeting and included seven additional outcomes. Seventeen stakeholders reviewed these 52 outcomes in a second consensus meeting, the threshold was ≥80% of all participants voting for inclusion. The final core outcome set included 11 outcomes. The five maternal outcomes were as follows: maternal death, severe maternal morbidity, change in existing long-term conditions (physical and mental), quality and experience of care and development of new mental health conditions. The six child outcomes were as follows: survival of baby, gestational age at birth, neurodevelopmental conditions/impairment, quality of life, birth weight and separation of baby from mother for health care needs.

Conclusions

Multimorbidity in pregnancy is a new and complex clinical research area. Following a rigorous process, this complexity was meaningfully reduced to a core outcome set that balances the views of a diverse stakeholder group.",,doi:https://doi.org/10.1186/s12916-023-03013-3; html:https://europepmc.org/articles/PMC10441728; pdf:https://europepmc.org/articles/PMC10441728?pdf=render 33821553,https://doi.org/10.1002/jia2.25697,The impact of disruptions due to COVID-19 on HIV transmission and control among men who have sex with men in China.,"Booton RD, Fu G, MacGregor L, Li J, Ong JJ, Tucker JD, Turner KM, Tang W, Vickerman P, Mitchell KM.",,Journal of the International AIDS Society,2021,2021-04-01,Y,Modelling; Hiv Transmission; Men Who Have Sex With Men; People’s Republic Of China; Key And Vulnerable Populations; Covid-19 Pandemic,,,"

Introduction

The COVID-19 pandemic is impacting HIV care globally, with gaps in HIV treatment expected to increase HIV transmission and HIV-related mortality. We estimated how COVID-19-related disruptions could impact HIV transmission and mortality among men who have sex with men (MSM) in four cities in China, over a one- and five-year time horizon.

Methods

Regional data from China indicated that the number of MSM undergoing facility-based HIV testing reduced by 59% during the COVID-19 pandemic, alongside reductions in ART initiation (34%), numbers of all sexual partners (62%) and consistency of condom use (25%), but initial data indicated no change in viral suppression. A mathematical model of HIV transmission/treatment among MSM was used to estimate the impact of disruptions on HIV infections/HIV-related deaths. Disruption scenarios were assessed for their individual and combined impact over one and five years for 3/4/6-month disruption periods, starting from 1 January 2020.

Results

Our model predicted new HIV infections and HIV-related deaths would be increased most by disruptions to viral suppression, with 25% reductions (25% virally suppressed MSM stop taking ART) for a three-month period increasing HIV infections by 5% to 14% over one year and deaths by 7% to 12%. Observed reductions in condom use increased HIV infections by 5% to 14% but had minimal impact (<1%) on deaths. Smaller impacts on infections and deaths (<3%) were seen for disruptions to facility HIV testing and ART initiation, but reduced partner numbers resulted in 11% to 23% fewer infections and 0.4% to 1.0% fewer deaths. Longer disruption periods (4/6 months) amplified the impact of disruption scenarios. When realistic disruptions were modelled simultaneously, an overall decrease in new HIV infections occurred over one year (3% to 17%), but not for five years (1% increase to 4% decrease), whereas deaths mostly increased over one year (1% to 2%) and five years (1.2 increase to 0.3 decrease).

Conclusions

The overall impact of COVID-19 on new HIV infections and HIV-related deaths is dependent on the nature, scale and length of the various disruptions. Resources should be directed to ensuring levels of viral suppression and condom use are maintained to mitigate any adverse effects of COVID-19-related disruption on HIV transmission and control among MSM in China.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jia2.25697; doi:https://doi.org/10.1002/jia2.25697; html:https://europepmc.org/articles/PMC8022092; pdf:https://europepmc.org/articles/PMC8022092?pdf=render 35354069,https://doi.org/10.1016/j.cmet.2022.03.002,Early prediction of incident liver disease using conventional risk factors and gut-microbiome-augmented gradient boosting.,"Liu Y, Méric G, Havulinna AS, Teo SM, Åberg F, Ruuskanen M, Sanders J, Zhu Q, Tripathi A, Verspoor K, Cheng S, Jain M, Jousilahti P, Vázquez-Baeza Y, Loomba R, Lahti L, Niiranen T, Salomaa V, Knight R, Inouye M.",,Cell metabolism,2022,2022-03-29,Y,Prediction; Gut; Disease; Microbiota; liver disease; Metagenomics; Microbiome,,,"The gut microbiome has shown promise as a predictive biomarker for various diseases. However, the potential of gut microbiota for prospective risk prediction of liver disease has not been assessed. Here, we utilized shallow shotgun metagenomic sequencing of a large population-based cohort (N > 7,000) with ∼15 years of follow-up in combination with machine learning to investigate the predictive capacity of gut microbial predictors individually and in conjunction with conventional risk factors for incident liver disease. Separately, conventional and microbial factors showed comparable predictive capacity. However, microbiome augmentation of conventional risk factors using machine learning significantly improved the performance. Similarly, disease-free survival analysis showed significantly improved stratification using microbiome-augmented models. Investigation of predictive microbial signatures revealed previously unknown taxa for liver disease, as well as those previously associated with hepatic function and disease. This study supports the potential clinical validity of gut metagenomic sequencing to complement conventional risk factors for prediction of liver diseases.",,pdf:http://www.cell.com/article/S1550413122000900/pdf; doi:https://doi.org/10.1016/j.cmet.2022.03.002; html:https://europepmc.org/articles/PMC9097589 33493066,https://doi.org/10.1161/strokeaha.120.031659,"Sex, Age, and Socioeconomic Differences in Nonfatal Stroke Incidence and Subsequent Major Adverse Outcomes.","Akyea RK, Vinogradova Y, Qureshi N, Patel RS, Kontopantelis E, Ntaios G, Asselbergs FW, Kai J, Weng SF.",,Stroke,2021,2021-01-25,Y,Population; Cardiovascular diseases; epidemiology; incidence; Secondary Prevention,,,"

Background and purpose

Data about variations in stroke incidence and subsequent major adverse outcomes are essential to inform secondary prevention and prioritizing resources to those at the greatest risk of major adverse end points. We aimed to describe the age, sex, and socioeconomic differences in the rates of first nonfatal stroke and subsequent major adverse outcomes.

Methods

The cohort study used linked Clinical Practice Research Datalink and Hospital Episode Statistics data from the United Kingdom. The incidence rate (IR) ratio of first nonfatal stroke and subsequent major adverse outcomes (composite major adverse cardiovascular events, recurrent stroke, cardiovascular disease-related, and all-cause mortality) were calculated and presented by year, sex, age group, and socioeconomic status based on an individual's location of residence, in adults with incident nonfatal stroke diagnosis between 1998 and 2017.

Results

A total of 82 774 first nonfatal stroke events were recorded in either primary care or hospital data-an IR of 109.20 per 100 000 person-years (95% CI, 108.46-109.95). Incidence was significantly higher in women compared with men (IR ratio, 1.13 [95% CI, 1.12-1.15]; P<0.001). Rates adjusted for age and sex were higher in the lowest compared with the highest socioeconomic status group (IR ratio, 1.10 [95% CI, 1.08-1.13]; P<0.001). For subsequent major adverse outcomes, the overall incidence for major adverse cardiovascular event was 38.05 per 100 person-years (95% CI, 37.71-38.39) with a slightly higher incidence in women compared with men (38.42 versus 37.62; IR ratio, 1.02 [95% CI, 1.00-1.04]; P=0.0229). Age and socioeconomic status largely accounted for the observed higher incidence of adverse outcomes in women.

Conclusions

In the United Kingdom, incidence of initial stroke and subsequent major adverse outcomes are higher in women, older populations, and people living in socially deprived areas.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.120.031659; doi:https://doi.org/10.1161/STROKEAHA.120.031659; html:https://europepmc.org/articles/PMC7834661; pdf:https://europepmc.org/articles/PMC7834661?pdf=render @@ -1979,24 +1979,24 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 37006331,https://doi.org/10.1093/braincomms/fcad041,Polygenic risk score prediction of multiple sclerosis in individuals of South Asian ancestry.,"Breedon JR, Marshall CR, Giovannoni G, van Heel DA, Genes & Health Research Team , Dobson R, Jacobs BM.",,Brain communications,2023,2023-02-22,Y,Genetics; Multiple sclerosis; Ethnicity,,,"Polygenic risk scores aggregate an individual's burden of risk alleles to estimate the overall genetic risk for a specific trait or disease. Polygenic risk scores derived from genome-wide association studies of European populations perform poorly for other ancestral groups. Given the potential for future clinical utility, underperformance of polygenic risk scores in South Asian populations has the potential to reinforce health inequalities. To determine whether European-derived polygenic risk scores underperform at multiple sclerosis prediction in a South Asian-ancestry population compared with a European-ancestry cohort, we used data from two longitudinal genetic cohort studies: Genes & Health (2015-present), a study of ∼50 000 British-Bangladeshi and British-Pakistani individuals, and UK Biobank (2006-present), which is comprised of ∼500 000 predominantly White British individuals. We compared individuals with and without multiple sclerosis in both studies (Genes & Health: N Cases = 42, N Control = 40 490; UK Biobank: N Cases = 2091, N Control = 374 866). Polygenic risk scores were calculated using clumping and thresholding with risk allele effect sizes obtained from the largest multiple sclerosis genome-wide association study to date. Scores were calculated with and without the major histocompatibility complex region, the most influential locus in determining multiple sclerosis risk. Polygenic risk score prediction was evaluated using Nagelkerke's pseudo-R 2 metric adjusted for case ascertainment, age, sex and the first four genetic principal components. We found that, as expected, European-derived polygenic risk scores perform poorly in the Genes & Health cohort, explaining 1.1% (including the major histocompatibility complex) and 1.5% (excluding the major histocompatibility complex) of disease risk. In contrast, multiple sclerosis polygenic risk scores explained 4.8% (including the major histocompatibility complex) and 2.8% (excluding the major histocompatibility complex) of disease risk in European-ancestry UK Biobank participants. These findings suggest that polygenic risk score prediction of multiple sclerosis based on European genome-wide association study results is less accurate in a South Asian population. Genetic studies of ancestrally diverse populations are required to ensure that polygenic risk scores can be useful across ancestries.",,pdf:https://academic.oup.com/braincomms/article-pdf/5/2/fcad041/49521070/fcad041.pdf; doi:https://doi.org/10.1093/braincomms/fcad041; html:https://europepmc.org/articles/PMC10053643; pdf:https://europepmc.org/articles/PMC10053643?pdf=render 32285648,https://doi.org/10.1002/ehf2.12689,Predicting sustained ventricular arrhythmias in dilated cardiomyopathy: a meta-analysis and systematic review.,"Sammani A, Kayvanpour E, Bosman LP, Sedaghat-Hamedani F, Proctor T, Gi WT, Broezel A, Jensen K, Katus HA, Te Riele ASJM, Meder B, Asselbergs FW.",,ESC heart failure,2020,2020-04-14,Y,Prognosis; Dilated cardiomyopathy; risk; Sudden Cardiac Death; Implantable Cardiac-defibrillator,,,"

Aims

Patients with non-ischaemic dilated cardiomyopathy (DCM) are at increased risk of sudden cardiac death. Identification of patients that may benefit from implantable cardioverter-defibrillator implantation remains challenging. In this study, we aimed to determine predictors of sustained ventricular arrhythmias in patients with DCM.

Methods and results

We searched MEDLINE/Embase for studies describing predictors of sustained ventricular arrhythmias in patients with DCM. Quality and bias were assessed using the Quality in Prognostic Studies tool, articles with high risk of bias in ≥2 areas were excluded. Unadjusted hazard ratios (HRs) of uniformly defined predictors were pooled, while all other predictors were evaluated in a systematic review. We included 55 studies (11 451 patients and 3.7 ± 2.3 years follow-up). Crude annual event rate was 4.5%. Younger age [HR 0.82; 95% CI (0.74-1.00)], hypertension [HR 1.95; 95% CI (1.26-3.00)], prior sustained ventricular arrhythmia [HR 4.15; 95% CI (1.32-13.02)], left ventricular ejection fraction on ultrasound [HR 1.45; 95% CI (1.19-1.78)], left ventricular dilatation (HR 1.10), and presence of late gadolinium enhancement [HR 5.55; 95% CI (4.02-7.67)] were associated with arrhythmic outcome in pooled analyses. Prior non-sustained ventricular arrhythmia and several genotypes [mutations in Phospholamban (PLN), Lamin A/C (LMNA), and Filamin-C (FLNC)] were associated with arrhythmic outcome in non-pooled analyses. Quality of evidence was moderate, and heterogeneity among studies was moderate to high.

Conclusions

In patients with DCM, the annual event rate of sustained ventricular arrhythmias is approximately 4.5%. This risk is considerably higher in younger patients with hypertension, prior (non-)sustained ventricular arrhythmia, decreased left ventricular ejection fraction, left ventricular dilatation, late gadolinium enhancement, and genetic mutations (PLN, LMNA, and FLNC). These results may help determine appropriate candidates for implantable cardioverter-defibrillator implantation.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.12689; doi:https://doi.org/10.1002/ehf2.12689; html:https://europepmc.org/articles/PMC7373946; pdf:https://europepmc.org/articles/PMC7373946?pdf=render 36998408,https://doi.org/10.3389/fmicb.2023.1070340,A longitudinal study reveals persistence of antimicrobial resistance on livestock farms is not due to antimicrobial usage alone.,"Smith RP, May HE, AbuOun M, Stubberfield E, Gilson D, Chau KK, Crook DW, Shaw LP, Read DS, Stoesser N, Vilar MJ, Anjum MF.",,Frontiers in microbiology,2023,2023-03-14,Y,Sheep; Cattle; Pigs; Antimicrobial resistance; Longitudinal; Antimicrobial Usage,,,"

Introduction

There are concerns that antimicrobial usage (AMU) is driving an increase in multi-drug resistant (MDR) bacteria so treatment of microbial infections is becoming harder in humans and animals. The aim of this study was to evaluate factors, including usage, that affect antimicrobial resistance (AMR) on farm over time.

Methods

A population of 14 cattle, sheep and pig farms within a defined area of England were sampled three times over a year to collect data on AMR in faecal Enterobacterales flora; AMU; and husbandry or management practices. Ten pooled samples were collected at each visit, with each comprising of 10 pinches of fresh faeces. Up to 14 isolates per visit were whole genome sequenced to determine presence of AMR genes.

Results

Sheep farms had very low AMU in comparison to the other species and very few sheep isolates were genotypically resistant at any time point. AMR genes were detected persistently across pig farms at all visits, even on farms with low AMU, whereas AMR bacteria was consistently lower on cattle farms than pigs, even for those with comparably high AMU. MDR bacteria was also more commonly detected on pig farms than any other livestock species.

Discussion

The results may be explained by a complex combination of factors on pig farms including historic AMU; co-selection of AMR bacteria; variation in amounts of antimicrobials used between visits; potential persistence in environmental reservoirs of AMR bacteria; or importation of pigs with AMR microbiota from supplying farms. Pig farms may also be at increased risk of AMR due to the greater use of oral routes of group antimicrobial treatment, which were less targeted than cattle treatments; the latter mostly administered to individual animals. Also, farms which exhibited either increasing or decreasing trends of AMR across the study did not have corresponding trends in their AMU. Therefore, our results suggest that factors other than AMU on individual farms are important for persistence of AMR bacteria on farms, which may be operating at the farm and livestock species level.",,pdf:https://www.frontiersin.org/articles/10.3389/fmicb.2023.1070340/pdf; doi:https://doi.org/10.3389/fmicb.2023.1070340; html:https://europepmc.org/articles/PMC10043416; pdf:https://europepmc.org/articles/PMC10043416?pdf=render +33325834,https://doi.org/10.2196/23530,Cystic Fibrosis Point of Personalized Detection (CFPOPD): An Interactive Web Application.,"Wolfe C, Pestian T, Gecili E, Su W, Keogh RH, Pestian JP, Seid M, Diggle PJ, Ziady A, Clancy JP, Grossoehme DH, Szczesniak RD, Brokamp C.",,JMIR medical informatics,2020,2020-12-16,Y,Chronic disease; Clinical Decision Support; Medical Monitoring; Clinical Decision Rules; Application Programming Interface,,,"

Background

Despite steady gains in life expectancy, individuals with cystic fibrosis (CF) lung disease still experience rapid pulmonary decline throughout their clinical course, which can ultimately end in respiratory failure. Point-of-care tools for accurate and timely information regarding the risk of rapid decline is essential for clinical decision support.

Objective

This study aims to translate a novel algorithm for earlier, more accurate prediction of rapid lung function decline in patients with CF into an interactive web-based application that can be integrated within electronic health record systems, via collaborative development with clinicians.

Methods

Longitudinal clinical history, lung function measurements, and time-invariant characteristics were obtained for 30,879 patients with CF who were followed in the US Cystic Fibrosis Foundation Patient Registry (2003-2015). We iteratively developed the application using the R Shiny framework and by conducting a qualitative study with care provider focus groups (N=17).

Results

A clinical conceptual model and 4 themes were identified through coded feedback from application users: (1) ambiguity in rapid decline, (2) clinical utility, (3) clinical significance, and (4) specific suggested revisions. These themes were used to revise our application to the currently released version, available online for exploration. This study has advanced the application's potential prognostic utility for monitoring individuals with CF lung disease. Further application development will incorporate additional clinical characteristics requested by the users and also a more modular layout that can be useful for care provider and family interactions.

Conclusions

Our framework for creating an interactive and visual analytics platform enables generalized development of applications to synthesize, model, and translate electronic health data, thereby enhancing clinical decision support and improving care and health outcomes for chronic diseases and disorders. A prospective implementation study is necessary to evaluate this tool's effectiveness regarding increased communication, enhanced shared decision-making, and improved clinical outcomes for patients with CF.",,pdf:https://medinform.jmir.org/2020/12/e23530/PDF; doi:https://doi.org/10.2196/23530; html:https://europepmc.org/articles/PMC7773511 32951912,https://doi.org/10.1016/j.jhep.2020.08.030,"Corrigendum to: ""Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis"" [J Hepatol (2020) 241-251].","Parisinos CA, Wilman HR, Thomas EL, Kelly M, Nicholls RC, McGonigle J, Neubauer S, Hingorani AD, Patel RS, Hemingway H, Bell JD, Banerjee R, Yaghootkar H.",,Journal of hepatology,2020,2020-09-18,Y,,,,,,pdf:http://www.journal-of-hepatology.eu/article/S0168827820336035/pdf; doi:https://doi.org/10.1016/j.jhep.2020.08.030; html:https://europepmc.org/articles/PMC8055539; pdf:https://europepmc.org/articles/PMC8055539?pdf=render 37208429,https://doi.org/10.1038/s41598-023-33391-w,Rare variant contribution to cholestatic liver disease in a South Asian population in the United Kingdom.,"Zöllner J, Finer S, Linton KJ, Genes and Health Research Team, van Heel DA, Williamson C, Dixon PH.",,Scientific reports,2023,2023-05-19,Y,,,,"This study assessed the contribution of five genes previously known to be involved in cholestatic liver disease in British Bangladeshi and Pakistani people. Five genes (ABCB4, ABCB11, ATP8B1, NR1H4, TJP2) were interrogated by exome sequencing data of 5236 volunteers. Included were non-synonymous or loss of function (LoF) variants with a minor allele frequency < 5%. Variants were filtered, and annotated to perform rare variant burden analysis, protein structure, and modelling analysis in-silico. Out of 314 non-synonymous variants, 180 fulfilled the inclusion criteria and were mostly heterozygous unless specified. 90 were novel and of those variants, 22 were considered likely pathogenic and 9 pathogenic. We identified variants in volunteers with gallstone disease (n = 31), intrahepatic cholestasis of pregnancy (ICP, n = 16), cholangiocarcinoma and cirrhosis (n = 2). Fourteen novel LoF variants were identified: 7 frameshift, 5 introduction of premature stop codon and 2 splice acceptor variants. The rare variant burden was significantly increased in ABCB11. Protein modelling demonstrated variants that appeared to likely cause significant structural alterations. This study highlights the significant genetic burden contributing to cholestatic liver disease. Novel likely pathogenic and pathogenic variants were identified addressing the underrepresentation of diverse ancestry groups in genomic research.",,doi:https://doi.org/10.1038/s41598-023-33391-w; doi:https://doi.org/10.1038/s41598-023-33391-w; html:https://europepmc.org/articles/PMC10199085; pdf:https://europepmc.org/articles/PMC10199085?pdf=render -33325834,https://doi.org/10.2196/23530,Cystic Fibrosis Point of Personalized Detection (CFPOPD): An Interactive Web Application.,"Wolfe C, Pestian T, Gecili E, Su W, Keogh RH, Pestian JP, Seid M, Diggle PJ, Ziady A, Clancy JP, Grossoehme DH, Szczesniak RD, Brokamp C.",,JMIR medical informatics,2020,2020-12-16,Y,Chronic disease; Clinical Decision Support; Medical Monitoring; Clinical Decision Rules; Application Programming Interface,,,"

Background

Despite steady gains in life expectancy, individuals with cystic fibrosis (CF) lung disease still experience rapid pulmonary decline throughout their clinical course, which can ultimately end in respiratory failure. Point-of-care tools for accurate and timely information regarding the risk of rapid decline is essential for clinical decision support.

Objective

This study aims to translate a novel algorithm for earlier, more accurate prediction of rapid lung function decline in patients with CF into an interactive web-based application that can be integrated within electronic health record systems, via collaborative development with clinicians.

Methods

Longitudinal clinical history, lung function measurements, and time-invariant characteristics were obtained for 30,879 patients with CF who were followed in the US Cystic Fibrosis Foundation Patient Registry (2003-2015). We iteratively developed the application using the R Shiny framework and by conducting a qualitative study with care provider focus groups (N=17).

Results

A clinical conceptual model and 4 themes were identified through coded feedback from application users: (1) ambiguity in rapid decline, (2) clinical utility, (3) clinical significance, and (4) specific suggested revisions. These themes were used to revise our application to the currently released version, available online for exploration. This study has advanced the application's potential prognostic utility for monitoring individuals with CF lung disease. Further application development will incorporate additional clinical characteristics requested by the users and also a more modular layout that can be useful for care provider and family interactions.

Conclusions

Our framework for creating an interactive and visual analytics platform enables generalized development of applications to synthesize, model, and translate electronic health data, thereby enhancing clinical decision support and improving care and health outcomes for chronic diseases and disorders. A prospective implementation study is necessary to evaluate this tool's effectiveness regarding increased communication, enhanced shared decision-making, and improved clinical outcomes for patients with CF.",,pdf:https://medinform.jmir.org/2020/12/e23530/PDF; doi:https://doi.org/10.2196/23530; html:https://europepmc.org/articles/PMC7773511 -37647632,https://doi.org/10.1182/blood.2023020118,The effects of pathogenic and likely pathogenic variants for inherited hemostasis disorders in 140 214 UK Biobank participants.,"Stefanucci L, Collins J, Sims MC, Barrio-Hernandez I, Sun L, Burren OS, Perfetto L, Bender I, Callahan TJ, Fleming K, Guerrero JA, Hermjakob H, Martin MJ, Stephenson J, Paneerselvam K, Petrovski S, Porras P, Robinson PN, Wang Q, Watkins X, Frontini M, Laskowski RA, Beltrao P, Di Angelantonio E, Gomez K, Laffan M, Ouwehand WH, Mumford AD, Freson K, Carss K, Downes K, Gleadall N, Megy K, Bruford E, Vuckovic D.",,Blood,2023,2023-12-01,Y,,,,"Rare genetic diseases affect millions, and identifying causal DNA variants is essential for patient care. Therefore, it is imperative to estimate the effect of each independent variant and improve their pathogenicity classification. Our study of 140 214 unrelated UK Biobank (UKB) participants found that each of them carries a median of 7 variants previously reported as pathogenic or likely pathogenic. We focused on 967 diagnostic-grade gene (DGG) variants for rare bleeding, thrombotic, and platelet disorders (BTPDs) observed in 12 367 UKB participants. By association analysis, for a subset of these variants, we estimated effect sizes for platelet count and volume, and odds ratios for bleeding and thrombosis. Variants causal of some autosomal recessive platelet disorders revealed phenotypic consequences in carriers. Loss-of-function variants in MPL, which cause chronic amegakaryocytic thrombocytopenia if biallelic, were unexpectedly associated with increased platelet counts in carriers. We also demonstrated that common variants identified by genome-wide association studies (GWAS) for platelet count or thrombosis risk may influence the penetrance of rare variants in BTPD DGGs on their associated hemostasis disorders. Network-propagation analysis applied to an interactome of 18 410 nodes and 571 917 edges showed that GWAS variants with large effect sizes are enriched in DGGs and their first-order interactors. Finally, we illustrate the modifying effect of polygenic scores for platelet count and thrombosis risk on disease severity in participants carrying rare variants in TUBB1 or PROC and PROS1, respectively. Our findings demonstrate the power of association analyses using large population datasets in improving pathogenicity classifications of rare variants.",,doi:https://doi.org/10.1182/blood.2023020118; html:https://europepmc.org/articles/PMC10733830 34965929,https://doi.org/10.1136/bmj-2021-065834,GP consultation rates for sequelae after acute covid-19 in patients managed in the community or hospital in the UK: population based study.,"Whittaker HR, Gulea C, Koteci A, Kallis C, Morgan AD, Iwundu C, Weeks M, Gupta R, Quint JK.",,BMJ (Clinical research ed.),2021,2021-12-29,Y,,,,"

Objectives

To describe the rates for consulting a general practitioner (GP) for sequelae after acute covid-19 in patients admitted to hospital with covid-19 and those managed in the community, and to determine how the rates change over time for patients in the community and after vaccination for covid-19.

Design

Population based study.

Setting

1392 general practices in England contributing to the Clinical Practice Research Datalink Aurum database.

Participants

456 002 patients with a diagnosis of covid-19 between 1 August 2020 and 14 February 2021 (44.7% men; median age 61 years), admitted to hospital within two weeks of diagnosis or managed in the community, and followed-up for a maximum of 9.2 months. A negative control group included individuals without covid-19 (n=38 511) and patients with influenza before the pandemic (n=21 803).

Main outcome measures

Comparison of rates for consulting a GP for new symptoms, diseases, prescriptions, and healthcare use in individuals admitted to hospital and those managed in the community, separately, before and after covid-19 infection, using Cox regression and negative binomial regression for healthcare use. The analysis was repeated for the negative control and influenza cohorts. In individuals in the community, outcomes were also described over time after a diagnosis of covid-19, and compared before and after vaccination for individuals who were symptomatic after covid-19 infection, using negative binomial regression.

Results

Relative to the negative control and influenza cohorts, patients in the community (n=437 943) had significantly higher GP consultation rates for multiple sequelae, and the most common were loss of smell or taste, or both (adjusted hazard ratio 5.28, 95% confidence interval 3.89 to 7.17, P<0.001); venous thromboembolism (3.35, 2.87 to 3.91, P<0.001); lung fibrosis (2.41, 1.37 to 4.25, P=0.002), and muscle pain (1.89, 1.63 to 2.20, P<0.001); and also for healthcare use after a diagnosis of covid-19 compared with 12 months before infection. For absolute proportions, the most common outcomes ≥4 weeks after a covid-19 diagnosis in patients in the community were joint pain (2.5%), anxiety (1.2%), and prescriptions for non-steroidal anti-inflammatory drugs (1.2%). Patients admitted to hospital (n=18 059) also had significantly higher GP consultation rates for multiple sequelae, most commonly for venous thromboembolism (16.21, 11.28 to 23.31, P<0.001), nausea (4.64, 2.24 to 9.21, P<0.001), prescriptions for paracetamol (3.68, 2.86 to 4.74, P<0.001), renal failure (3.42, 2.67 to 4.38, P<0.001), and healthcare use after a covid-19 diagnosis compared with 12 months before infection. For absolute proportions, the most common outcomes ≥4 weeks after a covid-19 diagnosis in patients admitted to hospital were venous thromboembolism (3.5%), joint pain (2.7%), and breathlessness (2.8%). In patients in the community, anxiety and depression, abdominal pain, diarrhoea, general pain, nausea, chest tightness, and tinnitus persisted throughout follow-up. GP consultation rates were reduced for all symptoms, prescriptions, and healthcare use, except for neuropathic pain, cognitive impairment, strong opiates, and paracetamol use in patients in the community after the first vaccination dose for covid-19 relative to before vaccination. GP consultation rates were also reduced for ischaemic heart disease, asthma, and gastro-oesophageal disease.

Conclusions

GP consultation rates for sequelae after acute covid-19 infection differed between patients with covid-19 who were admitted to hospital and those managed in the community. For individuals in the community, rates of some sequelae decreased over time but those for others, such as anxiety and depression, persisted. Rates of some outcomes decreased after vaccination in this group.",,pdf:https://www.bmj.com/content/bmj/375/bmj-2021-065834.full.pdf; doi:https://doi.org/10.1136/bmj-2021-065834; html:https://europepmc.org/articles/PMC8715128; pdf:https://europepmc.org/articles/PMC8715128?pdf=render -32680743,https://doi.org/10.1016/j.jphys.2020.06.008,"Adaptation, self-motivation and support services are key to physical activity participation three to five years after major trauma: a qualitative study.","Ekegren CL, Braaf S, Ameratunga S, Ponsford J, Nunn A, Cameron P, Lyons RA, Gabbe BJ.",,Journal of physiotherapy,2020,2020-07-14,N,Trauma; Recovery; Exercise; wounds and injuries; Sedentary Lifestyle,,,"

Questions

What are the perceived long-term impacts of major trauma on physical activity participation over time? What factors influence physical activity participation in people recovering from major trauma?

Design

Longitudinal qualitative study.

Participants

Sixty-six people aged ≥ 16 years with non-neurological major trauma.

Methods

Participants were interviewed 3 years (n = 66), 4 years (n = 63) and 5 years (n = 57) after their injury. A thematic analysis was performed.

Results

Despite wanting to be physically active, many participants experienced significant, long-term physical activity restriction after their injury, which persisted over time. Restrictions were often related to a fear of re-injury or of exacerbating pain and fatigue levels. These restrictions were a source of distress and frustration for many participants, given the perceived impacts on their social life, family roles and enjoyment of life. Participants were also concerned about weight gain, health decline and reduced physical fitness. Participants valued the support of insurers and specialised services in facilitating access to modified activities, such as clinical Pilates and hydrotherapy. Many participants also recognised the importance of adaptation, goal-setting, self-motivation and determination to be physically active despite limitations.

Conclusion

People recovering from major trauma experienced significant and persistent physical activity restriction after their injury. Given the high prevalence of activity restrictions, distress and health concerns that were reported, there is an urgent need to develop and evaluate support strategies to improve physical activity participation in this group.",,doi:https://doi.org/10.1016/j.jphys.2020.06.008; doi:https://doi.org/10.1016/j.jphys.2020.06.008 +37647632,https://doi.org/10.1182/blood.2023020118,The effects of pathogenic and likely pathogenic variants for inherited hemostasis disorders in 140 214 UK Biobank participants.,"Stefanucci L, Collins J, Sims MC, Barrio-Hernandez I, Sun L, Burren OS, Perfetto L, Bender I, Callahan TJ, Fleming K, Guerrero JA, Hermjakob H, Martin MJ, Stephenson J, Paneerselvam K, Petrovski S, Porras P, Robinson PN, Wang Q, Watkins X, Frontini M, Laskowski RA, Beltrao P, Di Angelantonio E, Gomez K, Laffan M, Ouwehand WH, Mumford AD, Freson K, Carss K, Downes K, Gleadall N, Megy K, Bruford E, Vuckovic D.",,Blood,2023,2023-12-01,Y,,,,"Rare genetic diseases affect millions, and identifying causal DNA variants is essential for patient care. Therefore, it is imperative to estimate the effect of each independent variant and improve their pathogenicity classification. Our study of 140 214 unrelated UK Biobank (UKB) participants found that each of them carries a median of 7 variants previously reported as pathogenic or likely pathogenic. We focused on 967 diagnostic-grade gene (DGG) variants for rare bleeding, thrombotic, and platelet disorders (BTPDs) observed in 12 367 UKB participants. By association analysis, for a subset of these variants, we estimated effect sizes for platelet count and volume, and odds ratios for bleeding and thrombosis. Variants causal of some autosomal recessive platelet disorders revealed phenotypic consequences in carriers. Loss-of-function variants in MPL, which cause chronic amegakaryocytic thrombocytopenia if biallelic, were unexpectedly associated with increased platelet counts in carriers. We also demonstrated that common variants identified by genome-wide association studies (GWAS) for platelet count or thrombosis risk may influence the penetrance of rare variants in BTPD DGGs on their associated hemostasis disorders. Network-propagation analysis applied to an interactome of 18 410 nodes and 571 917 edges showed that GWAS variants with large effect sizes are enriched in DGGs and their first-order interactors. Finally, we illustrate the modifying effect of polygenic scores for platelet count and thrombosis risk on disease severity in participants carrying rare variants in TUBB1 or PROC and PROS1, respectively. Our findings demonstrate the power of association analyses using large population datasets in improving pathogenicity classifications of rare variants.",,doi:https://doi.org/10.1182/blood.2023020118; html:https://europepmc.org/articles/PMC10733830 30649175,https://doi.org/10.1001/jamacardio.2018.4537,Cardiovascular Risk Factors Associated With Venous Thromboembolism.,"Gregson J, Kaptoge S, Bolton T, Pennells L, Willeit P, Burgess S, Bell S, Sweeting M, Rimm EB, Kabrhel C, Zöller B, Assmann G, Gudnason V, Folsom AR, Arndt V, Fletcher A, Norman PE, Nordestgaard BG, Kitamura A, Mahmoodi BK, Whincup PH, Knuiman M, Salomaa V, Meisinger C, Koenig W, Kavousi M, Völzke H, Cooper JA, Ninomiya T, Casiglia E, Rodriguez B, Ben-Shlomo Y, Després JP, Simons L, Barrett-Connor E, Björkelund C, Notdurfter M, Kromhout D, Price J, Sutherland SE, Sundström J, Kauhanen J, Gallacher J, Beulens JWJ, Dankner R, Cooper C, Giampaoli S, Deen JF, Gómez de la Cámara A, Kuller LH, Rosengren A, Svensson PJ, Nagel D, Crespo CJ, Brenner H, Albertorio-Diaz JR, Atkins R, Brunner EJ, Shipley M, Njølstad I, Lawlor DA, van der Schouw YT, Selmer RM, Trevisan M, Verschuren WMM, Greenland P, Wassertheil-Smoller S, Lowe GDO, Wood AM, Butterworth AS, Thompson SG, Danesh J, Di Angelantonio E, Meade T, Emerging Risk Factors Collaboration.",,JAMA cardiology,2019,2019-02-01,Y,,Understanding the Causes of Disease,,"

Importance

It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE).

Objective

To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism.

Design, setting, and participants

This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018.

Exposures

A panel of several established cardiovascular risk factors.

Main outcomes and measures

Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI).

Results

Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers.

Conclusions and relevance

Older age, smoking, and adiposity were consistently associated with higher VTE risk.",,pdf:https://pdxscholar.library.pdx.edu/cgi/viewcontent.cgi?article=1451&context=sph_facpub; doi:https://doi.org/10.1001/jamacardio.2018.4537; html:https://europepmc.org/articles/PMC6386140 +32680743,https://doi.org/10.1016/j.jphys.2020.06.008,"Adaptation, self-motivation and support services are key to physical activity participation three to five years after major trauma: a qualitative study.","Ekegren CL, Braaf S, Ameratunga S, Ponsford J, Nunn A, Cameron P, Lyons RA, Gabbe BJ.",,Journal of physiotherapy,2020,2020-07-14,N,Trauma; Recovery; Exercise; wounds and injuries; Sedentary Lifestyle,,,"

Questions

What are the perceived long-term impacts of major trauma on physical activity participation over time? What factors influence physical activity participation in people recovering from major trauma?

Design

Longitudinal qualitative study.

Participants

Sixty-six people aged ≥ 16 years with non-neurological major trauma.

Methods

Participants were interviewed 3 years (n = 66), 4 years (n = 63) and 5 years (n = 57) after their injury. A thematic analysis was performed.

Results

Despite wanting to be physically active, many participants experienced significant, long-term physical activity restriction after their injury, which persisted over time. Restrictions were often related to a fear of re-injury or of exacerbating pain and fatigue levels. These restrictions were a source of distress and frustration for many participants, given the perceived impacts on their social life, family roles and enjoyment of life. Participants were also concerned about weight gain, health decline and reduced physical fitness. Participants valued the support of insurers and specialised services in facilitating access to modified activities, such as clinical Pilates and hydrotherapy. Many participants also recognised the importance of adaptation, goal-setting, self-motivation and determination to be physically active despite limitations.

Conclusion

People recovering from major trauma experienced significant and persistent physical activity restriction after their injury. Given the high prevalence of activity restrictions, distress and health concerns that were reported, there is an urgent need to develop and evaluate support strategies to improve physical activity participation in this group.",,doi:https://doi.org/10.1016/j.jphys.2020.06.008; doi:https://doi.org/10.1016/j.jphys.2020.06.008 35849350,https://doi.org/10.1093/nar/gkac612,Whole-genome long-read TAPS deciphers DNA methylation patterns at base resolution using PacBio SMRT sequencing technology.,"Chen J, Cheng J, Chen X, Inoue M, Liu Y, Song CX.",,Nucleic acids research,2022,2022-10-01,Y,,,,"Long-read sequencing provides valuable information on difficult-to-map genomic regions, which can complement short-read sequencing to improve genome assembly, yet limited methods are available to accurately detect DNA methylation over long distances at a whole-genome scale. By combining our recently developed TET-assisted pyridine borane sequencing (TAPS) method, which enables direct detection of 5-methylcytosine and 5-hydroxymethylcytosine, with PacBio single-molecule real-time sequencing, we present here whole-genome long-read TAPS (wglrTAPS). To evaluate the performance of wglrTAPS, we applied it to mouse embryonic stem cells as a proof of concept, and an N50 read length of 3.5 kb is achieved. By sequencing wglrTAPS to 8.2× depth, we discovered a significant proportion of CpG sites that were not covered in previous 27.5× short-read TAPS. Our results demonstrate that wglrTAPS facilitates methylation profiling on problematic genomic regions with repetitive elements or structural variations, and also in an allelic manner, all of which are extremely difficult for short-read sequencing methods to resolve. This method therefore enhances applications of third-generation sequencing technologies for DNA epigenetics.",,pdf:https://academic.oup.com/nar/article-pdf/50/18/e104/46501243/gkac612.pdf; doi:https://doi.org/10.1093/nar/gkac612; html:https://europepmc.org/articles/PMC9561279; pdf:https://europepmc.org/articles/PMC9561279?pdf=render 35188939,https://doi.org/10.1097/pts.0000000000000867,Optimizing Hospital Electronic Prescribing Systems: A Systematic Scoping Review.,"Williams J, Malden S, Heeney C, Bouamrane M, Holder M, Perera U, Bates DW, Sheikh A.",,Journal of patient safety,2022,2022-03-01,Y,,,,"

Objective

Considerable international investment in hospital electronic prescribing (ePrescribing) systems has been made, but despite this, it is proving difficult for most organizations to realize safety, quality, and efficiency gains in prescribing. The objective of this work was to develop policy-relevant insights into the optimization of hospital ePrescribing systems to maximize the benefits and minimize the risks of these expensive digital health infrastructures.

Methods

We undertook a systematic scoping review of the literature by searching MEDLINE, Embase, and CINAHL databases. We searched for primary studies reporting on ePrescribing optimization strategies and independently screened and abstracted data until saturation was achieved. Findings were theoretically and thematically synthesized taking a medicine life-cycle perspective, incorporating consultative phases with domain experts.

Results

We identified 23,609 potentially eligible studies from which 1367 satisfied our inclusion criteria. Thematic synthesis was conducted on a data set of 76 studies, of which 48 were based in the United States. Key approaches to optimization included the following: stakeholder engagement, system or process redesign, technological innovations, and education and training packages. Single-component interventions (n = 26) described technological optimization strategies focusing on a single, specific step in the prescribing process. Multicomponent interventions (n = 50) used a combination of optimization strategies, typically targeting multiple steps in the medicines management process.

Discussion

We identified numerous optimization strategies for enhancing the performance of ePrescribing systems. Key considerations for ePrescribing optimization include meaningful stakeholder engagement to reconceptualize the service delivery model and implementing technological innovations with supporting training packages to simultaneously impact on different facets of the medicines management process.",,html:https://journals.lww.com/journalpatientsafety/Fulltext/2022/03000/Optimizing_Hospital_Electronic_Prescribing.36.aspx; doi:https://doi.org/10.1097/PTS.0000000000000867; html:https://europepmc.org/articles/PMC8855945; pdf:https://europepmc.org/articles/PMC8855945?pdf=render 34437535,https://doi.org/10.1371/journal.pgen.1009723,The impact of age on genetic risk for common diseases.,"Jiang X, Holmes C, McVean G.",,PLoS genetics,2021,2021-08-26,Y,,,,"Inherited genetic variation contributes to individual risk for many complex diseases and is increasingly being used for predictive patient stratification. Previous work has shown that genetic factors are not equally relevant to human traits across age and other contexts, though the reasons for such variation are not clear. Here, we introduce methods to infer the form of the longitudinal relationship between genetic relative risk for disease and age and to test whether all genetic risk factors behave similarly. We use a proportional hazards model within an interval-based censoring methodology to estimate age-varying individual variant contributions to genetic relative risk for 24 common diseases within the British ancestry subset of UK Biobank, applying a Bayesian clustering approach to group variants by their relative risk profile over age and permutation tests for age dependency and multiplicity of profiles. We find evidence for age-varying relative risk profiles in nine diseases, including hypertension, skin cancer, atherosclerotic heart disease, hypothyroidism and calculus of gallbladder, several of which show evidence, albeit weak, for multiple distinct profiles of genetic relative risk. The predominant pattern shows genetic risk factors having the greatest relative impact on risk of early disease, with a monotonic decrease over time, at least for the majority of variants, although the magnitude and form of the decrease varies among diseases. As a consequence, for diseases where genetic relative risk decreases over age, genetic risk factors have stronger explanatory power among younger populations, compared to older ones. We show that these patterns cannot be explained by a simple model involving the presence of unobserved covariates such as environmental factors. We discuss possible models that can explain our observations and the implications for genetic risk prediction.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009723&type=printable; doi:https://doi.org/10.1371/journal.pgen.1009723; html:https://europepmc.org/articles/PMC8389405; pdf:https://europepmc.org/articles/PMC8389405?pdf=render 30887727,https://doi.org/10.1002/ppul.24314,Physical activity among children with asthma: Cross-sectional analysis in the UK millennium cohort.,"Pike KC, Griffiths LJ, Dezateux C, Pearce A.",,Pediatric pulmonology,2019,2019-03-18,Y,Children; Cohort study; epidemiology; Physical Activity; Asthma And Early Wheeze,Improving Public Health,,"

Background

Although beneficial for health and well-being, most children do not achieve recommended levels of physical activity. Evidence for children with asthma is mixed, with symptom severity rarely considered. This paper aimed to address this gap.

Methods

We analyzed cross-sectional associations between physical activity and parent-reported asthma symptoms and severity for 6497 UK Millennium Cohort Study 7-year-old participants (3321, [49%] girls). Primary outcomes were daily moderate-to-vigorous physical activity (MVPA, minutes) and proportion of children achieving recommended minimum daily levels of 60 minutes of MVPA. Daily steps, sedentary time, and total activity counts per minute (cpm) were recorded, as were parent-reported asthma symptoms, medications, and recent hospital admissions. Associations were investigated using quantile (continuous outcomes) and Poisson (binary outcomes) regression, adjusting for demographic, socioeconomic, health, and environmental factors.

Results

Neither asthma status nor severity was associated with MVPA; children recently hospitalized for asthma were less likely to achieve recommended daily MVPA (risk ratio [95% confidence interval [CI]]: 0.67 [0.44, 1.03]). Recent wheeze, current asthma, and severe asthma symptoms were associated with fewer sedentary hours (difference in medians [95% CI]: -0.18 [-0.27, -0.08]; -0.14 [-0.24, -0.05]; -0.15, [-0.28, -0.02], respectively) and hospital admission with lower total activity (-48 cpm [-68, -28]).

Conclusion

Children with asthma are as physically active as their asthma-free counterparts, while those recently hospitalized for asthma are less active. Qualitative studies are needed to understand the perceptions of children and families about physical activity following hospital admission and to inform support and advice needed to maintain active lifestyles for children with asthma.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ppul.24314; doi:https://doi.org/10.1002/ppul.24314; html:https://europepmc.org/articles/PMC6617805; pdf:https://europepmc.org/articles/PMC6617805?pdf=render -38548763,https://doi.org/10.1038/s41467-024-46982-6,The SARS-CoV-2 neutralizing antibody response to SD1 and its evasion by BA.2.86.,"Zhou D, Supasa P, Liu C, Dijokaite-Guraliuc A, Duyvesteyn HME, Selvaraj M, Mentzer AJ, Das R, Dejnirattisai W, Temperton N, Klenerman P, Dunachie SJ, Fry EE, Mongkolsapaya J, Ren J, Stuart DI, Screaton GR.",,Nature communications,2024,2024-03-28,Y,,,,"Under pressure from neutralising antibodies induced by vaccination or infection the SARS-CoV-2 spike gene has become a hotspot for evolutionary change, leading to the failure of all mAbs developed for clinical use. Most potent antibodies bind to the receptor binding domain which has become heavily mutated. Here we study responses to a conserved epitope in sub-domain-1 (SD1) of spike which have become more prominent because of mutational escape from antibodies directed to the receptor binding domain. Some SD1 reactive mAbs show potent and broad neutralization of SARS-CoV-2 variants. We structurally map the dominant SD1 epitope and provide a mechanism of action by blocking interaction with ACE2. Mutations in SD1 have not been sustained to date, but one, E554K, leads to escape from mAbs. This mutation has now emerged in several sublineages including BA.2.86, reflecting selection pressure on the virus exerted by the increasing prominence of the anti-SD1 response.",,pdf:https://www.nature.com/articles/s41467-024-46982-6.pdf; doi:https://doi.org/10.1038/s41467-024-46982-6; html:https://europepmc.org/articles/PMC10978878; pdf:https://europepmc.org/articles/PMC10978878?pdf=render 35103484,https://doi.org/10.1161/circgen.121.003553,Genetically Predicted Neutrophil-to-Lymphocyte Ratio and Coronary Artery Disease: Evidence From Mendelian Randomization.,"Cupido AJ, Kraaijenhof JM, Burgess S, Asselbergs FW, Hovingh GK, Gill D.",,Circulation. Genomic and precision medicine,2022,2022-02-01,Y,Neutrophils; Cardiovascular diseases; Inflammation; Causality; Linear Models,,,,,pdf:https://discovery.ucl.ac.uk/10145750/1/CIRCGEN.121.003553.pdf; doi:https://doi.org/10.1161/CIRCGEN.121.003553; html:https://europepmc.org/articles/PMC7612391; pdf:https://europepmc.org/articles/PMC7612391?pdf=render +38548763,https://doi.org/10.1038/s41467-024-46982-6,The SARS-CoV-2 neutralizing antibody response to SD1 and its evasion by BA.2.86.,"Zhou D, Supasa P, Liu C, Dijokaite-Guraliuc A, Duyvesteyn HME, Selvaraj M, Mentzer AJ, Das R, Dejnirattisai W, Temperton N, Klenerman P, Dunachie SJ, Fry EE, Mongkolsapaya J, Ren J, Stuart DI, Screaton GR.",,Nature communications,2024,2024-03-28,Y,,,,"Under pressure from neutralising antibodies induced by vaccination or infection the SARS-CoV-2 spike gene has become a hotspot for evolutionary change, leading to the failure of all mAbs developed for clinical use. Most potent antibodies bind to the receptor binding domain which has become heavily mutated. Here we study responses to a conserved epitope in sub-domain-1 (SD1) of spike which have become more prominent because of mutational escape from antibodies directed to the receptor binding domain. Some SD1 reactive mAbs show potent and broad neutralization of SARS-CoV-2 variants. We structurally map the dominant SD1 epitope and provide a mechanism of action by blocking interaction with ACE2. Mutations in SD1 have not been sustained to date, but one, E554K, leads to escape from mAbs. This mutation has now emerged in several sublineages including BA.2.86, reflecting selection pressure on the virus exerted by the increasing prominence of the anti-SD1 response.",,pdf:https://www.nature.com/articles/s41467-024-46982-6.pdf; doi:https://doi.org/10.1038/s41467-024-46982-6; html:https://europepmc.org/articles/PMC10978878; pdf:https://europepmc.org/articles/PMC10978878?pdf=render 32413819,https://doi.org/10.1016/j.dsx.2020.04.050,Vitamin D concentrations and COVID-19 infection in UK Biobank.,"Hastie CE, Mackay DF, Ho F, Celis-Morales CA, Katikireddi SV, Niedzwiedz CL, Jani BD, Welsh P, Mair FS, Gray SR, O'Donnell CA, Gill JM, Sattar N, Pell JP.",,Diabetes & metabolic syndrome,2020,2020-05-07,Y,Vitamin D; Ethnicity; Covid-19,,,"

Background and aims

COVID-19 and low levels of vitamin D appear to disproportionately affect black and minority ethnic individuals. We aimed to establish whether blood 25-hydroxyvitamin D (25(OH)D) concentration was associated with COVID-19 risk, and whether it explained the higher incidence of COVID-19 in black and South Asian people.

Methods

UK Biobank recruited 502,624 participants aged 37-73 years between 2006 and 2010. Baseline exposure data, including 25(OH)D concentration and ethnicity, were linked to COVID-19 test results. Univariable and multivariable logistic regression analyses were performed for the association between 25(OH)D and confirmed COVID-19, and the association between ethnicity and both 25(OH)D and COVID-19.

Results

Complete data were available for 348,598 UK Biobank participants. Of these, 449 had confirmed COVID-19 infection. Vitamin D was associated with COVID-19 infection univariably (OR = 0.99; 95% CI 0.99-0.999; p = 0.013), but not after adjustment for confounders (OR = 1.00; 95% CI = 0.998-1.01; p = 0.208). Ethnicity was associated with COVID-19 infection univariably (blacks versus whites OR = 5.32, 95% CI = 3.68-7.70, p-value<0.001; South Asians versus whites OR = 2.65, 95% CI = 1.65-4.25, p-value<0.001). Adjustment for 25(OH)D concentration made little difference to the magnitude of the association.

Conclusions

Our findings do not support a potential link between vitamin D concentrations and risk of COVID-19 infection, nor that vitamin D concentration may explain ethnic differences in COVID-19 infection.","This study aimed to investigate if low levels of vitamin D were associated with a higher likelihood of having COVID-19, which could be a cause of higher rates of COVID infection amoung black and South Asian people.",doi:https://doi.org/10.1016/j.dsx.2020.04.050; doi:https://doi.org/10.1016/j.dsx.2020.04.050; html:https://europepmc.org/articles/PMC7204679 36168404,https://doi.org/10.1016/j.lanepe.2022.100501,Risk factors for SARS-CoV-2 infection after primary vaccination with ChAdOx1 nCoV-19 or BNT162b2 and after booster vaccination with BNT162b2 or mRNA-1273: A population-based cohort study (COVIDENCE UK).,"Vivaldi G, Jolliffe DA, Holt H, Tydeman F, Talaei M, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Shaheen SO, Martineau AR.",,The Lancet regional health. Europe,2022,2022-09-23,Y,Vaccination; Breakthrough Infection; Chadox1; Sars-cov-2; Mrna-1273; Bnt162b2,,,"

Background

Little is known about how demographic, behavioural, and vaccine-related factors affect risk of post-vaccination SARS-CoV-2 infection. We aimed to identify risk factors for SARS-CoV-2 infection after primary and booster vaccinations.

Methods

This prospective, population-based, UK study in adults (≥16 years) vaccinated against SARS-CoV-2 assessed risk of breakthrough SARS-CoV-2 infection up to February, 2022, for participants who completed a primary vaccination course (ChAdOx1 nCoV-19 or BNT162b2) and those who received a booster dose (BNT162b2 or mRNA-1273). Cox regression models explored associations between sociodemographic, behavioural, clinical, pharmacological, and nutritional factors and test-positive breakthrough infection, adjusted for local weekly SARS-CoV-2 incidence.

Findings

1051 (7·1%) of 14 713 post-primary participants and 1009 (9·5%) of 10 665 post-booster participants reported breakthrough infection, over a median follow-up of 203 days (IQR 195-216) and 85 days (66-103), respectively. Primary vaccination with ChAdOx1 (vs BNT162b2) was associated with higher risk of infection in both post-primary analysis (adjusted hazard ratio 1·63, 95% CI 1·41-1·88) and after an mRNA-1273 booster (1·26 [1·00-1·57] vs BNT162b2 primary and booster). Lower risk of infection was associated with older age (post-primary: 0·97 [0·96-0·97] per year; post-booster: 0·97 [0·97-0·98]), whereas higher risk of infection was associated with lower educational attainment (post-primary: 1·78 [1·44-2·20] for primary/secondary vs postgraduate; post-booster: 1·46 [1·16-1·83]) and at least three weekly visits to indoor public places (post-primary: 1·36 [1·13-1·63] vs none; post-booster: 1·29 [1·07-1·56]).

Interpretation

Vaccine type, socioeconomic status, age, and behaviours affect risk of breakthrough infection after primary and booster vaccinations.

Funding

Barts Charity, UK Research and Innovation Industrial Strategy Challenge Fund.",,doi:https://doi.org/10.1016/j.lanepe.2022.100501; doi:https://doi.org/10.1016/j.lanepe.2022.100501; html:https://europepmc.org/articles/PMC9499825; pdf:https://europepmc.org/articles/PMC9499825?pdf=render 33025017,https://doi.org/10.1093/schbul/sbaa126,Using Natural Language Processing on Electronic Health Records to Enhance Detection and Prediction of Psychosis Risk.,"Irving J, Patel R, Oliver D, Colling C, Pritchard M, Broadbent M, Baldwin H, Stahl D, Stewart R, Fusar-Poli P.",,Schizophrenia bulletin,2021,2021-03-01,N,Prediction; Prevention; Psychosis; Machine Learning; Electronic Health Records; Natural Language Processing,,,"

Background

Using novel data mining methods such as natural language processing (NLP) on electronic health records (EHRs) for screening and detecting individuals at risk for psychosis.

Method

The study included all patients receiving a first index diagnosis of nonorganic and nonpsychotic mental disorder within the South London and Maudsley (SLaM) NHS Foundation Trust between January 1, 2008, and July 28, 2018. Least Absolute Shrinkage and Selection Operator (LASSO)-regularized Cox regression was used to refine and externally validate a refined version of a five-item individualized, transdiagnostic, clinically based risk calculator previously developed (Harrell's C = 0.79) and piloted for implementation. The refined version included 14 additional NLP-predictors: tearfulness, poor appetite, weight loss, insomnia, cannabis, cocaine, guilt, irritability, delusions, hopelessness, disturbed sleep, poor insight, agitation, and paranoia.

Results

A total of 92 151 patients with a first index diagnosis of nonorganic and nonpsychotic mental disorder within the SLaM Trust were included in the derivation (n = 28 297) or external validation (n = 63 854) data sets. Mean age was 33.6 years, 50.7% were women, and 67.0% were of white race/ethnicity. Mean follow-up was 1590 days. The overall 6-year risk of psychosis in secondary mental health care was 3.4 (95% CI, 3.3-3.6). External validation indicated strong performance on unseen data (Harrell's C 0.85, 95% CI 0.84-0.86), an increase of 0.06 from the original model.

Conclusions

Using NLP on EHRs can considerably enhance the prognostic accuracy of psychosis risk calculators. This can help identify patients at risk of psychosis who require assessment and specialized care, facilitating earlier detection and potentially improving patient outcomes.",,pdf:https://academic.oup.com/schizophreniabulletin/article-pdf/47/2/405/36620462/sbaa126.pdf; doi:https://doi.org/10.1093/schbul/sbaa126; html:https://europepmc.org/articles/PMC7965059; pdf:https://europepmc.org/articles/PMC7965059?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa126 -31780306,https://doi.org/10.1016/s2215-0366(19)30298-6,Pharmacoepidemiology research: delivering evidence about drug safety and effectiveness in mental health.,"Davis KAS, Farooq S, Hayes JF, John A, Lee W, MacCabe JH, McIntosh A, Osborn DPJ, Stewart RJ, Woelbert E.",,The lancet. Psychiatry,2020,2019-11-25,N,,,,"Research that provides an evidence base for the pharmacotherapy of people with mental disorders is needed. The abundance of digital data has facilitated pharmacoepidemiology and, in particular, observational research on the effectiveness of real-world medication. Advantages of pharmacoepidemiological research are the availability of large patient samples, and coverage of under-researched subpopulations in their naturalistic conditions. Such research is also cheaper and quicker to do than randomised controlled trials, meaning that issues regarding generic medication, stopping medication (deprescribing), and long-term outcomes are more likely to be addressed. Pharmacoepidemiological methods can also be extended to pharmacovigilance and to aid the development of new purposes for existing drugs. Drawbacks of observational pharmacoepidemiological studies come from the non-randomised nature of treatment selection, leading to confounding by indication. Potential methods for managing this drawback include active comparison groups, within-individual designs, and propensity scoring. Many of the more rigorous pharmacoepidemiology studies have been strengthened through multiple analytical approaches triangulated to improve confidence in inferred causal relationships. With developments in data resources and analytical techniques, it is encouraging that guidelines are beginning to include evidence from robust observational pharmacoepidemiological studies alongside randomised controlled trials. Collaboration between guideline writers and researchers involved in pharmacoepidemiology could help researchers to answer the questions that are important to policy makers and ensure that results are integrated into the evidence base. Further development of statistical and data science techniques, alongside public engagement and capacity building (data resources and researcher base), will be necessary to take full advantage of future opportunities.",,html:https://eprints.keele.ac.uk/6650/1/Pharamcoepidemiology%20Lancet%20Psych%202019%20submitted%20version.docx; doi:https://doi.org/10.1016/S2215-0366(19)30298-6 33185016,https://doi.org/10.1002/art.41593,Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID-19.,"Chandan JS, Zemedikun DT, Thayakaran R, Byne N, Dhalla S, Acosta-Mena D, Gokhale KM, Thomas T, Sainsbury C, Subramanian A, Cooper J, Anand A, Okoth KO, Wang J, Adderley NJ, Taverner T, Denniston AK, Lord J, Thomas GN, Buckley CD, Raza K, Bhala N, Nirantharakumar K, Haroon S.",,"Arthritis & rheumatology (Hoboken, N.J.)",2021,2021-05-01,Y,,,,"

Objective

To identify whether active use of nonsteroidal antiinflammatory drugs (NSAIDs) increases susceptibility to developing suspected or confirmed coronavirus disease 2019 (COVID-19) compared to the use of other common analgesics.

Methods

We performed a propensity score-matched cohort study with active comparators, using a large UK primary care data set. The cohort consisted of adult patients age ≥18 years with osteoarthritis (OA) who were followed up from January 30 to July 31, 2020. Patients prescribed an NSAID (excluding topical preparations) were compared to those prescribed either co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine). A total of 13,202 patients prescribed NSAIDs were identified, compared to 12,457 patients prescribed the comparator drugs. The primary outcome measure was the documentation of suspected or confirmed COVID-19, and the secondary outcome measure was all-cause mortality.

Results

During follow-up, the incidence rates of suspected/confirmed COVID-19 were 15.4 and 19.9 per 1,000 person-years in the NSAID-exposed group and comparator group, respectively. Adjusted hazard ratios for suspected or confirmed COVID-19 among the unmatched and propensity score-matched OA cohorts, using data from clinical consultations in primary care settings, were 0.82 (95% confidence interval [95% CI] 0.62-1.10) and 0.79 (95% CI 0.57-1.11), respectively, and adjusted hazard ratios for the risk of all-cause mortality were 0.97 (95% CI 0.75-1.27) and 0.85 (95% CI 0.61-1.20), respectively. There was no effect modification by age or sex.

Conclusion

No increase in the risk of suspected or confirmed COVID-19 or mortality was observed among patients with OA in a primary care setting who were prescribed NSAIDs as compared to those who received comparator drugs. These results are reassuring and suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/art.41593; doi:https://doi.org/10.1002/art.41593; html:https://europepmc.org/articles/PMC8252419; pdf:https://europepmc.org/articles/PMC8252419?pdf=render +31780306,https://doi.org/10.1016/s2215-0366(19)30298-6,Pharmacoepidemiology research: delivering evidence about drug safety and effectiveness in mental health.,"Davis KAS, Farooq S, Hayes JF, John A, Lee W, MacCabe JH, McIntosh A, Osborn DPJ, Stewart RJ, Woelbert E.",,The lancet. Psychiatry,2020,2019-11-25,N,,,,"Research that provides an evidence base for the pharmacotherapy of people with mental disorders is needed. The abundance of digital data has facilitated pharmacoepidemiology and, in particular, observational research on the effectiveness of real-world medication. Advantages of pharmacoepidemiological research are the availability of large patient samples, and coverage of under-researched subpopulations in their naturalistic conditions. Such research is also cheaper and quicker to do than randomised controlled trials, meaning that issues regarding generic medication, stopping medication (deprescribing), and long-term outcomes are more likely to be addressed. Pharmacoepidemiological methods can also be extended to pharmacovigilance and to aid the development of new purposes for existing drugs. Drawbacks of observational pharmacoepidemiological studies come from the non-randomised nature of treatment selection, leading to confounding by indication. Potential methods for managing this drawback include active comparison groups, within-individual designs, and propensity scoring. Many of the more rigorous pharmacoepidemiology studies have been strengthened through multiple analytical approaches triangulated to improve confidence in inferred causal relationships. With developments in data resources and analytical techniques, it is encouraging that guidelines are beginning to include evidence from robust observational pharmacoepidemiological studies alongside randomised controlled trials. Collaboration between guideline writers and researchers involved in pharmacoepidemiology could help researchers to answer the questions that are important to policy makers and ensure that results are integrated into the evidence base. Further development of statistical and data science techniques, alongside public engagement and capacity building (data resources and researcher base), will be necessary to take full advantage of future opportunities.",,html:https://eprints.keele.ac.uk/6650/1/Pharamcoepidemiology%20Lancet%20Psych%202019%20submitted%20version.docx; doi:https://doi.org/10.1016/S2215-0366(19)30298-6 35068290,https://doi.org/10.1080/09537104.2021.2003317,Higher body mass index raises immature platelet count: potential contribution to obesity-related thrombosis.,"Goudswaard LJ, Corbin LJ, Burley KL, Mumford A, Akbari P, Soranzo N, Butterworth AS, Watkins NA, Pournaras DJ, Harris J, Timpson NJ, Hers I.",,Platelets,2022,2022-01-24,N,Obesity; Aggregation; epidemiology; Mendelian Randomization; Immature Platelets,,,"Higher body mass index (BMI) is a risk factor for thrombosis. Platelets are essential for hemostasis but contribute to thrombosis when activated pathologically. We hypothesized that higher BMI leads to changes in platelet characteristics, thereby increasing thrombotic risk. The effect of BMI on platelet traits (measured by Sysmex) was explored in 33 388 UK blood donors (INTERVAL study). Linear regression showed that higher BMI was positively associated with greater plateletcrit (PCT), platelet count (PLT), immature platelet count (IPC), and side fluorescence (SFL, a measure of mRNA content used to derive IPC). Mendelian randomization (MR), applied to estimate a causal effect with BMI proxied by a genetic risk score, provided causal estimates for a positive effect of BMI on both SFL and IPC, but there was little evidence for a causal effect of BMI on PCT or PLT. Follow-up analyses explored the functional relevance of platelet characteristics in a pre-operative cardiac cohort (COPTIC). Linear regression provided observational evidence for a positive association between IPC and agonist-induced whole blood platelet aggregation. Results indicate that higher BMI raises the number of immature platelets, which is associated with greater whole blood platelet aggregation in a cardiac cohort. Higher IPC could therefore contribute to obesity-related thrombosis.",,doi:https://doi.org/10.1080/09537104.2021.2003317; doi:https://doi.org/10.1080/09537104.2021.2003317 31163036,https://doi.org/10.1371/journal.pone.0217158,Differences in the epidemiology of out-of-hospital and in-hospital trauma deaths.,"Beck B, Smith K, Mercier E, Gabbe B, Bassed R, Mitra B, Teague W, Siedenburg J, McLellan S, Cameron P.",,PloS one,2019,2019-06-04,Y,,Improving Public Health,,"

Background

Trauma is a leading cause of mortality. Holistic views of trauma systems consider injury as a public health problem that requires efforts in primary, secondary and tertiary prevention. However, the performance of trauma systems is commonly judged on the in-hospital mortality rate. Such a focus misses opportunities to consider all deaths within a population, to understand differences in in-hospital and out-of-hospital trauma deaths and to inform population-level injury prevention efforts. The aim of this study was to provide an epidemiological overview of out-of-hospital and in-hospital trauma deaths in a geographically-defined area over a 10-year period.

Methods

We performed a population-based review of out-of-hospital and in-hospital trauma deaths over the period of 01 July 2006 to 30 June 2016 in Victoria, Australia, using data from the National Coronial Information System and the Victorian State Trauma Registry. Temporal trends in population-based incidence rates were evaluated.

Results

Over the study period, there were 11,246 trauma deaths, of which 71% were out-of-hospital deaths. Out-of-hospital trauma deaths commonly resulted from intentional self-harm events (50%) and transport events (35%), while in-hospital trauma deaths commonly resulted from low falls (≤1 metre) (50%). The incidence of overall trauma deaths did not change over the study period (incidence rate ratio 0.998; 95%CI: 0.991, 1.004; P = 0.56).

Conclusions

Out-of-hospital deaths accounted for most trauma deaths. Given the notable differences between out-of-hospital and in-hospital trauma deaths, monitoring of all trauma deaths is necessary to inform injury prevention activities and to reduce trauma mortality. The absence of a change in the incidence of both out-of-hospital and in-hospital trauma deaths demonstrates the need for enhanced activities across all aspects of injury prevention.",,doi:https://doi.org/10.1371/journal.pone.0217158; doi:https://doi.org/10.1371/journal.pone.0217158; html:https://europepmc.org/articles/PMC6548370; pdf:https://europepmc.org/articles/PMC6548370?pdf=render 31196949,https://doi.org/10.1183/13993003.02309-2018,Educational and health outcomes of children treated for asthma: Scotland-wide record linkage study of 683 716 children.,"Fleming M, Fitton CA, Steiner MFC, McLay JS, Clark D, King A, Mackay DF, Pell JP.",,The European respiratory journal,2019,2019-09-05,Y,,Improving Public Health,,"

Background

The global prevalence of childhood asthma is increasing. The condition impacts physical and psychosocial morbidity; therefore, wide-ranging effects on health and education outcomes are plausible.

Methods

Linkage of eight Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, examinations, school absences/exclusions and unemployment, provided data on 683 716 children attending Scottish schools between 2009 and 2013. We compared schoolchildren on medication for asthma with peers, adjusting for sociodemographic, maternity and comorbidity confounders, and explored effect modifiers and mediators.

Results

The 45 900 (6.0%) children treated for asthma had an increased risk of hospitalisation, particularly within the first year of treatment (incidence rate ratio 1.98, 95% CI 1.93-2.04), and increased mortality (HR 1.77, 95% CI 1.30-2.40). They were more likely to have special educational need for mental (OR 1.76, 95% CI 1.49-2.08) and physical (OR 2.76, 95% CI 2.57-2.95) health reasons, and performed worse in school exams (OR 1.11, 95% CI 1.06-1.16). Higher absenteeism (incidence rate ratio 1.25, 95% CI 1.24-1.26) partially explained their poorer attainment.

Conclusions

Children with treated asthma have poorer education and health outcomes than their peers. Educational interventions that mitigate the adverse effects of absenteeism should be considered.",,pdf:https://erj.ersjournals.com/content/erj/54/3/1802309.full.pdf; doi:https://doi.org/10.1183/13993003.02309-2018; html:https://europepmc.org/articles/PMC6727030; pdf:https://europepmc.org/articles/PMC6727030?pdf=render @@ -2012,14 +2012,14 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 35388009,https://doi.org/10.1038/s41467-022-29641-6,Publisher Correction: Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus.,"Stacey D, Chen L, Stanczyk PJ, Howson JMM, Mason AM, Burgess S, MacDonald S, Langdown J, McKinney H, Downes K, Farahi N, Peters JE, Basu S, Pankow JS, Tang W, Pankratz N, Sabater-Lleal M, de Vries PS, Smith NL, CHARGE Hemostasis Working Group, Gelinas AD, Schneider DJ, Janjic N, Samani NJ, Ye S, Summers C, Chilvers ER, Danesh J, Paul DS.",,Nature communications,2022,2022-04-06,Y,,,,,,pdf:https://www.nature.com/articles/s41467-022-29641-6.pdf; doi:https://doi.org/10.1038/s41467-022-29641-6; html:https://europepmc.org/articles/PMC8986867; pdf:https://europepmc.org/articles/PMC8986867?pdf=render 34432797,https://doi.org/10.1371/journal.pone.0255748,Regional performance variation in external validation of four prediction models for severity of COVID-19 at hospital admission: An observational multi-centre cohort study.,"Wickstrøm KE, Vitelli V, Carr E, Holten AR, Bendayan R, Reiner AH, Bean D, Searle T, Shek A, Kraljevic Z, Teo J, Dobson R, Tonby K, Köhn-Luque A, Amundsen EK.",,PloS one,2021,2021-08-25,Y,,,,"

Background

Prediction models should be externally validated to assess their performance before implementation. Several prediction models for coronavirus disease-19 (COVID-19) have been published. This observational cohort study aimed to validate published models of severity for hospitalized patients with COVID-19 using clinical and laboratory predictors.

Methods

Prediction models fitting relevant inclusion criteria were chosen for validation. The outcome was either mortality or a composite outcome of mortality and ICU admission (severe disease). 1295 patients admitted with symptoms of COVID-19 at Kings Cross Hospital (KCH) in London, United Kingdom, and 307 patients at Oslo University Hospital (OUH) in Oslo, Norway were included. The performance of the models was assessed in terms of discrimination and calibration.

Results

We identified two models for prediction of mortality (referred to as Xie and Zhang1) and two models for prediction of severe disease (Allenbach and Zhang2). The performance of the models was variable. For prediction of mortality Xie had good discrimination at OUH with an area under the receiver-operating characteristic (AUROC) 0.87 [95% confidence interval (CI) 0.79-0.95] and acceptable discrimination at KCH, AUROC 0.79 [0.76-0.82]. In prediction of severe disease, Allenbach had acceptable discrimination (OUH AUROC 0.81 [0.74-0.88] and KCH AUROC 0.72 [0.68-0.75]). The Zhang models had moderate to poor discrimination. Initial calibration was poor for all models but improved with recalibration.

Conclusions

The performance of the four prediction models was variable. The Xie model had the best discrimination for mortality, while the Allenbach model had acceptable results for prediction of severe disease.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0255748&type=printable; doi:https://doi.org/10.1371/journal.pone.0255748; html:https://europepmc.org/articles/PMC8386866; pdf:https://europepmc.org/articles/PMC8386866?pdf=render 35380004,https://doi.org/10.1042/bcj20220105,Development of a colorimetric assay for the detection of SARS-CoV-2 3CLpro activity.,"Garland GD, Harvey RF, Mulroney TE, Monti M, Fuller S, Haigh R, Gerber PP, Barer MR, Matheson NJ, Willis AE.",,The Biochemical journal,2022,2022-04-01,Y,Coronavirus; Assay Development; Covid 19,,,"Diagnostic testing continues to be an integral component of the strategy to contain the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) global pandemic, the causative agent of Coronavirus Disease 2019 (COVID-19). The SARS-CoV-2 genome encodes the 3C-like protease (3CLpro) which is essential for coronavirus replication. This study adapts an in vitro colorimetric gold nanoparticle (AuNP) based protease assay to specifically detect the activity of SARS-CoV-2 3CLpro as a purified recombinant protein and as a cellular protein exogenously expressed in HEK293T human cells. We also demonstrate that the specific sensitivity of the assay for SARS-CoV-2 3CLpro can be improved by use of an optimised peptide substrate and through hybrid dimerisation with inactive 3CLpro mutant monomers. These findings highlight the potential for further development of the AuNP protease assay to detect SARS-CoV-2 3CLpro activity as a novel, accessible and cost-effective diagnostic test for SARS-CoV-2 infection at the point-of-care. Importantly, this versatile assay could also be easily adapted to detect specific protease activity associated with other viruses or diseases conditions.",,pdf:https://portlandpress.com/biochemj/article-pdf/479/8/901/932114/bcj-2022-0105.pdf; doi:https://doi.org/10.1042/BCJ20220105; html:https://europepmc.org/articles/PMC9162461; pdf:https://europepmc.org/articles/PMC9162461?pdf=render -35717168,https://doi.org/10.1186/s12879-022-07490-4,The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020.,"Knight GM, Pham TM, Stimson J, Funk S, Jafari Y, Pople D, Evans S, Yin M, Brown CS, Bhattacharya A, Hope R, Semple MG, ISARIC4C Investigators, CMMID COVID-19 Working Group, Read JM, Cooper BS, Robotham JV.",,BMC infectious diseases,2022,2022-06-18,Y,Mathematical Modelling; Nosocomial Transmission; Covid-19; Sars-cov-2,,,"

Background

SARS-CoV-2 is known to transmit in hospital settings, but the contribution of infections acquired in hospitals to the epidemic at a national scale is unknown.

Methods

We used comprehensive national English datasets to determine the number of COVID-19 patients with identified hospital-acquired infections (with symptom onset > 7 days after admission and before discharge) in acute English hospitals up to August 2020. As patients may leave the hospital prior to detection of infection or have rapid symptom onset, we combined measures of the length of stay and the incubation period distribution to estimate how many hospital-acquired infections may have been missed. We used simulations to estimate the total number (identified and unidentified) of symptomatic hospital-acquired infections, as well as infections due to onward community transmission from missed hospital-acquired infections, to 31st July 2020.

Results

In our dataset of hospitalised COVID-19 patients in acute English hospitals with a recorded symptom onset date (n = 65,028), 7% were classified as hospital-acquired. We estimated that only 30% (range across weeks and 200 simulations: 20-41%) of symptomatic hospital-acquired infections would be identified, with up to 15% (mean, 95% range over 200 simulations: 14.1-15.8%) of cases currently classified as community-acquired COVID-19 potentially linked to hospital transmission. We estimated that 26,600 (25,900 to 27,700) individuals acquired a symptomatic SARS-CoV-2 infection in an acute Trust in England before 31st July 2020, resulting in 15,900 (15,200-16,400) or 20.1% (19.2-20.7%) of all identified hospitalised COVID-19 cases.

Conclusions

Transmission of SARS-CoV-2 to hospitalised patients likely caused approximately a fifth of identified cases of hospitalised COVID-19 in the ""first wave"" in England, but less than 1% of all infections in England. Using time to symptom onset from admission for inpatients as a detection method likely misses a substantial proportion (> 60%) of hospital-acquired infections.",,pdf:https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-022-07490-4; doi:https://doi.org/10.1186/s12879-022-07490-4; html:https://europepmc.org/articles/PMC9206097; pdf:https://europepmc.org/articles/PMC9206097?pdf=render 35000827,https://doi.org/10.1016/j.clon.2021.12.017,Can Real-world Data and Rapid Learning Drive Improvements in Lung Cancer Survival? The RAPID-RT Study.,"Price G, Devaney S, French DP, Holley R, Holm S, Kontopantelis E, McWilliam A, Payne K, Proudlove N, Sanders C, Willans R, van Staa T, Hamrang L, Turner B, Parsons S, Faivre-Finn C.",,Clinical oncology (Royal College of Radiologists (Great Britain)),2022,2022-01-06,N,,,,,,pdf:http://www.clinicaloncologyonline.net/article/S0936655521005161/pdf; doi:https://doi.org/10.1016/j.clon.2021.12.017 +35717168,https://doi.org/10.1186/s12879-022-07490-4,The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020.,"Knight GM, Pham TM, Stimson J, Funk S, Jafari Y, Pople D, Evans S, Yin M, Brown CS, Bhattacharya A, Hope R, Semple MG, ISARIC4C Investigators, CMMID COVID-19 Working Group, Read JM, Cooper BS, Robotham JV.",,BMC infectious diseases,2022,2022-06-18,Y,Mathematical Modelling; Nosocomial Transmission; Covid-19; Sars-cov-2,,,"

Background

SARS-CoV-2 is known to transmit in hospital settings, but the contribution of infections acquired in hospitals to the epidemic at a national scale is unknown.

Methods

We used comprehensive national English datasets to determine the number of COVID-19 patients with identified hospital-acquired infections (with symptom onset > 7 days after admission and before discharge) in acute English hospitals up to August 2020. As patients may leave the hospital prior to detection of infection or have rapid symptom onset, we combined measures of the length of stay and the incubation period distribution to estimate how many hospital-acquired infections may have been missed. We used simulations to estimate the total number (identified and unidentified) of symptomatic hospital-acquired infections, as well as infections due to onward community transmission from missed hospital-acquired infections, to 31st July 2020.

Results

In our dataset of hospitalised COVID-19 patients in acute English hospitals with a recorded symptom onset date (n = 65,028), 7% were classified as hospital-acquired. We estimated that only 30% (range across weeks and 200 simulations: 20-41%) of symptomatic hospital-acquired infections would be identified, with up to 15% (mean, 95% range over 200 simulations: 14.1-15.8%) of cases currently classified as community-acquired COVID-19 potentially linked to hospital transmission. We estimated that 26,600 (25,900 to 27,700) individuals acquired a symptomatic SARS-CoV-2 infection in an acute Trust in England before 31st July 2020, resulting in 15,900 (15,200-16,400) or 20.1% (19.2-20.7%) of all identified hospitalised COVID-19 cases.

Conclusions

Transmission of SARS-CoV-2 to hospitalised patients likely caused approximately a fifth of identified cases of hospitalised COVID-19 in the ""first wave"" in England, but less than 1% of all infections in England. Using time to symptom onset from admission for inpatients as a detection method likely misses a substantial proportion (> 60%) of hospital-acquired infections.",,pdf:https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-022-07490-4; doi:https://doi.org/10.1186/s12879-022-07490-4; html:https://europepmc.org/articles/PMC9206097; pdf:https://europepmc.org/articles/PMC9206097?pdf=render 34910136,https://doi.org/10.1093/eurheartj/ehab863,Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease.,"HPS3/TIMI55-REVEAL Collaborative Group, Writing Committee, Sammons E, Hopewell JC, Chen F, Stevens W, Wallendszus K, Valdes-Marquez E, Dayanandan R, Knott C, Murphy K, Wincott E, Baxter A, Goodenough R, Lay M, Hill M, Macdonnell S, Fabbri G, Lucci D, Fajardo-Moser M, Brenner S, Hao D, Zhang H, Liu J, Wuhan B, Mosegaard S, Herrington W, Wanner C, Angermann C, Ertl G, Maggioni A, Barter P, Mihaylova B, Mitchel Y, Blaustein R, Goto S, Tobert J, DeLucca P, Chen Y, Chen Z, Gray A, Haynes R, Armitage J, Baigent C, Wiviott S, Cannon C, Braunwald E, Collins R, Bowman L, Landray M, REVEAL Collaborative Group.",,European heart journal,2022,2022-04-01,Y,Randomized Trial; Cetp Inhibitor Therapy,,,"

Aims

REVEAL was the first randomized controlled trial to demonstrate that adding cholesteryl ester transfer protein inhibitor therapy to intensive statin therapy reduced the risk of major coronary events. We now report results from extended follow-up beyond the scheduled study treatment period.

Methods and results

A total of 30 449 adults with prior atherosclerotic vascular disease were randomly allocated to anacetrapib 100 mg daily or matching placebo, in addition to open-label atorvastatin therapy. After stopping the randomly allocated treatment, 26 129 survivors entered a post-trial follow-up period, blind to their original treatment allocation. The primary outcome was first post-randomization major coronary event (i.e. coronary death, myocardial infarction, or coronary revascularization) during the in-trial and post-trial treatment periods, with analysis by intention-to-treat. Allocation to anacetrapib conferred a 9% [95% confidence interval (CI) 3-15%; P = 0.004] proportional reduction in the incidence of major coronary events during the study treatment period (median 4.1 years). During extended follow-up (median 2.2 years), there was a further 20% (95% CI 10-29%; P < 0.001) reduction. Overall, there was a 12% (95% CI 7-17%, P < 0.001) proportional reduction in major coronary events during the overall follow-up period (median 6.3 years), corresponding to a 1.8% (95% CI 1.0-2.6%) absolute reduction. There were no significant effects on non-vascular mortality, site-specific cancer, or other serious adverse events. Morbidity follow-up was obtained for 25 784 (99%) participants.

Conclusion

The beneficial effects of anacetrapib on major coronary events increased with longer follow-up, and no adverse effects emerged on non-vascular mortality or morbidity. These findings illustrate the importance of sufficiently long treatment and follow-up duration in randomized trials of lipid-modifying agents to assess their full benefits and potential harms.

Trial registration

International Standard Randomized Controlled Trial Number (ISRCTN) 48678192; ClinicalTrials.gov No. NCT01252953; EudraCT No. 2010-023467-18.",,pdf:https://academic.oup.com/eurheartj/article-pdf/43/14/1416/43292041/ehab863.pdf; doi:https://doi.org/10.1093/eurheartj/ehab863; html:https://europepmc.org/articles/PMC8986460; pdf:https://europepmc.org/articles/PMC8986460?pdf=render 35421974,https://doi.org/10.1186/s12911-022-01842-5,An implementation framework and a feasibility evaluation of a clinical decision support system for diabetes management in secondary mental healthcare using CogStack.,"Patel D, Msosa YJ, Wang T, Mustafa OG, Gee S, Williams J, Roberts A, Dobson RJ, Gaughran F.",,BMC medical informatics and decision making,2022,2022-04-14,Y,Monitoring; Diabetes; Clinical Decision Support; Pre-diabetes; Ehealth; Alerting; Cogstack,,,"

Background

Improvements to the primary prevention of physical health illnesses like diabetes in the general population have not been mirrored to the same extent in people with serious mental illness (SMI). This work evaluates the technical feasibility of implementing an electronic clinical decision support system (eCDSS) for supporting the management of dysglycaemia and diabetes in patients with serious mental illness in a secondary mental healthcare setting.

Methods

A stepwise approach was taken as an overarching and guiding framework for this work. Participatory methods were employed to design and deploy a monitoring and alerting eCDSS. The eCDSS was evaluated for its technical feasibility. The initial part of the feasibility evaluation was conducted in an outpatient community mental health team. Thereafter, the evaluation of the eCDSS progressed to a more in-depth in silico validation.

Results

A digital health intervention that enables monitoring and alerting of at-risk patients based on an approved diabetes management guideline was developed. The eCDSS generated alerts according to expected standards and in line with clinical guideline recommendations.

Conclusions

It is feasible to design and deploy a functional monitoring and alerting eCDSS in secondary mental healthcare. Further work is required in order to fully evaluate the integration of the eCDSS into routine clinical workflows. By describing and sharing the steps that were and will be taken from concept to clinical testing, useful insights could be provided to teams that are interested in building similar digital health interventions.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-022-01842-5; doi:https://doi.org/10.1186/s12911-022-01842-5; html:https://europepmc.org/articles/PMC9009062; pdf:https://europepmc.org/articles/PMC9009062?pdf=render 33905882,https://doi.org/10.1016/j.media.2021.102050,Phenotype discovery from population brain imaging.,"Gong W, Beckmann CF, Smith SM.",,Medical image analysis,2021,2021-03-31,Y,Neuroimaging; Uk Biobank; Behaviour Prediction; Multimodal Independent Component Analysis; Phenotype Discovery,,,"Neuroimaging allows for the non-invasive study of the brain in rich detail. Data-driven discovery of patterns of population variability in the brain has the potential to be extremely valuable for early disease diagnosis and understanding the brain. The resulting patterns can be used as imaging-derived phenotypes (IDPs), and may complement existing expert-curated IDPs. However, population datasets, comprising many different structural and functional imaging modalities from thousands of subjects, provide a computational challenge not previously addressed. Here, for the first time, a multimodal independent component analysis approach is presented that is scalable for data fusion of voxel-level neuroimaging data in the full UK Biobank (UKB) dataset, that will soon reach 100,000 imaged subjects. This new computational approach can estimate modes of population variability that enhance the ability to predict thousands of phenotypic and behavioural variables using data from UKB and the Human Connectome Project. A high-dimensional decomposition achieved improved predictive power compared with widely-used analysis strategies, single-modality decompositions and existing IDPs. In UKB data (14,503 subjects with 47 different data modalities), many interpretable associations with non-imaging phenotypes were identified, including multimodal spatial maps related to fluid intelligence, handedness and disease, in some cases where IDP-based approaches failed.",,doi:https://doi.org/10.1016/j.media.2021.102050; doi:https://doi.org/10.1016/j.media.2021.102050; html:https://europepmc.org/articles/PMC8850869; pdf:https://europepmc.org/articles/PMC8850869?pdf=render 33299071,https://doi.org/10.1038/s41746-020-00357-5,Belief of having had unconfirmed Covid-19 infection reduces willingness to participate in app-based contact tracing.,"Bachtiger P, Adamson A, Quint JK, Peters NS.",,NPJ digital medicine,2020,2020-11-06,Y,,,,"Contact tracing and lockdown are health policies being used worldwide to combat the coronavirus (COVID-19). The UK National Health Service (NHS) Track and Trace Service has plans for a nationwide app that notifies the need for self-isolation to those in contact with a person testing positive for COVID-19. To be successful, such an app will require high uptake, the determinants and willingness for which are unclear but essential to understand for effective public health benefit. The objective of this study was to measure the determinants of willingness to participate in an NHS app-based contact-tracing programme using a questionnaire within the Care Information Exchange (CIE)-the largest patient-facing electronic health record in the NHS. Among 47,708 registered NHS users of the CIE, 27% completed a questionnaire asking about willingness to participate in app-based contact tracing, understanding of government advice, mental and physical wellbeing and their healthcare utilisation-related or not to COVID-19. Descriptive statistics are reported alongside univariate and multivariable logistic regression models, with positive or negative responses to a question on app-based contact tracing as the dependent variable. 26.1% of all CIE participants were included in the analysis (N = 12,434, 43.0% male, mean age 55.2). 60.3% of respondents were willing to participate in app-based contact tracing. Out of those who responded 'no', 67.2% stated that this was due to privacy concerns. In univariate analysis, worsening mood, fear and anxiety in relation to changes in government rules around lockdown were associated with lower willingness to participate. Multivariable analysis showed that difficulty understanding government rules was associated with a decreased inclination to download the app, with those scoring 1-2 and 3-4 in their understanding of the new government rules being 45% and 27% less inclined to download the contact-tracing app, respectively; when compared to those who rated their understanding as 5-6/10 (OR for 1-2/10 = 0.57 [CI 0.48-0.67]; OR for 3-4/10 = 0.744 [CI 0.64-0.87]), whereas scores of 7-8 and 9-10 showed a 43% and 31% respective increase. Those reporting an unconfirmed belief of having previously had and recovered from COVID-19 were 27% less likely to be willing to download the app; belief of previous recovery from COVID-19 infection OR 0.727 [0.585-0.908]). In this large UK-wide questionnaire of wellbeing in lockdown, a willingness for app-based contact tracing over an appropriate age range is 60%-close to the estimated 56% population uptake, and substantially less than the smartphone-user uptake considered necessary for an app-based contact tracing to be an effective intervention to help suppress an epidemic. Difficulty comprehending government advice and uncertainty of diagnosis, based on a public health policy of not testing to confirm self-reported COVID-19 infection during lockdown, therefore reduce willingness to adopt a government contact-tracing app to a level below the threshold for effectiveness as a tool to suppress an epidemic.",,pdf:https://www.nature.com/articles/s41746-020-00357-5.pdf; doi:https://doi.org/10.1038/s41746-020-00357-5; html:https://europepmc.org/articles/PMC7648058; pdf:https://europepmc.org/articles/PMC7648058?pdf=render -37789377,https://doi.org/10.1186/s12943-023-01863-2,Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures.,"Figiel S, Yin W, Doultsinos D, Erickson A, Poulose N, Singh R, Magnussen A, Anbarasan T, Teague R, He M, Lundeberg J, Loda M, Verrill C, Colling R, Gill PS, Bryant RJ, Hamdy FC, Woodcock DJ, Mills IG, Cussenot O, Lamb AD.",,Molecular cancer,2023,2023-10-03,Y,prostate cancer; Virtual Biopsy; Spatial Transcriptomics; Prognostic Genetic Signatures,,,"Genetic signatures have added a molecular dimension to prognostics and therapeutic decision-making. However, tumour heterogeneity in prostate cancer and current sampling methods could confound accurate assessment. Based on previously published spatial transcriptomic data from multifocal prostate cancer, we created virtual biopsy models that mimic conventional biopsy placement and core size. We then analysed the gene expression of different prognostic signatures (OncotypeDx®, Decipher®, Prostadiag®) using a step-wise approach with increasing resolution from pseudo-bulk analysis of the whole biopsy, to differentiation by tissue subtype (benign, stroma, tumour), followed by distinct tumour grade and finally clonal resolution. The gene expression profile of virtual tumour biopsies revealed clear differences between grade groups and tumour clones, compared to a benign control, which were not reflected in bulk analyses. This suggests that bulk analyses of whole biopsies or tumour-only areas, as used in clinical practice, may provide an inaccurate assessment of gene profiles. The type of tissue, the grade of the tumour and the clonal composition all influence the gene expression in a biopsy. Clinical decision making based on biopsy genomics should be made with caution while we await more precise targeting and cost-effective spatial analyses.",,pdf:https://molecular-cancer.biomedcentral.com/counter/pdf/10.1186/s12943-023-01863-2; doi:https://doi.org/10.1186/s12943-023-01863-2; html:https://europepmc.org/articles/PMC10546768; pdf:https://europepmc.org/articles/PMC10546768?pdf=render 35482474,https://doi.org/10.1111/bjd.21627,Biomarkers of disease progression in people with psoriasis: a scoping review.,"Ramessur R, Corbett M, Marshall D, Acencio ML, Barbosa IA, Dand N, Di Meglio P, Haddad S, Jensen AHM, Koopmann W, Mahil SK, Ostaszewski M, Rahmatulla S, Rastrick J, Saklatvala J, Weidinger S, Wright K, Eyerich K, Ndlovu M, Barker JN, Skov L, Conrad C, Smith CH, BIOMAP consortium.",,The British journal of dermatology,2022,2022-07-11,Y,,,,"

Background

Identification of those at risk of more severe psoriasis and/or associated morbidities offers opportunity for early intervention, reduced disease burden and more cost-effective healthcare. Prognostic biomarkers of disease progression have thus been the focus of intense research, but none are part of routine practice.

Objectives

To identify and catalogue candidate biomarkers of disease progression in psoriasis for the translational research community.

Methods

A systematic search of CENTRAL, Embase, LILACS and MEDLINE was performed for relevant articles published between 1990 and December 2021. Eligibility criteria were studies involving patients with psoriasis (any age, n ≥ 50) reporting biomarkers associated with disease progression. The main outcomes were any measure of skin severity or any prespecified psoriasis comorbidity. Data were extracted by one reviewer and checked by a second; studies meeting minimal quality criteria (longitudinal design and/or use of methods to control for confounding) were formally assessed for bias. Candidate biomarkers were identified by an expert multistakeholder group using a majority voting consensus exercise, and mapped to relevant cellular and molecular pathways.

Results

Of 181 included studies, most investigated genomic or proteomic biomarkers associated with disease severity (n = 145) or psoriatic arthritis (n = 30). Methodological and reporting limitations compromised interpretation of findings, most notably a lack of longitudinal studies, and inadequate control for key prognostic factors. The following candidate biomarkers with future potential utility were identified for predicting disease severity: LCE3D, interleukin (IL)23R, IL23A, NFKBIL1 loci, HLA-C*06:02 (genomic), IL-17A, IgG aHDL, GlycA, I-FABP and kallikrein 8 (proteomic), tyramine (metabolomic); psoriatic arthritis: HLA-C*06:02, HLA-B*27, HLA-B*38, HLA-B*08, and variation at the IL23R and IL13 loci (genomic); IL-17A, CXCL10, Mac-2 binding protein, integrin b5, matrix metalloproteinase-3 and macrophage-colony stimulating factor (proteomic) and tyramine and mucic acid (metabolomic); and type 2 diabetes mellitus: variation in IL12B and IL23R loci (genomic). No biomarkers were supported by sufficient evidence for clinical use without further validation.

Conclusions

This review provides a comprehensive catalogue of investigated biomarkers of disease progression in psoriasis. Future studies must address the common methodological limitations identified herein to expedite discovery and validation of biomarkers for clinical use. What is already known about this topic? The current treatment paradigm in psoriasis is reactive. There is a need to develop effective risk-stratified management approaches that can proactively attenuate the substantial burden of disease. Prognostic biomarkers of disease progression have therefore been the focus of intense research. What does this study add? This review is the first to scope, collate and catalogue research investigating biomarkers of disease progression in psoriasis. The review identifies potentially promising candidate biomarkers for further investigation and highlights common important limitations that should be considered when designing and conducting future studies in this area.",,pdf:https://kclpure.kcl.ac.uk/ws/files/177671246/Br_J_Dermatol_2022_Ramessur_Biomarkers_of_disease_progression_in_people_with_psoriasis_a_scoping_review.pdf; doi:https://doi.org/10.1111/bjd.21627; html:https://europepmc.org/articles/PMC9796834; pdf:https://europepmc.org/articles/PMC9796834?pdf=render +37789377,https://doi.org/10.1186/s12943-023-01863-2,Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures.,"Figiel S, Yin W, Doultsinos D, Erickson A, Poulose N, Singh R, Magnussen A, Anbarasan T, Teague R, He M, Lundeberg J, Loda M, Verrill C, Colling R, Gill PS, Bryant RJ, Hamdy FC, Woodcock DJ, Mills IG, Cussenot O, Lamb AD.",,Molecular cancer,2023,2023-10-03,Y,prostate cancer; Virtual Biopsy; Spatial Transcriptomics; Prognostic Genetic Signatures,,,"Genetic signatures have added a molecular dimension to prognostics and therapeutic decision-making. However, tumour heterogeneity in prostate cancer and current sampling methods could confound accurate assessment. Based on previously published spatial transcriptomic data from multifocal prostate cancer, we created virtual biopsy models that mimic conventional biopsy placement and core size. We then analysed the gene expression of different prognostic signatures (OncotypeDx®, Decipher®, Prostadiag®) using a step-wise approach with increasing resolution from pseudo-bulk analysis of the whole biopsy, to differentiation by tissue subtype (benign, stroma, tumour), followed by distinct tumour grade and finally clonal resolution. The gene expression profile of virtual tumour biopsies revealed clear differences between grade groups and tumour clones, compared to a benign control, which were not reflected in bulk analyses. This suggests that bulk analyses of whole biopsies or tumour-only areas, as used in clinical practice, may provide an inaccurate assessment of gene profiles. The type of tissue, the grade of the tumour and the clonal composition all influence the gene expression in a biopsy. Clinical decision making based on biopsy genomics should be made with caution while we await more precise targeting and cost-effective spatial analyses.",,pdf:https://molecular-cancer.biomedcentral.com/counter/pdf/10.1186/s12943-023-01863-2; doi:https://doi.org/10.1186/s12943-023-01863-2; html:https://europepmc.org/articles/PMC10546768; pdf:https://europepmc.org/articles/PMC10546768?pdf=render 31588514,https://doi.org/10.1093/ptj/pzz151,Physical Activity and Sedentary Behavior 6 Months After Musculoskeletal Trauma: What Factors Predict Recovery?,"Ekegren CL, Climie RE, Simpson PM, Owen N, Dunstan DW, Veitch W, Gabbe BJ.",,Physical therapy,2020,2020-02-01,N,,,,"

Background

Physical activity is increasingly recognized as an important marker of functional recovery following fracture.

Objective

The objectives of this study were to measure sedentary behavior and physical activity 2 weeks and 6 months following fracture and to determine associated demographic and injury factors.

Design

This was an observational study.

Methods

Two weeks and 6 months following fracture, 83 adults who were 18 to 69 years old and had upper limb (UL) or lower limb (LL) fractures wore an accelerometer and an inclinometer for 10 days. We calculated sitting time, steps, moderate-intensity physical activity (MPA), and vigorous-intensity physical activity and conducted linear mixed-effects multivariable regression analyses to determine factors associated with temporal changes in activity.

Results

At 6 months versus 2 weeks after fracture, participants sat less, took more steps, and engaged in more MPA. Participants with LL fractures sat 2 hours more, took 66% fewer steps, and engaged in 77% less MPA than participants with UL fractures. Greater reductions in sitting time were observed for participants in the youngest age group and with LL fractures, participants with high preinjury activity, and participants who were overweight or obese. For steps, greater improvement was observed for participants in the youngest and middle-aged groups and those with LL fractures. For MPA, greater improvement was observed for middle-aged participants and those with LL fractures.

Limitations

Although this study was sufficiently powered for the analysis of major categories, a convenience sample that may not be representative of all people with musculoskeletal trauma was used.

Conclusions

Working-age adults with LL fractures had lower levels of physical activity 6 months after fracture than those with UL fractures. Older adults showed less improvement over time, suggesting that they are an important target group for interventions aimed at regaining preinjury activity levels.",,pdf:https://academic.oup.com/ptj/article-pdf/100/2/332/32901113/pzz151.pdf; doi:https://doi.org/10.1093/ptj/pzz151 34173574,https://doi.org/10.1016/j.puhip.2020.100039,Schools and COVID-19: Reopening Pandora's box?,"Ziauddeen N, Woods-Townsend K, Saxena S, Gilbert R, Alwan NA.",,"Public health in practice (Oxford, England)",2020,2020-11-01,Y,Safety; Covid-19; School Re-Opening,,,"Schools in countries across the world are reopening as lockdown to slow progression of COVID-19 is eased. The UK government ordered school closures in England from March 20, 2020, later than the rest of Europe. A temporary and limited return for some year groups was trialled from June 2020. Teachers, school governors, the public and doctors have openly challenged the decision. The UK government has struggled to provide enough detailed information to convince the public, teachers and health practitioners, that effective systems for protection, including test, trace and isolate, are in place to prevent and manage outbreaks in schools. Risks of infection on reopening to children, staff and families must be weighed against the harms of closure to children's education and social development. The potential consequences, if the re-opening of schools is managed badly, is subsequent waves of COVID-19 infection leading to more deaths, further school closures and prolonged restrictions, losing any ground gained thus far. This article weighs the evidence for risks and benefits of reopening schools during the pandemic.",,doi:https://doi.org/10.1016/j.puhip.2020.100039; doi:https://doi.org/10.1016/j.puhip.2020.100039; html:https://europepmc.org/articles/PMC7486860; pdf:https://europepmc.org/articles/PMC7486860?pdf=render 34767555,https://doi.org/10.1371/journal.pmed.1003832,Educational and health outcomes of schoolchildren in local authority care in Scotland: A retrospective record linkage study.,"Fleming M, McLay JS, Clark D, King A, Mackay DF, Minnis H, Pell JP.",,PLoS medicine,2021,2021-11-12,Y,,,,"

Background

Looked after children are defined as children who are in the care of their local authority. Previous studies have reported that looked after children have poorer mental and physical health, increased behavioural problems, and increased self-harm and mortality compared to peers. They also experience poorer educational outcomes, yet population-wide research into the latter is lacking, particularly in the United Kingdom. Education and health share a bidirectional relationship; therefore, it is important to dually investigate both outcomes. Our study aimed to compare educational and health outcomes for looked after children with peers, adjusting for sociodemographic, maternity, and comorbidity confounders.

Methods and findings

Linkage of 9 Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, examinations, school absences/exclusions, unemployment, and looked after children provided retrospective data on 715,111 children attending Scottish schools between 2009 and 2012 (13,898 [1.9%] looked after). Compared to peers, 13,898 (1.9%) looked after children were more likely to be absent (adjusted incidence rate ratio [AIRR] 1.27, 95% confidence interval [CI] 1.24 to 1.30) and excluded (AIRR 4.09, 95% CI 3.86 to 4.33) from school, have special educational need (SEN; adjusted odds ratio [AOR] 3.48, 95% CI 3.35 to 3.62) and neurodevelopmental multimorbidity (AOR 2.45, 95% CI 2.34 to 2.57), achieve the lowest level of academic attainment (AOR 5.92, 95% CI 5.17 to 6.78), and be unemployed after leaving school (AOR 2.12, 95% CI 1.96 to 2.29). They were more likely to require treatment for epilepsy (AOR 1.50, 95% CI 1.27 to 1.78), attention deficit hyperactivity disorder (ADHD; AOR 3.01, 95% CI 2.76 to 3.27), and depression (AOR 1.90, 95% CI 1.62 to 2.22), be hospitalised overall (adjusted hazard ratio [AHR] 1.23, 95% CI 1.19 to 1.28) for injury (AHR 1.80, 95% CI 1.69 to 1.91) and self-harm (AHR 5.19, 95% CI 4.66 to 5.78), and die prematurely (AHR 3.21, 95% CI 2.16 to 4.77). Compared to children looked after at home, children looked after away from home had less absenteeism (AIRR 0.35, 95% CI 0.33 to 0.36), less exclusion (AIRR 0.63, 95% CI 0.56 to 0.71), less unemployment (AOR 0.53, 95% CI 0.46 to 0.62), and better attainment (AIRR 0.31, 95% CI 0.23 to 0.40). Therefore, among those in care, being cared for away from home appeared to be a protective factor resulting in better educational outcomes. The main limitations of this study were lack of data on local authority care preschool or before 2009, total time spent in care, and age of first contact with social care.

Conclusions

Looked after children had poorer health and educational outcomes than peers independent of increased neurodevelopmental conditions and SEN. Further work is required to understand whether poorer outcomes relate to reasons for entering care, including maltreatment and adverse childhood events, neurodevelopmental vulnerabilities, or characteristics of the care system.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003832&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003832; html:https://europepmc.org/articles/PMC8589203; pdf:https://europepmc.org/articles/PMC8589203?pdf=render @@ -2031,8 +2031,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 35991675,https://doi.org/10.1016/j.lana.2022.100335,Primary healthcare protects vulnerable populations from inequity in COVID-19 vaccination: An ecological analysis of nationwide data from Brazil.,"Bastos LSL, Aguilar S, Rache B, Maçaira P, Baião F, Cerbino-Neto J, Rocha R, Hamacher S, Ranzani OT, Bozza FA.",,Lancet regional health. Americas,2022,2022-08-17,Y,Vaccine; Socioeconomic Factors; Human Development; Primary Healthcare; Low-and-middle-income Countries; Covid19,,,"

Background

There is limited information on the inequity of access to vaccination in low-and-middle-income countries during the COVID-19 pandemic. Here, we described the progression of the Brazilian immunisation program for COVID-19, and the association of socioeconomic development with vaccination rates, considering the potential protective effect of primary health care coverage.

Methods

We performed an ecological analysis of COVID-19 immunisation data from the Brazilian National Immunization Program from January 17 to August 31, 2021. We analysed the dynamics of vaccine coverage in the adult population of 5,570 Brazilian municipalities. We estimated the association of human development index (HDI) levels (low, medium, and high) with age-sex standardised first dose coverage using a multivariable negative binomial regression model. We evaluated the interaction between the HDI and primary health care coverage. Finally, we compared the adjusted monthly progression of vaccination rates, hospital admission and in-hospital death rates among HDI levels.

Findings

From January 17 to August 31, 2021, 202,427,355 COVID-19 vaccine doses were administered in Brazil. By the end of the period, 64·2% of adults had first and 31·4% second doses, with more than 90% of those aged ≥60 years with primary scheme completed. Four distinct vaccine platforms were used in the country, ChAdOx1-S/nCoV-19, Sinovac-CoronaVac, BNT162b2, Ad26.COV2.S, composing 44·8%, 33·2%, 19·6%, and 2·4% of total doses, respectively. First dose coverage differed between municipalities with high, medium, and low HDI (Median [interquartile range] 72 [66, 79], 68 [61, 75] and 63 [55, 70] doses per 100 people, respectively). Municipalities with low (Rate Ratio [RR, 95% confidence interval]: 0·87 [0·85-0·88]) and medium (RR [95% CI]: 0·94 [0·93-0·95]) development were independently associated with lower vaccination rates compared to those with high HDI. Primary health care coverage modified the association of HDI and vaccination rate, improving vaccination rates in those municipalities of low HDI and high primary health care coverage. Low HDI municipalities presented a delayed decrease in adjusted in-hospital death rates by first dose coverage compared to high HDI locations.

Interpretation

In Brazil, socioeconomic disparities negatively impacted the first dose vaccination rate. However, the primary health care mitigated these disparities, suggesting that the primary health care coverage guarantees more equitable access to vaccines in vulnerable locations.

Funding

This work is part of the Grand Challenges ICODA pilot initiative, delivered by Health Data Research UK and funded by the Bill & Melinda Gates Foundation and the Minderoo Foundation. This study was supported by the National Council for Scientific and Technological Development (CNPq), the Coordination for the Improvement of Higher Education Personnel (CAPES) - Finance Code 001, Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ) and the Pontifical Catholic University of Rio de Janeiro.",,doi:https://doi.org/10.1016/j.lana.2022.100335; doi:https://doi.org/10.1016/j.lana.2022.100335; html:https://europepmc.org/articles/PMC9381845; pdf:https://europepmc.org/articles/PMC9381845?pdf=render 37770476,https://doi.org/10.1038/s41467-023-41249-y,Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration.,"Austin-Zimmerman I, Levey DF, Giannakopoulou O, Deak JD, Galimberti M, Adhikari K, Zhou H, Denaxas S, Irizar H, Kuchenbaecker K, McQuillin A, Million Veteran Program, Concato J, Buysse DJ, Gaziano JM, Gottlieb DJ, Polimanti R, Stein MB, Bramon E, Gelernter J.",,Nature communications,2023,2023-09-28,Y,,,,"Sleep duration has been linked to a wide range of negative health outcomes and to reduced life expectancy. We present genome-wide association studies of short ( ≤ 5 h) and long ( ≥ 10 h) sleep duration in adults of European (N = 445,966), African (N = 27,785), East Asian (N = 3141), and admixed-American (N = 16,250) ancestry from UK Biobank and the Million Veteran Programme. In a cross-population meta-analysis, we identify 84 independent loci for short sleep and 1 for long sleep. We estimate SNP-based heritability for both sleep traits in each ancestry based on population derived linkage disequilibrium (LD) scores using cov-LDSC. We identify positive genetic correlation between short and long sleep traits (rg = 0.16 ± 0.04; p = 0.0002), as well as similar patterns of genetic correlation with other psychiatric and cardiometabolic phenotypes. Mendelian randomisation reveals a directional causal relationship between short sleep and depression, and a bidirectional causal relationship between long sleep and depression.",,pdf:https://www.nature.com/articles/s41467-023-41249-y.pdf; doi:https://doi.org/10.1038/s41467-023-41249-y; html:https://europepmc.org/articles/PMC10539313; pdf:https://europepmc.org/articles/PMC10539313?pdf=render 34091032,https://doi.org/10.1016/j.neuroimage.2021.118235,Subspace-constrained approaches to low-rank fMRI acceleration.,"Mason HT, Graedel NN, Miller KL, Chiew M.",,NeuroImage,2021,2021-06-03,Y,fMRI; Tikhonov regularization; Acceleration; temporal resolution; Low Rank; Temporal Smoothing; K-t Faster; Low Resolution Priors,,,"Acceleration methods in fMRI aim to reconstruct high fidelity images from under-sampled k-space, allowing fMRI datasets to achieve higher temporal resolution, reduced physiological noise aliasing, and increased statistical degrees of freedom. While low levels of acceleration are typically part of standard fMRI protocols through parallel imaging, there exists the potential for approaches that allow much greater acceleration. One such existing approach is k-t FASTER, which exploits the inherent low-rank nature of fMRI. In this paper, we present a reformulated version of k-t FASTER which includes additional L2 constraints within a low-rank framework. We evaluated the effect of three different constraints against existing low-rank approaches to fMRI reconstruction: Tikhonov constraints, low-resolution priors, and temporal subspace smoothness. The different approaches are separately tested for robustness to under-sampling and thermal noise levels, in both retrospectively and prospectively-undersampled finger-tapping task fMRI data. Reconstruction quality is evaluated by accurate reconstruction of low-rank subspaces and activation maps. The use of L2 constraints was found to achieve consistently improved results, producing high fidelity reconstructions of statistical parameter maps at higher acceleration factors and lower SNR values than existing methods, but at a cost of longer computation time. In particular, the Tikhonov constraint proved very robust across all tested datasets, and the temporal subspace smoothness constraint provided the best reconstruction scores in the prospectively-undersampled dataset. These results demonstrate that regularized low-rank reconstruction of fMRI data can recover functional information at high acceleration factors without the use of any model-based spatial constraints.",,doi:https://doi.org/10.1016/j.neuroimage.2021.118235; doi:https://doi.org/10.1016/j.neuroimage.2021.118235; html:https://europepmc.org/articles/PMC7611820; pdf:https://europepmc.org/articles/PMC7611820?pdf=render -36717723,https://doi.org/10.1038/s41590-022-01380-2,A patient-centric modeling framework captures recovery from SARS-CoV-2 infection.,"Ruffieux H, Hanson AL, Lodge S, Lawler NG, Whiley L, Gray N, Nolan TH, Bergamaschi L, Mescia F, Turner L, de Sa A, Pelly VS, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) BioResource COVID-19 Collaboration, Kotagiri P, Kingston N, Bradley JR, Holmes E, Wist J, Nicholson JK, Lyons PA, Smith KGC, Richardson S, Bantug GR, Hess C.",,Nature immunology,2023,2023-01-30,Y,,,,"The biology driving individual patient responses to severe acute respiratory syndrome coronavirus 2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data and covering a year after disease onset, from 215 infected individuals with differing disease severities. Our analyses revealed distinct 'systemic recovery' profiles, with specific progression and resolution of the inflammatory, immune cell, metabolic and clinical responses. In particular, we found a strong inter-patient and intra-patient temporal covariation of innate immune cell numbers, kynurenine metabolites and lipid metabolites, which highlighted candidate immunologic and metabolic pathways influencing the restoration of homeostasis, the risk of death and that of long COVID. Based on these data, we identified a composite signature predictive of systemic recovery, using a joint model on cellular and molecular parameters measured soon after disease onset. New predictions can be generated using the online tool http://shiny.mrc-bsu.cam.ac.uk/apps/covid-19-systemic-recovery-prediction-app , designed to test our findings prospectively.",,pdf:https://www.nature.com/articles/s41590-022-01380-2.pdf; doi:https://doi.org/10.1038/s41590-022-01380-2; html:https://europepmc.org/articles/PMC9892000; pdf:https://europepmc.org/articles/PMC9892000?pdf=render 30382236,https://doi.org/10.1038/s41433-018-0229-6,The diagnostic accuracy of OCT angiography in naive and treated neovascular age-related macular degeneration: a review.,"Perrott-Reynolds R, Cann R, Cronbach N, Neo YN, Ho V, McNally O, Madi HA, Cochran C, Chakravarthy U.",,"Eye (London, England)",2019,2018-10-31,N,,,,"Optical coherence tomography angiography (OCTA) is a non-invasive retinal imaging innovation that has been gaining popularity for the evaluation of the retinal vasculature. Of clinical importance is its current use either as an alternative or in conjunction with conventional dye-based angiography in neovascular age-related macular degeneration. OCTA is not without limitations and these include image artefact, a relatively small field of view and failure of the segmentation algorithms, which can confound the interpretation of findings. While there are numerous publications on OCTA in neovascular AMD, few have examined the diagnostic accuracy of this new technology compared with the accepted gold standard of fundus fluorescein angiography (FFA). In this review, we summarise the literature on the clinical application of OCTA in nAMD. In particular, we have reviewed the published articles that have reported the sensitivity and specificity of OCTA in the diagnosis of nAMD, and those that have described and or correlated the morphological findings and compared them to dye-based angiography.",Perrott et al. reviewed strengths and limitations of an eye (retinal) imagining method for diagnosis of a condition affecting the central part of the retina (the macula). This degenerative condition may result in loss of central vision in older adults. Perrott et al. concluded that diagnostic accuracy depends on both method and equipment. ,pdf:https://www.nature.com/articles/s41433-018-0229-6.pdf; doi:https://doi.org/10.1038/s41433-018-0229-6; html:https://europepmc.org/articles/PMC6367454; pdf:https://europepmc.org/articles/PMC6367454?pdf=render; doi:https://doi.org/10.1038/s41433-018-0229-6 +36717723,https://doi.org/10.1038/s41590-022-01380-2,A patient-centric modeling framework captures recovery from SARS-CoV-2 infection.,"Ruffieux H, Hanson AL, Lodge S, Lawler NG, Whiley L, Gray N, Nolan TH, Bergamaschi L, Mescia F, Turner L, de Sa A, Pelly VS, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) BioResource COVID-19 Collaboration, Kotagiri P, Kingston N, Bradley JR, Holmes E, Wist J, Nicholson JK, Lyons PA, Smith KGC, Richardson S, Bantug GR, Hess C.",,Nature immunology,2023,2023-01-30,Y,,,,"The biology driving individual patient responses to severe acute respiratory syndrome coronavirus 2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data and covering a year after disease onset, from 215 infected individuals with differing disease severities. Our analyses revealed distinct 'systemic recovery' profiles, with specific progression and resolution of the inflammatory, immune cell, metabolic and clinical responses. In particular, we found a strong inter-patient and intra-patient temporal covariation of innate immune cell numbers, kynurenine metabolites and lipid metabolites, which highlighted candidate immunologic and metabolic pathways influencing the restoration of homeostasis, the risk of death and that of long COVID. Based on these data, we identified a composite signature predictive of systemic recovery, using a joint model on cellular and molecular parameters measured soon after disease onset. New predictions can be generated using the online tool http://shiny.mrc-bsu.cam.ac.uk/apps/covid-19-systemic-recovery-prediction-app , designed to test our findings prospectively.",,pdf:https://www.nature.com/articles/s41590-022-01380-2.pdf; doi:https://doi.org/10.1038/s41590-022-01380-2; html:https://europepmc.org/articles/PMC9892000; pdf:https://europepmc.org/articles/PMC9892000?pdf=render 37542272,https://doi.org/10.1186/s12916-023-02948-x,Common mental health disorders in adults with inflammatory skin conditions: nationwide population-based matched cohort studies in the UK.,"Henderson AD, Adesanya E, Mulick A, Matthewman J, Vu N, Davies F, Smith CH, Hayes J, Mansfield KE, Langan SM.",,BMC medicine,2023,2023-08-04,Y,Depression; Anxiety; Skin Disease; Electronic Health Records,,,"

Background

Psoriasis and atopic eczema are common inflammatory skin diseases. Existing research has identified increased risks of common mental disorders (anxiety, depression) in people with eczema and psoriasis; however, explanations for the associations remain unclear. We aimed to establish the risk factors for mental illness in those with eczema or psoriasis and identify the population groups most at risk.

Methods

We used routinely collected data from the UK Clinical Practice Research Datalink (CPRD) GOLD. Adults registered with a general practice in CPRD (1997-2019) were eligible for inclusion. Individuals with eczema/psoriasis were matched (age, sex, practice) to up to five adults without eczema/psoriasis. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for hazards of anxiety or depression in people with eczema/psoriasis compared to people without. We adjusted for known confounders (deprivation, asthma [eczema], psoriatic arthritis [psoriasis], Charlson comorbidity index, calendar period) and potential mediators (harmful alcohol use, body mass index [BMI], smoking status, and, in eczema only, sleep quality [insomnia diagnoses, specific sleep problem medications] and high-dose oral glucocorticoids).

Results

We identified two cohorts with and without eczema (1,032,782, matched to 4,990,125 without), and with and without psoriasis (366,884, matched to 1,834,330 without). Sleep quality was imbalanced in the eczema cohorts, twice as many people with eczema had evidence of poor sleep at baseline than those without eczema, including over 20% of those with severe eczema. After adjusting for potential confounders and mediators, eczema and psoriasis were associated with anxiety (adjusted HR [95% CI]: eczema 1.14 [1.13-1.16], psoriasis 1.17 [1.15-1.19]) and depression (adjusted HR [95% CI]: eczema 1.11 [1.1-1.12], psoriasis 1.21 [1.19-1.22]). However, we found evidence that these increased hazards are unlikely to be constant over time and were especially high 1-year after study entry.

Conclusions

Atopic eczema and psoriasis are associated with increased incidence of anxiety and depression in adults. These associations may be mediated through known modifiable risk factors, especially sleep quality in people with eczema. Our findings highlight potential opportunities for the prevention of anxiety and depression in people with eczema/psoriasis through treatment of modifiable risk factors and enhanced eczema/psoriasis management.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02948-x; doi:https://doi.org/10.1186/s12916-023-02948-x; html:https://europepmc.org/articles/PMC10403838; pdf:https://europepmc.org/articles/PMC10403838?pdf=render 32887683,https://doi.org/10.1136/annrheumdis-2020-217421,Genomic risk scores for juvenile idiopathic arthritis and its subtypes.,"Cánovas R, Cobb J, Brozynska M, Bowes J, Li YR, Smith SL, Hakonarson H, Thomson W, Ellis JA, Abraham G, Munro JE, Inouye M.",,Annals of the rheumatic diseases,2020,2020-09-04,Y,Polymorphism; Arthritis; Genetic; Juvenile; Rheumatoid,,,"

Objectives

Juvenile idiopathic arthritis (JIA) is an autoimmune disease and a common cause of chronic disability in children. Diagnosis of JIA is based purely on clinical symptoms, which can be variable, leading to diagnosis and treatment delays. Despite JIA having substantial heritability, the construction of genomic risk scores (GRSs) to aid or expedite diagnosis has not been assessed. Here, we generate GRSs for JIA and its subtypes and evaluate their performance.

Methods

We examined three case/control cohorts (UK, US-based and Australia) with genome-wide single nucleotide polymorphism (SNP) genotypes. We trained GRSs for JIA and its subtypes using lasso-penalised linear models in cross-validation on the UK cohort, and externally tested it in the other cohorts.

Results

The JIA GRS alone achieved cross-validated area under the receiver operating characteristic curve (AUC)=0.670 in the UK cohort and externally-validated AUCs of 0.657 and 0.671 in the US-based and Australian cohorts, respectively. In logistic regression of case/control status, the corresponding odds ratios (ORs) per standard deviation (SD) of GRS were 1.831 (1.685 to 1.991) and 2.008 (1.731 to 2.345), and were unattenuated by adjustment for sex or the top 10 genetic principal components. Extending our analysis to JIA subtypes revealed that the enthesitis-related JIA had both the longest time-to-referral and the subtype GRS with the strongest predictive capacity overall across data sets: AUCs 0.82 in UK; 0.84 in Australian; and 0.70 in US-based. The particularly common oligoarthritis JIA also had a GRS that outperformed those for JIA overall, with AUCs of 0.72, 0.74 and 0.77, respectively.

Conclusions

A GRS for JIA has potential to augment clinical JIA diagnosis protocols, prioritising higher-risk individuals for follow-up and treatment. Consistent with JIA heterogeneity, subtype-specific GRSs showed particularly high performance for enthesitis-related and oligoarthritis JIA.",,pdf:https://ard.bmj.com/content/annrheumdis/79/12/1572.full.pdf; doi:https://doi.org/10.1136/annrheumdis-2020-217421; html:https://europepmc.org/articles/PMC7677485; pdf:https://europepmc.org/articles/PMC7677485?pdf=render 34310590,https://doi.org/10.1371/journal.pcbi.1009098,Projecting contact matrices in 177 geographical regions: An update and comparison with empirical data for the COVID-19 era.,"Prem K, Zandvoort KV, Klepac P, Eggo RM, Davies NG, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Cook AR, Jit M.",,PLoS computational biology,2021,2021-07-26,Y,,,,"Mathematical models have played a key role in understanding the spread of directly-transmissible infectious diseases such as Coronavirus Disease 2019 (COVID-19), as well as the effectiveness of public health responses. As the risk of contracting directly-transmitted infections depends on who interacts with whom, mathematical models often use contact matrices to characterise the spread of infectious pathogens. These contact matrices are usually generated from diary-based contact surveys. However, the majority of places in the world do not have representative empirical contact studies, so synthetic contact matrices have been constructed using more widely available setting-specific survey data on household, school, classroom, and workplace composition combined with empirical data on contact patterns in Europe. In 2017, the largest set of synthetic contact matrices to date were published for 152 geographical locations. In this study, we update these matrices with the most recent data and extend our analysis to 177 geographical locations. Due to the observed geographic differences within countries, we also quantify contact patterns in rural and urban settings where data is available. Further, we compare both the 2017 and 2020 synthetic matrices to out-of-sample empirically-constructed contact matrices, and explore the effects of using both the empirical and synthetic contact matrices when modelling physical distancing interventions for the COVID-19 pandemic. We found that the synthetic contact matrices show qualitative similarities to the contact patterns in the empirically-constructed contact matrices. Models parameterised with the empirical and synthetic matrices generated similar findings with few differences observed in age groups where the empirical matrices have missing or aggregated age groups. This finding means that synthetic contact matrices may be used in modelling outbreaks in settings for which empirical studies have yet to be conducted.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009098&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1009098; html:https://europepmc.org/articles/PMC8354454; pdf:https://europepmc.org/articles/PMC8354454?pdf=render @@ -2057,18 +2057,18 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 32073627,https://doi.org/10.1093/ije/dyaa002,Educational and health outcomes of children and adolescents receiving antidepressant medication: Scotland-wide retrospective record linkage cohort study of 766 237 schoolchildren.,"Fleming M, Fitton CA, Steiner MFC, McLay JS, Clark D, King A, Mackay DF, Pell JP.",,International journal of epidemiology,2020,2020-08-01,Y,Depression; Health; Prescribing; Educational Outcomes; Record Linkage; Population Cohort,,,"

Background

Childhood depression is relatively common, under-researched and can impact social and cognitive function and self-esteem.

Methods

Record linkage of routinely collected Scotland-wide administrative databases covering prescriptions [prescribing information system (PIS)], hospitalizations (Scottish Morbidity Records 01 and 04), maternity records (Scottish Morbidity Records 02), deaths (National Records of Scotland), annual pupil census, school absences/exclusions, special educational needs (Scottish Exchange of Educational Data; ScotXed), examinations (Scottish Qualifications Authority) and (un)employment (ScotXed) provided data on 766 237 children attending Scottish schools between 2009 and 2013 inclusively. We compared educational and health outcomes of children receiving antidepressant medication with their peers, adjusting for confounders (socio-demographic, maternity and comorbidity) and explored effect modifiers and mediators.

Results

Compared with peers, children receiving antidepressants were more likely to be absent [adjusted incidence rate ratio (IRR) 1.90, 95% confidence interval (CI) 1.85-1.95] or excluded (adjusted IRR 1.48, 95% CI 1.29-1.69) from school, have special educational needs [adjusted odds ratio (OR) 1.77, 95% CI 1.65-1.90], have the lowest level of academic attainment (adjusted OR 3.00, 95% CI 2.51-3.58) and be unemployed after leaving school (adjusted OR 1.88, 95% CI 1.71-2.08). They had increased hospitalization [adjusted hazard ratio (HR) 2.07, 95% CI 1.98-2.18] and mortality (adjusted HR 2.73, 95% CI 1.73-4.29) over 5 years' follow-up. Higher absenteeism partially explained poorer attainment and unemployment. Treatment with antidepressants was less common among boys than girls (0.5% vs 1.0%) but the associations with special educational need and unemployment were stronger in boys.

Conclusions

Children receiving antidepressants fare worse than their peers across a wide range of education and health outcomes. Interventions to reduce absenteeism or mitigate its effects should be investigated.",,pdf:https://academic.oup.com/ije/article-pdf/49/4/1380/34275416/dyaa002.pdf; doi:https://doi.org/10.1093/ije/dyaa002; html:https://europepmc.org/articles/PMC7660154; pdf:https://europepmc.org/articles/PMC7660154?pdf=render 31950165,https://doi.org/10.1093/pubmed/fdz188,Is child weight status correctly reported to parents? Cross-sectional analysis of National Child Measurement Programme data using ethnic-specific BMI adjustments.,"Firman N, Boomla K, Hudda MT, Robson J, Whincup P, Dezateux C.",,"Journal of public health (Oxford, England)",2020,2020-11-01,Y,Obesity; Children; Ethnicity,,,"

Background

BMI underestimates and overestimates body fat in children from South Asian and Black ethnic groups, respectively.

Methods

We used cross-sectional NCMP data (2015-17) for 38 270 children in three inner-London local authorities: City & Hackney, Newham and Tower Hamlets (41% South Asian, 18.8% Black): 20 439 4-5 year-olds (48.9% girls) and 17 831 10-11 year-olds (49.1% girls). We estimated the proportion of parents who would have received different information about their child's weight status, and the area-level prevalence of obesity-defined as ≥98th centile-had ethnic-specific BMI adjustments been employed in the English National Child Measurement Programme (NCMP).

Results

Had ethnic-specific adjustment been employed, 19.7% (3112/15 830) of parents of children from South Asian backgrounds would have been informed that their child was in a heavier weight category, and 19.1% (1381/7217) of parents of children from Black backgrounds would have been informed that their child was in a lighter weight category. Ethnic-specific adjustment increased obesity prevalence from 7.9% (95% CI: 7.6, 8.3) to 9.1% (8.7, 9.5) amongst 4-5 year-olds and from 17.5% (16.9, 18.1) to 18.8% (18.2, 19.4) amongst 10-11 year-olds.

Conclusions

Ethnic-specific adjustment in the NCMP would ensure equitable categorization of weight status, provide correct information to parents and support local service provision for families.",,pdf:https://academic.oup.com/jpubhealth/article-pdf/42/4/e541/34469388/fdz188.pdf; doi:https://doi.org/10.1093/pubmed/fdz188; html:https://europepmc.org/articles/PMC7685848; pdf:https://europepmc.org/articles/PMC7685848?pdf=render 33407780,https://doi.org/10.1186/s13063-020-04951-6,Reporting guidelines for clinical trials of artificial intelligence interventions: the SPIRIT-AI and CONSORT-AI guidelines.,"Ibrahim H, Liu X, Rivera SC, Moher D, Chan AW, Sydes MR, Calvert MJ, Denniston AK.",,Trials,2021,2021-01-06,Y,Artificial intelligence; Checklist; RANDOMISED CONTROLLED TRIALS; Research Report; Clinical Trials; Guidelines; Research Design; Machine Learning,,,"

Background

The application of artificial intelligence (AI) in healthcare is an area of immense interest. The high profile of 'AI in health' means that there are unusually strong drivers to accelerate the introduction and implementation of innovative AI interventions, which may not be supported by the available evidence, and for which the usual systems of appraisal may not yet be sufficient.

Main text

We are beginning to see the emergence of randomised clinical trials evaluating AI interventions in real-world settings. It is imperative that these studies are conducted and reported to the highest standards to enable effective evaluation because they will potentially be a key part of the evidence that is used when deciding whether an AI intervention is sufficiently safe and effective to be approved and commissioned. Minimum reporting guidelines for clinical trial protocols and reports have been instrumental in improving the quality of clinical trials and promoting completeness and transparency of reporting for the evaluation of new health interventions. The current guidelines-SPIRIT and CONSORT-are suited to traditional health interventions but research has revealed that they do not adequately address potential sources of bias specific to AI systems. Examples of elements that require specific reporting include algorithm version and the procedure for acquiring input data. In response, the SPIRIT-AI and CONSORT-AI guidelines were developed by a multidisciplinary group of international experts using a consensus building methodological process. The extensions include a number of new items that should be reported in addition to the core items. Each item, where possible, was informed by challenges identified in existing studies of AI systems in health settings.

Conclusion

The SPIRIT-AI and CONSORT-AI guidelines provide the first international standards for clinical trials of AI systems. The guidelines are designed to ensure complete and transparent reporting of clinical trial protocols and reports involving AI interventions and have the potential to improve the quality of these clinical trials through improvements in their design and delivery. Their use will help to efficiently identify the safest and most effective AI interventions and commission them with confidence for the benefit of patients and the public.",,pdf:https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-020-04951-6; doi:https://doi.org/10.1186/s13063-020-04951-6; html:https://europepmc.org/articles/PMC7788716; pdf:https://europepmc.org/articles/PMC7788716?pdf=render -35288697,https://doi.org/10.1038/s41591-022-01750-1,COVID-19 and resilience of healthcare systems in ten countries.,"Arsenault C, Gage A, Kim MK, Kapoor NR, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bedregal P, Doubova SV, Dulal M, Gadeka DD, Gordon-Strachan G, Mariam DH, Hensman D, Joseph JP, Kaewkamjornchai P, Eshetu MK, Gelaw SK, Kubota S, Leerapan B, Margozzini P, Mebratie AD, Mehata S, Moshabela M, Mthethwa L, Nega A, Oh J, Park S, Passi-Solar Á, Pérez-Cuevas R, Phengsavanh A, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Valenzuela Guiñez F, Bauhoff S, Kruk ME.",,Nature medicine,2022,2022-03-14,Y,,,,"Declines in health service use during the Coronavirus Disease 2019 (COVID-19) pandemic could have important effects on population health. In this study, we used an interrupted time series design to assess the immediate effect of the pandemic on 31 health services in two low-income (Ethiopia and Haiti), six middle-income (Ghana, Lao People's Democratic Republic, Mexico, Nepal, South Africa and Thailand) and high-income (Chile and South Korea) countries. Despite efforts to maintain health services, disruptions of varying magnitude and duration were found in every country, with no clear patterns by country income group or pandemic intensity. Disruptions in health services often preceded COVID-19 waves. Cancer screenings, TB screening and detection and HIV testing were most affected (26-96% declines). Total outpatient visits declined by 9-40% at national levels and remained lower than predicted by the end of 2020. Maternal health services were disrupted in approximately half of the countries, with declines ranging from 5% to 33%. Child vaccinations were disrupted for shorter periods, but we estimate that catch-up campaigns might not have reached all children missed. By contrast, provision of antiretrovirals for HIV was not affected. By the end of 2020, substantial disruptions remained in half of the countries. Preliminary data for 2021 indicate that disruptions likely persisted. Although a portion of the declines observed might result from decreased needs during lockdowns (from fewer infectious illnesses or injuries), a larger share likely reflects a shortfall of health system resilience. Countries must plan to compensate for missed healthcare during the current pandemic and invest in strategies for better health system resilience for future emergencies.",,pdf:https://www.nature.com/articles/s41591-022-01750-1.pdf; doi:https://doi.org/10.1038/s41591-022-01750-1; html:https://europepmc.org/articles/PMC9205770; pdf:https://europepmc.org/articles/PMC9205770?pdf=render 32835195,https://doi.org/10.1016/s2589-7500(20)30134-5,The effects of physical distancing on population mobility during the COVID-19 pandemic in the UK.,"Drake TM, Docherty AB, Weiser TG, Yule S, Sheikh A, Harrison EM.",,The Lancet. Digital health,2020,2020-06-12,Y,,,,,,doi:https://doi.org/10.1016/s2589-7500(20)30134-5; doi:https://doi.org/10.1016/S2589-7500(20)30134-5; html:https://europepmc.org/articles/PMC7292602; pdf:https://europepmc.org/articles/PMC7292602?pdf=render +35288697,https://doi.org/10.1038/s41591-022-01750-1,COVID-19 and resilience of healthcare systems in ten countries.,"Arsenault C, Gage A, Kim MK, Kapoor NR, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bedregal P, Doubova SV, Dulal M, Gadeka DD, Gordon-Strachan G, Mariam DH, Hensman D, Joseph JP, Kaewkamjornchai P, Eshetu MK, Gelaw SK, Kubota S, Leerapan B, Margozzini P, Mebratie AD, Mehata S, Moshabela M, Mthethwa L, Nega A, Oh J, Park S, Passi-Solar Á, Pérez-Cuevas R, Phengsavanh A, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Valenzuela Guiñez F, Bauhoff S, Kruk ME.",,Nature medicine,2022,2022-03-14,Y,,,,"Declines in health service use during the Coronavirus Disease 2019 (COVID-19) pandemic could have important effects on population health. In this study, we used an interrupted time series design to assess the immediate effect of the pandemic on 31 health services in two low-income (Ethiopia and Haiti), six middle-income (Ghana, Lao People's Democratic Republic, Mexico, Nepal, South Africa and Thailand) and high-income (Chile and South Korea) countries. Despite efforts to maintain health services, disruptions of varying magnitude and duration were found in every country, with no clear patterns by country income group or pandemic intensity. Disruptions in health services often preceded COVID-19 waves. Cancer screenings, TB screening and detection and HIV testing were most affected (26-96% declines). Total outpatient visits declined by 9-40% at national levels and remained lower than predicted by the end of 2020. Maternal health services were disrupted in approximately half of the countries, with declines ranging from 5% to 33%. Child vaccinations were disrupted for shorter periods, but we estimate that catch-up campaigns might not have reached all children missed. By contrast, provision of antiretrovirals for HIV was not affected. By the end of 2020, substantial disruptions remained in half of the countries. Preliminary data for 2021 indicate that disruptions likely persisted. Although a portion of the declines observed might result from decreased needs during lockdowns (from fewer infectious illnesses or injuries), a larger share likely reflects a shortfall of health system resilience. Countries must plan to compensate for missed healthcare during the current pandemic and invest in strategies for better health system resilience for future emergencies.",,pdf:https://www.nature.com/articles/s41591-022-01750-1.pdf; doi:https://doi.org/10.1038/s41591-022-01750-1; html:https://europepmc.org/articles/PMC9205770; pdf:https://europepmc.org/articles/PMC9205770?pdf=render 34555069,https://doi.org/10.1371/journal.pone.0257361,Predicting fracture outcomes from clinical registry data using artificial intelligence supplemented models for evidence-informed treatment (PRAISE) study protocol.,"Dipnall JF, Page R, Du L, Costa M, Lyons RA, Cameron P, de Steiger R, Hau R, Bucknill A, Oppy A, Edwards E, Varma D, Jung MC, Gabbe BJ.",,PloS one,2021,2021-09-23,Y,,,,"

Background

Distal radius (wrist) fractures are the second most common fracture admitted to hospital. The anatomical pattern of these types of injuries is diverse, with variation in clinical management, guidelines for management remain inconclusive, and the uptake of findings from clinical trials into routine practice limited. Robust predictive modelling, which considers both the characteristics of the fracture and patient, provides the best opportunity to reduce variation in care and improve patient outcomes. This type of data is housed in unstructured data sources with no particular format or schema. The ""Predicting fracture outcomes from clinical Registry data using Artificial Intelligence (AI) Supplemented models for Evidence-informed treatment (PRAISE)"" study aims to use AI methods on unstructured data to describe the fracture characteristics and test if using this information improves identification of key fracture characteristics and prediction of patient-reported outcome measures and clinical outcomes following wrist fractures compared to prediction models based on standard registry data.

Methods and design

Adult (16+ years) patients presenting to the emergency department, treated in a short stay unit, or admitted to hospital for >24h for management of a wrist fracture in four Victorian hospitals will be included in this study. The study will use routine registry data from the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR), and electronic medical record (EMR) information (e.g. X-rays, surgical reports, radiology reports, images). A multimodal deep learning fracture reasoning system (DLFRS) will be developed that reasons on EMR information. Machine learning prediction models will test the performance with/without output from the DLFRS.

Discussion

The PRAISE study will establish the use of AI techniques to provide enhanced information about fracture characteristics in people with wrist fractures. Prediction models using AI derived characteristics are expected to provide better prediction of clinical and patient-reported outcomes following distal radius fracture.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0257361&type=printable; doi:https://doi.org/10.1371/journal.pone.0257361; html:https://europepmc.org/articles/PMC8460020; pdf:https://europepmc.org/articles/PMC8460020?pdf=render 37127670,https://doi.org/10.1038/s41588-023-01379-x,Biobank-scale inference of ancestral recombination graphs enables genealogical analysis of complex traits.,"Zhang BC, Biddanda A, Gunnarsson ÁF, Cooper F, Palamara PF.",,Nature genetics,2023,2023-05-01,Y,,,,"Genome-wide genealogies compactly represent the evolutionary history of a set of genomes and inferring them from genetic data has the potential to facilitate a wide range of analyses. We introduce a method, ARG-Needle, for accurately inferring biobank-scale genealogies from sequencing or genotyping array data, as well as strategies to utilize genealogies to perform association and other complex trait analyses. We use these methods to build genome-wide genealogies using genotyping data for 337,464 UK Biobank individuals and test for association across seven complex traits. Genealogy-based association detects more rare and ultra-rare signals (N = 134, frequency range 0.0007-0.1%) than genotype imputation using ~65,000 sequenced haplotypes (N = 64). In a subset of 138,039 exome sequencing samples, these associations strongly tag (average r = 0.72) underlying sequencing variants enriched (4.8×) for loss-of-function variation. These results demonstrate that inferred genome-wide genealogies may be leveraged in the analysis of complex traits, complementing approaches that require the availability of large, population-specific sequencing panels.",,doi:https://doi.org/10.1038/s41588-023-01379-x; doi:https://doi.org/10.1038/s41588-023-01379-x; html:https://europepmc.org/articles/PMC10181934; pdf:https://europepmc.org/articles/PMC10181934?pdf=render 35073907,https://doi.org/10.1186/s12916-021-02218-8,Association between hypertensive disorders of pregnancy and later risk of cardiovascular outcomes.,"Oliver-Williams C, Stevens D, Payne RA, Wilkinson IB, Smith GCS, Wood A.",,BMC medicine,2022,2022-01-25,Y,Pregnancy; Cardiovascular disease; Pre-eclampsia; Women; Gestational Hypertension,,,"

Background

Hypertensive disorders of pregnancy are common pregnancy complications that are associated with greater cardiovascular disease risk for mothers. However, risk of cardiovascular disease subtypes associated with gestational hypertension or pre-eclampsia is unclear. The present study aims to compare the risk of cardiovascular disease outcomes for women with and without a history of gestational hypertension and pre-eclampsia using national hospital admissions data.

Methods

This was a retrospective cohort study of national medical records from all National Health Service hospitals in England. Women who had one or more singleton live births in England between 1997 and 2015 were included in the analysis. Risk of total cardiovascular disease and 19 pre-specified cardiovascular disease subtypes, including stroke, coronary heart disease, cardiomyopathy and peripheral arterial disease, was calculated separately for women with a history of gestational hypertension and pre-eclampsia compared to normotensive pregnancies.

Results

Amongst 2,359,386 first live births, there were 85,277 and 74,542 hospital admissions with a diagnosis of gestational hypertension and pre-eclampsia, respectively. During 18 years (16,309,386 person-years) of follow-up, the number and incidence of total CVD for normotensive women, women with prior gestational hypertension and women with prior pre-eclampsia were n = 8668, 57.1 (95% CI: 55.9-58.3) per 100,000 person-years; n = 521, 85.8 (78.6-93.5) per 100,000 person-years; and n = 518, 99.3 (90.9-108.2) per 100,000 person-years, respectively. Adjusted HRs (aHR) for total CVD were aHR (95% CI) = 1.45 (1.33-1.59) for women with prior gestational hypertension and aHR = 1.62 (1.48-1.78) for women with prior pre-eclampsia. Gestational hypertension was strongly associated with dilated cardiomyopathy, aHR = 2.85 (1.67-4.86), and unstable angina, aHR = 1.92 (1.33-2.77). Pre-eclampsia was strongly associated with hypertrophic cardiomyopathy, aHR = 3.27 (1.49-7.19), and acute myocardial infarction, aHR = 2.46 (1.72-3.53). Associations were broadly homogenous across cardiovascular disease subtypes and increased with a greater number of affected pregnancies.

Conclusions

Women with either previous gestational hypertension or pre-eclampsia are at greater risk of a range of cardiovascular outcomes. These women may benefit from clinical risk assessment or early interventions to mitigate their greater risk of various cardiovascular outcomes.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02218-8; doi:https://doi.org/10.1186/s12916-021-02218-8; html:https://europepmc.org/articles/PMC8787919; pdf:https://europepmc.org/articles/PMC8787919?pdf=render +33064085,https://doi.org/10.2196/17003,"Impact of Electronic Health Record Interface Design on Unsafe Prescribing of Ciclosporin, Tacrolimus, and Diltiazem: Cohort Study in English National Health Service Primary Care.","MacKenna B, Bacon S, Walker AJ, Curtis HJ, Croker R, Goldacre B.",,Journal of medical Internet research,2020,2020-10-16,Y,Diltiazem; Prescribing; Ciclosporin; Primary Care; Tacrolimus; Electronic Health Records; Clinical Software; Branded Prescribing,,,"

Background

In England, national safety guidance recommends that ciclosporin, tacrolimus, and diltiazem are prescribed by brand name due to their narrow therapeutic windows and, in the case of tacrolimus, to reduce the chance of organ transplantation rejection. Various small studies have shown that changes to electronic health record (EHR) system interfaces can affect prescribing choices.

Objective

Our objectives were to assess variation by EHR systems in breach of safety guidance around prescribing of ciclosporin, tacrolimus, and diltiazem, and to conduct user-interface research into the causes of such breaches.

Methods

We carried out a retrospective cohort study using prescribing data in English primary care. Participants were English general practices and their respective EHR systems. The main outcome measures were (1) the variation in ratio of safety breaches to adherent prescribing in all practices and (2) the description of observations of EHR system usage.

Results

A total of 2,575,411 prescriptions were issued in 2018 for ciclosporin, tacrolimus, and diltiazem (over 60 mg); of these, 316,119 prescriptions breached NHS guidance (12.27%). Breaches were most common among users of the EMIS EHR system (breaches in 18.81% of ciclosporin and tacrolimus prescriptions and in 17.99% of diltiazem prescriptions), but breaches were observed in all EHR systems.

Conclusions

Design choices in EHR systems strongly influence safe prescribing of ciclosporin, tacrolimus, and diltiazem, and breaches are prevalent in general practices in England. We recommend that all EHR vendors review their systems to increase safe prescribing of these medicines in line with national guidance. Almost all clinical practice is now mediated through an EHR system; further quantitative research into the effect of EHR system design on clinical practice is long overdue.",,pdf:https://www.jmir.org/2020/10/e17003/PDF; doi:https://doi.org/10.2196/17003; html:https://europepmc.org/articles/PMC7600019 34725404,https://doi.org/10.1038/s41598-021-00748-y,Probabilistic modelling of effects of antibiotics and calendar time on transmission of healthcare-associated infection.,"Laager M, Cooper BS, Eyre DW, CDC Modeling Infectious Diseases in Healthcare Program (MInD-Healthcare).",,Scientific reports,2021,2021-11-01,Y,,,,"Healthcare-associated infection and antimicrobial resistance are major concerns. However, the extent to which antibiotic exposure affects transmission and detection of infections such as MRSA is unclear. Additionally, temporal trends are typically reported in terms of changes in incidence, rather than analysing underling transmission processes. We present a data-augmented Markov chain Monte Carlo approach for inferring changing transmission parameters over time, screening test sensitivity, and the effect of antibiotics on detection and transmission. We expand a basic model to allow use of typing information when inferring sources of infections. Using simulated data, we show that the algorithms are accurate, well-calibrated and able to identify antibiotic effects in sufficiently large datasets. We apply the models to study MRSA transmission in an intensive care unit in Oxford, UK with 7924 admissions over 10 years. We find that falls in MRSA incidence over time were associated with decreases in both the number of patients admitted to the ICU colonised with MRSA and in transmission rates. In our inference model, the data were not informative about the effect of antibiotics on risk of transmission or acquisition of MRSA, a consequence of the limited number of possible transmission events in the data. Our approach has potential to be applied to a range of healthcare-associated infections and settings and could be applied to study the impact of other potential risk factors for transmission. Evidence generated could be used to direct infection control interventions.",,pdf:https://www.nature.com/articles/s41598-021-00748-y.pdf; doi:https://doi.org/10.1038/s41598-021-00748-y; html:https://europepmc.org/articles/PMC8560804; pdf:https://europepmc.org/articles/PMC8560804?pdf=render 35505938,https://doi.org/10.1016/j.eclinm.2022.101417,Multivariate profile and acute-phase correlates of cognitive deficits in a COVID-19 hospitalised cohort.,"Hampshire A, Chatfield DA, MPhil AM, Jolly A, Trender W, Hellyer PJ, Giovane MD, Newcombe VFJ, Outtrim JG, Warne B, Bhatti J, Pointon L, Elmer A, Sithole N, Bradley J, Kingston N, Sawcer SJ, Bullmore ET, Rowe JB, Menon DK, Cambridge NeuroCOVID Group, the NIHR COVID-19 BioResource, and Cambridge NIHR Clinical Research Facility.",,EClinicalMedicine,2022,2022-04-28,Y,Memory; Cognition; Attention; Planning; Cognitive Assessment; Reasoning; Covid-19,,,"

Background

Preliminary evidence has highlighted a possible association between severe COVID-19 and persistent cognitive deficits. Further research is required to confirm this association, determine whether cognitive deficits relate to clinical features from the acute phase or to mental health status at the point of assessment, and quantify rate of recovery.

Methods

46 individuals who received critical care for COVID-19 at Addenbrooke's hospital between 10th March 2020 and 31st July 2020 (16 mechanically ventilated) underwent detailed computerised cognitive assessment alongside scales measuring anxiety, depression and post-traumatic stress disorder under supervised conditions at a mean follow up of 6.0 (± 2.1) months following acute illness. Patient and matched control (N = 460) performances were transformed into standard deviation from expected scores, accounting for age and demographic factors using N = 66,008 normative datasets. Global accuracy and response time composites were calculated (G_SScore & G_RT). Linear modelling predicted composite score deficits from acute severity, mental-health status at assessment, and time from hospital admission. The pattern of deficits across tasks was qualitatively compared with normal age-related decline, and early-stage dementia.

Findings

COVID-19 survivors were less accurate (G_SScore=-0.53SDs) and slower (G_RT=+0.89SDs) in their responses than expected compared to their matched controls. Acute illness, but not chronic mental health, significantly predicted cognitive deviation from expected scores (G_SScore (p=​​0.0037) and G_RT (p = 0.0366)). The most prominent task associations with COVID-19 were for higher cognition and processing speed, which was qualitatively distinct from the profiles of normal ageing and dementia and similar in magnitude to the effects of ageing between 50 and 70 years of age. A trend towards reduced deficits with time from illness (r∼=0.15) did not reach statistical significance.

Interpretation

Cognitive deficits after severe COVID-19 relate most strongly to acute illness severity, persist long into the chronic phase, and recover slowly if at all, with a characteristic profile highlighting higher cognitive functions and processing speed.

Funding

This work was funded by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC), NIHR Cambridge Clinical Research Facility (BRC-1215-20014), the Addenbrooke's Charities Trust and NIHR COVID-19 BioResource RG9402. AH is funded by the UK Dementia Research Institute Care Research and Technology Centre and Imperial College London Biomedical Research Centre. ETB and DKM are supported by NIHR Senior Investigator awards. JBR is supported by the Wellcome Trust (220258) and Medical Research Council (SUAG/051 G101400). VFJN is funded by an Academy of Medical Sciences/ The Health Foundation Clinician Scientist Fellowship. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.",,pdf:http://www.thelancet.com/article/S258953702200147X/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101417; html:https://europepmc.org/articles/PMC9048584; pdf:https://europepmc.org/articles/PMC9048584?pdf=render -33064085,https://doi.org/10.2196/17003,"Impact of Electronic Health Record Interface Design on Unsafe Prescribing of Ciclosporin, Tacrolimus, and Diltiazem: Cohort Study in English National Health Service Primary Care.","MacKenna B, Bacon S, Walker AJ, Curtis HJ, Croker R, Goldacre B.",,Journal of medical Internet research,2020,2020-10-16,Y,Diltiazem; Prescribing; Ciclosporin; Primary Care; Tacrolimus; Electronic Health Records; Clinical Software; Branded Prescribing,,,"

Background

In England, national safety guidance recommends that ciclosporin, tacrolimus, and diltiazem are prescribed by brand name due to their narrow therapeutic windows and, in the case of tacrolimus, to reduce the chance of organ transplantation rejection. Various small studies have shown that changes to electronic health record (EHR) system interfaces can affect prescribing choices.

Objective

Our objectives were to assess variation by EHR systems in breach of safety guidance around prescribing of ciclosporin, tacrolimus, and diltiazem, and to conduct user-interface research into the causes of such breaches.

Methods

We carried out a retrospective cohort study using prescribing data in English primary care. Participants were English general practices and their respective EHR systems. The main outcome measures were (1) the variation in ratio of safety breaches to adherent prescribing in all practices and (2) the description of observations of EHR system usage.

Results

A total of 2,575,411 prescriptions were issued in 2018 for ciclosporin, tacrolimus, and diltiazem (over 60 mg); of these, 316,119 prescriptions breached NHS guidance (12.27%). Breaches were most common among users of the EMIS EHR system (breaches in 18.81% of ciclosporin and tacrolimus prescriptions and in 17.99% of diltiazem prescriptions), but breaches were observed in all EHR systems.

Conclusions

Design choices in EHR systems strongly influence safe prescribing of ciclosporin, tacrolimus, and diltiazem, and breaches are prevalent in general practices in England. We recommend that all EHR vendors review their systems to increase safe prescribing of these medicines in line with national guidance. Almost all clinical practice is now mediated through an EHR system; further quantitative research into the effect of EHR system design on clinical practice is long overdue.",,pdf:https://www.jmir.org/2020/10/e17003/PDF; doi:https://doi.org/10.2196/17003; html:https://europepmc.org/articles/PMC7600019 -35710247,https://doi.org/10.1136/bmjopen-2021-060280,Structured follow-up pathway to support people after transient ischaemic attack and minor stroke (SUPPORT TIA): protocol for a feasibility study and process evaluation.,"Turner GM, Jones R, Collis P, Patel S, Jowett S, Tearne S, Foy R, Atkins L, Mant J, Calvert M.",,BMJ open,2022,2022-06-16,Y,Qualitative Research; Rehabilitation Medicine; Stroke Medicine; Protocols & Guidelines; Organisation Of Health Services; Depression & Mood Disorders,,,"

Introduction

People who experience transient ischaemic attack (TIA) and minor stroke have limited follow-up despite rapid specialist review in hospital. This means they often have unmet needs and feel abandoned following discharge. Care needs after TIA/minor stroke include information provision (diagnosis and stroke risk), stroke prevention (medication and lifestyle change) and holistic care (residual problems and return to work or usual activities). This protocol describes a feasibility study and process evaluation of an intervention to support people after TIA/minor stroke. The study aims to assess the feasibility and acceptability of (1) the intervention and (2) the trial procedures for a future randomised controlled trial of this intervention.

Methods and analysis

This is a multicentre, randomised (1:1) feasibility study with a mixed-methods process evaluation. Sixty participants will be recruited from TIA clinics or stroke wards at three hospital sites (England). Intervention arm participants will be offered a nurse or allied health professional-led follow-up appointment 4 weeks after TIA/minor stroke. The multifaceted intervention includes: a needs checklist, action plan, resources to support management of needs, a general practitioner letter and training to deliver the intervention. Control arm participants will receive usual care. Follow-up will be self-completed questionnaires (12 weeks and 24 weeks) and a clinic appointment (24 weeks). Follow-up questionnaires will measure anxiety, depression, fatigue, health related quality of life, self-efficacy and medication adherence. The clinic appointment will collect body mass index, blood pressure, cholesterol and medication. Assessment of feasibility and acceptability will include quantitative process variables (such as recruitment and questionnaire response rates), structured observations of study processes, and interviews with a subsample of participants and clinical staff.

Ethics and dissemination

Favourable ethical opinion was gained from the Wales Research Ethics Committee (REC) 1 (23 February 2021, REC reference: 21/WA/0036). Study results will be published in peer-reviewed journals and presented at conferences. A lay summary and dissemination strategy will be codesigned with consumers. The lay summary and journal publication will be distributed on social media.

Trial registration number

ISRCTN39864003.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/6/e060280.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-060280; html:https://europepmc.org/articles/PMC9207897; pdf:https://europepmc.org/articles/PMC9207897?pdf=render 33829489,https://doi.org/10.1111/bjd.20140,Defining trajectories of response in patients with psoriasis treated with biologic therapies.,"Geifman N, Azadbakht N, Zeng J, Wilkinson T, Dand N, Buchan I, Stocken D, Di Meglio P, Warren RB, Barker JN, Reynolds NJ, Barnes MR, Smith CH, Griffiths CEM, Peek N, BADBIR Study Group, on behalf of the PSORT Consortium.",,The British journal of dermatology,2021,2021-06-04,N,,,,"

Background

The effectiveness and cost-effectiveness of biologic therapies for psoriasis are significantly compromised by variable treatment responses. Thus, more precise management of psoriasis is needed.

Objectives

To identify subgroups of patients with psoriasis treated with biologic therapies, based on changes in their disease activity over time, that may better inform patient management.

Methods

We applied latent class mixed modelling to identify trajectory-based patient subgroups from longitudinal, routine clinical data on disease severity, as measured by the Psoriasis Area and Severity Index (PASI), from 3546 patients in the British Association of Dermatologists Biologics and Immunomodulators Register, as well as in an independent cohort of 2889 patients pooled across four clinical trials.

Results

We discovered four discrete classes of global response trajectories, each characterized in terms of time to response, size of effect and relapse. Each class was associated with differing clinical characteristics, e.g. body mass index, baseline PASI and prevalence of different manifestations. The results were verified in a second cohort of clinical trial participants, where similar trajectories following the initiation of biologic therapy were identified. Further, we found differential associations of the genetic marker HLA-C*06:02 between our registry-identified trajectories.

Conclusions

These subgroups, defined by change in disease over time, may be indicative of distinct endotypes driven by different biological mechanisms and may help inform the management of patients with psoriasis. Future work will aim to further delineate these mechanisms by extensively characterizing the subgroups with additional molecular and pharmacological data.",,doi:https://doi.org/10.1111/bjd.20140 -32247823,https://doi.org/10.1016/j.jhep.2020.03.032,Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis.,"Parisinos CA, Wilman HR, Thomas EL, Kelly M, Nicholls RC, McGonigle J, Neubauer S, Hingorani AD, Patel RS, Hemingway H, Bell JD, Banerjee R, Yaghootkar H.",,Journal of hepatology,2020,2020-04-02,Y,metabolic syndrome; Magnetic Resonance Imaging; fibrosis; Transaminases; Genome-wide Association Study; Steatohepatitis; Ct1,Understanding the Causes of Disease,oral and gastrointestinal,"

Background & aims

MRI-based corrected T1 (cT1) is a non-invasive method to grade the severity of steatohepatitis and liver fibrosis. We aimed to identify genetic variants influencing liver cT1 and use genetics to understand mechanisms underlying liver fibroinflammatory disease and its link with other metabolic traits and diseases.

Methods

First, we performed a genome-wide association study (GWAS) in 14,440 Europeans, with liver cT1 measures, from the UK Biobank. Second, we explored the effects of the cT1 variants on liver blood tests, and a range of metabolic traits and diseases. Third, we used Mendelian randomisation to test the causal effects of 24 predominantly metabolic traits on liver cT1 measures.

Results

We identified 6 independent genetic variants associated with liver cT1 that reached the GWAS significance threshold (p <5×10-8). Four of the variants (rs759359281 in SLC30A10, rs13107325 in SLC39A8, rs58542926 in TM6SF2, rs738409 in PNPLA3) were also associated with elevated aminotransferases and had variable effects on liver fat and other metabolic traits. Insulin resistance, type 2 diabetes, non-alcoholic fatty liver and body mass index were causally associated with elevated cT1, whilst favourable adiposity (instrumented by variants associated with higher adiposity but lower risk of cardiometabolic disease and lower liver fat) was found to be protective.

Conclusion

The association between 2 metal ion transporters and cT1 indicates an important new mechanism in steatohepatitis. Future studies are needed to determine whether interventions targeting the identified transporters might prevent liver disease in at-risk individuals.

Lay summary

We estimated levels of liver inflammation and scarring based on magnetic resonance imaging of 14,440 UK Biobank participants. We performed a genetic study and identified variations in 6 genes associated with levels of liver inflammation and scarring. Participants with variations in 4 of these genes also had higher levels of markers of liver cell injury in blood samples, further validating their role in liver health. Two identified genes are involved in the transport of metal ions in our body. Further investigation of these variations may lead to better detection, assessment, and/or treatment of liver inflammation and scarring.",,pdf:http://www.journal-of-hepatology.eu/article/S016882782030194X/pdf; doi:https://doi.org/10.1016/j.jhep.2020.03.032; html:https://europepmc.org/articles/PMC7372222; pdf:https://europepmc.org/articles/PMC7372222?pdf=render +35710247,https://doi.org/10.1136/bmjopen-2021-060280,Structured follow-up pathway to support people after transient ischaemic attack and minor stroke (SUPPORT TIA): protocol for a feasibility study and process evaluation.,"Turner GM, Jones R, Collis P, Patel S, Jowett S, Tearne S, Foy R, Atkins L, Mant J, Calvert M.",,BMJ open,2022,2022-06-16,Y,Qualitative Research; Rehabilitation Medicine; Stroke Medicine; Protocols & Guidelines; Organisation Of Health Services; Depression & Mood Disorders,,,"

Introduction

People who experience transient ischaemic attack (TIA) and minor stroke have limited follow-up despite rapid specialist review in hospital. This means they often have unmet needs and feel abandoned following discharge. Care needs after TIA/minor stroke include information provision (diagnosis and stroke risk), stroke prevention (medication and lifestyle change) and holistic care (residual problems and return to work or usual activities). This protocol describes a feasibility study and process evaluation of an intervention to support people after TIA/minor stroke. The study aims to assess the feasibility and acceptability of (1) the intervention and (2) the trial procedures for a future randomised controlled trial of this intervention.

Methods and analysis

This is a multicentre, randomised (1:1) feasibility study with a mixed-methods process evaluation. Sixty participants will be recruited from TIA clinics or stroke wards at three hospital sites (England). Intervention arm participants will be offered a nurse or allied health professional-led follow-up appointment 4 weeks after TIA/minor stroke. The multifaceted intervention includes: a needs checklist, action plan, resources to support management of needs, a general practitioner letter and training to deliver the intervention. Control arm participants will receive usual care. Follow-up will be self-completed questionnaires (12 weeks and 24 weeks) and a clinic appointment (24 weeks). Follow-up questionnaires will measure anxiety, depression, fatigue, health related quality of life, self-efficacy and medication adherence. The clinic appointment will collect body mass index, blood pressure, cholesterol and medication. Assessment of feasibility and acceptability will include quantitative process variables (such as recruitment and questionnaire response rates), structured observations of study processes, and interviews with a subsample of participants and clinical staff.

Ethics and dissemination

Favourable ethical opinion was gained from the Wales Research Ethics Committee (REC) 1 (23 February 2021, REC reference: 21/WA/0036). Study results will be published in peer-reviewed journals and presented at conferences. A lay summary and dissemination strategy will be codesigned with consumers. The lay summary and journal publication will be distributed on social media.

Trial registration number

ISRCTN39864003.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/6/e060280.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-060280; html:https://europepmc.org/articles/PMC9207897; pdf:https://europepmc.org/articles/PMC9207897?pdf=render 33742045,https://doi.org/10.1038/s41598-021-85354-8,Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma.,"Roberts HE, Lopopolo M, Pagnamenta AT, Sharma E, Parkes D, Lonie L, Freeman C, Knight SJL, Lunter G, Dreau H, Lockstone H, Taylor JC, Schuh A, Bowden R, Buck D.",,Scientific reports,2021,2021-03-19,Y,,,,"Recent advances in throughput and accuracy mean that the Oxford Nanopore Technologies PromethION platform is a now a viable solution for genome sequencing. Much of the validation of bioinformatic tools for this long-read data has focussed on calling germline variants (including structural variants). Somatic variants are outnumbered many-fold by germline variants and their detection is further complicated by the effects of tumour purity/subclonality. Here, we evaluate the extent to which Nanopore sequencing enables detection and analysis of somatic variation. We do this through sequencing tumour and germline genomes for a patient with diffuse B-cell lymphoma and comparing results with 150 bp short-read sequencing of the same samples. Calling germline single nucleotide variants (SNVs) from specific chromosomes of the long-read data achieved good specificity and sensitivity. However, results of somatic SNV calling highlight the need for the development of specialised joint calling algorithms. We find the comparative genome-wide performance of different tools varies significantly between structural variant types, and suggest long reads are especially advantageous for calling large somatic deletions and duplications. Finally, we highlight the utility of long reads for phasing clinically relevant variants, confirming that a somatic 1.6 Mb deletion and a p.(Arg249Met) mutation involving TP53 are oriented in trans.",,pdf:https://www.nature.com/articles/s41598-021-85354-8.pdf; doi:https://doi.org/10.1038/s41598-021-85354-8; html:https://europepmc.org/articles/PMC7979876; pdf:https://europepmc.org/articles/PMC7979876?pdf=render +32247823,https://doi.org/10.1016/j.jhep.2020.03.032,Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis.,"Parisinos CA, Wilman HR, Thomas EL, Kelly M, Nicholls RC, McGonigle J, Neubauer S, Hingorani AD, Patel RS, Hemingway H, Bell JD, Banerjee R, Yaghootkar H.",,Journal of hepatology,2020,2020-04-02,Y,metabolic syndrome; Magnetic Resonance Imaging; fibrosis; Transaminases; Genome-wide Association Study; Steatohepatitis; Ct1,Understanding the Causes of Disease,oral and gastrointestinal,"

Background & aims

MRI-based corrected T1 (cT1) is a non-invasive method to grade the severity of steatohepatitis and liver fibrosis. We aimed to identify genetic variants influencing liver cT1 and use genetics to understand mechanisms underlying liver fibroinflammatory disease and its link with other metabolic traits and diseases.

Methods

First, we performed a genome-wide association study (GWAS) in 14,440 Europeans, with liver cT1 measures, from the UK Biobank. Second, we explored the effects of the cT1 variants on liver blood tests, and a range of metabolic traits and diseases. Third, we used Mendelian randomisation to test the causal effects of 24 predominantly metabolic traits on liver cT1 measures.

Results

We identified 6 independent genetic variants associated with liver cT1 that reached the GWAS significance threshold (p <5×10-8). Four of the variants (rs759359281 in SLC30A10, rs13107325 in SLC39A8, rs58542926 in TM6SF2, rs738409 in PNPLA3) were also associated with elevated aminotransferases and had variable effects on liver fat and other metabolic traits. Insulin resistance, type 2 diabetes, non-alcoholic fatty liver and body mass index were causally associated with elevated cT1, whilst favourable adiposity (instrumented by variants associated with higher adiposity but lower risk of cardiometabolic disease and lower liver fat) was found to be protective.

Conclusion

The association between 2 metal ion transporters and cT1 indicates an important new mechanism in steatohepatitis. Future studies are needed to determine whether interventions targeting the identified transporters might prevent liver disease in at-risk individuals.

Lay summary

We estimated levels of liver inflammation and scarring based on magnetic resonance imaging of 14,440 UK Biobank participants. We performed a genetic study and identified variations in 6 genes associated with levels of liver inflammation and scarring. Participants with variations in 4 of these genes also had higher levels of markers of liver cell injury in blood samples, further validating their role in liver health. Two identified genes are involved in the transport of metal ions in our body. Further investigation of these variations may lead to better detection, assessment, and/or treatment of liver inflammation and scarring.",,pdf:http://www.journal-of-hepatology.eu/article/S016882782030194X/pdf; doi:https://doi.org/10.1016/j.jhep.2020.03.032; html:https://europepmc.org/articles/PMC7372222; pdf:https://europepmc.org/articles/PMC7372222?pdf=render 33480434,https://doi.org/10.1093/pubmed/fdaa267,"Complex differences in infection rates between ethnic groups in Scotland: a retrospective, national census-linked cohort study of 1.65 million cases.","Gruer LD, Cézard GI, Wallace LA, Hutchinson SJ, Douglas AF, Buchanan D, Katikireddi SV, Millard AD, Goldberg DJ, Sheikh A, Bhopal RS.",,"Journal of public health (Oxford, England)",2022,2022-03-01,Y,Infectious disease; epidemiology; Ethnicity,,,"

Background

Ethnicity can influence susceptibility to infection, as COVID-19 has shown. Few countries have systematically investigated ethnic variations in infection.

Methods

We linked the Scotland 2001 Census, including ethnic group, to national databases of hospitalizations/deaths and serological diagnoses of bloodborne viruses for 2001-2013. We calculated age-adjusted rate ratios (RRs) in 12 ethnic groups for all infections combined, 15 infection categories, and human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) viruses.

Results

We analysed over 1.65 million infection-related hospitalisations/deaths. Compared with White Scottish, RRs for all infections combined were 0.8 or lower for Other White British, Other White and Chinese males and females, and 1.2-1.4 for Pakistani and African males and females. Adjustment for socioeconomic status or birthplace had little effect. RRs for specific infection categories followed similar patterns with striking exceptions. For HIV, RRs were 136 in African females and 14 in males; for HBV, 125 in Chinese females and 59 in males, 55 in African females and 24 in males; and for HCV, 2.3-3.1 in Pakistanis and Africans.

Conclusions

Ethnic differences were found in overall rates and many infection categories, suggesting multiple causative pathways. We recommend census linkage as a powerful method for studying the disproportionate impact of COVID-19.",,pdf:https://academic.oup.com/jpubhealth/advance-article-pdf/doi/10.1093/pubmed/fdaa267/36684631/fdaa267.pdf; doi:https://doi.org/10.1093/pubmed/fdaa267; html:https://europepmc.org/articles/PMC7928762; pdf:https://europepmc.org/articles/PMC7928762?pdf=render 36470992,https://doi.org/10.1038/s41375-022-01773-0,Continuous Indexing of Fibrosis (CIF): improving the assessment and classification of MPN patients.,"Ryou H, Sirinukunwattana K, Aberdeen A, Grindstaff G, Stolz BJ, Byrne H, Harrington HA, Sousos N, Godfrey AL, Harrison CN, Psaila B, Mead AJ, Rees G, Turner GDH, Rittscher J, Royston D.",,Leukemia,2023,2022-12-05,Y,,,,"The grading of fibrosis in myeloproliferative neoplasms (MPN) is an important component of disease classification, prognostication and monitoring. However, current fibrosis grading systems are only semi-quantitative and fail to fully capture sample heterogeneity. To improve the quantitation of reticulin fibrosis, we developed a machine learning approach using bone marrow trephine (BMT) samples (n = 107) from patients diagnosed with MPN or a reactive marrow. The resulting Continuous Indexing of Fibrosis (CIF) enhances the detection and monitoring of fibrosis within BMTs, and aids MPN subtyping. When combined with megakaryocyte feature analysis, CIF discriminates between the frequently challenging differential diagnosis of essential thrombocythemia (ET) and pre-fibrotic myelofibrosis with high predictive accuracy [area under the curve = 0.94]. CIF also shows promise in the identification of MPN patients at risk of disease progression; analysis of samples from 35 patients diagnosed with ET and enrolled in the Primary Thrombocythemia-1 trial identified features predictive of post-ET myelofibrosis (area under the curve = 0.77). In addition to these clinical applications, automated analysis of fibrosis has clear potential to further refine disease classification boundaries and inform future studies of the micro-environmental factors driving disease initiation and progression in MPN and other stem cell disorders.",,pdf:https://www.nature.com/articles/s41375-022-01773-0.pdf; doi:https://doi.org/10.1038/s41375-022-01773-0; html:https://europepmc.org/articles/PMC9898027; pdf:https://europepmc.org/articles/PMC9898027?pdf=render 32678323,https://doi.org/10.1038/s41366-020-0642-3,"Cross-sectional associations between central and general adiposity with albuminuria: observations from 400,000 people in UK Biobank.","Zhu P, Lewington S, Haynes R, Emberson J, Landray MJ, Cherney D, Woodward M, Baigent C, Herrington WG, Staplin N.",,International journal of obesity (2005),2020,2020-07-16,Y,,,,"

Background

Whether measures of central adiposity are more or less strongly associated with risk of albuminuria than body mass index (BMI), and by how much diabetes/levels of glycosylated haemoglobin (HbA1c) explain or modify these associations, is uncertain.

Methods

Ordinal logistic regression was used to estimate associations between values of central adiposity (waist-to-hip ratio) and, separately, general adiposity (BMI) with categories of urinary albumin-to-creatinine ratio (uACR) in 408,527 UK Biobank participants. Separate central and general adiposity-based models were initially adjusted for potential confounders and measurement error, then sequentially, models were mutually adjusted (e.g. waist-to-hip ratio adjusted for BMI, and vice versa), and finally they were adjusted for potential mediators.

Results

Levels of albuminuria were generally low: 20,425 (5%) had a uACR ≥3 mg/mmol. After adjustment for confounders and measurement error, each 0.06 higher waist-to-hip ratio was associated with a 55% (95%CI 53-57%) increase in the odds of being in a higher uACR category. After adjustment for baseline BMI, this association was reduced to 32% (30-34%). Each 5 kg/m2 higher BMI was associated with a 47% (46-49%) increase in the odds of being in a higher uACR category. Adjustment for baseline waist-to-hip ratio reduced this association to 35% (33-37%). Those with higher HbA1c were at progressively higher odds of albuminuria, but positive associations between both waist-to-hip ratio and BMI were apparent irrespective of HbA1c. Altogether, about 40% of central adiposity associations appeared to be mediated by diabetes, vascular disease and blood pressure.

Conclusions

Conventional epidemiological approaches suggest that higher waist-to-hip ratio and BMI are independently positively associated with albuminuria. Adiposity-albuminuria associations appear strong among people with normal HbA1c, as well as people with pre-diabetes or diabetes.",,pdf:https://www.nature.com/articles/s41366-020-0642-3.pdf; doi:https://doi.org/10.1038/s41366-020-0642-3; html:https://europepmc.org/articles/PMC7577847; pdf:https://europepmc.org/articles/PMC7577847?pdf=render @@ -2085,8 +2085,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 35614427,https://doi.org/10.1186/s12889-022-13457-6,"The association between childhood hearing loss and self-reported peer victimisation, depressive symptoms, and self-harm: longitudinal analyses of a prospective, nationally representative cohort study.","Butcher E, Cortina-Borja M, Dezateux C, Knowles R.",,BMC public health,2022,2022-05-25,Y,Child; Hearing loss; Cohort studies; Mental health; Self-harm; Depressive Symptoms; Peer Victimisation,,,"

Background

Childhood hearing loss (HL) predicts poor mental health and is associated with a higher risk of communication difficulties. The relationship of childhood HL with specific types of poor mental health (such as depressive symptoms or self-harm) and peer victimisation remains unclear.

Methods

We analysed data from the Millennium Cohort Study (MCS), a prospective observational cohort study of children living in the UK at age 9 months and born between 2000 to 2002. Data were available on the children and their families at ages 9 months, then at 3, 5, 7, 11, and 14 years. Participants were 10,858 singleton children with self-reported data on peer victimisation, depressive symptoms, and self-harm at age 14 years. Multivariable logistic regression models were fitted to estimate odds ratios (OR) for HL with peer victimisation, depressive symptoms, and self-harm. HL presence was examined in terms of any HL between ages 9 months and 14 years, as well as by HL trajectory type (defined by onset and persistence). Analyses were adjusted for potential sources of confounding, survey design, and attrition at age 14 years. Interactions between sex and HL were examined in each model and multiple imputation procedures used to address missing data.

Results

Children with any HL had increased odds of depressive symptoms (OR: 1.32, 95% CI: 1.09-1.60), self-harm (1.41, 1.12-1.78) and, in girls only, peer victimisation (girls: 1.81, 1.29-2.55; boys: 1.05, 0.73-1.51), compared to those without HL. HL with later age at onset and persistence to age 14 years was the only trajectory associated with all outcomes.

Conclusions

Childhood HL may predict peer victimisation (in girls), depressive symptoms, and self-harm. Further research is needed to identify HL trajectories and methods to facilitate good mental health in children with HL.",,pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-022-13457-6; doi:https://doi.org/10.1186/s12889-022-13457-6; html:https://europepmc.org/articles/PMC9131522; pdf:https://europepmc.org/articles/PMC9131522?pdf=render 32479194,https://doi.org/10.1161/circulationaha.120.045826,"Lipoprotein(a) in Alzheimer, Atherosclerotic, Cerebrovascular, Thrombotic, and Valvular Disease: Mendelian Randomization Investigation.","Larsson SC, Gill D, Mason AM, Jiang T, Bäck M, Butterworth AS, Burgess S.",,Circulation,2020,2020-06-01,N,Atherosclerosis; Lipoprotein(a); Alzheimer disease; Stroke; Heart valve diseases; Mendelian Randomization Analysis,,,,,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.045826; doi:https://doi.org/10.1161/CIRCULATIONAHA.120.045826; html:https://europepmc.org/articles/PMC7614586; pdf:https://europepmc.org/articles/PMC7614586?pdf=render; doi:https://doi.org/10.1161/circulationaha.120.045826 30949070,https://doi.org/10.3389/fpsyt.2019.00109,Real World Implementation of a Transdiagnostic Risk Calculator for the Automatic Detection of Individuals at Risk of Psychosis in Clinical Routine: Study Protocol.,"Fusar-Poli P, Oliver D, Spada G, Patel R, Stewart R, Dobson R, McGuire P.",,Frontiers in psychiatry,2019,2019-03-13,Y,Schizophrenia; Prevention; risk; Psychosis; Transdiagnostic,"Applied Analytics, Better Care",,"Background: Primary indicated prevention in individuals at-risk for psychosis has the potential to improve the outcomes of this disorder. The ability to detect the majority of at-risk individuals is the main barrier toward extending benefits for the lives of many adolescents and young adults. Current detection strategies are highly inefficient. Only 5% (standalone specialized early detection services) to 12% (youth mental health services) of individuals who will develop a first psychotic disorder can be detected at the time of their at-risk stage. To overcome these challenges a pragmatic, clinically-based, individualized, transdiagnostic risk calculator has been developed to detect individuals at-risk of psychosis in secondary mental health care at scale. This calculator has been externally validated and has demonstrated good prognostic performance. However, it is not known whether it can be used in the real world clinical routine. For example, clinicians may not be willing to adhere to the recommendations made by the transdiagnostic risk calculator. Implementation studies are needed to address pragmatic challenges relating to the real world use of the transdiagnostic risk calculator. The aim of the current study is to provide in-vitro and in-vivo feasibility data to support the implementation of the transdiagnostic risk calculator in clinical routine. Method: This is a study which comprises of two subsequent phases: an in-vitro phase of 1 month and an in-vivo phase of 11 months. The in-vitro phase aims at developing and integrating the transdiagnostic risk calculator in the local electronic health register (primary outcome). The in-vivo phase aims at addressing the clinicians' adherence to the recommendations made by the transdiagnostic risk calculator (primary outcome) and other secondary feasibility parameters that are necessary to estimate the resources needed for its implementation. Discussion: This is the first implementation study for risk prediction models in individuals at-risk for psychosis. Ultimately, successful implementation is the true measure of a prediction model's utility. Therefore, the overall translational deliverable of the current study would be to extend the benefits of primary indicated prevention and improve outcomes of first episode psychosis. This may produce significant social benefits for many adolescents and young adults and their families.",,pdf:https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00109/pdf; doi:https://doi.org/10.3389/fpsyt.2019.00109; html:https://europepmc.org/articles/PMC6436079; pdf:https://europepmc.org/articles/PMC6436079?pdf=render -37269091,https://doi.org/10.1177/10870547231172763,Remote Administration of ADHD-Sensitive Cognitive Tasks: A Pilot Study.,"Sun S, Denyer H, Sankesara H, Deng Q, Ranjan Y, Conde P, Rashid Z, Bendayan R, Asherson P, Bilbow A, Groom M, Hollis C, Folarin AA, Dobson RJB, Kuntsi J.",,Journal of attention disorders,2023,2023-06-02,Y,ADHD; Remote Monitoring; Response Inhibition; Attention Regulation; Radar-base,,,"

Objective

We assessed the feasibility and validity of remote researcher-led administration and self-administration of modified versions of two cognitive tasks sensitive to ADHD, a four-choice reaction time task (Fast task) and a combined Continuous Performance Test/Go No-Go task (CPT/GNG), through a new remote measurement technology system.

Method

We compared the cognitive performance measures (mean and variability of reaction times (MRT, RTV), omission errors (OE) and commission errors (CE)) at a remote baseline researcher-led administration and three remote self-administration sessions between participants with and without ADHD (n = 40).

Results

The most consistent group differences were found for RTV, MRT and CE at the baseline researcher-led administration and the first self-administration, with 8 of the 10 comparisons statistically significant and all comparisons indicating medium to large effect sizes.

Conclusion

Remote administration of cognitive tasks successfully captured the difficulties with response inhibition and regulation of attention, supporting the feasibility and validity of remote assessments.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/10870547231172763; doi:https://doi.org/10.1177/10870547231172763; html:https://europepmc.org/articles/PMC10291103; pdf:https://europepmc.org/articles/PMC10291103?pdf=render 31040096,https://doi.org/10.1016/s2352-4642(19)30114-2,"Antimicrobial-impregnated central venous catheters for prevention of neonatal bloodstream infection (PREVAIL): an open-label, parallel-group, pragmatic, randomised controlled trial.","Gilbert R, Brown M, Rainford N, Donohue C, Fraser C, Sinha A, Dorling J, Gray J, McGuire W, Gamble C, Oddie SJ, PREVAIL trial team.",,The Lancet. Child & adolescent health,2019,2019-04-27,N,,"Better, Faster and More Efficient Clinical Trials",,"

Background

Bloodstream infection is associated with high mortality and serious morbidity in preterm babies. Evidence from clinical trials shows that antimicrobial-impregnated central venous catheters (CVCs) reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is a paucity of similar evidence for babies receiving neonatal intensive care.

Methods

This open-label, parallel-group, pragmatic, randomised controlled trial was done in 18 neonatal intensive care units in England. Newborn babies who needed a peripherally inserted CVC (PICC) were allocated randomly (1:1) to receive either a PICC impregnated with miconazole and rifampicin or a standard (non-antimicrobial-impregnated) PICC. Random allocation was done with a web-based program, which was centrally controlled to ensure allocation concealment. Randomisation sequences were computer-generated in random blocks of two and four, and stratified by site. Masking of clinicians to PICC allocation was impractical because rifampicin caused brown staining of the antimicrobial-impregnated PICC. However, participant inclusion in analyses and occurrence of outcome events were determined following an analysis plan that was specified before individuals saw the unblinded data. The primary outcome was the time from random allocation to first microbiologically confirmed bloodstream or cerebrospinal fluid (CSF) infection between 24 h after randomisation and 48 h after PICC removal or death. We analysed outcome data according to the intention-to-treat principle. We excluded babies for whom a PICC was not inserted from safety analyses, as these analyses were done with groups defined by the PICC used. This trial is registered with ISRCTN, number 81931394.

Findings

Between Aug 12, 2015, and Jan 11, 2017, we randomly assigned 861 babies (754 [88%] born before 32 weeks of gestation) to receive an antimicrobial-impregnated PICC (430 babies) or standard PICC (431 babies). The median time to PICC removal was 8·20 days (IQR 4·77-12·13) in the antimicrobial-impregnated PICC group versus 7·86 days (5·00-12·53) days in the standard PICC group (hazard ratio [HR] 1·03, 95% CI 0·89-1·18, p=0·73), with 46 (11%) of 430 babies versus 44 (10%) of 431 babies having a microbiologically confirmed bloodstream or CSF infection. The time from random allocation to first bloodstream or CSF infection was similar between the two groups (HR 1·11, 95% CI 0·73-1·67, p=0·63). Secondary outcomes relating to infection, rifampicin resistance in positive blood or CSF cultures, mortality, clinical outcomes at neonatal unit discharge, and time to PICC removal were similar between the two groups, although rifampicin resistance in positive cultures of PICC tips was higher in the antimicrobial-impregnated PICC group (relative risk 3·51, 95% CI 1·16-10·57, p=0·018). 60 adverse events were reported from 49 (13%) patients in the antimicrobial-impregnated PICC group and 50 events from 45 (10%) babies in the standard PICC group.

Interpretation

We found no evidence of benefit or harm associated with miconazole and rifampicin-impregnated PICCs compared with standard PICCs for newborn babies. Future research should focus on other types of antimicrobial impregnation of PICCs and alternative approaches for preventing infection.

Funding

UK National Institute for Health Research Health Technology Assessment programme.",,pdf:http://www.thelancet.com/article/S2352464219301142/pdf; doi:https://doi.org/10.1016/S2352-4642(19)30114-2 +37269091,https://doi.org/10.1177/10870547231172763,Remote Administration of ADHD-Sensitive Cognitive Tasks: A Pilot Study.,"Sun S, Denyer H, Sankesara H, Deng Q, Ranjan Y, Conde P, Rashid Z, Bendayan R, Asherson P, Bilbow A, Groom M, Hollis C, Folarin AA, Dobson RJB, Kuntsi J.",,Journal of attention disorders,2023,2023-06-02,Y,ADHD; Remote Monitoring; Response Inhibition; Attention Regulation; Radar-base,,,"

Objective

We assessed the feasibility and validity of remote researcher-led administration and self-administration of modified versions of two cognitive tasks sensitive to ADHD, a four-choice reaction time task (Fast task) and a combined Continuous Performance Test/Go No-Go task (CPT/GNG), through a new remote measurement technology system.

Method

We compared the cognitive performance measures (mean and variability of reaction times (MRT, RTV), omission errors (OE) and commission errors (CE)) at a remote baseline researcher-led administration and three remote self-administration sessions between participants with and without ADHD (n = 40).

Results

The most consistent group differences were found for RTV, MRT and CE at the baseline researcher-led administration and the first self-administration, with 8 of the 10 comparisons statistically significant and all comparisons indicating medium to large effect sizes.

Conclusion

Remote administration of cognitive tasks successfully captured the difficulties with response inhibition and regulation of attention, supporting the feasibility and validity of remote assessments.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/10870547231172763; doi:https://doi.org/10.1177/10870547231172763; html:https://europepmc.org/articles/PMC10291103; pdf:https://europepmc.org/articles/PMC10291103?pdf=render 30014898,https://doi.org/10.1016/j.envres.2018.07.015,Estimation of TETRA radio use in the Airwave Health Monitoring Study of the British police forces.,"Vergnaud AC, Aresu M, Kongsgård HW, McRobie D, Singh D, Spear J, Heard A, Gao H, Carpenter JR, Elliott P.",,Environmental research,2018,2018-07-09,N,Tetra; Occupational Exposure; Occupational Cohort; Radiofrequency Electromagnetic Fields,Improving Public Health,,"

Background

The Airwave Health Monitoring Study aims to investigate the possible long-term health effects of Terrestrial Trunked Radio (TETRA) use among the police forces in Great Britain. Here, we investigate whether objective data from the network operator could be used to correct for misreporting in self-reported data and expand the radio usage availability in our cohort.

Methods

We estimated average monthly usage of personal radio in the 12 months prior to enrolment from a missing value imputation model and evaluated its performance against objective and self-reported data. Factors associated with TETRA radio usage variables were investigated using Chi-square tests and analysis of variance.

Results

The imputed data were better correlated with objective than self-reported usage (Spearman correlation coefficient = 0.72 vs. 0. 52 and kappa 0.56 [95% confidence interval 0.55, 0.56] vs. 0.46 [0.45, 0.47]), although the imputation model tended to under-estimate use for higher users. Participants with higher personal radio usage were more likely to be younger, men vs. women and officer vs. staff. The median average monthly usage level for the entire cohort was estimated to be 29.3 min (95% CI: [7.2, 66.6]).

Conclusion

The availability of objective personal radio records for a large proportion of users allowed us to develop a robust imputation model and hence obtain personal radio usage estimates for ~50,000 participants. This substantially reduced exposure misclassification compared to using self-reported data and will allow us to carry out analyses of TETRA usage for the entire cohort in future work.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4648566/1/Estimation%20of%20TETRA%20radio_GREEN%20AAM.pdf; doi:https://doi.org/10.1016/j.envres.2018.07.015 32719032,https://doi.org/10.1128/jcm.00670-20,DNA Thermo-Protection Facilitates Whole-Genome Sequencing of Mycobacteria Direct from Clinical Samples.,"George S, Xu Y, Rodger G, Morgan M, Sanderson ND, Hoosdally SJ, Thulborn S, Robinson E, Rathod P, Walker AS, Peto TEA, Crook DW, Dingle KE.",,Journal of clinical microbiology,2020,2020-09-22,Y,DNA sequencing; Mycobacterium tuberculosis; Mycobacteria; Clinical Diagnostics; Nanopore Dna Sequencing; Direct-from-sample Sequencing,,,"Mycobacterium tuberculosis is the leading cause of death from bacterial infection. Improved rapid diagnosis and antimicrobial resistance determination, such as by whole-genome sequencing, are required. Our aim was to develop a simple, low-cost method of preparing DNA for sequencing direct from M. tuberculosis-positive clinical samples (without culture). Simultaneous sputum liquefaction, bacteria heat inactivation (99°C/30 min), and enrichment for mycobacteria DNA were achieved using an equal volume of thermo-protection buffer (4 M KCl, 0.05 M HEPES buffer, pH 7.5, 0.1% dithiothreitol [DTT]). The buffer emulated intracellular conditions found in hyperthermophiles, thus protecting DNA from rapid thermodegradation, which renders it a poor template for sequencing. Initial validation experiments employed mycobacteria DNA, either extracted or intracellular. Next, mock clinical samples (infection-negative human sputum spiked with 0 to 105Mycobacterium bovis BCG cells/ml) underwent liquefaction in thermo-protection buffer and heat inactivation. DNA was extracted and sequenced. Human DNA degraded faster than mycobacteria DNA, resulting in target enrichment. Four replicate experiments achieved M. tuberculosis detection at 101 BCG cells/ml, with 31 to 59 M. tuberculosis complex reads. Maximal genome coverage (>97% at 5× depth) occurred at 104 BCG cells/ml; >91% coverage (1× depth) occurred at 103 BCG cells/ml. Final validation employed M. tuberculosis-positive clinical samples (n = 20), revealing that initial sample volumes of ≥1 ml typically yielded higher mean depths of M. tuberculosis genome coverage, with an overall range of 0.55 to 81.02. A mean depth of 3 gave >96% 1-fold tuberculosis (TB) genome coverage (in 15/20 clinical samples). A mean depth of 15 achieved >99% 5-fold genome coverage (in 9/20 clinical samples). In summary, direct-from-sample sequencing of M. tuberculosis genomes was facilitated by a low-cost thermo-protection buffer.",,doi:https://doi.org/10.1128/jcm.00670-20; doi:https://doi.org/10.1128/JCM.00670-20; html:https://europepmc.org/articles/PMC7512152; pdf:https://europepmc.org/articles/PMC7512152?pdf=render 33664499,https://doi.org/10.1038/s41431-021-00835-8,Colocalization analysis of polycystic ovary syndrome to identify potential disease-mediating genes and proteins.,"Censin JC, Bovijn J, Holmes MV, Lindgren CM.",,European journal of human genetics : EJHG,2021,2021-03-04,Y,,,,"Polycystic ovary syndrome (PCOS) is a common complex disease in women with a strong genetic component and downstream consequences for reproductive, metabolic and psychological health. There are currently 19 known PCOS risk loci, primarily identified in women of Han Chinese or European ancestry, and 14 of these risk loci were identified or replicated in a genome-wide association study of PCOS performed in up to 10,074 cases and 103,164 controls of European descent. However, for most of these loci the gene responsible for the association is unknown. We therefore use a Bayesian colocalization approach (Coloc) to highlight genes in PCOS-associated regions that may have a role in mediating the disease risk. We evaluated the posterior probabilities of evidence consistent with shared causal variants between 14 PCOS genetic risk loci and intermediate cellular phenotypes in one protein (N = 3301) and two expression quantitative trait locus datasets (N = 31,684 and N = 80-491). Through these analyses, we identified seven proteins or genes with evidence of a possibly shared causal variant for almost 30% of known PCOS signals, including follicle stimulating hormone and ERBB3, IKZF4, RPS26, SUOX, ZFP36L2, and C8orf49. Several of these potential effector proteins and genes have been implicated in the hypothalamic-pituitary-gonadal signalling pathway and provide an avenue for functional follow-up in order to demonstrate a causal role in PCOS pathophysiology.",,pdf:https://www.nature.com/articles/s41431-021-00835-8.pdf; doi:https://doi.org/10.1038/s41431-021-00835-8; html:https://europepmc.org/articles/PMC8440598; pdf:https://europepmc.org/articles/PMC8440598?pdf=render @@ -2108,15 +2108,15 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 35246709,https://doi.org/10.1007/s00127-022-02257-3,Ethnic inequalities in clozapine use among people with treatment-resistant schizophrenia: a retrospective cohort study using data from electronic clinical records.,"de Freitas DF, Patel I, Kadra-Scalzo G, Pritchard M, Shetty H, Broadbent M, Patel R, Downs J, Segev A, Khondoker M, MacCabe JH, Bhui K, Hayes RD.",,Social psychiatry and psychiatric epidemiology,2022,2022-03-04,Y,Clozapine; Health Inequalities; Benign Ethnic Neutropenia; Black British; Refractory Psychosis; Asian British,,,"

Purpose

Clozapine is the most effective intervention for treatment-resistant schizophrenia (TRS). Several studies report ethnic disparities in clozapine treatment. However, few studies restrict analyses to TRS cohorts alone or address confounding by benign ethnic neutropenia. This study investigates ethnic equity in access to clozapine treatment for people with treatment-resistant schizophrenia spectrum disorder.

Methods

A retrospective cohort study, using information from 11 years of clinical records (2007-2017) from the South London and Maudsley NHS Trust. We identified a cohort of service-users with TRS using a validated algorithm. We investigated associations between ethnicity and clozapine treatment, adjusting for sociodemographic factors, psychiatric multi-morbidity, substance misuse, neutropenia, and service-use.

Results

Among 2239 cases of TRS, Black service-users were less likely to be receive clozapine compared with White British service-users after adjusting for confounders (Black African aOR = 0.49, 95% CI [0.33, 0.74], p = 0.001; Black Caribbean aOR = 0.64, 95% CI [0.43, 0.93], p = 0.019; Black British aOR = 0.61, 95% CI [0.41, 0.91], p = 0.016). It was additionally observed that neutropenia was not related to treatment with clozapine. Also, a detention under the Mental Health Act was negatively associated clozapine receipt, suggesting people with TRS who were detained are less likely to be treated with clozapine.

Conclusion

Black service-users with TRS were less likely to receive clozapine than White British service-users. Considering the protective effect of treatment with clozapine, these inequities may place Black service-users at higher risk for hospital admissions and mortality.",,pdf:https://link.springer.com/content/pdf/10.1007/s00127-022-02257-3.pdf; doi:https://doi.org/10.1007/s00127-022-02257-3; html:https://europepmc.org/articles/PMC9246775; pdf:https://europepmc.org/articles/PMC9246775?pdf=render 36539756,https://doi.org/10.1186/s12888-022-04429-6,ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA): a multi-centre prospective cohort study protocol.,"Denyer H, Ramos-Quiroga JA, Folarin A, Ramos C, Nemeth P, Bilbow A, Woodward E, Whitwell S, Müller-Sedgwick U, Larsson H, Dobson RJ, Kuntsi J.",,BMC psychiatry,2022,2022-12-20,Y,ADHD; Cardiovascular disease; Attention Deficit Hyperactivity Disorder; Medication Adherence; Remote Monitoring; Mhealth; Digital Phenotyping; Remote Measurement Technology,,,"

Background

Emerging evidence points at substantial comorbidity between adult attention deficit hyperactivity disorder (ADHD) and cardiometabolic diseases, but our understanding of the comorbidity and how to manage cardiometabolic disease in adults with ADHD is limited. The ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA) project uses remote measurement technology to obtain real-world data from daily life to assess the extent to which ADHD medication treatment and physical activity, individually and jointly, may influence cardiometabolic risks in adults with ADHD. Our second main aim is to obtain valuable real-world data on adherence to pharmacological treatment and its predictors and correlates during daily life from adults with ADHD.

Methods

ART-CARMA is a multi-site prospective cohort study within the EU-funded collaboration 'TIMESPAN' (Management of chronic cardiometabolic disease and treatment discontinuity in adult ADHD patients) that will recruit 300 adults from adult ADHD waiting lists. The participants will be monitored remotely over a period of 12 months that starts from pre-treatment initiation. Passive monitoring, which involves the participants wearing a wrist-worn device (EmbracePlus) and downloading the RADAR-base Passive App and the Empatica Care App on their smartphone, provides ongoing data collection on a wide range of variables, such as physical activity, sleep, pulse rate (PR) and pulse rate variability (PRV), systolic peaks, electrodermal activity (EDA), oxygen saturation (SpO2), peripheral temperature, smartphone usage including social connectivity, and the environment (e.g. ambient noise, light levels, relative location). By combining data across these variables measured, processes such as physical activity, sleep, autonomic arousal, and indicators of cardiovascular health can be captured. Active remote monitoring involves the participant completing tasks using a smartphone app (such as completing clinical questionnaires or speech tasks), measuring their blood pressure and weight, or using a PC/laptop (cognitive tasks). The ART system is built on the RADAR-base mobile-health platform.

Discussion

The long-term goal is to use these data to improve the management of cardiometabolic disease in adults with ADHD, and to improve ADHD medication treatment adherence and the personalisation of treatment.",,pdf:https://bmcpsychiatry.biomedcentral.com/counter/pdf/10.1186/s12888-022-04429-6; doi:https://doi.org/10.1186/s12888-022-04429-6; html:https://europepmc.org/articles/PMC9764531; pdf:https://europepmc.org/articles/PMC9764531?pdf=render 30984759,https://doi.org/10.3389/fmed.2019.00048,"Direct-to-Consumer Genetic Testing's Red Herring: ""Genetic Ancestry"" and Personalized Medicine.","Blell M, Hunter MA.",,Frontiers in medicine,2019,2019-03-29,Y,RACE; Ethics; Ethnicity; Genetic Testing; Personalized Medicine,Understanding the Causes of Disease,,"The growth in the direct-to-consumer genetic testing industry poses a number of challenges for healthcare practice, among a number of other areas of concern. Several companies providing this service send their customers reports including information variously referred to as genetic ethnicity, genetic heritage, biogeographic ancestry, and genetic ancestry. In this article, we argue that such information should not be used in healthcare consultations or to assess health risks. Far from representing a move toward personalized medicine, use of this information poses risks both to patients as individuals and to racialized ethnic groups because of the way it misrepresents human genetic diversity.",,pdf:https://www.frontiersin.org/articles/10.3389/fmed.2019.00048/pdf; doi:https://doi.org/10.3389/fmed.2019.00048; html:https://europepmc.org/articles/PMC6449432; pdf:https://europepmc.org/articles/PMC6449432?pdf=render -31358974,https://doi.org/10.1038/s41562-019-0653-z,New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders.,"Evangelou E, Gao H, Chu C, Ntritsos G, Blakeley P, Butts AR, Pazoki R, Suzuki H, Koskeridis F, Yiorkas AM, Karaman I, Elliott J, Luo Q, Aeschbacher S, Bartz TM, Baumeister SE, Braund PS, Brown MR, Brody JA, Clarke TK, Dimou N, Faul JD, Homuth G, Jackson AU, Kentistou KA, Joshi PK, Lemaitre RN, Lind PA, Lyytikäinen LP, Mangino M, Milaneschi Y, Nelson CP, Nolte IM, Perälä MM, Polasek O, Porteous D, Ratliff SM, Smith JA, Stančáková A, Teumer A, Tuominen S, Thériault S, Vangipurapu J, Whitfield JB, Wood A, Yao J, Yu B, Zhao W, Arking DE, Auvinen J, Liu C, Männikkö M, Risch L, Rotter JI, Snieder H, Veijola J, Blakemore AI, Boehnke M, Campbell H, Conen D, Eriksson JG, Grabe HJ, Guo X, van der Harst P, Hartman CA, Hayward C, Heath AC, Jarvelin MR, Kähönen M, Kardia SLR, Kühne M, Kuusisto J, Laakso M, Lahti J, Lehtimäki T, McIntosh AM, Mohlke KL, Morrison AC, Martin NG, Oldehinkel AJ, Penninx BWJH, Psaty BM, Raitakari OT, Rudan I, Samani NJ, Scott LJ, Spector TD, Verweij N, Weir DR, Wilson JF, Levy D, Tzoulaki I, Bell JD, Matthews PM, Rothenfluh A, Desrivières S, Schumann G, Elliott P.",,Nature human behaviour,2019,2019-07-29,N,,,,"Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g d-1) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 new common loci and investigated their potential functional importance using magnetic resonance imaging data and gene expression studies. We identify genetic pathways associated with alcohol consumption and suggest genetic mechanisms that are shared with neuropsychiatric disorders such as schizophrenia.",,pdf:https://boris.unibe.ch/174991/1/nihms-1649425.pdf; doi:https://doi.org/10.1038/s41562-019-0653-z; html:https://europepmc.org/articles/PMC7711277; pdf:https://europepmc.org/articles/PMC7711277?pdf=render; doi:https://doi.org/10.1038/s41562-019-0653-z 36204496,https://doi.org/10.1177/23992026211048421,Beyond trust: Amplifying unheard voices on concerns about harm resulting from health data-sharing.,"Mulrine S, Blell M, Murtagh M.",,Medicine access @ point of care,2021,2021-01-01,Y,Data; Qualitative Methods; Data-sharing; Underrepresented Groups,,,"

Background

The point of care in many health systems is increasingly a point of health data generation, data which may be shared and used in a variety of ways by a range of different actors.

Aim

We set out to gather data about the perspectives on health data-sharing of people living in North East England who have been underrepresented within other public engagement activities and who are marginalized in society.

Methods

Multi-site ethnographic fieldwork was carried out in the Teesside region of England over a 6-month period in 2019 as part of a large-scale health data innovation program called Connected Health Cities. Organizations working with marginalized groups were contacted to recruit staff, volunteers, and beneficiaries for participation in qualitative research. The data gathered were analyzed thematically and vignettes constructed to illustrate findings.

Results

Previous encounters with health and social care professionals and the broader socio-political contexts of people's lives shape the perspectives of people from marginalized groups about sharing of data from their health records. While many would welcome improved care, the risks to people with socially produced vulnerabilities must be appreciated by those advocating systems that share data for personalized medicine or other forms of data-driven care.

Conclusion

Forms of innovation in medicine which rely on greater data-sharing may present risks to groups and individuals with existing vulnerabilities, and advocates of these innovations should address the lack of trustworthiness of those receiving data before asking that people trust new systems to provide health benefits.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/23992026211048421; doi:https://doi.org/10.1177/23992026211048421; html:https://europepmc.org/articles/PMC9413596; pdf:https://europepmc.org/articles/PMC9413596?pdf=render +31358974,https://doi.org/10.1038/s41562-019-0653-z,New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders.,"Evangelou E, Gao H, Chu C, Ntritsos G, Blakeley P, Butts AR, Pazoki R, Suzuki H, Koskeridis F, Yiorkas AM, Karaman I, Elliott J, Luo Q, Aeschbacher S, Bartz TM, Baumeister SE, Braund PS, Brown MR, Brody JA, Clarke TK, Dimou N, Faul JD, Homuth G, Jackson AU, Kentistou KA, Joshi PK, Lemaitre RN, Lind PA, Lyytikäinen LP, Mangino M, Milaneschi Y, Nelson CP, Nolte IM, Perälä MM, Polasek O, Porteous D, Ratliff SM, Smith JA, Stančáková A, Teumer A, Tuominen S, Thériault S, Vangipurapu J, Whitfield JB, Wood A, Yao J, Yu B, Zhao W, Arking DE, Auvinen J, Liu C, Männikkö M, Risch L, Rotter JI, Snieder H, Veijola J, Blakemore AI, Boehnke M, Campbell H, Conen D, Eriksson JG, Grabe HJ, Guo X, van der Harst P, Hartman CA, Hayward C, Heath AC, Jarvelin MR, Kähönen M, Kardia SLR, Kühne M, Kuusisto J, Laakso M, Lahti J, Lehtimäki T, McIntosh AM, Mohlke KL, Morrison AC, Martin NG, Oldehinkel AJ, Penninx BWJH, Psaty BM, Raitakari OT, Rudan I, Samani NJ, Scott LJ, Spector TD, Verweij N, Weir DR, Wilson JF, Levy D, Tzoulaki I, Bell JD, Matthews PM, Rothenfluh A, Desrivières S, Schumann G, Elliott P.",,Nature human behaviour,2019,2019-07-29,N,,,,"Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g d-1) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 new common loci and investigated their potential functional importance using magnetic resonance imaging data and gene expression studies. We identify genetic pathways associated with alcohol consumption and suggest genetic mechanisms that are shared with neuropsychiatric disorders such as schizophrenia.",,pdf:https://boris.unibe.ch/174991/1/nihms-1649425.pdf; doi:https://doi.org/10.1038/s41562-019-0653-z; html:https://europepmc.org/articles/PMC7711277; pdf:https://europepmc.org/articles/PMC7711277?pdf=render; doi:https://doi.org/10.1038/s41562-019-0653-z 36208161,https://doi.org/10.1093/eurheartj/ehac426,CODE-EHR best practice framework for the use of structured electronic healthcare records in clinical research.,"Kotecha D, Asselbergs FW, Achenbach S, Anker SD, Atar D, Baigent C, Banerjee A, Beger B, Brobert G, Casadei B, Ceccarelli C, Cowie MR, Crea F, Cronin M, Denaxas S, Derix A, Fitzsimons D, Fredriksson M, Gale CP, Gkoutos GV, Goettsch W, Hemingway H, Ingvar M, Jonas A, Kazmierski R, Løgstrup S, Thomas Lumbers R, Lüscher TF, McGreavy P, Piña IL, Roessig L, Steinbeisser C, Sundgren M, Tyl B, van Thiel G, van Bochove K, Vardas PE, Villanueva T, Vrana M, Weber W, Weidinger F, Windecker S, Wood A, Grobbee DE, Innovative Medicines Initiative BigData@Heart Consortium, European Society of Cardiology, CODE-EHR international consensus group.",,European heart journal,2022,2022-10-01,Y,,,,"Big data is central to new developments in global clinical science aiming to improve the lives of patients. Technological advances have led to the routine use of structured electronic healthcare records with the potential to address key gaps in clinical evidence. The covid-19 pandemic has demonstrated the potential of big data and related analytics, but also important pitfalls. Verification, validation, and data privacy, as well as the social mandate to undertake research are key challenges. The European Society of Cardiology and the BigData@Heart consortium have brought together a range of international stakeholders, including patient representatives, clinicians, scientists, regulators, journal editors and industry. We propose the CODE-EHR Minimum Standards Framework as a means to improve the design of studies, enhance transparency and develop a roadmap towards more robust and effective utilisation of healthcare data for research purposes.",,pdf:https://academic.oup.com/eurheartj/article-pdf/43/37/3578/46535456/ehac426.pdf; doi:https://doi.org/10.1093/eurheartj/ehac426; html:https://europepmc.org/articles/PMC9452067; pdf:https://europepmc.org/articles/PMC9452067?pdf=render 34442458,https://doi.org/10.3390/jpm11080814,Reduced MIP-1β as a Trait Marker and Reduced IL-7 and IL-12 as State Markers of Anorexia Nervosa.,"Keeler JL, Patsalos O, Chung R, Schmidt U, Breen G, Treasure J, Himmerich H, Dalton B.",,Journal of personalized medicine,2021,2021-08-20,Y,Cytokines; Chemokines; Brain-derived neurotrophic factor; Anorexia Nervosa; cross-sectional; Inflammatory Markers,,,"Alterations in certain inflammatory markers have been found in individuals with anorexia nervosa (AN). However, their relation to clinical characteristics has not been extensively explored, nor is it clear whether they are trait or state features of the disorder. This cross-sectional study measured serum concentrations of 36 inflammatory markers in people with acute AN (n = 56), recovered AN (rec-AN; n = 24) and healthy controls (HC; n = 51). The relationship between body mass index (BMI), eating disorder psychopathology, depression symptoms and inflammatory markers was assessed. Statistical models controlled for variables known to influence cytokine concentrations (i.e., age, ethnicity, smoking status and medication usage). Overall, most inflammatory markers including pro-inflammatory cytokines were unchanged in AN and rec-AN. However, in AN and rec-AN, concentrations of macrophage inflammatory protein (MIP)-1β were lower than HCs. Interleukin (IL)-7 and IL-12/IL-23p40 were reduced in AN, and concentrations of macrophage-derived chemokine, MIP-1α and tumor necrosis factor-α were reduced in rec-AN compared to HC. In conclusion, a reduction in MIP-1β may be a trait marker of the illness, whereas reductions in IL-7 and IL-12/IL-23p40 may be state markers. The absence of increased pro-inflammatory cytokines in AN is contradictory to the wider literature, although the inclusion of covariates may explain our differing findings.",,pdf:https://www.mdpi.com/2075-4426/11/8/814/pdf?version=1629458822; doi:https://doi.org/10.3390/jpm11080814; html:https://europepmc.org/articles/PMC8399452; pdf:https://europepmc.org/articles/PMC8399452?pdf=render 38701403,https://doi.org/10.1212/wnl.0000000000209388,Patent Foramen Ovale Closure in Older Patients With Stroke: Patient Selection for Trial Feasibility.,"Wang AY, Rothwell PM, Nelson J, Saver JL, Kasner SE, Carroll J, Mas JL, Derumeaux G, Chatellier G, Furlan AJ, Herrmann HC, Jüni P, Kim JS, Koethe B, Lee PH, Lefebvre B, Mattle HP, Meier B, Reisman M, Smalling RW, Sondergaard L, Song JK, Di Angelantonio E, DiTullio M, Elkind MSV, Homma S, Jaigobin C, Michel P, Mono ML, Nedeltchev K, Papetti F, Serena J, Weimar C, Li L, Mazzucco S, Silver LE, van Klaveren D, Thaler DE, Kent DM.",,Neurology,2024,2024-05-03,N,,,,"

Background and objectives

Whether patent foramen ovale (PFO) closure benefits older patients with PFO and cryptogenic stroke is unknown because randomized controlled trials (RCTs) have predominantly enrolled patients younger than 60 years of age. Our objective was to estimate anticipated effects of PFO closure in older patients to predict the numbers needed to plan an RCT.

Methods

Effectiveness estimates are derived from major observational studies (Risk of Paradoxical Embolism [RoPE] Study and Oxford Vascular Study, together referred to as the ""RoPE-Ox"" database) and all 6 major RCTs (Systematic, Collaborative, PFO Closure Evaluation [SCOPE] Consortium). To estimate stroke recurrence risk, observed outcomes were calculated for patients older than 60 years in the age-inclusive observational databases (n = 549). To estimate the reduction in the rate of recurrent stroke associated with PFO closure vs medical therapy based on the RoPE score and the presence of high-risk PFO features, a Cox proportional hazards regression model was developed on the RCT data in the SCOPE database (n = 3,740). These estimates were used to calculate sample sizes required for a future RCT.

Results

Five-year risk of stroke recurrence using Kaplan-Meier estimates was 13.7 (95% CI 10.5-17.9) overall, 14.9% (95% CI 10.2-21.6) in those with high-risk PFO features. Predicted relative reduction in the event rate with PFO closure was 12.9% overall, 48.8% in those with a high-risk PFO feature. Using these estimates, enrolling all older patients with cryptogenic stroke and PFO would require much larger samples than those used for prior PFO closure trials, but selectively enrolling patients with high-risk PFO features would require totals of 630 patients for 90% power and 471 patients for 80% power, with an average of 5 years of follow-up.

Discussion

Based on our projections, anticipated effect sizes in older patients with high-risk features make a trial in these subjects feasible. With lengthening life expectancy in almost all regions of the world, the utility of PFO closure in older adults is increasingly important to explore.",,doi:https://doi.org/10.1212/WNL.0000000000209388 34167318,https://doi.org/10.1161/circulationaha.121.054302,Cardiac Troponin Thresholds and Kinetics to Differentiate Myocardial Injury and Myocardial Infarction.,"Wereski R, Kimenai DM, Taggart C, Doudesis D, Lee KK, Lowry MTH, Bularga A, Lowe DJ, Fujisawa T, Apple FS, Collinson PO, Anand A, Chapman AR, Mills NL.",,Circulation,2021,2021-06-25,Y,Kinetics; Troponin; Myocardial infarction; Predictive Value Of Tests,,,"

Background

Although the 99th percentile is the recommended diagnostic threshold for myocardial infarction, some guidelines also advocate the use of higher troponin thresholds to rule in myocardial infarction at presentation. It is unclear whether the magnitude or change in troponin concentration can differentiate causes of myocardial injury and infarction in practice.

Methods

In a secondary analysis of a multicenter randomized controlled trial, we identified 46 092 consecutive patients presenting with suspected acute coronary syndrome without ST-segment-elevation myocardial infarction. High-sensitivity cardiac troponin I concentrations at presentation and on serial testing were compared between patients with myocardial injury and infarction. The positive predictive value and specificity were determined at the sex-specific 99th percentile upper reference limit and rule-in thresholds of 64 ng/L and 5-fold of the upper reference limit for a diagnosis of type 1 myocardial infarction.

Results

Troponin was above the 99th percentile in 8188 patients (18%). The diagnosis was type 1 or type 2 myocardial infarction in 50% and 14% and acute or chronic myocardial injury in 20% and 16%, respectively. Troponin concentrations were similar at presentation in type 1 (median [25th-75th percentile] 91 [30-493] ng/L) and type 2 (50 [22-147] ng/L) myocardial infarction and in acute (50 [26-134] ng/L) and chronic (51 [31-130] ng/L) myocardial injury. The 99th percentile and rule-in thresholds of 64 ng/L and 5-fold upper reference limit gave a positive predictive value of 57% (95% CI, 56%-58%), 59% (58%-61%), and 62% (60%-64%) and a specificity of 96% (96%-96%), 96% (96%-96%), and 98% (97%-98%), respectively. The absolute, relative, and rate of change in troponin concentration were highest in patients with type 1 myocardial infarction (P<0.001 for all). Discrimination improved when troponin concentration and change in troponin were combined compared with troponin concentration at presentation alone (area under the curve, 0.661 [0.642-0.680] versus 0.613 [0.594-0.633]).

Conclusions

Although we observed important differences in the kinetics, cardiac troponin concentrations at presentation are insufficient to distinguish type 1 myocardial infarction from other causes of myocardial injury or infarction in practice and should not guide management decisions in isolation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01852123.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.054302; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.054302; html:https://europepmc.org/articles/PMC8360674; pdf:https://europepmc.org/articles/PMC8360674?pdf=render -32327693,https://doi.org/10.1038/s42003-020-0921-5,Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis.,"Oskarsson GR, Oddsson A, Magnusson MK, Kristjansson RP, Halldorsson GH, Ferkingstad E, Zink F, Helgadottir A, Ivarsdottir EV, Arnadottir GA, Jensson BO, Katrinardottir H, Sveinbjornsson G, Kristinsdottir AM, Lee AL, Saemundsdottir J, Stefansdottir L, Sigurdsson JK, Davidsson OB, Benonisdottir S, Jonasdottir A, Jonasdottir A, Jonsson S, Gudmundsson RL, Asselbergs FW, Tragante V, Gunnarsson B, Masson G, Thorleifsson G, Rafnar T, Holm H, Olafsson I, Onundarson PT, Gudbjartsson DF, Norddahl GL, Thorsteinsdottir U, Sulem P, Stefansson K.",,Communications biology,2020,2020-04-23,Y,,,,"Hemoglobin is the essential oxygen-carrying molecule in humans and is regulated by cellular iron and oxygen sensing mechanisms. To search for novel variants associated with hemoglobin concentration, we performed genome-wide association studies of hemoglobin concentration using a combined set of 684,122 individuals from Iceland and the UK. Notably, we found seven novel variants, six rare coding and one common, at the ACO1 locus associating with either decreased or increased hemoglobin concentration. Of these variants, the missense Cys506Ser and the stop-gained Lys334Ter mutations are specific to eight and ten generation pedigrees, respectively, and have the two largest effects in the study (EffectCys506Ser = -1.61 SD, CI95 = [-1.98, -1.35]; EffectLys334Ter = 0.63 SD, CI95 = [0.36, 0.91]). We also find Cys506Ser to associate with increased risk of persistent anemia (OR = 17.1, P = 2 × 10-14). The strong bidirectional effects seen in this study implicate ACO1, a known iron sensing molecule, as a major homeostatic regulator of hemoglobin concentration.",,pdf:https://www.nature.com/articles/s42003-020-0921-5.pdf; doi:https://doi.org/10.1038/s42003-020-0921-5; html:https://europepmc.org/articles/PMC7181819; pdf:https://europepmc.org/articles/PMC7181819?pdf=render -36696816,https://doi.org/10.1016/j.ebiom.2023.104441,Causal effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation study.,"Zhao J, Stewart ID, Baird D, Mason D, Wright J, Zheng J, Gaunt TR, Evans DM, Freathy RM, Langenberg C, Warrington NM, Lawlor DA, Borges MC, MR-PREG Consortium.",,EBioMedicine,2023,2023-01-23,Y,Amino acids; Gwas; Birthweight; Causal Effect; Mendelian Randomisation,,,"

Background

Amino acids are key to protein synthesis, energy metabolism, cell signaling and gene expression; however, the contribution of specific maternal amino acids to fetal growth is unclear.

Methods

We explored the effect of maternal circulating amino acids on fetal growth, proxied by birthweight, using two-sample Mendelian randomisation (MR) and summary data from a genome-wide association study (GWAS) of serum amino acids levels (sample 1, n = 86,507) and a maternal GWAS of offspring birthweight in UK Biobank and Early Growth Genetics Consortium, adjusting for fetal genotype effects (sample 2, n = 406,063 with maternal and/or fetal genotype effect estimates). A total of 106 independent single nucleotide polymorphisms robustly associated with 19 amino acids (p < 4.9 × 10-10) were used as genetic instrumental variables (IV). Wald ratio and inverse variance weighted methods were used in MR main analysis. A series of sensitivity analyses were performed to explore IV assumption violations.

Findings

Our results provide evidence that maternal circulating glutamine (59 g offspring birthweight increase per standard deviation increase in maternal amino acid level, 95% CI: 7, 110) and serine (27 g, 95% CI: 9, 46) raise, while leucine (-59 g, 95% CI: -106, -11) and phenylalanine (-25 g, 95% CI: -47, -4) lower offspring birthweight. These findings are supported by sensitivity analyses.

Interpretation

Our findings strengthen evidence for key roles of maternal circulating amino acids during pregnancy in healthy fetal growth.

Funding

A full list of funding bodies that contributed to this study can be found under Acknowledgments.",,doi:https://doi.org/10.1016/j.ebiom.2023.104441; doi:https://doi.org/10.1016/j.ebiom.2023.104441; html:https://europepmc.org/articles/PMC9879767; pdf:https://europepmc.org/articles/PMC9879767?pdf=render 31204027,https://doi.org/10.1016/j.injury.2019.06.012,"Comparing the outcomes of isolated, serious traumatic brain injury in older adults managed at major trauma centres and neurosurgical services: A registry-based cohort study.","Dunn MS, Beck B, Simpson PM, Cameron PA, Kennedy M, Maiden M, Judson R, Gabbe BJ.",,Injury,2019,2019-06-10,N,Traumatic brain injury; Functional Outcome; Older Adult; Tbi; Trauma Systems,,,"

Background

The incidence of older adult traumatic brain injury (TBI) is increasing in both high and middle to low-income countries. It is unknown whether older adults with isolated, serious TBI can be safely managed outside of major trauma centres. This registry based cohort study aimed to compare mortality and functional outcomes of older adults with isolated, serious TBI who were managed at specialised Major Trauma Services (MTS) and Metropolitan Neurosurgical Services (MNS).

Method

Older adults (65 years and over) who sustained an isolated, serious TBI following a low fall (from standing or ≤ 1 m) were extracted from the Victorian State Trauma Registry from 2007 to 2016. Multivariable models were fitted to assess the association between hospital designation (MTS vs. MNS) and the two outcomes of interest: in-hospital mortality and functional outcome, adjusting for potential confounders. Functional outcomes were measured using the Glasgow Outcome Scale Extended at six months post-injury.

Results

From 2007-2016, there were 1904 older adults who sustained an isolated, serious TBI from a low fall who received definitive care at an MTS (n = 1124) or an MNS (n = 780). After adjusting for confounders, there was no mortality benefit for patients managed at an MTS over an MNS (OR = 0.84; 95% CI: 0.65, 1.08; P = 0.17) or improvement in functional outcome six months post-injury (OR = 1.13; 95% CI: 0.94, 1.36; P = 0.21).

Conclusion

For older adults with isolated, serious TBI following a low fall, there was no difference in mortality or functional outcome based on definitive management at an MTS or an MNS. This confirms that MNS without the added designation of a major trauma centre are a suitable destination for the management of isolated, serious TBI in older adults.",,doi:https://doi.org/10.1016/j.injury.2019.06.012 +36696816,https://doi.org/10.1016/j.ebiom.2023.104441,Causal effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation study.,"Zhao J, Stewart ID, Baird D, Mason D, Wright J, Zheng J, Gaunt TR, Evans DM, Freathy RM, Langenberg C, Warrington NM, Lawlor DA, Borges MC, MR-PREG Consortium.",,EBioMedicine,2023,2023-01-23,Y,Amino acids; Gwas; Birthweight; Causal Effect; Mendelian Randomisation,,,"

Background

Amino acids are key to protein synthesis, energy metabolism, cell signaling and gene expression; however, the contribution of specific maternal amino acids to fetal growth is unclear.

Methods

We explored the effect of maternal circulating amino acids on fetal growth, proxied by birthweight, using two-sample Mendelian randomisation (MR) and summary data from a genome-wide association study (GWAS) of serum amino acids levels (sample 1, n = 86,507) and a maternal GWAS of offspring birthweight in UK Biobank and Early Growth Genetics Consortium, adjusting for fetal genotype effects (sample 2, n = 406,063 with maternal and/or fetal genotype effect estimates). A total of 106 independent single nucleotide polymorphisms robustly associated with 19 amino acids (p < 4.9 × 10-10) were used as genetic instrumental variables (IV). Wald ratio and inverse variance weighted methods were used in MR main analysis. A series of sensitivity analyses were performed to explore IV assumption violations.

Findings

Our results provide evidence that maternal circulating glutamine (59 g offspring birthweight increase per standard deviation increase in maternal amino acid level, 95% CI: 7, 110) and serine (27 g, 95% CI: 9, 46) raise, while leucine (-59 g, 95% CI: -106, -11) and phenylalanine (-25 g, 95% CI: -47, -4) lower offspring birthweight. These findings are supported by sensitivity analyses.

Interpretation

Our findings strengthen evidence for key roles of maternal circulating amino acids during pregnancy in healthy fetal growth.

Funding

A full list of funding bodies that contributed to this study can be found under Acknowledgments.",,doi:https://doi.org/10.1016/j.ebiom.2023.104441; doi:https://doi.org/10.1016/j.ebiom.2023.104441; html:https://europepmc.org/articles/PMC9879767; pdf:https://europepmc.org/articles/PMC9879767?pdf=render +32327693,https://doi.org/10.1038/s42003-020-0921-5,Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis.,"Oskarsson GR, Oddsson A, Magnusson MK, Kristjansson RP, Halldorsson GH, Ferkingstad E, Zink F, Helgadottir A, Ivarsdottir EV, Arnadottir GA, Jensson BO, Katrinardottir H, Sveinbjornsson G, Kristinsdottir AM, Lee AL, Saemundsdottir J, Stefansdottir L, Sigurdsson JK, Davidsson OB, Benonisdottir S, Jonasdottir A, Jonasdottir A, Jonsson S, Gudmundsson RL, Asselbergs FW, Tragante V, Gunnarsson B, Masson G, Thorleifsson G, Rafnar T, Holm H, Olafsson I, Onundarson PT, Gudbjartsson DF, Norddahl GL, Thorsteinsdottir U, Sulem P, Stefansson K.",,Communications biology,2020,2020-04-23,Y,,,,"Hemoglobin is the essential oxygen-carrying molecule in humans and is regulated by cellular iron and oxygen sensing mechanisms. To search for novel variants associated with hemoglobin concentration, we performed genome-wide association studies of hemoglobin concentration using a combined set of 684,122 individuals from Iceland and the UK. Notably, we found seven novel variants, six rare coding and one common, at the ACO1 locus associating with either decreased or increased hemoglobin concentration. Of these variants, the missense Cys506Ser and the stop-gained Lys334Ter mutations are specific to eight and ten generation pedigrees, respectively, and have the two largest effects in the study (EffectCys506Ser = -1.61 SD, CI95 = [-1.98, -1.35]; EffectLys334Ter = 0.63 SD, CI95 = [0.36, 0.91]). We also find Cys506Ser to associate with increased risk of persistent anemia (OR = 17.1, P = 2 × 10-14). The strong bidirectional effects seen in this study implicate ACO1, a known iron sensing molecule, as a major homeostatic regulator of hemoglobin concentration.",,pdf:https://www.nature.com/articles/s42003-020-0921-5.pdf; doi:https://doi.org/10.1038/s42003-020-0921-5; html:https://europepmc.org/articles/PMC7181819; pdf:https://europepmc.org/articles/PMC7181819?pdf=render 36541441,https://doi.org/10.1002/hbm.26182,"Predicting sex, age, general cognition and mental health with machine learning on brain structural connectomes.","Yeung HW, Stolicyn A, Buchanan CR, Tucker-Drob EM, Bastin ME, Luz S, McIntosh AM, Whalley HC, Cox SR, Smith K.",,Human brain mapping,2023,2022-12-21,Y,Cognition; Diffusion Tensor Imaging; General Psychopathology; Deep Learning; Structural Connectomes,,,"There is an increasing expectation that advanced, computationally expensive machine learning (ML) techniques, when applied to large population-wide neuroimaging datasets, will help to uncover key differences in the human brain in health and disease. We take a comprehensive approach to explore how multiple aspects of brain structural connectivity can predict sex, age, general cognitive function and general psychopathology, testing different ML algorithms from deep learning (DL) model (BrainNetCNN) to classical ML methods. We modelled N = 8183 structural connectomes from UK Biobank using six different structural network weightings obtained from diffusion MRI. Streamline count generally provided the highest prediction accuracies in all prediction tasks. DL did not improve on prediction accuracies from simpler linear models. Further, high correlations between gradient attribution coefficients from DL and model coefficients from linear models suggested the models ranked the importance of features in similar ways, which indirectly suggested the similarity in models' strategies for making predictive decision to some extent. This highlights that model complexity is unlikely to improve detection of associations between structural connectomes and complex phenotypes with the current sample size.",,doi:https://doi.org/10.1002/hbm.26182; doi:https://doi.org/10.1002/hbm.26182; html:https://europepmc.org/articles/PMC9980898; pdf:https://europepmc.org/articles/PMC9980898?pdf=render 33541353,https://doi.org/10.1186/s12916-020-01872-8,The impact of non-pharmaceutical interventions on SARS-CoV-2 transmission across 130 countries and territories.,"Liu Y, Morgenstern C, Kelly J, Lowe R, CMMID COVID-19 Working Group, Jit M.",,BMC medicine,2021,2021-02-05,Y,Quantitative; Pandemic; Health Impact Assessment; Public Health Intervention; Longitudinal Analysis; Policy Evaluation; Non-pharmaceutical Interventions; Covid-19; Sars-cov-2,,,"

Background

Non-pharmaceutical interventions (NPIs) are used to reduce transmission of SARS coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). However, empirical evidence of the effectiveness of specific NPIs has been inconsistent. We assessed the effectiveness of NPIs around internal containment and closure, international travel restrictions, economic measures, and health system actions on SARS-CoV-2 transmission in 130 countries and territories.

Methods

We used panel (longitudinal) regression to estimate the effectiveness of 13 categories of NPIs in reducing SARS-CoV-2 transmission using data from January to June 2020. First, we examined the temporal association between NPIs using hierarchical cluster analyses. We then regressed the time-varying reproduction number (Rt) of COVID-19 against different NPIs. We examined different model specifications to account for the temporal lag between NPIs and changes in Rt, levels of NPI intensity, time-varying changes in NPI effect, and variable selection criteria. Results were interpreted taking into account both the range of model specifications and temporal clustering of NPIs.

Results

There was strong evidence for an association between two NPIs (school closure, internal movement restrictions) and reduced Rt. Another three NPIs (workplace closure, income support, and debt/contract relief) had strong evidence of effectiveness when ignoring their level of intensity, while two NPIs (public events cancellation, restriction on gatherings) had strong evidence of their effectiveness only when evaluating their implementation at maximum capacity (e.g. restrictions on 1000+ people gathering were not effective, restrictions on < 10 people gathering were). Evidence about the effectiveness of the remaining NPIs (stay-at-home requirements, public information campaigns, public transport closure, international travel controls, testing, contact tracing) was inconsistent and inconclusive. We found temporal clustering between many of the NPIs. Effect sizes varied depending on whether or not we included data after peak NPI intensity.

Conclusion

Understanding the impact that specific NPIs have had on SARS-CoV-2 transmission is complicated by temporal clustering, time-dependent variation in effects, and differences in NPI intensity. However, the effectiveness of school closure and internal movement restrictions appears robust across different model specifications, with some evidence that other NPIs may also be effective under particular conditions. This provides empirical evidence for the potential effectiveness of many, although not all, actions policy-makers are taking to respond to the COVID-19 pandemic.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01872-8; doi:https://doi.org/10.1186/s12916-020-01872-8; html:https://europepmc.org/articles/PMC7861967; pdf:https://europepmc.org/articles/PMC7861967?pdf=render 32891970,https://doi.org/10.1016/j.chiabu.2020.104689,Exploring placement stability for children in out-of-home care in England: a sequence analysis of longitudinal administrative data.,"Mc Grath-Lone L, Harron K, Dearden L, Gilbert R.",,Child abuse & neglect,2020,2020-09-03,N,Sequence analysis; Administrative Data; Longitudinal Care Histories,,,"

Background

To monitor stability of care, the proportion of children in England who have experienced three or more placements in the preceding 12-month period is published in government statistics. However, these annual snapshots cannot capture the complexity and heterogeneity of children's longitudinal care histories.

Objective

To describe the stability of care histories from birth to age 18 for children in England using a national administrative social care dataset, the Children Looked After return (CLA).

Participants and setting

We analyzed CLA data for a large, representative sample of children born between 1992 and 1994 (N = 16,000).

Methods

Using sequence analysis methods, we identified distinct patterns of stability, based on the number, duration, and timing of care placements throughout childhood.

Results

Although care histories were varied, six distinct patterns of stability were evident including; adolescent 1st entries (17.6%), long-term complex care (13.1%) and early intervention (6.9%). Overall, most children (58.4%) had a care history that we classified as shorter term care with an average of 276 days and 2.48 placements in care throughout childhood. Few children (4.0%) had a care history that could be described as long-term stable care.

Conclusions

Longitudinal analyses of administrative data can refine our understanding of how out-of-home care is used as a social care intervention. Sequence analysis is a particularly useful tool for exploring heterogeneous and complex care histories. Considering out-of-home care histories from a life course perspective over the entire childhood period could enable service providers to better understand and address the needs of looked after children.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613165; doi:https://doi.org/10.1016/j.chiabu.2020.104689; html:https://europepmc.org/articles/PMC7613165; pdf:https://europepmc.org/articles/PMC7613165?pdf=render; doi:https://doi.org/10.1016/j.chiabu.2020.104689 @@ -2137,19 +2137,19 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 33628949,https://doi.org/10.12688/wellcomeopenres.16020.2,The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Questionnaire data capture April-May 2020.,"Northstone K, Howarth S, Smith D, Bowring C, Wells N, Timpson NJ.",,Wellcome open research,2020,2020-11-20,Y,Coronavirus; Mental health; Alspac; Birth Cohort Study; Online Questionnaire; Children Of The 90S; Covid-19,,,"The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992. The resource provides an informative and efficient setting for collecting data on the current coronavirus 2019 (COVID-19) pandemic. In early March 2020, a questionnaire was developed in collaboration with other longitudinal population studies to ensure cross-cohort comparability. It targeted retrospective and current COVID-19 infection information (exposure assessment, symptom tracking and reported clinical outcomes) and the impact of both disease and mitigating measures implemented to manage the COVID-19 crisis more broadly. Data were collected on symptoms of COVID-19 and seasonal flu, travel prior to the pandemic, mental health and social, behavioural and lifestyle factors. The online questionnaire was deployed across parent (G0) and offspring (G1) generations between 9 th April and 15 th May 2020. 6807 participants completed the questionnaire (2706 original mothers, 1014 original fathers/partners, 2973 offspring (mean age ~28 years) and 114 offspring partners). Eight (0.01%) participants (4 G0 and 4 G1) reported a positive test for COVID-19, 77 (1.13%; 28 G0 and 49 G1) reported that they had been told by a doctor they likely had COVID-19 and 865 (12.7%; 426 G0 and 439 G1) suspected that they have had COVID-19.  Using algorithmically defined cases, we estimate that the predicted proportion of COVID-19 cases ranged from 1.03% - 4.19% depending on timing during the period of reporting (October 2019-March 2020). Data from this first questionnaire will be complemented with at least two more follow-up questionnaires, linkage to health records and results of biological testing as they become available. Data has been released as: 1) a standard dataset containing all participant responses with key sociodemographic factors and 2) as a composite release coordinating data from the existing resource, thus enabling bespoke research across all areas supported by the study.",,doi:https://doi.org/10.12688/wellcomeopenres.16020.2; html:https://europepmc.org/articles/PMC7883314; pdf:https://europepmc.org/articles/PMC7883314?pdf=render 36084617,https://doi.org/10.1016/j.ebiom.2022.104243,Machine learning integration of multimodal data identifies key features of blood pressure regulation.,"Louca P, Tran TQB, Toit CD, Christofidou P, Spector TD, Mangino M, Suhre K, Padmanabhan S, Menni C.",,EBioMedicine,2022,2022-09-06,Y,Diet; Blood pressure; Genomics; Metabolomics; Machine Learning,,,"

Background

Association studies have identified several biomarkers for blood pressure and hypertension, but a thorough understanding of their mutual dependencies is lacking. By integrating two different high-throughput datasets, biochemical and dietary data, we aim to understand the multifactorial contributors of blood pressure (BP).

Methods

We included 4,863 participants from TwinsUK with concurrent BP, metabolomics, genomics, biochemical measures, and dietary data. We used 5-fold cross-validation with the machine learning XGBoost algorithm to identify features of importance in context of one another in TwinsUK (80% training, 20% test). The features tested in TwinsUK were then probed using the same algorithm in an independent dataset of 2,807 individuals from the Qatari Biobank (QBB).

Findings

Our model explained 39·2% [4·5%, MAE:11·32 mmHg (95%CI, +/- 0·65)] of the variance in systolic BP (SBP) in TwinsUK. Of the top 50 features, the most influential non-demographic variables were dihomo-linolenate, cis-4-decenoyl carnitine, lactate, chloride, urate, and creatinine along with dietary intakes of total, trans and saturated fat. We also highlight the incremental value of each included dimension. Furthermore, we replicated our model in the QBB [SBP variance explained = 45·2% (13·39%)] cohort and 30 of the top 50 features overlapped between cohorts.

Interpretation

We show that an integrated analysis of omics, biochemical and dietary data improves our understanding of their in-between relationships and expands the range of potential biomarkers for blood pressure. Our results point to potentially key biological pathways to be prioritised for mechanistic studies.

Funding

Chronic Disease Research Foundation, Medical Research Council, Wellcome Trust, Qatar Foundation.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9463529; doi:https://doi.org/10.1016/j.ebiom.2022.104243; html:https://europepmc.org/articles/PMC9463529; pdf:https://europepmc.org/articles/PMC9463529?pdf=render 34740937,https://doi.org/10.1136/bmjopen-2021-056601,Analysis of mental and physical disorders associated with COVID-19 in online health forums: a natural language processing study.,"Patel R, Smeraldi F, Abdollahyan M, Irving J, Bessant C.",,BMJ open,2021,2021-11-05,Y,information technology; Health Informatics; Covid-19,,,"

Objectives

Online health forums provide rich and untapped real-time data on population health. Through novel data extraction and natural language processing (NLP) techniques, we characterise the evolution of mental and physical health concerns relating to the COVID-19 pandemic among online health forum users.

Setting and design

We obtained data from three leading online health forums: HealthBoards, Inspire and HealthUnlocked, from the period 1 January 2020 to 31 May 2020. Using NLP, we analysed the content of posts related to COVID-19.

Primary outcome measures

(1) Proportion of forum posts containing COVID-19 keywords; (2) proportion of forum users making their very first post about COVID-19; (3) proportion of COVID-19-related posts containing content related to physical and mental health comorbidities.

Results

Data from 739 434 posts created by 53 134 unique users were analysed. A total of 35 581 posts (4.8%) contained a COVID-19 keyword. Posts discussing COVID-19 and related comorbid disorders spiked in early March to mid-March around the time of global implementation of lockdowns prompting a large number of users to post on online health forums for the first time. Over a quarter of COVID-19-related thread titles mentioned a physical or mental health comorbidity.

Conclusions

We demonstrate that it is feasible to characterise the content of online health forum user posts regarding COVID-19 and measure changes over time. The pandemic and corresponding public response has had a significant impact on posters' queries regarding mental health. Social media data sources such as online health forums can be harnessed to strengthen population-level mental health surveillance.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/11/e056601.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-056601; html:https://europepmc.org/articles/PMC8573296; pdf:https://europepmc.org/articles/PMC8573296?pdf=render -38296292,https://doi.org/10.1136/bmjopen-2023-078135,"Risk factor associations for severe COVID-19, influenza and pneumonia in people with diabetes to inform future pandemic preparations: UK population-based cohort study.","Hopkins R, Young KG, Thomas NJ, Godwin J, Raja D, Mateen BA, Challen RJ, Vollmer SJ, Shields BM, McGovern AP, Dennis JM.",,BMJ open,2024,2024-01-31,Y,risk factors; Electronic Health Records; Diabetes & Endocrinology; Covid-19,,,"

Objective

This study aimed to compare clinical and sociodemographic risk factors for severe COVID-19, influenza and pneumonia, in people with diabetes.

Design

Population-based cohort study.

Setting

UK primary care records (Clinical Practice Research Datalink) linked to mortality and hospital records.

Participants

Individuals with type 1 and type 2 diabetes (COVID-19 cohort: n=43 033 type 1 diabetes and n=584 854 type 2 diabetes, influenza and pneumonia cohort: n=42 488 type 1 diabetes and n=585 289 type 2 diabetes).

Primary and secondary outcome measures

COVID-19 hospitalisation from 1 February 2020 to 31 October 2020 (pre-COVID-19 vaccination roll-out), and influenza and pneumonia hospitalisation from 1 September 2016 to 31 May 2019 (pre-COVID-19 pandemic). Secondary outcomes were COVID-19 and pneumonia mortality. Associations between clinical and sociodemographic risk factors and each outcome were assessed using multivariable Cox proportional hazards models. In people with type 2 diabetes, we explored modifying effects of glycated haemoglobin (HbA1c) and body mass index (BMI) by age, sex and ethnicity.

Results

In type 2 diabetes, poor glycaemic control and severe obesity were consistently associated with increased risk of hospitalisation for COVID-19, influenza and pneumonia. The highest HbA1c and BMI-associated relative risks were observed in people aged under 70 years. Sociodemographic-associated risk differed markedly by respiratory infection, particularly for ethnicity. Compared with people of white ethnicity, black and south Asian groups had a greater risk of COVID-19 hospitalisation, but a lesser risk of pneumonia hospitalisation. Risk factor associations for type 1 diabetes and for type 2 diabetes mortality were broadly consistent with the primary analysis.

Conclusions

Clinical risk factors of high HbA1c and severe obesity are consistently associated with severe outcomes from COVID-19, influenza and pneumonia, especially in younger people. In contrast, associations with sociodemographic risk factors differed by type of respiratory infection. This emphasises that risk stratification should be specific to individual respiratory infections.",,doi:https://doi.org/10.1136/bmjopen-2023-078135; html:https://europepmc.org/articles/PMC10831438; pdf:https://europepmc.org/articles/PMC10831438?pdf=render 34732839,https://doi.org/10.1038/s41379-021-00953-0,Stratification of chemotherapy-treated stage III colorectal cancer patients using multiplexed imaging and single-cell analysis of T-cell populations.,"Stachtea X, Loughrey MB, Salvucci M, Lindner AU, Cho S, McDonough E, Sood A, Graf J, Santamaria-Pang A, Corwin A, Laurent-Puig P, Dasgupta S, Shia J, Owens JR, Abate S, Van Schaeybroeck S, Lawler M, Prehn JHM, Ginty F, Longley DB.",,"Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc",2022,2021-11-03,Y,,,,"Colorectal cancer (CRC) has one of the highest cancer incidences and mortality rates. In stage III, postoperative chemotherapy benefits <20% of patients, while more than 50% will develop distant metastases. Biomarkers for identification of patients at increased risk of disease recurrence following adjuvant chemotherapy are currently lacking. In this study, we assessed immune signatures in the tumor and tumor microenvironment (TME) using an in situ multiplexed immunofluorescence imaging and single-cell analysis technology (Cell DIVETM) and evaluated their correlations with patient outcomes. Tissue microarrays (TMAs) with up to three 1 mm diameter cores per patient were prepared from 117 stage III CRC patients treated with adjuvant fluoropyrimidine/oxaliplatin (FOLFOX) chemotherapy. Single sections underwent multiplexed immunofluorescence staining for immune cell markers (CD45, CD3, CD4, CD8, FOXP3, PD1) and tumor/cell segmentation markers (DAPI, pan-cytokeratin, AE1, NaKATPase, and S6). We used annotations and a probabilistic classification algorithm to build statistical models of immune cell types. Images were also qualitatively assessed independently by a Pathologist as 'high', 'moderate' or 'low', for stromal and total immune cell content. Excellent agreement was found between manual assessment and total automated scores (p < 0.0001). Moreover, compared to single markers, a multi-marker classification of regulatory T cells (Tregs: CD3+/CD4+FOXP3+/PD1-) was significantly associated with disease-free survival (DFS) and overall survival (OS) (p = 0.049 and 0.032) of FOLFOX-treated patients. Our results also showed that PD1- Tregs rather than PD1+ Tregs were associated with improved survival. These findings were supported by results from an independent FOLFOX-treated cohort of 191 stage III CRC patients, where higher PD1- Tregs were associated with an increase overall survival (p = 0.015) for CD3+/CD4+/FOXP3+/PD1-. Overall, compared to single markers, multi-marker classification provided more accurate quantitation of immune cell types with stronger correlations with outcomes.",,pdf:https://www.nature.com/articles/s41379-021-00953-0.pdf; doi:https://doi.org/10.1038/s41379-021-00953-0; html:https://europepmc.org/articles/PMC8964416; pdf:https://europepmc.org/articles/PMC8964416?pdf=render +38296292,https://doi.org/10.1136/bmjopen-2023-078135,"Risk factor associations for severe COVID-19, influenza and pneumonia in people with diabetes to inform future pandemic preparations: UK population-based cohort study.","Hopkins R, Young KG, Thomas NJ, Godwin J, Raja D, Mateen BA, Challen RJ, Vollmer SJ, Shields BM, McGovern AP, Dennis JM.",,BMJ open,2024,2024-01-31,Y,risk factors; Electronic Health Records; Diabetes & Endocrinology; Covid-19,,,"

Objective

This study aimed to compare clinical and sociodemographic risk factors for severe COVID-19, influenza and pneumonia, in people with diabetes.

Design

Population-based cohort study.

Setting

UK primary care records (Clinical Practice Research Datalink) linked to mortality and hospital records.

Participants

Individuals with type 1 and type 2 diabetes (COVID-19 cohort: n=43 033 type 1 diabetes and n=584 854 type 2 diabetes, influenza and pneumonia cohort: n=42 488 type 1 diabetes and n=585 289 type 2 diabetes).

Primary and secondary outcome measures

COVID-19 hospitalisation from 1 February 2020 to 31 October 2020 (pre-COVID-19 vaccination roll-out), and influenza and pneumonia hospitalisation from 1 September 2016 to 31 May 2019 (pre-COVID-19 pandemic). Secondary outcomes were COVID-19 and pneumonia mortality. Associations between clinical and sociodemographic risk factors and each outcome were assessed using multivariable Cox proportional hazards models. In people with type 2 diabetes, we explored modifying effects of glycated haemoglobin (HbA1c) and body mass index (BMI) by age, sex and ethnicity.

Results

In type 2 diabetes, poor glycaemic control and severe obesity were consistently associated with increased risk of hospitalisation for COVID-19, influenza and pneumonia. The highest HbA1c and BMI-associated relative risks were observed in people aged under 70 years. Sociodemographic-associated risk differed markedly by respiratory infection, particularly for ethnicity. Compared with people of white ethnicity, black and south Asian groups had a greater risk of COVID-19 hospitalisation, but a lesser risk of pneumonia hospitalisation. Risk factor associations for type 1 diabetes and for type 2 diabetes mortality were broadly consistent with the primary analysis.

Conclusions

Clinical risk factors of high HbA1c and severe obesity are consistently associated with severe outcomes from COVID-19, influenza and pneumonia, especially in younger people. In contrast, associations with sociodemographic risk factors differed by type of respiratory infection. This emphasises that risk stratification should be specific to individual respiratory infections.",,doi:https://doi.org/10.1136/bmjopen-2023-078135; html:https://europepmc.org/articles/PMC10831438; pdf:https://europepmc.org/articles/PMC10831438?pdf=render 35211795,https://doi.org/10.1007/s00467-022-05440-5,Exploring the relevance of NUP93 variants in steroid-resistant nephrotic syndrome using next generation sequencing and a fly kidney model.,"Bierzynska A, Bull K, Miellet S, Dean P, Neal C, Colby E, McCarthy HJ, Hegde S, Sinha MD, Bugarin Diz C, Stirrups K, Megy K, Mapeta R, Penkett C, Marsh S, Forrester N, Afzal M, Stark H, BioResource N, Williams M, Welsh GI, Koziell AB, Hartley PS, Saleem MA.",,"Pediatric nephrology (Berlin, Germany)",2022,2022-02-24,Y,Podocyte; Fsgs; Srns; Nephrocyte; Nup93,,,"

Background

Variants in genes encoding nuclear pore complex (NPC) proteins are a newly identified cause of paediatric steroid-resistant nephrotic syndrome (SRNS). Recent reports describing NUP93 variants suggest these could be a significant cause of paediatric onset SRNS. We report NUP93 cases in the UK and demonstrate in vivo functional effects of Nup93 depletion in a fly (Drosophila melanogaster) nephrocyte model.

Methods

Three hundred thirty-seven paediatric SRNS patients from the National cohort of patients with Nephrotic Syndrome (NephroS) were whole exome and/or whole genome sequenced. Patients were screened for over 70 genes known to be associated with Nephrotic Syndrome (NS). D. melanogaster Nup93 knockdown was achieved by RNA interference using nephrocyte-restricted drivers.

Results

Six novel homozygous and compound heterozygous NUP93 variants were detected in 3 sporadic and 2 familial paediatric onset SRNS characterised histologically by focal segmental glomerulosclerosis (FSGS) and progressing to kidney failure by 12 months from clinical diagnosis. Silencing of the two orthologs of human NUP93 expressed in D. melanogaster, Nup93-1, and Nup93-2 resulted in significant signal reduction of up to 82% in adult pericardial nephrocytes with concomitant disruption of NPC protein expression. Additionally, nephrocyte morphology was highly abnormal in Nup93-1 and Nup93-2 silenced flies surviving to adulthood.

Conclusion

We expand the spectrum of NUP93 variants detected in paediatric onset SRNS and demonstrate its incidence within a national cohort. Silencing of either D. melanogaster Nup93 ortholog caused a severe nephrocyte phenotype, signaling an important role for the nucleoporin complex in podocyte biology. A higher resolution version of the Graphical abstract is available as Supplementary information.",,pdf:https://link.springer.com/content/pdf/10.1007/s00467-022-05440-5.pdf; doi:https://doi.org/10.1007/s00467-022-05440-5; html:https://europepmc.org/articles/PMC9489583; pdf:https://europepmc.org/articles/PMC9489583?pdf=render 31021418,https://doi.org/10.1111/bjd.18046,'It's like the bad guy in a movie who just doesn't die': a qualitative exploration of young people's adaptation to eczema and implications for self-care.,"Ghio D, Muller I, Greenwell K, Roberts A, McNiven A, Langan SM, Santer M.",,The British journal of dermatology,2020,2019-07-28,Y,,,,"

Background

Eczema is a common childhood inflammatory skin condition, affecting more than one in five children. A popular perception is that children 'outgrow eczema', although epidemiological studies have shown that, for many, eczema follows a lifelong episodic course.

Objectives

To explore the perceptions of young people about the nature of their eczema and how these perceptions relate to their self-care and adapting to living with eczema.

Methods

This is a secondary inductive thematic analysis of interviews conducted for Healthtalk.org. In total 23 interviews with young people with eczema were included. Of the 23 participants, 17 were female and six male, ranging from 17 to 25 years old.

Results

Participants generally experienced eczema as an episodic long-term condition and reported a mismatch between information received about eczema and their experiences. The experience of eczema as long term and episodic had implications for self-care, challenging the process of identifying triggers of eczema flare-ups and evaluating the success of treatment regimens. Participants' experiences of eczema over time also had implications for adaptation and finding a balance between accepting eczema as long term and hoping it would go away. This linked to a gradual shift in treatment expectations from 'cure' to 'control' of eczema.

Conclusions

For young people who continue to experience eczema beyond childhood, a greater focus on self-care for a long-term condition may be helpful. Greater awareness of the impact of early messages around 'growing out of' eczema and provision of high-quality information may help patients to manage expectations and support adaptation to treatment regimens. What's already known about this topic? There is a common perception that people 'grow out of' eczema, but for many people eczema follows a lifelong episodic course. Qualitative work has shown that parents can find that being told their child will grow out of eczema is dismissive, and that they have difficulty with messages about 'control not cure' of eczema. It is unclear how young people perceive their eczema and the implications of this perception for their adaptation and self-care. What does this study add? The message that many people 'grow out of' eczema has a potentially detrimental effect for young people where the condition persists. This has implications for young people's perceptions of their eczema, their learning to self-care and how they adapt to living with eczema and eczema treatments. What are the clinical implications of this work? Clinicians need to promote awareness among young people that eczema is a long-term episodic condition in order to engage them with effective self-care. Young people transitioning to self-care need evidence-based information that is specific and relatable to them.", ,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.18046; doi:https://doi.org/10.1111/bjd.18046; html:https://europepmc.org/articles/PMC6972719; pdf:https://europepmc.org/articles/PMC6972719?pdf=render 37221222,https://doi.org/10.1038/s41397-023-00307-w,SLCO1B1*5 is protective against non-senile cataracts in cohort prescribed statins: analysis in a British-South Asian cohort.,"Magavern EF, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.",,The pharmacogenomics journal,2023,2023-05-23,Y,,,,"

Background

Reported association between statin use and cataract risk is controversial. The SLCO1B1 gene encodes a transport protein responsible for statin clearance. The aim of this study was to investigate a possible association between the SLCO1B1*5 reduced function variant and cataract risk in statin users of South Asian ethnicity.

Methods

The Genes & Health cohort consists of British-Bangladeshi and British-Pakistani participants from East London, Manchester and Bradford, UK. SLCO1B1*5 genotype was assessed with the Illumina GSAMD-24v3-0-EA chip. Medication data from primary care health record linkage was used to compare those who had regularly used statins compared to those who had not. Multivariable logistic regression was used to test for association between statin use and cataracts, adjusting for population characteristics and potential confounders in 36,513 participants. Multivariable logistic regression was used to test association between SLCO1B1*5 heterozygotes or homozygotes and cataracts, in subgroups having been regularly prescribed statins versus not.

Results

Statins were prescribed to 35% (12,704) of participants (average age 41 years old, 45% male). Non-senile cataract was diagnosed in 5% (1686) of participants. An apparent association between statins and non-senile cataract (12% in statin users and 0.8% in non-statin users) was negated by inclusion of confounders. In those prescribed a statin, presence of the SLCO1B1*5 genotype was independently associated with a decreased risk of non-senile cataract (OR 0.7 (CI 0.5-0.9, p 0.007)).

Conclusions

Our findings suggest that there is no independent association between statin use and non-senile cataract risk after adjusting for confounders. Among statin users, the SLCO1B1*5 genotype is associated with a 30% risk reduction of non-senile cataracts. Stratification of on-drug cohorts by validated pharmacogenomic variants is a useful tool to support or repudiate adverse drug events in observational cohorts.",,pdf:https://www.nature.com/articles/s41397-023-00307-w.pdf; doi:https://doi.org/10.1038/s41397-023-00307-w; html:https://europepmc.org/articles/PMC10506906; pdf:https://europepmc.org/articles/PMC10506906?pdf=render -34937765,https://doi.org/10.1136/injuryprev-2021-044309,Predictors of health-related quality of life following injury in childhood and adolescence: a pooled analysis.,"Dipnall JF, Rivara FP, Lyons RA, Ameratunga S, Brussoni M, Lecky FE, Bradley C, Beck B, Lyons J, Schneeberg A, Harrison JE, Gabbe BJ.",,Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention,2022,2021-12-22,N,Public Health; Disability; Longitudinal,,,"

Background

Injury is a leading contributor to the global disease burden in children and places children at risk for adverse and lasting impacts on their health-related quality of life (HRQoL) and development. This study aimed to identify key predictors of HRQoL following injury in childhood and adolescence.

Methods

Data from 2259 injury survivors (<18 years when injured) were pooled from four longitudinal cohort studies (Australia, Canada, UK, USA) from the paediatric Validating Injury Burden Estimates Study (VIBES-Junior). Outcomes were the Paediatric Quality of Life Inventory (PedsQL) total, physical, psychosocial functioning scores at 1, 3-4, 6, 12, 24 months postinjury.

Results

Mean PedsQL total score increased with higher socioeconomic status and decreased with increasing age. It was lower for transport-related incidents, ≥1 comorbidities, intentional injuries, spinal cord injury, vertebral column fracture, moderate/severe traumatic brain injury and fracture of patella/tibia/fibula/ankle. Mean PedsQL physical score was lower for females, fracture of femur, fracture of pelvis and burns. Mean PedsQL psychosocial score was lower for asphyxiation/non-fatal submersion and muscle/tendon/dislocation injuries.

Conclusions

Postinjury HRQoL was associated with survivors' socioeconomic status, intent, mechanism of injury and comorbidity status. Patterns of physical and psychosocial functioning postinjury differed according to sex and nature of injury sustained. The findings improve understanding of the long-term individual and societal impacts of injury in the early part of life and guide the prioritisation of prevention efforts, inform health and social service planning to help reduce injury burden, and help guide future Global Burden of Disease estimates.",,doi:https://doi.org/10.1136/injuryprev-2021-044309 31950891,https://doi.org/10.1192/bjo.2019.96,Predicting high-cost care in a mental health setting.,"Colling C, Khondoker M, Patel R, Fok M, Harland R, Broadbent M, McCrone P, Stewart R.",,BJPsych open,2020,2020-01-17,Y,Prediction; Natural Language Processing; Mental Health Service; Digital Health Records,,,"

Background

The density of information in digital health records offers new potential opportunities for automated prediction of cost-relevant outcomes.

Aims

We investigated the extent to which routinely recorded data held in the electronic health record (EHR) predict priority service outcomes and whether natural language processing tools enhance the predictions. We evaluated three high priority outcomes: in-patient duration, readmission following in-patient care and high service cost after first presentation.

Method

We used data obtained from a clinical database derived from the EHR of a large mental healthcare provider within the UK. We combined structured data with text-derived data relating to diagnosis statements, medication and psychiatric symptomatology. Predictors of the three different clinical outcomes were modelled using logistic regression with performance evaluated against a validation set to derive areas under receiver operating characteristic curves.

Results

In validation samples, the full models (using all available data) achieved areas under receiver operating characteristic curves between 0.59 and 0.85 (in-patient duration 0.63, readmission 0.59, high service use 0.85). Adding natural language processing-derived data to the models increased the variance explained across all clinical scenarios (observed increase in r2 = 12-46%).

Conclusions

EHR data offer the potential to improve routine clinical predictions by utilising previously inaccessible data. Of our scenarios, prediction of high service use after initial presentation achieved the highest performance.","This study uses data from a mental healthcare provider to predict 3 things: 1) extended duration of stay in a hospital, 2) the likelihood of needing to be admitted to hospital again after discharge, and 3) likehood of needing 'high intesity service' (high cost services). The authors developed a natural language processing model (a computer system than aims to interpret text and draw out useful information) to review the text, diagnoses, medications and the patient symptoms to work out which patients would fall within those 3 categories. They conclude that their model could be used to improve services through predicting users who will require the most intense and costly care.",pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/6EF9FC74DC5A744C9D841DD649992ABE/S2056472419000966a.pdf/div-class-title-predicting-high-cost-care-in-a-mental-health-setting-div.pdf; doi:https://doi.org/10.1192/bjo.2019.96; html:https://europepmc.org/articles/PMC7001466; pdf:https://europepmc.org/articles/PMC7001466?pdf=render -34441449,https://doi.org/10.3390/diagnostics11081516,Stability of OCT and OCTA in the Intensive Therapy Unit Setting.,"Courtie EF, Kale AU, Hui BTK, Liu X, Capewell NI, Bishop JRB, Whitehouse T, Veenith T, Logan A, Denniston AK, Blanch RJ.",,"Diagnostics (Basel, Switzerland)",2021,2021-08-23,Y,Stability; Critical Care; Optical Coherence Tomography Angiography,,,"To assess the stability of retinal structure and blood flow measures over time and in different clinical settings using portable optical coherence tomography angiography (OCTA) as a potential biomarker of central perfusion in critical illness, 18 oesophagectomy patients completed retinal structure and blood flow measurements by portable OCT and OCTA in the eye clinic and intensive therapy unit (ITU) across three timepoints: (1) pre-operation in a clinic setting; (2) 24-48 h post-operation during ITU admission; and (3) seven days post-operation, if the patient was still admitted. Blood flow and macular structural measures were stable between the examination settings, with no consistent variation between pre- and post-operation scans, while retinal nerve fibre layer thickness increased in the post-operative scans (+2.31 µm, p = 0.001). Foveal avascular zone (FAZ) measurements were the most stable, with an intraclass correlation coefficient of up to 0.92 for right eye FAZ area. Blood flow and structural measures were lower in left eyes than right eyes. Retinal blood flow assessed in patients before and during an ITU stay using portable OCTA showed no systematic differences between the clinical settings. The stability of retinal blood flow measures suggests the potential for portable OCTA to provide clinically useful measures in ITU patients.",,pdf:https://www.mdpi.com/2075-4418/11/8/1516/pdf?version=1629792973; doi:https://doi.org/10.3390/diagnostics11081516; html:https://europepmc.org/articles/PMC8394026; pdf:https://europepmc.org/articles/PMC8394026?pdf=render +34937765,https://doi.org/10.1136/injuryprev-2021-044309,Predictors of health-related quality of life following injury in childhood and adolescence: a pooled analysis.,"Dipnall JF, Rivara FP, Lyons RA, Ameratunga S, Brussoni M, Lecky FE, Bradley C, Beck B, Lyons J, Schneeberg A, Harrison JE, Gabbe BJ.",,Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention,2022,2021-12-22,N,Public Health; Disability; Longitudinal,,,"

Background

Injury is a leading contributor to the global disease burden in children and places children at risk for adverse and lasting impacts on their health-related quality of life (HRQoL) and development. This study aimed to identify key predictors of HRQoL following injury in childhood and adolescence.

Methods

Data from 2259 injury survivors (<18 years when injured) were pooled from four longitudinal cohort studies (Australia, Canada, UK, USA) from the paediatric Validating Injury Burden Estimates Study (VIBES-Junior). Outcomes were the Paediatric Quality of Life Inventory (PedsQL) total, physical, psychosocial functioning scores at 1, 3-4, 6, 12, 24 months postinjury.

Results

Mean PedsQL total score increased with higher socioeconomic status and decreased with increasing age. It was lower for transport-related incidents, ≥1 comorbidities, intentional injuries, spinal cord injury, vertebral column fracture, moderate/severe traumatic brain injury and fracture of patella/tibia/fibula/ankle. Mean PedsQL physical score was lower for females, fracture of femur, fracture of pelvis and burns. Mean PedsQL psychosocial score was lower for asphyxiation/non-fatal submersion and muscle/tendon/dislocation injuries.

Conclusions

Postinjury HRQoL was associated with survivors' socioeconomic status, intent, mechanism of injury and comorbidity status. Patterns of physical and psychosocial functioning postinjury differed according to sex and nature of injury sustained. The findings improve understanding of the long-term individual and societal impacts of injury in the early part of life and guide the prioritisation of prevention efforts, inform health and social service planning to help reduce injury burden, and help guide future Global Burden of Disease estimates.",,doi:https://doi.org/10.1136/injuryprev-2021-044309 34151246,https://doi.org/10.1016/j.cjco.2021.05.020,Cardiovascular and Renal Risk Factors and Complications Associated With COVID-19.,"Touyz RM, Boyd MOE, Guzik T, Padmanabhan S, McCallum L, Delles C, Mark PB, Petrie JR, Rios F, Montezano AC, Sykes R, Berry C.",,CJC open,2021,2021-06-16,Y,,,,"The current COVID-19 pandemic, caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus, represents the largest medical challenge in decades. It has exposed unexpected cardiovascular vulnerabilities at all stages of the disease (pre-infection, acute phase, and subsequent chronic phase). The major cardiometabolic drivers identified as having epidemiologic and mechanistic associations with COVID-19 are abnormal adiposity, dysglycemia, dyslipidemia, and hypertension. Hypertension is of particular interest, because components of the renin-angiotensin system (RAS), which are critically involved in the pathophysiology of hypertension, are also implicated in COVID-19. Specifically, angiotensin-converting enzyme-2 (ACE2), a multifunctional protein of the RAS, which is part of the protective axis of the RAS, is also the receptor through which SARS-CoV-2 enters host cells, causing viral infection. Cardiovascular and cardiometabolic comorbidities not only predispose people to COVID-19, but also are complications of SARS-CoV-2 infection. In addition, increasing evidence indicates that acute kidney injury is common in COVID-19, occurs early and in temporal association with respiratory failure, and is associated with poor prognosis, especially in the presence of cardiovascular risk factors. Here, we discuss cardiovascular and kidney disease in the context of COVID-19 and provide recent advances on putative pathophysiological mechanisms linking cardiovascular disease and COVID-19, focusing on the RAS and ACE2, as well as the immune system and inflammation. We provide up-to-date information on the relationships among hypertension, diabetes, and COVID-19 and emphasize the major cardiovascular diseases associated with COVID-19. We also briefly discuss emerging cardiovascular complications associated with long COVID-19, notably postural tachycardia syndrome (POTS).",,pdf:http://www.cjcopen.ca/article/S2589790X21001554/pdf; doi:https://doi.org/10.1016/j.cjco.2021.05.020; html:https://europepmc.org/articles/PMC8205551; pdf:https://europepmc.org/articles/PMC8205551?pdf=render +34441449,https://doi.org/10.3390/diagnostics11081516,Stability of OCT and OCTA in the Intensive Therapy Unit Setting.,"Courtie EF, Kale AU, Hui BTK, Liu X, Capewell NI, Bishop JRB, Whitehouse T, Veenith T, Logan A, Denniston AK, Blanch RJ.",,"Diagnostics (Basel, Switzerland)",2021,2021-08-23,Y,Stability; Critical Care; Optical Coherence Tomography Angiography,,,"To assess the stability of retinal structure and blood flow measures over time and in different clinical settings using portable optical coherence tomography angiography (OCTA) as a potential biomarker of central perfusion in critical illness, 18 oesophagectomy patients completed retinal structure and blood flow measurements by portable OCT and OCTA in the eye clinic and intensive therapy unit (ITU) across three timepoints: (1) pre-operation in a clinic setting; (2) 24-48 h post-operation during ITU admission; and (3) seven days post-operation, if the patient was still admitted. Blood flow and macular structural measures were stable between the examination settings, with no consistent variation between pre- and post-operation scans, while retinal nerve fibre layer thickness increased in the post-operative scans (+2.31 µm, p = 0.001). Foveal avascular zone (FAZ) measurements were the most stable, with an intraclass correlation coefficient of up to 0.92 for right eye FAZ area. Blood flow and structural measures were lower in left eyes than right eyes. Retinal blood flow assessed in patients before and during an ITU stay using portable OCTA showed no systematic differences between the clinical settings. The stability of retinal blood flow measures suggests the potential for portable OCTA to provide clinically useful measures in ITU patients.",,pdf:https://www.mdpi.com/2075-4418/11/8/1516/pdf?version=1629792973; doi:https://doi.org/10.3390/diagnostics11081516; html:https://europepmc.org/articles/PMC8394026; pdf:https://europepmc.org/articles/PMC8394026?pdf=render 30928767,https://doi.org/10.1016/j.evalprogplan.2019.03.002,Understanding the factors that influence health promotion evaluation: The development and validation of the evaluation practice analysis survey.,"Schwarzman J, Bauman A, Gabbe BJ, Rissel C, Shilton T, Smith BJ.",,Evaluation and program planning,2019,2019-03-22,N,Measurement; Validity; reliability; Health Promotion; Evaluation Capacity Building; Evaluation Practice,,,"The demand for improved quality of health promotion evaluation and greater capacity to undertake evaluation is growing, yet evidence of the challenges and facilitators to evaluation practice within the health promotion field is lacking. A limited number of evaluation capacity measurement instruments have been validated in government or non-government organisations (NGO), however there is no instrument designed for health promotion organisations. This study aimed to develop and validate an Evaluation Practice Analysis Survey (EPAS) to examine evaluation practices in health promotion organisations. Qualitative interviews, existing frameworks and instruments informed the survey development. Health promotion practitioners from government agencies and NGOs completed the survey (n = 169). Principal components analysis was used to determine scale structure and Cronbach's α used to estimate internal reliability. Logistic regression was conducted to assess predictive validity of selected EPAS scale. The final survey instrument included 25 scales (125 items). The EPAS demonstrated good internal reliability (α > 0.7) for 23 scales. Dedicated resources and time for evaluation, leadership, organisational culture and internal support for evaluation showed promising predictive validity. The EPAS can be used to describe elements of evaluation capacity at the individual, organisational and system levels and to guide initiatives to improve evaluation practice in health promotion organisations.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa49960/Download/0049960-14052019134527.pdf; doi:https://doi.org/10.1016/j.evalprogplan.2019.03.002 37920851,https://doi.org/10.1038/s44161-022-00171-0,Transcriptomic-based clustering of human atherosclerotic plaques identifies subgroups with different underlying biology and clinical presentation.,"Mokry M, Boltjes A, Slenders L, Bel-Bordes G, Cui K, Brouwer E, Mekke JM, Depuydt MAC, Timmerman N, Waissi F, Verwer MC, Turner AW, Khan MD, Hodonsky CJ, Benavente ED, Hartman RJG, van den Dungen NAM, Lansu N, Nagyova E, Prange KHM, Kovacic JC, Björkegren JLM, Pavlos E, Andreakos E, Schunkert H, Owens GK, Monaco C, Finn AV, Virmani R, Leeper NJ, de Winther MPJ, Kuiper J, de Borst GJ, Stroes ESG, Civelek M, de Kleijn DPV, den Ruijter HM, Asselbergs FW, van der Laan SW, Miller CL, Pasterkamp G.",,Nature cardiovascular research,2022,2022-12-12,N,,,,"Histopathological studies have revealed key processes of atherosclerotic plaque thrombosis. However, the diversity and complexity of lesion types highlight the need for improved sub-phenotyping. Here we analyze the gene expression profiles of 654 advanced human carotid plaques. The unsupervised, transcriptome-driven clustering revealed five dominant plaque types. These plaque phenotypes were associated with clinical presentation and showed differences in cellular compositions. Validation in coronary segments showed that the molecular signature of these plaques was linked to coronary ischemia. One of the plaque types with the most severe clinical symptoms pointed to both inflammatory and fibrotic cell lineages. Further, we did a preliminary analysis of potential circulating biomarkers that mark the different plaques phenotypes. In conclusion, the definition of the plaque at risk for a thrombotic event can be fine-tuned by in-depth transcriptomic-based phenotyping. These differential plaque phenotypes prove clinically relevant for both carotid and coronary artery plaques and point to distinct underlying biology of symptomatic lesions.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621615; doi:https://doi.org/10.1038/s44161-022-00171-0; html:https://europepmc.org/articles/PMC10621615; pdf:https://europepmc.org/articles/PMC10621615?pdf=render; doi:https://doi.org/10.1038/s44161-022-00171-0 -35606419,https://doi.org/10.1038/s41593-022-01074-w,Phenotypic and genetic associations of quantitative magnetic susceptibility in UK Biobank brain imaging.,"Wang C, Martins-Bach AB, Alfaro-Almagro F, Douaud G, Klein JC, Llera A, Fiscone C, Bowtell R, Elliott LT, Smith SM, Tendler BC, Miller KL.",,Nature neuroscience,2022,2022-05-23,Y,,,,"A key aim in epidemiological neuroscience is identification of markers to assess brain health and monitor therapeutic interventions. Quantitative susceptibility mapping (QSM) is an emerging magnetic resonance imaging technique that measures tissue magnetic susceptibility and has been shown to detect pathological changes in tissue iron, myelin and calcification. We present an open resource of QSM-based imaging measures of multiple brain structures in 35,273 individuals from the UK Biobank prospective epidemiological study. We identify statistically significant associations of 251 phenotypes with magnetic susceptibility that include body iron, disease, diet and alcohol consumption. Genome-wide associations relate magnetic susceptibility to 76 replicating clusters of genetic variants with biological functions involving iron, calcium, myelin and extracellular matrix. These patterns of associations include relationships that are unique to QSM, in particular being complementary to T2* signal decay time measures. These new imaging phenotypes are being integrated into the core UK Biobank measures provided to researchers worldwide, creating the potential to discover new, non-invasive markers of brain health.",,pdf:https://www.nature.com/articles/s41593-022-01074-w.pdf; doi:https://doi.org/10.1038/s41593-022-01074-w; html:https://europepmc.org/articles/PMC9174052; pdf:https://europepmc.org/articles/PMC9174052?pdf=render 35509371,https://doi.org/10.12688/wellcomeopenres.16883.2,Single-cell multi-omics analysis reveals IFN-driven alterations in T lymphocytes and natural killer cells in systemic lupus erythematosus.,"Trzupek D, Lee M, Hamey F, Wicker LS, Todd JA, Ferreira RC.",,Wellcome open research,2021,2021-01-01,Y,Biomarker; Systemic Lupus Erythematosus (Sle); Type I Interferon (Ifn); Multi-omics; Single-cell Rna-sequencing (Scrna-seq); Abseq; Bd Rhapsody; Cytotoxic Cd4+ T Cells (Ctls),,,"Background: The characterisation of the peripheral immune system in the autoimmune disease systemic lupus erythematosus (SLE) at the single-cell level has been limited by the reduced sensitivity of current whole-transcriptomic technologies. Here we employ a targeted single-cell multi-omics approach, combining protein and mRNA quantification, to generate a high-resolution map of the T lymphocyte and natural killer (NK) cell populations in blood from SLE patients. Methods: We designed a custom panel to quantify the transcription of 534 genes in parallel with the expression of 51 surface protein targets using the BD Rhapsody AbSeq single-cell system. We applied this technology to profile 20,656 T and NK cells isolated from peripheral blood from an SLE patient with a type I interferon (IFN)-induced gene expression signature (IFN hi), and an age- and sex- matched IFN low SLE patient and healthy donor. Results: We confirmed the presence of a rare cytotoxic CD4 + T cell (CTL) subset, which was exclusively present in the IFN hi patient. Furthermore, we identified additional alterations consistent with increased immune activation in this patient, most notably a shift towards terminally differentiated CD57 + CD8 + T cell and CD16 + NK dim phenotypes, and the presence of a subset of recently-activated naïve CD4 + T cells. Conclusions: Our results identify IFN-driven changes in the composition and phenotype of T and NK cells that are consistent with a systemic immune activation within the IFN hi patient, and underscore the added resolving power of this multi-omics approach to identify rare immune subsets. Consequently, we were able to find evidence for novel cellular peripheral biomarkers of SLE disease activity, including a subpopulation of CD57 + CD4 + CTLs.",,pdf:https://wellcomeopenresearch.org/articles/6-149/v2/pdf; doi:https://doi.org/10.12688/wellcomeopenres.16883.2; html:https://europepmc.org/articles/PMC9046903; pdf:https://europepmc.org/articles/PMC9046903?pdf=render +35606419,https://doi.org/10.1038/s41593-022-01074-w,Phenotypic and genetic associations of quantitative magnetic susceptibility in UK Biobank brain imaging.,"Wang C, Martins-Bach AB, Alfaro-Almagro F, Douaud G, Klein JC, Llera A, Fiscone C, Bowtell R, Elliott LT, Smith SM, Tendler BC, Miller KL.",,Nature neuroscience,2022,2022-05-23,Y,,,,"A key aim in epidemiological neuroscience is identification of markers to assess brain health and monitor therapeutic interventions. Quantitative susceptibility mapping (QSM) is an emerging magnetic resonance imaging technique that measures tissue magnetic susceptibility and has been shown to detect pathological changes in tissue iron, myelin and calcification. We present an open resource of QSM-based imaging measures of multiple brain structures in 35,273 individuals from the UK Biobank prospective epidemiological study. We identify statistically significant associations of 251 phenotypes with magnetic susceptibility that include body iron, disease, diet and alcohol consumption. Genome-wide associations relate magnetic susceptibility to 76 replicating clusters of genetic variants with biological functions involving iron, calcium, myelin and extracellular matrix. These patterns of associations include relationships that are unique to QSM, in particular being complementary to T2* signal decay time measures. These new imaging phenotypes are being integrated into the core UK Biobank measures provided to researchers worldwide, creating the potential to discover new, non-invasive markers of brain health.",,pdf:https://www.nature.com/articles/s41593-022-01074-w.pdf; doi:https://doi.org/10.1038/s41593-022-01074-w; html:https://europepmc.org/articles/PMC9174052; pdf:https://europepmc.org/articles/PMC9174052?pdf=render 35258317,https://doi.org/10.1161/jaha.121.024260,Prognostic Significance of Ventricular Arrhythmias in 13 444 Patients With Acute Coronary Syndrome: A Retrospective Cohort Study Based on Routine Clinical Data (NIHR Health Informatics Collaborative VA-ACS Study).,"Sau A, Kaura A, Kaura A, Ahmed A, Patel KHK, Li X, Mulla A, Glampson B, Panoulas V, Davies J, Woods K, Gautama S, Shah AD, Elliott P, Hemingway H, Williams B, Asselbergs FW, Melikian N, Peters NS, Shah AM, Perera D, Kharbanda R, Patel RS, Channon KM, Mayet J, Ng FS.",,Journal of the American Heart Association,2022,2022-03-08,Y,Cardiac arrest; acute coronary syndrome; ventricular arrhythmia,,,"Background A minority of acute coronary syndrome (ACS) cases are associated with ventricular arrhythmias (VA) and/or cardiac arrest (CA). We investigated the effect of VA/CA at the time of ACS on long-term outcomes. Methods and Results We analyzed routine clinical data from 5 National Health Service trusts in the United Kingdom, collected between 2010 and 2017 by the National Institute for Health Research Health Informatics Collaborative. A total of 13 444 patients with ACS, 376 (2.8%) of whom had concurrent VA, survived to hospital discharge and were followed up for a median of 3.42 years. Patients with VA or CA at index presentation had significantly increased risks of subsequent VA during follow-up (VA group: adjusted hazard ratio [HR], 4.15 [95% CI, 2.42-7.09]; CA group: adjusted HR, 2.60 [95% CI, 1.23-5.48]). Patients who suffered a CA in the context of ACS and survived to discharge also had a 36% increase in long-term mortality (adjusted HR, 1.36 [95% CI, 1.04-1.78]), although the concurrent diagnosis of VA alone during ACS did not affect all-cause mortality (adjusted HR, 1.03 [95% CI, 0.80-1.33]). Conclusions Patients who develop VA or CA during ACS who survive to discharge have increased risks of subsequent VA, whereas those who have CA during ACS also have an increase in long-term mortality. These individuals may represent a subgroup at greater risk of subsequent arrhythmic events as a result of intrinsically lower thresholds for developing VA.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.024260; doi:https://doi.org/10.1161/JAHA.121.024260; html:https://europepmc.org/articles/PMC9075290; pdf:https://europepmc.org/articles/PMC9075290?pdf=render 33444378,https://doi.org/10.1371/journal.pcbi.1008417,Probabilistic transmission models incorporating sequencing data for healthcare-associated Clostridioides difficile outperform heuristic rules and identify strain-specific differences in transmission.,"Eyre DW, Laager M, Walker AS, Cooper BS, Wilson DJ, CDC Modeling Infectious Diseases in Healthcare Program (MInD-Healthcare).",,PLoS computational biology,2021,2021-01-14,Y,,,,"Fitting stochastic transmission models to electronic patient data can offer detailed insights into the transmission of healthcare-associated infections and improve infection control. Pathogen whole-genome sequencing may improve the precision of model inferences, but computational constraints have limited modelling applications predominantly to small datasets and specific outbreaks, whereas large-scale sequencing studies have mostly relied on simple rules for identifying/excluding plausible transmission. We present a novel approach for integrating detailed epidemiological data on patient contact networks in hospitals with large-scale pathogen sequencing data. We apply our approach to study Clostridioides difficile transmission using a dataset of 1223 infections in Oxfordshire, UK, 2007-2011. 262 (21% [95% credibility interval 20-22%]) infections were estimated to have been acquired from another known case. There was heterogeneity by sequence type (ST) in the proportion of cases acquired from another case with the highest rates in ST1 (ribotype-027), ST42 (ribotype-106) and ST3 (ribotype-001). These same STs also had higher rates of transmission mediated via environmental contamination/spores persisting after patient discharge/recovery; for ST1 these persisted longer than for most other STs except ST3 and ST42. We also identified variation in transmission between hospitals, medical specialties and over time; by 2011 nearly all transmission from known cases had ceased in our hospitals. Our findings support previous work suggesting only a minority of C. difficile infections are acquired from known cases but highlight a greater role for environmental contamination than previously thought. Our approach is applicable to other healthcare-associated infections. Our findings have important implications for effective control of C. difficile.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008417&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1008417; html:https://europepmc.org/articles/PMC7840057; pdf:https://europepmc.org/articles/PMC7840057?pdf=render 32934998,https://doi.org/10.23889/ijpds.v3i1.412,Creating individual level air pollution exposures in an anonymised data safe haven: a platform for evaluating impact on educational attainment.,"Mizen A, Lyons J, Doherty R, Berridge D, Wilkinson P, Milojevic A, Carruthers D, Akbari A, Lake I, Davies GA, Sallakh MA, Mavrogianni A, Dearden L, Johnson R, Rodgers SE.",,International journal of population data science,2018,2018-08-21,Y,Air pollution; Cognition; Asthma; Data Linkage; Seasonal Allergic Rhinitis,,,"

Introduction

There is a lack of evidence on the adverse effects of air pollution on cognition for people with air quality-related health conditions. We propose that educational attainment, as a proxy for cognition, may increase with improved air quality. This study will explore whether asthma and seasonal allergic rhinitis, when exacerbated by acute exposure to air pollution, is associated with educational attainment.

Objective

To describe the preparation of individual and household-level linked environmental and health data for analysis within an anonymised safe haven. Also to introduce our statistical analysis plan for our study: COgnition, Respiratory Tract illness and Effects of eXposure (CORTEX).

Methods

We imported daily air pollution and aeroallergen data, and individual level education data into the SAIL databank, an anonymised safe haven for person-based records. We linked individual-level education, socioeconomic and health data to air quality data for home and school locations, creating tailored exposures for individuals across a city. We developed daily exposure data for all pupils in repeated cross sectional exam cohorts (2009-2015).

Conclusion

We have used the SAIL databank, an innovative, data safe haven to create individual-level exposures to air pollution and pollen for multiple daily home and school locations. The analysis platform will allow us to evaluate retrospectively the impact of air quality on attainment for multiple cross-sectional cohorts of pupils. Our methods will allow us to distinguish between the pollution impacts on educational attainment for pupils with and without respiratory health conditions. The results from this study will further our understanding of the effects of air quality and respiratory-related health conditions on cognition.

Highlights

This city-wide study includes longitudinal routinely-recorded educational attainment data for all pupils taking exams over seven years;High spatial resolution air pollution data were linked within a privacy protected databank to obtain individual exposure at multiple daily locations;This study will use health data linked at the individual level to explore associations between air pollution, related morbidity, and educational attainment.",,pdf:https://ijpds.org/article/download/412/533; doi:https://doi.org/10.23889/ijpds.v3i1.412; html:https://europepmc.org/articles/PMC7299475; pdf:https://europepmc.org/articles/PMC7299475?pdf=render @@ -2162,8 +2162,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 35353173,https://doi.org/10.1001/jamapsychiatry.2022.0407,Inflammation and Brain Structure in Schizophrenia and Other Neuropsychiatric Disorders: A Mendelian Randomization Study.,"Williams JA, Burgess S, Suckling J, Lalousis PA, Batool F, Griffiths SL, Palmer E, Karwath A, Barsky A, Gkoutos GV, Wood S, Barnes NM, David AS, Donohoe G, Neill JC, Deakin B, Khandaker GM, Upthegrove R, PIMS Collaboration.",,JAMA psychiatry,2022,2022-05-01,Y,,,,"

Importance

Previous in vitro and postmortem research suggests that inflammation may lead to structural brain changes via activation of microglia and/or astrocytic dysfunction in a range of neuropsychiatric disorders.

Objective

To investigate the relationship between inflammation and changes in brain structures in vivo and to explore a transcriptome-driven functional basis with relevance to mental illness.

Design, setting, and participants

This study used multistage linked analyses, including mendelian randomization (MR), gene expression correlation, and connectivity analyses. A total of 20 688 participants in the UK Biobank, which includes clinical, genomic, and neuroimaging data, and 6 postmortem brains from neurotypical individuals in the Allen Human Brain Atlas (AHBA), including RNA microarray data. Data were extracted in February 2021 and analyzed between March and October 2021.

Exposures

Genetic variants regulating levels and activity of circulating interleukin 1 (IL-1), IL-2, IL-6, C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF) were used as exposures in MR analyses.

Main outcomes and measures

Brain imaging measures, including gray matter volume (GMV) and cortical thickness (CT), were used as outcomes. Associations were considered significant at a multiple testing-corrected threshold of P < 1.1 × 10-4. Differential gene expression in AHBA data was modeled in brain regions mapped to areas significant in MR analyses; genes were tested for biological and disease overrepresentation in annotation databases and for connectivity in protein-protein interaction networks.

Results

Of 20 688 participants in the UK Biobank sample, 10 828 (52.3%) were female, and the mean (SD) age was 55.5 (7.5) years. In the UK Biobank sample, genetically predicted levels of IL-6 were associated with GMV in the middle temporal cortex (z score, 5.76; P = 8.39 × 10-9), inferior temporal (z score, 3.38; P = 7.20 × 10-5), fusiform (z score, 4.70; P = 2.60 × 10-7), and frontal (z score, -3.59; P = 3.30 × 10-5) cortex together with CT in the superior frontal region (z score, -5.11; P = 3.22 × 10-7). No significant associations were found for IL-1, IL-2, CRP, or BDNF after correction for multiple comparison. In the AHBA sample, 5 of 6 participants (83%) were male, and the mean (SD) age was 42.5 (13.4) years. Brain-wide coexpression analysis showed a highly interconnected network of genes preferentially expressed in the middle temporal gyrus (MTG), which further formed a highly connected protein-protein interaction network with IL-6 (enrichment test of expected vs observed network given the prevalence and degree of interactions in the STRING database: 43 nodes/30 edges observed vs 8 edges expected; mean node degree, 1.4; genome-wide significance, P = 4.54 × 10-9). MTG differentially expressed genes that were functionally enriched for biological processes in schizophrenia, autism spectrum disorder, and epilepsy.

Conclusions and relevance

In this study, genetically determined IL-6 was associated with brain structure and potentially affects areas implicated in developmental neuropsychiatric disorders, including schizophrenia and autism.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968718; doi:https://doi.org/10.1001/jamapsychiatry.2022.0407; html:https://europepmc.org/articles/PMC8968718 37253531,https://doi.org/10.1136/bmjgh-2022-009997,Effectiveness of a multicomponent intervention to face the COVID-19 pandemic in Rio de Janeiro's favelas: difference-in-differences analysis.,"Batista-da-Silva AA, Moraes CB, Bozza HR, Bastos LDSL, Ranzani OT, Hamacher S, Bozza FA, Comitê Gestor Conexão Saúde.",,BMJ global health,2023,2023-05-01,Y,"Control strategies; Public Health; Intervention Study; Infections, Diseases, Disorders, Injuries; Covid-19",,,"

Introduction

Few community-based interventions addressing the transmission control and clinical management of COVID-19 cases have been reported, especially in poor urban communities from low-income and middle-income countries. Here, we analyse the impact of a multicomponent intervention that combines community engagement, mobile surveillance, massive testing and telehealth on COVID-19 cases detection and mortality rates in a large vulnerable community (Complexo da Maré) in Rio de Janeiro, Brazil.

Methods

We performed a difference-in-differences (DID) analysis to estimate the impact of the multicomponent intervention in Maré, before (March-August 2020) and after the intervention (September 2020 to April 2021), compared with equivalent local vulnerable communities. We applied a negative binomial regression model to estimate the intervention effect in weekly cases and mortality rates in Maré.

Results

Before the intervention, Maré presented lower rates of reported COVID-19 cases compared with the control group (1373 vs 1579 cases/100 000 population), comparable mortality rates (309 vs 287 deaths/100 000 population) and higher case fatality rates (13.7% vs 12.2%). After the intervention, Maré displayed a 154% (95% CI 138.6% to 170.4%) relative increase in reported case rates. Relative changes in reported death rates were -60% (95% CI -69.0% to -47.9%) in Maré and -28% (95% CI -42.0% to -9.8%) in the control group. The case fatality rate was reduced by 77% (95% CI -93.1% to -21.1%) in Maré and 52% (95% CI -81.8% to -29.4%) in the control group. The DID showed a reduction of 46% (95% CI 17% to 65%) of weekly reported deaths and an increased 23% (95% CI 5% to 44%) of reported cases in Maré after intervention onset.

Conclusion

An integrated intervention combining communication, surveillance and telehealth, with a strong community engagement component, could reduce COVID-19 mortality and increase case detection in a large vulnerable community in Rio de Janeiro. These findings show that investment in community-based interventions may reduce mortality and improve pandemic control in poor communities from low-income and middle-income countries.",,doi:https://doi.org/10.1136/bmjgh-2022-009997; doi:https://doi.org/10.1136/bmjgh-2022-009997; html:https://europepmc.org/articles/PMC10230340; pdf:https://europepmc.org/articles/PMC10230340?pdf=render 34371093,https://doi.org/10.1016/j.jaad.2021.07.066,The impact of psoriasis and sexual orientation on mental and physical health among adults in the United States.,"Mansh MD, Mulick A, Langan SM.",,Journal of the American Academy of Dermatology,2022,2021-08-08,Y,,,,,,doi:https://doi.org/10.1016/j.jaad.2021.07.066; doi:https://doi.org/10.1016/j.jaad.2021.07.066; html:https://europepmc.org/articles/PMC7612892; pdf:https://europepmc.org/articles/PMC7612892?pdf=render -36245269,https://doi.org/10.15252/embj.2022111857,Cryo-EM structures of perforin-2 in isolation and assembled on a membrane suggest a mechanism for pore formation.,"Yu X, Ni T, Munson G, Zhang P, Gilbert RJC.",,The EMBO journal,2022,2022-10-17,Y,Cryo-electron Tomography; Cryo-em; Subtomogram Averaging; Pore-forming Protein; Perforin-2,,,"Perforin-2 (PFN2, MPEG1) is a key pore-forming protein in mammalian innate immunity restricting intracellular bacteria proliferation. It forms a membrane-bound pre-pore complex that converts to a pore-forming structure upon acidification; but its mechanism of conformational transition has been debated. Here we used cryo-electron microscopy, tomography and subtomogram averaging to determine structures of PFN2 in pre-pore and pore conformations in isolation and bound to liposomes. In isolation and upon acidification, the pre-assembled complete pre-pore rings convert to pores in both flat ring and twisted conformations. On membranes, in situ assembled PFN2 pre-pores display various degrees of completeness; whereas PFN2 pores are mainly incomplete arc structures that follow the same subunit packing arrangements as found in isolation. Both assemblies on membranes use their P2 β-hairpin for binding to the lipid membrane surface. Overall, these structural snapshots suggest a molecular mechanism for PFN2 pre-pore to pore transition on a targeted membrane, potentially using the twisted pore as an intermediate or alternative state to the flat conformation, with the capacity to cause bilayer distortion during membrane insertion.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.15252/embj.2022111857; doi:https://doi.org/10.15252/embj.2022111857; html:https://europepmc.org/articles/PMC9713709; pdf:https://europepmc.org/articles/PMC9713709?pdf=render 34110679,https://doi.org/10.1002/1878-0261.13038,Cost-effectiveness of precision diagnostic testing for precision medicine approaches against non-small-cell lung cancer: A systematic review.,"Henderson R, Keeling P, French D, Smart D, Sullivan R, Lawler M.",,Molecular oncology,2021,2021-07-19,Y,Biomarker; Economic evaluation; non-small-cell lung cancer; Cost-effectiveness Analysis; Precision Medicine; Precision Diagnostic Test,,,"Precision diagnostic testing (PDT) employs appropriate biomarkers to identify cancer patients that may optimally respond to precision medicine (PM) approaches, such as treatments with targeted agents and immuno-oncology drugs. To date, there are no published systematic appraisals evaluating the cost-effectiveness of PDT in non-small-cell lung cancer (NSCLC). To address this gap, we conducted Preferred Reporting Items for Systematic Reviews and Meta-Analyses searches for the years 2009-2019. Consolidated Health Economic Evaluation Reporting Standards were employed to screen, assess and extract data. Employing base costs, life years gained or quality-adjusted life years, as well as willingness-to-pay (WTP) threshold for each country, net monetary benefit was calculated to determine cost-effectiveness of each intervention. Thirty-seven studies (50%) were included for analysis; a further 37 (50%) were excluded, having failed population-, intervention-, comparator-, outcomes- and study-design criteria. Within the 37 studies included, we defined 64 scenarios. Eleven scenarios compared PDT-guided PM with non-guided therapy [epidermal growth factor receptor (EGFR), n = 5; programmed death-ligand 1 (PD-L1), n = 6]. Twenty-eight scenarios compared PDT-guided PM with chemotherapy alone (anaplastic lymphoma kinase, n = 3; EGFR, n = 17; PD-L1, n = 8). Twenty-five scenarios compared PDT-guided PM with chemotherapy alone, while varying the PDT approach. Thirty-four scenarios (53%) were cost-effective, 28 (44%) were not cost-effective, and two were marginal, dependent on their country's WTP threshold. When PDT-guided therapy was compared with a therapy-for-all patients approach, all scenarios (100%) proved cost-effective. Seven of 37 studies had been structured appropriately to assess PDT-PM cost-effectiveness. Within these seven studies, all evaluated scenarios were cost-effective. However, 81% of studies had been poorly designed. Our systematic analysis implies that more robust health economic evaluation could help identify additional approaches towards PDT cost-effectiveness, underpinning value-based care and enhanced outcomes for patients with NSCLC.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/1878-0261.13038; doi:https://doi.org/10.1002/1878-0261.13038; html:https://europepmc.org/articles/PMC8486593; pdf:https://europepmc.org/articles/PMC8486593?pdf=render +36245269,https://doi.org/10.15252/embj.2022111857,Cryo-EM structures of perforin-2 in isolation and assembled on a membrane suggest a mechanism for pore formation.,"Yu X, Ni T, Munson G, Zhang P, Gilbert RJC.",,The EMBO journal,2022,2022-10-17,Y,Cryo-electron Tomography; Cryo-em; Subtomogram Averaging; Pore-forming Protein; Perforin-2,,,"Perforin-2 (PFN2, MPEG1) is a key pore-forming protein in mammalian innate immunity restricting intracellular bacteria proliferation. It forms a membrane-bound pre-pore complex that converts to a pore-forming structure upon acidification; but its mechanism of conformational transition has been debated. Here we used cryo-electron microscopy, tomography and subtomogram averaging to determine structures of PFN2 in pre-pore and pore conformations in isolation and bound to liposomes. In isolation and upon acidification, the pre-assembled complete pre-pore rings convert to pores in both flat ring and twisted conformations. On membranes, in situ assembled PFN2 pre-pores display various degrees of completeness; whereas PFN2 pores are mainly incomplete arc structures that follow the same subunit packing arrangements as found in isolation. Both assemblies on membranes use their P2 β-hairpin for binding to the lipid membrane surface. Overall, these structural snapshots suggest a molecular mechanism for PFN2 pre-pore to pore transition on a targeted membrane, potentially using the twisted pore as an intermediate or alternative state to the flat conformation, with the capacity to cause bilayer distortion during membrane insertion.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.15252/embj.2022111857; doi:https://doi.org/10.15252/embj.2022111857; html:https://europepmc.org/articles/PMC9713709; pdf:https://europepmc.org/articles/PMC9713709?pdf=render 35051442,https://doi.org/10.1016/j.jviromet.2022.114471,Reduced amplification efficiency of the RNA-dependent-RNA-polymerase target enables tracking of the Delta SARS-CoV-2 variant using routine diagnostic tests.,"Valley-Omar Z, Marais G, Iranzadeh A, Naidoo M, Korsman S, Maponga T, Hussey H, Davies MA, Boulle A, Doolabh D, Laubscher M, Wojno J, Deetlefs JD, Maritz J, Scott L, Msomi N, Naicker C, Tegally H, de Oliveira T, Bhiman J, Williamson C, Preiser W, Hardie D, Hsiao NY.",,Journal of virological methods,2022,2022-01-18,Y,Surveillance; Diagnostic test; South Africa; Covid-19; Sars-cov-2; Delta Variant,,,"Routine SARS-CoV-2 surveillance in the Western Cape region of South Africa (January-August 2021) found a reduced RT-PCR amplification efficiency of the RdRp-gene target of the Seegene, Allplex 2019-nCoV diagnostic assay from June 2021 when detecting the Delta variant. We investigated whether the reduced amplification efficiency denoted by an increased RT-PCR cycle threshold value (RΔE) can be used as an indirect measure of SARS-CoV-2 Delta variant prevalence. We found a significant increase in the median RΔE for patient samples tested from June 2021, which coincided with the emergence of the SARS-CoV-2 Delta variant within our sample set. Whole genome sequencing on a subset of patient samples identified a highly conserved G15451A, non-synonymous mutation exclusively within the RdRp gene of Delta variants, which may cause reduced RT-PCR amplification efficiency. While whole genome sequencing plays an important in identifying novel SARS-CoV-2 variants, monitoring RΔE value can serve as a useful surrogate for rapid tracking of Delta variant prevalence.",,doi:https://doi.org/10.1016/j.jviromet.2022.114471; doi:https://doi.org/10.1016/j.jviromet.2022.114471; html:https://europepmc.org/articles/PMC8763409; pdf:https://europepmc.org/articles/PMC8763409?pdf=render 32576090,https://doi.org/10.1161/strokeaha.120.029042,Telemedicine Cognitive Behavioral Therapy for Anxiety After Stroke: Proof-of-Concept Randomized Controlled Trial.,"Chun HY, Carson AJ, Tsanas A, Dennis MS, Mead GE, Calabria C, Whiteley WN.",,Stroke,2020,2020-06-24,Y,Stroke; Anxiety; Workflow; Telemedicine; psychotherapy,,,"

Background and purpose

Disabling anxiety affects a quarter of stroke survivors but access to treatment is poor. We developed a telemedicine model for delivering guided self-help cognitive behavioral therapy (CBT) for anxiety after stroke (TASK-CBT). We aimed to evaluate the feasibility of TASK-CBT in a randomized controlled trial workflow that enabled all trial procedures to be carried out remotely. In addition, we explored the feasibility of wrist-worn actigraphy sensor as a way of measuring objective outcomes in this clinical trial.

Methods

We recruited adult community-based stroke patients (n=27) and randomly allocated them to TASK-CBT (n=14) or relaxation therapy (TASK-Relax), an active comparator (n=13).

Results

In our sample (mean age 65 [±10]; 56% men; 63% stroke, 37% transient ischemic attacks), remote self-enrolment, electronic signature, intervention delivery, and automated follow-up were feasible. All participants completed all TASK-CBT sessions (14/14). Lower levels of anxiety were observed in TASK-CBT when compared with TASK-Relax at both weeks 6 and 20. Mean actigraphy sensor wearing-time was 33 days (±15).

Conclusions

Our preliminary feasibility data from the current study support a larger definitive clinical trial and the use of wrist-worn actigraphy sensor in anxious stroke survivors. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03439813.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.120.029042; doi:https://doi.org/10.1161/STROKEAHA.120.029042; html:https://europepmc.org/articles/PMC7382539; pdf:https://europepmc.org/articles/PMC7382539?pdf=render 35477868,https://doi.org/10.1136/bmjopen-2021-057579,Public opinion on sharing data from health services for clinical and research purposes without explicit consent: an anonymous online survey in the UK.,"Jones LA, Nelder JR, Fryer JM, Alsop PH, Geary MR, Prince M, Cardinal RN.",,BMJ open,2022,2022-04-27,Y,Information management; Mental health; Health Policy; Health Informatics,,,"

Objectives

UK National Health Service/Health and Social Care (NHS/HSC) data are variably shared between healthcare organisations for direct care, and increasingly de-identified for research. Few large-scale studies have examined public opinion on sharing, including of mental health (MH) versus physical health (PH) data. We measured data sharing preferences.

Design/setting/interventions/outcomes

Pre-registered anonymous online survey, measuring expressed preferences, recruiting February to September 2020. Participants were randomised to one of three framing statements regarding MH versus PH data.

Participants

Open to all UK residents. Participants numbered 29 275; 40% had experienced an MH condition.

Results

Most (76%) supported identifiable data sharing for direct clinical care without explicit consent, but 20% opposed this. Preference for clinical/identifiable sharing decreased with geographical distance and was slightly less for MH than PH data, with small framing effects. Preference for research/de-identified data sharing without explicit consent showed the same small PH/MH and framing effects, plus greater preference for sharing structured data than de-identified free text. There was net support for research sharing to the NHS, academic institutions, and national research charities, net ambivalence about sharing to profit-making companies researching treatments, and net opposition to sharing to other companies (similar to sharing publicly). De-identified linkage to non-health data was generally supported, except to data held by private companies. We report demographic influences on preference. A majority (89%) supported a single NHS mechanism to choose uses of their data. Support for data sharing increased during COVID-19.

Conclusions

Support for healthcare data sharing for direct care without explicit consent is broad but not universal. There is net support for the sharing of de-identified data for research to the NHS, academia, and the charitable sector, but not the commercial sector. A single national NHS-hosted system for patients to control the use of their NHS data for clinical purposes and for research would have broad support.

Trial registration number

ISRCTN37444142.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057579.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057579; html:https://europepmc.org/articles/PMC9058801; pdf:https://europepmc.org/articles/PMC9058801?pdf=render @@ -2171,11 +2171,11 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 35386118,https://doi.org/10.3389/fnagi.2022.840651,Genome-Wide Association Study of Alzheimer's Disease Brain Imaging Biomarkers and Neuropsychological Phenotypes in the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery Dataset.,"Homann J, Osburg T, Ohlei O, Dobricic V, Deecke L, Bos I, Vandenberghe R, Gabel S, Scheltens P, Teunissen CE, Engelborghs S, Frisoni G, Blin O, Richardson JC, Bordet R, Lleó A, Alcolea D, Popp J, Clark C, Peyratout G, Martinez-Lage P, Tainta M, Dobson RJB, Legido-Quigley C, Sleegers K, Van Broeckhoven C, Wittig M, Franke A, Lill CM, Blennow K, Zetterberg H, Lovestone S, Streffer J, Ten Kate M, Vos SJB, Barkhof F, Visser PJ, Bertram L.",,Frontiers in aging neuroscience,2022,2022-03-21,Y,X chromosome; MRI; Imaging; Cognitive function; Genome-wide Association Study; Gwas; Alzheimer’s Disease (Ad),,,"Alzheimer's disease (AD) is the most frequent neurodegenerative disease with an increasing prevalence in industrialized, aging populations. AD susceptibility has an established genetic basis which has been the focus of a large number of genome-wide association studies (GWAS) published over the last decade. Most of these GWAS used dichotomized clinical diagnostic status, i.e., case vs. control classification, as outcome phenotypes, without the use of biomarkers. An alternative and potentially more powerful study design is afforded by using quantitative AD-related phenotypes as GWAS outcome traits, an analysis paradigm that we followed in this work. Specifically, we utilized genotype and phenotype data from n = 931 individuals collected under the auspices of the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study to perform a total of 19 separate GWAS analyses. As outcomes we used five magnetic resonance imaging (MRI) traits and seven cognitive performance traits. For the latter, longitudinal data from at least two timepoints were available in addition to cross-sectional assessments at baseline. Our GWAS analyses revealed several genome-wide significant associations for the neuropsychological performance measures, in particular those assayed longitudinally. Among the most noteworthy signals were associations in or near EHBP1 (EH domain binding protein 1; on chromosome 2p15) and CEP112 (centrosomal protein 112; 17q24.1) with delayed recall as well as SMOC2 (SPARC related modular calcium binding 2; 6p27) with immediate recall in a memory performance test. On the X chromosome, which is often excluded in other GWAS, we identified a genome-wide significant signal near IL1RAPL1 (interleukin 1 receptor accessory protein like 1; Xp21.3). While polygenic score (PGS) analyses showed the expected strong associations with SNPs highlighted in relevant previous GWAS on hippocampal volume and cognitive function, they did not show noteworthy associations with recent AD risk GWAS findings. In summary, our study highlights the power of using quantitative endophenotypes as outcome traits in AD-related GWAS analyses and nominates several new loci not previously implicated in cognitive decline.",,pdf:https://www.frontiersin.org/articles/10.3389/fnagi.2022.840651/pdf; doi:https://doi.org/10.3389/fnagi.2022.840651; html:https://europepmc.org/articles/PMC8979334; pdf:https://europepmc.org/articles/PMC8979334?pdf=render 34244281,https://doi.org/10.1136/bmjopen-2021-049611,"Ethnicity and COVID-19 outcomes among healthcare workers in the UK: UK-REACH ethico-legal research, qualitative research on healthcare workers' experiences and stakeholder engagement protocol.","Gogoi M, Reed-Berendt R, Al-Oraibi A, Hassan O, Wobi F, Gupta A, Abubakar I, Dove E, Nellums LB, Pareek M, UK-REACH Collaborative Group.",,BMJ open,2021,2021-07-09,Y,Medical Ethics; Qualitative Research; Medical Law; Covid-19,,,"

Introduction

As the world continues to grapple with the COVID-19 pandemic, emerging evidence suggests that individuals from ethnic minority backgrounds may be disproportionately affected. The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH) project has been initiated to generate rapid evidence on whether and why ethnicity affects COVID-19 diagnosis and clinical outcomes in healthcare workers (HCWs) in the UK, through five interlinked work packages/work streams, three of which form the basis of this protocol. The ethico-legal work (Work Package 3) aims to understand and address legal, ethical and acceptability issues around big data research; the HCWs' experiences study (Work Package 4) explores their work and personal experiences, perceptions of risk, support and coping mechanisms; the stakeholder engagement work (Work Package 5) aims to provide feedback and support with the formulation and dissemination of the project recommendations.

Methods and analysis

Work Package 3 has two different research strands: (A) desk-based doctrinal research; and (B) empirical qualitative research with key opinion leaders. For the empirical research, in-depth interviews will be conducted digitally and recorded with participants' permission. Recordings will be transcribed, coded and analysed using thematic analysis. In Work Package 4, online in-depth interviews and focus groups will be conducted with approximately 150 HCWs, from across the UK, and these will be recorded with participants' consent. The recordings will be transcribed and coded and data will be analysed using thematic analysis. Work Package 5 will achieve its objectives through regular group meetings and in-group discussions.

Ethics and dissemination

Ethical approval has been received from the London-Brighton & Sussex Research Ethics Committee of the Health Research Authority (Ref No 20/HRA/4718). Results of the study will be published in open-access journals, and disseminated through conference presentations, project website, stakeholder organisations, media and scientific advisory groups.

Trial registration number

ISRCTN11811602.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/7/e049611.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049611; html:https://europepmc.org/articles/PMC8275361; pdf:https://europepmc.org/articles/PMC8275361?pdf=render 33664493,https://doi.org/10.1038/s41591-021-01275-z,The need for ethical guidance for the use of patient-reported outcomes in research and clinical practice.,"Cruz Rivera S, Mercieca-Bebber R, Aiyegbusi OL, Scott J, Hunn A, Fernandez C, Ives J, Ells C, Price G, Draper H, Calvert MJ.",,Nature medicine,2021,2021-04-01,N,,,,,,pdf:https://www.nature.com/articles/s41591-021-01275-z.pdf; doi:https://doi.org/10.1038/s41591-021-01275-z -36647047,https://doi.org/10.1186/s12916-022-02722-5,"Polypharmacy during pregnancy and associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019.","Subramanian A, Azcoaga-Lorenzo A, Anand A, Phillips K, Lee SI, Cockburn N, Fagbamigbe AF, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Hope H, Kennedy JI, Abel KM, Eastwood KA, Locock L, Black M, Loane M, Moss N, Plachcinski R, Thangaratinam S, Brophy S, Agrawal U, Vowles Z, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",,BMC medicine,2023,2023-01-16,Y,Pregnancy; Prescriptions; Polypharmacy; Medications; Multimorbidity; Multiple Medications; Multiple Long-term Conditions,,,"

Background

The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy.

Methods

A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register. Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period. Logistic regression models were performed to identify risk factors for polypharmacy.

Results

During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%. Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs). Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese [aOR: 1.16 (1.14-1.18) and 1.55 (1.53-1.57)], belonging to an ethnic minority group [aOR: 2.40 (2.33-2.47), 1.71 (1.65-1.76), 1.41 (1.35-1.47) and 1.39 (1.30-1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women] and smoking or previously smoking [aOR: 1.19 (1.18-1.20) and 1.05 (1.03-1.06)]. Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy.

Conclusions

The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02722-5; doi:https://doi.org/10.1186/s12916-022-02722-5; html:https://europepmc.org/articles/PMC9843951; pdf:https://europepmc.org/articles/PMC9843951?pdf=render 31675503,https://doi.org/10.1016/j.cell.2019.10.004,Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.,"Gurdasani D, Carstensen T, Fatumo S, Chen G, Franklin CS, Prado-Martinez J, Bouman H, Abascal F, Haber M, Tachmazidou I, Mathieson I, Ekoru K, DeGorter MK, Nsubuga RN, Finan C, Wheeler E, Chen L, Cooper DN, Schiffels S, Chen Y, Ritchie GRS, Pollard MO, Fortune MD, Mentzer AJ, Garrison E, Bergström A, Hatzikotoulas K, Adeyemo A, Doumatey A, Elding H, Wain LV, Ehret G, Auer PL, Kooperberg CL, Reiner AP, Franceschini N, Maher D, Montgomery SB, Kadie C, Widmer C, Xue Y, Seeley J, Asiki G, Kamali A, Young EH, Pomilla C, Soranzo N, Zeggini E, Pirie F, Morris AP, Heckerman D, Tyler-Smith C, Motala AA, Rotimi C, Kaleebu P, Barroso I, Sandhu MS.",,Cell,2019,2019-10-01,N,,,,"Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.",,pdf:http://www.cell.com/article/S0092867419311201/pdf; doi:https://doi.org/10.1016/j.cell.2019.10.004; html:https://europepmc.org/articles/PMC7202134; pdf:https://europepmc.org/articles/PMC7202134?pdf=render; doi:https://doi.org/10.1016/j.cell.2019.10.004 +36647047,https://doi.org/10.1186/s12916-022-02722-5,"Polypharmacy during pregnancy and associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019.","Subramanian A, Azcoaga-Lorenzo A, Anand A, Phillips K, Lee SI, Cockburn N, Fagbamigbe AF, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Hope H, Kennedy JI, Abel KM, Eastwood KA, Locock L, Black M, Loane M, Moss N, Plachcinski R, Thangaratinam S, Brophy S, Agrawal U, Vowles Z, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",,BMC medicine,2023,2023-01-16,Y,Pregnancy; Prescriptions; Polypharmacy; Medications; Multimorbidity; Multiple Medications; Multiple Long-term Conditions,,,"

Background

The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy.

Methods

A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register. Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period. Logistic regression models were performed to identify risk factors for polypharmacy.

Results

During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%. Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs). Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese [aOR: 1.16 (1.14-1.18) and 1.55 (1.53-1.57)], belonging to an ethnic minority group [aOR: 2.40 (2.33-2.47), 1.71 (1.65-1.76), 1.41 (1.35-1.47) and 1.39 (1.30-1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women] and smoking or previously smoking [aOR: 1.19 (1.18-1.20) and 1.05 (1.03-1.06)]. Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy.

Conclusions

The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02722-5; doi:https://doi.org/10.1186/s12916-022-02722-5; html:https://europepmc.org/articles/PMC9843951; pdf:https://europepmc.org/articles/PMC9843951?pdf=render 34732073,https://doi.org/10.1161/strokeaha.121.034787,"Risk, Clinical Course, and Outcome of Ischemic Stroke in Patients Hospitalized With COVID-19: A Multicenter Cohort Study.","Sluis WM, Linschoten M, Buijs JE, Biesbroek JM, den Hertog HM, Ribbers T, Nieuwkamp DJ, van Houwelingen RC, Dias A, van Uden IWM, Kerklaan JP, Bienfait HP, Vermeer SE, de Jong SW, Ali M, Wermer MJH, de Graaf MT, Brouwers PJAM, Asselbergs FW, Kappelle LJ, van der Worp HB, Algra AM, CAPACITY-COVID Collaborative Consortium*.",,Stroke,2021,2021-11-04,N,Intensive care units; Pulmonary embolism; incidence; Hospital Mortality; Patient Discharge; Covid-19,,,"

Background and purpose

The frequency of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) varies in the current literature, and risk factors are unknown. We assessed the incidence, risk factors, and outcomes of acute ischemic stroke in hospitalized patients with COVID-19.

Methods

We included patients with a laboratory-confirmed SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection admitted in 16 Dutch hospitals participating in the international CAPACITY-COVID registry between March 1 and August 1, 2020. Patients were screened for the occurrence of acute ischemic stroke. We calculated the cumulative incidence of ischemic stroke and compared risk factors, cardiovascular complications, and in-hospital mortality in patients with and without ischemic stroke.

Results

We included 2147 patients with COVID-19, of whom 586 (27.3%) needed treatment at an intensive care unit. Thirty-eight patients (1.8%) had an ischemic stroke. Patients with stroke were older but did not differ in sex or cardiovascular risk factors. Median time between the onset of COVID-19 symptoms and diagnosis of stroke was 2 weeks. The incidence of ischemic stroke was higher among patients who were treated at an intensive care unit (16/586; 2.7% versus nonintensive care unit, 22/1561; 1.4%; P=0.039). Pulmonary embolism was more common in patients with (8/38; 21.1%) than in those without stroke (160/2109; 7.6%; adjusted risk ratio, 2.08 [95% CI, 1.52-2.84]). Twenty-seven patients with ischemic stroke (71.1%) died during admission or were functionally dependent at discharge. Patients with ischemic stroke were at a higher risk of in-hospital mortality (adjusted risk ratio, 1.56 [95% CI, 1.13-2.15]) than patients without stroke.

Conclusions

In this multicenter cohort study, the cumulative incidence of acute ischemic stroke in hospitalized patients with COVID-19 was ≈2%, with a higher risk in patients treated at an intensive care unit. The majority of stroke patients had a poor outcome. The association between ischemic stroke and pulmonary embolism warrants further investigation.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.121.034787; doi:https://doi.org/10.1161/STROKEAHA.121.034787; html:https://europepmc.org/articles/PMC8607920; pdf:https://europepmc.org/articles/PMC8607920?pdf=render; doi:https://doi.org/10.1161/strokeaha.121.034787 -34216337,https://doi.org/10.1007/s10552-021-01466-6,"Physical activity in relation to circulating hormone concentrations in 117,100 men in UK Biobank.","Watts EL, Perez-Cornago A, Doherty A, Allen NE, Fensom GK, Tin Tin S, Key TJ, Travis RC.",,Cancer causes & control : CCC,2021,2021-07-03,Y,Testosterone; IGF-I; Physical Activity; Accelerometer; Shbg; Uk Biobank,,,"

Purpose

Physical activity may reduce the risk of some types of cancer in men. Biological mechanisms may involve changes in hormone concentrations; however, this relationship is not well established. Therefore, we aimed to investigate the associations of physical activity with circulating insulin-like growth factor-I (IGF-I), sex hormone-binding globulin (SHBG, which modifies sex hormone activity), and total and free testosterone concentrations, and the extent these associations might be mediated by body mass index (BMI).

Methods

Circulating concentrations of these hormones and anthropometric measurements and self-reported physical activity data were available for 117,100 healthy male UK Biobank participants at recruitment. Objectively measured accelerometer physical activity levels were also collected on average 5.7 years after recruitment in 28,000 men. Geometric means of hormone concentrations were estimated using multivariable-adjusted analysis of variance, with and without adjustment for BMI.

Results

The associations between physical activity and hormones were modest and similar for objectively measured (accelerometer) and self-reported physical activity. Compared to men with the lowest objectively measured physical activity, men with high physical activity levels had 14% and 8% higher concentrations of SHBG and total testosterone, respectively, and these differences were attenuated to 6% and 3% following adjustment for BMI.

Conclusion

Our results suggest that the associations of physical activity with the hormones investigated are, at most, modest; and following adjustment for BMI, the small associations with SHBG and total testosterone were largely attenuated. Therefore, it is unlikely that changes in these circulating hormones explain the associations of physical activity with risk of cancer either independently or via BMI.",,pdf:https://link.springer.com/content/pdf/10.1007/s10552-021-01466-6.pdf; doi:https://doi.org/10.1007/s10552-021-01466-6; html:https://europepmc.org/articles/PMC8492588; pdf:https://europepmc.org/articles/PMC8492588?pdf=render 31073125,https://doi.org/10.1038/s41533-019-0132-z,Systematic review of clinical prediction models to support the diagnosis of asthma in primary care.,"Daines L, McLean S, Buelo A, Lewis S, Sheikh A, Pinnock H.",,NPJ primary care respiratory medicine,2019,2019-05-09,Y,,The Human Phenome,,"Diagnosing asthma is challenging. Misdiagnosis can lead to untreated symptoms, incorrect treatment and avoidable deaths. The best combination of clinical features and tests to achieve a diagnosis of asthma is unclear. As asthma is usually diagnosed in non-specialist settings, a clinical prediction model to aid the assessment of the probability of asthma in primary care may improve diagnostic accuracy. We aimed to identify and describe existing prediction models to support the diagnosis of asthma in children and adults in primary care. We searched Medline, Embase, CINAHL, TRIP and US National Guidelines Clearinghouse databases from 1 January 1990 to 23 November 17. We included prediction models designed for use in primary care or equivalent settings to aid the diagnostic decision-making of clinicians assessing patients with symptoms suggesting asthma. Two reviewers independently screened titles, abstracts and full texts for eligibility, extracted data and assessed risk of bias. From 13,798 records, 53 full-text articles were reviewed. We included seven modelling studies; all were at high risk of bias. Model performance varied, and the area under the receiving operating characteristic curve ranged from 0.61 to 0.82. Patient-reported wheeze, symptom variability and history of allergy or allergic rhinitis were associated with asthma. In conclusion, clinical prediction models may support the diagnosis of asthma in primary care, but existing models are at high risk of bias and thus unreliable for informing practice. Future studies should adhere to recognised standards, conduct model validation and include a broader range of clinical data to derive a prediction model of value for clinicians.",,pdf:https://www.nature.com/articles/s41533-019-0132-z.pdf; doi:https://doi.org/10.1038/s41533-019-0132-z; html:https://europepmc.org/articles/PMC6509212; pdf:https://europepmc.org/articles/PMC6509212?pdf=render +34216337,https://doi.org/10.1007/s10552-021-01466-6,"Physical activity in relation to circulating hormone concentrations in 117,100 men in UK Biobank.","Watts EL, Perez-Cornago A, Doherty A, Allen NE, Fensom GK, Tin Tin S, Key TJ, Travis RC.",,Cancer causes & control : CCC,2021,2021-07-03,Y,Testosterone; IGF-I; Physical Activity; Accelerometer; Shbg; Uk Biobank,,,"

Purpose

Physical activity may reduce the risk of some types of cancer in men. Biological mechanisms may involve changes in hormone concentrations; however, this relationship is not well established. Therefore, we aimed to investigate the associations of physical activity with circulating insulin-like growth factor-I (IGF-I), sex hormone-binding globulin (SHBG, which modifies sex hormone activity), and total and free testosterone concentrations, and the extent these associations might be mediated by body mass index (BMI).

Methods

Circulating concentrations of these hormones and anthropometric measurements and self-reported physical activity data were available for 117,100 healthy male UK Biobank participants at recruitment. Objectively measured accelerometer physical activity levels were also collected on average 5.7 years after recruitment in 28,000 men. Geometric means of hormone concentrations were estimated using multivariable-adjusted analysis of variance, with and without adjustment for BMI.

Results

The associations between physical activity and hormones were modest and similar for objectively measured (accelerometer) and self-reported physical activity. Compared to men with the lowest objectively measured physical activity, men with high physical activity levels had 14% and 8% higher concentrations of SHBG and total testosterone, respectively, and these differences were attenuated to 6% and 3% following adjustment for BMI.

Conclusion

Our results suggest that the associations of physical activity with the hormones investigated are, at most, modest; and following adjustment for BMI, the small associations with SHBG and total testosterone were largely attenuated. Therefore, it is unlikely that changes in these circulating hormones explain the associations of physical activity with risk of cancer either independently or via BMI.",,pdf:https://link.springer.com/content/pdf/10.1007/s10552-021-01466-6.pdf; doi:https://doi.org/10.1007/s10552-021-01466-6; html:https://europepmc.org/articles/PMC8492588; pdf:https://europepmc.org/articles/PMC8492588?pdf=render 32514173,https://doi.org/10.1038/s41591-020-0941-1,Developing specific reporting guidelines for diagnostic accuracy studies assessing AI interventions: The STARD-AI Steering Group.,"Sounderajah V, Ashrafian H, Aggarwal R, De Fauw J, Denniston AK, Greaves F, Karthikesalingam A, King D, Liu X, Markar SR, McInnes MDF, Panch T, Pearson-Stuttard J, Ting DSW, Golub RM, Moher D, Bossuyt PM, Darzi A.",,Nature medicine,2020,2020-06-01,N,,,,,,html:http://hdl.handle.net/10044/1/85586; doi:https://doi.org/10.1038/s41591-020-0941-1 31787481,https://doi.org/10.1016/j.schres.2019.10.061,Association of physical health multimorbidity with mortality in people with schizophrenia spectrum disorders: Using a novel semantic search system that captures physical diseases in electronic patient records.,"Kugathasan P, Wu H, Gaughran F, Nielsen RE, Pritchard M, Dobson R, Stewart R, Stubbs B.",,Schizophrenia research,2020,2019-11-28,N,Mortality; Schizophrenia; Somatic; Comorbidity; Severe Mental Illness,,,"

Objective

Single physical comorbidities have been associated with the premature mortality in people with schizophrenia-spectrum disorders (SSD). We investigated the association of physical multimorbidity (≥two physical health conditions) with mortality in people with SSD.

Methods

A retrospective cohort study between 2013 and 2017. All people with a diagnosis of SSD (ICD-10: F20-F29), who had contact with secondary mental healthcare within South London during 2011-2012 were included. A novel semantic search system captured conditions from electronic mental health records, and all-cause mortality were retrieved. Hazard ratios (HRs) and population attributable fractions (PAFs) were calculated for associations between physical multimorbidity and all-cause mortality.

Results

Among the 9775 people with SSD (mean (SD) age, 45.9 (15.4); males, 59.3%), 6262 (64%) had physical multimorbidity, and 880 (9%) died during the 5-year follow-up. The top three physical multimorbidity combinations with highest mortality were cardiovascular-respiratory (HR: 2.23; 95% CI, 1.49-3.32), respiratory-skin (HR: 2.06; 95% CI, 1.31-3.24), and respiratory-digestive (HR: 1.88; 95% CI, 1.14-3.11), when adjusted for age, gender, and all other physical disease systems. Combinations of physical diseases with highest PAFs were cardiovascular-respiratory (PAF: 35.7%), neurologic-respiratory (PAF: 32.7%), as well as respiratory-skin (PAF: 29.8%).

Conclusions

Approximately 2/3 of patients with SSD had physical multimorbidity and the risk of mortality in these patients was further increased compared to those with none or single physical conditions. These findings suggest that in order to reduce the physical health burden and subsequent mortality in people with SSD, proactive coordinated prevention and management efforts are required and should extend beyond the current focus on single physical comorbidities.",,pdf:https://www.pure.ed.ac.uk/ws/files/124987758/AAM_Association_of_physical_health_multimorbidity....pdf; doi:https://doi.org/10.1016/j.schres.2019.10.061 33024096,https://doi.org/10.1038/s41467-020-18783-0,Changing travel patterns in China during the early stages of the COVID-19 pandemic.,"Gibbs H, Liu Y, Pearson CAB, Jarvis CI, Grundy C, Quilty BJ, Diamond C, LSHTM CMMID COVID-19 working group, Eggo RM.",,Nature communications,2020,2020-10-06,Y,,,,"Understanding changes in human mobility in the early stages of the COVID-19 pandemic is crucial for assessing the impacts of travel restrictions designed to reduce disease spread. Here, relying on data from mainland China, we investigate the spatio-temporal characteristics of human mobility between 1st January and 1st March 2020, and discuss their public health implications. An outbound travel surge from Wuhan before travel restrictions were implemented was also observed across China due to the Lunar New Year, indicating that holiday travel may have played a larger role in mobility changes compared to impending travel restrictions. Holiday travel also shifted healthcare pressure related to COVID-19 towards locations with lower healthcare capacity. Network analyses showed no sign of major changes in the transportation network after Lunar New Year. Changes observed were temporary and did not lead to structural reorganisation of the transportation network during the study period.",,pdf:https://www.nature.com/articles/s41467-020-18783-0.pdf; doi:https://doi.org/10.1038/s41467-020-18783-0; html:https://europepmc.org/articles/PMC7538915; pdf:https://europepmc.org/articles/PMC7538915?pdf=render @@ -2189,8 +2189,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 33436814,https://doi.org/10.1038/s41598-020-80457-0,A natural language processing approach for identifying temporal disease onset information from mental healthcare text.,"Viani N, Botelle R, Kerwin J, Yin L, Patel R, Stewart R, Velupillai S.",,Scientific reports,2021,2021-01-12,Y,,,,"Receiving timely and appropriate treatment is crucial for better health outcomes, and research on the contribution of specific variables is essential. In the mental health domain, an important research variable is the date of psychosis symptom onset, as longer delays in treatment are associated with worse intervention outcomes. The growing adoption of electronic health records (EHRs) within mental health services provides an invaluable opportunity to study this problem at scale retrospectively. However, disease onset information is often only available in open text fields, requiring natural language processing (NLP) techniques for automated analyses. Since this variable can be documented at different points during a patient's care, NLP methods that model clinical and temporal associations are needed. We address the identification of psychosis onset by: 1) manually annotating a corpus of mental health EHRs with disease onset mentions, 2) modelling the underlying NLP problem as a paragraph classification approach, and 3) combining multiple onset paragraphs at the patient level to generate a ranked list of likely disease onset dates. For 22/31 test patients (71%) the correct onset date was found among the top-3 NLP predictions. The proposed approach was also applied at scale, allowing an onset date to be estimated for 2483 patients.",,pdf:https://www.nature.com/articles/s41598-020-80457-0.pdf; doi:https://doi.org/10.1038/s41598-020-80457-0; html:https://europepmc.org/articles/PMC7804184; pdf:https://europepmc.org/articles/PMC7804184?pdf=render 31196905,https://doi.org/10.1136/bmjopen-2019-028929,Recorded poor insight as a predictor of service use outcomes: cohort study of patients with first-episode psychosis in a large mental healthcare database.,"Ramu N, Kolliakou A, Sanyal J, Patel R, Stewart R.",,BMJ open,2019,2019-06-12,Y,Insight; Psychosis; Natural Language Processing; Mental Health Outcomes; Cris; Service Use Outcomes,Applied Analytics,,"

Objectives

To investigate recorded poor insight in relation to mental health and service use outcomes in a cohort with first-episode psychosis.

Design

We developed a natural language processing algorithm to ascertain statements of poor or diminished insight and tested this in a cohort of patients with first-episode psychosis.

Setting

The clinical record text at the South London and Maudsley National Health Service Trust in the UK was used.

Participants

We applied the algorithm to characterise a cohort of 2026 patients with first-episode psychosis attending an early intervention service.

Primary and secondary outcome measures

Recorded poor insight within 1 month of registration was investigated in relation to (1) incidence of psychiatric hospitalisation, (2) odds of legally enforced hospitalisation, (3) number of days spent as a mental health inpatient and (4) number of different antipsychotic agents prescribed; outcomes were measured over varying follow-up periods from 12 months to 60 months, adjusting for a range of sociodemographic and clinical covariates.

Results

Recorded poor insight, present in 48.9% of the sample, was positively associated with youngest and oldest age groups, unemployment and schizophrenia (compared with bipolar disorder) and was negatively associated with Asian ethnicity, married status, home ownership and recorded cannabis use. It was significantly associated with higher levels of all four outcomes over the succeeding 12 months. Associations with hospitalisation incidence and number of antipsychotics remained independently significant when measured over 60 and 48 months, respectively.

Conclusions

Recorded poor insight in people with recent onset psychosis predicted higher subsequent inpatient mental healthcare use. Improving insight might benefit patients' course of illness as well as reduce mental health service use.",,pdf:https://bmjopen.bmj.com/content/bmjopen/9/6/e028929.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-028929; html:https://europepmc.org/articles/PMC6577359; pdf:https://europepmc.org/articles/PMC6577359?pdf=render 32032817,https://doi.org/10.1016/j.nicl.2020.102172,Distinguishing between paediatric brain tumour types using multi-parametric magnetic resonance imaging and machine learning: A multi-site study.,"Grist JT, Withey S, MacPherson L, Oates A, Powell S, Novak J, Abernethy L, Pizer B, Grundy R, Bailey S, Mitra D, Arvanitis TN, Auer DP, Avula S, Peet AC.",,NeuroImage. Clinical,2020,2020-01-23,Y,Diffusion; Perfusion; Machine Learning,Understanding the Causes of Disease,cancer and neoplasms,"The imaging and subsequent accurate diagnosis of paediatric brain tumours presents a radiological challenge, with magnetic resonance imaging playing a key role in providing tumour specific imaging information. Diffusion weighted and perfusion imaging are commonly used to aid the non-invasive diagnosis of children's brain tumours, but are usually evaluated by expert qualitative review. Quantitative studies are mainly single centre and single modality. The aim of this work was to combine multi-centre diffusion and perfusion imaging, with machine learning, to develop machine learning based classifiers to discriminate between three common paediatric tumour types. The results show that diffusion and perfusion weighted imaging of both the tumour and whole brain provide significant features which differ between tumour types, and that combining these features gives the optimal machine learning classifier with >80% predictive precision. This work represents a step forward to aid in the non-invasive diagnosis of paediatric brain tumours, using advanced clinical imaging.",Grist et al. team trained computers to analyse brain images from children for identification of tumours. They’ve shown that applying analytical methods to enable machine distinguishes between the entire brain area and the tumour area in the images more than 80% improves how machine analyses the image to identify exact tumour area. ,doi:https://doi.org/10.1016/j.nicl.2020.102172; doi:https://doi.org/10.1016/j.nicl.2020.102172; html:https://europepmc.org/articles/PMC7005468; pdf:https://europepmc.org/articles/PMC7005468?pdf=render -35322056,https://doi.org/10.1038/s41598-022-08351-5,Automated quality assessment of large digitised histology cohorts by artificial intelligence.,"Haghighat M, Browning L, Sirinukunwattana K, Malacrino S, Khalid Alham N, Colling R, Cui Y, Rakha E, Hamdy FC, Verrill C, Rittscher J.",,Scientific reports,2022,2022-03-23,Y,,,,"Research using whole slide images (WSIs) of histopathology slides has increased exponentially over recent years. Glass slides from retrospective cohorts, some with patient follow-up data are digitised for the development and validation of artificial intelligence (AI) tools. Such resources, therefore, become very important, with the need to ensure that their quality is of the standard necessary for downstream AI development. However, manual quality control of large cohorts of WSIs by visual assessment is unfeasible, and whilst quality control AI algorithms exist, these focus on bespoke aspects of image quality, e.g. focus, or use traditional machine-learning methods, which are unable to classify the range of potential image artefacts that should be considered. In this study, we have trained and validated a multi-task deep neural network to automate the process of quality control of a large retrospective cohort of prostate cases from which glass slides have been scanned several years after production, to determine both the usability of the images at the diagnostic level (considered in this study to be the minimal standard for research) and the common image artefacts present. Using a two-layer approach, quality overlays of WSIs were generated from a quality assessment (QA) undertaken at patch-level at [Formula: see text] magnification. From these quality overlays the slide-level quality scores were predicted and then compared to those generated by three specialist urological pathologists, with a Pearson correlation of 0.89 for overall 'usability' (at a diagnostic level), and 0.87 and 0.82 for focus and H&E staining quality scores respectively. To demonstrate its wider potential utility, we subsequently applied our QA pipeline to the TCGA prostate cancer cohort and to a colorectal cancer cohort, for comparison. Our model, designated as PathProfiler, indicates comparable predicted usability of images from the cohorts assessed (86-90% of WSIs predicted to be usable), and perhaps more significantly is able to predict WSIs that could benefit from an intervention such as re-scanning or re-staining for quality improvement. We have shown in this study that AI can be used to automate the process of quality control of large retrospective WSI cohorts to maximise their utility for research.",,pdf:https://www.nature.com/articles/s41598-022-08351-5.pdf; doi:https://doi.org/10.1038/s41598-022-08351-5; html:https://europepmc.org/articles/PMC8943120; pdf:https://europepmc.org/articles/PMC8943120?pdf=render 33012285,https://doi.org/10.1186/s12916-020-01779-4,The impact of COVID-19 control measures on social contacts and transmission in Kenyan informal settlements.,"Quaife M, van Zandvoort K, Gimma A, Shah K, McCreesh N, Prem K, Barasa E, Mwanga D, Kangwana B, Pinchoff J, CMMID COVID-19 Working Group, Edmunds WJ, Jarvis CI, Austrian K.",,BMC medicine,2020,2020-10-05,Y,Social Contacts; Covid-19; Sars-cov-2; Physical Distancing,,,"

Background

Many low- and middle-income countries have implemented control measures against coronavirus disease 2019 (COVID-19). However, it is not clear to what extent these measures explain the low numbers of recorded COVID-19 cases and deaths in Africa. One of the main aims of control measures is to reduce respiratory pathogen transmission through direct contact with others. In this study, we collect contact data from residents of informal settlements around Nairobi, Kenya, to assess if control measures have changed contact patterns, and estimate the impact of changes on the basic reproduction number (R0).

Methods

We conducted a social contact survey with 213 residents of five informal settlements around Nairobi in early May 2020, 4 weeks after the Kenyan government introduced enhanced physical distancing measures and a curfew between 7 pm and 5 am. Respondents were asked to report all direct physical and non-physical contacts made the previous day, alongside a questionnaire asking about the social and economic impact of COVID-19 and control measures. We examined contact patterns by demographic factors, including socioeconomic status. We described the impact of COVID-19 and control measures on income and food security. We compared contact patterns during control measures to patterns from non-pandemic periods to estimate the change in R0.

Results

We estimate that control measures reduced physical contacts by 62% and non-physical contacts by either 63% or 67%, depending on the pre-COVID-19 comparison matrix used. Masks were worn by at least one person in 92% of contacts. Respondents in the poorest socioeconomic quintile reported 1.5 times more contacts than those in the richest. Eighty-six percent of respondents reported a total or partial loss of income due to COVID-19, and 74% reported eating less or skipping meals due to having too little money for food.

Conclusion

COVID-19 control measures have had a large impact on direct contacts and therefore transmission, but have also caused considerable economic and food insecurity. Reductions in R0 are consistent with the comparatively low epidemic growth in Kenya and other sub-Saharan African countries that implemented similar, early control measures. However, negative and inequitable impacts on economic and food security may mean control measures are not sustainable in the longer term.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01779-4; doi:https://doi.org/10.1186/s12916-020-01779-4; html:https://europepmc.org/articles/PMC7533154; pdf:https://europepmc.org/articles/PMC7533154?pdf=render +35322056,https://doi.org/10.1038/s41598-022-08351-5,Automated quality assessment of large digitised histology cohorts by artificial intelligence.,"Haghighat M, Browning L, Sirinukunwattana K, Malacrino S, Khalid Alham N, Colling R, Cui Y, Rakha E, Hamdy FC, Verrill C, Rittscher J.",,Scientific reports,2022,2022-03-23,Y,,,,"Research using whole slide images (WSIs) of histopathology slides has increased exponentially over recent years. Glass slides from retrospective cohorts, some with patient follow-up data are digitised for the development and validation of artificial intelligence (AI) tools. Such resources, therefore, become very important, with the need to ensure that their quality is of the standard necessary for downstream AI development. However, manual quality control of large cohorts of WSIs by visual assessment is unfeasible, and whilst quality control AI algorithms exist, these focus on bespoke aspects of image quality, e.g. focus, or use traditional machine-learning methods, which are unable to classify the range of potential image artefacts that should be considered. In this study, we have trained and validated a multi-task deep neural network to automate the process of quality control of a large retrospective cohort of prostate cases from which glass slides have been scanned several years after production, to determine both the usability of the images at the diagnostic level (considered in this study to be the minimal standard for research) and the common image artefacts present. Using a two-layer approach, quality overlays of WSIs were generated from a quality assessment (QA) undertaken at patch-level at [Formula: see text] magnification. From these quality overlays the slide-level quality scores were predicted and then compared to those generated by three specialist urological pathologists, with a Pearson correlation of 0.89 for overall 'usability' (at a diagnostic level), and 0.87 and 0.82 for focus and H&E staining quality scores respectively. To demonstrate its wider potential utility, we subsequently applied our QA pipeline to the TCGA prostate cancer cohort and to a colorectal cancer cohort, for comparison. Our model, designated as PathProfiler, indicates comparable predicted usability of images from the cohorts assessed (86-90% of WSIs predicted to be usable), and perhaps more significantly is able to predict WSIs that could benefit from an intervention such as re-scanning or re-staining for quality improvement. We have shown in this study that AI can be used to automate the process of quality control of large retrospective WSI cohorts to maximise their utility for research.",,pdf:https://www.nature.com/articles/s41598-022-08351-5.pdf; doi:https://doi.org/10.1038/s41598-022-08351-5; html:https://europepmc.org/articles/PMC8943120; pdf:https://europepmc.org/articles/PMC8943120?pdf=render 32360702,https://doi.org/10.1016/j.ijcard.2020.04.068,Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum: A blueprint for clinical trial design.,"Savarese G, Settergren C, Schrage B, Thorvaldsen T, Löfman I, Sartipy U, Mellbin L, Meyers A, Farsani SF, Brueckmann M, Brodovicz KG, Vedin O, Asselbergs FW, Dahlström U, Cosentino F, Lund LH.",,International journal of cardiology,2020,2020-04-30,N,Type 2 diabetes mellitus; Atrial fibrillation; Ejection fraction; Heart Failure; Chronic Kidney Disease; Trial Design,,,"

Background

Comorbidities may differently affect treatment response and cause-specific outcomes in heart failure (HF) with preserved (HFpEF) vs. mid-range/mildly-reduced (HFmrEF) vs. reduced (HFrEF) ejection fraction (EF), complicating trial design. In patients with HF, we performed a comprehensive analysis of type 2 diabetes (T2DM), atrial fibrillation (AF) chronic kidney disease (CKD), and cause-specific outcomes.

Methods and results

Of 42,583 patients from the Swedish HF registry (23% HFpEF, 21% HFmrEF, 56% HFrEF), 24% had T2DM, 51% CKD, 56% AF, and 8% all three comorbidities. HFpEF had higher prevalence of CKD and AF, HFmrEF had intermediate prevalence of AF, and prevalence of T2DM was similar across the EF spectrum. Patients with T2DM, AF and/or CKD were more likely to have also other comorbidities and more severe HF. Risk of cardiovascular (CV) events was highest in HFrEF vs. HFpEF and HFmrEF; non-CV risk was highest in HFpEF vs. HFmrEF vs. HFrEF. T2DM increased CV and non-CV events similarly but less so in HFpEF. CKD increased CV events somewhat more than non-CV events and less so in HFpEF. AF increased CV events considerably more than non-CV events and more so in HFpEF and HFmrEF.

Conclusion

HFpEF is distinguished from HFmrEF and HFrEF by more comorbidities, non-CV events, but lower effect of T2DM and CKD on events. CV events are most frequent in HFrEF. To enrich for CV vs. non-CV events, trialists should not exclude patients with lower EF, AF and/or CKD, who report higher CV risk.",,pdf:http://www.internationaljournalofcardiology.com/article/S016752732031679X/pdf; doi:https://doi.org/10.1016/j.ijcard.2020.04.068 34503493,https://doi.org/10.1186/s12916-021-02107-0,"Estimating the impact of reopening schools on the reproduction number of SARS-CoV-2 in England, using weekly contact survey data.","Munday JD, Jarvis CI, Gimma A, Wong KLM, van Zandvoort K, CMMID COVID-19 Working Group, Funk S, Edmunds WJ.",,BMC medicine,2021,2021-09-10,Y,School Closure; Reproduction Number; Social Contacts; Covid-19; Sars-cov-2; Comix,,,"

Background

Schools were closed in England on 4 January 2021 as part of increased national restrictions to curb transmission of SARS-CoV-2. The UK government reopened schools on 8 March. Although there was evidence of lower individual-level transmission risk amongst children compared to adults, the combined effects of this with increased contact rates in school settings and the resulting impact on the overall transmission rate in the population were not clear.

Methods

We measured social contacts of > 5000 participants weekly from March 2020, including periods when schools were both open and closed, amongst other restrictions. We combined these data with estimates of the susceptibility and infectiousness of children compared with adults to estimate the impact of reopening schools on the reproduction number.

Results

Our analysis indicates that reopening all schools under the same measures as previous periods that combined lockdown with face-to-face schooling would be likely to increase the reproduction number substantially. Assuming a baseline of 0.8, we estimated a likely increase to between 1.0 and 1.5 with the reopening of all schools or to between 0.9 and 1.2 reopening primary or secondary schools alone.

Conclusion

Our results suggest that reopening schools would likely halt the fall in cases observed between January and March 2021 and would risk a return to rising infections, but these estimates relied heavily on the latest estimates or reproduction number and the validity of the susceptibility and infectiousness profiles we used at the time of reopening.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02107-0; doi:https://doi.org/10.1186/s12916-021-02107-0; html:https://europepmc.org/articles/PMC8428960; pdf:https://europepmc.org/articles/PMC8428960?pdf=render 33004356,https://doi.org/10.3399/bjgp20x712673,First do no harm: valproate and medicines safety in pregnancy.,"Robson J, Moss N, McGettigan P, Beardsley SJ, Lovegrove E, Dezateux C.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2020,2020-10-01,N,,,,,,pdf:https://bjgp.org/content/bjgp/70/699/477.full.pdf; doi:https://doi.org/10.3399/bjgp20X712673; html:https://europepmc.org/articles/PMC7518898; pdf:https://europepmc.org/articles/PMC7518898?pdf=render; doi:https://doi.org/10.3399/bjgp20x712673 @@ -2202,8 +2202,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 32305733,https://doi.org/10.1016/j.atherosclerosis.2020.03.022,The relation between healthy lifestyle changes and decrease in systemic inflammation in patients with stable cardiovascular disease.,"van 't Klooster CC, van der Graaf Y, Ridker PM, Westerink J, Hjortnaes J, Sluijs I, Asselbergs FW, Bots ML, Kappelle LJ, Visseren FLJ, UCC-SMART study group.",,Atherosclerosis,2020,2020-04-06,N,C-reactive Protein; Lifestyle Changes; Low-grade Inflammation; Patients With Stable Cardiovascular Disease,,,"

Background and aims

Pharmacological lowering of inflammation has proven effective in reducing recurrent cardiovascular event rates. Aim of the current study is to evaluate lifestyle changes (smoking cessation, weight loss, physical activity level increase, alcohol moderation, and a summary lifestyle improvement score) in relation to change in plasma C-reactive protein (CRP) concentration in patients with established cardiovascular disease.

Methods

In total, 1794 patients from the UCC-SMART cohort with stable cardiovascular disease and CRP levels ≤10 mg/L, who returned for a follow-up study visit after median 9.9 years (IQR 5.4-10.8), were included. The relation between changes in smoking status, weight, physical activity, alcohol consumption, a summary lifestyle improvement score and change in plasma CRP concentration was evaluated with linear regression analyses.

Results

Smoking cessation was related to a 0.40 mg/L decline in CRP concentration (β-coefficient -0.40; 95%CI -0.73,-0.07). Weight loss (per 1SD = 6.4 kg) and increase in physical activity (per 1 SD = 48 MET hours per week) were related to a decrease in CRP concentration (β-coefficients -0.25; 95%CI -0.33,-0.16 and -0.09; 95%CI -0.17,-0.01 per SD). Change in alcohol consumption was not related to CRP difference. Every point higher in the summary lifestyle improvement score was related to a decrease in CRP concentration of 0.17 mg/L (β-coefficient -0.17; 95%CI -0.26,-0.07).

Conclusions

Smoking cessation, increase in physical activity, and weight loss are related to a decrease in CRP concentration in patients with stable cardiovascular disease. Patients with the highest summary lifestyle improvement score have the most decrease in CRP concentration. These results may indicate that healthy lifestyle changes contribute to lowering systemic inflammation, potentially leading to a lower cardiovascular risk in patients with established cardiovascular disease.",,pdf:http://www.atherosclerosis-journal.com/article/S0021915020301763/pdf; doi:https://doi.org/10.1016/j.atherosclerosis.2020.03.022 35584845,https://doi.org/10.1136/bmj-2022-070904,Reporting guideline for the early stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI.,"Vasey B, Nagendran M, Campbell B, Clifton DA, Collins GS, Denaxas S, Denniston AK, Faes L, Geerts B, Ibrahim M, Liu X, Mateen BA, Mathur P, McCradden MD, Morgan L, Ordish J, Rogers C, Saria S, Ting DSW, Watkinson P, Weber W, Wheatstone P, McCulloch P, DECIDE-AI expert group.",,BMJ (Clinical research ed.),2022,2022-05-18,Y,,,,,,pdf:https://www.bmj.com/content/bmj/377/bmj-2022-070904.full.pdf; doi:https://doi.org/10.1136/bmj-2022-070904; html:https://europepmc.org/articles/PMC9116198 32080192,https://doi.org/10.1038/s41467-020-14717-y,Author Correction: Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke.,"Abraham G, Malik R, Yonova-Doing E, Salim A, Wang T, Danesh J, Butterworth AS, Howson JMM, Inouye M, Dichgans M.",,Nature communications,2020,2020-02-20,Y,,,,An amendment to this paper has been published and can be accessed via a link at the top of the paper.,,pdf:https://www.nature.com/articles/s41467-020-14717-y.pdf; doi:https://doi.org/10.1038/s41467-020-14717-y; html:https://europepmc.org/articles/PMC7033171; pdf:https://europepmc.org/articles/PMC7033171?pdf=render -33617936,https://doi.org/10.1016/j.jhin.2021.02.012,Global and national estimates of the number of healthcare workers at high risk of SARS-CoV-2 infection.,"McCarthy CV, Sandmann FG, CMMID COVID-19 Working Group, Jit M.",,The Journal of hospital infection,2021,2021-02-20,Y,,,,,,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4660358/1/Global%20and%20national%20estimates%20of%20the%20number%20of%20healthcare%20workers%20at%20high%20risk%20of%20SARS-CoV-2%20infection.pdf; doi:https://doi.org/10.1016/j.jhin.2021.02.012; html:https://europepmc.org/articles/PMC7896121; pdf:https://europepmc.org/articles/PMC7896121?pdf=render 33714592,https://doi.org/10.1016/j.mayocp.2021.02.007,"Place and Underlying Cause of Death During the COVID-19 Pandemic: Retrospective Cohort Study of 3.5 Million Deaths in England and Wales, 2014 to 2020.","Wu J, Mafham M, Mamas MA, Rashid M, Kontopantelis E, Deanfield JE, de Belder MA, Gale CP.",,Mayo Clinic proceedings,2021,2021-02-16,Y,,,,"

Objective

To describe the place and cause of death during the coronavirus disease 2019 (COVID-19) pandemic to assess its impact on excess mortality.

Methods

This national death registry included all adult (aged ≥18 years) deaths in England and Wales between January 1, 2014, and June 30, 2020. Daily deaths during the COVID-19 pandemic were compared against the expected daily deaths, estimated with use of the Farrington surveillance algorithm for daily historical data between 2014 and 2020 by place and cause of death.

Results

Between March 2 and June 30, 2020, there was an excess mortality of 57,860 (a proportional increase of 35%) compared with the expected deaths, of which 50,603 (87%) were COVID-19 related. At home, only 14% (2267) of the 16,190 excess deaths were related to COVID-19, with 5963 deaths due to cancer and 2485 deaths due to cardiac disease, few of which involved COVID-19. In care homes or hospices, 61% (15,623) of the 25,611 excess deaths were related to COVID-19, 5539 of which were due to respiratory disease, and most of these (4315 deaths) involved COVID-19. In the hospital, there were 16,174 fewer deaths than expected that did not involve COVID-19, with 4088 fewer deaths due to cancer and 1398 fewer deaths due to cardiac disease than expected.

Conclusion

The COVID-19 pandemic has resulted in a large excess of deaths in care homes that were poorly characterized and likely to be the result of undiagnosed COVID-19. There was a smaller but important and ongoing excess in deaths at home, particularly from cancer and cardiac disease, suggesting public avoidance of hospital care for non-COVID-19 conditions.",,pdf:http://www.mayoclinicproceedings.org/article/S0025619621001397/pdf; doi:https://doi.org/10.1016/j.mayocp.2021.02.007; html:https://europepmc.org/articles/PMC7885692; pdf:https://europepmc.org/articles/PMC7885692?pdf=render +33617936,https://doi.org/10.1016/j.jhin.2021.02.012,Global and national estimates of the number of healthcare workers at high risk of SARS-CoV-2 infection.,"McCarthy CV, Sandmann FG, CMMID COVID-19 Working Group, Jit M.",,The Journal of hospital infection,2021,2021-02-20,Y,,,,,,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4660358/1/Global%20and%20national%20estimates%20of%20the%20number%20of%20healthcare%20workers%20at%20high%20risk%20of%20SARS-CoV-2%20infection.pdf; doi:https://doi.org/10.1016/j.jhin.2021.02.012; html:https://europepmc.org/articles/PMC7896121; pdf:https://europepmc.org/articles/PMC7896121?pdf=render 38448586,https://doi.org/10.1038/s41586-024-07148-y,Genome-wide characterization of circulating metabolic biomarkers.,"Karjalainen MK, Karthikeyan S, Oliver-Williams C, Sliz E, Allara E, Fung WT, Surendran P, Zhang W, Jousilahti P, Kristiansson K, Salomaa V, Goodwin M, Hughes DA, Boehnke M, Fernandes Silva L, Yin X, Mahajan A, Neville MJ, van Zuydam NR, de Mutsert R, Li-Gao R, Mook-Kanamori DO, Demirkan A, Liu J, Noordam R, Trompet S, Chen Z, Kartsonaki C, Li L, Lin K, Hagenbeek FA, Hottenga JJ, Pool R, Ikram MA, van Meurs J, Haller T, Milaneschi Y, Kähönen M, Mishra PP, Joshi PK, Macdonald-Dunlop E, Mangino M, Zierer J, Acar IE, Hoyng CB, Lechanteur YTE, Franke L, Kurilshikov A, Zhernakova A, Beekman M, van den Akker EB, Kolcic I, Polasek O, Rudan I, Gieger C, Waldenberger M, Asselbergs FW, China Kadoorie Biobank Collaborative Group, Estonian Biobank Research Team, FinnGen, Hayward C, Fu J, den Hollander AI, Menni C, Spector TD, Wilson JF, Lehtimäki T, Raitakari OT, Penninx BWJH, Esko T, Walters RG, Jukema JW, Sattar N, Ghanbari M, Willems van Dijk K, Karpe F, McCarthy MI, Laakso M, Järvelin MR, Timpson NJ, Perola M, Kooner JS, Chambers JC, van Duijn C, Slagboom PE, Boomsma DI, Danesh J, Ala-Korpela M, Butterworth AS, Kettunen J.",,Nature,2024,2024-03-06,Y,,,,"Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism1-7. This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases8-11. Here we present a genome-wide association study for 233 circulating metabolic traits quantified by nuclear magnetic resonance spectroscopy in up to 136,016 participants from 33 cohorts. We identify more than 400 independent loci and assign probable causal genes at two-thirds of these using manual curation of plausible biological candidates. We highlight the importance of sample and participant characteristics that can have significant effects on genetic associations. We use detailed metabolic profiling of lipoprotein- and lipid-associated variants to better characterize how known lipid loci and novel loci affect lipoprotein metabolism at a granular level. We demonstrate the translational utility of comprehensively phenotyped molecular data, characterizing the metabolic associations of intrahepatic cholestasis of pregnancy. Finally, we observe substantial genetic pleiotropy for multiple metabolic pathways and illustrate the importance of careful instrument selection in Mendelian randomization analysis, revealing a putative causal relationship between acetone and hypertension. Our publicly available results provide a foundational resource for the community to examine the role of metabolism across diverse diseases.",,pdf:https://www.nature.com/articles/s41586-024-07148-y.pdf; doi:https://doi.org/10.1038/s41586-024-07148-y; html:https://europepmc.org/articles/PMC10990933; pdf:https://europepmc.org/articles/PMC10990933?pdf=render 33430602,https://doi.org/10.1161/circheartfailure.120.007022,Proteomic and Functional Studies Reveal Detyrosinated Tubulin as Treatment Target in Sarcomere Mutation-Induced Hypertrophic Cardiomyopathy.,"Schuldt M, Pei J, Harakalova M, Dorsch LM, Schlossarek S, Mokry M, Knol JC, Pham TV, Schelfhorst T, Piersma SR, Dos Remedios C, Dalinghaus M, Michels M, Asselbergs FW, Moutin MJ, Carrier L, Jimenez CR, van der Velden J, Kuster DWD.",,Circulation. Heart failure,2021,2021-01-12,Y,Mutation; Genotype; Tubulin; Heart diseases; Proteomics; Treatment; Cardiomyopathies,,,"

Background

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. While ≈50% of patients with HCM carry a sarcomere gene mutation (sarcomere mutation-positive, HCMSMP), the genetic background is unknown in the other half of the patients (sarcomere mutation-negative, HCMSMN). Genotype-specific differences have been reported in cardiac function. Moreover, HCMSMN patients have later disease onset and a better prognosis than HCMSMP patients. To define if genotype-specific derailments at the protein level may explain the heterogeneity in disease development, we performed a proteomic analysis in cardiac tissue from a clinically well-phenotyped HCM patient group.

Methods

A proteomics screen was performed in cardiac tissue from 39 HCMSMP patients, 11HCMSMN patients, and 8 nonfailing controls. Patients with HCM had obstructive cardiomyopathy with left ventricular outflow tract obstruction and diastolic dysfunction. A novel MYBPC32373insG mouse model was used to confirm functional relevance of our proteomic findings.

Results

In all HCM patient samples, we found lower levels of metabolic pathway proteins and higher levels of extracellular matrix proteins. Levels of total and detyrosinated α-tubulin were markedly higher in HCMSMP than in HCMSMN and controls. Higher tubulin detyrosination was also found in 2 unrelated MYBPC3 mouse models and its inhibition with parthenolide normalized contraction and relaxation time of isolated cardiomyocytes.

Conclusions

Our findings indicate that microtubules and especially its detyrosination contribute to the pathomechanism of patients with HCMSMP. This is of clinical importance since it represents a potential treatment target to improve cardiac function in patients with HCMSMP, whereas a beneficial effect may be limited in patients with HCMSMN.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCHEARTFAILURE.120.007022; doi:https://doi.org/10.1161/CIRCHEARTFAILURE.120.007022; html:https://europepmc.org/articles/PMC7819533; pdf:https://europepmc.org/articles/PMC7819533?pdf=render 35605170,https://doi.org/10.2196/37668,Differences in Clinical Presentation With Long COVID After Community and Hospital Infection and Associations With All-Cause Mortality: English Sentinel Network Database Study.,"Meza-Torres B, Delanerolle G, Okusi C, Mayor N, Anand S, Macartney J, Gatenby P, Glampson B, Chapman M, Curcin V, Mayer E, Joy M, Greenhalgh T, Delaney B, de Lusignan S.",,JMIR public health and surveillance,2022,2022-08-16,Y,Phenotype; Hospitalization; Social Class; General Practitioners; Ethnicity; Medical Record Systems; Covid-19; Sars-cov-2; Systematized Nomenclature Of Medicine; Biomedical Ontologies; Post–acute Covid-19 Syndrome; Data Extracts; Computerized; Data Accuracy; Long Covid; Post–covid-19 Syndrome,,,"

Background

Most studies of long COVID (symptoms of COVID-19 infection beyond 4 weeks) have focused on people hospitalized in their initial illness. Long COVID is thought to be underrecorded in UK primary care electronic records.

Objective

We sought to determine which symptoms people present to primary care after COVID-19 infection and whether presentation differs in people who were not hospitalized, as well as post-long COVID mortality rates.

Methods

We used routine data from the nationally representative primary care sentinel cohort of the Oxford-Royal College of General Practitioners Research and Surveillance Centre (N=7,396,702), applying a predefined long COVID phenotype and grouped by whether the index infection occurred in hospital or in the community. We included COVID-19 infection cases from March 1, 2020, to April 1, 2021. We conducted a before-and-after analysis of long COVID symptoms prespecified by the Office of National Statistics, comparing symptoms presented between 1 and 6 months after the index infection matched with the same months 1 year previously. We conducted logistic regression analysis, quoting odds ratios (ORs) with 95% CIs.

Results

In total, 5.63% (416,505/7,396,702) and 1.83% (7623/416,505) of the patients had received a coded diagnosis of COVID-19 infection and diagnosis of, or referral for, long COVID, respectively. People with diagnosis or referral of long COVID had higher odds of presenting the prespecified symptoms after versus before COVID-19 infection (OR 2.66, 95% CI 2.46-2.88, for those with index community infection and OR 2.42, 95% CI 2.03-2.89, for those hospitalized). After an index community infection, patients were more likely to present with nonspecific symptoms (OR 3.44, 95% CI 3.00-3.95; P<.001) compared with after a hospital admission (OR 2.09, 95% CI 1.56-2.80; P<.001). Mental health sequelae were more strongly associated with index hospital infections (OR 2.21, 95% CI 1.64-2.96) than with index community infections (OR 1.36, 95% CI 1.21-1.53; P<.001). People presenting to primary care after hospital infection were more likely to be men (OR 1.43, 95% CI 1.25-1.64; P<.001), more socioeconomically deprived (OR 1.42, 95% CI 1.24-1.63; P<.001), and with higher multimorbidity scores (OR 1.41, 95% CI 1.26-1.57; P<.001) than those presenting after an index community infection. All-cause mortality in people with long COVID was associated with increasing age, male sex (OR 3.32, 95% CI 1.34-9.24; P=.01), and higher multimorbidity score (OR 2.11, 95% CI 1.34-3.29; P<.001). Vaccination was associated with reduced odds of mortality (OR 0.10, 95% CI 0.03-0.35; P<.001).

Conclusions

The low percentage of people recorded as having long COVID after COVID-19 infection reflects either low prevalence or underrecording. The characteristics and comorbidities of those presenting with long COVID after a community infection are different from those hospitalized. This study provides insights into the presentation of long COVID in primary care and implications for workload.",,pdf:https://publichealth.jmir.org/2022/8/e37668/PDF; doi:https://doi.org/10.2196/37668; html:https://europepmc.org/articles/PMC9384859 @@ -2215,8 +2215,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 35545669,https://doi.org/10.1038/s41586-022-04712-2,Genetic and chemotherapeutic influences on germline hypermutation.,"Kaplanis J, Ide B, Sanghvi R, Neville M, Danecek P, Coorens T, Prigmore E, Short P, Gallone G, McRae J, Genomics England Research Consortium, Carmichael J, Barnicoat A, Firth H, O'Brien P, Rahbari R, Hurles M.",,Nature,2022,2022-05-11,Y,,,,"Mutations in the germline generates all evolutionary genetic variation and is a cause of genetic disease. Parental age is the primary determinant of the number of new germline mutations in an individual's genome1,2. Here we analysed the genome-wide sequences of 21,879 families with rare genetic diseases and identified 12 individuals with a hypermutated genome with between two and seven times more de novo single-nucleotide variants than expected. In most families (9 out of 12), the excess mutations came from the father. Two families had genetic drivers of germline hypermutation, with fathers carrying damaging genetic variation in DNA-repair genes. For five of the families, paternal exposure to chemotherapeutic agents before conception was probably a key driver of hypermutation. Our results suggest that the germline is well protected from mutagenic effects, hypermutation is rare, the number of excess mutations is relatively modest and most individuals with a hypermutated genome will not have a genetic disease.",,pdf:https://www.nature.com/articles/s41586-022-04712-2.pdf; doi:https://doi.org/10.1038/s41586-022-04712-2; html:https://europepmc.org/articles/PMC9117138; pdf:https://europepmc.org/articles/PMC9117138?pdf=render 33602244,https://doi.org/10.1186/s12916-021-01924-7,The impact of local and national restrictions in response to COVID-19 on social contacts in England: a longitudinal natural experiment.,"Jarvis CI, Gimma A, van Zandvoort K, Wong KLM, CMMID COVID-19 working group, Edmunds WJ.",,BMC medicine,2021,2021-02-19,Y,Pandemic; England; United Kingdom; Disease Outbreak; Non-pharmaceutical Interventions; Covid-19; Contact Survey; Lockdowns,,,"

Background

England's COVID-19 response transitioned from a national lockdown to localised interventions. In response to rising cases, these were supplemented by national restrictions on contacts (the Rule of Six), then 10 pm closing for bars and restaurants, and encouragement to work from home. These were quickly followed by a 3-tier system applying different restrictions in different localities. As cases continued to rise, a second national lockdown was declared. We used a national survey to quantify the impact of these restrictions on epidemiologically relevant contacts.

Methods

We compared paired measures on setting-specific contacts before and after each restriction started and tested for differences using paired permutation tests on the mean change in contacts and the proportion of individuals decreasing their contacts.

Results

Following the imposition of each measure, individuals tended to report fewer contacts than they had before. However, the magnitude of the changes was relatively small and variable. For instance, although early closure of bars and restaurants appeared to have no measurable effect on contacts, the work from home directive reduced mean daily work contacts by 0.99 (95% confidence interval CI] 0.03-1.94), and the Rule of Six reduced non-work and school contacts by a mean of 0.25 (0.01-0.5) per day. Whilst Tier 3 appeared to also reduce non-work and school contacts, the evidence for an effect of the lesser restrictions (Tiers 1 and 2) was much weaker. There may also have been some evidence of saturation of effects, with those who were in Tier 1 (least restrictive) reducing their contacts markedly when they entered lockdown, which was not reflected in similar changes in those who were already under tighter restrictions (Tiers 2 and 3).

Conclusions

The imposition of various local and national measures in England during the summer and autumn of 2020 has gradually reduced contacts. However, these changes are smaller than the initial lockdown in March. This may partly be because many individuals were already starting from a lower number of contacts.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-01924-7; doi:https://doi.org/10.1186/s12916-021-01924-7; html:https://europepmc.org/articles/PMC7892289; pdf:https://europepmc.org/articles/PMC7892289?pdf=render 33531015,https://doi.org/10.1186/s12916-021-01906-9,The importance of supplementary immunisation activities to prevent measles outbreaks during the COVID-19 pandemic in Kenya.,"Mburu CN, Ojal J, Chebet R, Akech D, Karia B, Tuju J, Sigilai A, Abbas K, Jit M, Funk S, Smits G, van Gageldonk PGM, van der Klis FRM, Tabu C, Nokes DJ, LSHTM CMMID COVID-19 Working Group, Scott J, Flasche S, Adetifa I.",,BMC medicine,2021,2021-02-03,Y,outbreak; Measles; Vaccination Coverage; Supplementary Immunisation Activities; Covid-19,,,"

Background

The COVID-19 pandemic has disrupted routine measles immunisation and supplementary immunisation activities (SIAs) in most countries including Kenya. We assessed the risk of measles outbreaks during the pandemic in Kenya as a case study for the African Region.

Methods

Combining measles serological data, local contact patterns, and vaccination coverage into a cohort model, we predicted the age-adjusted population immunity in Kenya and estimated the probability of outbreaks when contact-reducing COVID-19 interventions are lifted. We considered various scenarios for reduced measles vaccination coverage from April 2020.

Results

In February 2020, when a scheduled SIA was postponed, population immunity was close to the herd immunity threshold and the probability of a large outbreak was 34% (8-54). As the COVID-19 contact restrictions are nearly fully eased, from December 2020, the probability of a large measles outbreak will increase to 38% (19-54), 46% (30-59), and 54% (43-64) assuming a 15%, 50%, and 100% reduction in measles vaccination coverage. By December 2021, this risk increases further to 43% (25-56), 54% (43-63), and 67% (59-72) for the same coverage scenarios respectively. However, the increased risk of a measles outbreak following the lifting of all restrictions can be overcome by conducting a SIA with ≥ 95% coverage in under-fives.

Conclusion

While contact restrictions sufficient for SAR-CoV-2 control temporarily reduce measles transmissibility and the risk of an outbreak from a measles immunity gap, this risk rises rapidly once these restrictions are lifted. Implementing delayed SIAs will be critical for prevention of measles outbreaks given the roll-back of contact restrictions in Kenya.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-01906-9; doi:https://doi.org/10.1186/s12916-021-01906-9; html:https://europepmc.org/articles/PMC7854026; pdf:https://europepmc.org/articles/PMC7854026?pdf=render -35861824,https://doi.org/10.1161/jaha.121.025935,Candidate Plasma Biomarkers to Detect Anthracycline-Related Cardiomyopathy in Childhood Cancer Survivors: A Case Control Study in the Dutch Childhood Cancer Survivor Study.,"Leerink JM, Feijen EAM, Moerland PD, de Baat EC, Merkx R, van der Pal HJH, Tissing WJE, Louwerens M, van den Heuvel-Eibrink MM, Versluys AB, Asselbergs FW, Sammani A, Teske AJ, van Dalen EC, van der Heiden-van der Loo M, van Dulmen-den Broeder E, de Vries ACH, Kapusta L, Loonen J, Pinto YM, Kremer LCM, Mavinkurve-Groothuis AMC, Kok WEM.",,Journal of the American Heart Association,2022,2022-07-13,Y,Biomarkers; Childhood Cancer Survivors; Cardio‐oncology; Chemokine Ligands; Cancer Therapy–related Cardiac Dysfunction; Anthracycline‐related Cardiomyopathy,,,"Background Plasma biomarkers may aid in the detection of anthracycline-related cardiomyopathy (ACMP). However, the currently available biomarkers have limited diagnostic value in long-term childhood cancer survivors. This study sought to identify diagnostic plasma biomarkers for ACMP in childhood cancer survivors. Methods and Results We measured 275 plasma proteins in 28 ACMP cases with left ventricular ejection fraction <45%, 29 anthracycline-treated controls with left ventricular ejection fraction ≥53% matched on sex, time after cancer, and anthracycline dose, and 29 patients with genetically determined dilated cardiomyopathy with left ventricular ejection fraction <45%. Multivariable linear regression was used to identify differentially expressed proteins. Elastic net model, including clinical characteristics, was used to assess discrimination of proteins diagnostic for ACMP. NT-proBNP (N-terminal pro-B-type natriuretic peptide) and the inflammatory markers CCL19 (C-C motif chemokine ligands 19) and CCL20, PSPD (pulmonary surfactant protein-D), and PTN (pleiotrophin) were significantly upregulated in ACMP compared with controls. An elastic net model selected 45 proteins, including NT-proBNP, CCL19, CCL20 and PSPD, but not PTN, that discriminated ACMP cases from controls with an area under the receiver operating characteristic curve (AUC) of 0.78. This model was not superior to a model including NT-proBNP and clinical characteristics (AUC=0.75; P=0.766). However, when excluding 8 ACMP cases with heart failure, the full model was superior to that including only NT-proBNP and clinical characteristics (AUC=0.75 versus AUC=0.50; P=0.022). The same 45 proteins also showed good discrimination between dilated cardiomyopathy and controls (AUC=0.89), underscoring their association with cardiomyopathy. Conclusions We identified 3 specific inflammatory proteins as candidate plasma biomarkers for ACMP in long-term childhood cancer survivors and demonstrated protein overlap with dilated cardiomyopathy.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.025935; doi:https://doi.org/10.1161/JAHA.121.025935; html:https://europepmc.org/articles/PMC9707839; pdf:https://europepmc.org/articles/PMC9707839?pdf=render 30609404,https://doi.org/10.1016/j.ajhg.2018.11.014,Integrating Genomics into Healthcare: A Global Responsibility.,"Stark Z, Dolman L, Manolio TA, Ozenberger B, Hill SL, Caulfied MJ, Levy Y, Glazer D, Wilson J, Lawler M, Boughtwood T, Braithwaite J, Goodhand P, Birney E, North KN.",,American journal of human genetics,2019,2019-01-01,N,,Understanding the Causes of Disease,,"Genomic sequencing is rapidly transitioning into clinical practice, and implementation into healthcare systems has been supported by substantial government investment, totaling over US$4 billion, in at least 14 countries. These national genomic-medicine initiatives are driving transformative change under real-life conditions while simultaneously addressing barriers to implementation and gathering evidence for wider adoption. We review the diversity of approaches and current progress made by national genomic-medicine initiatives in the UK, France, Australia, and US and provide a roadmap for sharing strategies, standards, and data internationally to accelerate implementation.",,pdf:http://www.cell.com/article/S0002929718304221/pdf; doi:https://doi.org/10.1016/j.ajhg.2018.11.014; html:https://europepmc.org/articles/PMC6323624; pdf:https://europepmc.org/articles/PMC6323624?pdf=render; doi:https://doi.org/10.1016/j.ajhg.2018.11.014 +35861824,https://doi.org/10.1161/jaha.121.025935,Candidate Plasma Biomarkers to Detect Anthracycline-Related Cardiomyopathy in Childhood Cancer Survivors: A Case Control Study in the Dutch Childhood Cancer Survivor Study.,"Leerink JM, Feijen EAM, Moerland PD, de Baat EC, Merkx R, van der Pal HJH, Tissing WJE, Louwerens M, van den Heuvel-Eibrink MM, Versluys AB, Asselbergs FW, Sammani A, Teske AJ, van Dalen EC, van der Heiden-van der Loo M, van Dulmen-den Broeder E, de Vries ACH, Kapusta L, Loonen J, Pinto YM, Kremer LCM, Mavinkurve-Groothuis AMC, Kok WEM.",,Journal of the American Heart Association,2022,2022-07-13,Y,Biomarkers; Childhood Cancer Survivors; Cardio‐oncology; Chemokine Ligands; Cancer Therapy–related Cardiac Dysfunction; Anthracycline‐related Cardiomyopathy,,,"Background Plasma biomarkers may aid in the detection of anthracycline-related cardiomyopathy (ACMP). However, the currently available biomarkers have limited diagnostic value in long-term childhood cancer survivors. This study sought to identify diagnostic plasma biomarkers for ACMP in childhood cancer survivors. Methods and Results We measured 275 plasma proteins in 28 ACMP cases with left ventricular ejection fraction <45%, 29 anthracycline-treated controls with left ventricular ejection fraction ≥53% matched on sex, time after cancer, and anthracycline dose, and 29 patients with genetically determined dilated cardiomyopathy with left ventricular ejection fraction <45%. Multivariable linear regression was used to identify differentially expressed proteins. Elastic net model, including clinical characteristics, was used to assess discrimination of proteins diagnostic for ACMP. NT-proBNP (N-terminal pro-B-type natriuretic peptide) and the inflammatory markers CCL19 (C-C motif chemokine ligands 19) and CCL20, PSPD (pulmonary surfactant protein-D), and PTN (pleiotrophin) were significantly upregulated in ACMP compared with controls. An elastic net model selected 45 proteins, including NT-proBNP, CCL19, CCL20 and PSPD, but not PTN, that discriminated ACMP cases from controls with an area under the receiver operating characteristic curve (AUC) of 0.78. This model was not superior to a model including NT-proBNP and clinical characteristics (AUC=0.75; P=0.766). However, when excluding 8 ACMP cases with heart failure, the full model was superior to that including only NT-proBNP and clinical characteristics (AUC=0.75 versus AUC=0.50; P=0.022). The same 45 proteins also showed good discrimination between dilated cardiomyopathy and controls (AUC=0.89), underscoring their association with cardiomyopathy. Conclusions We identified 3 specific inflammatory proteins as candidate plasma biomarkers for ACMP in long-term childhood cancer survivors and demonstrated protein overlap with dilated cardiomyopathy.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.025935; doi:https://doi.org/10.1161/JAHA.121.025935; html:https://europepmc.org/articles/PMC9707839; pdf:https://europepmc.org/articles/PMC9707839?pdf=render 34645462,https://doi.org/10.1186/s12974-021-02287-9,T lymphocyte senescence is attenuated in Parkinson's disease.,"Kouli A, Jensen M, Papastavrou V, Scott KM, Kolenda C, Parker C, Solim IH, Camacho M, Martin-Ruiz C, Williams-Gray CH.",,Journal of neuroinflammation,2021,2021-10-13,Y,T lymphocytes; Immunosenescence; Parkinson’s Disease; Ageing Markers,,,"

Background

Immune involvement is well-described in Parkinson's disease (PD), including an adaptive T lymphocyte response. Given the increasing prevalence of Parkinson's disease in older age, age-related dysregulation of T lymphocytes may be relevant in this disorder, and we have previously observed changes in age-associated CD8+ T cell subsets in mid-stage PD. This study aimed to further characterise T cell immunosenescence in newly diagnosed PD patients, including shifts in CD4+ and CD8+ subpopulations, and changes in markers of cellular ageing in CD8+ T lymphocytes.

Methods

Peripheral blood mononuclear cells were extracted from the blood of 61 newly diagnosed PD patients and 63 age- and sex-matched controls. Flow cytometric analysis was used for immunophenotyping of CD8+ and CD4+ lymphocyte subsets, and analysis of recent thymic emigrant cells. Telomere length within CD8+ T lymphocytes was assessed, as well as the expression of the telomerase reverse transcriptase enzyme (hTERT), and the cell-ageing markers p16INK4a and p21CIP1/Waf1.

Results

The number of CD8+ TEMRA T cells was found to be significantly reduced in PD patients compared to controls. The expression of p16INK4a in CD8+ lymphocytes was also lower in patients versus controls. Chronic latent CMV infection was associated with increased senescent CD8+ lymphocytes in healthy controls, but this shift was less apparent in PD patients.

Conclusions

Taken together, our data demonstrate a reduction in CD8+ T cell replicative senescence which is present at the earliest stages of Parkinson's disease.",,pdf:https://jneuroinflammation.biomedcentral.com/track/pdf/10.1186/s12974-021-02287-9; doi:https://doi.org/10.1186/s12974-021-02287-9; html:https://europepmc.org/articles/PMC8513368; pdf:https://europepmc.org/articles/PMC8513368?pdf=render 36244350,https://doi.org/10.1016/s2468-2667(22)00225-0,The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis.,European Antimicrobial Resistance Collaborators.,,The Lancet. Public health,2022,2022-10-14,Y,,,,"

Background

Antimicrobial resistance (AMR) represents one of the most crucial threats to public health and modern health care. Previous studies have identified challenges with estimating the magnitude of the problem and its downstream effect on human health and mortality. To our knowledge, this study presents the most comprehensive set of regional and country-level estimates of AMR burden in the WHO European region to date.

Methods

We estimated deaths and disability-adjusted life-years attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen-drug combinations for the WHO European region and its countries in 2019. Our methodological approach consisted of five broad components: the number of deaths in which infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths attributable to AMR (considering an alternative scenario where infections with resistant pathogens are replaced with susceptible ones) and deaths associated with AMR (considering an alternative scenario where drug-resistant infections would not occur at all). Data were solicited from a wide array of international stakeholders; these included research hospitals, surveillance networks, and infection databases maintained by private laboratories and medical technology companies. We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity.

Findings

We estimated 541 000 deaths (95% UI 370 000-763 000) associated with bacterial AMR and 133 000 deaths (90 100-188 000) attributable to bacterial AMR in the whole WHO European region in 2019. The largest fatal burden of AMR in the region came from bloodstream infections, with 195 000 deaths (104 000-333 000) associated with resistance, followed by intra-abdominal infections (127 000 deaths [81 900-185 000]) and respiratory infections (120 000 deaths [94 500-154 000]). Seven leading pathogens were responsible for about 457 000 deaths associated with resistance in 53 countries of this region; these pathogens were, in descending order of mortality, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Streptococcus pneumoniae, and Acinetobacter baumannii. Methicillin-resistant S aureus was shown to be the leading pathogen-drug combination in 27 countries for deaths attributable to AMR, while aminopenicillin-resistant E coli predominated in 47 countries for deaths associated with AMR.

Interpretation

The high levels of resistance for several important bacterial pathogens and pathogen-drug combinations, together with the high mortality rates associated with these pathogens, show that AMR is a serious threat to public health in the WHO European region. Our regional and cross-country analyses open the door for strategies that can be tailored to leading pathogen-drug combinations and the available resources in a specific location. These results underscore that the most effective way to tackle AMR in this region will require targeted efforts and investments in conjunction with continuous outcome-based research endeavours.

Funding

Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.",,pdf:https://digital.library.adelaide.edu.au/dspace/bitstream/2440/136826/2/hdl_136826.pdf; doi:https://doi.org/10.1016/S2468-2667(22)00225-0; html:https://europepmc.org/articles/PMC9630253 33777379,https://doi.org/10.1093/ckj/sfaa045,Accelerometer-measured physical activity and functional behaviours among people on dialysis.,"Nawab KA, Storey BC, Staplin N, Walmsley R, Haynes R, Sutherland S, Crosbie S, Pugh CW, Harper CHS, Landray MJ, Doherty A, Herrington WG.",,Clinical kidney journal,2021,2020-08-31,Y,Age; Haemodialysis; epidemiology; Physical Activity; cardiovascular,,,"

Background

The feasibility of wrist-worn accelerometers, and the patterns and determinants of physical activity, among people on dialysis are uncertain.

Methods

People on maintenance dialysis were fitted with a wrist-worn AxivityAX3 accelerometer. Subsets also wore a 14-day electrocardiograph patch (Zio®PatchXT) and wearable cameras. Age-, sex- and season-matched UK Biobank control groups were derived for comparison.

Results

Median (interquartile range) accelerometer wear time for the 101 recruits was 12.5 (10.4-13.5) days, of which 73 participants (mean age 66.5 years) had excellent wear on both dialysis and non-dialysis days. Mean (standard error) overall physical activity levels were 15.5 (0.7) milligravity units (mg), 14.8 (0.7) mg on dialysis days versus 16.2 (0.8) mg on non-dialysis days. This compared with 28.1 (0.5) mg for apparently healthy controls, 23.4 (0.4) mg for controls with prior cardiovascular disease (CVD) and/or diabetes mellitus and 22.9 (0.6) mg for heart failure controls. Each day, we estimated that those on dialysis spent an average of about 1 hour (h/day) walking, 0.6 h/day engaging in moderate-intensity activity, 0.7 h/day on light tasks, 13.2 h/day sedentary and 8.6 h/day asleep. Older age and self-reported leg weakness were associated with decreased levels of physical activity, but the presence of prior CVD, arrhythmias and listing for transplantation were not.

Conclusions

Wrist-worn accelerometers are an acceptable and reliable method to measure physical activity in people on dialysis and may also be used to estimate functional behaviours. Among people on dialysis, who are broadly half as active as general population controls, age and leg weakness appear to be more important determinants of low activity levels than CVD.",,pdf:https://academic.oup.com/ckj/article-pdf/14/3/950/36670473/sfaa045.pdf; doi:https://doi.org/10.1093/ckj/sfaa045; html:https://europepmc.org/articles/PMC7986362; pdf:https://europepmc.org/articles/PMC7986362?pdf=render @@ -2233,11 +2233,11 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 32591531,https://doi.org/10.1038/s41467-020-16969-0,Genetic drug target validation using Mendelian randomisation.,"Schmidt AF, Finan C, Gordillo-Marañón M, Asselbergs FW, Freitag DF, Patel RS, Tyl B, Chopade S, Faraway R, Zwierzyna M, Hingorani AD.",,Nature communications,2020,2020-06-26,Y,,,,"Mendelian randomisation (MR) analysis is an important tool to elucidate the causal relevance of environmental and biological risk factors for disease. However, causal inference is undermined if genetic variants used to instrument a risk factor also influence alternative disease-pathways (horizontal pleiotropy). Here we report how the 'no horizontal pleiotropy assumption' is strengthened when proteins are the risk factors of interest. Proteins are typically the proximal effectors of biological processes encoded in the genome. Moreover, proteins are the targets of most medicines, so MR studies of drug targets are becoming a fundamental tool in drug development. To enable such studies, we introduce a mathematical framework that contrasts MR analysis of proteins with that of risk factors located more distally in the causal chain from gene to disease. We illustrate key model decisions and introduce an analytical framework for maximising power and evaluating the robustness of analyses.",,pdf:https://www.nature.com/articles/s41467-020-16969-0.pdf; doi:https://doi.org/10.1038/s41467-020-16969-0; html:https://europepmc.org/articles/PMC7320010; pdf:https://europepmc.org/articles/PMC7320010?pdf=render 36865374,https://doi.org/10.12688/wellcomeopenres.18175.1,GroundsWell: Community-engaged and data-informed systems transformation of Urban Green and Blue Space for population health - a new initiative.,"Hunter RF, Rodgers SE, Hilton J, Clarke M, Garcia L, Ward Thompson C, Geary R, Green MA, O'Neill C, Longo A, Lovell R, Nurse A, Wheeler BW, Clement S, Porroche-Escudero A, Mitchell R, Barr B, Barry J, Bell S, Bryan D, Buchan I, Butters O, Clemens T, Clewley N, Corcoran R, Elliott L, Ellis G, Guell C, Jurek-Loughrey A, Kee F, Maguire A, Maskell S, Murtagh B, Smith G, Taylor T, Jepson R, GroundsWell Consortium.",,Wellcome open research,2022,2022-09-20,Y,Public Health; Non-Communicable Disease; Green And Blue Space; Complex Systems; Data Science; Citizen Science; Interdisciplinary; Health Inequalities,,,"Natural environments, such as parks, woodlands and lakes, have positive impacts on health and wellbeing. Urban Green and Blue Spaces (UGBS), and the activities that take place in them, can significantly influence the health outcomes of all communities, and reduce health inequalities. Improving access and quality of UGBS needs understanding of the range of systems (e.g. planning, transport, environment, community) in which UGBS are located. UGBS offers an ideal exemplar for testing systems innovations as it reflects place-based and whole society processes , with potential to reduce non-communicable disease (NCD) risk and associated social inequalities in health. UGBS can impact multiple behavioural and environmental aetiological pathways. However, the systems which desire, design, develop, and deliver UGBS are fragmented and siloed, with ineffective mechanisms for data generation, knowledge exchange and mobilisation. Further, UGBS need to be co-designed with and by those whose health could benefit most from them, so they are appropriate, accessible, valued and used well. This paper describes a major new prevention research programme and partnership, GroundsWell, which aims to transform UGBS-related systems by improving how we plan, design, evaluate and manage UGBS so that it benefits all communities, especially those who are in poorest health. We use a broad definition of health to include physical, mental, social wellbeing and quality of life. Our objectives are to transform systems so that UGBS are planned, developed, implemented, maintained and evaluated with our communities and data systems to enhance health and reduce inequalities. GroundsWell will use interdisciplinary, problem-solving approaches to accelerate and optimise community collaborations among citizens, users, implementers, policymakers and researchers to impact research, policy, practice and active citizenship. GroundsWell will be shaped and developed in three pioneer cities (Belfast, Edinburgh, Liverpool) and their regional contexts, with embedded translational mechanisms to ensure that outputs and impact have UK-wide and international application.",,doi:https://doi.org/10.12688/wellcomeopenres.18175.1; doi:https://doi.org/10.12688/wellcomeopenres.18175.1; html:https://europepmc.org/articles/PMC9971655; pdf:https://europepmc.org/articles/PMC9971655?pdf=render 34515361,https://doi.org/10.15252/embj.2021108610,Porin threading drives receptor disengagement and establishes active colicin transport through Escherichia coli OmpF.,"Francis MR, Webby MN, Housden NG, Kaminska R, Elliston E, Chinthammit B, Lukoyanova N, Kleanthous C.",,The EMBO journal,2021,2021-09-13,Y,Cryo-electron microscopy; Outer membrane; Bacteriocins; Gram-negative Bacteria; fluorescent microscopy,,,"Bacteria deploy weapons to kill their neighbours during competition for resources and to aid survival within microbiomes. Colicins were the first such antibacterial system identified, yet how these bacteriocins cross the outer membrane (OM) of Escherichia coli is unknown. Here, by solving the structures of translocation intermediates via cryo-EM and by imaging toxin import, we uncover the mechanism by which the Tol-dependent nuclease colicin E9 (ColE9) crosses the bacterial OM. We show that threading of ColE9's disordered N-terminal domain through two pores of the trimeric porin OmpF causes the colicin to disengage from its primary receptor, BtuB, and reorganises the translocon either side of the membrane. Subsequent import of ColE9 through the lumen of a single OmpF subunit is driven by the proton-motive force, which is delivered by the TolQ-TolR-TolA-TolB assembly. Our study answers longstanding questions, such as why OmpF is a better translocator than OmpC, and reconciles the mechanisms by which both Tol- and Ton-dependent bacteriocins cross the bacterial outer membrane.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.15252/embj.2021108610; doi:https://doi.org/10.15252/embj.2021108610; html:https://europepmc.org/articles/PMC8561637; pdf:https://europepmc.org/articles/PMC8561637?pdf=render -33722066,https://doi.org/10.1161/circinterventions.120.009434,Clopidogrel Versus Ticagrelor or Prasugrel After Primary Percutaneous Coronary Intervention According to CYP2C19 Genotype: A POPular Genetics Subanalysis.,"Claassens DMF, Bergmeijer TO, Vos GJA, Hermanides RS, van 't Hof AWJ, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, Asselbergs FW, Mosterd A, Herrman JR, Dewilde WJM, Janssen PWA, Kelder JC, Mahmoodi BK, Deneer VHM, Ten Berg JM.",,Circulation. Cardiovascular interventions,2021,2021-03-16,N,Myocardial infarction; Percutaneous coronary intervention; acute coronary syndrome; Clopidogrel; Genetic Testing; Pharmacogenetics; Ticagrelor,,,[Figure: see text].,,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCINTERVENTIONS.120.009434; doi:https://doi.org/10.1161/CIRCINTERVENTIONS.120.009434 33332257,https://doi.org/10.1099/mgen.0.000434,Read trimming has minimal effect on bacterial SNP-calling accuracy.,Bush SJ.,,Microbial genomics,2020,2020-12-11,Y,Variant Calling; Snp Calling; Read Trimming; Read Pre-processing,,,"Read alignment is the central step of many analytic pipelines that perform variant calling. To reduce error, it is common practice to pre-process raw sequencing reads to remove low-quality bases and residual adapter contamination, a procedure collectively known as 'trimming'. Trimming is widely assumed to increase the accuracy of variant calling, although there are relatively few systematic evaluations of its effects and no clear consensus on its efficacy. As sequencing datasets increase both in number and size, it is worthwhile reappraising computational operations of ambiguous benefit, particularly when the scope of many analyses now routinely incorporates thousands of samples, increasing the time and cost required. Using a curated set of 17 Gram-negative bacterial genomes, this study initially evaluated the impact of four read-trimming utilities (Atropos, fastp, Trim Galore and Trimmomatic), each used with a range of stringencies, on the accuracy and completeness of three bacterial SNP-calling pipelines. It was found that read trimming made only small, and statistically insignificant, increases in SNP-calling accuracy even when using the highest-performing pre-processor in this study, fastp. To extend these findings, >6500 publicly archived sequencing datasets from Escherichia coli, Mycobacterium tuberculosis and Staphylococcus aureus were re-analysed using a common analytic pipeline. Of the approximately 125 million SNPs and 1.25 million indels called across all samples, the same bases were called in 98.8 and 91.9 % of cases, respectively, irrespective of whether raw reads or trimmed reads were used. Nevertheless, the proportion of mixed calls (i.e. calls where <100 % of the reads support the variant allele; considered a proxy of false positives) was significantly reduced after trimming, which suggests that while trimming rarely alters the set of variant bases, it can affect the proportion of reads supporting each call. It was concluded that read quality- and adapter-trimming add relatively little value to a SNP-calling pipeline and may only be necessary if small differences in the absolute number of SNP calls, or the false call rate, are critical. Broadly similar conclusions can be drawn about the utility of trimming to an indel-calling pipeline. Read trimming remains routinely performed prior to variant calling likely out of concern that doing otherwise would typically have negative consequences. While historically this may have been the case, the data in this study suggests that read trimming is not always a practical necessity.",,doi:https://doi.org/10.1099/mgen.0.000434; doi:https://doi.org/10.1099/mgen.0.000434; html:https://europepmc.org/articles/PMC8116680; pdf:https://europepmc.org/articles/PMC8116680?pdf=render +33722066,https://doi.org/10.1161/circinterventions.120.009434,Clopidogrel Versus Ticagrelor or Prasugrel After Primary Percutaneous Coronary Intervention According to CYP2C19 Genotype: A POPular Genetics Subanalysis.,"Claassens DMF, Bergmeijer TO, Vos GJA, Hermanides RS, van 't Hof AWJ, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, Asselbergs FW, Mosterd A, Herrman JR, Dewilde WJM, Janssen PWA, Kelder JC, Mahmoodi BK, Deneer VHM, Ten Berg JM.",,Circulation. Cardiovascular interventions,2021,2021-03-16,N,Myocardial infarction; Percutaneous coronary intervention; acute coronary syndrome; Clopidogrel; Genetic Testing; Pharmacogenetics; Ticagrelor,,,[Figure: see text].,,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCINTERVENTIONS.120.009434; doi:https://doi.org/10.1161/CIRCINTERVENTIONS.120.009434 32895551,https://doi.org/10.1038/s41588-020-0682-6,Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases.,"Zheng J, Haberland V, Baird D, Walker V, Haycock PC, Hurle MR, Gutteridge A, Erola P, Liu Y, Luo S, Robinson J, Richardson TG, Staley JR, Elsworth B, Burgess S, Sun BB, Danesh J, Runz H, Maranville JC, Martin HM, Yarmolinsky J, Laurin C, Holmes MV, Liu JZ, Estrada K, Santos R, McCarthy L, Waterworth D, Nelson MR, Smith GD, Butterworth AS, Hemani G, Scott RA, Gaunt TR.",,Nature genetics,2020,2020-09-07,Y,,,,"The human proteome is a major source of therapeutic targets. Recent genetic association analyses of the plasma proteome enable systematic evaluation of the causal consequences of variation in plasma protein levels. Here we estimated the effects of 1,002 proteins on 225 phenotypes using two-sample Mendelian randomization (MR) and colocalization. Of 413 associations supported by evidence from MR, 130 (31.5%) were not supported by results of colocalization analyses, suggesting that genetic confounding due to linkage disequilibrium is widespread in naïve phenome-wide association studies of proteins. Combining MR and colocalization evidence in cis-only analyses, we identified 111 putatively causal effects between 65 proteins and 52 disease-related phenotypes ( https://www.epigraphdb.org/pqtl/ ). Evaluation of data from historic drug development programs showed that target-indication pairs with MR and colocalization support were more likely to be approved, evidencing the value of this approach in identifying and prioritizing potential therapeutic targets.",,pdf:https://ueaeprints.uea.ac.uk/id/eprint/76368/1/Zheng_et_al_final_manuscript.pdf; doi:https://doi.org/10.1038/s41588-020-0682-6; html:https://europepmc.org/articles/PMC7610464; pdf:https://europepmc.org/articles/PMC7610464?pdf=render -37188768,https://doi.org/10.1038/s42003-023-04836-9,Fine-mapping of retinal vascular complexity loci identifies Notch regulation as a shared mechanism with myocardial infarction outcomes.,"Villaplana-Velasco A, Pigeyre M, Engelmann J, Rawlik K, Canela-Xandri O, Tochel C, Lona-Durazo F, Mookiah MRK, Doney A, Parra EJ, Trucco E, MacGillivray T, Rannikmae K, Tenesa A, Pairo-Castineira E, Bernabeu MO.",,Communications biology,2023,2023-05-15,Y,,,,"There is increasing evidence that the complexity of the retinal vasculature measured as fractal dimension, Df, might offer earlier insights into the progression of coronary artery disease (CAD) before traditional biomarkers can be detected. This association could be partly explained by a common genetic basis; however, the genetic component of Df is poorly understood. We present a genome-wide association study (GWAS) of 38,000 individuals with white British ancestry from the UK Biobank aimed to comprehensively study the genetic component of Df and analyse its relationship with CAD. We replicated 5 Df loci and found 4 additional loci with suggestive significance (P < 1e-05) to contribute to Df variation, which previously were reported in retinal tortuosity and complexity, hypertension, and CAD studies. Significant negative genetic correlation estimates support the inverse relationship between Df and CAD, and between Df and myocardial infarction (MI), one of CAD's fatal outcomes. Fine-mapping of Df loci revealed Notch signalling regulatory variants supporting a shared mechanism with MI outcomes. We developed a predictive model for MI incident cases, recorded over a 10-year period following clinical and ophthalmic evaluation, combining clinical information, Df, and a CAD polygenic risk score. Internal cross-validation demonstrated a considerable improvement in the area under the curve (AUC) of our predictive model (AUC = 0.770 ± 0.001) when comparing with an established risk model, SCORE, (AUC = 0.741 ± 0.002) and extensions thereof leveraging the PRS (AUC = 0.728 ± 0.001). This evidences that Df provides risk information beyond demographic, lifestyle, and genetic risk factors. Our findings shed new light on the genetic basis of Df, unveiling a common control with MI, and highlighting the benefits of its application in individualised MI risk prediction.",,doi:https://doi.org/10.1038/s42003-023-04836-9; html:https://europepmc.org/articles/PMC10185685; pdf:https://europepmc.org/articles/PMC10185685?pdf=render 35908569,https://doi.org/10.1016/s0140-6736(22)01109-6,"Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2022,2022-07-01,Y,,,,"

Background

We aimed to evaluate the use of baricitinib, a Janus kinase (JAK) 1-2 inhibitor, for the treatment of patients admitted to hospital with COVID-19.

Methods

This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated (1:1) to either usual standard of care alone (usual care group) or usual care plus baricitinib 4 mg once daily by mouth for 10 days or until discharge if sooner (baricitinib group). The primary outcome was 28-day mortality assessed in the intention-to-treat population. A meta-analysis was done, which included the results from the RECOVERY trial and all previous randomised controlled trials of baricitinib or other JAK inhibitor in patients hospitalised with COVID-19. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936) and is ongoing.

Findings

Between Feb 2 and Dec 29, 2021, from 10 852 enrolled, 8156 patients were randomly allocated to receive usual care plus baricitinib versus usual care alone. At randomisation, 95% of patients were receiving corticosteroids and 23% were receiving tocilizumab (with planned use within the next 24 h recorded for a further 9%). Overall, 514 (12%) of 4148 patients allocated to baricitinib versus 546 (14%) of 4008 patients allocated to usual care died within 28 days (age-adjusted rate ratio 0·87; 95% CI 0·77-0·99; p=0·028). This 13% proportional reduction in mortality was somewhat smaller than that seen in a meta-analysis of eight previous trials of a JAK inhibitor (involving 3732 patients and 425 deaths), in which allocation to a JAK inhibitor was associated with a 43% proportional reduction in mortality (rate ratio 0·57; 95% CI 0·45-0·72). Including the results from RECOVERY in an updated meta-analysis of all nine completed trials (involving 11 888 randomly assigned patients and 1485 deaths) allocation to baricitinib or another JAK inhibitor was associated with a 20% proportional reduction in mortality (rate ratio 0·80; 95% CI 0·72-0·89; p<0·0001). In RECOVERY, there was no significant excess in death or infection due to non-COVID-19 causes and no significant excess of thrombosis, or other safety outcomes.

Interpretation

In patients hospitalised with COVID-19, baricitinib significantly reduced the risk of death but the size of benefit was somewhat smaller than that suggested by previous trials. The total randomised evidence to date suggests that JAK inhibitors (chiefly baricitinib) reduce mortality in patients hospitalised for COVID-19 by about one-fifth.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,pdf:http://www.thelancet.com/article/S0140673622011096/pdf; doi:https://doi.org/10.1016/S0140-6736(22)01109-6; html:https://europepmc.org/articles/PMC9333998; pdf:https://europepmc.org/articles/PMC9333998?pdf=render +37188768,https://doi.org/10.1038/s42003-023-04836-9,Fine-mapping of retinal vascular complexity loci identifies Notch regulation as a shared mechanism with myocardial infarction outcomes.,"Villaplana-Velasco A, Pigeyre M, Engelmann J, Rawlik K, Canela-Xandri O, Tochel C, Lona-Durazo F, Mookiah MRK, Doney A, Parra EJ, Trucco E, MacGillivray T, Rannikmae K, Tenesa A, Pairo-Castineira E, Bernabeu MO.",,Communications biology,2023,2023-05-15,Y,,,,"There is increasing evidence that the complexity of the retinal vasculature measured as fractal dimension, Df, might offer earlier insights into the progression of coronary artery disease (CAD) before traditional biomarkers can be detected. This association could be partly explained by a common genetic basis; however, the genetic component of Df is poorly understood. We present a genome-wide association study (GWAS) of 38,000 individuals with white British ancestry from the UK Biobank aimed to comprehensively study the genetic component of Df and analyse its relationship with CAD. We replicated 5 Df loci and found 4 additional loci with suggestive significance (P < 1e-05) to contribute to Df variation, which previously were reported in retinal tortuosity and complexity, hypertension, and CAD studies. Significant negative genetic correlation estimates support the inverse relationship between Df and CAD, and between Df and myocardial infarction (MI), one of CAD's fatal outcomes. Fine-mapping of Df loci revealed Notch signalling regulatory variants supporting a shared mechanism with MI outcomes. We developed a predictive model for MI incident cases, recorded over a 10-year period following clinical and ophthalmic evaluation, combining clinical information, Df, and a CAD polygenic risk score. Internal cross-validation demonstrated a considerable improvement in the area under the curve (AUC) of our predictive model (AUC = 0.770 ± 0.001) when comparing with an established risk model, SCORE, (AUC = 0.741 ± 0.002) and extensions thereof leveraging the PRS (AUC = 0.728 ± 0.001). This evidences that Df provides risk information beyond demographic, lifestyle, and genetic risk factors. Our findings shed new light on the genetic basis of Df, unveiling a common control with MI, and highlighting the benefits of its application in individualised MI risk prediction.",,doi:https://doi.org/10.1038/s42003-023-04836-9; html:https://europepmc.org/articles/PMC10185685; pdf:https://europepmc.org/articles/PMC10185685?pdf=render 37538507,https://doi.org/10.1016/j.rpth.2023.100175,PIK3R3 is a candidate regulator of platelet count in people of Bangladeshi ancestry.,"Burley K, Fitzgibbon L, van Heel D, Genes & Health Research Team@EastLondonGenes, Vuckovic D, Mumford AD, Genes & Health Research Team.",,Research and practice in thrombosis and haemostasis,2023,2023-05-14,Y,Blood platelets; Cardiovascular diseases; Bangladesh; Genome-wide Association Study; Phosphatidylinositol 3-Kinases,,,"

Background

Blood platelets are mediators of atherothrombotic disease and are regulated by complex sets of genes. Association studies in European ancestry populations have already detected informative platelet regulatory loci. Studies in other ancestries can potentially reveal new associations because of different allele frequencies, linkage structures, and variant effects.

Objectives

To reveal new regulatory genes for platelet count (PLT).

Methods

Genome-wide association studies (GWAS) were performed in 20,218 Bangladeshi and 9198 Pakistani individuals from the Genes & Health study. Loci significantly associated with PLT underwent fine-mapping to identify candidate genes.

Results

Of 1588 significantly associated variants (P < 5 × 10-8) at 20 loci in the Bangladeshi analysis, most replicated findings in prior transancestry GWAS and in the Pakistani analysis. However, the Bangladeshi locus defined by rs946528 (chr1:46019890) did not associate with PLT in the Pakistani analysis but was in the same linkage disequilibrium block (r2 ≥ 0.5) as PLT-associated variants in prior East Asian GWAS. The single independent association signal was refined to a 95% credible set of 343 variants spanning 8 coding genes. Functional annotation, mapping to megakaryocyte regulatory regions, and colocalization with blood expression quantitative trait loci identified the likely mediator of the PLT phenotype to be PIK3R3 encoding a regulator of phosphoinositol 3-kinase (PI3K).

Conclusion

Abnormal PI3K activity in the vessel wall is already implicated in the pathogenesis of atherothrombosis. Our identification of a new association between PIK3R3 and PLT provides further mechanistic insights into the contribution of the PI3K pathway to platelet biology.",,doi:https://doi.org/10.1016/j.rpth.2023.100175; html:https://europepmc.org/articles/PMC10394561; pdf:https://europepmc.org/articles/PMC10394561?pdf=render 32546850,https://doi.org/10.1038/s41598-020-66737-9,Genetic aetiology of self-harm ideation and behaviour.,"Campos AI, Verweij KJH, Statham DJ, Madden PAF, Maciejewski DF, Davis KAS, John A, Hotopf M, Heath AC, Martin NG, Rentería ME.",,Scientific reports,2020,2020-06-16,Y,,,,"Family studies have identified a heritable component to self-harm that is partially independent from comorbid psychiatric disorders. However, the genetic aetiology of broad sense (non-suicidal and suicidal) self-harm has not been characterised on the molecular level. In addition, controversy exists about the degree to which suicidal and non-suicidal self-harm share a common genetic aetiology. In the present study, we conduct genome-wide association studies (GWAS) on lifetime self-harm ideation and self-harm behaviour (i.e. any lifetime self-harm act regardless of suicidal intent) using data from the UK Biobank (n > 156,000). We also perform genome wide gene-based tests and characterize the SNP heritability and genetic correlations between these traits. Finally, we test whether polygenic risk scores (PRS) for self-harm ideation and self-harm behaviour predict suicide attempt, suicide thoughts and non-suicidal self-harm (NSSH) in an independent target sample of 8,703 Australian adults. Our GWAS results identified one genome-wide significant locus associated with each of the two phenotypes. SNP heritability (hsnp2) estimates were ~10%, and both traits were highly genetically correlated (LDSC rg > 0.8). Gene-based tests identified seven genes associated with self-harm ideation and four with self-harm behaviour. Furthermore, in the target sample, PRS for self-harm ideation were significantly associated with suicide thoughts and NSSH, and PRS for self-harm behaviour predicted suicide thoughts and suicide attempt. Follow up regressions identified a shared genetic aetiology between NSSH and suicide thoughts, and between suicide thoughts and suicide attempt. Evidence for shared genetic aetiology between NSSH and suicide attempt was not statistically significant.",,pdf:https://www.nature.com/articles/s41598-020-66737-9.pdf; doi:https://doi.org/10.1038/s41598-020-66737-9; html:https://europepmc.org/articles/PMC7297971; pdf:https://europepmc.org/articles/PMC7297971?pdf=render 32505923,https://doi.org/10.1016/j.ebiom.2020.102818,"Children first, or last?",Modi N.,,EBioMedicine,2020,2020-06-04,Y,,,,,,pdf:http://www.thelancet.com/article/S2352396420301936/pdf; doi:https://doi.org/10.1016/j.ebiom.2020.102818; html:https://europepmc.org/articles/PMC7276509; pdf:https://europepmc.org/articles/PMC7276509?pdf=render @@ -2245,8 +2245,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 35231023,https://doi.org/10.1371/journal.pmed.1003907,Changes in social contacts in England during the COVID-19 pandemic between March 2020 and March 2021 as measured by the CoMix survey: A repeated cross-sectional study.,"Gimma A, Munday JD, Wong KLM, Coletti P, van Zandvoort K, Prem K, CMMID COVID-19 working group, Klepac P, Rubin GJ, Funk S, Edmunds WJ, Jarvis CI.",,PLoS medicine,2022,2022-03-01,Y,,,,"

Background

During the Coronavirus Disease 2019 (COVID-19) pandemic, the United Kingdom government imposed public health policies in England to reduce social contacts in hopes of curbing virus transmission. We conducted a repeated cross-sectional study to measure contact patterns weekly from March 2020 to March 2021 to estimate the impact of these policies, covering 3 national lockdowns interspersed by periods of less restrictive policies.

Methods and findings

The repeated cross-sectional survey data were collected using online surveys of representative samples of the UK population by age and gender. Survey participants were recruited by the online market research company Ipsos MORI through internet-based banner and social media ads and email campaigns. The participant data used for this analysis are restricted to those who reported living in England. We calculated the mean daily contacts reported using a (clustered) bootstrap and fitted a censored negative binomial model to estimate age-stratified contact matrices and estimate proportional changes to the basic reproduction number under controlled conditions using the change in contacts as a scaling factor. To put the findings in perspective, we discuss contact rates recorded throughout the year in terms of previously recorded rates from the POLYMOD study social contact study. The survey recorded 101,350 observations from 19,914 participants who reported 466,710 contacts over 53 weeks. We observed changes in social contact patterns in England over time and by participants' age, personal risk factors, and perception of risk. The mean reported contacts for adults 18 to 59 years old ranged between 2.39 (95% confidence interval [CI] 2.20 to 2.60) contacts and 4.93 (95% CI 4.65 to 5.19) contacts during the study period. The mean contacts for school-age children (5 to 17 years old) ranged from 3.07 (95% CI 2.89 to 3.27) to 15.11 (95% CI 13.87 to 16.41). This demonstrates a sustained decrease in social contacts compared to a mean of 11.08 (95% CI 10.54 to 11.57) contacts per participant in all age groups combined as measured by the POLYMOD social contact study in 2005 to 2006. Contacts measured during periods of lockdowns were lower than in periods of eased social restrictions. The use of face coverings outside the home has remained high since the government mandated use in some settings in July 2020. The main limitations of this analysis are the potential for selection bias, as participants are recruited through internet-based campaigns, and recall bias, in which participants may under- or overreport the number of contacts they have made.

Conclusions

In this study, we observed that recorded contacts reduced dramatically compared to prepandemic levels (as measured in the POLYMOD study), with changes in reported contacts correlated with government interventions throughout the pandemic. Despite easing of restrictions in the summer of 2020, the mean number of reported contacts only returned to about half of that observed prepandemic at its highest recorded level. The CoMix survey provides a unique repeated cross-sectional data set for a full year in England, from the first day of the first lockdown, for use in statistical analyses and mathematical modelling of COVID-19 and other diseases.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003907&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003907; html:https://europepmc.org/articles/PMC8887739; pdf:https://europepmc.org/articles/PMC8887739?pdf=render 32724860,https://doi.org/10.12688/wellcomeopenres.15651.2,Using a knowledge exchange event to assess study participants' attitudes to research in a rapidly evolving research context.,"Beange I, Kirkham EJ, Fletcher-Watson S, Iveson MH, Lawrie SM, Batty GD, Boardman JP, Deary IJ, Black C, Porteous DJ, McIntosh AM.",,Wellcome open research,2020,2020-08-28,Y,Health; Cohort; Scotland; Data Linkage; Public Engagement; Opinion; Knowledge Exchange; Big Data; Data Science; Guthrie,,,"Background: The UK hosts some of the world's longest-running longitudinal cohort studies, which make repeated observations of their participants and use these data to explore health outcomes. An alternative method for data collection is record linkage; the linking together of electronic health and administrative records. Applied nationally, this could provide unrivalled opportunities to follow a large number of people in perpetuity. However, public attitudes to the use of data in research are currently unclear. Here we report on an event where we collected attitudes towards recent opportunities and controversies within health data science. Methods: The event was attended by ~250 individuals (cohort members and their guests), who had been invited through the offices of their participating cohort studies. There were a series of presentations describing key research results and the audience participated in 15 multiple-choice questions using interactive voting pads. Results: Our participants showed a high level of trust in researchers (87% scoring them 4/5 or 5/5) and doctors (81%); but less trust in commercial companies (35%). They supported the idea of researchers using information from both neonatal blood spots (Guthrie spots) (97% yes) and from electronic health records (95% yes). Our respondents were willing to wear devices like a 'Fit-bit' (88% agreed) or take a brain scan that might predict later mental illness (73%). However, they were less willing to take a new drug for research purposes (45%). They were keen to encourage others to take part in research; whether that be offering the opportunity to pregnant mothers (97% agreed) or extending invitations to their own children and grandchildren (98%). Conclusions: Our participants were broadly supportive of research access to data, albeit less supportive when commercial interests were involved. Public engagement events that facilitate two-way interactions can influence and support future research and public engagement efforts.",,pdf:https://wellcomeopenresearch.org/articles/5-24/v2/pdf; doi:https://doi.org/10.12688/wellcomeopenres.15651.2; html:https://europepmc.org/articles/PMC7361507; pdf:https://europepmc.org/articles/PMC7361507?pdf=render 33220850,https://doi.org/10.1016/s0140-6736(20)32465-x,Urgent actions and policies needed to address COVID-19 among UK ethnic minorities.,"Mathur R, Bear L, Khunti K, Eggo RM.",,"Lancet (London, England)",2020,2020-11-19,Y,,,,,,pdf:http://www.thelancet.com/article/S014067362032465X/pdf; doi:https://doi.org/10.1016/S0140-6736(20)32465-X; html:https://europepmc.org/articles/PMC7831890; pdf:https://europepmc.org/articles/PMC7831890?pdf=render -35962208,https://doi.org/10.1038/s41591-022-01951-8,Publisher Correction: Reporting guideline for the early-stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI.,"Vasey B, Nagendran M, Campbell B, Clifton DA, Collins GS, Denaxas S, Denniston AK, Faes L, Geerts B, Ibrahim M, Liu X, Mateen BA, Mathur P, McCradden MD, Morgan L, Ordish J, Rogers C, Saria S, Ting DSW, Watkinson P, Weber W, Wheatstone P, McCulloch P, DECIDE-AI expert group.",,Nature medicine,2022,2022-10-01,N,,,,,,pdf:https://www.nature.com/articles/s41591-022-01951-8.pdf; doi:https://doi.org/10.1038/s41591-022-01951-8 31792462,https://doi.org/10.1038/s41591-019-0665-2,Plasma protein patterns as comprehensive indicators of health.,"Williams SA, Kivimaki M, Langenberg C, Hingorani AD, Casas JP, Bouchard C, Jonasson C, Sarzynski MA, Shipley MJ, Alexander L, Ash J, Bauer T, Chadwick J, Datta G, DeLisle RK, Hagar Y, Hinterberg M, Ostroff R, Weiss S, Ganz P, Wareham NJ.",,Nature medicine,2019,2019-12-02,N,,,,"Proteins are effector molecules that mediate the functions of genes1,2 and modulate comorbidities3-10, behaviors and drug treatments11. They represent an enormous potential resource for personalized, systemic and data-driven diagnosis, prevention, monitoring and treatment. However, the concept of using plasma proteins for individualized health assessment across many health conditions simultaneously has not been tested. Here, we show that plasma protein expression patterns strongly encode for multiple different health states, future disease risks and lifestyle behaviors. We developed and validated protein-phenotype models for 11 different health indicators: liver fat, kidney filtration, percentage body fat, visceral fat mass, lean body mass, cardiopulmonary fitness, physical activity, alcohol consumption, cigarette smoking, diabetes risk and primary cardiovascular event risk. The analyses were prospectively planned, documented and executed at scale on archived samples and clinical data, with a total of ~85 million protein measurements in 16,894 participants. Our proof-of-concept study demonstrates that protein expression patterns reliably encode for many different health issues, and that large-scale protein scanning12-16 coupled with machine learning is viable for the development and future simultaneous delivery of multiple measures of health. We anticipate that, with further validation and the addition of more protein-phenotype models, this approach could enable a single-source, individualized so-called liquid health check.",,pdf:https://europepmc.org/articles/pmc6922049?pdf=render; doi:https://doi.org/10.1038/s41591-019-0665-2; html:https://europepmc.org/articles/PMC6922049; pdf:https://europepmc.org/articles/PMC6922049?pdf=render; doi:https://doi.org/10.1038/s41591-019-0665-2 +35962208,https://doi.org/10.1038/s41591-022-01951-8,Publisher Correction: Reporting guideline for the early-stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI.,"Vasey B, Nagendran M, Campbell B, Clifton DA, Collins GS, Denaxas S, Denniston AK, Faes L, Geerts B, Ibrahim M, Liu X, Mateen BA, Mathur P, McCradden MD, Morgan L, Ordish J, Rogers C, Saria S, Ting DSW, Watkinson P, Weber W, Wheatstone P, McCulloch P, DECIDE-AI expert group.",,Nature medicine,2022,2022-10-01,N,,,,,,pdf:https://www.nature.com/articles/s41591-022-01951-8.pdf; doi:https://doi.org/10.1038/s41591-022-01951-8 34458849,https://doi.org/10.1093/oxfimm/iqab014,Protease inhibitor plasma concentrations associate with COVID-19 infection.,"Medjeral-Thomas NR, Troldborg A, Hansen AG, Pihl R, Clarke CL, Peters JE, Thomas DC, Willicombe M, Palarasah Y, Botto M, Pickering MC, Thiel S.",,Oxford open immunology,2021,2021-07-07,Y,Coronavirus; Protease inhibitors; innate immunity; Covid-19,,,"Protease inhibitors influence a range of innate immunity and inflammatory pathways. We quantified plasma concentrations of key anti-inflammatory protease inhibitors in chronic haemodialysis patients with coronavirus disease 2019 (COVID-19). The samples were collected early in the disease course to determine whether plasma protease inhibitor levels associated with the presence and severity of COVID-19. We used antibody-based immunoassays to measure plasma concentrations of C1 esterase inhibitor, alpha2-macroglobulin, antithrombin and inter-alpha-inhibitor heavy chain 4 (ITIH4) in 100 serial samples from 27 haemodialysis patients with COVID-19. ITIH4 was tested in two assays, one measuring intact ITIH4 and another also detecting any fragmented ITIH4 (total ITIH4). Control cohorts were 32 haemodialysis patients without COVID-19 and 32 healthy controls. We compared protease inhibitor concentration based on current and future COVID-19 severity and with C-reactive protein. Results were adjusted for repeated measures and multiple comparisons. Analysis of all available samples demonstrated lower plasma C1 esterase inhibitor and α2M and higher total ITIH4 in COVID-19 compared with dialysis controls. These differences were also seen in the first sample collected after COVID-19 diagnosis, a median of 4 days from diagnostic swab. Plasma ITIH4 levels were higher in severe than the non-severe COVID-19. Serum C-reactive protein correlated positively with plasma levels of antithrombin, intact ITIH4 and total ITIH4. In conclusion, plasma protease inhibitor concentrations are altered in COVID-19.",,pdf:https://academic.oup.com/ooim/article-pdf/2/1/iqab014/48744499/iqab014.pdf; doi:https://doi.org/10.1093/oxfimm/iqab014; html:https://europepmc.org/articles/PMC8371939; pdf:https://europepmc.org/articles/PMC8371939?pdf=render 33623826,https://doi.org/10.12688/wellcomeopenres.16164.2,"The effectiveness of social bubbles as part of a Covid-19 lockdown exit strategy, a modelling study.","Leng T, White C, Hilton J, Kucharski A, Pellis L, Stage H, Davies NG, Centre for Mathematical Modelling of Infectious Disease 2019 nCoV Working Group, Keeling MJ, Flasche S.",,Wellcome open research,2020,2020-01-01,Y,Exit Strategy; Covid-19; Contact Clustering; Social Bubble,,,"Background: ​ During the coronavirus disease 2019 (COVID-19) lockdown, contact clustering in social bubbles may allow extending contacts beyond the household at minimal additional risk and hence has been considered as part of modified lockdown policy or a gradual lockdown exit strategy. We estimated the impact of such strategies on epidemic and mortality risk using the UK as a case study. Methods: ​ We used an individual based model for a synthetic population similar to the UK, stratified into transmission risks from the community, within the household and from other households in the same social bubble. The base case considers a situation where non-essential shops and schools are closed, the secondary household attack rate is 20% and the initial reproduction number is 0.8. We simulate social bubble strategies (where two households form an exclusive pair) for households including children, for single occupancy households, and for all households. We test the sensitivity of results to a range of alternative model assumptions and parameters. Results:  Clustering contacts outside the household into exclusive bubbles is an effective strategy of increasing contacts while limiting the associated increase in epidemic risk. In the base case, social bubbles reduced fatalities by 42% compared to an unclustered increase of contacts. We find that if all households were to form social bubbles the reproduction number would likely increase to above the epidemic threshold of R=1. Strategies allowing households with young children or single occupancy households to form social bubbles increased the reproduction number by less than 11%. The corresponding increase in mortality is proportional to the increase in the epidemic risk but is focussed in older adults irrespective of inclusion in social bubbles. Conclusions: ​ If managed appropriately, social bubbles can be an effective way of extending contacts beyond the household while limiting the increase in epidemic risk.",,doi:https://doi.org/10.12688/wellcomeopenres.16164.2; doi:https://doi.org/10.12688/wellcomeopenres.16164.2; html:https://europepmc.org/articles/PMC7871360; pdf:https://europepmc.org/articles/PMC7871360?pdf=render 31113941,https://doi.org/10.1038/s41467-019-10417-4,Author Correction: Towards a data-integrated cell.,"Malod-Dognin N, Petschnigg J, Windels SFL, Povh J, Hemingway H, Ketteler R, Pržulj N.",,Nature communications,2019,2019-05-21,Y,,,,"The original version of this Article contained an error in the spelling of the author Harry Hemingway, which was incorrectly given as Harry Hemmingway. This has been corrected in both the PDF and HTML versions of the Article.",,pdf:https://www.nature.com/articles/s41467-019-10417-4.pdf; doi:https://doi.org/10.1038/s41467-019-10417-4; html:https://europepmc.org/articles/PMC6529418; pdf:https://europepmc.org/articles/PMC6529418?pdf=render @@ -2259,25 +2259,25 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 34330923,https://doi.org/10.1038/s41467-021-24930-y,Toxin import through the antibiotic efflux channel TolC.,"Housden NG, Webby MN, Lowe ED, El-Baba TJ, Kaminska R, Redfield C, Robinson CV, Kleanthous C.",,Nature communications,2021,2021-07-30,Y,,,,"Bacteria often secrete diffusible protein toxins (bacteriocins) to kill bystander cells during interbacterial competition. Here, we use biochemical, biophysical and structural analyses to show how a bacteriocin exploits TolC, a major outer-membrane antibiotic efflux channel in Gram-negative bacteria, to transport itself across the outer membrane of target cells. Klebicin C (KlebC), a rRNase toxin produced by Klebsiella pneumoniae, binds TolC of a related species (K. quasipneumoniae) with high affinity through an N-terminal, elongated helical hairpin domain common amongst bacteriocins. The KlebC helical hairpin opens like a switchblade to bind TolC. A cryo-EM structure of this partially translocated state, at 3.1 Å resolution, reveals that KlebC associates along the length of the TolC channel. Thereafter, the unstructured N-terminus of KlebC protrudes beyond the TolC iris, presenting a TonB-box sequence to the periplasm. Association with proton-motive force-linked TonB in the inner membrane drives toxin import through the channel. Finally, we demonstrate that KlebC binding to TolC blocks drug efflux from bacteria. Our results indicate that TolC, in addition to its known role in antibiotic export, can function as a protein import channel for bacteriocins.",,pdf:https://www.nature.com/articles/s41467-021-24930-y.pdf; doi:https://doi.org/10.1038/s41467-021-24930-y; html:https://europepmc.org/articles/PMC8324772; pdf:https://europepmc.org/articles/PMC8324772?pdf=render 35142634,https://doi.org/10.2196/31885,Investigating Genetic and Other Determinants of First-Onset Myocardial Infarction in Malaysia: Protocol for the Malaysian Acute Vascular Events Risk Study.,"Chowdhury R, Noh MFM, Ismail SR, van Daalen KR, Kamaruddin PSNM, Zulkiply SH, Azizul NH, Khalid NM, Ali A, Idris IM, Mei YS, Abdullah SR, Faridus N, Yusof NAM, Yusoff NNFM, Jamal R, Rahim AAA, Ghapar AKA, Radhakrishnan AK, Fong AYY, Ismail O, Krishinan S, Lee CY, Bang LH, Mageswaren E, Mahendran K, Amin NHM, Muthusamy G, Jin AOH, Ramli AW, Ross NT, Ruhani AI, Yahya M, Yusoff Y, Abidin SKZ, Amado L, Bolton T, Weston S, Crawte J, Ovenden N, Michielsen A, Monower MM, Mahiyuddin WRW, Wood A, Di Angelantonio E, Sulaiman NS, Danesh J, Butterworth AS.",,JMIR research protocols,2022,2022-02-10,Y,Myocardial infarction; Malaysia; Cardiovascular disease; Case-control study,,,"

Background

Although the burden of premature myocardial infarction (MI) is high in Malaysia, direct evidence on the determinants of MI in this multi-ethnic population remains sparse.

Objective

The Malaysian Acute Vascular Events Risk (MAVERIK) study is a retrospective case-control study established to investigate the genomic, lipid-related, and other determinants of acute MI in Malaysia. In this paper, we report the study protocol and early results.

Methods

By June 2019, we had enrolled approximately 2500 patients with their first MI and 2500 controls without cardiovascular disease, who were frequency-matched by age, sex, and ethnicity, from 17 hospitals in Malaysia. For each participant, serum and whole blood have been collected and stored. Clinical, demographic, and behavioral information has been obtained using a 200-item questionnaire.

Results

Tobacco consumption, a history of diabetes, hypertension, markers of visceral adiposity, indicators of lower socioeconomic status, and a family history of coronary disease were more prevalent in cases than in controls. Adjusted (age and sex) logistic regression models for traditional risk factors indicated that current smoking (odds ratio [OR] 4.11, 95% CI 3.56-4.75; P<.001), previous smoking (OR 1.34, 95% CI 1.12-1.60; P=.001), a history of high blood pressure (OR 2.13, 95% CI 1.86-2.44; P<.001), a history of diabetes mellitus (OR 2.72, 95% CI 2.34-3.17; P<.001), a family history of coronary heart disease (OR 1.28, 95% CI 1.07-1.55; P=.009), and obesity (BMI >30 kg/m2; OR 1.19, 95% CI 1.05-1.34; P=.009) were associated with MI in age- and sex-adjusted models.

Conclusions

The MAVERIK study can serve as a useful platform to investigate genetic and other risk factors for MI in an understudied Southeast Asian population. It should help to hasten the discovery of disease-causing pathways and inform regionally appropriate strategies that optimize public health action.

International registered report identifier (irrid)

RR1-10.2196/31885.",,pdf:https://www.researchprotocols.org/2022/2/e31885/PDF; doi:https://doi.org/10.2196/31885; html:https://europepmc.org/articles/PMC8874931 35235826,https://doi.org/10.1016/j.ijid.2022.02.051,"Assessing the clinical severity of the Omicron variant in the Western Cape Province, South Africa, using the diagnostic PCR proxy marker of RdRp target delay to distinguish between Omicron and Delta infections - a survival analysis.","Hussey H, Davies MA, Heekes A, Williamson C, Valley-Omar Z, Hardie D, Korsman S, Doolabh D, Preiser W, Maponga T, Iranzadeh A, Wasserman S, Boloko L, Symons G, Raubenheimer P, Parker A, Schrueder N, Solomon W, Rousseau P, Wolter N, Jassat W, Cohen C, Lessells R, Wilkinson RJ, Boulle A, Hsiao NY.",,International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases,2022,2022-02-27,Y,South Africa; Clinical Severity; Sars-cov-2; Omicron Variant; Rdrp Target Delay,,,"

Background

At present, it is unclear whether the extent of reduced risk of severe disease seen with SARS-Cov-2 Omicron variant infection is caused by a decrease in variant virulence or by higher levels of population immunity.

Methods

RdRp target delay (RTD) in the Seegene AllplexTM 2019-nCoV PCR assay is a proxy marker for the Delta variant. The absence of this proxy marker in the transition period was used to identify suspected Omicron infections. Cox regression was performed for the outcome of hospital admission in those who tested positive for SARS-CoV-2 on the Seegene AllplexTM assay from November 1 to December 14, 2021 in the Western Cape Province, South Africa, in the public sector. Adjustments were made for vaccination status and prior diagnosis of infection.

Results

A total of 150 cases with RTD and 1486 cases without RTD were included. Cases without RTD had a lower hazard of admission (adjusted hazard ratio [aHR], 0.56; 95% confidence interval [CI], 0.34-0.91). Complete vaccination was protective against admission, with an aHR of 0.45 (95% CI, 0.26-0.77).

Conclusion

Omicron has resulted in a lower risk of hospital admission compared with contemporaneous Delta infection, when using the proxy marker of RTD. Under-ascertainment of reinfections with an immune escape variant remains a challenge to accurately assessing variant virulence.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/95846/7/1-s2.0-S1201971222001291-main.pdf; doi:https://doi.org/10.1016/j.ijid.2022.02.051; html:https://europepmc.org/articles/PMC8882068; pdf:https://europepmc.org/articles/PMC8882068?pdf=render -34796246,https://doi.org/10.1093/ofid/ofab496,"Acceptability, Usability, and Performance of Lateral Flow Immunoassay Tests for Severe Acute Respiratory Syndrome Coronavirus 2 Antibodies: REACT-2 Study of Self-Testing in Nonhealthcare Key Workers.","Davies B, Araghi M, Moshe M, Gao H, Bennet K, Jenkins J, Atchison C, Darzi A, Ashby D, Riley S, Barclay W, Elliott P, Ward H, Cooke G.",,Open forum infectious diseases,2021,2021-10-04,Y,Sensitivity and specificity; Antibody testing; Sars-cov-2; Covid-19 Diagnostic Testing,,,"

Background

Seroprevalence studies are essential to understand the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Various technologies, including laboratory assays and point-of-care self-tests, are available for antibody testing. The interpretation of seroprevalence studies requires comparative data on the performance of antibody tests.

Methods

In June 2020, current and former members of the United Kingdom police forces and fire service performed a self-test lateral flow immunoassay (LFIA), had a nurse-performed LFIA, and provided a venous blood sample for enzyme-linked immunosorbent assay (ELISA). We present the prevalence of antibodies to SARS-CoV-2 and the acceptability and usability of self-test LFIAs, and we determine the sensitivity and specificity of LFIAs compared with laboratory ELISA.

Results

In this cohort of 5189 current and former members of the police service and 263 members of the fire service, 7.4% (396 of 5348; 95% confidence interval [CI], 6.7-8.1) were antibody positive. Seroprevalence was 8.9% (95% CI, 6.9-11.4) in those under 40 years, 11.5% (95% CI, 8.8-15.0) in those of nonwhite ethnicity, and 7.8% (95% CI, 7.1-8.7) in those currently working. Self-test LFIA had an acceptability of 97.7% and a usability of 90.0%. There was substantial agreement between within-participant LFIA results (kappa 0.80; 95% CI, 0.77-0.83). The LFIAs had a similar performance: compared with ELISA, sensitivity was 82.1% (95% CI, 77.7-86.0) self-test and 76.4% (95% CI, 71.9-80.5) nurse-performed with specificity of 97.8% (95% CI, 97.3-98.2) and 98.5% (95% CI, 98.1-98.8), respectively.

Conclusions

A greater proportion of this nonhealthcare key worker cohort showed evidence of previous infection with SARS-CoV-2 than the general population at 6.0% (95% CI, 5.8-6.1) after the first wave in England. The high acceptability and usability reported by participants and similar performance of self-test and nurse-performed LFIAs indicate that the self-test LFIA is fit for purpose for home testing in occupational and community prevalence studies.",,pdf:https://academic.oup.com/ofid/article-pdf/8/11/ofab496/41174715/ofab496.pdf; doi:https://doi.org/10.1093/ofid/ofab496; html:https://europepmc.org/articles/PMC8522420; pdf:https://europepmc.org/articles/PMC8522420?pdf=render 31478583,https://doi.org/10.1002/ejhf.1615,Association between beta-blocker use and mortality/morbidity in older patients with heart failure with reduced ejection fraction. A propensity score-matched analysis from the Swedish Heart Failure Registry.,"Stolfo D, Uijl A, Benson L, Schrage B, Fudim M, Asselbergs FW, Koudstaal S, Sinagra G, Dahlström U, Rosano G, Savarese G.",,European journal of heart failure,2020,2019-10-23,N,Elderly; Heart Failure; Beta-blocker; Registry; Swedehf,Improving Public Health,cardiovascular,"

Background

Beta-blockers reduce mortality and morbidity in heart failure (HF) with reduced ejection fraction (HFrEF). However, patients older than 80 years are poorly represented in randomized controlled trials. We assessed the association between beta-blocker use and outcomes in HFrEF patients aged ≥80 years.

Methods and results

We included patients with an ejection fraction <40% and aged ≥80 years from the Swedish HF Registry. The association between beta-blocker use, all-cause mortality and cardiovascular (CV) mortality/HF hospitalization was assessed by Cox proportional hazard models in a 1:1 propensity score-matched cohort. To assess consistency, the same analyses were performed in a positive control cohort with age <80 years. A negative control outcome analysis was run using hospitalization for cancer as endpoint. Of 6562 patients aged ≥80 years, 5640 (86%) received beta-blockers. In the matched cohort including 1732 patients, beta-blocker use was associated with a significant reduction in the risk of all-cause mortality [hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.79-0.99]. Reduction in CV mortality/HF hospitalization was not significant (HR 0.94, 95% CI 0.85-1.05) due to the lack of association with HF hospitalization, whereas CV death was significantly reduced. After adjustment rather than matching for the propensity score in the overall cohort, beta-blocker use was associated with reduced risk of all outcomes. In patients aged <80 years, use of beta-blockers was associated with reduced risk of all-cause death (HR 0.79, 95% CI 0.68-0.92) and of the composite outcome (HR 0.88, 95% CI 0.77-0.99).

Conclusions

In HFrEF patients ≥80 years of age, use of beta-blockers was high and was associated with improved all-cause and CV survival.",This study looked at 6562 people with severe heart failure and whether there was an association between taking beta-blockers (a drug to control heart rate) and heart disease. They used a national Swedish registry of patients with heart failure and compared those who were taking beta blockers (866 patients) to those not taking beta blockers (866 patients). The study found that patients who were taking beta blockers tended also to have lower risk of heart complications and were more likely to survive.,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejhf.1615; doi:https://doi.org/10.1002/ejhf.1615 +34796246,https://doi.org/10.1093/ofid/ofab496,"Acceptability, Usability, and Performance of Lateral Flow Immunoassay Tests for Severe Acute Respiratory Syndrome Coronavirus 2 Antibodies: REACT-2 Study of Self-Testing in Nonhealthcare Key Workers.","Davies B, Araghi M, Moshe M, Gao H, Bennet K, Jenkins J, Atchison C, Darzi A, Ashby D, Riley S, Barclay W, Elliott P, Ward H, Cooke G.",,Open forum infectious diseases,2021,2021-10-04,Y,Sensitivity and specificity; Antibody testing; Sars-cov-2; Covid-19 Diagnostic Testing,,,"

Background

Seroprevalence studies are essential to understand the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Various technologies, including laboratory assays and point-of-care self-tests, are available for antibody testing. The interpretation of seroprevalence studies requires comparative data on the performance of antibody tests.

Methods

In June 2020, current and former members of the United Kingdom police forces and fire service performed a self-test lateral flow immunoassay (LFIA), had a nurse-performed LFIA, and provided a venous blood sample for enzyme-linked immunosorbent assay (ELISA). We present the prevalence of antibodies to SARS-CoV-2 and the acceptability and usability of self-test LFIAs, and we determine the sensitivity and specificity of LFIAs compared with laboratory ELISA.

Results

In this cohort of 5189 current and former members of the police service and 263 members of the fire service, 7.4% (396 of 5348; 95% confidence interval [CI], 6.7-8.1) were antibody positive. Seroprevalence was 8.9% (95% CI, 6.9-11.4) in those under 40 years, 11.5% (95% CI, 8.8-15.0) in those of nonwhite ethnicity, and 7.8% (95% CI, 7.1-8.7) in those currently working. Self-test LFIA had an acceptability of 97.7% and a usability of 90.0%. There was substantial agreement between within-participant LFIA results (kappa 0.80; 95% CI, 0.77-0.83). The LFIAs had a similar performance: compared with ELISA, sensitivity was 82.1% (95% CI, 77.7-86.0) self-test and 76.4% (95% CI, 71.9-80.5) nurse-performed with specificity of 97.8% (95% CI, 97.3-98.2) and 98.5% (95% CI, 98.1-98.8), respectively.

Conclusions

A greater proportion of this nonhealthcare key worker cohort showed evidence of previous infection with SARS-CoV-2 than the general population at 6.0% (95% CI, 5.8-6.1) after the first wave in England. The high acceptability and usability reported by participants and similar performance of self-test and nurse-performed LFIAs indicate that the self-test LFIA is fit for purpose for home testing in occupational and community prevalence studies.",,pdf:https://academic.oup.com/ofid/article-pdf/8/11/ofab496/41174715/ofab496.pdf; doi:https://doi.org/10.1093/ofid/ofab496; html:https://europepmc.org/articles/PMC8522420; pdf:https://europepmc.org/articles/PMC8522420?pdf=render 33087179,https://doi.org/10.1186/s12916-020-01790-9,Reconstructing the early global dynamics of under-ascertained COVID-19 cases and infections.,"Russell TW, Golding N, Hellewell J, Abbott S, Wright L, Pearson CAB, van Zandvoort K, Jarvis CI, Gibbs H, Liu Y, Eggo RM, Edmunds WJ, Kucharski AJ, CMMID COVID-19 working group.",,BMC medicine,2020,2020-10-22,Y,Surveillance; Situational Awareness; Under-reporting; Case Ascertainment; Outbreak Analysis; Covid-19; Sars-cov-2,,,"

Background

Asymptomatic or subclinical SARS-CoV-2 infections are often unreported, which means that confirmed case counts may not accurately reflect underlying epidemic dynamics. Understanding the level of ascertainment (the ratio of confirmed symptomatic cases to the true number of symptomatic individuals) and undetected epidemic progression is crucial to informing COVID-19 response planning, including the introduction and relaxation of control measures. Estimating case ascertainment over time allows for accurate estimates of specific outcomes such as seroprevalence, which is essential for planning control measures.

Methods

Using reported data on COVID-19 cases and fatalities globally, we estimated the proportion of symptomatic cases (i.e. any person with any of fever ≥ 37.5 °C, cough, shortness of breath, sudden onset of anosmia, ageusia or dysgeusia illness) that were reported in 210 countries and territories, given those countries had experienced more than ten deaths. We used published estimates of the baseline case fatality ratio (CFR), which was adjusted for delays and under-ascertainment, then calculated the ratio of this baseline CFR to an estimated local delay-adjusted CFR to estimate the level of under-ascertainment in a particular location. We then fit a Bayesian Gaussian process model to estimate the temporal pattern of under-ascertainment.

Results

Based on reported cases and deaths, we estimated that, during March 2020, the median percentage of symptomatic cases detected across the 84 countries which experienced more than ten deaths ranged from 2.4% (Bangladesh) to 100% (Chile). Across the ten countries with the highest number of total confirmed cases as of 6 July 2020, we estimated that the peak number of symptomatic cases ranged from 1.4 times (Chile) to 18 times (France) larger than reported. Comparing our model with national and regional seroprevalence data where available, we find that our estimates are consistent with observed values. Finally, we estimated seroprevalence for each country. As of 7 June, our seroprevalence estimates range from 0% (many countries) to 13% (95% CrI 5.6-24%) (Belgium).

Conclusions

We found substantial under-ascertainment of symptomatic cases, particularly at the peak of the first wave of the SARS-CoV-2 pandemic, in many countries. Reported case counts will therefore likely underestimate the rate of outbreak growth initially and underestimate the decline in the later stages of an epidemic. Although there was considerable under-reporting in many locations, our estimates were consistent with emerging serological data, suggesting that the proportion of each country's population infected with SARS-CoV-2 worldwide is generally low.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01790-9; doi:https://doi.org/10.1186/s12916-020-01790-9; html:https://europepmc.org/articles/PMC7577796; pdf:https://europepmc.org/articles/PMC7577796?pdf=render 34039579,https://doi.org/10.1136/bmjopen-2021-049721,Changes in daily mental health service use and mortality at the commencement and lifting of COVID-19 'lockdown' policy in 10 UK sites: a regression discontinuity in time design.,"Bakolis I, Stewart R, Baldwin D, Beenstock J, Bibby P, Broadbent M, Cardinal R, Chen S, Chinnasamy K, Cipriani A, Douglas S, Horner P, Jackson CA, John A, Joyce DW, Lee SC, Lewis J, McIntosh A, Nixon N, Osborn D, Phiri P, Rathod S, Smith T, Sokal R, Waller R, Landau S.",,BMJ open,2021,2021-05-26,Y,Mental health; Adult Psychiatry; Old Age Psychiatry; Organisation Of Health Services; Covid-19,,,"

Objectives

To investigate changes in daily mental health (MH) service use and mortality in response to the introduction and the lifting of the COVID-19 'lockdown' policy in Spring 2020.

Design

A regression discontinuity in time (RDiT) analysis of daily service-level activity.

Setting and participants

Mental healthcare data were extracted from 10 UK providers.

Outcome measures

Daily (weekly for one site) deaths from all causes, referrals and discharges, inpatient care (admissions, discharges, caseloads) and community services (face-to-face (f2f)/non-f2f contacts, caseloads): Adult, older adult and child/adolescent mental health; early intervention in psychosis; home treatment teams and liaison/Accident and Emergency (A&E). Data were extracted from 1 Jan 2019 to 31 May 2020 for all sites, supplemented to 31 July 2020 for four sites. Changes around the commencement and lifting of COVID-19 'lockdown' policy (23 March and 10 May, respectively) were estimated using a RDiT design with a difference-in-difference approach generating incidence rate ratios (IRRs), meta-analysed across sites.

Results

Pooled estimates for the lockdown transition showed increased daily deaths (IRR 2.31, 95% CI 1.86 to 2.87), reduced referrals (IRR 0.62, 95% CI 0.55 to 0.70) and reduced inpatient admissions (IRR 0.75, 95% CI 0.67 to 0.83) and caseloads (IRR 0.85, 95% CI 0.79 to 0.91) compared with the pre lockdown period. All community services saw shifts from f2f to non-f2f contacts, but varied in caseload changes. Lift of lockdown was associated with reduced deaths (IRR 0.42, 95% CI 0.27 to 0.66), increased referrals (IRR 1.36, 95% CI 1.15 to 1.60) and increased inpatient admissions (IRR 1.21, 95% CI 1.04 to 1.42) and caseloads (IRR 1.06, 95% CI 1.00 to 1.12) compared with the lockdown period. Site-wide activity, inpatient care and community services did not return to pre lockdown levels after lift of lockdown, while number of deaths did. Between-site heterogeneity most often indicated variation in size rather than direction of effect.

Conclusions

MH service delivery underwent sizeable changes during the first national lockdown, with as-yet unknown and unevaluated consequences.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/5/e049721.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049721; html:https://europepmc.org/articles/PMC8159668; pdf:https://europepmc.org/articles/PMC8159668?pdf=render 33415961,https://doi.org/10.19191/ep20.5-6.s1.p179.088,Initial plans for a large-scale investigation into the chronic health effects of earthquakes in Italy: building on Barbara Pacelli's legacy.,"Allara E, Ripoll Gallardo A, Fabiani L, Barone Adesi F, Sofianopoulou E, Ragazzoni L, Wood A, Faggiano F, Della Corte F.",,Epidemiologia e prevenzione,2020,2020-09-01,N,,,,"Barbara Pacelli, a young Italian epidemiologist, passed away unexpectedly in September 2019. During her prolific professional life, she gave several scientific contributions to natural disaster epidemiology, particularly in relation to the medium and long-term health effects of earthquakes. In this opinion paper, we reflect on Barbara's legacy and outline potential actions that could arise from her work. Particularly, availability of electronic health records would enable a systematic and large-scale investigation into the long-term health effects of earthquakes in Italy, a country with high seismic risk. This effort would have high societal value as it would likely enable mitigation of substantial morbidity and mortality in areas affected by earthquakes. In this paper, we define scope, objectives, potential data sources, and analysis methods that could be used to systematically assess the chronic health effects of recent earthquakes in Italy. Keywords: earthquakes; chronic diseases; electronic health records; retrospective cohort; case crossover study.",,doi:https://doi.org/10.19191/EP20.5-6.S1.P179.088 -37286573,https://doi.org/10.1038/s41467-023-38383-y,Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism.,"Iglesias MJ, Sanchez-Rivera L, Ibrahim-Kosta M, Naudin C, Munsch G, Goumidi L, Farm M, Smith PM, Thibord F, Kral-Pointner JB, Hong MG, Suchon P, Germain M, Schrottmaier W, Dusart P, Boland A, Kotol D, Edfors F, Koprulu M, Pietzner M, Langenberg C, Damrauer SM, Johnson AD, Klarin DM, Smith NL, Smadja DM, Holmström M, Magnusson M, Silveira A, Uhlén M, Renné T, Martinez-Perez A, Emmerich J, Deleuze JF, Antovic J, Soria Fernandez JM, Assinger A, Schwenk JM, Souto Andres JC, Morange PE, Butler LM, Trégouët DA, Odeberg J.",,Nature communications,2023,2023-06-07,Y,,,,"Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement Factor H Related 5 protein (CFHR5), a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.",,pdf:https://www.nature.com/articles/s41467-023-38383-y.pdf; doi:https://doi.org/10.1038/s41467-023-38383-y; html:https://europepmc.org/articles/PMC10247781; pdf:https://europepmc.org/articles/PMC10247781?pdf=render 32097451,https://doi.org/10.1093/ije/dyaa015,Commentary: Using human genetics to guide the repurposing of medicines.,"Bovijn J, Censin JC, Lindgren CM, Holmes MV.",,International journal of epidemiology,2020,2020-08-01,N,,,,,,pdf:https://academic.oup.com/ije/article-pdf/49/4/1140/34275903/dyaa015.pdf; doi:https://doi.org/10.1093/ije/dyaa015; html:https://europepmc.org/articles/PMC7660148; pdf:https://europepmc.org/articles/PMC7660148?pdf=render; doi:https://doi.org/10.1093/ije/dyaa015 +37286573,https://doi.org/10.1038/s41467-023-38383-y,Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism.,"Iglesias MJ, Sanchez-Rivera L, Ibrahim-Kosta M, Naudin C, Munsch G, Goumidi L, Farm M, Smith PM, Thibord F, Kral-Pointner JB, Hong MG, Suchon P, Germain M, Schrottmaier W, Dusart P, Boland A, Kotol D, Edfors F, Koprulu M, Pietzner M, Langenberg C, Damrauer SM, Johnson AD, Klarin DM, Smith NL, Smadja DM, Holmström M, Magnusson M, Silveira A, Uhlén M, Renné T, Martinez-Perez A, Emmerich J, Deleuze JF, Antovic J, Soria Fernandez JM, Assinger A, Schwenk JM, Souto Andres JC, Morange PE, Butler LM, Trégouët DA, Odeberg J.",,Nature communications,2023,2023-06-07,Y,,,,"Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement Factor H Related 5 protein (CFHR5), a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.",,pdf:https://www.nature.com/articles/s41467-023-38383-y.pdf; doi:https://doi.org/10.1038/s41467-023-38383-y; html:https://europepmc.org/articles/PMC10247781; pdf:https://europepmc.org/articles/PMC10247781?pdf=render 32706893,https://doi.org/10.1182/bloodadvances.2020002230,Artificial intelligence-based morphological fingerprinting of megakaryocytes: a new tool for assessing disease in MPN patients.,"Sirinukunwattana K, Aberdeen A, Theissen H, Sousos N, Psaila B, Mead AJ, Turner GDH, Rees G, Rittscher J, Royston D.",,Blood advances,2020,2020-07-01,N,,,,"Accurate diagnosis and classification of myeloproliferative neoplasms (MPNs) requires integration of clinical, morphological, and genetic findings. Despite major advances in our understanding of the molecular and genetic basis of MPNs, the morphological assessment of bone marrow trephines (BMT) is critical in differentiating MPN subtypes and their reactive mimics. However, morphological assessment is heavily constrained by a reliance on subjective, qualitative, and poorly reproducible criteria. To improve the morphological assessment of MPNs, we have developed a machine learning approach for the automated identification, quantitative analysis, and abstract representation of megakaryocyte features using reactive/nonneoplastic BMT samples (n = 43) and those from patients with established diagnoses of essential thrombocythemia (n = 45), polycythemia vera (n = 18), or myelofibrosis (n = 25). We describe the application of an automated workflow for the identification and delineation of relevant histological features from routinely prepared BMTs. Subsequent analysis enabled the tissue diagnosis of MPN with a high predictive accuracy (area under the curve = 0.95) and revealed clear evidence of the potential to discriminate between important MPN subtypes. Our method of visually representing abstracted megakaryocyte features in the context of analyzed patient cohorts facilitates the interpretation and monitoring of samples in a manner that is beyond conventional approaches. The automated BMT phenotyping approach described here has significant potential as an adjunct to standard genetic and molecular testing in established or suspected MPN patients, either as part of the routine diagnostic pathway or in the assessment of disease progression/response to treatment.",,pdf:https://ashpublications.org/bloodadvances/article-pdf/4/14/3284/1749738/advancesadv2020002230.pdf; doi:https://doi.org/10.1182/bloodadvances.2020002230; html:https://europepmc.org/articles/PMC7391156; pdf:https://europepmc.org/articles/PMC7391156?pdf=render; doi:https://doi.org/10.1182/bloodadvances.2020002230 32184442,https://doi.org/10.1038/s42003-020-0857-9,Genome-wide association identifies seven loci for pelvic organ prolapse in Iceland and the UK Biobank.,"Olafsdottir T, Thorleifsson G, Sulem P, Stefansson OA, Medek H, Olafsson K, Ingthorsson O, Gudmundsson V, Jonsdottir I, Halldorsson GH, Kristjansson RP, Frigge ML, Stefansdottir L, Sigurdsson JK, Oddsson A, Sigurdsson A, Eggertsson HP, Melsted P, Halldorsson BV, Lund SH, Styrkarsdottir U, Steinthorsdottir V, Gudmundsson J, Holm H, Tragante V, Asselbergs FW, Thorsteinsdottir U, Gudbjartsson DF, Jonsdottir K, Rafnar T, Stefansson K.",,Communications biology,2020,2020-03-17,Y,,,,"Pelvic organ prolapse (POP) is a downward descent of one or more of the pelvic organs, resulting in a protrusion of the vaginal wall and/or uterus. We performed a genome-wide association study of POP using data from Iceland and the UK Biobank, a total of 15,010 cases with hospital-based diagnosis code and 340,734 female controls, and found eight sequence variants at seven loci associating with POP (P < 5 × 10-8); seven common (minor allele frequency >5%) and one with minor allele frequency of 4.87%. Some of the variants associating with POP also associated with traits of similar pathophysiology. Of these, rs3820282, which may alter the estrogen-based regulation of WNT4, also associates with leiomyoma of uterus, gestational duration and endometriosis. Rs3791675 at EFEMP1, a gene involved in connective tissue homeostasis, also associates with hernias and carpal tunnel syndrome. Our results highlight the role of connective tissue metabolism and estrogen exposure in the etiology of POP.",,pdf:https://www.nature.com/articles/s42003-020-0857-9.pdf; doi:https://doi.org/10.1038/s42003-020-0857-9; html:https://europepmc.org/articles/PMC7078216; pdf:https://europepmc.org/articles/PMC7078216?pdf=render 33905495,https://doi.org/10.1093/nar/gkab291,Endonuclease enrichment TAPS for cost-effective genome-wide base-resolution DNA methylation detection.,"Cheng J, Siejka-Zielińska P, Liu Y, Chandran A, Kriaucionis S, Song CX.",,Nucleic acids research,2021,2021-07-01,Y,,,,"Whole genome base-resolution methylome sequencing allows for the most comprehensive analysis of DNA methylation, however, the considerable sequencing cost often limits its applications. While reduced representation sequencing can be an affordable alternative, over 80% of CpGs in the genome are not covered. Building on our recently developed TET-assisted pyridine borane sequencing (TAPS) method, we here described endonuclease enrichment TAPS (eeTAPS), which utilizes dihydrouracil (DHU)-cleaving endonuclease digestion of TAPS-converted DNA to enrich methylated CpG sites (mCpGs). eeTAPS can accurately detect 87% of mCpGs in the mouse genome with a sequencing depth equivalent to 4× whole genome sequencing. In comparison, reduced representation TAPS (rrTAPS) detected less than 4% of mCpGs with 2.5× sequencing depth. Our results demonstrate eeTAPS to be a new strategy for cost-effective genome-wide methylation analysis at single-CpG resolution that can fill the gap between whole-genome and reduced representation sequencing.",,pdf:https://ora.ox.ac.uk/objects/uuid:3e48f9e0-d3c3-41ec-99ff-cc64d141d6cf/files/rcz30pt21m; doi:https://doi.org/10.1093/nar/gkab291; html:https://europepmc.org/articles/PMC8287915; pdf:https://europepmc.org/articles/PMC8287915?pdf=render -35103486,https://doi.org/10.1128/msystems.01132-21,Using Community Ecology Theory and Computational Microbiome Methods To Study Human Milk as a Biological System.,"Shenhav L, Azad MB.",,mSystems,2022,2022-02-01,Y,Lactation; Human Milk; Breastfeeding; Chronobiology; Computational Methods; System Biology; Human Microbiome; Community Ecology Theory,,,"Human milk is a complex and dynamic biological system that has evolved to optimally nourish and protect human infants. Yet, according to a recent priority-setting review, ""our current understanding of human milk composition and its individual components and their functions fails to fully recognize the importance of the chronobiology and systems biology of human milk in the context of milk synthesis, optimal timing and duration of feeding, and period of lactation"" (P. Christian et al., Am J Clin Nutr 113:1063-1072, 2021, https://doi.org/10.1093/ajcn/nqab075). We attribute this critical knowledge gap to three major reasons as follows. (i) Studies have typically examined each subsystem of the mother-milk-infant ""triad"" in isolation and often focus on a single element or component (e.g., maternal lactation physiology or milk microbiome or milk oligosaccharides or infant microbiome or infant gut physiology). This undermines our ability to develop comprehensive representations of the interactions between these elements and study their response to external perturbations. (ii) Multiomics studies are often cross-sectional, presenting a snapshot of milk composition, largely ignoring the temporal variability during lactation. The lack of temporal resolution precludes the characterization and inference of robust interactions between the dynamic subsystems of the triad. (iii) We lack computational methods to represent and decipher the complex ecosystem of the mother-milk-infant triad and its environment. In this review, we advocate for longitudinal multiomics data collection and demonstrate how incorporating knowledge gleaned from microbial community ecology and computational methods developed for microbiome research can serve as an anchor to advance the study of human milk and its many components as a ""system within a system.""",,doi:https://doi.org/10.1128/msystems.01132-21; doi:https://doi.org/10.1128/msystems.01132-21; html:https://europepmc.org/articles/PMC8805635; pdf:https://europepmc.org/articles/PMC8805635?pdf=render 30681347,https://doi.org/10.1161/circgen.118.002328,Integrative Functional Annotation of 52 Genetic Loci Influencing Myocardial Mass Identifies Candidate Regulatory Variants and Target Genes.,"Hemerich D, Pei J, Harakalova M, van Setten J, Boymans S, Boukens BJ, Efimov IR, Michels M, van der Velden J, Vink A, Cheng C, van der Harst P, Moore JH, Mokry M, Tragante V, Asselbergs FW.",,Circulation. Genomic and precision medicine,2019,2019-02-01,N,Genetics; Electrocardiography; Acetylation; Heart Failure; Cardiomyopathies,The Human Phenome,,"

Background

Regulatory elements may be involved in the mechanisms by which 52 loci influence myocardial mass, reflected by abnormal amplitude and duration of the QRS complex on the ECG. Functional annotation thus far did not take into account how these elements are affected in disease context.

Methods

We generated maps of regulatory elements on hypertrophic cardiomyopathy patients (ChIP-seq N=14 and RNA-seq N=11) and nondiseased hearts (ChIP-seq N=4 and RNA-seq N=11). We tested enrichment of QRS-associated loci on elements differentially acetylated and directly regulating differentially expressed genes between hypertrophic cardiomyopathy patients and controls. We further performed functional annotation on QRS-associated loci using these maps of differentially active regulatory elements.

Results

Regions differentially affected in disease showed a stronger enrichment ( P=8.6×10-5) for QRS-associated variants than those not showing differential activity ( P=0.01). Promoters of genes differentially regulated between hypertrophic cardiomyopathy patients and controls showed more enrichment ( P=0.001) than differentially acetylated enhancers ( P=0.8) and super-enhancers ( P=0.025). We also identified 74 potential causal variants overlapping these differential regulatory elements. Eighteen of the genes mapped confirmed previous findings, now also pinpointing the potentially affected regulatory elements and candidate causal variants. Fourteen new genes were also mapped.

Conclusions

Our results suggest differentially active regulatory elements between hypertrophic cardiomyopathy patients and controls can offer more insights into the mechanisms of QRS-associated loci than elements not affected by disease.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.118.002328; doi:https://doi.org/10.1161/CIRCGEN.118.002328; html:https://europepmc.org/articles/PMC6380958; pdf:https://europepmc.org/articles/PMC6380958?pdf=render; doi:https://doi.org/10.1161/circgen.118.002328 +35103486,https://doi.org/10.1128/msystems.01132-21,Using Community Ecology Theory and Computational Microbiome Methods To Study Human Milk as a Biological System.,"Shenhav L, Azad MB.",,mSystems,2022,2022-02-01,Y,Lactation; Human Milk; Breastfeeding; Chronobiology; Computational Methods; System Biology; Human Microbiome; Community Ecology Theory,,,"Human milk is a complex and dynamic biological system that has evolved to optimally nourish and protect human infants. Yet, according to a recent priority-setting review, ""our current understanding of human milk composition and its individual components and their functions fails to fully recognize the importance of the chronobiology and systems biology of human milk in the context of milk synthesis, optimal timing and duration of feeding, and period of lactation"" (P. Christian et al., Am J Clin Nutr 113:1063-1072, 2021, https://doi.org/10.1093/ajcn/nqab075). We attribute this critical knowledge gap to three major reasons as follows. (i) Studies have typically examined each subsystem of the mother-milk-infant ""triad"" in isolation and often focus on a single element or component (e.g., maternal lactation physiology or milk microbiome or milk oligosaccharides or infant microbiome or infant gut physiology). This undermines our ability to develop comprehensive representations of the interactions between these elements and study their response to external perturbations. (ii) Multiomics studies are often cross-sectional, presenting a snapshot of milk composition, largely ignoring the temporal variability during lactation. The lack of temporal resolution precludes the characterization and inference of robust interactions between the dynamic subsystems of the triad. (iii) We lack computational methods to represent and decipher the complex ecosystem of the mother-milk-infant triad and its environment. In this review, we advocate for longitudinal multiomics data collection and demonstrate how incorporating knowledge gleaned from microbial community ecology and computational methods developed for microbiome research can serve as an anchor to advance the study of human milk and its many components as a ""system within a system.""",,doi:https://doi.org/10.1128/msystems.01132-21; doi:https://doi.org/10.1128/msystems.01132-21; html:https://europepmc.org/articles/PMC8805635; pdf:https://europepmc.org/articles/PMC8805635?pdf=render 30772400,https://doi.org/10.1016/j.neuroimage.2019.02.028,Hierarchical complexity of the adult human structural connectome.,"Smith K, Bastin ME, Cox SR, Valdés Hernández MC, Wiseman S, Escudero J, Sudlow C.",,NeuroImage,2019,2019-02-14,Y,MRI; Brain Networks; Hierarchical Complexity; Human Structural Connectome,The Human Phenome,,"The structural network of the human brain has a rich topology which many have sought to characterise using standard network science measures and concepts. However, this characterisation remains incomplete and the non-obvious features of this topology have largely confounded attempts towards comprehensive constructive modelling. This calls for new perspectives. Hierarchical complexity is an emerging paradigm of complex network topology based on the observation that complex systems are composed of hierarchies within which the roles of hierarchically equivalent nodes display highly variable connectivity patterns. Here we test the hierarchical complexity of the human structural connectomes of a group of seventy-nine healthy adults. Binary connectomes are found to be more hierarchically complex than three benchmark random network models. This provides a new key description of brain structure, revealing a rich diversity of connectivity patterns within hierarchically equivalent nodes. Dividing the connectomes into four tiers based on degree magnitudes indicates that the most complex nodes are neither those with the highest nor lowest degrees but are instead found in the middle tiers. Spatial mapping of the brain regions in each hierarchical tier reveals consistency with the current anatomical, functional and neuropsychological knowledge of the human brain. The most complex tier (Tier 3) involves regions believed to bridge high-order cognitive (Tier 1) and low-order sensorimotor processing (Tier 2). We then show that such diversity of connectivity patterns aligns with the diversity of functional roles played out across the brain, demonstrating that hierarchical complexity can characterise functional diversity strictly from the network topology.",,doi:https://doi.org/10.1016/j.neuroimage.2019.02.028; doi:https://doi.org/10.1016/j.neuroimage.2019.02.028; html:https://europepmc.org/articles/PMC6503942 37247330,https://doi.org/10.1093/eurheartj/ehad260,SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe.,SCORE2-Diabetes Working Group and the ESC Cardiovascular Risk Collaboration.,,European heart journal,2023,2023-07-01,Y,Cardiovascular diseases; Prediction model; Diabetes,,,"

Aims

To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in individuals with type 2 diabetes in Europe.

Methods and results

SCORE2-Diabetes was developed by extending SCORE2 algorithms using individual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further individuals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on individuals' levels of diabetes-related factors. For example, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively.

Conclusion

SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in individuals with type 2 diabetes, enhances identification of individuals at higher risk of developing CVD across Europe.",,pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad260/50482240/ehad260.pdf; doi:https://doi.org/10.1093/eurheartj/ehad260; html:https://europepmc.org/articles/PMC10361012; pdf:https://europepmc.org/articles/PMC10361012?pdf=render 35487729,https://doi.org/10.1136/bmjopen-2021-056541,"Associations of presenting symptoms and subsequent adverse clinical outcomes in people with unipolar depression: a prospective natural language processing (NLP), transdiagnostic, network analysis of electronic health record (EHR) data.","Patel R, Irving J, Brinn A, Taylor M, Shetty H, Pritchard M, Stewart R, Fusar-Poli P, McGuire P.",,BMJ open,2022,2022-04-29,Y,epidemiology; Health Informatics; Schizophrenia & Psychotic Disorders; Depression & Mood Disorders,,,"

Objective

To investigate the associations of symptoms of mania and depression with clinical outcomes in people with unipolar depression.

Design

A natural language processing electronic health record study. We used network analysis to determine symptom network structure and multivariable Cox regression to investigate associations with clinical outcomes.

Setting

The South London and Maudsley Clinical Record Interactive Search database.

Participants

All patients presenting with unipolar depression between 1 April 2006 and 31 March 2018.

Exposure

(1) Symptoms of mania: Elation; Grandiosity; Flight of ideas; Irritability; Pressured speech. (2) Symptoms of depression: Disturbed mood; Anhedonia; Guilt; Hopelessness; Helplessness; Worthlessness; Tearfulness; Low energy; Reduced appetite; Weight loss. (3) Symptoms of mania or depression (overlapping symptoms): Poor concentration; Insomnia; Disturbed sleep; Agitation; Mood instability.

Main outcomes

(1) Bipolar or psychotic disorder diagnosis. (2) Psychiatric hospital admission.

Results

Out of 19 707 patients, at least 1 depression, overlapping or mania symptom was present in 18 998 (96.4%), 15 954 (81.0%) and 4671 (23.7%) patients, respectively. 2772 (14.1%) patients subsequently developed bipolar or psychotic disorder during the follow-up period. The presence of at least one mania (HR 2.00, 95% CI 1.85 to 2.16), overlapping symptom (HR 1.71, 95% CI 1.52 to 1.92) or symptom of depression (HR 1.31, 95% CI 1.07 to 1.61) were associated with significantly increased risk of onset of a bipolar or psychotic disorder. Mania (HR 1.95, 95% CI 1.77 to 2.15) and overlapping symptoms (HR 1.76, 95% CI 1.52 to 2.04) were associated with greater risk for psychiatric hospital admission than symptoms of depression (HR 1.41, 95% CI 1.06 to 1.88).

Conclusions

The presence of mania or overlapping symptoms in people with unipolar depression is associated with worse clinical outcomes. Symptom-based approaches to defining clinical phenotype may facilitate a more personalised treatment approach and better predict subsequent clinical outcomes than psychiatric diagnosis alone.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e056541.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-056541; html:https://europepmc.org/articles/PMC9058769; pdf:https://europepmc.org/articles/PMC9058769?pdf=render 31794059,https://doi.org/10.1111/bjd.18778,What is the evidence for interactions between filaggrin null mutations and environmental exposures in the aetiology of atopic dermatitis? A systematic review.,"Blakeway H, Van-de-Velde V, Allen VB, Kravvas G, Palla L, Page MJ, Flohr C, Weller RB, Irvine AD, McPherson T, Roberts A, Williams HC, Reynolds N, Brown SJ, Paternoster L, Langan SM, (on behalf of UK TREND Eczema Network).",,The British journal of dermatology,2020,2020-02-11,Y,,,,"

Background

Epidemiological studies indicate that gene-environment interactions play a role in atopic dermatitis (AD).

Objectives

To review the evidence for gene-environment interactions in AD aetiology, focusing on filaggrin (FLG) loss-of-function mutations.

Methods

A systematic search from inception to September 2018 in Embase, MEDLINE and BIOSIS was performed. Search terms included all synonyms for AD and filaggrin/FLG; any genetic or epidemiological study design using any statistical methods were included. Quality assessment using criteria modified from guidance (ROBINS-I and Human Genome Epidemiology Network) for nonrandomized and genetic studies was completed, including consideration of power. Heterogeneity of study design and analyses precluded the use of meta-analysis.

Results

Of 1817 papers identified, 12 studies fulfilled the inclusion criteria required and performed formal interaction testing. There was some evidence for FLG-environment interactions in six of the studies (P-value for interaction ≤ 0·05), including early-life cat ownership, older siblings, water hardness, phthalate exposure, higher urinary phthalate metabolite levels (which all increased AD risk additional to FLG null genotype) and prolonged breastfeeding (which decreased AD risk in the context of FLG null genotype). Major limitations of published studies were the low numbers of individuals (ranging from five to 94) with AD and FLG loss-of-function mutations and exposure to specific environmental factors, and variation in exposure definitions.

Conclusions

Evidence on FLG-environment interactions in AD aetiology is limited. However, many of the studies lacked large enough sample sizes to assess these interactions fully. Further research is needed with larger sample sizes and clearly defined exposure assessment. Linked Comment: Park and Seo. Br J Dermatol 2020; 183:411.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.18778; doi:https://doi.org/10.1111/bjd.18778; html:https://europepmc.org/articles/PMC7496176; pdf:https://europepmc.org/articles/PMC7496176?pdf=render 34321180,https://doi.org/10.1016/j.aucc.2021.05.013,The impact of distance on post-ICU disability.,"D'Arcy J, Haines K, Paul E, Doherty Z, Goodwin A, Bailey M, Barrett J, Bellomo R, Bucknall T, Gabbe BJ, Higgins AM, Iwashyna TJ, Murray LJ, Myles PS, Ponsford J, Pilcher D, Udy AA, Walker C, Young M, Cooper DJJ, Hodgson CL, ICU-Recovery Investigators.",,Australian critical care : official journal of the Confederation of Australian Critical Care Nurses,2022,2021-07-25,N,Quality of life; Mechanical ventilation; Distance; Disability; Intensive Care,,,"

Background

Nonurban residential living is associated with adverse outcomes for a number of chronic health conditions. However, it is unclear what effect it has amongst survivors of critical illness.

Objectives

The purpose of this study is to determine whether patients living greater than 50 km from the treating intensive care unit (ICU) have disability outcomes at 6 months that differ from people living within 50 km.

Methods

This was a multicentre, prospective cohort study conducted in five metropolitan ICUs. Participants were adults admitted to the ICU, who received >24 h of mechanical ventilation and survived to hospital discharge. In a secondary analysis of these data, the cohort was dichotomised based on residential distance from the treating ICU: <50 km and ≥50 km. The primary outcome was patient-reported disability using the 12-item World Health Organization's Disability Assessment Schedule (WHODAS 2.0). This was recorded at 6 months after ICU admission by telephone interview. Secondary outcomes included health status as measured by EQ-5D-5L return to work and psychological function as measured by the Hospital Anxiety and Depression Scale (HADS). Multivariable logistic regression was used to assess the association between distance from the ICU and moderate to severe disability, adjusted for potential confounders. Variables included in the multivariable model were deemed to be clinically relevant and had baseline imbalance between groups (p < 0.10). These included marital status and hours of mechanical ventilation. Sensitivity analysis was also conducted using distance in kilometres as a continuous variable.

Results

A total of 262 patients were enrolled, and 169 (65%) lived within 50 km of the treating ICU and 93 (35%) lived ≥50 km from the treating ICU (interquartile range [IQR] 10-664 km). There was no difference in patient-reported disability at 6 months between patients living <50 km and those living ≥50 km (WHODAS total disability % [IQR] 10.4 [2.08-25] v 14.6 [2.08-20.8], P = 0.74). There was also no difference between groups for the six major life domains of the WHODAS. There was no difference in rates of anxiety or depression as measured by HADS score (HADS anxiety median [IQR] 4 [1-7] v 3 [1-7], P = 0.60) (HADS depression median [IQR] 3 [1-6] v 3 [1-6], P = 0.62); health status as measured by EQ-5D (mean [SD] 66.7 [20] v 69.8 [22.2], P = 0.24); or health-related unemployment (% (N) 39 [26] v 25 [29.1], P = 0.61). After adjusting for confounders, living ≥50 km from the treating ICU was not associated with increased disability (odds ratio 0.61, 95% confidence interval: 0.33-1.16; P = 0.13) CONCLUSIONS: Survivors of intensive care in Victoria, Australia, who live at least 50 km from the treating ICU did not have greater disability than people living less than 50 km at 6 months after discharge. Living 50 km or more from the treating ICU was not associated with disability, nor was it associated with anxiety or depression, health status, or unemployment due to health.",,doi:https://doi.org/10.1016/j.aucc.2021.05.013 -37565978,https://doi.org/10.1016/j.jchf.2023.07.007,Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies: Results From a Dutch Multicenter Cohort Study.,"Jansen M, de Brouwer R, Hassanzada F, Schoemaker AE, Schmidt AF, Kooijman-Reumerman MD, Bracun V, Slieker MG, Dooijes D, Vermeer AMC, Wilde AAM, Amin AS, Lekanne Deprez RH, Herkert JC, Christiaans I, de Boer RA, Jongbloed JDH, van Tintelen JP, Asselbergs FW, Baas AF.",,JACC. Heart failure,2024,2023-08-09,N,Myosin; Screening; Prognosis; Cardiomyopathy; Penetrance; Myh7,,,"

Background

MYH7 variants cause hypertrophic cardiomyopathy (HCM), noncompaction cardiomyopathy (NCCM), and dilated cardiomyopathy (DCM). Screening of relatives of patients with genetic cardiomyopathy is recommended from 10 to 12 years of age onward, irrespective of the affected gene.

Objectives

This study sought to study the penetrance and prognosis of MYH7 variant-associated cardiomyopathies.

Methods

In this multicenter cohort study, penetrance and major cardiomyopathy-related events (MCEs) were assessed in carriers of (likely) pathogenic MYH7 variants by using Kaplan-Meier curves and log-rank tests. Prognostic factors were evaluated using Cox regression with time-dependent coefficients.

Results

In total, 581 subjects (30.1% index patients, 48.4% male, median age 37.0 years [IQR: 19.5-50.2 years]) were included. HCM was diagnosed in 226 subjects, NCCM in 70, and DCM in 55. Early penetrance and MCEs (age <12 years) were common among NCCM-associated variant carriers (21.2% and 12.0%, respectively) and DCM-associated variant carriers (15.3% and 10.0%, respectively), compared with HCM-associated variant carriers (2.9% and 2.1%, respectively). Penetrance was significantly increased in carriers of converter region variants (adjusted HR: 1.87; 95% CI: 1.15-3.04; P = 0.012) and at age ≤1 year in NCCM-associated or DCM-associated variant carriers (adjusted HR: 21.17; 95% CI: 4.81-93.20; P < 0.001) and subjects with a family history of early MCEs (adjusted HR: 2.45; 95% CI: 1.09-5.50; P = 0.030). The risk of MCE was increased in subjects with a family history of early MCEs (adjusted HR: 1.82; 95% CI: 1.15-2.87; P = 0.010) and at age ≤5 years in NCCM-associated or DCM-associated variant carriers (adjusted HR: 38.82; 95% CI: 5.16-291.88; P < 0.001).

Conclusions

MYH7 variants can cause cardiomyopathies and MCEs at a young age. Screening at younger ages may be warranted, particularly in carriers of NCCM- or DCM-associated variants and/or with a family history of MCEs at <12 years.",,doi:https://doi.org/10.1016/j.jchf.2023.07.007 32862087,https://doi.org/10.1016/j.atherosclerosis.2020.07.014,Sex-specific predictors of PCSK9 levels in a European population: The IMPROVE study.,"Ferri N, Ruscica M, Coggi D, Bonomi A, Amato M, Frigerio B, Sansaro D, Ravani A, Veglia F, Capra N, Lupo MG, Macchi C, Castelnuovo S, Savonen K, Silveira A, Kurl S, Giral P, Pirro M, Strawbridge RJ, Gigante B, Smit AJ, Tremoli E, Colombo GI, Baldassarre D, IMPROVE study group.",,Atherosclerosis,2020,2020-07-30,N,Atherosclerosis; Cardiovascular risk factors; Sex differences; Pcsk9 Predictors,,,"

Background and aims

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key regulators of low-density lipoprotein cholesterol plasma levels. Circulating PCSK9, which differs between genders, represents a valid pharmacological target for preventing cardiovascular (CV) events. We aimed to investigate sex-related associations between PCSK9 plasma levels and biochemical and anthropomorphic factors, and familial and personal morbidities, in a large European cohort (n = 3673) of men (47.9%) and women (52.1%).

Methods

Individuals (aged 54-79 years) free of CV diseases were enrolled in seven centers of five European countries: Finland, France, Italy, the Netherlands, and Sweden. PCSK9 plasma levels were measured by ELISA.

Results

PCSK9 was higher in women than in men. Multiple linear regression analysis showed that latitude, sex, and treatments with statins and fibrates were the strongest predictors of PCSK9 in the whole group. These variables, together with triglycerides and high-density lipoprotein cholesterol, were also associated with PCSK9 in men or women. Mean corpuscular hemoglobin concentration and pack-years were PCSK9 independent predictors in women, whereas hypercholesterolemia and physical activity were independent predictors in men. The associations between PCSK9 and latitude, uric acid, diabetes, hypercholesterolemia and physical activity were significantly different in men and women (pinteraction <0.05 for all).

Conclusions

Besides confirming the association with lipids in the whole group, our study revealed previously unknown differences in PCSK9 predictors in men and women. These might be taken into account when defining individual risk for CV events and/or for refining PCSK9 lowering treatments.",,pdf:http://www.atherosclerosis-journal.com/article/S0021915020303816/pdf; doi:https://doi.org/10.1016/j.atherosclerosis.2020.07.014 +37565978,https://doi.org/10.1016/j.jchf.2023.07.007,Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies: Results From a Dutch Multicenter Cohort Study.,"Jansen M, de Brouwer R, Hassanzada F, Schoemaker AE, Schmidt AF, Kooijman-Reumerman MD, Bracun V, Slieker MG, Dooijes D, Vermeer AMC, Wilde AAM, Amin AS, Lekanne Deprez RH, Herkert JC, Christiaans I, de Boer RA, Jongbloed JDH, van Tintelen JP, Asselbergs FW, Baas AF.",,JACC. Heart failure,2024,2023-08-09,N,Myosin; Screening; Prognosis; Cardiomyopathy; Penetrance; Myh7,,,"

Background

MYH7 variants cause hypertrophic cardiomyopathy (HCM), noncompaction cardiomyopathy (NCCM), and dilated cardiomyopathy (DCM). Screening of relatives of patients with genetic cardiomyopathy is recommended from 10 to 12 years of age onward, irrespective of the affected gene.

Objectives

This study sought to study the penetrance and prognosis of MYH7 variant-associated cardiomyopathies.

Methods

In this multicenter cohort study, penetrance and major cardiomyopathy-related events (MCEs) were assessed in carriers of (likely) pathogenic MYH7 variants by using Kaplan-Meier curves and log-rank tests. Prognostic factors were evaluated using Cox regression with time-dependent coefficients.

Results

In total, 581 subjects (30.1% index patients, 48.4% male, median age 37.0 years [IQR: 19.5-50.2 years]) were included. HCM was diagnosed in 226 subjects, NCCM in 70, and DCM in 55. Early penetrance and MCEs (age <12 years) were common among NCCM-associated variant carriers (21.2% and 12.0%, respectively) and DCM-associated variant carriers (15.3% and 10.0%, respectively), compared with HCM-associated variant carriers (2.9% and 2.1%, respectively). Penetrance was significantly increased in carriers of converter region variants (adjusted HR: 1.87; 95% CI: 1.15-3.04; P = 0.012) and at age ≤1 year in NCCM-associated or DCM-associated variant carriers (adjusted HR: 21.17; 95% CI: 4.81-93.20; P < 0.001) and subjects with a family history of early MCEs (adjusted HR: 2.45; 95% CI: 1.09-5.50; P = 0.030). The risk of MCE was increased in subjects with a family history of early MCEs (adjusted HR: 1.82; 95% CI: 1.15-2.87; P = 0.010) and at age ≤5 years in NCCM-associated or DCM-associated variant carriers (adjusted HR: 38.82; 95% CI: 5.16-291.88; P < 0.001).

Conclusions

MYH7 variants can cause cardiomyopathies and MCEs at a young age. Screening at younger ages may be warranted, particularly in carriers of NCCM- or DCM-associated variants and/or with a family history of MCEs at <12 years.",,doi:https://doi.org/10.1016/j.jchf.2023.07.007 31382511,https://doi.org/10.3390/toxins11080454,Indoxyl Sulfate Stimulates Angiogenesis by Regulating Reactive Oxygen Species Production via CYP1B1.,"Pei J, Juni R, Harakalova M, Duncker DJ, Asselbergs FW, Koolwijk P, Hinsbergh VV, Verhaar MC, Mokry M, Cheng C.",,Toxins,2019,2019-08-02,Y,Reactive oxygen species; Angiogenesis; Chronic Kidney Disease; Cyp1b1; Indoxyl Sulfate,Understanding the Causes of Disease,,"Indoxyl sulfate (IS) is an accumulative protein-bound uremic toxin found in patients with kidney disease. It is reported that IS impairs the vascular endothelium, but a comprehensive overview of all mechanisms active in IS-injury currently remains lacking. Here we performed RNA sequencing in human umbilical vein endothelial cells (HUVECs) after IS or control medium treatment and identified 1293 genes that were affected in a IS-induced response. Gene enrichment analysis highlighted pathways involved in altered vascular formation and cell metabolism. We confirmed these transcriptome profiles at the functional level by demonstrating decreased viability and increased cell senescence in response to IS treatment. In line with the additional pathways highlighted by the transcriptome analysis, we further could demonstrate that IS exposure of HUVECs promoted tubule formation as shown by the increase in total tubule length in a 3D HUVECs/pericytes co-culture assay. Notably, the pro-angiogenic response of IS and increased ROS production were abolished when CYP1B1, one of the main target genes that was highly upregulated by IS, was silenced. This observation indicates IS-induced ROS in endothelial cells is CYP1B1-dependent. Taken together, our findings demonstrate that IS promotes angiogenesis and CYP1B1 is an important factor in IS-activated angiogenic response.",,pdf:https://www.mdpi.com/2072-6651/11/8/454/pdf?version=1565690179; doi:https://doi.org/10.3390/toxins11080454; html:https://europepmc.org/articles/PMC6723868; pdf:https://europepmc.org/articles/PMC6723868?pdf=render 32681152,https://doi.org/10.1038/s41596-020-0343-3,Identifying unknown metabolites using NMR-based metabolic profiling techniques.,"Garcia-Perez I, Posma JM, Serrano-Contreras JI, Boulangé CL, Chan Q, Frost G, Stamler J, Elliott P, Lindon JC, Holmes E, Nicholson JK.",,Nature protocols,2020,2020-07-17,N,,,,"Metabolic profiling of biological samples provides important insights into multiple physiological and pathological processes but is hindered by a lack of automated annotation and standardized methods for structure elucidation of candidate disease biomarkers. Here we describe a system for identifying molecular species derived from nuclear magnetic resonance (NMR) spectroscopy-based metabolic phenotyping studies, with detailed information on sample preparation, data acquisition and data modeling. We provide eight different modular workflows to be followed in a recommended sequential order according to their level of difficulty. This multi-platform system involves the use of statistical spectroscopic tools such as Statistical Total Correlation Spectroscopy (STOCSY), Subset Optimization by Reference Matching (STORM) and Resolution-Enhanced (RED)-STORM to identify other signals in the NMR spectra relating to the same molecule. It also uses two-dimensional NMR spectroscopic analysis, separation and pre-concentration techniques, multiple hyphenated analytical platforms and data extraction from existing databases. The complete system, using all eight workflows, would take up to a month, as it includes multi-dimensional NMR experiments that require prolonged experiment times. However, easier identification cases using fewer steps would take 2 or 3 days. This approach to biomarker discovery is efficient and cost-effective and offers increased chemical space coverage of the metabolome, resulting in faster and more accurate assignment of NMR-generated biomarkers arising from metabolic phenotyping studies. It requires a basic understanding of MATLAB to use the statistical spectroscopic tools and analytical skills to perform solid phase extraction (SPE), liquid chromatography (LC) fraction collection, LC-NMR-mass spectroscopy and one-dimensional and two-dimensional NMR experiments.",,doi:https://doi.org/10.1038/s41596-020-0343-3 34609275,https://doi.org/10.1099/mgen.0.000630,"A genomic epidemiological study shows that prevalence of antimicrobial resistance in Enterobacterales is associated with the livestock host, as well as antimicrobial usage.","AbuOun M, Jones H, Stubberfield E, Gilson D, Shaw LP, Hubbard ATM, Chau KK, Sebra R, Peto TEA, Crook DW, Read DS, Gweon HS, Walker AS, Stoesser N, Smith RP, Anjum MF, On Behalf Of The Rehab Consortium.",,Microbial genomics,2021,2021-10-01,Y,Plasmid; Livestock; Antimicrobial resistance; Antimicrobial Usage,,,,,doi:https://doi.org/10.1099/mgen.0.000630; doi:https://doi.org/10.1099/mgen.0.000630; html:https://europepmc.org/articles/PMC8627209; pdf:https://europepmc.org/articles/PMC8627209?pdf=render @@ -2302,8 +2302,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 35189575,https://doi.org/10.1016/j.ebiom.2022.103878,The impact of hypoxia on B cells in COVID-19.,"Kotagiri P, Mescia F, Hanson AL, Turner L, Bergamaschi L, Peñalver A, Richoz N, Moore SD, Ortmann BM, Dunmore BJ, Morgan MD, Tuong ZK, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, Göttgens B, Toshner M, Hess C, Maxwell PH, Clatworthy MR, Nathan JA, Bradley JR, Lyons PA, Burrows N, Smith KGC.",,EBioMedicine,2022,2022-02-19,Y,Hypoxia; B cells; Lymphopenia; Covid-19,,,"

Background

Prominent early features of COVID-19 include severe, often clinically silent, hypoxia and a pronounced reduction in B cells, the latter important in defence against SARS-CoV-2. This presentation resembles the phenotype of mice with VHL-deficient B cells, in which Hypoxia-Inducible Factors are constitutively active, suggesting hypoxia might drive B cell abnormalities in COVID-19.

Methods

Detailed B cell phenotyping was undertaken by flow-cytometry on longitudinal samples from patients with COVID-19 across a range of severities (NIHR Cambridge BioResource). The impact of hypoxia on the transcriptome was assessed by single-cell and whole blood RNA sequencing analysis. The direct effect of hypoxia on B cells was determined through immunisation studies in genetically modified and hypoxia-exposed mice.

Findings

We demonstrate the breadth of early and persistent defects in B cell subsets in moderate/severe COVID-19, including reduced marginal zone-like, memory and transitional B cells, changes also observed in B cell VHL-deficient mice. These findings were associated with hypoxia-related transcriptional changes in COVID-19 patient B cells, and similar B cell abnormalities were seen in mice kept in hypoxic conditions.

Interpretation

Hypoxia may contribute to the pronounced and persistent B cell pathology observed in acute COVID-19 pneumonia. Assessment of the impact of early oxygen therapy on these immune defects should be considered, as their correction could contribute to improved outcomes.

Funding

Evelyn Trust, Addenbrooke's Charitable Trust, UKRI/NIHR, Wellcome Trust.",,pdf:http://www.thelancet.com/article/S2352396422000627/pdf; doi:https://doi.org/10.1016/j.ebiom.2022.103878; html:https://europepmc.org/articles/PMC8856886; pdf:https://europepmc.org/articles/PMC8856886?pdf=render 33186544,https://doi.org/10.1016/j.ajhg.2020.10.009,A Multi-omic Integrative Scheme Characterizes Tissues of Action at Loci Associated with Type 2 Diabetes.,"Torres JM, Abdalla M, Payne A, Fernandez-Tajes J, Thurner M, Nylander V, Gloyn AL, Mahajan A, McCarthy MI.",,American journal of human genetics,2020,2020-11-12,Y,Type 2 diabetes; chromatin; Gene Expression; Gwas; Complex Traits; Eqtl; Fine-mapping; Tactical; Molecular Epigenomics; Multi-omic,,,"Resolving the molecular processes that mediate genetic risk remains a challenge because most disease-associated variants are non-coding and functional characterization of these signals requires knowledge of the specific tissues and cell-types in which they operate. To address this challenge, we developed a framework for integrating tissue-specific gene expression and epigenomic maps to obtain ""tissue-of-action"" (TOA) scores for each association signal by systematically partitioning posterior probabilities from Bayesian fine-mapping. We applied this scheme to credible set variants for 380 association signals from a recent GWAS meta-analysis of type 2 diabetes (T2D) in Europeans. The resulting tissue profiles underscored a predominant role for pancreatic islets and, to a lesser extent, adipose and liver, particularly among signals with greater fine-mapping resolution. We incorporated resulting TOA scores into a rule-based classifier and validated the tissue assignments through comparison with data from cis-eQTL enrichment, functional fine-mapping, RNA co-expression, and patterns of physiological association. In addition to implicating signals with a single TOA, we found evidence for signals with shared effects in multiple tissues as well as distinct tissue profiles between independent signals within heterogeneous loci. Lastly, we demonstrated that TOA scores can be directly coupled with eQTL colocalization to further resolve effector transcripts at T2D signals. This framework guides mechanistic inference by directing functional validation studies to the most relevant tissues and can gain power as fine-mapping resolution and cell-specific annotations become richer. This method is generalizable to all complex traits with relevant annotation data and is made available as an R package.",,pdf:http://www.cell.com/article/S0002929720303670/pdf; doi:https://doi.org/10.1016/j.ajhg.2020.10.009; html:https://europepmc.org/articles/PMC7820628; pdf:https://europepmc.org/articles/PMC7820628?pdf=render 31013802,https://doi.org/10.3390/ijerph16081325,Using Patient-Reported Outcomes to Predict Revision Arthroplasty Following Femoral Neck Fracture: Enhancing the Value of Clinical Registries through Data Linkage.,"Ekegren CL, de Steiger R, Edwards ER, Page RS, Hau R, Liew S, Oppy A, Gabbe BJ.",,International journal of environmental research and public health,2019,2019-04-12,Y,Pain; Femoral neck fractures; Arthroplasty; Registries; Patient Reported Outcome Measures,Improving Public Health,,"The aim of this study was to determine the association between patient-reported outcome measures (PROMs) six months following femoral neck fracture after a low fall and future arthroplasty, and the factors associated with this. Six-month post-fracture PROMs were collected from the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR) for patients aged >55 years who were admitted for a femoral neck fracture after a low fall between March 2007 and June 2015. These cases were linked with those registered by Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) up to October 2016. Multivariable analysis was performed using a Cox proportional hazards model to determine factors associated with future arthroplasty, including six-month PROMs. Of the 7077 hip fracture patients registered by VOTOR during the study period, 2325 met the inclusion criteria. Internal fixation being used for the initial hip fracture surgery, being younger and having no pre-injury disability were all independently associated with future revision or conversion to arthroplasty. Out of all PROMs, reporting pain and discomfort six months post-fracture was associated with a 9.5-fold increase in the risk of future arthroplasty (95% CI: 3.81, 23.67). The value of clinical registries can be enhanced via data linkage, in this case by using PROMs to predict arthroplasty following femoral neck fracture.",,pdf:https://www.mdpi.com/1660-4601/16/8/1325/pdf?version=1555077276; doi:https://doi.org/10.3390/ijerph16081325; html:https://europepmc.org/articles/PMC6517898; pdf:https://europepmc.org/articles/PMC6517898?pdf=render -35523486,https://doi.org/10.1136/bmjopen-2021-059258,Using digital health tools for the Remote Assessment of Treatment Prognosis in Depression (RAPID): a study protocol for a feasibility study.,"de Angel V, Lewis S, Munir S, Matcham F, Dobson R, Hotopf M.",,BMJ open,2022,2022-05-06,Y,Mental health; Anxiety Disorders; Health Informatics; Depression & Mood Disorders,,,"

Introduction

Digital health tools such as smartphones and wearable devices could improve psychological treatment outcomes in depression through more accurate and comprehensive measures of patient behaviour. However, in this emerging field, most studies are small and based on student populations outside of a clinical setting. The current study aims to determine the feasibility and acceptability of using smartphones and wearable devices to collect behavioural and clinical data in people undergoing therapy for depressive disorders and establish the extent to which they can be potentially useful biomarkers of depression and recovery after treatment.

Methods and analysis

This is an observational, prospective cohort study of 65 people attending psychological therapy for depression in multiple London-based sites. It will collect continuous passive data from smartphone sensors and a Fitbit fitness tracker, and deliver questionnaires, speech tasks and cognitive assessments through smartphone-based apps. Objective data on sleep, physical activity, location, Bluetooth contact, smartphone use and heart rate will be gathered for 7 months, and compared with clinical and contextual data. A mixed methods design, including a qualitative interview of patient experiences, will be used to evaluate key feasibility indicators, digital phenotypes of depression and therapy prognosis. Patient and public involvement was sought for participant-facing documents and the study design of the current research proposal.

Ethics and dissemination

Ethical approval has been obtained from the London Westminster Research Ethics Committee, and the Health Research Authority, Integrated Research Application System (project ID: 270918). Privacy and confidentiality will be guaranteed and the procedures for handling, processing, storage and destruction of the data will comply with the General Data Protection Regulation. Findings from this study will form part of a doctoral thesis, will be presented at national and international meetings or academic conferences and will generate manuscripts to be submitted to peer-reviewed journals.

Trial registration number

https://doi.org/10.17605/OSF.IO/PMYTA.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/5/e059258.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-059258; html:https://europepmc.org/articles/PMC9083394; pdf:https://europepmc.org/articles/PMC9083394?pdf=render 31806382,https://doi.org/10.1016/j.injury.2019.11.023,Variation in documented inhalation injury rates following burn injury in Australia and New Zealand.,"Tracy LM, Dyson K, Mercier LL, Cleland H, McInnes JA, Cameron PA, Singer Y, Edgar DW, Darton A, Gabbe BJ.",,Injury,2020,2019-11-17,N,Variation; Australia; New Zealand; Inhalation Injury; Burn Registry,,,"

Introduction

The negative impact of inhalation injuries on in-hospital outcomes for burn patients is well known, but the burns community is yet to form a consensus on diagnostic criteria and clinical definitions. The diagnosis of inhalation injuries is consequently highly subjective. This study aimed to assess the variation in the rate of documented inhalation injury for adult patients in Australian and New Zealand burn units.

Methods

Data for sequential admissions collected from eight adult burn centres across Australia and New Zealand between July 2009 and June 2016 were extracted from the Burns Registry of Australia and New Zealand (BRANZ). Inhalation injury was classified in two ways: (i) a field in the BRANZ data dictionary, and (ii) through a series of International Classification of Disease 10th Revision Australian Modification (ICD-10-AM) codes. Variation in inhalation injury prevalence was assessed using descriptive statistics, funnel plots, logistic regression, and predicted probabilities.

Results

There were 11,206 admissions to BRANZ sites over the study period. Inhalation injury prevalence was the highest at Site D (13.1% for the BRANZ field and 11.8% for the ICD-10-AM codes), but there was significant variation between the contributing sites and the inhalation injury classification methods.

Conclusion

There is significant variation in the prevalence of documented inhalation injury among Australian and New Zealand burns units. The variation in the prevalence of documented inhalation injury across Australian and New Zealand sites reinforces the need for a consensus definition in the diagnosis of these injuries. Further work is required to improve data quality and reconcile the differences between clinical and ICD-10-AM coding prevalence before changes in clinical practice can be recommended from these data.",,doi:https://doi.org/10.1016/j.injury.2019.11.023 +35523486,https://doi.org/10.1136/bmjopen-2021-059258,Using digital health tools for the Remote Assessment of Treatment Prognosis in Depression (RAPID): a study protocol for a feasibility study.,"de Angel V, Lewis S, Munir S, Matcham F, Dobson R, Hotopf M.",,BMJ open,2022,2022-05-06,Y,Mental health; Anxiety Disorders; Health Informatics; Depression & Mood Disorders,,,"

Introduction

Digital health tools such as smartphones and wearable devices could improve psychological treatment outcomes in depression through more accurate and comprehensive measures of patient behaviour. However, in this emerging field, most studies are small and based on student populations outside of a clinical setting. The current study aims to determine the feasibility and acceptability of using smartphones and wearable devices to collect behavioural and clinical data in people undergoing therapy for depressive disorders and establish the extent to which they can be potentially useful biomarkers of depression and recovery after treatment.

Methods and analysis

This is an observational, prospective cohort study of 65 people attending psychological therapy for depression in multiple London-based sites. It will collect continuous passive data from smartphone sensors and a Fitbit fitness tracker, and deliver questionnaires, speech tasks and cognitive assessments through smartphone-based apps. Objective data on sleep, physical activity, location, Bluetooth contact, smartphone use and heart rate will be gathered for 7 months, and compared with clinical and contextual data. A mixed methods design, including a qualitative interview of patient experiences, will be used to evaluate key feasibility indicators, digital phenotypes of depression and therapy prognosis. Patient and public involvement was sought for participant-facing documents and the study design of the current research proposal.

Ethics and dissemination

Ethical approval has been obtained from the London Westminster Research Ethics Committee, and the Health Research Authority, Integrated Research Application System (project ID: 270918). Privacy and confidentiality will be guaranteed and the procedures for handling, processing, storage and destruction of the data will comply with the General Data Protection Regulation. Findings from this study will form part of a doctoral thesis, will be presented at national and international meetings or academic conferences and will generate manuscripts to be submitted to peer-reviewed journals.

Trial registration number

https://doi.org/10.17605/OSF.IO/PMYTA.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/5/e059258.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-059258; html:https://europepmc.org/articles/PMC9083394; pdf:https://europepmc.org/articles/PMC9083394?pdf=render 36568709,https://doi.org/10.1136/bmjmed-2022-000215,Burden and treatment of chronic obstructive pulmonary disease among people using illicit opioids: matched cohort study in England.,"Lewer D, Cox S, Hurst JR, Padmanathan P, Petersen I, Quint JK.",,BMJ medicine,2022,2022-09-28,Y,"Substance-related disorders; Pulmonary disease, chronic obstructive; epidemiology; Health Services; Primary Health Care; Healthcare Disparities",,,"

Objective

To understand the burden of chronic obstructive pulmonary disease among people who use illicit opioids such as heroin, and evaluate inequalities in treatment.

Design

Cohort study.

Setting

Patients registered at primary care practices in England.

Participants

106 789 patients in the Clinical Practice Research Datalink with illicit opioid use recorded between 2001 and 2018, and a subcohort of 3903 patients with a diagnosis of chronic obstructive pulmonary disease. For both cohorts, the study sampled a comparison group with no history of illicit opioids that was matched by age, sex, and general practice.

Main outcome measures

In the base cohort: diagnosis of chronic obstructive pulmonary disease and death due to the disease. In the subcohort: five treatments (influenza vaccine, pneumococcal vaccine, pulmonary rehabilitation, bronchodilators or corticosteroids, and smoking cessation support) and exacerbations requiring hospital admission.

Results

680 of 106 789 participants died due to chronic obstructive pulmonary disease, representing 5.1% of all cause deaths. Illicit opioid use was associated with 14.59 times (95% confidence interval 12.28 to 17.33) the risk of death related to chronic obstructive pulmonary disease, and 5.89 times (5.62 to 6.18) the risk of a diagnosis of the disease. Among patients with a new diagnosis, comorbid illicit opioid use was associated with current smoking, underweight, worse lung function, and more severe breathlessness. After adjusting for these differences, illicit opioids were associated with 1.96 times (1.82 to 2.12) times the risk of exacerbations requiring hospital admission, but not associated with a substantially different probability of the five treatments.

Conclusions

Death due to chronic obstructive pulmonary disease is about 15 times more common among people who use illicit opioids than the general population. This inequality does not appear to be explained by differences in treatment, but late diagnosis of the disease among people who use illicit opioids might contribute.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000215.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000215; html:https://europepmc.org/articles/PMC9770021; pdf:https://europepmc.org/articles/PMC9770021?pdf=render 35296488,https://doi.org/10.1136/bmjopen-2021-058552,"AlzEye: longitudinal record-level linkage of ophthalmic imaging and hospital admissions of 353 157 patients in London, UK.","Wagner SK, Hughes F, Cortina-Borja M, Pontikos N, Struyven R, Liu X, Montgomery H, Alexander DC, Topol E, Petersen SE, Balaskas K, Hindley J, Petzold A, Rahi JS, Denniston AK, Keane PA.",,BMJ open,2022,2022-03-16,Y,Ophthalmology; Health Informatics; Medical Retina; Medical Ophthalmology,,,"

Purpose

Retinal signatures of systemic disease ('oculomics') are increasingly being revealed through a combination of high-resolution ophthalmic imaging and sophisticated modelling strategies. Progress is currently limited not mainly by technical issues, but by the lack of large labelled datasets, a sine qua non for deep learning. Such data are derived from prospective epidemiological studies, in which retinal imaging is typically unimodal, cross-sectional, of modest number and relates to cohorts, which are not enriched with subpopulations of interest, such as those with systemic disease. We thus linked longitudinal multimodal retinal imaging from routinely collected National Health Service (NHS) data with systemic disease data from hospital admissions using a privacy-by-design third-party linkage approach.

Participants

Between 1 January 2008 and 1 April 2018, 353 157 participants aged 40 years or older, who attended Moorfields Eye Hospital NHS Foundation Trust, a tertiary ophthalmic institution incorporating a principal central site, four district hubs and five satellite clinics in and around London, UK serving a catchment population of approximately six million people.

Findings to date

Among the 353 157 individuals, 186 651 had a total of 1 337 711 Hospital Episode Statistics admitted patient care episodes. Systemic diagnoses recorded at these episodes include 12 022 patients with myocardial infarction, 11 735 with all-cause stroke and 13 363 with all-cause dementia. A total of 6 261 931 retinal images of seven different modalities and across three manufacturers were acquired from 1 54 830 patients. The majority of retinal images were retinal photographs (n=1 874 175) followed by optical coherence tomography (n=1 567 358).

Future plans

AlzEye combines the world's largest single institution retinal imaging database with nationally collected systemic data to create an exceptional large-scale, enriched cohort that reflects the diversity of the population served. First analyses will address cardiovascular diseases and dementia, with a view to identifying hidden retinal signatures that may lead to earlier detection and risk management of these life-threatening conditions.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/3/e058552.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-058552; html:https://europepmc.org/articles/PMC8928293; pdf:https://europepmc.org/articles/PMC8928293?pdf=render 36434067,https://doi.org/10.1038/s42003-022-04252-5,A conserved glutathione binding site in poliovirus is a target for antivirals and vaccine stabilisation.,"Bahar MW, Nasta V, Fox H, Sherry L, Grehan K, Porta C, Macadam AJ, Stonehouse NJ, Rowlands DJ, Fry EE, Stuart DI.",,Communications biology,2022,2022-11-25,Y,,,,"Strategies to prevent the recurrence of poliovirus (PV) after eradication may utilise non-infectious, recombinant virus-like particle (VLP) vaccines. Despite clear advantages over inactivated or attenuated virus vaccines, instability of VLPs can compromise their immunogenicity. Glutathione (GSH), an important cellular reducing agent, is a crucial co-factor for the morphogenesis of enteroviruses, including PV. We report cryo-EM structures of GSH bound to PV serotype 3 VLPs showing that it can enhance particle stability. GSH binds the positively charged pocket at the interprotomer interface shown recently to bind GSH in enterovirus F3 and putative antiviral benzene sulphonamide compounds in other enteroviruses. We show, using high-resolution cryo-EM, the binding of a benzene sulphonamide compound with a PV serotype 2 VLP, consistent with antiviral activity through over-stabilizing the interprotomer pocket, preventing the capsid rearrangements necessary for viral infection. Collectively, these results suggest GSH or an analogous tight-binding antiviral offers the potential for stabilizing VLP vaccines.",,pdf:https://www.nature.com/articles/s42003-022-04252-5.pdf; doi:https://doi.org/10.1038/s42003-022-04252-5; html:https://europepmc.org/articles/PMC9700776; pdf:https://europepmc.org/articles/PMC9700776?pdf=render @@ -2317,34 +2317,34 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 33226834,https://doi.org/10.1164/rccm.202008-3211le,Proportion of Idiopathic Pulmonary Fibrosis Risk Explained by Known Common Genetic Loci in European Populations.,"Leavy OC, Ma SF, Molyneaux PL, Maher TM, Oldham JM, Flores C, Noth I, Jenkins RG, Dudbridge F, Wain LV, Allen RJ.",,American journal of respiratory and critical care medicine,2021,2021-03-01,Y,,,,,,pdf:https://europepmc.org/articles/pmc7958523?pdf=render; doi:https://doi.org/10.1164/rccm.202008-3211LE; html:https://europepmc.org/articles/PMC7958523; pdf:https://europepmc.org/articles/PMC7958523?pdf=render 34193492,https://doi.org/10.1136/bmjopen-2020-046450,"'Give Us The Tools!': development of knowledge transfer tools to support the involvement of patient partners in the development of clinical trial protocols with patient-reported outcomes (PROs), in accordance with SPIRIT-PRO Extension.","Cruz Rivera S, Stephens R, Mercieca-Bebber R, Retzer A, Rutherford C, Price G, Slade A, Aiyegbusi OL, Edge P, Roberts L, Gosden L, Verdi R, Wilson R, Calvert M.",,BMJ open,2021,2021-06-30,Y,Qualitative Research; Protocols & Guidelines; Quality In Health Care,,,"

Objectives

(a) To adapt the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)-patient-reported outcome (PRO) Extension guidance to a user-friendly format for patient partners and (b) to codesign a web-based tool to support the dissemination and uptake of the SPIRIT-PRO Extension by patient partners.

Design

A 1-day patient and public involvement session.

Participants

Seven patient partners.

Methods

A patient partner produced an initial lay summary of the SPIRIT-PRO guideline and a glossary. We held a 1-day PPI session in November 2019 at the University of Birmingham. Five patient partners discussed the draft lay summary, agreed on the final wording, codesigned and agreed the final content for both tools. Two additional patient partners were involved in writing the manuscript. The study compiled with INVOLVE guidelines and was reported according to the Guidance for Reporting Involvement of Patients and the Public 2 checklist.

Results

Two user-friendly tools were developed to help patients and members of the public be involved in the codesign of clinical trials collecting PROs. The first tool presents a lay version of the SPIRIT-PRO Extension guidance. The second depicts the most relevant points, identified by the patient partners, of the guidance through an interactive flow diagram.

Conclusions

These tools have the potential to support the involvement of patient partners in making informed contributions to the development of PRO aspects of clinical trial protocols, in accordance with the SPIRIT-PRO Extension guidelines. The involvement of patient partners ensured the tools focused on issues most relevant to them.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e046450.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-046450; html:https://europepmc.org/articles/PMC8246365; pdf:https://europepmc.org/articles/PMC8246365?pdf=render 32724858,https://doi.org/10.1136/bmjophth-2020-000481,Outcomes important to patients with non-infectious posterior segment-involving uveitis: a qualitative study.,"Tallouzi MO, Moore DJ, Bucknall N, Murray PI, Calvert MJ, Denniston AK, Mathers JM.",,BMJ open ophthalmology,2020,2020-07-21,Y,Inflammation; Public Health; Treatment Other,,,"

Objective

Uveitis, a group of disorders characterised by intraocular inflammation, causes 10%-15% of total blindness in the developed world. The most sight-threatening forms of non-infectious uveitis are those affecting the posterior segment of the eye, collectively known as posterior segment-involving uveitis (PSIU). Numerous different clinical outcomes have been used in trials evaluating treatments for PSIU, but these may not represent patients' and carers' concerns. Therefore, the aims of this study were to understand the impact of PSIU on adult patients' and carers' lives and to explore what outcomes of treatment are important to them.

Methods and analysis

Four focus group discussions were undertaken to understand the perspectives of adult patients (=18) and carers (10) with PSIU. Participants were grouped according to whether or not their uveitis was complicated by the sight-threatening condition uveitic macular oedema. Discussions were audio-recorded, transcribed and analysed using the framework analytical approach. Outcomes were identified and grouped into outcome domains.

Results

Eleven core domains were identified as important to patients and carers undergoing treatment for PSIU, comprising (1) visual function, (2) symptoms, (3) functional ability, (4) impact on relationships, (5) financial impact, (6) psychological morbidity and emotional well-being, (7) psychosocial adjustment to uveitis, (8) doctor/patient/interprofessional relationships and access to healthcare, (9) treatment burden, (10) treatment side effects, and (11) disease control.

Conclusion

The domains identified represent patients' and carers' experience and perspectives and can be used to reflect on outcomes assessed in PSIU. They will directly inform the development of a core outcome set for PSIU clinical trials.",,pdf:https://bmjophth.bmj.com/content/bmjophth/5/1/e000481.full.pdf; doi:https://doi.org/10.1136/bmjophth-2020-000481; html:https://europepmc.org/articles/PMC7375431; pdf:https://europepmc.org/articles/PMC7375431?pdf=render -35585198,https://doi.org/10.1038/s41591-022-01772-9,Reporting guideline for the early-stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI.,"Vasey B, Nagendran M, Campbell B, Clifton DA, Collins GS, Denaxas S, Denniston AK, Faes L, Geerts B, Ibrahim M, Liu X, Mateen BA, Mathur P, McCradden MD, Morgan L, Ordish J, Rogers C, Saria S, Ting DSW, Watkinson P, Weber W, Wheatstone P, McCulloch P, DECIDE-AI expert group.",,Nature medicine,2022,2022-05-18,N,,,,"A growing number of artificial intelligence (AI)-based clinical decision support systems are showing promising performance in preclinical, in silico evaluation, but few have yet demonstrated real benefit to patient care. Early-stage clinical evaluation is important to assess an AI system's actual clinical performance at small scale, ensure its safety, evaluate the human factors surrounding its use and pave the way to further large-scale trials. However, the reporting of these early studies remains inadequate. The present statement provides a multi-stakeholder, consensus-based reporting guideline for the Developmental and Exploratory Clinical Investigations of DEcision support systems driven by Artificial Intelligence (DECIDE-AI). We conducted a two-round, modified Delphi process to collect and analyze expert opinion on the reporting of early clinical evaluation of AI systems. Experts were recruited from 20 pre-defined stakeholder categories. The final composition and wording of the guideline was determined at a virtual consensus meeting. The checklist and the Explanation & Elaboration (E&E) sections were refined based on feedback from a qualitative evaluation process. In total, 123 experts participated in the first round of Delphi, 138 in the second round, 16 in the consensus meeting and 16 in the qualitative evaluation. The DECIDE-AI reporting guideline comprises 17 AI-specific reporting items (made of 28 subitems) and ten generic reporting items, with an E&E paragraph provided for each. Through consultation and consensus with a range of stakeholders, we developed a guideline comprising key items that should be reported in early-stage clinical studies of AI-based decision support systems in healthcare. By providing an actionable checklist of minimal reporting items, the DECIDE-AI guideline will facilitate the appraisal of these studies and replicability of their findings.",,pdf:https://www.nature.com/articles/s41591-022-01772-9.pdf; doi:https://doi.org/10.1038/s41591-022-01772-9 35042708,https://doi.org/10.1136/bmjopen-2021-055572,Use of the kidney failure risk equation to inform clinical care of patients with chronic kidney disease: a mixed-methods systematic review.,"Bhachu HK, Fenton A, Cockwell P, Aiyegbusi O, Kyte D, Calvert M.",,BMJ open,2022,2022-01-18,Y,Dialysis; Renal transplantation; Chronic Renal Failure; End Stage Renal Failure,,,"

Rationale and objective

The Kidney Failure Risk Equation (KFRE) predicts the risk of end-stage kidney disease in patients with chronic kidney disease (CKD). This study aimed to evaluate the impact of the utility of KFRE in clinical practice.

Study design

Systematic review.

Setting and study populations

Adult patients with CKD but not receiving renal replacement therapy enrolled in studies where KFRE was used in clinical care pathways.

Selection criteria for studies

All studies published from April 2011 to October 2021 identified from Medline, Cumulative Index to Nursing and Allied Health Literature, Embase and reference and citation searches of included studies.

Data extraction

Relevant data were extracted, and two reviewers independently assessed study quality using appropriate appraisal tools.

Analytical approach

Findings reported as a narrative synthesis due to heterogeneity of the included studies.

Results

Of 1635 studies identified, 440 duplicates were removed. The remaining 1195 titles and abstracts were screened. All five studies for full-text review were included in the analysis. Three uses of KFRE were assessed: (1) primary to specialty care interface; (2) general nephrology to multidisciplinary care transition; and (3) treatment planning. Evidence of impact on number of patient referrals into nephrology care was conflicting. However, wait times improved in one study. Although KFRE identified high-risk patients for increased multidisciplinary support, there was concern patients stepped down, no longer meeting eligibility criteria, may lack access to services.

Conclusions

This is the first systematic review of studies that have assessed the actual impact of KFRE in clinical practice with five studies of varying quality reported to date. Trials are in progress assessing the impact on clinical outcomes of using KFRE in clinical practice, and KFRE is being incorporated into guidelines for CKD management. Further studies are needed to assess the impact of KFRE on clinical care.

Trial registration number

Protocol registered on PROSPERO before initiation of the study (Ref: CRD42020219926).",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/1/e055572.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055572; html:https://europepmc.org/articles/PMC8768913; pdf:https://europepmc.org/articles/PMC8768913?pdf=render +35585198,https://doi.org/10.1038/s41591-022-01772-9,Reporting guideline for the early-stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI.,"Vasey B, Nagendran M, Campbell B, Clifton DA, Collins GS, Denaxas S, Denniston AK, Faes L, Geerts B, Ibrahim M, Liu X, Mateen BA, Mathur P, McCradden MD, Morgan L, Ordish J, Rogers C, Saria S, Ting DSW, Watkinson P, Weber W, Wheatstone P, McCulloch P, DECIDE-AI expert group.",,Nature medicine,2022,2022-05-18,N,,,,"A growing number of artificial intelligence (AI)-based clinical decision support systems are showing promising performance in preclinical, in silico evaluation, but few have yet demonstrated real benefit to patient care. Early-stage clinical evaluation is important to assess an AI system's actual clinical performance at small scale, ensure its safety, evaluate the human factors surrounding its use and pave the way to further large-scale trials. However, the reporting of these early studies remains inadequate. The present statement provides a multi-stakeholder, consensus-based reporting guideline for the Developmental and Exploratory Clinical Investigations of DEcision support systems driven by Artificial Intelligence (DECIDE-AI). We conducted a two-round, modified Delphi process to collect and analyze expert opinion on the reporting of early clinical evaluation of AI systems. Experts were recruited from 20 pre-defined stakeholder categories. The final composition and wording of the guideline was determined at a virtual consensus meeting. The checklist and the Explanation & Elaboration (E&E) sections were refined based on feedback from a qualitative evaluation process. In total, 123 experts participated in the first round of Delphi, 138 in the second round, 16 in the consensus meeting and 16 in the qualitative evaluation. The DECIDE-AI reporting guideline comprises 17 AI-specific reporting items (made of 28 subitems) and ten generic reporting items, with an E&E paragraph provided for each. Through consultation and consensus with a range of stakeholders, we developed a guideline comprising key items that should be reported in early-stage clinical studies of AI-based decision support systems in healthcare. By providing an actionable checklist of minimal reporting items, the DECIDE-AI guideline will facilitate the appraisal of these studies and replicability of their findings.",,pdf:https://www.nature.com/articles/s41591-022-01772-9.pdf; doi:https://doi.org/10.1038/s41591-022-01772-9 37067557,https://doi.org/10.1007/s00134-023-07039-2,Variants of concern and clinical outcomes in critically ill COVID-19 patients.,DP-EFFECT-BRAZIL investigators.,,Intensive care medicine,2023,2023-04-17,Y,,,,,,pdf:https://link.springer.com/content/pdf/10.1007/s00134-023-07039-2.pdf; doi:https://doi.org/10.1007/s00134-023-07039-2; html:https://europepmc.org/articles/PMC10108805; pdf:https://europepmc.org/articles/PMC10108805?pdf=render 36697134,https://doi.org/10.1016/j.jacc.2022.10.034,Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis.,"Ćorović A, Wall C, Nus M, Gopalan D, Huang Y, Imaz M, Zulcinski M, Peverelli M, Uryga A, Lambert J, Bressan D, Maughan RT, Pericleous C, Dubash S, Jordan N, Jayne DR, Hoole SP, Calvert PA, Dean AF, Rassl D, Barwick T, Iles M, Frontini M, Hannon G, Manavaki R, Fryer TD, Aloj L, Graves MJ, Gilbert FJ, Dweck MR, Newby DE, Fayad ZA, Reynolds G, Morgan AW, Aboagye EO, Davenport AP, Jørgensen HF, Mallat Z, Bennett MR, Peters JE, Rudd JHF, Mason JC, Tarkin JM.",,Journal of the American College of Cardiology,2023,2023-01-01,Y,Atherosclerosis; Inflammation; Molecular Imaging; Giant Cell Arteritis; Takayasu Arteritis; Somatostatin Receptor,,,"

Background

Assessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures.

Objectives

We aimed to investigate somatostatin receptor 2 (SST2) as a novel inflammation-specific molecular imaging target in LVV.

Methods

In a prospective, observational cohort study, in vivo arterial SST2 expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using 68Ga-DOTATATE and 18F-FET-βAG-TOCA. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy; imaging mass cytometry; and bulk, single-cell, and single-nucleus RNA sequencing.

Results

Sixty-one participants (LVV: n = 27; recent atherosclerotic myocardial infarction of ≤2 weeks: n = 25; control subjects with an oncologic indication for imaging: n = 9) were included. Index vessel SST2 maximum tissue-to-blood ratio was 61.8% (P < 0.0001) higher in active/grumbling LVV than inactive LVV and 34.6% (P = 0.0002) higher than myocardial infarction, with good diagnostic accuracy (area under the curve: ≥0.86; P < 0.001 for both). Arterial SST2 signal was not elevated in any of the control subjects. SST2 PET/MRI was generally consistent with 18F-fluorodeoxyglucose PET/computed tomography imaging in LVV patients with contemporaneous clinical scans but with very low background signal in the brain and heart, allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. Clinically effective treatment for LVV was associated with a 0.49 ± 0.24 (standard error of the mean [SEM]) (P = 0.04; 22.3%) reduction in the SST2 maximum tissue-to-blood ratio after 9.3 ± 3.2 months. SST2 expression was localized to macrophages, pericytes, and perivascular adipocytes in vasculitis specimens, with specific receptor binding confirmed by autoradiography. SSTR2-expressing macrophages coexpressed proinflammatory markers.

Conclusions

SST2 PET/MRI holds major promise for diagnosis and therapeutic monitoring in LVV. (PET Imaging of Giant Cell and Takayasu Arteritis [PITA], NCT04071691; Residual Inflammation and Plaque Progression Long-Term Evaluation [RIPPLE], NCT04073810).",,doi:https://doi.org/10.1016/j.jacc.2022.10.034; doi:https://doi.org/10.1016/j.jacc.2022.10.034; html:https://europepmc.org/articles/PMC9883634; pdf:https://europepmc.org/articles/PMC9883634?pdf=render 36820079,https://doi.org/10.1183/23120541.00274-2022,Characteristics and risk factors for post-COVID-19 breathlessness after hospitalisation for COVID-19.,"Daines L, Zheng B, Elneima O, Harrison E, Lone NI, Hurst JR, Brown JS, Sapey E, Chalmers JD, Quint JK, Pfeffer P, Siddiqui S, Walker S, Poinasamy K, McAuley H, Sereno M, Shikotra A, Singapuri A, Docherty AB, Marks M, Toshner M, Howard LS, Horsley A, Jenkins G, Porter JC, Ho LP, Raman B, Wain LV, Brightling CE, Evans RA, Heaney LG, De Soyza A, Sheikh A.",,ERJ open research,2023,2023-01-01,Y,,,,"

Background

Persistence of respiratory symptoms, particularly breathlessness, after acute coronavirus disease 2019 (COVID-19) infection has emerged as a significant clinical problem. We aimed to characterise and identify risk factors for patients with persistent breathlessness following COVID-19 hospitalisation.

Methods

PHOSP-COVID is a multicentre prospective cohort study of UK adults hospitalised for COVID-19. Clinical data were collected during hospitalisation and at a follow-up visit. Breathlessness was measured by a numeric rating scale of 0-10. We defined post-COVID-19 breathlessness as an increase in score of ≥1 compared to the pre-COVID-19 level. Multivariable logistic regression was used to identify risk factors and to develop a prediction model for post-COVID-19 breathlessness.

Results

We included 1226 participants (37% female, median age 59 years, 22% mechanically ventilated). At a median 5 months after discharge, 50% reported post-COVID-19 breathlessness. Risk factors for post-COVID-19 breathlessness were socioeconomic deprivation (adjusted OR 1.67, 95% CI 1.14-2.44), pre-existing depression/anxiety (adjusted OR 1.58, 95% CI 1.06-2.35), female sex (adjusted OR 1.56, 95% CI 1.21-2.00) and admission duration (adjusted OR 1.01, 95% CI 1.00-1.02). Black ethnicity (adjusted OR 0.56, 95% CI 0.35-0.89) and older age groups (adjusted OR 0.31, 95% CI 0.14-0.66) were less likely to report post-COVID-19 breathlessness. Post-COVID-19 breathlessness was associated with worse performance on the shuttle walk test and forced vital capacity, but not with obstructive airflow limitation. The prediction model had fair discrimination (concordance statistic 0.66, 95% CI 0.63-0.69) and good calibration (calibration slope 1.00, 95% CI 0.80-1.21).

Conclusions

Post-COVID-19 breathlessness was commonly reported in this national cohort of patients hospitalised for COVID-19 and is likely to be a multifactorial problem with physical and emotional components.",,pdf:https://openres.ersjournals.com/content/erjor/early/2023/01/26/23120541.00274-2022.full.pdf; doi:https://doi.org/10.1183/23120541.00274-2022; html:https://europepmc.org/articles/PMC9790090; pdf:https://europepmc.org/articles/PMC9790090?pdf=render 34593009,https://doi.org/10.1186/s13058-021-01465-0,Genomic risk prediction of coronary artery disease in women with breast cancer: a prospective cohort study.,"Liou L, Kaptoge S, Dennis J, Shah M, Tyrer J, Inouye M, Easton DF, Pharoah PDP.",,Breast cancer research : BCR,2021,2021-09-30,Y,Breast cancer; Cardiovascular disease; coronary artery disease; Coronary Heart Disease; Search; Polygenic Risk Score,,,"

Background

Advancements in cancer therapeutics have resulted in increases in cancer-related survival; however, there is a growing clinical dilemma. The current balancing of survival benefits and future cardiotoxic harms of oncotherapies has resulted in an increased burden of cardiovascular disease in breast cancer survivors. Risk stratification may help address this clinical dilemma. This study is the first to assess the association between a coronary artery disease-specific polygenic risk score and incident coronary artery events in female breast cancer survivors.

Methods

We utilized the Studies in Epidemiology and Research in Cancer Heredity prospective cohort involving 12,413 women with breast cancer with genotype information and without a baseline history of cardiovascular disease. Cause-specific hazard ratios for association of the polygenic risk score and incident coronary artery disease (CAD) were obtained using left-truncated Cox regression adjusting for age, genotype array, conventional risk factors such as smoking and body mass index, as well as other sociodemographic, lifestyle, and medical variables.

Results

Over a median follow-up of 10.3 years (IQR: 16.8) years, 750 incident fatal or non-fatal coronary artery events were recorded. A 1 standard deviation higher polygenic risk score was associated with an adjusted hazard ratio of 1.33 (95% CI 1.20, 1.47) for incident CAD.

Conclusions

This study provides evidence that a coronary artery disease-specific polygenic risk score can risk-stratify breast cancer survivors independently of other established cardiovascular risk factors.",,pdf:https://breast-cancer-research.biomedcentral.com/track/pdf/10.1186/s13058-021-01465-0; doi:https://doi.org/10.1186/s13058-021-01465-0; html:https://europepmc.org/articles/PMC8482562; pdf:https://europepmc.org/articles/PMC8482562?pdf=render -36029521,https://doi.org/10.1093/ije/dyac171,Cohort Profile: The United Kingdom Research study into Ethnicity and COVID-19 outcomes in Healthcare workers (UK-REACH).,"Bryant L, Free RC, Woolf K, Melbourne C, Guyatt AL, John C, Gupta A, Gray LJ, Nellums L, Martin CA, McManus IC, Garwood C, Modhawdia V, Carr S, Wain LV, Tobin MD, Khunti K, Akubakar I, Pareek M, UK-REACH Collaborative Group+.",,International journal of epidemiology,2023,2023-02-01,Y,,,,,,pdf:https://academic.oup.com/ije/article-pdf/52/1/e38/49127215/dyac171.pdf; doi:https://doi.org/10.1093/ije/dyac171; html:https://europepmc.org/articles/PMC9452183; pdf:https://europepmc.org/articles/PMC9452183?pdf=render 32558637,https://doi.org/10.1099/mgen.0.000393,Evaluation of methods for detecting human reads in microbial sequencing datasets.,"Bush SJ, Connor TR, Peto TEA, Crook DW, Walker AS.",,Microbial genomics,2020,2020-07-01,Y,Human; Contamination; Read Depletion; Read Removal,,,"Sequencing data from host-associated microbes can often be contaminated by the body of the investigator or research subject. Human DNA is typically removed from microbial reads either by subtractive alignment (dropping all reads that map to the human genome) or by using a read classification tool to predict those of human origin, and then discarding them. To inform best practice guidelines, we benchmarked eight alignment-based and two classification-based methods of human read detection using simulated data from 10 clinically prevalent bacteria and three viruses, into which contaminating human reads had been added. While the majority of methods successfully detected >99 % of the human reads, they were distinguishable by variance. The most precise methods, with negligible variance, were Bowtie2 and SNAP, both of which misidentified few, if any, bacterial reads (and no viral reads) as human. While correctly detecting a similar number of human reads, methods based on taxonomic classification, such as Kraken2 and Centrifuge, could misclassify bacterial reads as human, although the extent of this was species-specific. Among the most sensitive methods of human read detection was BWA, although this also made the greatest number of false positive classifications. Across all methods, the set of human reads not identified as such, although often representing <0.1 % of the total reads, were non-randomly distributed along the human genome with many originating from the repeat-rich sex chromosomes. For viral reads and longer (>300 bp) bacterial reads, the highest performing approaches were classification-based, using Kraken2 or Centrifuge. For shorter (c. 150 bp) bacterial reads, combining multiple methods of human read detection maximized the recovery of human reads from contaminated short read datasets without being compromised by false positives. A particularly high-performance approach with shorter bacterial reads was a two-stage classification using Bowtie2 followed by SNAP. Using this approach, we re-examined 11 577 publicly archived bacterial read sets for hitherto undetected human contamination. We were able to extract a sufficient number of reads to call known human SNPs, including those with clinical significance, in 6 % of the samples. These results show that phenotypically distinct human sequence is detectable in publicly archived microbial read datasets.",,doi:https://doi.org/10.1099/mgen.0.000393; doi:https://doi.org/10.1099/mgen.0.000393; html:https://europepmc.org/articles/PMC7478626; pdf:https://europepmc.org/articles/PMC7478626?pdf=render +36029521,https://doi.org/10.1093/ije/dyac171,Cohort Profile: The United Kingdom Research study into Ethnicity and COVID-19 outcomes in Healthcare workers (UK-REACH).,"Bryant L, Free RC, Woolf K, Melbourne C, Guyatt AL, John C, Gupta A, Gray LJ, Nellums L, Martin CA, McManus IC, Garwood C, Modhawdia V, Carr S, Wain LV, Tobin MD, Khunti K, Akubakar I, Pareek M, UK-REACH Collaborative Group+.",,International journal of epidemiology,2023,2023-02-01,Y,,,,,,pdf:https://academic.oup.com/ije/article-pdf/52/1/e38/49127215/dyac171.pdf; doi:https://doi.org/10.1093/ije/dyac171; html:https://europepmc.org/articles/PMC9452183; pdf:https://europepmc.org/articles/PMC9452183?pdf=render 31171806,https://doi.org/10.1038/s41598-019-44907-8,On neighbourhood degree sequences of complex networks.,Smith KM.,,Scientific reports,2019,2019-06-06,Y,,Applied Analytics,,"Network topology is a fundamental aspect of network science that allows us to gather insights into the complicated relational architectures of the world we inhabit. We provide a first specific study of neighbourhood degree sequences in complex networks. We consider how to explicitly characterise important physical concepts such as similarity, heterogeneity and organization in these sequences, as well as updating the notion of hierarchical complexity to reflect previously unnoticed organizational principles. We also point out that neighbourhood degree sequences are related to a powerful subtree kernel for unlabeled graph classification. We study these newly defined sequence properties in a comprehensive array of graph models and over 200 real-world networks. We find that these indices are neither highly correlated with each other nor with classical network indices. Importantly, the sequences of a wide variety of real world networks are found to have greater similarity and organisation than is expected for networks of their given degree distributions. Notably, while biological, social and technological networks all showed consistently large neighbourhood similarity and organisation, hierarchical complexity was not a consistent feature of real world networks. Neighbourhood degree sequences are an interesting tool for describing unique and important characteristics of complex networks.",,pdf:https://www.nature.com/articles/s41598-019-44907-8.pdf; doi:https://doi.org/10.1038/s41598-019-44907-8; html:https://europepmc.org/articles/PMC6554413; pdf:https://europepmc.org/articles/PMC6554413?pdf=render 35587468,https://doi.org/10.1371/journal.pmed.1003981,Integrating polygenic risk scores in the prediction of type 2 diabetes risk and subtypes in British Pakistanis and Bangladeshis: A population-based cohort study.,"Hodgson S, Huang QQ, Sallah N, Genes & Health Research Team, Griffiths CJ, Newman WG, Trembath RC, Wright J, Lumbers RT, Kuchenbaecker K, van Heel DA, Mathur R, Martin HC, Finer S.",,PLoS medicine,2022,2022-05-19,Y,,,,"

Background

Type 2 diabetes (T2D) is highly prevalent in British South Asians, yet they are underrepresented in research. Genes & Health (G&H) is a large, population study of British Pakistanis and Bangladeshis (BPB) comprising genomic and routine health data. We assessed the extent to which genetic risk for T2D is shared between BPB and European populations (EUR). We then investigated whether the integration of a polygenic risk score (PRS) for T2D with an existing risk tool (QDiabetes) could improve prediction of incident disease and the characterisation of disease subtypes.

Methods and findings

In this observational cohort study, we assessed whether common genetic loci associated with T2D in EUR individuals were replicated in 22,490 BPB individuals in G&H. We replicated fewer loci in G&H (n = 76/338, 22%) than would be expected given power if all EUR-ascertained loci were transferable (n = 101, 30%; p = 0.001). Of the 27 transferable loci that were powered to interrogate this, only 9 showed evidence of shared causal variants. We constructed a T2D PRS and combined it with a clinical risk instrument (QDiabetes) in a novel, integrated risk tool (IRT) to assess risk of incident diabetes. To assess model performance, we compared categorical net reclassification index (NRI) versus QDiabetes alone. In 13,648 patients free from T2D followed up for 10 years, NRI was 3.2% for IRT versus QDiabetes (95% confidence interval (CI): 2.0% to 4.4%). IRT performed best in reclassification of individuals aged less than 40 years deemed low risk by QDiabetes alone (NRI 5.6%, 95% CI 3.6% to 7.6%), who tended to be free from comorbidities and slim. After adjustment for QDiabetes score, PRS was independently associated with progression to T2D after gestational diabetes (hazard ratio (HR) per SD of PRS 1.23, 95% CI 1.05 to 1.42, p = 0.028). Using cluster analysis of clinical features at diabetes diagnosis, we replicated previously reported disease subgroups, including Mild Age-Related, Mild Obesity-related, and Insulin-Resistant Diabetes, and showed that PRS distribution differs between subgroups (p = 0.002). Integrating PRS in this cluster analysis revealed a Probable Severe Insulin Deficient Diabetes (pSIDD) subgroup, despite the absence of clinical measures of insulin secretion or resistance. We also observed differences in rates of progression to micro- and macrovascular complications between subgroups after adjustment for confounders. Study limitations include the absence of an external replication cohort and the potential biases arising from missing or incorrect routine health data.

Conclusions

Our analysis of the transferability of T2D loci between EUR and BPB indicates the need for larger, multiancestry studies to better characterise the genetic contribution to disease and its varied aetiology. We show that a T2D PRS optimised for this high-risk BPB population has potential clinical application in BPB, improving the identification of T2D risk (especially in the young) on top of an established clinical risk algorithm and aiding identification of subgroups at diagnosis, which may help future efforts to stratify care and treatment of the disease.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003981&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003981; html:https://europepmc.org/articles/PMC9119501; pdf:https://europepmc.org/articles/PMC9119501?pdf=render 30819382,https://doi.org/10.1016/j.jchf.2019.01.009,Adverse Drug Reactions to Guideline-Recommended Heart Failure Drugs in Women: A Systematic Review of the Literature.,"Bots SH, Groepenhoff F, Eikendal ALM, Tannenbaum C, Rochon PA, Regitz-Zagrosek V, Miller VM, Day D, Asselbergs FW, den Ruijter HM.",,JACC. Heart failure,2019,2019-03-01,N,Women; Sex differences; Heart Failure; Adverse drug reactions; Sex-specific Reporting,The Human Phenome,,"

Objectives

This study sought to summarize all available evidence on sex differences in adverse drug reactions (ADRs) to heart failure (HF) medication.

Background

Women are more likely to experience ADRs than men, and these reactions may negatively affect women's immediate and long-term health. HF in particular is associated with increased ADR risk because of the high number of comorbidities and older age. However, little is known about ADRs in women with HF who are treated with guideline-recommended drugs.

Methods

A systematic search of PubMed and EMBASE was performed to collect all available information on ADRs to angiotensin-converting enzyme inhibitors, β-blockers, angiotensin II receptor blockers, mineralocorticoid receptor antagonists, ivabradine, and digoxin in both women and men with HF.

Results

The search identified 155 eligible records, of which only 11 (7%) reported ADR data for women and men separately. Sex-stratified reporting of ADRs did not increase over the last decades. Six of the 11 studies did not report sex differences. Three studies reported a higher risk of angiotensin-converting enzyme inhibitor-related ADRs in women, 1 study showed higher digoxin-related mortality risk for women, and 1 study reported a higher risk of mineralocorticoid receptor antagonist-related ADRs in men. No sex differences in ADRs were reported for angiotensin II receptor blockers and β-blockers. Sex-stratified data were not available for ivabradine.

Conclusions

These results underline the scarcity of ADR data stratified by sex. The study investigators call for a change in standard scientific practice toward reporting of ADR data for women and men separately.",,doi:https://doi.org/10.1016/j.jchf.2019.01.009; doi:https://doi.org/10.1016/j.jchf.2019.01.009 36269859,https://doi.org/10.1073/pnas.2206083119,Metabolome-wide association study on ABCA7 indicates a role of ceramide metabolism in Alzheimer's disease.,"Dehghan A, Pinto RC, Karaman I, Huang J, Durainayagam BR, Ghanbari M, Nazeer A, Zhong Q, Liggi S, Whiley L, Mustafa R, Kivipelto M, Solomon A, Ngandu T, Kanekiyo T, Aikawa T, Radulescu CI, Barnes SJ, Graça G, Chekmeneva E, Camuzeaux S, Lewis MR, Kaluarachchi MR, Ikram MA, Holmes E, Tzoulaki I, Matthews PM, Griffin JL, Elliott P.",,Proceedings of the National Academy of Sciences of the United States of America,2022,2022-10-21,Y,Ceramide; Alzheimer’s disease; Metabolomics; Genome-wide Association Study; Abca7,,,"Genome-wide association studies (GWASs) have identified genetic loci associated with the risk of Alzheimer's disease (AD), but the molecular mechanisms by which they confer risk are largely unknown. We conducted a metabolome-wide association study (MWAS) of AD-associated loci from GWASs using untargeted metabolic profiling (metabolomics) by ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). We identified an association of lactosylceramides (LacCer) with AD-related single-nucleotide polymorphisms (SNPs) in ABCA7 (P = 5.0 × 10-5 to 1.3 × 10-44). We showed that plasma LacCer concentrations are associated with cognitive performance and genetically modified levels of LacCer are associated with AD risk. We then showed that concentrations of sphingomyelins, ceramides, and hexosylceramides were altered in brain tissue from Abca7 knockout mice, compared with wild type (WT) (P = 0.049-1.4 × 10-5), but not in a mouse model of amyloidosis. Furthermore, activation of microglia increases intracellular concentrations of hexosylceramides in part through induction in the expression of sphingosine kinase, an enzyme with a high control coefficient for sphingolipid and ceramide synthesis. Our work suggests that the risk for AD arising from functional variations in ABCA7 is mediated at least in part through ceramides. Modulation of their metabolism or downstream signaling may offer new therapeutic opportunities for AD.",,doi:https://doi.org/10.1073/pnas.2206083119; doi:https://doi.org/10.1073/pnas.2206083119; html:https://europepmc.org/articles/PMC9618092; pdf:https://europepmc.org/articles/PMC9618092?pdf=render 37173061,https://doi.org/10.1016/j.ajcnut.2022.12.021,"Evidence for human milk as a biological system and recommendations for study design-a report from ""Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)"" Working Group 4.","Donovan SM, Aghaeepour N, Andres A, Azad MB, Becker M, Carlson SE, Järvinen KM, Lin W, Lönnerdal B, Slupsky CM, Steiber AL, Raiten DJ.",,The American journal of clinical nutrition,2023,2023-04-01,Y,Immune; systems biology; Human Milk; Microbiome; Infant Development,,,"Human milk contains all of the essential nutrients required by the infant within a complex matrix that enhances the bioavailability of many of those nutrients. In addition, human milk is a source of bioactive components, living cells and microbes that facilitate the transition to life outside the womb. Our ability to fully appreciate the importance of this matrix relies on the recognition of short- and long-term health benefits and, as highlighted in previous sections of this supplement, its ecology (i.e., interactions among the lactating parent and breastfed infant as well as within the context of the human milk matrix itself). Designing and interpreting studies to address this complexity depends on the availability of new tools and technologies that account for such complexity. Past efforts have often compared human milk to infant formula, which has provided some insight into the bioactivity of human milk, as a whole, or of individual milk components supplemented with formula. However, this experimental approach cannot capture the contributions of the individual components to the human milk ecology, the interaction between these components within the human milk matrix, or the significance of the matrix itself to enhance human milk bioactivity on outcomes of interest. This paper presents approaches to explore human milk as a biological system and the functional implications of that system and its components. Specifically, we discuss study design and data collection considerations and how emerging analytical technologies, bioinformatics, and systems biology approaches could be applied to advance our understanding of this critical aspect of human biology.",,doi:https://doi.org/10.1016/j.ajcnut.2022.12.021; html:https://europepmc.org/articles/PMC10356565; pdf:https://europepmc.org/articles/PMC10356565?pdf=render 36527096,https://doi.org/10.1186/s12910-022-00875-9,"""Data makes the story come to life:"" understanding the ethical and legal implications of Big Data research involving ethnic minority healthcare workers in the United Kingdom-a qualitative study.","Dove ES, Reed-Berendt R, Pareek M, UK-REACH Study Collaborative Group.",,BMC medical ethics,2022,2022-12-16,Y,Ethics; Public Health; United Kingdom; Healthcare Workers; Ethnic Minorities; Big Data; Covid-19,,,"The aim of UK-REACH (""The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers"") is to understand if, how, and why healthcare workers (HCWs) in the United Kingdom (UK) from ethnic minority groups are at increased risk of poor outcomes from COVID-19. In this article, we present findings from the ethical and legal stream of the study, which undertook qualitative research seeking to understand and address legal, ethical, and social acceptability issues around data protection, privacy, and information governance associated with the linkage of HCWs' registration data and healthcare data. We interviewed 22 key opinion leaders in healthcare and health research from across the UK in two-to-one semi-structured interviews. Transcripts were coded using qualitative thematic analysis. Participants told us that a significant aspect of Big Data research in public health is varying drivers of mistrust-of the research itself, research staff and funders, and broader concerns of mistrust within participant communities, particularly in the context of COVID-19 and those situated in more marginalised community settings. However, despite the challenges, participants also identified ways in which legally compliant and ethically informed approaches to research can be crafted to mitigate or overcome mistrust and establish greater confidence in Big Data public health research. Overall, our research indicates that a ""Big Data Ethics by Design"" approach to research in this area can help assure (1) that meaningful community and participant engagement is taking place and that extant challenges are addressed, and (2) that any new challenges or hitherto unknown unknowns can be rapidly and properly considered to ensure potential (but material) harms are identified and minimised where necessary. Our findings indicate such an approach, in turn, will help drive better scientific breakthroughs that translate into medical innovations and effective public health interventions, which benefit the publics studied, including those who are often marginalised in research.",,pdf:https://bmcmedethics.biomedcentral.com/counter/pdf/10.1186/s12910-022-00875-9; doi:https://doi.org/10.1186/s12910-022-00875-9; html:https://europepmc.org/articles/PMC9756740; pdf:https://europepmc.org/articles/PMC9756740?pdf=render -34490590,https://doi.org/10.1007/s40256-021-00496-4,Cost Effectiveness of a CYP2C19 Genotype-Guided Strategy in Patients with Acute Myocardial Infarction: Results from the POPular Genetics Trial.,"Claassens DMF, van Dorst PWM, Vos GJA, Bergmeijer TO, Hermanides RS, van 't Hof AWJ, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, Asselbergs FW, Mosterd A, Herrman JR, Dewilde WJM, Postma MJ, Deneer VHM, Ten Berg JM, Boersma C.",,"American journal of cardiovascular drugs : drugs, devices, and other interventions",2022,2021-09-07,N,,,,"

Introduction

The POPular Genetics trial demonstrated that a CYP2C19 genotype-guided P2Y12 inhibitor strategy reduced bleeding rates compared with standard treatment with ticagrelor or prasugrel without increasing thrombotic event rates after primary percutaneous coronary intervention (PCI).

Objective

In this analysis, we aimed to evaluate the cost effectiveness of a genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel.

Methods

A 1-year decision tree based on the POPular Genetics trial in combination with a lifelong Markov model was developed to compare costs and quality-adjusted life-years (QALYs) between a genotype-guided and a standard P2Y12 inhibitor strategy in patients with myocardial infarction undergoing primary PCI. The cost-effectiveness analysis was conducted from a Dutch healthcare system perspective. Within-trial survival and utility data were combined with lifetime projections to evaluate lifetime cost effectiveness for a cohort of 1000 patients. Costs and utilities were discounted at 4 and 1.5%, respectively, according to Dutch guidelines for health economic studies. Besides deterministic and probabilistic sensitivity analyses, several scenario analyses were also conducted (different time horizons, different discount rates, equal prices for P2Y12 inhibitors, and equal distribution of thrombotic events between the two strategies).

Results

Base-case analysis with a hypothetical cohort of 1000 subjects demonstrated 8.98 QALYs gained and €725,550.69 in cost savings for the genotype-guided strategy (dominant). The deterministic and probabilistic sensitivity analysis confirmed the robustness of the model and the cost-effectiveness results. In scenario analyses, the genotype-guided strategy remained dominant.

Conclusion

In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel resulted in QALYs gained and cost savings.

Trial registration

Clinicaltrials.gov number: NCT01761786, Netherlands trial register number: NL2872.",,pdf:https://pure.rug.nl/ws/files/223545267/Cost_Effectiveness_of_a_CYP2C19_Genotype_Guided_Strategy_in_Patients_with_Acute_Myocardial_Infarction_Results_from_the_POPular_Genetics_Trial.pdf; doi:https://doi.org/10.1007/s40256-021-00496-4 36522333,https://doi.org/10.1038/s41467-022-35454-4,Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence.,"Gisby JS, Buang NB, Papadaki A, Clarke CL, Malik TH, Medjeral-Thomas N, Pinheiro D, Mortimer PM, Lewis S, Sandhu E, McAdoo SP, Prendecki MF, Willicombe M, Pickering MC, Botto M, Thomas DC, Peters JE.",,Nature communications,2022,2022-12-15,Y,,,,"Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. Here, we perform longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Supervised learning reveals that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. We show that a decreasing trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, is associated with a more severe clinical course. We observe that two months after the acute infection, patients still display dysregulated gene expression related to vascular, platelet and coagulation pathways, including PF4 (platelet factor 4), which may explain the prolonged thrombotic risk following COVID-19.",,pdf:https://www.nature.com/articles/s41467-022-35454-4.pdf; doi:https://doi.org/10.1038/s41467-022-35454-4; html:https://europepmc.org/articles/PMC9753891; pdf:https://europepmc.org/articles/PMC9753891?pdf=render +34490590,https://doi.org/10.1007/s40256-021-00496-4,Cost Effectiveness of a CYP2C19 Genotype-Guided Strategy in Patients with Acute Myocardial Infarction: Results from the POPular Genetics Trial.,"Claassens DMF, van Dorst PWM, Vos GJA, Bergmeijer TO, Hermanides RS, van 't Hof AWJ, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, Asselbergs FW, Mosterd A, Herrman JR, Dewilde WJM, Postma MJ, Deneer VHM, Ten Berg JM, Boersma C.",,"American journal of cardiovascular drugs : drugs, devices, and other interventions",2022,2021-09-07,N,,,,"

Introduction

The POPular Genetics trial demonstrated that a CYP2C19 genotype-guided P2Y12 inhibitor strategy reduced bleeding rates compared with standard treatment with ticagrelor or prasugrel without increasing thrombotic event rates after primary percutaneous coronary intervention (PCI).

Objective

In this analysis, we aimed to evaluate the cost effectiveness of a genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel.

Methods

A 1-year decision tree based on the POPular Genetics trial in combination with a lifelong Markov model was developed to compare costs and quality-adjusted life-years (QALYs) between a genotype-guided and a standard P2Y12 inhibitor strategy in patients with myocardial infarction undergoing primary PCI. The cost-effectiveness analysis was conducted from a Dutch healthcare system perspective. Within-trial survival and utility data were combined with lifetime projections to evaluate lifetime cost effectiveness for a cohort of 1000 patients. Costs and utilities were discounted at 4 and 1.5%, respectively, according to Dutch guidelines for health economic studies. Besides deterministic and probabilistic sensitivity analyses, several scenario analyses were also conducted (different time horizons, different discount rates, equal prices for P2Y12 inhibitors, and equal distribution of thrombotic events between the two strategies).

Results

Base-case analysis with a hypothetical cohort of 1000 subjects demonstrated 8.98 QALYs gained and €725,550.69 in cost savings for the genotype-guided strategy (dominant). The deterministic and probabilistic sensitivity analysis confirmed the robustness of the model and the cost-effectiveness results. In scenario analyses, the genotype-guided strategy remained dominant.

Conclusion

In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel resulted in QALYs gained and cost savings.

Trial registration

Clinicaltrials.gov number: NCT01761786, Netherlands trial register number: NL2872.",,pdf:https://pure.rug.nl/ws/files/223545267/Cost_Effectiveness_of_a_CYP2C19_Genotype_Guided_Strategy_in_Patients_with_Acute_Myocardial_Infarction_Results_from_the_POPular_Genetics_Trial.pdf; doi:https://doi.org/10.1007/s40256-021-00496-4 37132645,https://doi.org/10.1017/s0033291721002257,"Life expectancy, mortality risks and cause of death in patients with serious mental illness in South East London: a comparison between 2008-2012 and 2013-2017.","Chang CK, Chesney E, Teng WN, Hollandt S, Pritchard M, Shetty H, Stewart R, McGuire P, Patel R.",,Psychological medicine,2023,2021-09-07,Y,Mortality; Schizophrenia; Life expectancy; Cause of death; Bipolar disorder; Standardised Mortality Ratio,,,"

Background

People with serious mental illness (SMI) have a significantly shorter life expectancy than the general population. This study investigates whether the mortality rate in this group has changed over the last decade.

Methods

Using Clinical Record Interactive Search software, we extracted data from a large electronic database of patients in South East London. All patients with schizophrenia, schizoaffective disorder or bipolar disorder from 2008 to 2012 and/or 2013 to 2017 were included. Estimates of life expectancy at birth, standardised mortality ratios and causes of death were obtained for each cohort according to diagnosis and gender. Comparisons were made between cohorts and with the general population using data obtained from the UK Office of National Statistics.

Results

In total, 26 005 patients were included. In men, life expectancy was greater in 2013-2017 (64.9 years; 95% CI 63.6-66.3) than in 2008-2012 (63.2 years; 95% CI 61.5-64.9). Similarly, in women, life expectancy was greater in 2013-2017 (69.1 years; 95% CI 67.5-70.7) than in 2008-2012 (68.1 years; 95% CI 66.2-69.9). The difference with general population life expectancy fell by 0.9 years between cohorts in men, and 0.5 years in women. In the 2013-2017 cohorts, cancer accounted for a similar proportion of deaths as cardiovascular disease.

Conclusions

Relative to the general population, life expectancy for people with SMI is still much worse, though it appears to be improving. The increased cancer-related mortality suggests that physical health monitoring should consider including cancer as well.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/F28CB69D452C5EFDAFF77D0FE59FC094/S0033291721002257a.pdf/div-class-title-life-expectancy-mortality-risks-and-cause-of-death-in-patients-with-serious-mental-illness-in-south-east-london-a-comparison-between-2008-2012-and-2013-2017-div.pdf; doi:https://doi.org/10.1017/S0033291721002257; html:https://europepmc.org/articles/PMC9975985; pdf:https://europepmc.org/articles/PMC9975985?pdf=render -38783292,https://doi.org/10.1186/s12939-024-02198-0,"Discrimination, disadvantage and disempowerment during COVID-19: a qualitative intrasectional analysis of the lived experiences of an ethnically diverse healthcare workforce in the United Kingdom.","Gogoi M, Qureshi I, Chaloner J, Al-Oraibi A, Reilly H, Wobi F, Agbonmwandolor JO, Ekezie W, Hassan O, Lal Z, Kapilashrami A, Nellums L, Pareek M, UK-REACH Study Collaborative Group Members.",,International journal for equity in health,2024,2024-05-23,Y,Discrimination; Healthcare Workers; Disadvantage; Disempowerment; Covid-19 Pandemic; Intersectionality; Intrasectionalism,,,"

Background

Healthcare workers (HCWs) in the United Kingdom (UK) have faced many challenges during the COVID-19 pandemic, some of these arising out of their social positions. Existing literature explicating these challenges (e.g., lack of appropriate PPE, redeployment, understaffing) have highlighted inequities in how these have been experienced by HCWs based on ethnicity, gender or, job role. In this paper, we move a step ahead and examine how the intersection of these social positions have impacted HCWs' experiences of challenges during the pandemic.

Methods

We collected qualitative data, using interviews and focus groups, from 164 HCWs from different ethnicities, gender, job roles, migration statuses, and regions in the United Kingdom (UK) between December 2020 and July 2021. Interviews and focus groups were conducted online or by telephone, and recorded with participants' permission. Recordings were transcribed and a hybrid thematic analytical approach integrating inductive data-driven codes with deductive ones informed by an intersectional framework was adopted to analyse the transcripts.

Results

Thematic analysis of transcripts identified disempowerment, disadvantage and, discrimination as the three main themes around which HCWs' experiences of challenges were centred, based on their intersecting identities (e.g., ethnicity gender, and/or migration status). Our analysis also acknowledges that disadvantages faced by HCWs were linked to systemic and structural factors at the micro, meso and macro ecosystemic levels. This merging of analysis which is grounded in intersectionality and considers the ecosystemic levels has been termed as 'intrasectionalism'.

Discussion

Our research demonstrates how an intrasectional lens can help better understand how different forms of mutually reinforcing inequities exist at all levels within the healthcare workforce and how these impact HCWs from certain backgrounds who face greater disadvantage, discrimination and disempowerment, particularly during times of crisis like the COVID-19 pandemic.",,pdf:https://equityhealthj.biomedcentral.com/counter/pdf/10.1186/s12939-024-02198-0; doi:https://doi.org/10.1186/s12939-024-02198-0; html:https://europepmc.org/articles/PMC11118759; pdf:https://europepmc.org/articles/PMC11118759?pdf=render 33199917,https://doi.org/10.1038/s41588-020-00725-7,Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors.,"Bakker MK, van der Spek RAA, van Rheenen W, Morel S, Bourcier R, Hostettler IC, Alg VS, van Eijk KR, Koido M, Akiyama M, Terao C, Matsuda K, Walters RG, Lin K, Li L, Millwood IY, Chen Z, Rouleau GA, Zhou S, Rannikmäe K, Sudlow CLM, Houlden H, van den Berg LH, Dina C, Naggara O, Gentric JC, Shotar E, Eugène F, Desal H, Winsvold BS, Børte S, Johnsen MB, Brumpton BM, Sandvei MS, Willer CJ, Hveem K, Zwart JA, Verschuren WMM, Friedrich CM, Hirsch S, Schilling S, Dauvillier J, Martin O, HUNT All-In Stroke, China Kadoorie Biobank Collaborative Group, BioBank Japan Project Consortium, ICAN Study Group, CADISP Group, Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study investigators, International Stroke Genetics Consortium (ISGC), Jones GT, Bown MJ, Ko NU, Kim H, Coleman JRI, Breen G, Zaroff JG, Klijn CJM, Malik R, Dichgans M, Sargurupremraj M, Tatlisumak T, Amouyel P, Debette S, Rinkel GJE, Worrall BB, Pera J, Slowik A, Gaál-Paavola EI, Niemelä M, Jääskeläinen JE, von Und Zu Fraunberg M, Lindgren A, Broderick JP, Werring DJ, Woo D, Redon R, Bijlenga P, Kamatani Y, Veldink JH, Ruigrok YM.",,Nature genetics,2020,2020-11-16,N,,,,"Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits.",,pdf:https://europepmc.org/articles/pmc7116530?pdf=render; doi:https://doi.org/10.1038/s41588-020-00725-7; html:https://europepmc.org/articles/PMC7116530; pdf:https://europepmc.org/articles/PMC7116530?pdf=render; doi:https://doi.org/10.1038/s41588-020-00725-7 +38783292,https://doi.org/10.1186/s12939-024-02198-0,"Discrimination, disadvantage and disempowerment during COVID-19: a qualitative intrasectional analysis of the lived experiences of an ethnically diverse healthcare workforce in the United Kingdom.","Gogoi M, Qureshi I, Chaloner J, Al-Oraibi A, Reilly H, Wobi F, Agbonmwandolor JO, Ekezie W, Hassan O, Lal Z, Kapilashrami A, Nellums L, Pareek M, UK-REACH Study Collaborative Group Members.",,International journal for equity in health,2024,2024-05-23,Y,Discrimination; Healthcare Workers; Disadvantage; Disempowerment; Covid-19 Pandemic; Intersectionality; Intrasectionalism,,,"

Background

Healthcare workers (HCWs) in the United Kingdom (UK) have faced many challenges during the COVID-19 pandemic, some of these arising out of their social positions. Existing literature explicating these challenges (e.g., lack of appropriate PPE, redeployment, understaffing) have highlighted inequities in how these have been experienced by HCWs based on ethnicity, gender or, job role. In this paper, we move a step ahead and examine how the intersection of these social positions have impacted HCWs' experiences of challenges during the pandemic.

Methods

We collected qualitative data, using interviews and focus groups, from 164 HCWs from different ethnicities, gender, job roles, migration statuses, and regions in the United Kingdom (UK) between December 2020 and July 2021. Interviews and focus groups were conducted online or by telephone, and recorded with participants' permission. Recordings were transcribed and a hybrid thematic analytical approach integrating inductive data-driven codes with deductive ones informed by an intersectional framework was adopted to analyse the transcripts.

Results

Thematic analysis of transcripts identified disempowerment, disadvantage and, discrimination as the three main themes around which HCWs' experiences of challenges were centred, based on their intersecting identities (e.g., ethnicity gender, and/or migration status). Our analysis also acknowledges that disadvantages faced by HCWs were linked to systemic and structural factors at the micro, meso and macro ecosystemic levels. This merging of analysis which is grounded in intersectionality and considers the ecosystemic levels has been termed as 'intrasectionalism'.

Discussion

Our research demonstrates how an intrasectional lens can help better understand how different forms of mutually reinforcing inequities exist at all levels within the healthcare workforce and how these impact HCWs from certain backgrounds who face greater disadvantage, discrimination and disempowerment, particularly during times of crisis like the COVID-19 pandemic.",,pdf:https://equityhealthj.biomedcentral.com/counter/pdf/10.1186/s12939-024-02198-0; doi:https://doi.org/10.1186/s12939-024-02198-0; html:https://europepmc.org/articles/PMC11118759; pdf:https://europepmc.org/articles/PMC11118759?pdf=render 32127008,https://doi.org/10.1186/s13059-020-01969-6,Accurate targeted long-read DNA methylation and hydroxymethylation sequencing with TAPS.,"Liu Y, Cheng J, Siejka-Zielińska P, Weldon C, Roberts H, Lopopolo M, Magri A, D'Arienzo V, Harris JM, McKeating JA, Song CX.",,Genome biology,2020,2020-03-03,Y,DNA methylation; 5-methylcytosine; Long-read Sequencing; Bisulfite-free; Epigenetic Phasing,Understanding the Causes of Disease,infection,"We present long-read Tet-assisted pyridine borane sequencing (lrTAPS) for targeted base-resolution sequencing of DNA methylation and hydroxymethylation in regions up to 10 kb from nanogram-level input. Compatible with both Oxford Nanopore and PacBio Single-Molecule Real-Time (SMRT) sequencing, lrTAPS detects methylation with accuracy comparable to short-read Illumina sequencing but with long-range epigenetic phasing. We applied lrTAPS to sequence difficult-to-map regions in mouse embryonic stem cells and to identify distinct methylation events in the integrated hepatitis B virus genome.",,pdf:https://genomebiology.biomedcentral.com/track/pdf/10.1186/s13059-020-01969-6; doi:https://doi.org/10.1186/s13059-020-01969-6; html:https://europepmc.org/articles/PMC7053107; pdf:https://europepmc.org/articles/PMC7053107?pdf=render -35617980,https://doi.org/10.1016/s0140-6736(22)00532-3,Measuring the availability of human resources for health and its relationship to universal health coverage for 204 countries and territories from 1990 to 2019: a systematic analysis for the Global Burden of Disease Study 2019.,GBD 2019 Human Resources for Health Collaborators.,,"Lancet (London, England)",2022,2022-05-23,Y,,,,"

Background

Human resources for health (HRH) include a range of occupations that aim to promote or improve human health. The UN Sustainable Development Goals (SDGs) and the WHO Health Workforce 2030 strategy have drawn attention to the importance of HRH for achieving policy priorities such as universal health coverage (UHC). Although previous research has found substantial global disparities in HRH, the absence of comparable cross-national estimates of existing workforces has hindered efforts to quantify workforce requirements to meet health system goals. We aimed to use comparable and standardised data sources to estimate HRH densities globally, and to examine the relationship between a subset of HRH cadres and UHC effective coverage performance.

Methods

Through the International Labour Organization and Global Health Data Exchange databases, we identified 1404 country-years of data from labour force surveys and 69 country-years of census data, with detailed microdata on health-related employment. From the WHO National Health Workforce Accounts, we identified 2950 country-years of data. We mapped data from all occupational coding systems to the International Standard Classification of Occupations 1988 (ISCO-88), allowing for standardised estimation of densities for 16 categories of health workers across the full time series. Using data from 1990 to 2019 for 196 of 204 countries and territories, covering seven Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) super-regions and 21 regions, we applied spatiotemporal Gaussian process regression (ST-GPR) to model HRH densities from 1990 to 2019 for all countries and territories. We used stochastic frontier meta-regression to model the relationship between the UHC effective coverage index and densities for the four categories of health workers enumerated in SDG indicator 3.c.1 pertaining to HRH: physicians, nurses and midwives, dentistry personnel, and pharmaceutical personnel. We identified minimum workforce density thresholds required to meet a specified target of 80 out of 100 on the UHC effective coverage index, and quantified national shortages with respect to those minimum thresholds.

Findings

We estimated that, in 2019, the world had 104·0 million (95% uncertainty interval 83·5-128·0) health workers, including 12·8 million (9·7-16·6) physicians, 29·8 million (23·3-37·7) nurses and midwives, 4·6 million (3·6-6·0) dentistry personnel, and 5·2 million (4·0-6·7) pharmaceutical personnel. We calculated a global physician density of 16·7 (12·6-21·6) per 10 000 population, and a nurse and midwife density of 38·6 (30·1-48·8) per 10 000 population. We found the GBD super-regions of sub-Saharan Africa, south Asia, and north Africa and the Middle East had the lowest HRH densities. To reach 80 out of 100 on the UHC effective coverage index, we estimated that, per 10 000 population, at least 20·7 physicians, 70·6 nurses and midwives, 8·2 dentistry personnel, and 9·4 pharmaceutical personnel would be needed. In total, the 2019 national health workforces fell short of these minimum thresholds by 6·4 million physicians, 30·6 million nurses and midwives, 3·3 million dentistry personnel, and 2·9 million pharmaceutical personnel.

Interpretation

Considerable expansion of the world's health workforce is needed to achieve high levels of UHC effective coverage. The largest shortages are in low-income settings, highlighting the need for increased financing and coordination to train, employ, and retain human resources in the health sector. Actual HRH shortages might be larger than estimated because minimum thresholds for each cadre of health workers are benchmarked on health systems that most efficiently translate human resources into UHC attainment.

Funding

Bill & Melinda Gates Foundation.",,pdf:http://www.thelancet.com/article/S0140673622005323/pdf; doi:https://doi.org/10.1016/S0140-6736(22)00532-3; html:https://europepmc.org/articles/PMC9168805 33075408,https://doi.org/10.1016/j.jaci.2020.10.007,Factors associated with adverse COVID-19 outcomes in patients with psoriasis-insights from a global registry-based study.,"Mahil SK, Dand N, Mason KJ, Yiu ZZN, Tsakok T, Meynell F, Coker B, McAteer H, Moorhead L, Mackenzie T, Rossi MT, Rivera R, Mahe E, Carugno A, Magnano M, Rech G, Balogh EA, Feldman SR, De La Cruz C, Choon SE, Naldi L, Lambert J, Spuls P, Jullien D, Bachelez H, McMahon DE, Freeman EE, Gisondi P, Puig L, Warren RB, Di Meglio P, Langan SM, Capon F, Griffiths CEM, Barker JN, Smith CH, PsoProtect study group.",,The Journal of allergy and clinical immunology,2021,2020-10-16,Y,Psoriasis; Immunosuppressants; risk factors; Hospitalization; Biologics; Covid-19,,,"

Background

The multimorbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse outcomes of coronavirus disease 2019 (COVID-19), but the data are limited.

Objective

Our aim was to characterize the course of COVID-19 in patients with psoriasis and identify factors associated with hospitalization.

Methods

Clinicians reported patients with psoriasis with confirmed/suspected COVID-19 via an international registry, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection. Multiple logistic regression was used to assess the association between clinical and/or demographic characteristics and hospitalization. A separate patient-facing registry characterized risk-mitigating behaviors.

Results

Of 374 clinician-reported patients from 25 countries, 71% were receiving a biologic, 18% were receiving a nonbiologic, and 10% were not receiving any systemic treatment for psoriasis. In all, 348 patients (93%) were fully recovered from COVID-19, 77 (21%) were hospitalized, and 9 (2%) died. Increased hospitalization risk was associated with older age (multivariable-adjusted odds ratio [OR] = 1.59 per 10 years; 95% CI = 1.19-2.13), male sex (OR = 2.51; 95% CI = 1.23-5.12), nonwhite ethnicity (OR = 3.15; 95% CI = 1.24-8.03), and comorbid chronic lung disease (OR = 3.87; 95% CI = 1.52-9.83). Hospitalization was more frequent in patients using nonbiologic systemic therapy than in those using biologics (OR = 2.84; 95% CI = 1.31-6.18). No significant differences were found between classes of biologics. Independent patient-reported data (n = 1626 across 48 countries) suggested lower levels of social isolation in individuals receiving nonbiologic systemic therapy than in those receiving biologics (OR = 0.68; 95% CI = 0.50-0.94).

Conclusion

In this international case series of patients with moderate-to-severe psoriasis, biologic use was associated with lower risk of COVID-19-related hospitalization than with use of nonbiologic systemic therapies; however, further investigation is warranted on account of potential selection bias and unmeasured confounding. Established risk factors (being older, being male, being of nonwhite ethnicity, and having comorbidities) were associated with higher hospitalization rates.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4659367/1/Factors%20associated%20with%20adverse%20COVID-19%20outcomes%20in%20patients%20with%20psoriasis-insights%20from%20a%20global%20registry-based%20study.pdf; doi:https://doi.org/10.1016/j.jaci.2020.10.007; html:https://europepmc.org/articles/PMC7566694; pdf:https://europepmc.org/articles/PMC7566694?pdf=render +35617980,https://doi.org/10.1016/s0140-6736(22)00532-3,Measuring the availability of human resources for health and its relationship to universal health coverage for 204 countries and territories from 1990 to 2019: a systematic analysis for the Global Burden of Disease Study 2019.,GBD 2019 Human Resources for Health Collaborators.,,"Lancet (London, England)",2022,2022-05-23,Y,,,,"

Background

Human resources for health (HRH) include a range of occupations that aim to promote or improve human health. The UN Sustainable Development Goals (SDGs) and the WHO Health Workforce 2030 strategy have drawn attention to the importance of HRH for achieving policy priorities such as universal health coverage (UHC). Although previous research has found substantial global disparities in HRH, the absence of comparable cross-national estimates of existing workforces has hindered efforts to quantify workforce requirements to meet health system goals. We aimed to use comparable and standardised data sources to estimate HRH densities globally, and to examine the relationship between a subset of HRH cadres and UHC effective coverage performance.

Methods

Through the International Labour Organization and Global Health Data Exchange databases, we identified 1404 country-years of data from labour force surveys and 69 country-years of census data, with detailed microdata on health-related employment. From the WHO National Health Workforce Accounts, we identified 2950 country-years of data. We mapped data from all occupational coding systems to the International Standard Classification of Occupations 1988 (ISCO-88), allowing for standardised estimation of densities for 16 categories of health workers across the full time series. Using data from 1990 to 2019 for 196 of 204 countries and territories, covering seven Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) super-regions and 21 regions, we applied spatiotemporal Gaussian process regression (ST-GPR) to model HRH densities from 1990 to 2019 for all countries and territories. We used stochastic frontier meta-regression to model the relationship between the UHC effective coverage index and densities for the four categories of health workers enumerated in SDG indicator 3.c.1 pertaining to HRH: physicians, nurses and midwives, dentistry personnel, and pharmaceutical personnel. We identified minimum workforce density thresholds required to meet a specified target of 80 out of 100 on the UHC effective coverage index, and quantified national shortages with respect to those minimum thresholds.

Findings

We estimated that, in 2019, the world had 104·0 million (95% uncertainty interval 83·5-128·0) health workers, including 12·8 million (9·7-16·6) physicians, 29·8 million (23·3-37·7) nurses and midwives, 4·6 million (3·6-6·0) dentistry personnel, and 5·2 million (4·0-6·7) pharmaceutical personnel. We calculated a global physician density of 16·7 (12·6-21·6) per 10 000 population, and a nurse and midwife density of 38·6 (30·1-48·8) per 10 000 population. We found the GBD super-regions of sub-Saharan Africa, south Asia, and north Africa and the Middle East had the lowest HRH densities. To reach 80 out of 100 on the UHC effective coverage index, we estimated that, per 10 000 population, at least 20·7 physicians, 70·6 nurses and midwives, 8·2 dentistry personnel, and 9·4 pharmaceutical personnel would be needed. In total, the 2019 national health workforces fell short of these minimum thresholds by 6·4 million physicians, 30·6 million nurses and midwives, 3·3 million dentistry personnel, and 2·9 million pharmaceutical personnel.

Interpretation

Considerable expansion of the world's health workforce is needed to achieve high levels of UHC effective coverage. The largest shortages are in low-income settings, highlighting the need for increased financing and coordination to train, employ, and retain human resources in the health sector. Actual HRH shortages might be larger than estimated because minimum thresholds for each cadre of health workers are benchmarked on health systems that most efficiently translate human resources into UHC attainment.

Funding

Bill & Melinda Gates Foundation.",,pdf:http://www.thelancet.com/article/S0140673622005323/pdf; doi:https://doi.org/10.1016/S0140-6736(22)00532-3; html:https://europepmc.org/articles/PMC9168805 37263751,https://doi.org/10.1183/13993003.01667-2022,Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection.,"Packer RJ, Shrine N, Hall R, Melbourne CA, Thompson R, Williams AT, Paynton ML, Guyatt AL, Allen RJ, Lee PH, John C, Campbell A, Hayward C, de Vries M, Vonk JM, Davitte J, Hessel E, Michalovich D, Betts JC, Sayers I, Yeo A, Hall IP, Tobin MD, Wain LV.",,The European respiratory journal,2023,2023-06-15,Y,,,,"

Background

Chronic sputum production impacts on quality of life and is a feature of many respiratory diseases. Identification of the genetic variants associated with chronic sputum production in a disease agnostic sample could improve understanding of its causes and identify new molecular targets for treatment.

Methods

We conducted a genome-wide association study (GWAS) of chronic sputum production in UK Biobank. Signals meeting genome-wide significance (p<5×10-8) were investigated in additional independent studies, were fine-mapped and putative causal genes identified by gene expression analysis. GWASs of respiratory traits were interrogated to identify whether the signals were driven by existing respiratory disease among the cases and variants were further investigated for wider pleiotropic effects using phenome-wide association studies (PheWASs).

Results

From a GWAS of 9714 cases and 48 471 controls, we identified six novel genome-wide significant signals for chronic sputum production including signals in the human leukocyte antigen (HLA) locus, chromosome 11 mucin locus (containing MUC2, MUC5AC and MUC5B) and FUT2 locus. The four common variant associations were supported by independent studies with a combined sample size of up to 2203 cases and 17 627 controls. The mucin locus signal had previously been reported for association with moderate-to-severe asthma. The HLA signal was fine-mapped to an amino acid change of threonine to arginine (frequency 36.8%) in HLA-DRB1 (HLA-DRB1*03:147). The signal near FUT2 was associated with expression of several genes including FUT2, for which the direction of effect was tissue dependent. Our PheWAS identified a wide range of associations including blood cell traits, liver biomarkers, infections, gastrointestinal and thyroid-associated diseases, and respiratory disease.

Conclusions

Novel signals at the FUT2 and mucin loci suggest that mucin fucosylation may be a driver of chronic sputum production even in the absence of diagnosed respiratory disease and provide genetic support for this pathway as a target for therapeutic intervention.",,pdf:https://erj.ersjournals.com/content/erj/61/6/2201667.full.pdf; doi:https://doi.org/10.1183/13993003.01667-2022; html:https://europepmc.org/articles/PMC10284065; pdf:https://europepmc.org/articles/PMC10284065?pdf=render 32423943,https://doi.org/10.1136/bmjopen-2020-038974,Study protocol for a multicentre longitudinal mixed methods study to explore the Outcomes of ChildrEn and fAmilies in the first year after paediatric Intensive Care: the OCEANIC study.,"Manning JC, Latour JM, Curley MAQ, Draper ES, Jilani T, Quinlan PR, Watson RS, Rennick JE, Colville G, Pinto N, Latif A, Popejoy E, Coad J, OCEANIC Study Investigators.",,BMJ open,2020,2020-05-17,Y,Qualitative Research; Statistics & Research Methods; Paediatric Intensive & Critical Care,,,"

Introduction

Annually in the UK, 20 000 children become very ill or injured and need specialist care within a paediatric intensive care unit (PICU). Most children survive. However, some children and their families may experience problems after they have left the PICU including physical, functional and/or emotional problems. It is unknown which children and families experience such problems, when these occur or what causes them. The aim of this mixed-method longitudinal cohort study is to understand the physical, functional, emotional and social impact of children surviving PICU (aged: 1 month-17 years), their parents and siblings, during the first year after a PICU admission.

Methods and analysis

A quantitative study involving 300 child survivors of PICU; 300 parents; and 150-300 siblings will collect data (using self-completion questionnaires) at baseline, PICU discharge, 1, 3, 6 and 12 months post-PICU discharge. Questionnaires will comprise validated and reliable instruments. Demographic data, PICU admission and treatment data, health-related quality of life, functional status, strengths and difficulties behaviour and post-traumatic stress symptoms will be collected from the child. Parent and sibling data will be collected on the impact of paediatric health conditions on the family's functioning capabilities, levels of anxiety and social impact of the child's PICU admission. Data will be analysed using descriptive and inferential statistics. Concurrently, an embedded qualitative study involving semistructured interviews with 24 enrolled families at 3 months and 9 months post-PICU discharge will be undertaken. Framework analysis will be used to analyse the qualitative data.

Ethics and dissemination

The study has received ethical approval from the National Health Services Research Ethics Committee (Ref: 19/WM/0290) and full governance clearance. This will be the first UK study to comprehensively investigate physical, functional, emotional and social consequences of PICU survival in the first-year postdischarge.Clinical Trials Registration Number: ISRCTN28072812 [Pre-results].",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/5/e038974.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-038974; html:https://europepmc.org/articles/PMC7239532; pdf:https://europepmc.org/articles/PMC7239532?pdf=render 31844048,https://doi.org/10.1038/s41467-019-13585-5,Genome-wide analysis identifies molecular systems and 149 genetic loci associated with income.,"Hill WD, Davies NM, Ritchie SJ, Skene NG, Bryois J, Bell S, Di Angelantonio E, Roberts DJ, Xueyi S, Davies G, Liewald DCM, Porteous DJ, Hayward C, Butterworth AS, McIntosh AM, Gale CR, Deary IJ.",,Nature communications,2019,2019-12-16,Y,,Understanding the Causes of Disease,,"Socioeconomic position (SEP) is a multi-dimensional construct reflecting (and influencing) multiple socio-cultural, physical, and environmental factors. In a sample of 286,301 participants from UK Biobank, we identify 30 (29 previously unreported) independent-loci associated with income. Using a method to meta-analyze data from genetically-correlated traits, we identify an additional 120 income-associated loci. These loci show clear evidence of functionality, with transcriptional differences identified across multiple cortical tissues, and links to GABAergic and serotonergic neurotransmission. By combining our genome wide association study on income with data from eQTL studies and chromatin interactions, 24 genes are prioritized for follow up, 18 of which were previously associated with intelligence. We identify intelligence as one of the likely causal, partly-heritable phenotypes that might bridge the gap between molecular genetic inheritance and phenotypic consequence in terms of income differences. These results indicate that, in modern era Great Britain, genetic effects contribute towards some of the observed socioeconomic inequalities.","This study linked genetic sequencing data and information on household income to identify parts of the genome that are more common in people who live in more affluent households. The authors identified 150 parts of the genome that were associated with income, and found that these genetic regions were more commonly expressed in the brain and testes. The results indicate that intelligence and income are causally linked, and suggest that genetics partly explain a small amount of variation (~2%) in household income in the UK.",pdf:https://www.nature.com/articles/s41467-019-13585-5.pdf; doi:https://doi.org/10.1038/s41467-019-13585-5; html:https://europepmc.org/articles/PMC6915786; pdf:https://europepmc.org/articles/PMC6915786?pdf=render -37923486,https://doi.org/10.1016/s2352-3018(23)00233-3,Integrase strand-transfer inhibitor use and cardiovascular events in adults with HIV: an emulation of target trials in the HIV-CAUSAL Collaboration and the Antiretroviral Therapy Cohort Collaboration.,"Rein SM, Lodi S, Logan RW, Touloumi G, Antoniadou A, Wittkop L, Bonnet F, van Sighem A, van der Valk M, Reiss P, Klein MB, Young J, Jarrin I, d'Arminio Monforte A, Tavelli A, Meyer L, Tran L, Gill MJ, Lang R, Surial B, Haas AD, Justice AC, Rentsch CT, Phillips A, Sabin CA, Miro JM, Trickey A, Ingle SM, Sterne JAC, Hernán MA, Antiretroviral Therapy Cohort Collaboration and the HIV-CAUSAL Collaboration.",,The lancet. HIV,2023,2023-11-01,N,,,,"

Background

A recent observational study suggested that the risk of cardiovascular events could be higher among antiretroviral therapy (ART)-naive individuals with HIV who receive integrase strand-transfer inhibitor (INSTI)-based ART than among those who receive other ART regimens. We aimed to emulate target trials separately in ART-naive and ART-experienced individuals with HIV to examine the effect of using INSTI-based regimens versus other ART regimens on the 4-year risk of cardiovascular events.

Methods

We used routinely recorded clinical data from 12 cohorts that collected information on cardiovascular events, BMI, and blood pressure from two international consortia of cohorts of people with HIV from Europe and North America. For the target trial in individuals who had previously never used ART (ie, ART-naive), eligibility criteria were aged 18 years or older, a detectable HIV-RNA measurement while ART-naive (>50 copies per mL), and no history of a cardiovascular event or cancer. Eligibility criteria for the target trial in those with previous use of non-INSTI-based ART (ie, ART-experienced) were the same except that individuals had to have been on at least one non-INSTI-based ART regimen and be virally suppressed (≤50 copies per mL). We assessed eligibility for both trials for each person-month between January, 2013, and January, 2023, and assigned individuals to the treatment strategy that was compatible with their data. We estimated the standardised 4-year risks of cardiovascular events (myocardial infarction, stroke, or invasive cardiovascular procedure) via pooled logistic regression models adjusting for time and baseline covariates. In per-protocol analyses, we censored individuals if they deviated from their assigned treatment strategy for more than 2 months and weighted uncensored individuals by the inverse of their time-varying probability of remaining uncensored. The denominator of the weight was estimated via a pooled logistic model that included baseline and time-varying covariates.

Findings

The analysis in ART-naive individuals included 10 767 INSTI initiators and 8292 non-initiators of INSTI. There were 43 cardiovascular events in INSTI initiators (median follow-up of 29 months; IQR 15-45) and 52 in non-initiators (39 months; 18-47): standardised 4-year risks were 0·76% (95% CI 0·51 to 1·04) in INSTI initiators and 0·75% (0·54 to 0·98) in non-INSTI initiators; risk ratio 1·01 (0·57 to 1·57); risk difference 0·0089% (-0·43 to 0·36). The analysis in ART-experienced individuals included 7875 INSTI initiators and 373 965 non-initiators. There were 56 events in INSTI initiators (median follow-up 18 months; IQR 9-29) and 3103 events (808 unique) in non-INSTI initiators (26 months; 15-37) in non-initiators: standardised 4-year risks 1·41% (95% CI 0·88 to 2·03) in INSTI initiators and 1·48% (1·28 to 1·71) in non-initiators; risk ratio 0·95 (0·60 to 1·36); risk difference -0·068% (-0·60 to 0·52).

Interpretation

We estimated that INSTI use did not result in a clinically meaningful increase of cardiovascular events in ART-naive and ART-experienced individuals with HIV.

Funding

National Institute of Allergy and Infectious Diseases and National Institute on Alcohol Abuse and Alcoholism.",,pdf:https://research-information.bris.ac.uk/files/382068016/Rev2_clean_InstiCVD.pdf; doi:https://doi.org/10.1016/S2352-3018(23)00233-3 -36914875,https://doi.org/10.1038/s41588-023-01314-0,Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.,"Shrine N, Izquierdo AG, Chen J, Packer R, Hall RJ, Guyatt AL, Batini C, Thompson RJ, Pavuluri C, Malik V, Hobbs BD, Moll M, Kim W, Tal-Singer R, Bakke P, Fawcett KA, John C, Coley K, Piga NN, Pozarickij A, Lin K, Millwood IY, Chen Z, Li L, China Kadoorie Biobank Collaborative Group, Wijnant SRA, Lahousse L, Brusselle G, Uitterlinden AG, Manichaikul A, Oelsner EC, Rich SS, Barr RG, Kerr SM, Vitart V, Brown MR, Wielscher M, Imboden M, Jeong A, Bartz TM, Gharib SA, Flexeder C, Karrasch S, Gieger C, Peters A, Stubbe B, Hu X, Ortega VE, Meyers DA, Bleecker ER, Gabriel SB, Gupta N, Smith AV, Luan J, Zhao JH, Hansen AF, Langhammer A, Willer C, Bhatta L, Porteous D, Smith BH, Campbell A, Sofer T, Lee J, Daviglus ML, Yu B, Lim E, Xu H, O'Connor GT, Thareja G, Albagha OME, Qatar Genome Program Research (QGPR) Consortium, Suhre K, Granell R, Faquih TO, Hiemstra PS, Slats AM, Mullin BH, Hui J, James A, Beilby J, Patasova K, Hysi P, Koskela JT, Wyss AB, Jin J, Sikdar S, Lee M, May-Wilson S, Pirastu N, Kentistou KA, Joshi PK, Timmers PRHJ, Williams AT, Free RC, Wang X, Morrison JL, Gilliland FD, Chen Z, Wang CA, Foong RE, Harris SE, Taylor A, Redmond P, Cook JP, Mahajan A, Lind L, Palviainen T, Lehtimäki T, Raitakari OT, Kaprio J, Rantanen T, Pietiläinen KH, Cox SR, Pennell CE, Hall GL, Gauderman WJ, Brightling C, Wilson JF, Vasankari T, Laitinen T, Salomaa V, Mook-Kanamori DO, Timpson NJ, Zeggini E, Dupuis J, Hayward C, Brumpton B, Langenberg C, Weiss S, Homuth G, Schmidt CO, Probst-Hensch N, Jarvelin MR, Morrison AC, Polasek O, Rudan I, Lee JH, Sayers I, Rawlins EL, Dudbridge F, Silverman EK, Strachan DP, Walters RG, Morris AP, London SJ, Cho MH, Wain LV, Hall IP, Tobin MD.",,Nature genetics,2023,2023-03-13,Y,,,,"Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.",,pdf:https://www.nature.com/articles/s41588-023-01314-0.pdf; doi:https://doi.org/10.1038/s41588-023-01314-0; html:https://europepmc.org/articles/PMC10011137; pdf:https://europepmc.org/articles/PMC10011137?pdf=render 31711539,https://doi.org/10.1186/s13326-019-0211-7,Text mining brain imaging reports.,"Alex B, Grover C, Tobin R, Sudlow C, Mair G, Whiteley W.",,Journal of biomedical semantics,2019,2019-11-12,Y,Stroke Classification; Text Mining; Electronic Healthcare Records; Neuroimaging Reports,,,"

Background

With the improvements to text mining technology and the availability of large unstructured Electronic Healthcare Records (EHR) datasets, it is now possible to extract structured information from raw text contained within EHR at reasonably high accuracy. We describe a text mining system for classifying radiologists' reports of CT and MRI brain scans, assigning labels indicating occurrence and type of stroke, as well as other observations. Our system, the Edinburgh Information Extraction for Radiology reports (EdIE-R) system, which we describe here, was developed and tested on a collection of radiology reports.The work reported in this paper is based on 1168 radiology reports from the Edinburgh Stroke Study (ESS), a hospital-based register of stroke and transient ischaemic attack patients. We manually created annotations for this data in parallel with developing the rule-based EdIE-R system to identify phenotype information related to stroke in radiology reports. This process was iterative and domain expert feedback was considered at each iteration to adapt and tune the EdIE-R text mining system which identifies entities, negation and relations between entities in each report and determines report-level labels (phenotypes).

Results

The inter-annotator agreement (IAA) for all types of annotations is high at 96.96 for entities, 96.46 for negation, 95.84 for relations and 94.02 for labels. The equivalent system scores on the blind test set are equally high at 95.49 for entities, 94.41 for negation, 98.27 for relations and 96.39 for labels for the first annotator and 96.86, 96.01, 96.53 and 92.61, respectively for the second annotator.

Conclusion

Automated reading of such EHR data at such high levels of accuracies opens up avenues for population health monitoring and audit, and can provide a resource for epidemiological studies. We are in the process of validating EdIE-R in separate larger cohorts in NHS England and Scotland. The manually annotated ESS corpus will be available for research purposes on application.",,pdf:https://jbiomedsem.biomedcentral.com/track/pdf/10.1186/s13326-019-0211-7; doi:https://doi.org/10.1186/s13326-019-0211-7; html:https://europepmc.org/articles/PMC6849161; pdf:https://europepmc.org/articles/PMC6849161?pdf=render +36914875,https://doi.org/10.1038/s41588-023-01314-0,Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.,"Shrine N, Izquierdo AG, Chen J, Packer R, Hall RJ, Guyatt AL, Batini C, Thompson RJ, Pavuluri C, Malik V, Hobbs BD, Moll M, Kim W, Tal-Singer R, Bakke P, Fawcett KA, John C, Coley K, Piga NN, Pozarickij A, Lin K, Millwood IY, Chen Z, Li L, China Kadoorie Biobank Collaborative Group, Wijnant SRA, Lahousse L, Brusselle G, Uitterlinden AG, Manichaikul A, Oelsner EC, Rich SS, Barr RG, Kerr SM, Vitart V, Brown MR, Wielscher M, Imboden M, Jeong A, Bartz TM, Gharib SA, Flexeder C, Karrasch S, Gieger C, Peters A, Stubbe B, Hu X, Ortega VE, Meyers DA, Bleecker ER, Gabriel SB, Gupta N, Smith AV, Luan J, Zhao JH, Hansen AF, Langhammer A, Willer C, Bhatta L, Porteous D, Smith BH, Campbell A, Sofer T, Lee J, Daviglus ML, Yu B, Lim E, Xu H, O'Connor GT, Thareja G, Albagha OME, Qatar Genome Program Research (QGPR) Consortium, Suhre K, Granell R, Faquih TO, Hiemstra PS, Slats AM, Mullin BH, Hui J, James A, Beilby J, Patasova K, Hysi P, Koskela JT, Wyss AB, Jin J, Sikdar S, Lee M, May-Wilson S, Pirastu N, Kentistou KA, Joshi PK, Timmers PRHJ, Williams AT, Free RC, Wang X, Morrison JL, Gilliland FD, Chen Z, Wang CA, Foong RE, Harris SE, Taylor A, Redmond P, Cook JP, Mahajan A, Lind L, Palviainen T, Lehtimäki T, Raitakari OT, Kaprio J, Rantanen T, Pietiläinen KH, Cox SR, Pennell CE, Hall GL, Gauderman WJ, Brightling C, Wilson JF, Vasankari T, Laitinen T, Salomaa V, Mook-Kanamori DO, Timpson NJ, Zeggini E, Dupuis J, Hayward C, Brumpton B, Langenberg C, Weiss S, Homuth G, Schmidt CO, Probst-Hensch N, Jarvelin MR, Morrison AC, Polasek O, Rudan I, Lee JH, Sayers I, Rawlins EL, Dudbridge F, Silverman EK, Strachan DP, Walters RG, Morris AP, London SJ, Cho MH, Wain LV, Hall IP, Tobin MD.",,Nature genetics,2023,2023-03-13,Y,,,,"Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.",,pdf:https://www.nature.com/articles/s41588-023-01314-0.pdf; doi:https://doi.org/10.1038/s41588-023-01314-0; html:https://europepmc.org/articles/PMC10011137; pdf:https://europepmc.org/articles/PMC10011137?pdf=render +37923486,https://doi.org/10.1016/s2352-3018(23)00233-3,Integrase strand-transfer inhibitor use and cardiovascular events in adults with HIV: an emulation of target trials in the HIV-CAUSAL Collaboration and the Antiretroviral Therapy Cohort Collaboration.,"Rein SM, Lodi S, Logan RW, Touloumi G, Antoniadou A, Wittkop L, Bonnet F, van Sighem A, van der Valk M, Reiss P, Klein MB, Young J, Jarrin I, d'Arminio Monforte A, Tavelli A, Meyer L, Tran L, Gill MJ, Lang R, Surial B, Haas AD, Justice AC, Rentsch CT, Phillips A, Sabin CA, Miro JM, Trickey A, Ingle SM, Sterne JAC, Hernán MA, Antiretroviral Therapy Cohort Collaboration and the HIV-CAUSAL Collaboration.",,The lancet. HIV,2023,2023-11-01,N,,,,"

Background

A recent observational study suggested that the risk of cardiovascular events could be higher among antiretroviral therapy (ART)-naive individuals with HIV who receive integrase strand-transfer inhibitor (INSTI)-based ART than among those who receive other ART regimens. We aimed to emulate target trials separately in ART-naive and ART-experienced individuals with HIV to examine the effect of using INSTI-based regimens versus other ART regimens on the 4-year risk of cardiovascular events.

Methods

We used routinely recorded clinical data from 12 cohorts that collected information on cardiovascular events, BMI, and blood pressure from two international consortia of cohorts of people with HIV from Europe and North America. For the target trial in individuals who had previously never used ART (ie, ART-naive), eligibility criteria were aged 18 years or older, a detectable HIV-RNA measurement while ART-naive (>50 copies per mL), and no history of a cardiovascular event or cancer. Eligibility criteria for the target trial in those with previous use of non-INSTI-based ART (ie, ART-experienced) were the same except that individuals had to have been on at least one non-INSTI-based ART regimen and be virally suppressed (≤50 copies per mL). We assessed eligibility for both trials for each person-month between January, 2013, and January, 2023, and assigned individuals to the treatment strategy that was compatible with their data. We estimated the standardised 4-year risks of cardiovascular events (myocardial infarction, stroke, or invasive cardiovascular procedure) via pooled logistic regression models adjusting for time and baseline covariates. In per-protocol analyses, we censored individuals if they deviated from their assigned treatment strategy for more than 2 months and weighted uncensored individuals by the inverse of their time-varying probability of remaining uncensored. The denominator of the weight was estimated via a pooled logistic model that included baseline and time-varying covariates.

Findings

The analysis in ART-naive individuals included 10 767 INSTI initiators and 8292 non-initiators of INSTI. There were 43 cardiovascular events in INSTI initiators (median follow-up of 29 months; IQR 15-45) and 52 in non-initiators (39 months; 18-47): standardised 4-year risks were 0·76% (95% CI 0·51 to 1·04) in INSTI initiators and 0·75% (0·54 to 0·98) in non-INSTI initiators; risk ratio 1·01 (0·57 to 1·57); risk difference 0·0089% (-0·43 to 0·36). The analysis in ART-experienced individuals included 7875 INSTI initiators and 373 965 non-initiators. There were 56 events in INSTI initiators (median follow-up 18 months; IQR 9-29) and 3103 events (808 unique) in non-INSTI initiators (26 months; 15-37) in non-initiators: standardised 4-year risks 1·41% (95% CI 0·88 to 2·03) in INSTI initiators and 1·48% (1·28 to 1·71) in non-initiators; risk ratio 0·95 (0·60 to 1·36); risk difference -0·068% (-0·60 to 0·52).

Interpretation

We estimated that INSTI use did not result in a clinically meaningful increase of cardiovascular events in ART-naive and ART-experienced individuals with HIV.

Funding

National Institute of Allergy and Infectious Diseases and National Institute on Alcohol Abuse and Alcoholism.",,pdf:https://research-information.bris.ac.uk/files/382068016/Rev2_clean_InstiCVD.pdf; doi:https://doi.org/10.1016/S2352-3018(23)00233-3 37418234,https://doi.org/10.1007/s12265-023-10403-8,A Systematic Analysis of the Clinical Outcome Associated with Multiple Reclassified Desmosomal Gene Variants in Arrhythmogenic Right Ventricular Cardiomyopathy Patients.,"Nagyova E, Hoorntje ET, Te Rijdt WP, Bosman LP, Syrris P, Protonotarios A, Elliott PM, Tsatsopoulou A, Mestroni L, Taylor MRG, Sinagra G, Merlo M, Wada Y, Horie M, Mogensen J, Christensen AH, Gerull B, Song L, Yao Y, Fan S, Saguner AM, Duru F, Koskenvuo JW, Cruz Marino T, Tichnell C, Judge DP, Dooijes D, Lekanne Deprez RH, Basso C, Pilichou K, Bauce B, Wilde AAM, Charron P, Fressart V, van der Heijden JF, van den Berg MP, Asselbergs FW, James CA, Jongbloed JDH, Harakalova M, van Tintelen JP.",,Journal of cardiovascular translational research,2023,2023-07-07,Y,Genetics; Arrhythmia; Arvc; Composite Endpoint; Multiple Variants; Desmosomal Genes,,,"The presence of multiple pathogenic variants in desmosomal genes (DSC2, DSG2, DSP, JUP, and PKP2) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to a severe phenotype. However, the pathogenicity of variants is reclassified frequently, which may result in a changed clinical risk prediction. Here, we present the collection, reclassification, and clinical outcome correlation for the largest series of ARVC patients carrying multiple desmosomal pathogenic variants to date (n = 331). After reclassification, only 29% of patients remained carriers of two (likely) pathogenic variants. They reached the composite endpoint (ventricular arrhythmias, heart failure, and death) significantly earlier than patients with one or no remaining reclassified variant (hazard ratios of 1.9 and 1.8, respectively). Periodic reclassification of variants contributes to more accurate risk stratification and subsequent clinical management strategy. Graphical Abstract.",,pdf:https://link.springer.com/content/pdf/10.1007/s12265-023-10403-8.pdf; doi:https://doi.org/10.1007/s12265-023-10403-8; html:https://europepmc.org/articles/PMC10721666; pdf:https://europepmc.org/articles/PMC10721666?pdf=render 31331193,https://doi.org/10.1161/circulationaha.119.041546,Impact of ADCY9 Genotype on Response to Anacetrapib.,"Hopewell JC, Ibrahim M, Hill M, Shaw PM, Braunwald E, Blaustein RO, Bowman L, Landray MJ, Sabatine MS, Collins R, HPS3/TIMI55–REVEAL Collaborative Group.",,Circulation,2019,2019-07-23,Y,Randomized controlled trial; Pharmacogenetics; Anacetrapib; Cholesterol Ester Transfer Protein; Adenylate Cyclase 9,"Better, Faster and More Efficient Clinical Trials",,"

Background

Exploratory analyses of previous randomized trials generated a hypothesis that the clinical response to cholesteryl ester transfer protein (CETP) inhibitor therapy differs by ADCY9 genotype, prompting the ongoing dal-GenE trial in individuals with a particular genetic profile. The randomized placebo-controlled REVEAL trial (Randomized Evaluation of the Effects of Anacetrapib through Lipid-Modification) demonstrated the clinical efficacy of the CETP inhibitor anacetrapib among patients with preexisting atherosclerotic vascular disease. In the present study, we examined the impact of ADCY9 genotype on response to anacetrapib in the REVEAL trial.

Methods

Individuals with stable atherosclerotic vascular disease who were treated with intensive atorvastatin therapy received either anacetrapib 100 mg daily or matching placebo. Cox proportional hazards models, adjusted for the first 5 principal components of ancestry, were used to estimate the effects of allocation to anacetrapib on major vascular events (a composite of coronary death, myocardial infarction, coronary revascularization, or presumed ischemic stroke) and the interaction with ADCY9 rs1967309 genotype.

Results

Among 19 210 genotyped individuals of European ancestry, 2504 (13.0%) had a first major vascular event during 4 years median follow-up: 1216 (12.6%) among anacetrapib-allocated participants and 1288 (13.4%) among placebo-allocated participants. Proportional reductions in the risk of major vascular events with anacetrapib did not differ significantly by ADCY9 genotype: hazard ratio (HR) = 0.92 (95% CI, 0.81-1.05) for GG; HR = 0.94 (95% CI, 0.84-1.06) for AG; and HR = 0.93 (95% CI, 0.76-1.13) for AA genotype carriers, respectively; genotypic P for interaction = 0.96. Furthermore, there were no associations between ADCY9 genotype and the proportional reductions in the separate components of major vascular events or meaningful differences in lipid response to anacetrapib.

Conclusions

The REVEAL trial is the single largest study to date evaluating the ADCY9 pharmacogenetic interaction. It provides no support for the hypothesis that ADCY9 genotype is materially relevant to the clinical effects of the CETP inhibitor anacetrapib. The ongoing dal-GenE study will provide direct evidence as to whether there is any specific pharmacogenetic interaction with dalcetrapib.

Clinical trial registration

URL: https://www.

Clinicaltrials

gov. Unique identifier: NCT01252953. URL: http://www.isrctn.com. Unique identifier: ISRCTN48678192. URL: https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18.",,doi:https://doi.org/10.1161/circulationaha.119.041546; doi:https://doi.org/10.1161/CIRCULATIONAHA.119.041546; html:https://europepmc.org/articles/PMC6749971; pdf:https://europepmc.org/articles/PMC6749971?pdf=render 33328634,https://doi.org/10.1038/s41586-020-03043-4,Mapping routine measles vaccination in low- and middle-income countries.,Local Burden of Disease Vaccine Coverage Collaborators.,,Nature,2021,2020-12-16,Y,,,,"The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)1-4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)5-8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km2 pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.",,pdf:https://www.nature.com/articles/s41586-020-03043-4.pdf; doi:https://doi.org/10.1038/s41586-020-03043-4; html:https://europepmc.org/articles/PMC7739806; pdf:https://europepmc.org/articles/PMC7739806?pdf=render @@ -2365,18 +2365,18 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 32198138,https://doi.org/10.1136/bmj.l6927,"Machine learning and artificial intelligence research for patient benefit: 20 critical questions on transparency, replicability, ethics, and effectiveness.","Vollmer S, Mateen BA, Bohner G, Király FJ, Ghani R, Jonsson P, Cumbers S, Jonas A, McAllister KSL, Myles P, Granger D, Birse M, Branson R, Moons KGM, Collins GS, Ioannidis JPA, Holmes C, Hemingway H.",,BMJ (Clinical research ed.),2020,2020-03-20,N,,,,,,pdf:https://www.bmj.com/content/bmj/368/bmj.l6927.full.pdf; doi:https://doi.org/10.1136/bmj.l6927 35347521,https://doi.org/10.1007/s11136-022-03119-w,Knowledge translation concerns for the CONSORT-PRO extension reporting guidance: a review of reviews.,"Mercieca-Bebber R, Aiyegbusi OL, King MT, Brundage M, Snyder C, Calvert M.",,"Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation",2022,2022-03-26,Y,Quality of life; research methodology; Reporting; Patient-reported Outcomes; Research Waste; Consort-pro,,,"This review of reviews aimed to appraise the use of the CONSORT-PRO Extension as an evaluation tool for assessing the reporting of patient-reported outcome (PROs) in publications, and to describe the reporting of PRO research across reviews. We also outlined how variation in such evaluations impacts knowledge translation and may lead to potential misuse of the CONSORT-PRO Extension. We systematically searched Medline, Pubmed and CINAHL from 2013 to 2025 March 2021 for reviews of the completeness of reporting of PRO endpoints according to CONSORT-PRO criteria. Two reviewers extracted details of each review, the percentage of included studies that addressed each CONSORT-PRO item, and key recommendations from each review. Fourteen reviews met inclusion criteria, and only six of these used the full CONSORT-PRO checklist with minimal justified modifications. The remaining eight studies made significant or unjustified adjustments to the CONSORT-PRO Extension. Review studies also varied in how they scored multi-component CONSORT-PRO items. CONSORT-PRO items were often unreported in trial reports, and certain CONSORT-PRO items were reported less often than others. The reporting of statistical approaches to dealing with missing PRO data were poor in RCTs included in all 14 review articles. Studies reviewing PRO publications often omitted recommended CONSORT-PRO items from their evaluations, which may cause confusion among readers regarding how best to report their PRO research according to the CONSORT-PRO extension. Many trials published since CONSORT-PRO's release did not report recommended CONSORT-PRO items, which may lead to misinterpretation and consequently to research waste.",,pdf:https://link.springer.com/content/pdf/10.1007/s11136-022-03119-w.pdf; doi:https://doi.org/10.1007/s11136-022-03119-w; html:https://europepmc.org/articles/PMC9470606; pdf:https://europepmc.org/articles/PMC9470606?pdf=render 31112426,https://doi.org/10.1161/circgen.118.002436,Mortality Risk Associated With Truncating Founder Mutations in Titin.,"Jansen M, Baas AF, van Spaendonck-Zwarts KY, Ummels AS, van den Wijngaard A, Jongbloed JDH, van Slegtenhorst MA, Lekanne Deprez RH, Wessels MW, Michels M, Houweling AC, Hoorntje ET, Helderman-van den Enden PJTM, Barge-Schaapveld DQCM, Peter van Tintelen J, van den Berg MP, Wilde AAM, Ploos van Amstel HK, Hennekam EAM, Asselbergs FW, Sijbrands EJG, Dooijes D.",,Circulation. Genomic and precision medicine,2019,2019-05-01,N,"Mutation; Mortality; Natural history; Cardiomyopathy, Dilated; Titin",,,"Background Truncating titin variants (TTNtv) are the most prevalent genetic cause of dilated cardiomyopathy, found in ≤25% of familial cases. Moreover, TTNtv associated with dilated cardiomyopathy are estimated to be present in 0.5% of the general population. The prognosis of asymptomatic carriers of TTNtv is poorly understood because TTNtv are associated with a highly variable phenotype. We aim to assess the natural history and clinical relevance of TTNtv by analyzing standardized mortality ratios (SMR) in multigenerational pedigrees and in close relatives of present-day patients. Methods Haplotype and genealogical analyses were performed on 3 recurrent TTNtv. Subsequently, the family tree mortality ratio method was used to compare all-cause mortality of subjects at an a priori 50% risk of carrying TTNtv to the general Dutch population. SMRs were stratified for sex, age, and calendar period. Subgroups were compared with Poisson regression. Similarly, SMRs were calculated in parents of 128 present-day dilated cardiomyopathy probands with TTNtv using the reverse parent-offspring method. Results The TTNtv were established as founder mutations and traced to 18th century ancestors. In 20 522 person-years, overall mortality was not significantly increased (SMR, 1.06; 95% CI, 0.95-1.18; P=0.162). However, mortality was significantly increased in subjects living after 1965 (SMR, 1.27; 95% CI, 1.04-1.53; P=0.009) and aged ≥60 years (SMR, 1.17; 95% CI, 1.01-1.35; P=0.02). The reverse parent-offspring analysis showed overall excess mortality (SMR, 1.26; 95% CI, 1.07-1.48; P=0.003), driven by subjects aged ≥60 years. Conclusions The natural history of the analyzed TTNtv shows a relatively mild disease course with significant excess mortality in elderly patients. With increasing life expectancy, TTNtv-associated morbidity and mortality will likely become more prevalent.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.118.002436; doi:https://doi.org/10.1161/CIRCGEN.118.002436 -33248277,https://doi.org/10.1016/j.jclinepi.2020.11.014,Text-mining in electronic healthcare records can be used as efficient tool for screening and data collection in cardiovascular trials: a multicenter validation study.,"van Dijk WB, Fiolet ATL, Schuit E, Sammani A, Groenhof TKJ, van der Graaf R, de Vries MC, Alings M, Schaap J, Asselbergs FW, Grobbee DE, Groenwold RHH, Mosterd A.",,Journal of clinical epidemiology,2021,2020-11-25,N,Screening; Recruitment; trials; Multicenter; cardiovascular; Text-mining; Data-mining; Electronic Medical Records (Emrs); Lodoco2; Data-collections; Electronic Healthcare Records (Ehrs),,,"

Objective

This study aimed to validate trial patient eligibility screening and baseline data collection using text-mining in electronic healthcare records (EHRs), comparing the results to those of an international trial.

Study design and setting

In three medical centers with different EHR vendors, EHR-based text-mining was used to automatically screen patients for trial eligibility and extract baseline data on nineteen characteristics. First, the yield of screening with automated EHR text-mining search was compared with manual screening by research personnel. Second, the accuracy of extracted baseline data by EHR text mining was compared to manual data entry by research personnel.

Results

Of the 92,466 patients visiting the out-patient cardiology departments, 568 (0.6%) were enrolled in the trial during its recruitment period using manual screening methods. Automated EHR data screening of all patients showed that the number of patients needed to screen could be reduced by 73,863 (79.9%). The remaining 18,603 (20.1%) contained 458 of the actual participants (82.4% of participants). In trial participants, automated EHR text-mining missed a median of 2.8% (Interquartile range [IQR] across all variables 0.4-8.5%) of all data points compared to manually collected data. The overall accuracy of automatically extracted data was 88.0% (IQR 84.7-92.8%).

Conclusion

Automatically extracting data from EHRs using text-mining can be used to identify trial participants and to collect baseline information.",,pdf:http://www.jclinepi.com/article/S0895435620311859/pdf; doi:https://doi.org/10.1016/j.jclinepi.2020.11.014 34972825,https://doi.org/10.1038/s41564-021-01029-0,Improving local prevalence estimates of SARS-CoV-2 infections using a causal debiasing framework.,"Nicholson G, Lehmann B, Padellini T, Pouwels KB, Jersakova R, Lomax J, King RE, Mallon AM, Diggle PJ, Richardson S, Blangiardo M, Holmes C.",,Nature microbiology,2022,2021-12-31,Y,,,,"Global and national surveillance of SARS-CoV-2 epidemiology is mostly based on targeted schemes focused on testing individuals with symptoms. These tested groups are often unrepresentative of the wider population and exhibit test positivity rates that are biased upwards compared with the true population prevalence. Such data are routinely used to infer infection prevalence and the effective reproduction number, Rt, which affects public health policy. Here, we describe a causal framework that provides debiased fine-scale spatiotemporal estimates by combining targeted test counts with data from a randomized surveillance study in the United Kingdom called REACT. Our probabilistic model includes a bias parameter that captures the increased probability of an infected individual being tested, relative to a non-infected individual, and transforms observed test counts to debiased estimates of the true underlying local prevalence and Rt. We validated our approach on held-out REACT data over a 7-month period. Furthermore, our local estimates of Rt are indicative of 1-week- and 2-week-ahead changes in SARS-CoV-2-positive case numbers. We also observed increases in estimated local prevalence and Rt that reflect the spread of the Alpha and Delta variants. Our results illustrate how randomized surveys can augment targeted testing to improve statistical accuracy in monitoring the spread of emerging and ongoing infectious disease.",,pdf:https://www.nature.com/articles/s41564-021-01029-0.pdf; doi:https://doi.org/10.1038/s41564-021-01029-0; html:https://europepmc.org/articles/PMC8727294; pdf:https://europepmc.org/articles/PMC8727294?pdf=render -37601966,https://doi.org/10.1016/j.xgen.2023.100361,Genotyping and population characteristics of the China Kadoorie Biobank.,"Walters RG, Millwood IY, Lin K, Schmidt Valle D, McDonnell P, Hacker A, Avery D, Edris A, Fry H, Cai N, Kretzschmar WW, Ansari MA, Lyons PA, Collins R, Donnelly P, Hill M, Peto R, Shen H, Jin X, Nie C, Xu X, Guo Y, Yu C, Lv J, Clarke RJ, Li L, Chen Z, China Kadoorie Biobank Collaborative Group.",,Cell genomics,2023,2023-07-20,Y,Genetics; Genetic epidemiology; Genotyping; complex disease; Gwas; Genetic Association Studies; Biobank; Omics; Prospective; Cardiovascular Health,,,"The China Kadoorie Biobank (CKB) is a population-based prospective cohort of >512,000 adults recruited from 2004 to 2008 from 10 geographically diverse regions across China. Detailed data from questionnaires and physical measurements were collected at baseline, with additional measurements at three resurveys involving ∼5% of surviving participants. Analyses of genome-wide genotyping, for >100,000 participants using custom-designed Axiom arrays, reveal extensive relatedness, recent consanguinity, and signatures reflecting large-scale population movements from recent Chinese history. Systematic genome-wide association studies of incident disease, captured through electronic linkage to death and disease registries and to the national health insurance system, replicate established disease loci and identify 14 novel disease associations. Together with studies of candidate drug targets and disease risk factors and contributions to international genetics consortia, these demonstrate the breadth, depth, and quality of the CKB data. Ongoing high-throughput omics assays of collected biosamples and planned whole-genome sequencing will further enhance the scientific value of this biobank.",,doi:https://doi.org/10.1016/j.xgen.2023.100361; doi:https://doi.org/10.1016/j.xgen.2023.100361; html:https://europepmc.org/articles/PMC10435379; pdf:https://europepmc.org/articles/PMC10435379?pdf=render +33248277,https://doi.org/10.1016/j.jclinepi.2020.11.014,Text-mining in electronic healthcare records can be used as efficient tool for screening and data collection in cardiovascular trials: a multicenter validation study.,"van Dijk WB, Fiolet ATL, Schuit E, Sammani A, Groenhof TKJ, van der Graaf R, de Vries MC, Alings M, Schaap J, Asselbergs FW, Grobbee DE, Groenwold RHH, Mosterd A.",,Journal of clinical epidemiology,2021,2020-11-25,N,Screening; Recruitment; trials; Multicenter; cardiovascular; Text-mining; Data-mining; Electronic Medical Records (Emrs); Lodoco2; Data-collections; Electronic Healthcare Records (Ehrs),,,"

Objective

This study aimed to validate trial patient eligibility screening and baseline data collection using text-mining in electronic healthcare records (EHRs), comparing the results to those of an international trial.

Study design and setting

In three medical centers with different EHR vendors, EHR-based text-mining was used to automatically screen patients for trial eligibility and extract baseline data on nineteen characteristics. First, the yield of screening with automated EHR text-mining search was compared with manual screening by research personnel. Second, the accuracy of extracted baseline data by EHR text mining was compared to manual data entry by research personnel.

Results

Of the 92,466 patients visiting the out-patient cardiology departments, 568 (0.6%) were enrolled in the trial during its recruitment period using manual screening methods. Automated EHR data screening of all patients showed that the number of patients needed to screen could be reduced by 73,863 (79.9%). The remaining 18,603 (20.1%) contained 458 of the actual participants (82.4% of participants). In trial participants, automated EHR text-mining missed a median of 2.8% (Interquartile range [IQR] across all variables 0.4-8.5%) of all data points compared to manually collected data. The overall accuracy of automatically extracted data was 88.0% (IQR 84.7-92.8%).

Conclusion

Automatically extracting data from EHRs using text-mining can be used to identify trial participants and to collect baseline information.",,pdf:http://www.jclinepi.com/article/S0895435620311859/pdf; doi:https://doi.org/10.1016/j.jclinepi.2020.11.014 36717224,https://doi.org/10.1136/archdischild-2022-324548,Parents' Experiences of Communication in Neonatal Care (PEC): a neonatal survey refined for real-time parent feedback.,"Sakonidou S, Kotzamanis S, Tallett A, Poots AJ, Modi N, Bell D, Gale C.",,Archives of disease in childhood. Fetal and neonatal edition,2023,2023-01-30,Y,"Intensive care units; Child Health Services; Paediatrics; Neonatology; Intensive Care Units, Neonatal",,,"

Objective

Assessing parent experiences of neonatal services can help improve quality of care; however, there is no formally evaluated UK instrument available to assess this prospectively. Our objective was to refine an existing retrospective survey for 'real-time' feedback.

Methods

Co-led by a parent representative, we recruited a convenience sample of parents of infants in a London tertiary neonatal unit. Our steering group selected questions from the existing retrospective 61-question Picker survey (2014), added and revised questions assessing communication and parent involvement. We established face validity, ensuring questions adequately captured the topic, conducted parent cognitive interviews to evaluate parental understanding of questions,and adapted the survey in three revision cycles. We evaluated survey performance.

Results

The revised Parents' Experiences of Communication in Neonatal Care (PEC) survey contains 28 questions (10 new) focusing on communication and parent involvement. We cognitively interviewed six parents, and 67 parents completed 197 PEC surveys in the survey performance evaluation. Missing entries exceeded 5% for nine questions; we removed one and format-adjusted the rest as they had performed well during cognitive testing. There was strong inter-item correlation between two question pairs; however, all were retained as they individually assessed important concepts.

Conclusion

Revised from the original 61-question Picker survey, the 28-question PEC survey is the first UK instrument formally evaluated to assess parent experience while infants are still receiving neonatal care. Developed with parents, it focuses on communication and parent involvement, enabling continuous assessment and iterative improvement of family-centred interventions in neonatal care.",,pdf:https://fn.bmj.com/content/fetalneonatal/early/2023/01/30/archdischild-2022-324548.full.pdf; doi:https://doi.org/10.1136/archdischild-2022-324548; html:https://europepmc.org/articles/PMC10314049; pdf:https://europepmc.org/articles/PMC10314049?pdf=render +37601966,https://doi.org/10.1016/j.xgen.2023.100361,Genotyping and population characteristics of the China Kadoorie Biobank.,"Walters RG, Millwood IY, Lin K, Schmidt Valle D, McDonnell P, Hacker A, Avery D, Edris A, Fry H, Cai N, Kretzschmar WW, Ansari MA, Lyons PA, Collins R, Donnelly P, Hill M, Peto R, Shen H, Jin X, Nie C, Xu X, Guo Y, Yu C, Lv J, Clarke RJ, Li L, Chen Z, China Kadoorie Biobank Collaborative Group.",,Cell genomics,2023,2023-07-20,Y,Genetics; Genetic epidemiology; Genotyping; complex disease; Gwas; Genetic Association Studies; Biobank; Omics; Prospective; Cardiovascular Health,,,"The China Kadoorie Biobank (CKB) is a population-based prospective cohort of >512,000 adults recruited from 2004 to 2008 from 10 geographically diverse regions across China. Detailed data from questionnaires and physical measurements were collected at baseline, with additional measurements at three resurveys involving ∼5% of surviving participants. Analyses of genome-wide genotyping, for >100,000 participants using custom-designed Axiom arrays, reveal extensive relatedness, recent consanguinity, and signatures reflecting large-scale population movements from recent Chinese history. Systematic genome-wide association studies of incident disease, captured through electronic linkage to death and disease registries and to the national health insurance system, replicate established disease loci and identify 14 novel disease associations. Together with studies of candidate drug targets and disease risk factors and contributions to international genetics consortia, these demonstrate the breadth, depth, and quality of the CKB data. Ongoing high-throughput omics assays of collected biosamples and planned whole-genome sequencing will further enhance the scientific value of this biobank.",,doi:https://doi.org/10.1016/j.xgen.2023.100361; doi:https://doi.org/10.1016/j.xgen.2023.100361; html:https://europepmc.org/articles/PMC10435379; pdf:https://europepmc.org/articles/PMC10435379?pdf=render 32435697,https://doi.org/10.1038/s41746-020-0267-x,Generation and evaluation of artificial mental health records for Natural Language Processing.,"Ive J, Viani N, Kam J, Yin L, Verma S, Puntis S, Cardinal RN, Roberts A, Stewart R, Velupillai S.",,NPJ digital medicine,2020,2020-05-14,Y,Medical research; Scientific Community,,,"A serious obstacle to the development of Natural Language Processing (NLP) methods in the clinical domain is the accessibility of textual data. The mental health domain is particularly challenging, partly because clinical documentation relies heavily on free text that is difficult to de-identify completely. This problem could be tackled by using artificial medical data. In this work, we present an approach to generate artificial clinical documents. We apply this approach to discharge summaries from a large mental healthcare provider and discharge summaries from an intensive care unit. We perform an extensive intrinsic evaluation where we (1) apply several measures of text preservation; (2) measure how much the model memorises training data; and (3) estimate clinical validity of the generated text based on a human evaluation task. Furthermore, we perform an extrinsic evaluation by studying the impact of using artificial text in a downstream NLP text classification task. We found that using this artificial data as training data can lead to classification results that are comparable to the original results. Additionally, using only a small amount of information from the original data to condition the generation of the artificial data is successful, which holds promise for reducing the risk of these artificial data retaining rare information from the original data. This is an important finding for our long-term goal of being able to generate artificial clinical data that can be released to the wider research community and accelerate advances in developing computational methods that use healthcare data.",,pdf:https://www.nature.com/articles/s41746-020-0267-x.pdf; doi:https://doi.org/10.1038/s41746-020-0267-x; html:https://europepmc.org/articles/PMC7224173; pdf:https://europepmc.org/articles/PMC7224173?pdf=render 35189842,https://doi.org/10.1186/s12888-022-03753-1,"Remote Assessment of Disease and Relapse in Major Depressive Disorder (RADAR-MDD): recruitment, retention, and data availability in a longitudinal remote measurement study.","Matcham F, Leightley D, Siddi S, Lamers F, White KM, Annas P, de Girolamo G, Difrancesco S, Haro JM, Horsfall M, Ivan A, Lavelle G, Li Q, Lombardini F, Mohr DC, Narayan VA, Oetzmann C, Penninx BWJH, Bruce S, Nica R, Simblett SK, Wykes T, Brasen JC, Myin-Germeys I, Rintala A, Conde P, Dobson RJB, Folarin AA, Stewart C, Ranjan Y, Rashid Z, Cummins N, Manyakov NV, Vairavan S, Hotopf M, RADAR-CNS consortium.",,BMC psychiatry,2022,2022-02-21,Y,Cohort study; Longitudinal; Major Depressive Disorder; Multicentre; Remote Measurement Technologies,,,"

Background

Major Depressive Disorder (MDD) is prevalent, often chronic, and requires ongoing monitoring of symptoms to track response to treatment and identify early indicators of relapse. Remote Measurement Technologies (RMT) provide an opportunity to transform the measurement and management of MDD, via data collected from inbuilt smartphone sensors and wearable devices alongside app-based questionnaires and tasks. A key question for the field is the extent to which participants can adhere to research protocols and the completeness of data collected. We aimed to describe drop out and data completeness in a naturalistic multimodal longitudinal RMT study, in people with a history of recurrent MDD. We further aimed to determine whether those experiencing a depressive relapse at baseline contributed less complete data.

Methods

Remote Assessment of Disease and Relapse - Major Depressive Disorder (RADAR-MDD) is a multi-centre, prospective observational cohort study conducted as part of the Remote Assessment of Disease and Relapse - Central Nervous System (RADAR-CNS) program. People with a history of MDD were provided with a wrist-worn wearable device, and smartphone apps designed to: a) collect data from smartphone sensors; and b) deliver questionnaires, speech tasks, and cognitive assessments. Participants were followed-up for a minimum of 11 months and maximum of 24 months.

Results

Individuals with a history of MDD (n = 623) were enrolled in the study,. We report 80% completion rates for primary outcome assessments across all follow-up timepoints. 79.8% of people participated for the maximum amount of time available and 20.2% withdrew prematurely. We found no evidence of an association between the severity of depression symptoms at baseline and the availability of data. In total, 110 participants had > 50% data available across all data types.

Conclusions

RADAR-MDD is the largest multimodal RMT study in the field of mental health. Here, we have shown that collecting RMT data from a clinical population is feasible. We found comparable levels of data availability in active and passive forms of data collection, demonstrating that both are feasible in this patient group.",,pdf:https://bmcpsychiatry.biomedcentral.com/track/pdf/10.1186/s12888-022-03753-1; doi:https://doi.org/10.1186/s12888-022-03753-1; html:https://europepmc.org/articles/PMC8860359; pdf:https://europepmc.org/articles/PMC8860359?pdf=render 34480422,https://doi.org/10.1002/ehf2.13517,The genomics of heart failure: design and rationale of the HERMES consortium.,"Lumbers RT, Shah S, Lin H, Czuba T, Henry A, Swerdlow DI, Mälarstig A, Andersson C, Verweij N, Holmes MV, Ärnlöv J, Svensson P, Hemingway H, Sallah N, Almgren P, Aragam KG, Asselin G, Backman JD, Biggs ML, Bloom HL, Boersma E, Brandimarto J, Brown MR, Brunner-La Rocca HP, Carey DJ, Chaffin MD, Chasman DI, Chazara O, Chen X, Chen X, Chung JH, Chutkow W, Cleland JGF, Cook JP, de Denus S, Dehghan A, Delgado GE, Denaxas S, Doney AS, Dörr M, Dudley SC, Engström G, Esko T, Fatemifar G, Felix SB, Finan C, Ford I, Fougerousse F, Fouodjio R, Ghanbari M, Ghasemi S, Giedraitis V, Giulianini F, Gottdiener JS, Gross S, Guðbjartsson DF, Gui H, Gutmann R, Haggerty CM, van der Harst P, Hedman ÅK, Helgadottir A, Hillege H, Hyde CL, Jacob J, Jukema JW, Kamanu F, Kardys I, Kavousi M, Khaw KT, Kleber ME, Køber L, Koekemoer A, Kraus B, Kuchenbaecker K, Langenberg C, Lind L, Lindgren CM, London B, Lotta LA, Lovering RC, Luan J, Magnusson P, Mahajan A, Mann D, Margulies KB, Marston NA, März W, McMurray JJV, Melander O, Melloni G, Mordi IR, Morley MP, Morris AD, Morris AP, Morrison AC, Nagle MW, Nelson CP, Newton-Cheh C, Niessner A, Niiranen T, Nowak C, O'Donoghue ML, Owens AT, Palmer CNA, Paré G, Perola M, Perreault LL, Portilla-Fernandez E, Psaty BM, Rice KM, Ridker PM, Romaine SPR, Roselli C, Rotter JI, Ruff CT, Sabatine MS, Salo P, Salomaa V, van Setten J, Shalaby AA, Smelser DT, Smith NL, Stefansson K, Stender S, Stott DJ, Sveinbjörnsson G, Tammesoo ML, Tardif JC, Taylor KD, Teder-Laving M, Teumer A, Thorgeirsson G, Thorsteinsdottir U, Torp-Pedersen C, Trompet S, Tuckwell D, Tyl B, Uitterlinden AG, Vaura F, Veluchamy A, Visscher PM, Völker U, Voors AA, Wang X, Wareham NJ, Weeke PE, Weiss R, White HD, Wiggins KL, Xing H, Yang J, Yang Y, Yerges-Armstrong LM, Yu B, Zannad F, Zhao F, Regeneron Genetics Center, Wilk JB, Holm H, Sattar N, Lubitz SA, Lanfear DE, Shah S, Dunn ME, Wells QS, Asselbergs FW, Hingorani AD, Dubé MP, Samani NJ, Lang CC, Cappola TP, Ellinor PT, Vasan RS, Smith JG.",,ESC heart failure,2021,2021-09-03,Y,Genetics; Biomarkers; Cardiomyopathy; Heart Failure; Association Studies,,,"

Aims

The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure.

Methods and results

The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 × 10-8 under an additive genetic model.

Conclusions

HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.13517; doi:https://doi.org/10.1002/ehf2.13517; html:https://europepmc.org/articles/PMC8712846; pdf:https://europepmc.org/articles/PMC8712846?pdf=render 35294976,https://doi.org/10.1007/s00127-022-02221-1,Mental health service use among mothers involved in public family law proceedings: linked data cohort study in South London 2007-2019.,"Pearson RJ, Grant C, Wijlaars L, Finch E, Bedston S, Broadhurst K, Gilbert R.",,Social psychiatry and psychiatric epidemiology,2022,2022-03-16,Y,Substance Misuse; Child Protection; Record Linkage; Maternal Mental Health; Family Court,,,"

Purpose

Mental health problems and substance misuse are common among the mothers of children who experience court-mandated placement into care in England, yet there is limited research characterising these health needs to inform evidence-based policy. In this descriptive study, we aimed to generate evidence about the type, severity, and timing of mental health and substance misuse needs among women involved in public family law proceedings concerning child placement into care ('care proceedings').

Methods

This is a retrospective, matched cohort study using linked family court and mental health service records for 2137 (66%) of the 3226 women involved in care proceedings between 2007 and 2019 in the South London and Maudsley NHS Mental Health Trust (SLaM) catchment area. We compared mental health service use and risk of dying with 17,096 female-matched controls who accessed SLaM between 2007 and 2019, aged 16-55 years, and were not involved in care proceedings.

Results

Most women (79%) were known to SLaM before care proceedings began. Women had higher rates of schizophrenia spectrum disorders (19% vs 11% matched controls), personality disorders (21% vs 11%), and substance misuse (33% vs 12%). They were more likely to have a SLaM inpatient admission (27% vs 14%) or to be sectioned (19% vs 8%). Women had a 2.15 (95% CI 1.68-2.74) times greater hazard of dying, compared to matched controls, adjusted for age.

Conclusion

Women involved in care proceedings experience a particularly high burden of severe and complex mental health and substance misuse need. Women's increased risk of mortality following proceedings highlights that interventions responding to maternal mental health and substance misuse within family courts should offer continued, long-term support.",,pdf:https://link.springer.com/content/pdf/10.1007/s00127-022-02221-1.pdf; doi:https://doi.org/10.1007/s00127-022-02221-1; html:https://europepmc.org/articles/PMC9477900; pdf:https://europepmc.org/articles/PMC9477900?pdf=render -35876478,https://doi.org/10.3201/eid2808.211787,Lack of Evidence for Ribavirin Treatment of Lassa Fever in Systematic Review of Published and Unpublished Studies1.,"Cheng HY, French CE, Salam AP, Dawson S, McAleenan A, McGuinness LA, Savović J, Horby PW, Sterne JAC.",,Emerging infectious diseases,2022,2022-08-01,Y,Viruses; Bias; Ribavirin; Systematic review; Observational Study; Lassa Fever,,,"Ribavirin has been used widely to treat Lassa fever in West Africa since the 1980s. However, few studies have systematically appraised the evidence for its use. We conducted a systematic review of published and unpublished literature retrieved from electronic databases and gray literature from inception to March 8, 2022. We identified 13 studies of the comparative effectiveness of ribavirin versus no ribavirin treatment on mortality outcomes, including unpublished data from a study in Sierra Leone provided through a US Freedom of Information Act request. Although ribavirin was associated with decreased mortality rates, results of these studies were at critical or serious risk for bias when appraised using the ROBINS-I tool. Important risks for bias related to lack of control for confounders, immortal time bias, and missing outcome data. Robust evidence supporting the use of ribavirin in Lassa fever is lacking. Well-conducted clinical trials to elucidate the effectiveness of ribavirin for Lassa fever are needed.",,pdf:https://wwwnc.cdc.gov/eid/article/28/8/pdfs/21-1787.pdf; doi:https://doi.org/10.3201/eid2808.211787; html:https://europepmc.org/articles/PMC9328902; pdf:https://europepmc.org/articles/PMC9328902?pdf=render 34151270,https://doi.org/10.1136/bmjno-2021-000133,"Variation in waiting times by diagnostic category: an observational study of 1,951 referrals to a neurology outpatient clinic.","Biggin F, Howcroft T, Davies Q, Knight J, Emsley HCA.",,BMJ neurology open,2021,2021-06-03,Y,Neurology; Outpatient; Observational Study; Waiting Times; Routinely Collected Data,,,"

Objective

To investigate the frequency of diagnoses seen among new referrals to neurology outpatient services; to understand how these services are used through exploratory analysis of diagnostic tests and follow-up appointments; and to examine the waiting times between referral and appointment.

Methods

Routine data from new National Health Service appointments at a single consultant-delivered clinic between September 2016 and January 2019 were collected. These clinical data were then linked to hospital administrative data. The combined data were assigned diagnostic categories based on working diagnoses to allow further analysis using descriptive statistics.

Results

Five diagnostic categories accounted for 62% of all patients seen within the study period, the most common of which was headache disorders. Following a first appointment, 50% of all patients were offered at least one diagnostic test, and 35% were offered a follow-up appointment, with variation in both measures by diagnostic category. Waiting times from referral to appointment also varied by diagnostic category. 65% of patients with a seizure/epilepsy disorder were seen within the 18-week referral to treatment target, compared with 38% of patients with a movement disorder.

Conclusions

A small number of diagnostic categories account for a large proportion of new patients. This information could be used in policy decision-making to describe a minimum subset of categories for diagnostic coding. We found significant differences in waiting times by diagnostic category, as well as tests ordered, and follow-up offered; further investigation could address causes of variation.",,pdf:https://neurologyopen.bmj.com/content/bmjno/3/1/e000133.full.pdf; doi:https://doi.org/10.1136/bmjno-2021-000133; html:https://europepmc.org/articles/PMC8183200; pdf:https://europepmc.org/articles/PMC8183200?pdf=render -38432242,https://doi.org/10.1016/s2352-3026(24)00030-9,Haemoglobin thresholds to define anaemia from age 6 months to 65 years: estimates from international data sources.,"Braat S, Fielding KL, Han J, Jackson VE, Zaloumis S, Xu JXH, Moir-Meyer G, Blaauwendraad SM, Jaddoe VWV, Gaillard R, Parkin PC, Borkhoff CM, Keown-Stoneman CDG, Birken CS, Maguire JL, Genes & Health Research Team, Bahlo M, Davidson EM, Pasricha SR.",,The Lancet. Haematology,2024,2024-02-29,Y,,,,"

Background

Detection of anaemia is crucial for clinical medicine and public health. Current WHO anaemia definitions are based on statistical thresholds (fifth centiles) set more than 50 years ago. We sought to establish evidence for the statistical haemoglobin thresholds for anaemia that can be applied globally and inform WHO and clinical guidelines.

Methods

In this analysis we identified international data sources from populations in the USA, England, Australia, China, the Netherlands, Canada, Ecuador, and Bangladesh with sufficient clinical and laboratory information collected between 1998 and 2020 to obtain a healthy reference sample. Individuals with clinical or biochemical evidence of a condition that could reduce haemoglobin concentrations were excluded. We estimated haemoglobin thresholds (ie, 5th centiles) for children aged 6-23 months, 24-59 months, 5-11 years, and 12-17 years, and adults aged 18-65 years (including during pregnancy) for individual datasets and pooled across data sources. We also collated findings from three large-scale genetic studies to summarise genetic variants affecting haemoglobin concentrations in different ancestral populations.

Findings

We identified eight data sources comprising 18 individual datasets that were eligible for inclusion in the analysis. In pooled analyses, the haemoglobin fifth centile was 104·4 g/L (90% CI 103·5-105·3) in 924 children aged 6-23 months, 110·2 g/L (109·5-110·9) in 1874 children aged 24-59 months, and 114·4 g/L (113·6-115·2) in 1839 children aged 5-11 years. Values diverged by sex in adolescents and adults. In pooled analyses, the fifth centile was 122·2 g/L (90% CI 121·3-123·1) in 1741 female adolescents aged 12-17 years and 128·2 g/L (126·4-130·0) in 1103 male adolescents aged 12-17 years. In pooled analyses of adults aged 18-65 years, the fifth centile was 119·7 g/L (90% CI 119·1-120·3) in 3640 non-pregnant females and 134·9 g/L (134·2-135·6) in 2377 males. Fifth centiles in pregnancy were 110·3 g/L (90% CI 109·5-111·0) in the first trimester (n=772) and 105·9 g/L (104·0-107·7) in the second trimester (n=111), with insufficient data for analysis in the third trimester. There were insufficient data for adults older than 65 years. We did not identify ancestry-specific high prevalence of non-clinically relevant genetic variants that influence haemoglobin concentrations.

Interpretation

Our results enable global harmonisation of clinical and public health haemoglobin thresholds for diagnosis of anaemia. Haemoglobin thresholds are similar between sexes until adolescence, after which males have higher thresholds than females. We did not find any evidence that thresholds should differ between people of differering ancestries.

Funding

World Health Organization and the Bill & Melinda Gates Foundation.",,doi:https://doi.org/10.1016/S2352-3026(24)00030-9; html:https://europepmc.org/articles/PMC10983828; pdf:https://europepmc.org/articles/PMC10983828?pdf=render +35876478,https://doi.org/10.3201/eid2808.211787,Lack of Evidence for Ribavirin Treatment of Lassa Fever in Systematic Review of Published and Unpublished Studies1.,"Cheng HY, French CE, Salam AP, Dawson S, McAleenan A, McGuinness LA, Savović J, Horby PW, Sterne JAC.",,Emerging infectious diseases,2022,2022-08-01,Y,Viruses; Bias; Ribavirin; Systematic review; Observational Study; Lassa Fever,,,"Ribavirin has been used widely to treat Lassa fever in West Africa since the 1980s. However, few studies have systematically appraised the evidence for its use. We conducted a systematic review of published and unpublished literature retrieved from electronic databases and gray literature from inception to March 8, 2022. We identified 13 studies of the comparative effectiveness of ribavirin versus no ribavirin treatment on mortality outcomes, including unpublished data from a study in Sierra Leone provided through a US Freedom of Information Act request. Although ribavirin was associated with decreased mortality rates, results of these studies were at critical or serious risk for bias when appraised using the ROBINS-I tool. Important risks for bias related to lack of control for confounders, immortal time bias, and missing outcome data. Robust evidence supporting the use of ribavirin in Lassa fever is lacking. Well-conducted clinical trials to elucidate the effectiveness of ribavirin for Lassa fever are needed.",,pdf:https://wwwnc.cdc.gov/eid/article/28/8/pdfs/21-1787.pdf; doi:https://doi.org/10.3201/eid2808.211787; html:https://europepmc.org/articles/PMC9328902; pdf:https://europepmc.org/articles/PMC9328902?pdf=render 31160290,https://doi.org/10.1128/aac.00400-19,Improved Performance Predicting Clarithromycin Resistance in Mycobacterium abscessus on an Independent Data Set.,"Lipworth S, Hough N, Buchanan R, Smith EG, Robinson E, Alexander E, Peto T, Crook D, Walker T.",,Antimicrobial agents and chemotherapy,2019,2019-07-25,N,Macrolides; Nontuberculous Mycobacteria; Mycobacterium Abscessus; Whole-genome Sequencing,,cancer and neoplasms,,,pdf:https://aac.asm.org/content/aac/63/8/e00400-19.full.pdf; doi:https://doi.org/10.1128/AAC.00400-19; html:https://europepmc.org/articles/PMC6658746; pdf:https://europepmc.org/articles/PMC6658746?pdf=render; doi:https://doi.org/10.1128/aac.00400-19 +38432242,https://doi.org/10.1016/s2352-3026(24)00030-9,Haemoglobin thresholds to define anaemia from age 6 months to 65 years: estimates from international data sources.,"Braat S, Fielding KL, Han J, Jackson VE, Zaloumis S, Xu JXH, Moir-Meyer G, Blaauwendraad SM, Jaddoe VWV, Gaillard R, Parkin PC, Borkhoff CM, Keown-Stoneman CDG, Birken CS, Maguire JL, Genes & Health Research Team, Bahlo M, Davidson EM, Pasricha SR.",,The Lancet. Haematology,2024,2024-02-29,Y,,,,"

Background

Detection of anaemia is crucial for clinical medicine and public health. Current WHO anaemia definitions are based on statistical thresholds (fifth centiles) set more than 50 years ago. We sought to establish evidence for the statistical haemoglobin thresholds for anaemia that can be applied globally and inform WHO and clinical guidelines.

Methods

In this analysis we identified international data sources from populations in the USA, England, Australia, China, the Netherlands, Canada, Ecuador, and Bangladesh with sufficient clinical and laboratory information collected between 1998 and 2020 to obtain a healthy reference sample. Individuals with clinical or biochemical evidence of a condition that could reduce haemoglobin concentrations were excluded. We estimated haemoglobin thresholds (ie, 5th centiles) for children aged 6-23 months, 24-59 months, 5-11 years, and 12-17 years, and adults aged 18-65 years (including during pregnancy) for individual datasets and pooled across data sources. We also collated findings from three large-scale genetic studies to summarise genetic variants affecting haemoglobin concentrations in different ancestral populations.

Findings

We identified eight data sources comprising 18 individual datasets that were eligible for inclusion in the analysis. In pooled analyses, the haemoglobin fifth centile was 104·4 g/L (90% CI 103·5-105·3) in 924 children aged 6-23 months, 110·2 g/L (109·5-110·9) in 1874 children aged 24-59 months, and 114·4 g/L (113·6-115·2) in 1839 children aged 5-11 years. Values diverged by sex in adolescents and adults. In pooled analyses, the fifth centile was 122·2 g/L (90% CI 121·3-123·1) in 1741 female adolescents aged 12-17 years and 128·2 g/L (126·4-130·0) in 1103 male adolescents aged 12-17 years. In pooled analyses of adults aged 18-65 years, the fifth centile was 119·7 g/L (90% CI 119·1-120·3) in 3640 non-pregnant females and 134·9 g/L (134·2-135·6) in 2377 males. Fifth centiles in pregnancy were 110·3 g/L (90% CI 109·5-111·0) in the first trimester (n=772) and 105·9 g/L (104·0-107·7) in the second trimester (n=111), with insufficient data for analysis in the third trimester. There were insufficient data for adults older than 65 years. We did not identify ancestry-specific high prevalence of non-clinically relevant genetic variants that influence haemoglobin concentrations.

Interpretation

Our results enable global harmonisation of clinical and public health haemoglobin thresholds for diagnosis of anaemia. Haemoglobin thresholds are similar between sexes until adolescence, after which males have higher thresholds than females. We did not find any evidence that thresholds should differ between people of differering ancestries.

Funding

World Health Organization and the Bill & Melinda Gates Foundation.",,doi:https://doi.org/10.1016/S2352-3026(24)00030-9; html:https://europepmc.org/articles/PMC10983828; pdf:https://europepmc.org/articles/PMC10983828?pdf=render 36180121,https://doi.org/10.1136/bmjopen-2021-057712,Development of a core outcome set and identification of patient-reportable outcomes for primary brain tumour trials: protocol for the COBra study.,"Retzer A, Sivell S, Scott H, Nelson A, Bulbeck H, Seddon K, Grant R, Adams R, Watts C, Aiyegbusi OL, Kearns P, Cruz Rivera S, Dirven L, Baddeley E, Calvert M, Byrne A.",,BMJ open,2022,2022-09-30,Y,Clinical Trials; Qualitative Research; Adult Palliative Care; Neurological Oncology,,,"

Introduction

Primary brain tumours, specifically gliomas, are a rare disease group. The disease and treatment negatively impacts on patients and those close to them. The high rates of physical and cognitive morbidity differ from other cancers causing reduced health-related quality of life. Glioma trials using outcomes that allow holistic analysis of treatment benefits and risks enable informed care decisions. Currently, outcome assessment in glioma trials is inconsistent, hindering evidence synthesis. A core outcome set (COS) - an agreed minimum set of outcomes to be measured and reported - may address this. International initiatives focus on defining core outcomes assessments across brain tumour types. This protocol describes the development of a COS involving UK stakeholders for use in glioma trials, applicable across glioma types, with provision to identify subsets as required. Due to stakeholder interest in data reported from the patient perspective, outcomes from the COS that can be patient-reported will be identified.

Methods and analysis

Stage I: (1) trial registry review to identify outcomes collected in glioma trials and (2) systematic review of qualitative literature exploring glioma patient and key stakeholder research priorities. Stage II: semi-structured interviews with glioma patients and caregivers. Outcome lists will be generated from stages I and II. Stage III: study team will remove duplicate items from the outcome lists and ensure accessible terminology for inclusion in the Delphi survey. Stage IV: a two-round Delphi process whereby the outcomes will be rated by key stakeholders. Stage V: a consensus meeting where participants will finalise the COS. The study team will identify the COS outcomes that can be patient-reported. Further research is needed to match patient-reported outcomes to available measures.

Ethics and dissemination

Ethical approval was obtained (REF SMREC 21/59, Cardiff University School of Medicine Research Ethics Committee). Study findings will be disseminated widely through conferences and journal publication. The final COS will be adopted and promoted by patient and carer groups and its use by funders encouraged.

Prospero registration number

CRD42021236979.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e057712.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057712; html:https://europepmc.org/articles/PMC9528585; pdf:https://europepmc.org/articles/PMC9528585?pdf=render 33323250,https://doi.org/10.1016/s2589-7500(19)30121-9,"Development and validation of multivariable prediction models of remission, recovery, and quality of life outcomes in people with first episode psychosis: a machine learning approach.","Leighton SP, Upthegrove R, Krishnadas R, Benros ME, Broome MR, Gkoutos GV, Liddle PF, Singh SP, Everard L, Jones PB, Fowler D, Sharma V, Freemantle N, Christensen RHB, Albert N, Nordentoft M, Schwannauer M, Cavanagh J, Gumley AI, Birchwood M, Mallikarjun PK.",,The Lancet. Digital health,2019,2019-09-12,N,,,,"

Background

Outcomes for people with first-episode psychosis are highly heterogeneous. Few reliable validated methods are available to predict the outcome for individual patients in the first clinical contact. In this study, we aimed to build multivariable prediction models of 1-year remission and recovery outcomes using baseline clinical variables in people with first-episode psychosis.

Methods

In this machine learning approach, we applied supervised machine learning, using regularised regression and nested leave-one-site-out cross-validation, to baseline clinical data from the English Evaluating the Development and Impact of Early Intervention Services (EDEN) study (n=1027), to develop and internally validate prediction models at 1-year follow-up. We assessed four binary outcomes that were recorded at 1 year: symptom remission, social recovery, vocational recovery, and quality of life (QoL). We externally validated the prediction models by selecting from the top predictor variables identified in the internal validation models the variables shared with the external validation datasets comprised of two Scottish longitudinal cohort studies (n=162) and the OPUS trial, a randomised controlled trial of specialised assertive intervention versus standard treatment (n=578).

Findings

The performance of prediction models was robust for the four 1-year outcomes of symptom remission (area under the receiver operating characteristic curve [AUC] 0·703, 95% CI 0·664-0·742), social recovery (0·731, 0·697-0·765), vocational recovery (0·736, 0·702-0·771), and QoL (0·704, 0·667-0·742; p<0·0001 for all outcomes), on internal validation. We externally validated the outcomes of symptom remission (AUC 0·680, 95% CI 0·587-0·773), vocational recovery (0·867, 0·805-0·930), and QoL (0·679, 0·522-0·836) in the Scottish datasets, and symptom remission (0·616, 0·553-0·679), social recovery (0·573, 0·504-0·643), vocational recovery (0·660, 0·610-0·710), and QoL (0·556, 0·481-0·631) in the OPUS dataset.

Interpretation

In our machine learning analysis, we showed that prediction models can reliably and prospectively identify poor remission and recovery outcomes at 1 year for patients with first-episode psychosis using baseline clinical variables at first clinical contact.

Funding

Lundbeck Foundation.",,pdf:http://www.thelancet.com/article/S2589750019301219/pdf; doi:https://doi.org/10.1016/S2589-7500(19)30121-9 31308017,https://doi.org/10.2337/dc18-2423,"Educational and Health Outcomes of Children Treated for Type 1 Diabetes: Scotland-Wide Record Linkage Study of 766,047 Children.","Fleming M, Fitton CA, Steiner MFC, McLay JS, Clark D, King A, Lindsay RS, Mackay DF, Pell JP.",,Diabetes care,2019,2019-07-15,N,,,,"

Objective

This study was conducted to determine the association between childhood type 1 diabetes and educational and health outcomes.

Research design and methods

Record linkage of nine Scotland-wide databases (diabetes register, dispensed prescriptions, maternity records, hospital admissions, death certificates, annual pupil census, school absences/exclusions, school examinations, and unemployment) produced a cohort of 766,047 singleton children born in Scotland who attended Scottish schools between 2009 and 2013. We compared the health and education outcomes of schoolchildren receiving insulin with their peers, adjusting for potential confounders.

Results

The 3,330 children (0.47%) treated for type 1 diabetes were more likely to be admitted to the hospital (adjusted hazard ratio [HR] 3.97, 95% CI 3.79-4.16), die (adjusted HR 3.84, 95% CI 1.98-7.43), be absent from school (adjusted incidence rate ratio [IRR] 1.34, 95% CI 1.30-1.39), and have learning difficulties (adjusted odds ratio [OR] 1.19, 95% CI 1.03-1.38). Among children with type 1 diabetes, higher mean HbA1c (particularly HbA1c in the highest quintile) was associated with greater absenteeism (adjusted IRR 1.75, 95% CI 1.56-1.96), increased school exclusion (adjusted IRR 2.82, 95% CI 1.14-6.98), poorer attainment (adjusted OR 3.52, 95% CI 1.72-7.18), and higher risk of unemployment (adjusted OR 2.01, 95% CI 1.05-3.85).

Conclusions

Children with type 1 diabetes fare worse than their peers in respect of education and health outcomes, especially if they have higher mean HbA1c. Interventions are required to minimize school absence and ensure that it does not affect educational attainment.",,pdf:https://care.diabetesjournals.org/content/diacare/42/9/1700.full.pdf; doi:https://doi.org/10.2337/dc18-2423; html:https://europepmc.org/articles/PMC6706279; pdf:https://europepmc.org/articles/PMC6706279?pdf=render; doi:https://doi.org/10.2337/dc18-2423 @@ -2391,8 +2391,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 31647808,https://doi.org/10.1371/journal.pgen.1008405,Causal relationships between obesity and the leading causes of death in women and men.,"Censin JC, Peters SAE, Bovijn J, Ferreira T, Pulit SL, Mägi R, Mahajan A, Holmes MV, Lindgren CM.",,PLoS genetics,2019,2019-10-24,Y,,Understanding the Causes of Disease,,"Obesity traits are causally implicated with risk of cardiometabolic diseases. It remains unclear whether there are similar causal effects of obesity traits on other non-communicable diseases. Also, it is largely unexplored whether there are any sex-specific differences in the causal effects of obesity traits on cardiometabolic diseases and other leading causes of death. We constructed sex-specific genetic risk scores (GRS) for three obesity traits; body mass index (BMI), waist-hip ratio (WHR), and WHR adjusted for BMI, including 565, 324, and 337 genetic variants, respectively. These GRSs were then used as instrumental variables to assess associations between the obesity traits and leading causes of mortality in the UK Biobank using Mendelian randomization. We also investigated associations with potential mediators, including smoking, glycemic and blood pressure traits. Sex-differences were subsequently assessed by Cochran's Q-test (Phet). A Mendelian randomization analysis of 228,466 women and 195,041 men showed that obesity causes coronary artery disease, stroke (particularly ischemic), chronic obstructive pulmonary disease, lung cancer, type 2 and 1 diabetes mellitus, non-alcoholic fatty liver disease, chronic liver disease, and acute and chronic renal failure. Higher BMI led to higher risk of type 2 diabetes in women than in men (Phet = 1.4×10-5). Waist-hip-ratio led to a higher risk of chronic obstructive pulmonary disease (Phet = 3.7×10-6) and higher risk of chronic renal failure (Phet = 1.0×10-4) in men than women. Obesity traits have an etiological role in the majority of the leading global causes of death. Sex differences exist in the effects of obesity traits on risk of type 2 diabetes, chronic obstructive pulmonary disease, and renal failure, which may have downstream implications for public health.","This study aimed to quantify (as genetic risk scores) the causal effects of obesity on leading causes of death, separately, in men and women. Analysis of genetic data for 228,466 women and 195,041 men showed that obesity causes coronary artery disease, stroke, chronic obstructive pulmonary disease, lung cancer, type 2 and 1 diabetes mellitus, non-alcoholic fatty liver disease, chronic liver disease, and acute and chronic renal failure. The authors identified some important differences in these causal effects for men and women.",pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1008405&type=printable; doi:https://doi.org/10.1371/journal.pgen.1008405; html:https://europepmc.org/articles/PMC6812754; pdf:https://europepmc.org/articles/PMC6812754?pdf=render 32792438,https://doi.org/10.1136/bmjopen-2019-036564,Association between health indicators of maternal adversity and the rate of infant entry to local authority care in England: a longitudinal ecological study.,"Pearson RJ, Jay MA, Wijlaars LPMM, De Stavola B, Syed S, Bedston SJ, Gilbert R.",,BMJ open,2020,2020-08-13,Y,epidemiology; Public Health; Child Protection,,,"

Objective

Infants enter care at varying rates across local authorities (LAs) in England, but evidence is lacking on what is driving these differences. With this ecological study, we aimed to explore the extent to which adversity indicated within women's hospitalisation histories, predelivery, explained the rate of infant entry into care.

Methods

We used two longitudinal person-level data sets on hospitalisations and entries to care to create annual measures for 131 English LAs, between 2006/2007 and 2013/2014 (April-March). We combined these measures by LA and financial year, along with other publicly available data on LA characteristics. We used linear mixed-effects models to analyse the relationship between the outcome-LA-specific rate of infant entry into care (per 10 000 infants in the LA population) - and LA-specific percentage of live births with maternal history of adversity-related hospital admissions (ie, substance misuse, mental health problems or violence-related admissions in the 3 years before delivery), adjusted for other predictors of entry into care.

Results

Rate of infant entry into care (mean: 85.16 per 10 000, SD: 41.07) and percentage of live births with maternal history of adversity-related hospital admissions (4.62%, 2.44%) varied greatly by LA. The prevalence of maternal adversity accounted for 24% of the variation in rate of entry (95% CI 14% to 35%). After adjustment, a percentage point increase in prevalence of maternal adversity-both within and between LAs-was associated with an estimated 2.56 (per 10 000) more infants entering care (1.31-3.82).

Conclusions

The prevalence of maternal adversity before birth helped to explain the variation in LA rates of infant entry into care. Preventive interventions are needed to improve maternal well-being before and during pregnancy, and potentially reduce risk of child maltreatment and therefore entries to care. Evidence on who to target and data to evaluate change require linkage between parent-child healthcare data and administrative data from children's social care.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/8/e036564.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-036564; html:https://europepmc.org/articles/PMC7430489; pdf:https://europepmc.org/articles/PMC7430489?pdf=render 33875891,https://doi.org/10.1038/s41593-021-00826-4,An expanded set of genome-wide association studies of brain imaging phenotypes in UK Biobank.,"Smith SM, Douaud G, Chen W, Hanayik T, Alfaro-Almagro F, Sharp K, Elliott LT.",,Nature neuroscience,2021,2021-04-19,Y,,,,"UK Biobank is a major prospective epidemiological study, including multimodal brain imaging, genetics and ongoing health outcomes. Previously, we published genome-wide associations of 3,144 brain imaging-derived phenotypes, with a discovery sample of 8,428 individuals. Here we present a new open resource of genome-wide association study summary statistics, using the 2020 data release, almost tripling the discovery sample size. We now include the X chromosome and new classes of imaging-derived phenotypes (subcortical volumes and tissue contrast). Previously, we found 148 replicated clusters of associations between genetic variants and imaging phenotypes; in this study, we found 692, including 12 on the X chromosome. We describe some of the newly found associations, focusing on the X chromosome and autosomal associations involving the new classes of imaging-derived phenotypes. Our novel associations implicate, for example, pathways involved in the rare X-linked STAR (syndactyly, telecanthus and anogenital and renal malformations) syndrome, Alzheimer's disease and mitochondrial disorders.",,pdf:https://ora.ox.ac.uk/objects/uuid:3a84eaef-5966-4690-b5d3-658070577382/files/s3197xm84x; doi:https://doi.org/10.1038/s41593-021-00826-4; html:https://europepmc.org/articles/PMC7610742; pdf:https://europepmc.org/articles/PMC7610742?pdf=render -31350032,https://doi.org/10.1016/j.burns.2019.07.003,"Epidemiology of burn-related fatalities in Australia and New Zealand, 2009-2015.","McInnes JA, Cleland HJ, Cameron PA, Darton A, Tracy LM, Wood FM, Singer Y, Gabbe BJ.",,Burns : journal of the International Society for Burn Injuries,2019,2019-07-24,N,Burns; Mortality; Australia; New Zealand; epidemiology; Fatality,,,"

Background

Knowledge of the epidemiology of burn-related fatalities is limited, with most previous studies based on hospital and burn centre data only.

Aims

To describe the epidemiological characteristics of all burn-related fatalities in Australia and New Zealand, and to identify any trends in burn-related fatality incidence over the study period.

Methods

Data from the National Coronial Information System, including data for pre-hospital and in-hospital burn-related fatality cases, was used to examine the characteristics of burn-related fatalities occurring in Australia and New Zealand from 2009 to 2015. Burn-related fatality rates per 100,000 population were estimated, and incidence trends assessed using Poisson regression analysis.

Results

Of the 310 burn-related fatalities that occurred in Australia and New Zealand, 2009-2015, 41% occurred in a pre-hospital setting. Overall, most burn-related fatality cases were fire related, occurred at home, and were of people aged 41-80 years. One quarter of all burn-related fatalities were a result of intentional self-harm. The population incidence of all burn-related fatalities combined, and for NSW, decreased over the study period.

Conclusions

This study has identified the importance of examining all burn-related fatalities. If this is not done, vulnerable population subgroups will be missed and prevention efforts poorly targeted.",,doi:https://doi.org/10.1016/j.burns.2019.07.003 32095773,https://doi.org/10.1159/000503957,Advancing the Use of Mobile Technologies in Clinical Trials: Recommendations from the Clinical Trials Transformation Initiative.,"Coran P, Goldsack JC, Grandinetti CA, Bakker JP, Bolognese M, Dorsey ER, Vasisht K, Amdur A, Dell C, Helfgott J, Kirchoff M, Miller CJ, Narayan A, Patel D, Peterson B, Ramirez E, Schiller D, Switzer T, Wing L, Forrest A, Doherty A.",,Digital biomarkers,2019,2019-09-01,N,Clinical Trials; Regulatory Approval; Wearable Sensors; Mobile Technologies,"Better, Faster and More Efficient Clinical Trials",,"Mobile technologies offer the potential to reduce the costs of conducting clinical trials by collecting high-quality information on health outcomes in real-world settings that are relevant to patients and clinicians. However, widespread use of mobile technologies in clinical trials has been impeded by their perceived challenges. To advance solutions to these challenges, the Clinical Trials Transformation Initiative (CTTI) has issued best practices and realistic approaches that clinical trial sponsors can now use. These include CTTI recommendations on technology selection; data collection, analysis, and interpretation; data management; protocol design and execution; and US Food and Drug Administration submission and inspection. The scientific principles underpinning the clinical trials enterprise continue to apply to studies using mobile technologies. These recommendations provide a framework for including mobile technologies in clinical trials that can lead to more efficient assessment of new therapies for patients.","The authors of this publication have developed a set of guidelines for planning, running and writing up research that uses mobile technologies in clinical trials. The guidelines they have put together should make it easer for patient experience to be recorded in clinical trials.",pdf:https://www.karger.com/Article/Pdf/503957; doi:https://doi.org/10.1159/000503957; html:https://europepmc.org/articles/PMC7011727; pdf:https://europepmc.org/articles/PMC7011727?pdf=render; doi:https://doi.org/10.1159/000503957 +31350032,https://doi.org/10.1016/j.burns.2019.07.003,"Epidemiology of burn-related fatalities in Australia and New Zealand, 2009-2015.","McInnes JA, Cleland HJ, Cameron PA, Darton A, Tracy LM, Wood FM, Singer Y, Gabbe BJ.",,Burns : journal of the International Society for Burn Injuries,2019,2019-07-24,N,Burns; Mortality; Australia; New Zealand; epidemiology; Fatality,,,"

Background

Knowledge of the epidemiology of burn-related fatalities is limited, with most previous studies based on hospital and burn centre data only.

Aims

To describe the epidemiological characteristics of all burn-related fatalities in Australia and New Zealand, and to identify any trends in burn-related fatality incidence over the study period.

Methods

Data from the National Coronial Information System, including data for pre-hospital and in-hospital burn-related fatality cases, was used to examine the characteristics of burn-related fatalities occurring in Australia and New Zealand from 2009 to 2015. Burn-related fatality rates per 100,000 population were estimated, and incidence trends assessed using Poisson regression analysis.

Results

Of the 310 burn-related fatalities that occurred in Australia and New Zealand, 2009-2015, 41% occurred in a pre-hospital setting. Overall, most burn-related fatality cases were fire related, occurred at home, and were of people aged 41-80 years. One quarter of all burn-related fatalities were a result of intentional self-harm. The population incidence of all burn-related fatalities combined, and for NSW, decreased over the study period.

Conclusions

This study has identified the importance of examining all burn-related fatalities. If this is not done, vulnerable population subgroups will be missed and prevention efforts poorly targeted.",,doi:https://doi.org/10.1016/j.burns.2019.07.003 32709645,https://doi.org/10.1136/bmjopen-2019-035968,Infant formula composition and educational performance: a protocol to extend follow-up for a set of randomised controlled trials using linked administrative education records.,"Verfürden M, Harron K, Jerrim J, Fewtrell M, Gilbert R.",,BMJ open,2020,2020-07-23,Y,Public Health; Clinical Trials; Paediatric Neurology; Nutrition & Dietetics,,,"

Introduction

The effect of infant nutrition on long-term cognition is important for parents and policy makers. However, most clinical trials typically have short follow-up periods, when measures of cognition are poorly predictive of later function. The few trials with longer-term follow-up have high levels of attrition, which can lead to selection bias, and in turn to erroneous interpretation of long-term harms and benefits of infant nutrition. We address the need for unbiased, long-term follow-up, by linking measures of educational performance from administrative education records. Educational performance is a meaningful marker of cognitive function in children and it is strongly correlated with IQ. We aim to evaluate educational performance for children who, as infants, were part of a series of trials that randomised participants to either nutritionally modified infant formula or standard formula. Most trialists anticipated positive effects of these interventions on later cognitive function.

Methods and analysis

Using data from 1923 participants of seven randomised infant formula trials linked to the English National Pupil Database (NPD), this study will provide new insights into the effect of nutrient intake in infancy on school achievement. Our primary outcome will be the mean differences in z-scores between intervention and control groups for a compulsory Mathematics exam sat at age 16. Secondary outcomes will be z-scores for a compulsory English exam at age 16 and z-scores for compulsory Mathematics and English exams at age 11. We will also evaluate intervention effects on the likelihood of receiving special educational needs (SEN) support. All analyses will be performed separately by trial.

Ethics and dissemination

Research ethics approval, and approval from the Health Research Authority Confidentiality Advisory Group, has been obtained for this study. The results of this study will be disseminated to scientific, practitioner, and lay audiences, submitted for publication in peer-reviewed journals, and will contribute towards a PhD dissertation.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/7/e035968.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-035968; html:https://europepmc.org/articles/PMC7380883; pdf:https://europepmc.org/articles/PMC7380883?pdf=render 35143473,https://doi.org/10.1371/journal.pbio.3001531,SARS-CoV-2 antibodies protect against reinfection for at least 6 months in a multicentre seroepidemiological workplace cohort.,"Finch E, Lowe R, Fischinger S, de St Aubin M, Siddiqui SM, Dayal D, Loesche MA, Rhee J, Beger S, Hu Y, Gluck MJ, Mormann B, Hasdianda MA, Musk ER, Alter G, Menon AS, Nilles EJ, Kucharski AJ, CMMID COVID-19 working group and the SpaceX COVID-19 Cohort Collaborative.",,PLoS biology,2022,2022-02-10,Y,,,,"Identifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders and the choice of baseline time point, and show how to account for both in reinfection analysis.",,pdf:https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001531&type=printable; doi:https://doi.org/10.1371/journal.pbio.3001531; html:https://europepmc.org/articles/PMC8865659; pdf:https://europepmc.org/articles/PMC8865659?pdf=render 35977952,https://doi.org/10.1038/s41467-022-29931-z,GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements.,"Dixon PH, Levine AP, Cebola I, Chan MMY, Amin AS, Aich A, Mozere M, Maude H, Mitchell AL, Zhang J, NIHR BioResource, Genomics England Research Consortium Collaborators, Chambers J, Syngelaki A, Donnelly J, Cooley S, Geary M, Nicolaides K, Thorsell M, Hague WM, Estiu MC, Marschall HU, Gale DP, Williamson C.",,Nature communications,2022,2022-08-17,Y,,,,"Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5-2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility.",,pdf:https://www.nature.com/articles/s41467-022-29931-z.pdf; doi:https://doi.org/10.1038/s41467-022-29931-z; html:https://europepmc.org/articles/PMC9385867; pdf:https://europepmc.org/articles/PMC9385867?pdf=render @@ -2413,20 +2413,20 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 36812516,https://doi.org/10.1371/journal.pdig.0000007,A proteomic survival predictor for COVID-19 patients in intensive care.,"Demichev V, Tober-Lau P, Nazarenko T, Lemke O, Kaur Aulakh S, Whitwell HJ, Röhl A, Freiwald A, Mittermaier M, Szyrwiel L, Ludwig D, Correia-Melo C, Lippert LJ, Helbig ET, Stubbemann P, Olk N, Thibeault C, Grüning NM, Blyuss O, Vernardis S, White M, Messner CB, Joannidis M, Sonnweber T, Klein SJ, Pizzini A, Wohlfarter Y, Sahanic S, Hilbe R, Schaefer B, Wagner S, Machleidt F, Garcia C, Ruwwe-Glösenkamp C, Lingscheid T, Bosquillon de Jarcy L, Stegemann MS, Pfeiffer M, Jürgens L, Denker S, Zickler D, Spies C, Edel A, Müller NB, Enghard P, Zelezniak A, Bellmann-Weiler R, Weiss G, Campbell A, Hayward C, Porteous DJ, Marioni RE, Uhrig A, Zoller H, Löffler-Ragg J, Keller MA, Tancevski I, Timms JF, Zaikin A, Hippenstiel S, Ramharter M, Müller-Redetzky H, Witzenrath M, Suttorp N, Lilley K, Mülleder M, Sander LE, PA-COVID-19 Study group, Kurth F, Ralser M.",,PLOS digital health,2022,2022-01-18,Y,,,,"Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Additional tools are also needed to monitor treatment, including experimental therapies in clinical trials. Comprehensively capturing human physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index, and APACHE II score showed limited performance in predicting the COVID-19 outcome. Instead, the quantification of 321 plasma protein groups at 349 timepoints in 50 critically ill patients receiving invasive mechanical ventilation revealed 14 proteins that showed trajectories different between survivors and non-survivors. A predictor trained on proteomic measurements obtained at the first time point at maximum treatment level (i.e. WHO grade 7), which was weeks before the outcome, achieved accurate classification of survivors (AUROC 0.81). We tested the established predictor on an independent validation cohort (AUROC 1.0). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that plasma proteomics can give rise to prognostic predictors substantially outperforming current prognostic markers in intensive care.",,pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000007&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000007; html:https://europepmc.org/articles/PMC9931303; pdf:https://europepmc.org/articles/PMC9931303?pdf=render 31289267,https://doi.org/10.1038/s41467-019-10724-w,Mapping the drivers of within-host pathogen evolution using massive data sets.,"Palmer DS, Turner I, Fidler S, Frater J, Goedhals D, Goulder P, Huang KG, Oxenius A, Phillips R, Shapiro R, Vuuren CV, McLean AR, McVean G.",,Nature communications,2019,2019-07-09,Y,,Applied Analytics,,"Differences among hosts, resulting from genetic variation in the immune system or heterogeneity in drug treatment, can impact within-host pathogen evolution. Genetic association studies can potentially identify such interactions. However, extensive and correlated genetic population structure in hosts and pathogens presents a substantial risk of confounding analyses. Moreover, the multiple testing burden of interaction scanning can potentially limit power. We present a Bayesian approach for detecting host influences on pathogen evolution that exploits vast existing data sets of pathogen diversity to improve power and control for stratification. The approach models key processes, including recombination and selection, and identifies regions of the pathogen genome affected by host factors. Our simulations and empirical analysis of drug-induced selection on the HIV-1 genome show that the method recovers known associations and has superior precision-recall characteristics compared to other approaches. We build a high-resolution map of HLA-induced selection in the HIV-1 genome, identifying novel epitope-allele combinations.",,pdf:https://www.nature.com/articles/s41467-019-10724-w.pdf; doi:https://doi.org/10.1038/s41467-019-10724-w; html:https://europepmc.org/articles/PMC6616926; pdf:https://europepmc.org/articles/PMC6616926?pdf=render 35876425,https://doi.org/10.1002/mds.29147,"MED27, SLC6A7, and MPPE1 Variants in a Complex Neurodevelopmental Disorder with Severe Dystonia.","Reid KM, Spaull R, Salian S, Barwick K, Meyer E, Zhen J, Hirata H, Sheipouri D, Benkerroum H, Gorman KM, Papandreou A, Simpson MA, Hirano Y, Farabella I, Topf M, Grozeva D, Carss K, Smith M, Pall H, Lunt P, De Gressi S, Kamsteeg EJ, Haack TB, Carr L, Guerreiro R, Bras J, Maher ER, Scott RH, Vandenberg RJ, Raymond FL, Chong WK, Sudhakar S, Mankad K, Reith ME, Campeau PM, Harvey RJ, Kurian MA.",,Movement disorders : official journal of the Movement Disorder Society,2022,2022-07-25,Y,Dystonia; Status Dystonicus; Med27; Mppe1; Slc6a7,,,"

Background

Despite advances in next generation sequencing technologies, the identification of variants of uncertain significance (VUS) can often hinder definitive diagnosis in patients with complex neurodevelopmental disorders.

Objective

The objective of this study was to identify and characterize the underlying cause of disease in a family with two children with severe developmental delay associated with generalized dystonia and episodic status dystonicus, chorea, epilepsy, and cataracts.

Methods

Candidate genes identified by autozygosity mapping and whole-exome sequencing were characterized using cellular and vertebrate model systems.

Results

Homozygous variants were found in three candidate genes: MED27, SLC6A7, and MPPE1. Although the patients had features of MED27-related disorder, the SLC6A7 and MPPE1 variants were functionally investigated. SLC6A7 variant in vitro overexpression caused decreased proline transport as a result of reduced cell-surface expression, and zebrafish knockdown of slc6a7 exhibited developmental delay and fragile motor neuron morphology that could not be rescued by L-proline transporter-G396S RNA. Lastly, patient fibroblasts displayed reduced cell-surface expression of glycophosphatidylinositol-anchored proteins linked to MPPE1 dysfunction.

Conclusions

We report a family harboring a homozygous MED27 variant with additional loss-of-function SLC6A7 and MPPE1 gene variants, which potentially contribute to a blended phenotype caused by multilocus pathogenic variants. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.",,pdf:https://research-information.bris.ac.uk/ws/files/338319463/Movement_Disorders_2022_Reid_MED27_SLC6A7_and_MPPE1_Variants_in_a_Complex_Neurodevelopmental_Disorder_with_Severe.pdf; doi:https://doi.org/10.1002/mds.29147; html:https://europepmc.org/articles/PMC9796674; pdf:https://europepmc.org/articles/PMC9796674?pdf=render -33185739,https://doi.org/10.1007/s00395-020-00828-6,Functional investigation of the coronary artery disease gene SVEP1.,"Winkler MJ, Müller P, Sharifi AM, Wobst J, Winter H, Mokry M, Ma L, van der Laan SW, Pang S, Miritsch B, Hinterdobler J, Werner J, Stiller B, Güldener U, Webb TR, Asselbergs FW, Björkegren JLM, Maegdefessel L, Schunkert H, Sager HB, Kessler T.",,Basic research in cardiology,2020,2020-11-13,Y,Genetics; Atherosclerosis; coronary artery disease; Svep1,,,"A missense variant of the sushi, von Willebrand factor type A, EGF and pentraxin domain containing protein 1 (SVEP1) is genome-wide significantly associated with coronary artery disease. The mechanisms how SVEP1 impacts atherosclerosis are not known. We found endothelial cells (EC) and vascular smooth muscle cells to represent the major cellular source of SVEP1 in plaques. Plaques were larger in atherosclerosis-prone Svep1 haploinsufficient (ApoE-/-Svep1+/-) compared to Svep1 wild-type mice (ApoE-/-Svep1+/+) and ApoE-/-Svep1+/- mice displayed elevated plaque neutrophil, Ly6Chigh monocyte, and macrophage numbers. We assessed how leukocytes accumulated more inside plaques in ApoE-/-Svep1+/- mice and found enhanced leukocyte recruitment from blood into plaques. In vitro, we examined how SVEP1 deficiency promotes leukocyte recruitment and found elevated expression of the leukocyte attractant chemokine (C-X-C motif) ligand 1 (CXCL1) in EC after incubation with missense compared to wild-type SVEP1. Increasing wild-type SVEP1 levels silenced endothelial CXCL1 release. In line, plasma Cxcl1 levels were elevated in ApoE-/-Svep1+/- mice. Our studies reveal an atheroprotective role of SVEP1. Deficiency of wild-type Svep1 increased endothelial CXCL1 expression leading to enhanced recruitment of proinflammatory leukocytes from blood to plaque. Consequently, elevated vascular inflammation resulted in enhanced plaque progression in Svep1 deficiency.",,pdf:https://link.springer.com/content/pdf/10.1007/s00395-020-00828-6.pdf; doi:https://doi.org/10.1007/s00395-020-00828-6; html:https://europepmc.org/articles/PMC7666586; pdf:https://europepmc.org/articles/PMC7666586?pdf=render 34563995,https://doi.org/10.1016/j.schres.2021.09.006,"The impact of cigarette smoking on life expectancy in schizophrenia, schizoaffective disorder and bipolar affective disorder: An electronic case register cohort study.","Chesney E, Robson D, Patel R, Shetty H, Richardson S, Chang CK, McGuire P, McNeill A.",,Schizophrenia research,2021,2021-09-23,Y,Mortality; Schizophrenia; Tobacco; Smoking; Life expectancy; Bipolar Affective Disorder,,,"Severe mental disorders are associated with a life expectancy that is 10-20 years shorter than the general population's. The prevalence of cigarette smoking in these populations is very high. We examined the effect of smoking on life expectancy and survival in patients with a diagnosis of schizophrenia, schizoaffective disorder or bipolar affective disorder from 2007 to 2018 in South East London, UK. Smoking status was determined using unstructured text data extracted from electronic health records. A total of 21,588 patients were identified of which 16,717, (77.4%) were classified as current smokers and 3438 (15.9%) as non-smokers. In female participants, life expectancy at birth was 67.6 years in current smokers (95% CI: 66.4-68.8) and 74.9 years in non-smokers (95% CI: 72.8-77.0), a difference of 7.3 years. In male participants, life expectancy at birth was 63.5 years in current smokers (95% CI: 62.5-64.5) and 68.5 years in non-smokers (95% CI, 64.4-72.6), a difference of 5.0 years. Adjusted survival models found that current smoking status was associated with an increased mortality risk for both females (aHR: 1.42, 95% CI: 1.21-1.66, p < 0.001) and males (aHR: 1.49; 95% CI: 1.25-1.79, p < 0.001). In terms of the effect sizes, these risks were similar to those associated with a diagnosis of co-morbid alcohol or opioid use disorder. Smoking may account for a substantial proportion of the reduced life expectancy in patients with psychotic disorders. Increased emphasis on reducing cigarette smoking in these populations may be the most effective way to reduce the mortality gap with the general population.",,doi:https://doi.org/10.1016/j.schres.2021.09.006; doi:https://doi.org/10.1016/j.schres.2021.09.006; html:https://europepmc.org/articles/PMC8653908 +33185739,https://doi.org/10.1007/s00395-020-00828-6,Functional investigation of the coronary artery disease gene SVEP1.,"Winkler MJ, Müller P, Sharifi AM, Wobst J, Winter H, Mokry M, Ma L, van der Laan SW, Pang S, Miritsch B, Hinterdobler J, Werner J, Stiller B, Güldener U, Webb TR, Asselbergs FW, Björkegren JLM, Maegdefessel L, Schunkert H, Sager HB, Kessler T.",,Basic research in cardiology,2020,2020-11-13,Y,Genetics; Atherosclerosis; coronary artery disease; Svep1,,,"A missense variant of the sushi, von Willebrand factor type A, EGF and pentraxin domain containing protein 1 (SVEP1) is genome-wide significantly associated with coronary artery disease. The mechanisms how SVEP1 impacts atherosclerosis are not known. We found endothelial cells (EC) and vascular smooth muscle cells to represent the major cellular source of SVEP1 in plaques. Plaques were larger in atherosclerosis-prone Svep1 haploinsufficient (ApoE-/-Svep1+/-) compared to Svep1 wild-type mice (ApoE-/-Svep1+/+) and ApoE-/-Svep1+/- mice displayed elevated plaque neutrophil, Ly6Chigh monocyte, and macrophage numbers. We assessed how leukocytes accumulated more inside plaques in ApoE-/-Svep1+/- mice and found enhanced leukocyte recruitment from blood into plaques. In vitro, we examined how SVEP1 deficiency promotes leukocyte recruitment and found elevated expression of the leukocyte attractant chemokine (C-X-C motif) ligand 1 (CXCL1) in EC after incubation with missense compared to wild-type SVEP1. Increasing wild-type SVEP1 levels silenced endothelial CXCL1 release. In line, plasma Cxcl1 levels were elevated in ApoE-/-Svep1+/- mice. Our studies reveal an atheroprotective role of SVEP1. Deficiency of wild-type Svep1 increased endothelial CXCL1 expression leading to enhanced recruitment of proinflammatory leukocytes from blood to plaque. Consequently, elevated vascular inflammation resulted in enhanced plaque progression in Svep1 deficiency.",,pdf:https://link.springer.com/content/pdf/10.1007/s00395-020-00828-6.pdf; doi:https://doi.org/10.1007/s00395-020-00828-6; html:https://europepmc.org/articles/PMC7666586; pdf:https://europepmc.org/articles/PMC7666586?pdf=render 36810190,https://doi.org/10.1136/bmjebm-2023-112253,Digitally enabled decentralised research: opportunities to improve the efficiency of clinical trials and observational studies.,"Aiyegbusi OL, Davies EH, Myles P, Williams T, Frost C, Haroon S, Hughes SE, Wilson R, McMullan C, Subramanian A, Nirantharakumar K, Calvert MJ.",,BMJ evidence-based medicine,2023,2023-02-21,Y,information technology; drug discovery; Drug Development; Covid-19,,,,,pdf:https://ebm.bmj.com/content/ebmed/early/2023/02/20/bmjebm-2023-112253.full.pdf; doi:https://doi.org/10.1136/bmjebm-2023-112253; html:https://europepmc.org/articles/PMC10579468; pdf:https://europepmc.org/articles/PMC10579468?pdf=render 31641117,https://doi.org/10.1038/s41467-019-12682-9,Sequence variants with large effects on cardiac electrophysiology and disease.,"Norland K, Sveinbjornsson G, Thorolfsdottir RB, Davidsson OB, Tragante V, Rajamani S, Helgadottir A, Gretarsdottir S, van Setten J, Asselbergs FW, Sverrisson JT, Stephensen SS, Oskarsson G, Sigurdsson EL, Andersen K, Danielsen R, Thorgeirsson G, Thorsteinsdottir U, Arnar DO, Sulem P, Holm H, Gudbjartsson DF, Stefansson K.",,Nature communications,2019,2019-10-22,Y,,,,"Features of the QRS complex of the electrocardiogram, reflecting ventricular depolarisation, associate with various physiologic functions and several pathologic conditions. We test 32.5 million variants for association with ten measures of the QRS complex in 12 leads, using 405,732 electrocardiograms from 81,192 Icelanders. We identify 190 associations at 130 loci, the majority of which have not been reported before, including associations with 21 rare or low-frequency coding variants. Assessment of genes expressed in the heart yields an additional 13 rare QRS coding variants at 12 loci. We find 51 unreported associations between the QRS variants and echocardiographic traits and cardiovascular diseases, including atrial fibrillation, complete AV block, heart failure and supraventricular tachycardia. We demonstrate the advantage of in-depth analysis of the QRS complex in conjunction with other cardiovascular phenotypes to enhance our understanding of the genetic basis of myocardial mass, cardiac conduction and disease.",,pdf:https://www.nature.com/articles/s41467-019-12682-9.pdf; doi:https://doi.org/10.1038/s41467-019-12682-9; html:https://europepmc.org/articles/PMC6805929; pdf:https://europepmc.org/articles/PMC6805929?pdf=render -36347531,https://doi.org/10.1136/bmj-2022-070918,Development and external validation of a risk prediction model for falls in patients with an indication for antihypertensive treatment: retrospective cohort study.,"Archer L, Koshiaris C, Lay-Flurrie S, Snell KIE, Riley RD, Stevens R, Banerjee A, Usher-Smith JA, Clegg A, Payne RA, Hobbs FDR, McManus RJ, Sheppard JP, STRAtifying Treatments In the multi-morbid Frail elderlY (STRATIFY) investigators.",,BMJ (Clinical research ed.),2022,2022-11-08,Y,,,,"

Objective

To develop and externally validate the STRAtifying Treatments In the multi-morbid Frail elderlY (STRATIFY)-Falls clinical prediction model to identify the risk of hospital admission or death from a fall in patients with an indication for antihypertensive treatment.

Design

Retrospective cohort study.

Setting

Primary care data from electronic health records contained within the UK Clinical Practice Research Datalink (CPRD).

Participants

Patients aged 40 years or older with at least one blood pressure measurement between 130 mm Hg and 179 mm Hg.

Main outcome measure

First serious fall, defined as hospital admission or death with a primary diagnosis of a fall within 10 years of the index date (12 months after cohort entry). Model development was conducted using a Fine-Gray approach in data from CPRD GOLD, accounting for the competing risk of death from other causes, with subsequent recalibration at one, five, and 10 years using pseudo values. External validation was conducted using data from CPRD Aurum, with performance assessed through calibration curves and the observed to expected ratio, C statistic, and D statistic, pooled across general practices, and clinical utility using decision curve analysis at thresholds around 10%.

Results

Analysis included 1 772 600 patients (experiencing 62 691 serious falls) from CPRD GOLD used in model development, and 3 805 366 (experiencing 206 956 serious falls) from CPRD Aurum in the external validation. The final model consisted of 24 predictors, including age, sex, ethnicity, alcohol consumption, living in an area of high social deprivation, a history of falls, multiple sclerosis, and prescriptions of antihypertensives, antidepressants, hypnotics, and anxiolytics. Upon external validation, the recalibrated model showed good discrimination, with pooled C statistics of 0.833 (95% confidence interval 0.831 to 0.835) and 0.843 (0.841 to 0.844) at five and 10 years, respectively. Original model calibration was poor on visual inspection and although this was improved with recalibration, under-prediction of risk remained (observed to expected ratio at 10 years 1.839, 95% confidence interval 1.811 to 1.865). Nevertheless, decision curve analysis suggests potential clinical utility, with net benefit larger than other strategies.

Conclusions

This prediction model uses commonly recorded clinical characteristics and distinguishes well between patients at high and low risk of falls in the next 1-10 years. Although miscalibration was evident on external validation, the model still had potential clinical utility around risk thresholds of 10% and so could be useful in routine clinical practice to help identify those at high risk of falls who might benefit from closer monitoring or early intervention to prevent future falls. Further studies are needed to explore the appropriate thresholds that maximise the model's clinical utility and cost effectiveness.",,pdf:https://www.bmj.com/content/bmj/379/bmj-2022-070918.full.pdf; doi:https://doi.org/10.1136/bmj-2022-070918; html:https://europepmc.org/articles/PMC9641577 35411997,https://doi.org/10.1111/tmi.13752,"Outcomes of laboratory-confirmed SARS-CoV-2 infection in the Omicron-driven fourth wave compared with previous waves in the Western Cape Province, South Africa.","Davies MA, Kassanjee R, Rousseau P, Morden E, Johnson L, Solomon W, Hsiao NY, Hussey H, Meintjes G, Paleker M, Jacobs T, Raubenheimer P, Heekes A, Dane P, Bam JL, Smith M, Preiser W, Pienaar D, Mendelson M, Naude J, Schrueder N, Mnguni A, Le Roux S, Murie K, Prozesky H, Mahomed H, Rossouw L, Wasserman S, Maughan D, Boloko L, Smith B, Taljaard J, Symons G, Ntusi NAB, Parker A, Wolter N, Jassat W, Cohen C, Lessells R, Wilkinson RJ, Arendse J, Kariem S, Moodley M, Wolmarans M, Cloete K, Boulle A, Western Cape and South African National Departments of Health in collaboration with the National Institute for Communicable Diseases in South Africa Affiliations.",,Tropical medicine & international health : TM & IH,2022,2022-05-10,Y,Vaccination; Immunity; DELTA; Sub-Saharan Africa; Covid-19; Prior Infection; Omicron,,,"

Objectives

The objective was to compare COVID-19 outcomes in the Omicron-driven fourth wave with prior waves in the Western Cape, assess the contribution of undiagnosed prior infection to differences in outcomes in a context of high seroprevalence due to prior infection and determine whether protection against severe disease conferred by prior infection and/or vaccination was maintained.

Methods

In this cohort study, we included public sector patients aged ≥20 years with a laboratory-confirmed COVID-19 diagnosis between 14 November and 11 December 2021 (wave four) and equivalent prior wave periods. We compared the risk between waves of the following outcomes using Cox regression: death, severe hospitalisation or death and any hospitalisation or death (all ≤14 days after diagnosis) adjusted for age, sex, comorbidities, geography, vaccination and prior infection.

Results

We included 5144 patients from wave four and 11,609 from prior waves. The risk of all outcomes was lower in wave four compared to the Delta-driven wave three (adjusted hazard ratio (aHR) [95% confidence interval (CI)] for death 0.27 [0.19; 0.38]. Risk reduction was lower when adjusting for vaccination and prior diagnosed infection (aHR: 0.41, 95% CI: 0.29; 0.59) and reduced further when accounting for unascertained prior infections (aHR: 0.72). Vaccine protection was maintained in wave four (aHR for outcome of death: 0.24; 95% CI: 0.10; 0.58).

Conclusions

In the Omicron-driven wave, severe COVID-19 outcomes were reduced mostly due to protection conferred by prior infection and/or vaccination, but intrinsically reduced virulence may account for a modest reduction in risk of severe hospitalisation or death compared to the Delta-driven wave.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/tmi.13752; doi:https://doi.org/10.1111/tmi.13752; html:https://europepmc.org/articles/PMC9115442; pdf:https://europepmc.org/articles/PMC9115442?pdf=render +36347531,https://doi.org/10.1136/bmj-2022-070918,Development and external validation of a risk prediction model for falls in patients with an indication for antihypertensive treatment: retrospective cohort study.,"Archer L, Koshiaris C, Lay-Flurrie S, Snell KIE, Riley RD, Stevens R, Banerjee A, Usher-Smith JA, Clegg A, Payne RA, Hobbs FDR, McManus RJ, Sheppard JP, STRAtifying Treatments In the multi-morbid Frail elderlY (STRATIFY) investigators.",,BMJ (Clinical research ed.),2022,2022-11-08,Y,,,,"

Objective

To develop and externally validate the STRAtifying Treatments In the multi-morbid Frail elderlY (STRATIFY)-Falls clinical prediction model to identify the risk of hospital admission or death from a fall in patients with an indication for antihypertensive treatment.

Design

Retrospective cohort study.

Setting

Primary care data from electronic health records contained within the UK Clinical Practice Research Datalink (CPRD).

Participants

Patients aged 40 years or older with at least one blood pressure measurement between 130 mm Hg and 179 mm Hg.

Main outcome measure

First serious fall, defined as hospital admission or death with a primary diagnosis of a fall within 10 years of the index date (12 months after cohort entry). Model development was conducted using a Fine-Gray approach in data from CPRD GOLD, accounting for the competing risk of death from other causes, with subsequent recalibration at one, five, and 10 years using pseudo values. External validation was conducted using data from CPRD Aurum, with performance assessed through calibration curves and the observed to expected ratio, C statistic, and D statistic, pooled across general practices, and clinical utility using decision curve analysis at thresholds around 10%.

Results

Analysis included 1 772 600 patients (experiencing 62 691 serious falls) from CPRD GOLD used in model development, and 3 805 366 (experiencing 206 956 serious falls) from CPRD Aurum in the external validation. The final model consisted of 24 predictors, including age, sex, ethnicity, alcohol consumption, living in an area of high social deprivation, a history of falls, multiple sclerosis, and prescriptions of antihypertensives, antidepressants, hypnotics, and anxiolytics. Upon external validation, the recalibrated model showed good discrimination, with pooled C statistics of 0.833 (95% confidence interval 0.831 to 0.835) and 0.843 (0.841 to 0.844) at five and 10 years, respectively. Original model calibration was poor on visual inspection and although this was improved with recalibration, under-prediction of risk remained (observed to expected ratio at 10 years 1.839, 95% confidence interval 1.811 to 1.865). Nevertheless, decision curve analysis suggests potential clinical utility, with net benefit larger than other strategies.

Conclusions

This prediction model uses commonly recorded clinical characteristics and distinguishes well between patients at high and low risk of falls in the next 1-10 years. Although miscalibration was evident on external validation, the model still had potential clinical utility around risk thresholds of 10% and so could be useful in routine clinical practice to help identify those at high risk of falls who might benefit from closer monitoring or early intervention to prevent future falls. Further studies are needed to explore the appropriate thresholds that maximise the model's clinical utility and cost effectiveness.",,pdf:https://www.bmj.com/content/bmj/379/bmj-2022-070918.full.pdf; doi:https://doi.org/10.1136/bmj-2022-070918; html:https://europepmc.org/articles/PMC9641577 31822727,https://doi.org/10.1038/s41598-019-55098-7,Co-incidence of RCC-susceptibility polymorphisms with HIF cis-acting sequences supports a pathway tuning model of cancer.,"Schmid V, Lafleur VN, Lombardi O, Li R, Salama R, Colli L, Choudhry H, Chanock S, Ratcliffe PJ, Mole DR.",,Scientific reports,2019,2019-12-10,Y,,Understanding the Causes of Disease,,"Emerging evidence suggests that dysregulation of oncogenic pathways requires precise tuning in order for cancer to develop. To test this, we examined the overlap between cis-acting elements of the hypoxia-inducible factor (HIF) pathway and cancer-susceptibility polymorphisms as defined in genome-wide association studies (GWAS). In renal cancer, where HIF is constitutively and un-physiologically activated by mutation of the von Hippel-Lindau tumour suppressor, we observed marked excess overlap, which extended to potential susceptibility polymorphisms that are below the conventional threshold applied in GWAS. In contrast, in other cancers where HIF is upregulated by different mechanisms, including micro-environmental hypoxia, we observed no excess in overlap. Our findings support a 'pathway tuning' model of cancer, whereby precise modulation of multiple outputs of specific, activated pathways is important in oncogenesis. This implies that selective pressures to modulate such pathways operate during cancer development and should focus attempts to identify their nature and consequences.",This study investigated the association between proteins responsible for DNA replication the susceptibility to cancer using GWAS. ,pdf:https://www.nature.com/articles/s41598-019-55098-7.pdf; doi:https://doi.org/10.1038/s41598-019-55098-7; html:https://europepmc.org/articles/PMC6904466; pdf:https://europepmc.org/articles/PMC6904466?pdf=render 31539079,https://doi.org/10.1001/jamanetworkopen.2019.11970,Association of Untargeted Urinary Metabolomics and Lung Cancer Risk Among Never-Smoking Women in China.,"Seow WJ, Shu XO, Nicholson JK, Holmes E, Walker DI, Hu W, Cai Q, Gao YT, Xiang YB, Moore SC, Bassig BA, Wong JYY, Zhang J, Ji BT, Boulangé CL, Kaluarachchi M, Wijeyesekera A, Zheng W, Elliott P, Rothman N, Lan Q.",,JAMA network open,2019,2019-09-04,Y,,Understanding the Causes of Disease,,"

Importance

Chinese women have the highest rate of lung cancer among female never-smokers in the world, and the etiology is poorly understood.

Objective

To assess the association between metabolomics and lung cancer risk among never-smoking women.

Design, setting, and participants

This nested case-control study included 275 never-smoking female patients with lung cancer and 289 never-smoking cancer-free control participants from the prospective Shanghai Women's Health Study recruited from December 28, 1996, to May 23, 2000. Validated food frequency questionnaires were used for the collection of dietary information. Metabolomic analysis was conducted from November 13, 2015, to January 6, 2016. Data analysis was conducted from January 6, 2016, to November 29, 2018.

Exposures

Untargeted ultra-high-performance liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance metabolomic profiles were characterized using prediagnosis urine samples. A total of 39 416 metabolites were measured.

Main outcomes and measures

Incident lung cancer.

Results

Among the 564 women, those who developed lung cancer (275 participants; median [interquartile range] age, 61.0 [52-65] years) and those who did not develop lung cancer (289 participants; median [interquartile range] age, 62.0 [53-66] years) at follow-up (median [interquartile range] follow-up, 10.9 [9.0-11.7] years) were similar in terms of their secondhand smoke exposure, history of respiratory diseases, and body mass index. A peak metabolite, identified as 5-methyl-2-furoic acid, was significantly associated with lower lung cancer risk (odds ratio, 0.57 [95% CI, 0.46-0.72]; P < .001; false discovery rate = 0.039). Furthermore, this peak was weakly correlated with self-reported dietary soy intake (ρ = 0.21; P < .001). Increasing tertiles of this metabolite were associated with lower lung cancer risk (in comparison with first tertile, odds ratio for second tertile, 0.52 [95% CI, 0.34-0.80]; and odds ratio for third tertile, 0.46 [95% CI, 0.30-0.70]), and the association was consistent across different histological subtypes and follow-up times. Additionally, metabolic pathway analysis found several systemic biological alterations that were associated with lung cancer risk, including 1-carbon metabolism, nucleotide metabolism, oxidative stress, and inflammation.

Conclusions and relevance

This prospective study of the untargeted urinary metabolome and lung cancer among never-smoking women in China provides support for the hypothesis that soy-based metabolites are associated with lower lung cancer risk in never-smoking women and suggests that biological processes linked to air pollution may be associated with higher lung cancer risk in this population.",,pdf:https://jamanetwork.com/journals/jamanetworkopen/articlepdf/2751559/seow_2019_oi_190459.pdf; doi:https://doi.org/10.1001/jamanetworkopen.2019.11970; html:https://europepmc.org/articles/PMC6755532 34022072,https://doi.org/10.1002/14651858.cd012721.pub3,Beta-blockers and inhibitors of the renin-angiotensin aldosterone system for chronic heart failure with preserved ejection fraction.,"Martin N, Manoharan K, Davies C, Lumbers RT.",,The Cochrane database of systematic reviews,2021,2021-05-22,N,,,,"

Background

Beta-blockers and inhibitors of the renin-angiotensin-aldosterone system improve survival and reduce morbidity in people with heart failure with reduced left ventricular ejection fraction (LVEF); a review of the evidence is required to determine whether these treatments are beneficial for people with heart failure with preserved ejection fraction (HFpEF).

Objectives

To assess the effects of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, and mineralocorticoid receptor antagonists in people with HFpEF.

Search methods

We updated searches of CENTRAL, MEDLINE, Embase, and one clinical trial register on 14 May 2020 to identify eligible studies, with no language or date restrictions. We checked references from trial reports and review articles for additional studies.  SELECTION CRITERIA: We included randomised controlled trials with a parallel group design, enrolling adults with HFpEF, defined by LVEF greater than 40%.

Data collection and analysis

We used standard methodological procedures expected by Cochrane.

Main results

We included 41 randomised controlled trials (231 reports), totalling 23,492 participants across all comparisons. The risk of bias was frequently unclear and only five studies had a low risk of bias in all domains. Beta-blockers (BBs) We included 10 studies (3087 participants) investigating BBs. Five studies used a placebo comparator and in five the comparator was usual care. The mean age of participants ranged from 30 years to 81 years. A possible reduction in cardiovascular mortality was observed (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.62 to 0.99; number needed to treat for an additional benefit (NNTB) 25; 1046 participants; three studies), however, the certainty of evidence was low. There may be little to no effect on all-cause mortality (RR 0.82, 95% CI 0.67 to 1.00; 1105 participants; four studies; low-certainty evidence). The effects on heart failure hospitalisation, hyperkalaemia, and quality of life remain uncertain. Mineralocorticoid receptor antagonists (MRAs) We included 13 studies (4459 participants) investigating MRA. Eight studies used a placebo comparator and in five the comparator was usual care. The mean age of participants ranged from 54.5 to 80 years. Pooled analysis indicated that MRA treatment probably reduces heart failure hospitalisation (RR 0.82, 95% CI 0.69 to 0.98; NNTB = 41; 3714 participants; three studies; moderate-certainty evidence). However, MRA treatment probably has little or no effect on all-cause mortality (RR 0.91, 95% CI 0.78 to 1.06; 4207 participants; five studies; moderate-certainty evidence) and cardiovascular mortality (RR 0.90, 95% CI 0.74 to 1.11; 4070 participants; three studies; moderate-certainty evidence). MRA treatment may have little or no effect on quality of life measures (mean difference (MD) 0.84, 95% CI -2.30 to 3.98; 511 participants; three studies; low-certainty evidence). MRA treatment was associated with a higher risk of hyperkalaemia (RR 2.11, 95% CI 1.77 to 2.51; number needed to treat for an additional harmful outcome (NNTH) = 11; 4291 participants; six studies; high-certainty evidence). Angiotensin-converting enzyme inhibitors (ACEIs) We included eight studies (2061 participants) investigating ACEIs. Three studies used a placebo comparator and in five the comparator was usual care. The mean age of participants ranged from 70 to 82 years. Pooled analyses with moderate-certainty evidence suggest that ACEI treatment likely has little or no effect on cardiovascular mortality (RR 0.93, 95% CI 0.61 to 1.42; 945 participants; two studies), all-cause mortality (RR 1.04, 95% CI 0.75 to 1.45; 1187 participants; five studies) and heart failure hospitalisation (RR 0.86, 95% CI 0.64 to 1.15; 1019 participants; three studies), and may result in little or no effect on the quality of life (MD -0.09, 95% CI -3.66 to 3.48; 154 participants; two studies; low-certainty evidence). The effects on hyperkalaemia remain uncertain. Angiotensin receptor blockers (ARBs) Eight studies (8755 participants) investigating ARBs were included. Five studies used a placebo comparator and in three the comparator was usual care. The mean age of participants ranged from 61 to 75 years. Pooled analyses with high certainty of evidence suggest that ARB treatment has little or no effect on cardiovascular mortality (RR 1.02, 95% 0.90 to 1.14; 7254 participants; three studies), all-cause mortality (RR 1.01, 95% CI 0.92 to 1.11; 7964 participants; four studies), heart failure hospitalisation (RR 0.92, 95% CI 0.83 to 1.02; 7254 participants; three studies), and quality of life (MD 0.41, 95% CI -0.86 to 1.67; 3117 participants; three studies). ARB was associated with a higher risk of hyperkalaemia (RR 1.88, 95% CI 1.07 to 3.33; 7148 participants; two studies; high-certainty evidence). Angiotensin receptor neprilysin inhibitors (ARNIs) Three studies (7702 participants) investigating ARNIs were included. Two studies used ARBs as the comparator and one used standardised medical therapy, based on participants' established treatments at enrolment. The mean age of participants ranged from 71 to 73 years. Results suggest that ARNIs may have little or no effect on cardiovascular mortality (RR 0.96, 95% CI 0.79 to 1.15; 4796 participants; one study; moderate-certainty evidence), all-cause mortality (RR 0.97, 95% CI 0.84 to 1.11; 7663 participants; three studies; high-certainty evidence), or quality of life (high-certainty evidence). However, ARNI treatment may result in a slight reduction in heart failure hospitalisation, compared to usual care (RR 0.89, 95% CI 0.80 to 1.00; 7362 participants; two studies; moderate-certainty evidence). ARNI treatment was associated with a reduced risk of hyperkalaemia compared with valsartan (RR 0.88, 95% CI 0.77 to 1.01; 5054 participants; two studies; moderate-certainty evidence).

Authors' conclusions

There is evidence that MRA and ARNI treatment in HFpEF probably reduces heart failure hospitalisation but probably has little or no effect on cardiovascular mortality and quality of life. BB treatment may reduce the risk of cardiovascular mortality, however, further trials are needed. The current evidence for BBs, ACEIs, and ARBs is limited and does not support their use in HFpEF in the absence of an alternative indication. Although MRAs and ARNIs are probably effective at reducing the risk of heart failure hospitalisation, the treatment effect sizes are modest. There is a need for improved approaches to patient stratification to identify the subgroup of patients who are most likely to benefit from MRAs and ARNIs, as well as for an improved understanding of disease biology, and for new therapeutic approaches.",,pdf:https://discovery.ucl.ac.uk/10044558/1/Lumbers_et_al-2017-.pdf; doi:https://doi.org/10.1002/14651858.CD012721.pub3; html:https://europepmc.org/articles/PMC8140651; pdf:https://europepmc.org/articles/PMC8140651?pdf=render; doi:https://doi.org/10.1002/14651858.cd012721.pub3 31477933,https://doi.org/10.1038/s41588-019-0484-x,A method for genome-wide genealogy estimation for thousands of samples.,"Speidel L, Forest M, Shi S, Myers SR.",,Nature genetics,2019,2019-09-02,N,,,,"Knowledge of genome-wide genealogies for thousands of individuals would simplify most evolutionary analyses for humans and other species, but has remained computationally infeasible. We have developed a method, Relate, scaling to >10,000 sequences while simultaneously estimating branch lengths, mutational ages and variable historical population sizes, as well as allowing for data errors. Application to 1,000 Genomes Project haplotypes produces joint genealogical histories for 26 human populations. Highly diverged lineages are present in all groups, but most frequent in Africa. Outside Africa, these mainly reflect ancient introgression from groups related to Neanderthals and Denisovans, while African signals instead reflect unknown events unique to that continent. Our approach allows more powerful inferences of natural selection than has previously been possible. We identify multiple regions under strong positive selection, and multi-allelic traits including hair color, body mass index and blood pressure, showing strong evidence of directional selection, varying among human groups.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610517; doi:https://doi.org/10.1038/s41588-019-0484-x; html:https://europepmc.org/articles/PMC7610517; pdf:https://europepmc.org/articles/PMC7610517?pdf=render; doi:https://doi.org/10.1038/s41588-019-0484-x 37946251,https://doi.org/10.1186/s13073-023-01240-0,Structural and non-coding variants increase the diagnostic yield of clinical whole genome sequencing for rare diseases.,"Pagnamenta AT, Camps C, Giacopuzzi E, Taylor JM, Hashim M, Calpena E, Kaisaki PJ, Hashimoto A, Yu J, Sanders E, Schwessinger R, Hughes JR, Lunter G, Dreau H, Ferla M, Lange L, Kesim Y, Ragoussis V, Vavoulis DV, Allroggen H, Ansorge O, Babbs C, Banka S, Baños-Piñero B, Beeson D, Ben-Ami T, Bennett DL, Bento C, Blair E, Brasch-Andersen C, Bull KR, Cario H, Cilliers D, Conti V, Davies EG, Dhalla F, Dacal BD, Dong Y, Dunford JE, Guerrini R, Harris AL, Hartley J, Hollander G, Javaid K, Kane M, Kelly D, Kelly D, Knight SJL, Kreins AY, Kvikstad EM, Langman CB, Lester T, Lines KE, Lord SR, Lu X, Mansour S, Manzur A, Maroofian R, Marsden B, Mason J, McGowan SJ, Mei D, Mlcochova H, Murakami Y, Németh AH, Okoli S, Ormondroyd E, Ousager LB, Palace J, Patel SY, Pentony MM, Pugh C, Rad A, Ramesh A, Riva SG, Roberts I, Roy N, Salminen O, Schilling KD, Scott C, Sen A, Smith C, Stevenson M, Thakker RV, Twigg SRF, Uhlig HH, van Wijk R, Vona B, Wall S, Wang J, Watkins H, Zak J, Schuh AH, Kini U, Wilkie AOM, Popitsch N, Taylor JC.",,Genome medicine,2023,2023-11-09,Y,Genome sequencing; Diagnostic Yield; Rare Diseases; Non-coding; Clinical Impact; Structural Variant; Splice Site Variant; Pipeline Optimisation; Bioinformatics Pipeline Development,,,"

Background

Whole genome sequencing is increasingly being used for the diagnosis of patients with rare diseases. However, the diagnostic yields of many studies, particularly those conducted in a healthcare setting, are often disappointingly low, at 25-30%. This is in part because although entire genomes are sequenced, analysis is often confined to in silico gene panels or coding regions of the genome.

Methods

We undertook WGS on a cohort of 122 unrelated rare disease patients and their relatives (300 genomes) who had been pre-screened by gene panels or arrays. Patients were recruited from a broad spectrum of clinical specialties. We applied a bioinformatics pipeline that would allow comprehensive analysis of all variant types. We combined established bioinformatics tools for phenotypic and genomic analysis with our novel algorithms (SVRare, ALTSPLICE and GREEN-DB) to detect and annotate structural, splice site and non-coding variants.

Results

Our diagnostic yield was 43/122 cases (35%), although 47/122 cases (39%) were considered solved when considering novel candidate genes with supporting functional data into account. Structural, splice site and deep intronic variants contributed to 20/47 (43%) of our solved cases. Five genes that are novel, or were novel at the time of discovery, were identified, whilst a further three genes are putative novel disease genes with evidence of causality. We identified variants of uncertain significance in a further fourteen candidate genes. The phenotypic spectrum associated with RMND1 was expanded to include polymicrogyria. Two patients with secondary findings in FBN1 and KCNQ1 were confirmed to have previously unidentified Marfan and long QT syndromes, respectively, and were referred for further clinical interventions. Clinical diagnoses were changed in six patients and treatment adjustments made for eight individuals, which for five patients was considered life-saving.

Conclusions

Genome sequencing is increasingly being considered as a first-line genetic test in routine clinical settings and can make a substantial contribution to rapidly identifying a causal aetiology for many patients, shortening their diagnostic odyssey. We have demonstrated that structural, splice site and intronic variants make a significant contribution to diagnostic yield and that comprehensive analysis of the entire genome is essential to maximise the value of clinical genome sequencing.",,doi:https://doi.org/10.1186/s13073-023-01240-0; html:https://europepmc.org/articles/PMC10636885; pdf:https://europepmc.org/articles/PMC10636885?pdf=render 34561430,https://doi.org/10.1038/s41467-021-25703-3,Cholesteryl ester transfer protein (CETP) as a drug target for cardiovascular disease.,"Schmidt AF, Hunt NB, Gordillo-Marañón M, Charoen P, Drenos F, Kivimaki M, Lawlor DA, Giambartolomei C, Papacosta O, Chaturvedi N, Bis JC, O'Donnell CJ, Wannamethee G, Wong A, Price JF, Hughes AD, Gaunt TR, Franceschini N, Mook-Kanamori DO, Zwierzyna M, Sofat R, Hingorani AD, Finan C.",,Nature communications,2021,2021-09-24,Y,,,,"Development of cholesteryl ester transfer protein (CETP) inhibitors for coronary heart disease (CHD) has yet to deliver licensed medicines. To distinguish compound from drug target failure, we compared evidence from clinical trials and drug target Mendelian randomization of CETP protein concentration, comparing this to Mendelian randomization of proprotein convertase subtilisin/kexin type 9 (PCSK9). We show that previous failures of CETP inhibitors are likely compound related, as illustrated by significant degrees of between-compound heterogeneity in effects on lipids, blood pressure, and clinical outcomes observed in trials. On-target CETP inhibition, assessed through Mendelian randomization, is expected to reduce the risk of CHD, heart failure, diabetes, and chronic kidney disease, while increasing the risk of age-related macular degeneration. In contrast, lower PCSK9 concentration is anticipated to decrease the risk of CHD, heart failure, atrial fibrillation, chronic kidney disease, multiple sclerosis, and stroke, while potentially increasing the risk of Alzheimer's disease and asthma. Due to distinct effects on lipoprotein metabolite profiles, joint inhibition of CETP and PCSK9 may provide added benefit. In conclusion, we provide genetic evidence that CETP is an effective target for CHD prevention but with a potential on-target adverse effect on age-related macular degeneration.",,pdf:https://www.nature.com/articles/s41467-021-25703-3.pdf; doi:https://doi.org/10.1038/s41467-021-25703-3; html:https://europepmc.org/articles/PMC8463530; pdf:https://europepmc.org/articles/PMC8463530?pdf=render -37414900,https://doi.org/10.1038/s41591-023-02429-x,A multi-ancestry polygenic risk score improves risk prediction for coronary artery disease.,"Patel AP, Wang M, Ruan Y, Koyama S, Clarke SL, Yang X, Tcheandjieu C, Agrawal S, Fahed AC, Ellinor PT, Genes & Health Research Team; the Million Veteran Program, Tsao PS, Sun YV, Cho K, Wilson PWF, Assimes TL, van Heel DA, Butterworth AS, Aragam KG, Natarajan P, Khera AV.",,Nature medicine,2023,2023-07-06,Y,,,,"Identification of individuals at highest risk of coronary artery disease (CAD)-ideally before onset-remains an important public health need. Prior studies have developed genome-wide polygenic scores to enable risk stratification, reflecting the substantial inherited component to CAD risk. Here we develop a new and significantly improved polygenic score for CAD, termed GPSMult, that incorporates genome-wide association data across five ancestries for CAD (>269,000 cases and >1,178,000 controls) and ten CAD risk factors. GPSMult strongly associated with prevalent CAD (odds ratio per standard deviation 2.14, 95% confidence interval 2.10-2.19, P < 0.001) in UK Biobank participants of European ancestry, identifying 20.0% of the population with 3-fold increased risk and conversely 13.9% with 3-fold decreased risk as compared with those in the middle quintile. GPSMult was also associated with incident CAD events (hazard ratio per standard deviation 1.73, 95% confidence interval 1.70-1.76, P < 0.001), identifying 3% of healthy individuals with risk of future CAD events equivalent to those with existing disease and significantly improving risk discrimination and reclassification. Across multiethnic, external validation datasets inclusive of 33,096, 124,467, 16,433 and 16,874 participants of African, European, Hispanic and South Asian ancestry, respectively, GPSMult demonstrated increased strength of associations across all ancestries and outperformed all available previously published CAD polygenic scores. These data contribute a new GPSMult for CAD to the field and provide a generalizable framework for how large-scale integration of genetic association data for CAD and related traits from diverse populations can meaningfully improve polygenic risk prediction.",,pdf:https://www.nature.com/articles/s41591-023-02429-x.pdf; doi:https://doi.org/10.1038/s41591-023-02429-x; html:https://europepmc.org/articles/PMC10353935; pdf:https://europepmc.org/articles/PMC10353935?pdf=render 37645200,https://doi.org/10.12688/openreseurope.13860.2,An agenda-setting paper on data sharing platforms: euCanSHare workshop.,"Devriendt T, Ammann C, W Asselbergs F, Bernier A, Costas R, Friedrich MG, Gelpi JL, Jarvelin MR, Kuulasmaa K, Lekadir K, Mayrhofer MT, Papez V, Pasterkamp G, Petersen SE, Schmidt CO, Schulz-Menger J, Söderberg S, Shabani M, Veronesi G, Viezzer DS, Borry P.",,Open research Europe,2021,2021-11-23,Y,data sharing; Incentives; Science Policy; Open Science; Data Infrastructure,,,"Various data sharing platforms are being developed to enhance the sharing of cohort data by addressing the fragmented state of data storage and access systems. However, policy challenges in several domains remain unresolved. The euCanSHare workshop was organized to identify and discuss these challenges and to set the future research agenda. Concerns over the multiplicity and long-term sustainability of platforms, lack of resources, access of commercial parties to medical data, credit and recognition mechanisms in academia and the organization of data access committees are outlined. Within these areas, solutions need to be devised to ensure an optimal functioning of platforms.",,doi:https://doi.org/10.12688/openreseurope.13860.2; html:https://europepmc.org/articles/PMC10445835; pdf:https://europepmc.org/articles/PMC10445835?pdf=render +37414900,https://doi.org/10.1038/s41591-023-02429-x,A multi-ancestry polygenic risk score improves risk prediction for coronary artery disease.,"Patel AP, Wang M, Ruan Y, Koyama S, Clarke SL, Yang X, Tcheandjieu C, Agrawal S, Fahed AC, Ellinor PT, Genes & Health Research Team; the Million Veteran Program, Tsao PS, Sun YV, Cho K, Wilson PWF, Assimes TL, van Heel DA, Butterworth AS, Aragam KG, Natarajan P, Khera AV.",,Nature medicine,2023,2023-07-06,Y,,,,"Identification of individuals at highest risk of coronary artery disease (CAD)-ideally before onset-remains an important public health need. Prior studies have developed genome-wide polygenic scores to enable risk stratification, reflecting the substantial inherited component to CAD risk. Here we develop a new and significantly improved polygenic score for CAD, termed GPSMult, that incorporates genome-wide association data across five ancestries for CAD (>269,000 cases and >1,178,000 controls) and ten CAD risk factors. GPSMult strongly associated with prevalent CAD (odds ratio per standard deviation 2.14, 95% confidence interval 2.10-2.19, P < 0.001) in UK Biobank participants of European ancestry, identifying 20.0% of the population with 3-fold increased risk and conversely 13.9% with 3-fold decreased risk as compared with those in the middle quintile. GPSMult was also associated with incident CAD events (hazard ratio per standard deviation 1.73, 95% confidence interval 1.70-1.76, P < 0.001), identifying 3% of healthy individuals with risk of future CAD events equivalent to those with existing disease and significantly improving risk discrimination and reclassification. Across multiethnic, external validation datasets inclusive of 33,096, 124,467, 16,433 and 16,874 participants of African, European, Hispanic and South Asian ancestry, respectively, GPSMult demonstrated increased strength of associations across all ancestries and outperformed all available previously published CAD polygenic scores. These data contribute a new GPSMult for CAD to the field and provide a generalizable framework for how large-scale integration of genetic association data for CAD and related traits from diverse populations can meaningfully improve polygenic risk prediction.",,pdf:https://www.nature.com/articles/s41591-023-02429-x.pdf; doi:https://doi.org/10.1038/s41591-023-02429-x; html:https://europepmc.org/articles/PMC10353935; pdf:https://europepmc.org/articles/PMC10353935?pdf=render 31317072,https://doi.org/10.1002/lrh2.10191,"Our data, our society, our health: A vision for inclusive and transparent health data science in the United Kingdom and beyond.","Ford E, Boyd A, Bowles JKF, Havard A, Aldridge RW, Curcin V, Greiver M, Harron K, Katikireddi V, Rodgers SE, Sperrin M.",,Learning health systems,2019,2019-03-25,Y,Transparency; Health Systems; Stakeholder Involvement; Data Flows; Health Data Science; Citizen‐driven Science,,,"The last 6 years have seen sustained investment in health data science in the United Kingdom and beyond, which should result in a data science community that is inclusive of all stakeholders, working together to use data to benefit society through the improvement of public health and well-being. However, opportunities made possible through the innovative use of data are still not being fully realised, resulting in research inefficiencies and avoidable health harms. In this paper, we identify the most important barriers to achieving higher productivity in health data science. We then draw on previous research, domain expertise, and theory to outline how to go about overcoming these barriers, applying our core values of inclusivity and transparency. We believe a step change can be achieved through meaningful stakeholder involvement at every stage of research planning, design, and execution and team-based data science, as well as harnessing novel and secure data technologies. Applying these values to health data science will safeguard a social licence for health data research and ensure transparent and secure data usage for public benefit.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/lrh2.10191; doi:https://doi.org/10.1002/lrh2.10191; html:https://europepmc.org/articles/PMC6628981; pdf:https://europepmc.org/articles/PMC6628981?pdf=render 35151371,https://doi.org/10.1016/j.immuni.2022.01.017,Immuno-proteomic profiling reveals aberrant immune cell regulation in the airways of individuals with ongoing post-COVID-19 respiratory disease.,"Vijayakumar B, Boustani K, Ogger PP, Papadaki A, Tonkin J, Orton CM, Ghai P, Suveizdyte K, Hewitt RJ, Desai SR, Devaraj A, Snelgrove RJ, Molyneaux PL, Garner JL, Peters JE, Shah PL, Lloyd CM, Harker JA.",,Immunity,2022,2022-01-26,Y,T cells; Proteomics; Respiratory Tract; Airways; Respiratory Viral Infection; Tissue-resident Memory; Covid-19; Sars-cov-2; Long Covid,,,"Some patients hospitalized with acute COVID-19 suffer respiratory symptoms that persist for many months. We delineated the immune-proteomic landscape in the airways and peripheral blood of healthy controls and post-COVID-19 patients 3 to 6 months after hospital discharge. Post-COVID-19 patients showed abnormal airway (but not plasma) proteomes, with an elevated concentration of proteins associated with apoptosis, tissue repair, and epithelial injury versus healthy individuals. Increased numbers of cytotoxic lymphocytes were observed in individuals with greater airway dysfunction, while increased B cell numbers and altered monocyte subsets were associated with more widespread lung abnormalities. A one-year follow-up of some post-COVID-19 patients indicated that these abnormalities resolved over time. In summary, COVID-19 causes a prolonged change to the airway immune landscape in those with persistent lung disease, with evidence of cell death and tissue repair linked to the ongoing activation of cytotoxic T cells.",,pdf:http://www.cell.com/article/S1074761322000462/pdf; doi:https://doi.org/10.1016/j.immuni.2022.01.017; html:https://europepmc.org/articles/PMC8789571; pdf:https://europepmc.org/articles/PMC8789571?pdf=render 34812717,https://doi.org/10.1099/mgen.0.000700,Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the healthcare environment: a bacterial genome-wide association study.,"Young BC, Wu CH, Charlesworth J, Earle S, Price JR, Gordon NC, Cole K, Dunn L, Liu E, Oakley S, Godwin H, Fung R, Miller R, Knox K, Votintseva A, Quan TP, Tilley R, Scarborough M, Crook DW, Peto TE, Walker AS, Llewelyn MJ, Wilson DJ.",,Microbial genomics,2021,2021-11-01,Y,Nosocomial infection; Bacterial Pathogens; Bacteraemia; Microbial Genomics; Microbial Epidemiology,,,"Staphylococcus aureus is a major bacterial pathogen in humans, and a dominant cause of severe bloodstream infections. Globally, antimicrobial resistance (AMR) in S. aureus remains challenging. While human risk factors for infection have been defined, contradictory evidence exists for the role of bacterial genomic variation in S. aureus disease. To investigate the contribution of bacterial lineage and genomic variation to the development of bloodstream infection, we undertook a genome-wide association study comparing bacteria from 1017 individuals with bacteraemia to 984 adults with asymptomatic S. aureus nasal carriage. Within 984 carriage isolates, we also compared healthcare-associated (HA) carriage with community-associated (CA) carriage. All major global lineages were represented in both bacteraemia and carriage, with no evidence for different infection rates. However, kmers tagging trimethoprim resistance-conferring mutation F99Y in dfrB were significantly associated with bacteraemia-vs-carriage (P=10-8.9-10-9.3). Pooling variation within genes, bacteraemia-vs-carriage was associated with the presence of mecA (HMP=10-5.3) as well as the presence of SCCmec (HMP=10-4.4). Among S. aureus carriers, no lineages were associated with HA-vs-CA carriage. However, we found a novel signal of HA-vs-CA carriage in the foldase protein prsA, where kmers representing conserved sequence allele were associated with CA carriage (P=10-7.1-10-19.4), while in gyrA, a ciprofloxacin resistance-conferring mutation, L84S, was associated with HA carriage (P=10-7.2). In an extensive study of S. aureus bacteraemia and nasal carriage in the UK, we found strong evidence that all S. aureus lineages are equally capable of causing bloodstream infection, and of being carried in the healthcare environment. Genomic variation in the foldase protein prsA is a novel genomic marker of healthcare origin in S. aureus but was not associated with bacteraemia. AMR determinants were associated with both bacteraemia and healthcare-associated carriage, suggesting that AMR increases the propensity not only to survive in healthcare environments, but also to cause invasive disease.",,doi:https://doi.org/10.1099/mgen.0.000700; doi:https://doi.org/10.1099/mgen.0.000700; html:https://europepmc.org/articles/PMC8743558; pdf:https://europepmc.org/articles/PMC8743558?pdf=render @@ -2457,14 +2457,14 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 33197716,https://doi.org/10.1016/j.media.2020.101871,Accurate brain age prediction with lightweight deep neural networks.,"Peng H, Gong W, Beckmann CF, Vedaldi A, Smith SM.",,Medical image analysis,2021,2020-10-19,Y,Neuroimaging; Predictive Analysis; Brain Age Prediction; Convolutional Neuralnetworks,,,"Deep learning has huge potential for accurate disease prediction with neuroimaging data, but the prediction performance is often limited by training-dataset size and computing memory requirements. To address this, we propose a deep convolutional neural network model, Simple Fully Convolutional Network (SFCN), for accurate prediction of brain age using T1-weighted structural MRI data. Compared with other popular deep network architectures, SFCN has fewer parameters, so is more compatible with small dataset size and 3D volume data. The network architecture was combined with several techniques for boosting performance, including data augmentation, pre-training, model regularization, model ensemble and prediction bias correction. We compared our overall SFCN approach with several widely-used machine learning models. It achieved state-of-the-art performance in UK Biobank data (N = 14,503), with mean absolute error (MAE) = 2.14y in brain age prediction and 99.5% in sex classification. SFCN also won (both parts of) the 2019 Predictive Analysis Challenge for brain age prediction, involving 79 competing teams (N = 2,638, MAE = 2.90y). We describe here the details of our approach, and its optimisation and validation. Our approach can easily be generalised to other tasks using different image modalities, and is released on GitHub.",,doi:https://doi.org/10.1016/j.media.2020.101871; doi:https://doi.org/10.1016/j.media.2020.101871; html:https://europepmc.org/articles/PMC7610710; pdf:https://europepmc.org/articles/PMC7610710?pdf=render 32907855,https://doi.org/10.1136/bmj.m3339,Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score.,"Knight SR, Ho A, Pius R, Buchan I, Carson G, Drake TM, Dunning J, Fairfield CJ, Gamble C, Green CA, Gupta R, Halpin S, Hardwick HE, Holden KA, Horby PW, Jackson C, Mclean KA, Merson L, Nguyen-Van-Tam JS, Norman L, Noursadeghi M, Olliaro PL, Pritchard MG, Russell CD, Shaw CA, Sheikh A, Solomon T, Sudlow C, Swann OV, Turtle LC, Openshaw PJ, Baillie JK, Semple MG, Docherty AB, Harrison EM, ISARIC4C investigators.",,BMJ (Clinical research ed.),2020,2020-09-09,Y,,,,"

Objective

To develop and validate a pragmatic risk score to predict mortality in patients admitted to hospital with coronavirus disease 2019 (covid-19).

Design

Prospective observational cohort study.

Setting

International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study (performed by the ISARIC Coronavirus Clinical Characterisation Consortium-ISARIC-4C) in 260 hospitals across England, Scotland, and Wales. Model training was performed on a cohort of patients recruited between 6 February and 20 May 2020, with validation conducted on a second cohort of patients recruited after model development between 21 May and 29 June 2020. PARTICIPANTS: Adults (age ≥18 years) admitted to hospital with covid-19 at least four weeks before final data extraction.

Main outcome measure

In-hospital mortality.

Results

35 463 patients were included in the derivation dataset (mortality rate 32.2%) and 22 361 in the validation dataset (mortality rate 30.1%). The final 4C Mortality Score included eight variables readily available at initial hospital assessment: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0-21 points). The 4C Score showed high discrimination for mortality (derivation cohort: area under the receiver operating characteristic curve 0.79, 95% confidence interval 0.78 to 0.79; validation cohort: 0.77, 0.76 to 0.77) with excellent calibration (validation: calibration-in-the-large=0, slope=1.0). Patients with a score of at least 15 (n=4158, 19%) had a 62% mortality (positive predictive value 62%) compared with 1% mortality for those with a score of 3 or less (n=1650, 7%; negative predictive value 99%). Discriminatory performance was higher than 15 pre-existing risk stratification scores (area under the receiver operating characteristic curve range 0.61-0.76), with scores developed in other covid-19 cohorts often performing poorly (range 0.63-0.73).

Conclusions

An easy-to-use risk stratification score has been developed and validated based on commonly available parameters at hospital presentation. The 4C Mortality Score outperformed existing scores, showed utility to directly inform clinical decision making, and can be used to stratify patients admitted to hospital with covid-19 into different management groups. The score should be further validated to determine its applicability in other populations.

Study registration

ISRCTN66726260.",,pdf:https://www.bmj.com/content/bmj/370/bmj.m3339.full.pdf; doi:https://doi.org/10.1136/bmj.m3339; html:https://europepmc.org/articles/PMC7116472; pdf:https://europepmc.org/articles/PMC7116472?pdf=render 35460409,https://doi.org/10.1093/ageing/afac090,New horizons in evidence-based care for older people: individual participant data meta-analysis.,"Clegg A, Bandeen-Roche K, Farrin A, Forster A, Gill TM, Gladman J, Kerse N, Lindley R, McManus RJ, Melis R, Mujica-Mota R, Raina P, Rockwood K, Teh R, van der Windt D, Witham M.",,Age and ageing,2022,2022-04-01,Y,Ageing; Meta-analysis; Frailty; Older People; Stratified Care; Individual Participant Data,,,"Evidence-based decisions on clinical and cost-effectiveness of interventions are ideally informed by meta-analyses of intervention trial data. However, when undertaken, such meta-analyses in ageing research have typically been conducted using standard methods whereby summary (aggregate) data are extracted from published trial reports. Although meta-analysis of aggregate data can provide useful insights into the average effect of interventions within a selected trial population, it has limitations regarding robust conclusions on which subgroups of people stand to gain the greatest benefit from an intervention or are at risk of experiencing harm. Future evidence synthesis using individual participant data from ageing research trials for meta-analysis could transform understanding of the effectiveness of interventions for older people, supporting evidence-based and sustainable commissioning. A major advantage of individual participant data meta-analysis (IPDMA) is that it enables examination of characteristics that predict treatment effects, such as frailty, disability, cognitive impairment, ethnicity, gender and other wider determinants of health. Key challenges of IPDMA relate to the complexity and resources needed for obtaining, managing and preparing datasets, requiring a meticulous approach involving experienced researchers, frequently with expertise in designing and analysing clinical trials. In anticipation of future IPDMA work in ageing research, we are establishing an international Ageing Research Trialists collective, to bring together trialists with a common focus on transforming care for older people as a shared ambition across nations.",,pdf:https://academic.oup.com/ageing/article-pdf/51/4/afac090/43408856/afac090.pdf; doi:https://doi.org/10.1093/ageing/afac090; html:https://europepmc.org/articles/PMC9034697; pdf:https://europepmc.org/articles/PMC9034697?pdf=render -38839884,https://doi.org/10.1038/s41588-024-01763-1,"Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction.","Schormair B, Zhao C, Bell S, Didriksen M, Nawaz MS, Schandra N, Stefani A, Högl B, Dauvilliers Y, Bachmann CG, Kemlink D, Sonka K, Paulus W, Trenkwalder C, Oertel WH, Hornyak M, Teder-Laving M, Metspalu A, Hadjigeorgiou GM, Polo O, Fietze I, Ross OA, Wszolek ZK, Ibrahim A, Bergmann M, Kittke V, Harrer P, Dowsett J, Chenini S, Ostrowski SR, Sørensen E, Erikstrup C, Pedersen OB, Topholm Bruun M, Nielsen KR, Butterworth AS, Soranzo N, Ouwehand WH, Roberts DJ, Danesh J, Burchell B, Furlotte NA, Nandakumar P, 23andMe Research Team, D.E.S.I.R. study group, Earley CJ, Ondo WG, Xiong L, Desautels A, Perola M, Vodicka P, Dina C, Stoll M, Franke A, Lieb W, Stewart AFR, Shah SH, Gieger C, Peters A, Rye DB, Rouleau GA, Berger K, Stefansson H, Ullum H, Stefansson K, Hinds DA, Di Angelantonio E, Oexle K, Winkelmann J.",,Nature genetics,2024,2024-06-05,N,,,,"Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes (rg = 0.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC) = 0.82-0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction.",,pdf:https://www.nature.com/articles/s41588-024-01763-1.pdf; doi:https://doi.org/10.1038/s41588-024-01763-1 34767815,https://doi.org/10.1016/j.jid.2021.08.446,"Differences in Clinical Features and Comorbid Burden between HLA-C∗06:02 Carrier Groups in >9,000 People with Psoriasis.","Douroudis K, Ramessur R, Barbosa IA, Baudry D, Duckworth M, Angit C, Capon F, Chung R, Curtis CJ, Di Meglio P, Goulding JMR, Griffiths CEM, Lee SH, Mahil SK, Parslew R, Reynolds NJ, Shipman AR, Warren RB, Yiu ZZN, Simpson MA, Barker JN, Dand N, Smith CH, BADBIR, BSTOP Study Groups.",,The Journal of investigative dermatology,2022,2021-11-10,N,,,,"The identification of robust endotypes-disease subgroups of clinical relevance-is fundamental to stratified medicine. We hypothesized that HLA-C∗06:02 status, the major genetic determinant of psoriasis, defines a psoriasis endotype of clinical relevance. Using two United Kingdom-based cross-sectional datasets-an observational severe-psoriasis study (Biomarkers of Systemic Treatment Outcomes in Psoriasis; n = 3,767) and a large population-based bioresource (UK Biobank, including n = 5,519 individuals with psoriasis)-we compared demographic, environmental, and clinical variables of interest in HLA-C∗06:02-positive (one or two copies of the HLA-C∗06:02 allele) with those in HLA-C∗06:02‒negative (no copies) individuals of European ancestry. We used multivariable regression analyses to account for mediation effects established a priori. We confirm previous observations that HLA-C∗06:02-positive status is associated with earlier age of psoriasis onset and extend findings to reveal an association with disease expressivity in females (Biomarkers of Systemic Treatment Outcomes in Psoriasis: P = 2.7 × 10-14, UK Biobank: P = 1.0 × 10-8). We also show HLA-C∗06:02-negative status to be associated with characteristic clinical features (large plaque disease, OR for HLA-C∗06:02 = 0.73, P = 7.4 × 10-4; nail involvement, OR = 0.70, P = 2.4 × 10-6); higher central adiposity (Biomarkers of Systemic Treatment Outcomes in Psoriasis: waist circumference difference of 2.0 cm, P = 8.4 × 10-4; UK Biobank: waist circumference difference of 1.4 cm, P = 1.5 × 10-4), especially in women; and a higher prevalence of other cardiometabolic comorbidities. These findings extend the clinical phenotype delineated by HLA-C∗06:02 and highlight its potential as an important biomarker to consider in future multimarker stratified medicine approaches.",,pdf:http://www.jidonline.org/article/S0022202X21024738/pdf; doi:https://doi.org/10.1016/j.jid.2021.08.446 +38839884,https://doi.org/10.1038/s41588-024-01763-1,"Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction.","Schormair B, Zhao C, Bell S, Didriksen M, Nawaz MS, Schandra N, Stefani A, Högl B, Dauvilliers Y, Bachmann CG, Kemlink D, Sonka K, Paulus W, Trenkwalder C, Oertel WH, Hornyak M, Teder-Laving M, Metspalu A, Hadjigeorgiou GM, Polo O, Fietze I, Ross OA, Wszolek ZK, Ibrahim A, Bergmann M, Kittke V, Harrer P, Dowsett J, Chenini S, Ostrowski SR, Sørensen E, Erikstrup C, Pedersen OB, Topholm Bruun M, Nielsen KR, Butterworth AS, Soranzo N, Ouwehand WH, Roberts DJ, Danesh J, Burchell B, Furlotte NA, Nandakumar P, 23andMe Research Team, D.E.S.I.R. study group, Earley CJ, Ondo WG, Xiong L, Desautels A, Perola M, Vodicka P, Dina C, Stoll M, Franke A, Lieb W, Stewart AFR, Shah SH, Gieger C, Peters A, Rye DB, Rouleau GA, Berger K, Stefansson H, Ullum H, Stefansson K, Hinds DA, Di Angelantonio E, Oexle K, Winkelmann J.",,Nature genetics,2024,2024-06-05,N,,,,"Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes (rg = 0.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC) = 0.82-0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction.",,pdf:https://www.nature.com/articles/s41588-024-01763-1.pdf; doi:https://doi.org/10.1038/s41588-024-01763-1 31479209,https://doi.org/10.1056/nejmoa1907096,A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI.,"Claassens DMF, Vos GJA, Bergmeijer TO, Hermanides RS, van 't Hof AWJ, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, Asselbergs FW, Mosterd A, Herrman JR, Dewilde WJM, Janssen PWA, Kelder JC, Postma MJ, de Boer A, Boersma C, Deneer VHM, Ten Berg JM.",,The New England journal of medicine,2019,2019-09-03,N,,Better Care,cardiovascular,"

Background

It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y12 inhibitors.

Methods

We conducted a randomized, open-label, assessor-blinded trial in which patients undergoing primary PCI with stent implantation were assigned in a 1:1 ratio to receive either a P2Y12 inhibitor on the basis of early CYP2C19 genetic testing (genotype-guided group) or standard treatment with either ticagrelor or prasugrel (standard-treatment group) for 12 months. In the genotype-guided group, carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and noncarriers received clopidogrel. The two primary outcomes were net adverse clinical events - defined as death from any cause, myocardial infarction, definite stent thrombosis, stroke, or major bleeding defined according to Platelet Inhibition and Patient Outcomes (PLATO) criteria - at 12 months (primary combined outcome; tested for noninferiority, with a noninferiority margin of 2 percentage points for the absolute difference) and PLATO major or minor bleeding at 12 months (primary bleeding outcome).

Results

For the primary analysis, 2488 patients were included: 1242 in the genotype-guided group and 1246 in the standard-treatment group. The primary combined outcome occurred in 63 patients (5.1%) in the genotype-guided group and in 73 patients (5.9%) in the standard-treatment group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.0 to 0.7; P<0.001 for noninferiority). The primary bleeding outcome occurred in 122 patients (9.8%) in the genotype-guided group and in 156 patients (12.5%) in the standard-treatment group (hazard ratio, 0.78; 95% CI, 0.61 to 0.98; P = 0.04).

Conclusions

In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy for selection of oral P2Y12 inhibitor therapy was noninferior to standard treatment with ticagrelor or prasugrel at 12 months with respect to thrombotic events and resulted in a lower incidence of bleeding. (Funded by the Netherlands Organization for Health Research and Development; POPular Genetics ClinicalTrials.gov number, NCT01761786; Netherlands Trial Register number, NL2872.).",,pdf:https://pure.rug.nl/ws/files/99703867/A_Genotype_Guided_Strategy_for_Oral_P2Y12_Inhibitors_in_Primary_PCI.pdf; doi:https://doi.org/10.1056/NEJMoa1907096 31775616,https://doi.org/10.1186/s12859-019-3201-y,Manhattan++: displaying genome-wide association summary statistics with multiple annotation layers.,"Grace C, Farrall M, Watkins H, Goel A.",,BMC bioinformatics,2019,2019-11-27,Y,Software; Meta-analysis; Gwas; R; Cran; Manhattan Plot,,,"

Background

Over the last 10 years, there have been over 3300 genome-wide association studies (GWAS). Almost every GWAS study provides a Manhattan plot either as a main figure or in the supplement. Several software packages can generate a Manhattan plot, but they are all limited in the extent to which they can annotate gene-names, allele frequencies, and variants having high impact on gene function or provide any other added information or flexibility. Furthermore, in a conventional Manhattan plot, there is no way of distinguishing a locus identified due to a single variant with very significant p-value from a locus with multiple variants which appear to be in a haplotype block having very similar p-values.

Results

Here we present a software tool written in R, which generates a transposed Manhattan plot along with additional features like variant consequence and minor allele frequency to annotate the plot and addresses these limitations. The software also gives flexibility on how and where the user wants to display the annotations. The software can be downloaded from CRAN repository and also from the GitHub project page.

Conclusions

We present a major step up to the existing conventional Manhattan plot generation tools. We hope this form of display along with the added annotations will bring more insight to the reader from this new Manhattan++ plot.",,pdf:https://bmcbioinformatics.biomedcentral.com/track/pdf/10.1186/s12859-019-3201-y; doi:https://doi.org/10.1186/s12859-019-3201-y; html:https://europepmc.org/articles/PMC6882345; pdf:https://europepmc.org/articles/PMC6882345?pdf=render 34672950,https://doi.org/10.1016/s2213-2600(21)00435-5,"Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,The Lancet. Respiratory medicine,2021,2021-10-18,Y,,,,"

Background

Colchicine has been proposed as a treatment for COVID-19 based on its anti-inflammatory actions. We aimed to evaluate the efficacy and safety of colchicine in patients admitted to hospital with COVID-19.

Methods

In this streamlined, randomised, controlled, open-label trial, underway at 177 hospitals in the UK, two hospitals in Indonesia, and two hospitals in Nepal, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Patients were eligible for inclusion in the study if they were admitted to hospital with clinically suspected or laboratory confirmed SARS-CoV-2 infection and had no medical history that might, in the opinion of the attending clinician, put the patient at significant risk if they were to participate in the trial. Eligible and consenting adults were randomly assigned (1:1) to receive either usual standard of care alone (usual care group) or usual standard of care plus colchicine (colchicine group) using web-based simple (unstratified) randomisation with allocation concealment. Participants received colchicine 1 mg after randomisation followed by 500 μg 12 h later and then 500 μg twice a day by mouth or nasogastric tube for 10 days in total or until discharge. Dose frequency was halved for patients receiving a moderate CYP3A4 inhibitor (eg, diltiazem), patients with an estimated glomerular filtration rate of less than 30 mL/min per 1·73m2, and those with an estimated bodyweight of less than 70 kg. The primary outcome was 28-day mortality, secondary endpoints included time to discharge, the proportion of patients discharged from hospital within 28 days, and, in patients not on invasive mechanical ventilation at randomisation, a composite endpoint of invasive mechanical ventilation or death. All analyses were by intention-to-treat. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.

Findings

Between Nov 27, 2020, and March 4, 2021, 11 340 (58%) of 19 423 patients enrolled into the RECOVERY trial were eligible to receive colchicine; 5610 (49%) patients were randomly assigned to the colchicine group and 5730 (51%) to the usual care group. Overall, 1173 (21%) patients in the colchicine group and 1190 (21%) patients in the usual care group died within 28 days (rate ratio 1·01 [95% CI 0·93 to 1·10]; p=0·77). Consistent results were seen in all prespecified subgroups of patients. Median time to discharge alive (10 days [IQR 5 to >28]) was the same in both groups, and there was no significant difference in the proportion of patients discharged from hospital alive within 28 days (3901 [70%] patients in the colchicine group and 4032 [70%] usual care group; rate ratio 0·98 [95% CI 0·94 to 1·03]; p=0·44). In those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (1344 [25%] in the colchicine group vs 1343 [25%] patients in the usual care group; risk ratio 1·02 [95% CI 0·96 to 1·09]; p=0·47).

Interpretation

In adults hospitalised with COVID-19, colchicine was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death.

Funding

UK Research and Innovation (Medical Research Council), National Institute of Health Research, and Wellcome Trust.",,pdf:http://www.thelancet.com/article/S2213260021004355/pdf; doi:https://doi.org/10.1016/S2213-2600(21)00435-5; html:https://europepmc.org/articles/PMC8523117 36315390,https://doi.org/10.1002/eat.23834,"Risk and protective factors for new-onset binge eating, low weight, and self-harm symptoms in >35,000 individuals in the UK during the COVID-19 pandemic.","Davies HL, Hübel C, Herle M, Kakar S, Mundy J, Peel AJ, Ter Kuile AR, Zvrskovec J, Monssen D, Lim KX, Davies MR, Palmos AB, Lin Y, Kalsi G, Rogers HC, Bristow S, Glen K, Malouf CM, Kelly EJ, Purves KL, Young KS, Hotopf M, Armour C, McIntosh AM, Eley TC, Treasure J, Breen G.",,The International journal of eating disorders,2023,2022-10-31,Y,Mental health; Psychiatric disorders; Eating Disorders; Comorbidity; Suicidal Ideation,,,"

Objective

The disruption caused by the COVID-19 pandemic has been associated with poor mental health, including increases in eating disorders and self-harm symptoms. We investigated risk and protective factors for the new onset of these symptoms during the pandemic.

Method

Data were from the COVID-19 Psychiatry and Neurological Genetics study and the Repeated Assessment of Mental health in Pandemics Study (n = 36,715). Exposures were socio-demographic characteristics, lifetime psychiatric disorder, and COVID-related variables, including SARS-CoV-2 infection/illness with COVID-19. We identified four subsamples of participants without pre-pandemic experience of our outcomes: binge eating (n = 24,211), low weight (n = 24,364), suicidal and/or self-harm ideation (n = 18,040), and self-harm (n = 29,948). Participants reported on our outcomes at frequent intervals (fortnightly to monthly). We fitted multiple logistic regression models to identify factors associated with the new onset of our outcomes.

Results

Within each subsample, new onset was reported by: 21% for binge eating, 10.8% for low weight, 23.5% for suicidal and/or self-harm ideation, and 3.5% for self-harm. Shared risk factors included having a lifetime psychiatric disorder, not being in paid employment, higher pandemic worry scores, and being racially minoritized. Conversely, infection with SARS-CoV-2/illness with COVID-19 was linked to lower odds of binge eating, low weight, and suicidal and/or self-harm ideation.

Discussion

Overall, we detected shared risk factors that may drive the comorbidity between eating disorders and self-harm. Subgroups of individuals with these risk factors may require more frequent monitoring during future pandemics.

Public significance

In a sample of 35,000 UK residents, people who had a psychiatric disorder, identified as being part of a racially minoritized group, were not in paid employment, or were more worried about the pandemic were more likely to experience binge eating, low weight, suicidal and/or self-harm ideation, and self-harm for the first time during the pandemic. People with these risk factors may need particular attention during future pandemics to enable early identification of new psychiatric symptoms.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/eat.23834; doi:https://doi.org/10.1002/eat.23834; html:https://europepmc.org/articles/PMC9874817; pdf:https://europepmc.org/articles/PMC9874817?pdf=render -32762905,https://doi.org/10.1016/j.jacc.2020.06.024,Validation of a Genome-Wide Polygenic Score for Coronary Artery Disease in South Asians.,"Wang M, Menon R, Mishra S, Patel AP, Chaffin M, Tanneeru D, Deshmukh M, Mathew O, Apte S, Devanboo CS, Sundaram S, Lakshmipathy P, Murugan S, Sharma KK, Rajendran K, Santhosh S, Thachathodiyl R, Ahamed H, Balegadde AV, Alexander T, Swaminathan K, Gupta R, Mullasari AS, Sigamani A, Kanchi M, Peterson AS, Butterworth AS, Danesh J, Di Angelantonio E, Naheed A, Inouye M, Chowdhury R, Vedam RL, Kathiresan S, Gupta R, Khera AV.",,Journal of the American College of Cardiology,2020,2020-08-01,N,coronary artery disease; Genomic Medicine; South Asian; Polygenic Score,,,"

Background

Genome-wide polygenic scores (GPS) integrate information from many common DNA variants into a single number. Because rates of coronary artery disease (CAD) are substantially higher among South Asians, a GPS to identify high-risk individuals may be particularly useful in this population.

Objectives

This analysis used summary statistics from a prior genome-wide association study to derive a new GPSCAD for South Asians.

Methods

This GPSCAD was validated in 7,244 South Asian UK Biobank participants and tested in 491 individuals from a case-control study in Bangladesh. Next, a static ancestry and GPSCAD reference distribution was built using whole-genome sequencing from 1,522 Indian individuals, and a framework was tested for projecting individuals onto this static ancestry and GPSCAD reference distribution using 1,800 CAD cases and 1,163 control subjects newly recruited in India.

Results

The GPSCAD, containing 6,630,150 common DNA variants, had an odds ratio (OR) per SD of 1.58 in South Asian UK Biobank participants and 1.60 in the Bangladeshi study (p < 0.001 for each). Next, individuals of the Indian case-control study were projected onto static reference distributions, observing an OR/SD of 1.66 (p < 0.001). Compared with the middle quintile, risk for CAD was most pronounced for those in the top 5% of the GPSCAD distribution-ORs of 4.16, 2.46, and 3.22 in the South Asian UK Biobank, Bangladeshi, and Indian studies, respectively (p < 0.05 for each).

Conclusions

The new GPSCAD has been developed and tested using 3 distinct South Asian studies, and provides a generalizable framework for ancestry-specific GPS assessment.",,doi:https://doi.org/10.1016/j.jacc.2020.06.024; doi:https://doi.org/10.1016/j.jacc.2020.06.024; html:https://europepmc.org/articles/PMC7592606; pdf:https://europepmc.org/articles/PMC7592606?pdf=render; doi:https://doi.org/10.1016/j.jacc.2020.06.024 31115347,https://doi.org/10.2196/12412,Health Data Processes: A Framework for Analyzing and Discussing Efficient Use and Reuse of Health Data With a Focus on Patient-Reported Outcome Measures.,"Hjollund NHI, Valderas JM, Kyte D, Calvert MJ.",,Journal of medical Internet research,2019,2019-05-21,Y,Data collection; Medical Informatics; Patient-physician Relationship; Patient-reported Outcome,,,"The collection and use of patient health data are central to any kind of activity in the health care system. These data may be produced during routine clinical processes or obtained directly from the patient using patient-reported outcome (PRO) measures. Although efficiency and other reasons justify data availability for a range of potentially relevant uses, these data are nearly always collected for a single specific purpose. The health care literature reflects this narrow scope, and there is limited literature on the joint use of health data for daily clinical use, clinical research, surveillance, and administrative purposes. The aim of this paper is to provide a framework for discussing the efficient use of health data with a specific focus on the role of PRO measures. PRO data may be used at an individual patient level to inform patient care or shared decision making and to tailor care to individual needs or group-level needs as a complement to health record data, such as that on mortality and readmission, in order to inform service delivery and measure the real-world effectiveness of treatment. PRO measures may be used either for their own sake, to provide valuable information from the patient perspective, or as a proxy for clinical data that would otherwise not be feasible to collect. We introduce a framework to analyze any health care activity that involves health data. The framework consists of four data processes (patient identification, data collection, data aggregation and data use), further structured into two dichotomous dimensions in each data process (level: group vs patient; timeframe: ad hoc vs systematic). This framework is used to analyze various health activities with respect to joint use of data, considering the technical, legal, organizational, and logistical challenges that characterize each data process. Finally, we propose a model for joint use of health data with data collected during follow-up as a base. Demands for health data will continue to increase, which will further add to the need for the concerted use and reuse of PRO data for parallel purposes. Repeated and uncoordinated PRO data collection for the same patient for different purposes results in misuse of resources for the patient and the health care system as well as reduced response rates owing to questionnaire fatigue. PRO data can be routinely collected both at the hospital (from inpatients as well as outpatients) and outside of hospital settings; in primary or social care settings; or in the patient's home, provided the health informatics infrastructure is in place. In the future, clinical settings are likely to be a prominent source of PRO data; however, we are also likely to see increased remote collection of PRO data by patients in their own home (telePRO). Data collection for research and quality surveillance will have to adapt to this circumstance and adopt complementary data capture methods that take advantage of the utility of PRO data collected during daily clinical practice. The European Union's regulation with respect to the protection of personal data-General Data Protection Regulation-imposes severe restrictions on the use of health data for parallel purposes, and steps should be taken to alleviate the consequences while still protecting personal data against misuse.",,pdf:https://www.jmir.org/2019/5/e12412/PDF; doi:https://doi.org/10.2196/12412; html:https://europepmc.org/articles/PMC6547770 +32762905,https://doi.org/10.1016/j.jacc.2020.06.024,Validation of a Genome-Wide Polygenic Score for Coronary Artery Disease in South Asians.,"Wang M, Menon R, Mishra S, Patel AP, Chaffin M, Tanneeru D, Deshmukh M, Mathew O, Apte S, Devanboo CS, Sundaram S, Lakshmipathy P, Murugan S, Sharma KK, Rajendran K, Santhosh S, Thachathodiyl R, Ahamed H, Balegadde AV, Alexander T, Swaminathan K, Gupta R, Mullasari AS, Sigamani A, Kanchi M, Peterson AS, Butterworth AS, Danesh J, Di Angelantonio E, Naheed A, Inouye M, Chowdhury R, Vedam RL, Kathiresan S, Gupta R, Khera AV.",,Journal of the American College of Cardiology,2020,2020-08-01,N,coronary artery disease; Genomic Medicine; South Asian; Polygenic Score,,,"

Background

Genome-wide polygenic scores (GPS) integrate information from many common DNA variants into a single number. Because rates of coronary artery disease (CAD) are substantially higher among South Asians, a GPS to identify high-risk individuals may be particularly useful in this population.

Objectives

This analysis used summary statistics from a prior genome-wide association study to derive a new GPSCAD for South Asians.

Methods

This GPSCAD was validated in 7,244 South Asian UK Biobank participants and tested in 491 individuals from a case-control study in Bangladesh. Next, a static ancestry and GPSCAD reference distribution was built using whole-genome sequencing from 1,522 Indian individuals, and a framework was tested for projecting individuals onto this static ancestry and GPSCAD reference distribution using 1,800 CAD cases and 1,163 control subjects newly recruited in India.

Results

The GPSCAD, containing 6,630,150 common DNA variants, had an odds ratio (OR) per SD of 1.58 in South Asian UK Biobank participants and 1.60 in the Bangladeshi study (p < 0.001 for each). Next, individuals of the Indian case-control study were projected onto static reference distributions, observing an OR/SD of 1.66 (p < 0.001). Compared with the middle quintile, risk for CAD was most pronounced for those in the top 5% of the GPSCAD distribution-ORs of 4.16, 2.46, and 3.22 in the South Asian UK Biobank, Bangladeshi, and Indian studies, respectively (p < 0.05 for each).

Conclusions

The new GPSCAD has been developed and tested using 3 distinct South Asian studies, and provides a generalizable framework for ancestry-specific GPS assessment.",,doi:https://doi.org/10.1016/j.jacc.2020.06.024; doi:https://doi.org/10.1016/j.jacc.2020.06.024; html:https://europepmc.org/articles/PMC7592606; pdf:https://europepmc.org/articles/PMC7592606?pdf=render; doi:https://doi.org/10.1016/j.jacc.2020.06.024 30842207,https://doi.org/10.1136/heartjnl-2019-314763,Proprotein convertase subtilisin/kexin 9 inhibitors in reducing cardiovascular outcomes: a systematic review and meta-analysis.,"Du H, Li X, Su N, Li L, Hao X, Gao H, Kwong JS, Vandvik PO, Yang X, Nemeth I, Mordi IR, Li Q, Zhang L, Rao L, Lang CC, Li J, Tian H, Li S.",,Heart (British Cardiac Society),2019,2019-03-06,N,Cardiovascular disease; Systematic review; Lipid-lowering Drugs; Low-density Lipoprotein Cholesterol; Proprotein Convertase Subtilisin/kexin Type 9 Inhibitors,,,"

Background

To evaluate the effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors on major adverse cardiovascular events (MACE).

Methods

Our systematic review included randomised controlled trials if they studied PCSK9 inhibitors in patients for primary and/or secondary prevention of cardiovascular diseases or with hypercholesterolaemia/hyperlipidaemia. Dichotomous variables from individual studies were pooled by relative risks (RR) and their 95% CIs using the random-effect model. Risk difference (RD) in the 10-year frame was also estimated using the pooled RR and the estimated baseline risk using the control group. Grading of Recommendation Assessment, Development and Evaluation was used to assess the quality of evidence.

Results

We included 54 trials with 97 910 patients in the analysis. Compared with controls, PCSK9 inhibitors significantly reduced the risk of MACE by 16% (RR, 0.84; 95% CI 0.79 to 0.89; RD: 47 fewer per 1000 vs 286 as the baseline risk; 95% CI 32 to 59 fewer), non-fatal myocardial infarction (MI) by 17% (RR, 0.83; 95% CI 0.74 to 0.93; RD, 35 fewer per 1000 vs 207 as the baseline; 95% CI 13 to 53 fewer) and any stroke by 25% (RR, 0.75; 95% CI 0.65 to 0.85; RD, 16 fewer per 1000 vs 61 as the baseline; 95% CI 9 to 21 fewer) with moderate quality evidence. No significant differences were found between PCSK9 inhibitors and control groups in all-cause mortality, cardiovascular death, heart failure or unstable angina with low-quality evidence.

Conclusions

This study demonstrated that PCSK9 inhibitors could significantly reduce the risk of MACE, non-fatal MI and stroke.

Trial registration

PROSPERO; CRD42017073904.",,pdf:https://discovery.dundee.ac.uk/ws/files/30348534/Author_Accepted_Manuscript.pdf; doi:https://doi.org/10.1136/heartjnl-2019-314763 34600575,https://doi.org/10.1186/s13104-021-05789-0,"Application of ensemble clustering and survival tree analysis for identifying prognostic clinicogenomic features in patients with colorectal cancer from the 100,000 Genomes Project.","Wei Y, Papachristou N, Mueller S, Genomics England Research Consortium, Chang WH, Lai AG.",,BMC research notes,2021,2021-10-02,Y,,,,"

Objective

The objective of this study was to employ ensemble clustering and tree-based risk model approaches to identify interactions between clinicogenomic features for colorectal cancer using the 100,000 Genomes Project.

Results

Among the 2211 patients with colorectal cancer (mean age of diagnosis: 67.7; 59.7% male), 16.3%, 36.3%, 39.0% and 8.4% had stage 1, 2, 3 and 4 cancers, respectively. Almost every patient had surgery (99.7%), 47.4% had chemotherapy, 7.6% had radiotherapy and 1.4% had immunotherapy. On average, tumour mutational burden (TMB) was 18 mutations/Mb and 34.4%, 31.3% and 25.7% of patients had structural or copy number mutations in KRAS, BRAF and NRAS, respectively. In the fully adjusted Cox model, patients with advanced cancer [stage 3 hazard ratio (HR)  =  3.2; p  <  0.001; stage 4 HR  =  10.2; p  <  0.001] and those who had immunotherapy (HR  =  1.8; p  <  0.04) or radiotherapy (HR  =  1.5; p  <  0.02) treatment had a higher risk of dying. The ensemble clustering approach generated four distinct clusters where patients in cluster 2 had the best survival outcomes (1-year: 98.7%; 2-year: 96.7%; 3-year: 93.0%) while patients in cluster 3 (1-year: 87.9; 2-year: 70.0%; 3-year: 53.1%) had the worst outcomes. Kaplan-Meier analysis and log rank test revealed that the clusters were separated into distinct prognostic groups (p  <  0.0001). Survival tree or recursive partitioning analyses were performed to further explore risk groups within each cluster. Among patients in cluster 2, for example, interactions between cancer stage, grade, radiotherapy, TMB, BRAF mutation status were identified. Patients with stage 4 cancer and TMB  ≥  1.6 mutations/Mb had 4 times higher risk of dying relative to the baseline hazard in that cluster.",,pdf:https://bmcresnotes.biomedcentral.com/track/pdf/10.1186/s13104-021-05789-0; doi:https://doi.org/10.1186/s13104-021-05789-0; html:https://europepmc.org/articles/PMC8487486; pdf:https://europepmc.org/articles/PMC8487486?pdf=render 35820692,https://doi.org/10.1136/bmj-2021-069881,Clinical prediction models for mortality in patients with covid-19: external validation and individual participant data meta-analysis.,"de Jong VMT, Rousset RZ, Antonio-Villa NE, Buenen AG, Van Calster B, Bello-Chavolla OY, Brunskill NJ, Curcin V, Damen JAA, Fermín-Martínez CA, Fernández-Chirino L, Ferrari D, Free RC, Gupta RK, Haldar P, Hedberg P, Korang SK, Kurstjens S, Kusters R, Major RW, Maxwell L, Nair R, Naucler P, Nguyen TL, Noursadeghi M, Rosa R, Soares F, Takada T, van Royen FS, van Smeden M, Wynants L, Modrák M, CovidRetro collaboration, Asselbergs FW, Linschoten M, CAPACITY-COVID consortium, Moons KGM, Debray TPA.",,BMJ (Clinical research ed.),2022,2022-07-12,Y,,,,"

Objective

To externally validate various prognostic models and scoring rules for predicting short term mortality in patients admitted to hospital for covid-19.

Design

Two stage individual participant data meta-analysis.

Setting

Secondary and tertiary care.

Participants

46 914 patients across 18 countries, admitted to a hospital with polymerase chain reaction confirmed covid-19 from November 2019 to April 2021.

Data sources

Multiple (clustered) cohorts in Brazil, Belgium, China, Czech Republic, Egypt, France, Iran, Israel, Italy, Mexico, Netherlands, Portugal, Russia, Saudi Arabia, Spain, Sweden, United Kingdom, and United States previously identified by a living systematic review of covid-19 prediction models published in The BMJ, and through PROSPERO, reference checking, and expert knowledge.

Model selection and eligibility criteria

Prognostic models identified by the living systematic review and through contacting experts. A priori models were excluded that had a high risk of bias in the participant domain of PROBAST (prediction model study risk of bias assessment tool) or for which the applicability was deemed poor.

Methods

Eight prognostic models with diverse predictors were identified and validated. A two stage individual participant data meta-analysis was performed of the estimated model concordance (C) statistic, calibration slope, calibration-in-the-large, and observed to expected ratio (O:E) across the included clusters.

Main outcome measures

30 day mortality or in-hospital mortality.

Results

Datasets included 27 clusters from 18 different countries and contained data on 46 914patients. The pooled estimates ranged from 0.67 to 0.80 (C statistic), 0.22 to 1.22 (calibration slope), and 0.18 to 2.59 (O:E ratio) and were prone to substantial between study heterogeneity. The 4C Mortality Score by Knight et al (pooled C statistic 0.80, 95% confidence interval 0.75 to 0.84, 95% prediction interval 0.72 to 0.86) and clinical model by Wang et al (0.77, 0.73 to 0.80, 0.63 to 0.87) had the highest discriminative ability. On average, 29% fewer deaths were observed than predicted by the 4C Mortality Score (pooled O:E 0.71, 95% confidence interval 0.45 to 1.11, 95% prediction interval 0.21 to 2.39), 35% fewer than predicted by the Wang clinical model (0.65, 0.52 to 0.82, 0.23 to 1.89), and 4% fewer than predicted by Xie et al's model (0.96, 0.59 to 1.55, 0.21 to 4.28).

Conclusion

The prognostic value of the included models varied greatly between the data sources. Although the Knight 4C Mortality Score and Wang clinical model appeared most promising, recalibration (intercept and slope updates) is needed before implementation in routine care.",,pdf:https://www.bmj.com/content/bmj/378/bmj-2021-069881.full.pdf; doi:https://doi.org/10.1136/bmj-2021-069881; html:https://europepmc.org/articles/PMC9273913; pdf:https://europepmc.org/articles/PMC9273913?pdf=render @@ -2478,8 +2478,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 34748544,https://doi.org/10.1371/journal.pbio.3001255,Predicting novel candidate human obesity genes and their site of action by systematic functional screening in Drosophila.,"Agrawal N, Lawler K, Davidson CM, Keogh JM, Legg R, INTERVAL, Barroso I, Farooqi IS, Brand AH.",,PLoS biology,2021,2021-11-08,Y,,,,"The discovery of human obesity-associated genes can reveal new mechanisms to target for weight loss therapy. Genetic studies of obese individuals and the analysis of rare genetic variants can identify novel obesity-associated genes. However, establishing a functional relationship between these candidate genes and adiposity remains a significant challenge. We uncovered a large number of rare homozygous gene variants by exome sequencing of severely obese children, including those from consanguineous families. By assessing the function of these genes in vivo in Drosophila, we identified 4 genes, not previously linked to human obesity, that regulate adiposity (itpr, dachsous, calpA, and sdk). Dachsous is a transmembrane protein upstream of the Hippo signalling pathway. We found that 3 further members of the Hippo pathway, fat, four-jointed, and hippo, also regulate adiposity and that they act in neurons, rather than in adipose tissue (fat body). Screening Hippo pathway genes in larger human cohorts revealed rare variants in TAOK2 associated with human obesity. Knockdown of Drosophila tao increased adiposity in vivo demonstrating the strength of our approach in predicting novel human obesity genes and signalling pathways and their site of action.",,pdf:https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001255&type=printable; doi:https://doi.org/10.1371/journal.pbio.3001255; html:https://europepmc.org/articles/PMC8575313; pdf:https://europepmc.org/articles/PMC8575313?pdf=render 34876579,https://doi.org/10.1038/s41467-021-27326-0,Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood.,"Kariotis S, Jammeh E, Swietlik EM, Pickworth JA, Rhodes CJ, Otero P, Wharton J, Iremonger J, Dunning MJ, Pandya D, Mascarenhas TS, Errington N, Thompson AAR, Romanoski CE, Rischard F, Garcia JGN, Yuan JX, An TS, Desai AA, Coghlan G, Lordan J, Corris PA, Howard LS, Condliffe R, Kiely DG, Church C, Pepke-Zaba J, Toshner M, Wort S, Gräf S, Morrell NW, Wilkins MR, Lawrie A, Wang D, UK National PAH Cohort Study Consortium.",,Nature communications,2021,2021-12-07,Y,,,,"Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease diagnosed by right heart catheterisation and the exclusion of other forms of pulmonary arterial hypertension, producing a heterogeneous population with varied treatment response. Here we show unsupervised machine learning identification of three major patient subgroups that account for 92% of the cohort, each with unique whole blood transcriptomic and clinical feature signatures. These subgroups are associated with poor, moderate, and good prognosis. The poor prognosis subgroup is associated with upregulation of the ALAS2 and downregulation of several immunoglobulin genes, while the good prognosis subgroup is defined by upregulation of the bone morphogenetic protein signalling regulator NOG, and the C/C variant of HLA-DPA1/DPB1 (independently associated with survival). These findings independently validated provide evidence for the existence of 3 major subgroups (endophenotypes) within the IPAH classification, could improve risk stratification and provide molecular insights into the pathogenesis of IPAH.",,pdf:https://www.nature.com/articles/s41467-021-27326-0.pdf; doi:https://doi.org/10.1038/s41467-021-27326-0; html:https://europepmc.org/articles/PMC8651638; pdf:https://europepmc.org/articles/PMC8651638?pdf=render 34988540,https://doi.org/10.1016/j.jadr.2021.100201,Comparison of depression and anxiety symptom networks in reporters and non-reporters of lifetime trauma in two samples of differing severity.,"Peel AJ, Armour C, Buckman JEJ, Coleman JRI, Curzons SCB, Davies MR, Hübel C, Jones I, Kalsi G, McAtarsney-Kovacs M, McIntosh AM, Monssen D, Mundy J, Rayner C, Rogers HC, Skelton M, Ter Kuile A, Thompson KN, Breen G, Danese A, Eley TC.",,Journal of affective disorders reports,2021,2021-12-01,Y,Trauma; Depression; Anxiety; Self-report; Network Analysis,,,"

Background

Reported trauma is associated with differences in the course and outcomes of depression and anxiety. However, no research has explored the association between reported trauma and patterns of clinically relevant symptoms of both depression and anxiety.

Methods

We used network analysis to investigate associations between reported trauma and depression and anxiety symptom interactions in affected individuals from the Genetic Links to Anxiety and Depression (GLAD) Study (n = 17720), and population volunteers from the UK Biobank (n = 11120). Participants with current moderate symptoms of depression or anxiety were grouped into reporters and non-reporters of lifetime trauma. Networks of 16 depression and anxiety symptoms in the two groups were compared using the network comparison test.

Results

In the GLAD Study, networks of reporters and non-reporters of lifetime trauma did not differ on any metric. In the UK Biobank, the symptom network of reporters had significantly greater density (7.80) than the network of non-reporters (7.05).

Limitations

The data collected in the GLAD Study and the UK Biobank are self-reported with validated or semi-validated questionnaires.

Conclusions

Reported lifetime trauma was associated with stronger interactions between symptoms of depression and anxiety in population volunteers. Differences between reporters and non-reporters may not be observed in individuals with severe depression and/or anxiety due to limited variance in the presentation of disorder.",,doi:https://doi.org/10.1016/j.jadr.2021.100201; doi:https://doi.org/10.1016/j.jadr.2021.100201; html:https://europepmc.org/articles/PMC8689407 -33887342,https://doi.org/10.1016/j.ijcard.2021.04.029,Clopidogrel in noncarriers of CYP2C19 loss-of-function alleles versus ticagrelor in elderly patients with acute coronary syndrome: A pre-specified sub analysis from the POPular Genetics and POPular Age trials CYP2C19 alleles in elderly patients.,"Claassens DMF, Gimbel ME, Bergmeijer TO, Vos GJA, Hermanides RS, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, de Vrey EA, Heestermans TACM, Jukema JW, von Birgelen C, Waalewijn RA, Hofma SH, den Hartog FR, Voskuil M, Van't Hof AWJ, Asselbergs FW, Mosterd A, Herrman JR, Dewilde W, Mahmoodi BK, Deneer VHM, Ten Berg JM.",,International journal of cardiology,2021,2021-04-20,N,Genotyping; Myocardial infarction; CYP2C19; Pharmacogenetics; Older; P2y12,,,"

Background

Patients with acute coronary syndrome (ACS) who are carrying CYP2C19 loss-of-function alleles derive less benefit from clopidogrel treatment. Despite this, in elderly patients, clopidogrel might be preferred over more potent P2Y12 inhibitors due to a lower bleeding risk. Whether CYP2C19 genotype-guided antiplatelet treatment in the elderly could be of benefit has not been studied specifically.

Methods

Patients aged 70 years and older with known CYP2C19*2 and *3 genotype were identified from the POPular Genetics and POPular Age trials. Noncarriers of loss-of-function alleles treated with clopidogrel were compared to patients, irrespective of CYP2C19 genotype, treated with ticagrelor and to clopidogrel treated carriers of loss-of-function alleles. We assessed net clinical benefit (all-cause death, myocardial infarction, stroke and Platelet Inhibition and Patient Outcomes (PLATO) major bleeding), atherothrombotic outcomes (cardiovascular death, myocardial infarction, stroke) and bleeding outcomes (PLATO major and minor bleeding).

Results

A total of 991 patients were assessed. There was no significant difference in net clinical benefit (17.2% vs. 15.1%, adjusted hazard ratio (adjHR) 1.05, 95% confidence interval (CI) 0.77-1.44), atherothrombotic outcomes (9.7% vs. 9.2%, adjHR 1.00, 95%CI 0.66-1.50), and bleeding outcomes (17.7% vs. 19.8%, adjHR 0.80, 95%CI 0.62-1.12) between clopidogrel in noncarriers of loss-of-function alleles and ticagrelor respectively.

Conclusion

In ACS patients aged 70 years and older, there was no significant difference in net clinical benefit and atherothrombotic outcomes between noncarriers of a loss-of-function allele treated with clopidogrel and patients treated with ticagrelor. The bleeding rate was numerically; though not statistically significant, lower in patients using clopidogrel.",,pdf:https://pure.rug.nl/ws/files/200111410/1_s2.0_S0167527321006653_main.pdf; doi:https://doi.org/10.1016/j.ijcard.2021.04.029 34820659,https://doi.org/10.1016/j.xgen.2021.100028,The Data Use Ontology to streamline responsible access to human biomedical datasets.,"Lawson J, Cabili MN, Kerry G, Boughtwood T, Thorogood A, Alper P, Bowers SR, Boyles RR, Brookes AJ, Brush M, Burdett T, Clissold H, Donnelly S, Dyke SOM, Freeberg MA, Haendel MA, Hata C, Holub P, Jeanson F, Jene A, Kawashima M, Kawashima S, Konopko M, Kyomugisha I, Li H, Linden M, Rodriguez LL, Morita M, Mulder N, Muller J, Nagaie S, Nasir J, Ogishima S, Ota Wang V, Paglione LD, Pandya RN, Parkinson H, Philippakis AA, Prasser F, Rambla J, Reinold K, Rushton GA, Saltzman A, Saunders G, Sofia HJ, Spalding JD, Swertz MA, Tulchinsky I, van Enckevort EJ, Varma S, Voisin C, Yamamoto N, Yamasaki C, Zass L, Guidry Auvil JM, Nyrönen TH, Courtot M.",,Cell genomics,2021,2021-11-10,Y,Standard; Consent; Ontology; Data Access; Fair; Secondary Data Use; Ga4gh; Data Restrictions; Controlled Access; Automated Data Access,,,"Human biomedical datasets that are critical for research and clinical studies to benefit human health also often contain sensitive or potentially identifying information of individual participants. Thus, care must be taken when they are processed and made available to comply with ethical and regulatory frameworks and informed consent data conditions. To enable and streamline data access for these biomedical datasets, the Global Alliance for Genomics and Health (GA4GH) Data Use and Researcher Identities (DURI) work stream developed and approved the Data Use Ontology (DUO) standard. DUO is a hierarchical vocabulary of human and machine-readable data use terms that consistently and unambiguously represents a dataset's allowable data uses. DUO has been implemented by major international stakeholders such as the Broad and Sanger Institutes and is currently used in annotation of over 200,000 datasets worldwide. Using DUO in data management and access facilitates researchers' discovery and access of relevant datasets. DUO annotations increase the FAIRness of datasets and support data linkages using common data use profiles when integrating the data for secondary analyses. DUO is implemented in the Web Ontology Language (OWL) and, to increase community awareness and engagement, hosted in an open, centralized GitHub repository. DUO, together with the GA4GH Passport standard, offers a new, efficient, and streamlined data authorization and access framework that has enabled increased sharing of biomedical datasets worldwide.",,doi:https://doi.org/10.1016/j.xgen.2021.100028; doi:https://doi.org/10.1016/j.xgen.2021.100028; html:https://europepmc.org/articles/PMC8591903; pdf:https://europepmc.org/articles/PMC8591903?pdf=render +33887342,https://doi.org/10.1016/j.ijcard.2021.04.029,Clopidogrel in noncarriers of CYP2C19 loss-of-function alleles versus ticagrelor in elderly patients with acute coronary syndrome: A pre-specified sub analysis from the POPular Genetics and POPular Age trials CYP2C19 alleles in elderly patients.,"Claassens DMF, Gimbel ME, Bergmeijer TO, Vos GJA, Hermanides RS, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, de Vrey EA, Heestermans TACM, Jukema JW, von Birgelen C, Waalewijn RA, Hofma SH, den Hartog FR, Voskuil M, Van't Hof AWJ, Asselbergs FW, Mosterd A, Herrman JR, Dewilde W, Mahmoodi BK, Deneer VHM, Ten Berg JM.",,International journal of cardiology,2021,2021-04-20,N,Genotyping; Myocardial infarction; CYP2C19; Pharmacogenetics; Older; P2y12,,,"

Background

Patients with acute coronary syndrome (ACS) who are carrying CYP2C19 loss-of-function alleles derive less benefit from clopidogrel treatment. Despite this, in elderly patients, clopidogrel might be preferred over more potent P2Y12 inhibitors due to a lower bleeding risk. Whether CYP2C19 genotype-guided antiplatelet treatment in the elderly could be of benefit has not been studied specifically.

Methods

Patients aged 70 years and older with known CYP2C19*2 and *3 genotype were identified from the POPular Genetics and POPular Age trials. Noncarriers of loss-of-function alleles treated with clopidogrel were compared to patients, irrespective of CYP2C19 genotype, treated with ticagrelor and to clopidogrel treated carriers of loss-of-function alleles. We assessed net clinical benefit (all-cause death, myocardial infarction, stroke and Platelet Inhibition and Patient Outcomes (PLATO) major bleeding), atherothrombotic outcomes (cardiovascular death, myocardial infarction, stroke) and bleeding outcomes (PLATO major and minor bleeding).

Results

A total of 991 patients were assessed. There was no significant difference in net clinical benefit (17.2% vs. 15.1%, adjusted hazard ratio (adjHR) 1.05, 95% confidence interval (CI) 0.77-1.44), atherothrombotic outcomes (9.7% vs. 9.2%, adjHR 1.00, 95%CI 0.66-1.50), and bleeding outcomes (17.7% vs. 19.8%, adjHR 0.80, 95%CI 0.62-1.12) between clopidogrel in noncarriers of loss-of-function alleles and ticagrelor respectively.

Conclusion

In ACS patients aged 70 years and older, there was no significant difference in net clinical benefit and atherothrombotic outcomes between noncarriers of a loss-of-function allele treated with clopidogrel and patients treated with ticagrelor. The bleeding rate was numerically; though not statistically significant, lower in patients using clopidogrel.",,pdf:https://pure.rug.nl/ws/files/200111410/1_s2.0_S0167527321006653_main.pdf; doi:https://doi.org/10.1016/j.ijcard.2021.04.029 31730918,https://doi.org/10.1016/j.jclinepi.2019.11.006,Data mining information from electronic health records produced high yield and accuracy for current smoking status.,"Groenhof TKJ, Koers LR, Blasse E, de Groot M, Grobbee DE, Bots ML, Asselbergs FW, Lely AT, Haitjema S, UPOD, UCC-CVRM Study Groups.",,Journal of clinical epidemiology,2020,2019-11-12,N,data mining; Data Quality; Electronic Health Records; Text Mining; Learning Healthcare System; Routine Clinical Data,The Human Phenome,,"

Objectives

Researchers are increasingly using routine clinical data for care evaluations and feedback to patients and clinicians. The quality of these evaluations depends on the quality and completeness of the input data.

Study design and setting

We assessed the performance of an electronic health record (EHR)-based data mining algorithm, using the example of the smoking status in a cardiovascular population. As a reference standard, we used the questionnaire from the Utrecht Cardiovascular Cohort (UCC). To assess diagnostic accuracy, we calculated sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV).

Results

We analyzed 1,661 patients included in the UCC to January 18, 2019. Of those, 14% (n = 238) had missing information on smoking status in the UCC questionnaire. Data mining provided information on smoking status in 99% of the 1,661 participants. Diagnostic accuracy for current smoking was sensitivity 88%, specificity 92%, NPV 98%, and PPV 63%. From false positives, 85% reported they had quit smoking at the time of the UCC.

Conclusion

Data mining showed great potential in retrieving information on smoking (a near complete yield). Its diagnostic performance is good for negative smoking statuses. The implications of misclassification with data mining are dependent on the application of the data.",Utilises data mining and routine data to identify a patients smoking status. Does not account for long term smoking behaviour and is limited by the smaller size the dataset.,pdf:http://www.jclinepi.com/article/S0895435619304846/pdf; doi:https://doi.org/10.1016/j.jclinepi.2019.11.006 34426706,https://doi.org/10.1038/s41591-021-01441-3,"Mitochondrial DNA variants modulate N-formylmethionine, proteostasis and risk of late-onset human diseases.","Cai N, Gomez-Duran A, Yonova-Doing E, Kundu K, Burgess AI, Golder ZJ, Calabrese C, Bonder MJ, Camacho M, Lawson RA, Li L, Williams-Gray CH, ICICLE-PD Study Group, Di Angelantonio E, Roberts DJ, Watkins NA, Ouwehand WH, Butterworth AS, Stewart ID, Pietzner M, Wareham NJ, Langenberg C, Danesh J, Walter K, Rothwell PM, Howson JMM, Stegle O, Chinnery PF, Soranzo N.",,Nature medicine,2021,2021-08-23,N,,,,"Mitochondrial DNA (mtDNA) variants influence the risk of late-onset human diseases, but the reasons for this are poorly understood. Undertaking a hypothesis-free analysis of 5,689 blood-derived biomarkers with mtDNA variants in 16,220 healthy donors, here we show that variants defining mtDNA haplogroups Uk and H4 modulate the level of circulating N-formylmethionine (fMet), which initiates mitochondrial protein translation. In human cytoplasmic hybrid (cybrid) lines, fMet modulated both mitochondrial and cytosolic proteins on multiple levels, through transcription, post-translational modification and proteolysis by an N-degron pathway, abolishing known differences between mtDNA haplogroups. In a further 11,966 individuals, fMet levels contributed to all-cause mortality and the disease risk of several common cardiovascular disorders. Together, these findings indicate that fMet plays a key role in common age-related disease through pleiotropic effects on cell proteostasis.",,pdf:https://push-zb.helmholtz-muenchen.de/deliver.php?id=34427; doi:https://doi.org/10.1038/s41591-021-01441-3 31504546,https://doi.org/10.1093/ije/dyz174,"Cohort Profile: East London Genes & Health (ELGH), a community-based population genomics and health study in British Bangladeshi and British Pakistani people.","Finer S, Martin HC, Khan A, Hunt KA, MacLaughlin B, Ahmed Z, Ashcroft R, Durham C, MacArthur DG, McCarthy MI, Robson J, Trivedi B, Griffiths C, Wright J, Trembath RC, van Heel DA.",,International journal of epidemiology,2020,2020-02-01,Y,,,,,,pdf:https://academic.oup.com/ije/article-pdf/49/1/20/32995529/dyz174.pdf; doi:https://doi.org/10.1093/ije/dyz174; html:https://europepmc.org/articles/PMC7124496; pdf:https://europepmc.org/articles/PMC7124496?pdf=render @@ -2510,8 +2510,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 31488387,https://doi.org/10.1016/s2214-109x(19)30318-3,World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions.,WHO CVD Risk Chart Working Group.,,The Lancet. Global health,2019,2019-09-02,Y,,,,"

Background

To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions.

Methods

In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance.

Findings

Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629-0·741) to 0·833 (0·783-0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt.

Interpretation

We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide.

Funding

World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S2214109X19303183/pdf; doi:https://doi.org/10.1016/S2214-109X(19)30318-3; html:https://europepmc.org/articles/PMC7025029 31477934,https://doi.org/10.1038/s41588-019-0483-y,Inferring whole-genome histories in large population datasets.,"Kelleher J, Wong Y, Wohns AW, Fadil C, Albers PK, McVean G.",,Nature genetics,2019,2019-09-02,Y,,The Human Phenome,,"Inferring the full genealogical history of a set of DNA sequences is a core problem in evolutionary biology, because this history encodes information about the events and forces that have influenced a species. However, current methods are limited, and the most accurate techniques are able to process no more than a hundred samples. As datasets that consist of millions of genomes are now being collected, there is a need for scalable and efficient inference methods to fully utilize these resources. Here we introduce an algorithm that is able to not only infer whole-genome histories with comparable accuracy to the state-of-the-art but also process four orders of magnitude more sequences. The approach also provides an 'evolutionary encoding' of the data, enabling efficient calculation of relevant statistics. We apply the method to human data from the 1000 Genomes Project, Simons Genome Diversity Project and UK Biobank, showing that the inferred genealogies are rich in biological signal and efficient to process.",,pdf:https://europepmc.org/articles/pmc6726478?pdf=render; doi:https://doi.org/10.1038/s41588-019-0483-y; html:https://europepmc.org/articles/PMC6726478; pdf:https://europepmc.org/articles/PMC6726478?pdf=render 33444330,https://doi.org/10.1371/journal.pmed.1003498,Polygenic risk scores in cardiovascular risk prediction: A cohort study and modelling analyses.,"Sun L, Pennells L, Kaptoge S, Nelson CP, Ritchie SC, Abraham G, Arnold M, Bell S, Bolton T, Burgess S, Dudbridge F, Guo Q, Sofianopoulou E, Stevens D, Thompson JR, Butterworth AS, Wood A, Danesh J, Samani NJ, Inouye M, Di Angelantonio E.",,PLoS medicine,2021,2021-01-14,Y,,,,"

Background

Polygenic risk scores (PRSs) can stratify populations into cardiovascular disease (CVD) risk groups. We aimed to quantify the potential advantage of adding information on PRSs to conventional risk factors in the primary prevention of CVD.

Methods and findings

Using data from UK Biobank on 306,654 individuals without a history of CVD and not on lipid-lowering treatments (mean age [SD]: 56.0 [8.0] years; females: 57%; median follow-up: 8.1 years), we calculated measures of risk discrimination and reclassification upon addition of PRSs to risk factors in a conventional risk prediction model (i.e., age, sex, systolic blood pressure, smoking status, history of diabetes, and total and high-density lipoprotein cholesterol). We then modelled the implications of initiating guideline-recommended statin therapy in a primary care setting using incidence rates from 2.1 million individuals from the Clinical Practice Research Datalink. The C-index, a measure of risk discrimination, was 0.710 (95% CI 0.703-0.717) for a CVD prediction model containing conventional risk predictors alone. Addition of information on PRSs increased the C-index by 0.012 (95% CI 0.009-0.015), and resulted in continuous net reclassification improvements of about 10% and 12% in cases and non-cases, respectively. If a PRS were assessed in the entire UK primary care population aged 40-75 years, assuming that statin therapy would be initiated in accordance with the UK National Institute for Health and Care Excellence guidelines (i.e., for persons with a predicted risk of ≥10% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), then it could help prevent 1 additional CVD event for approximately every 5,750 individuals screened. By contrast, targeted assessment only among people at intermediate (i.e., 5% to <10%) 10-year CVD risk could help prevent 1 additional CVD event for approximately every 340 individuals screened. Such a targeted strategy could help prevent 7% more CVD events than conventional risk prediction alone. Potential gains afforded by assessment of PRSs on top of conventional risk factors would be about 1.5-fold greater than those provided by assessment of C-reactive protein, a plasma biomarker included in some risk prediction guidelines. Potential limitations of this study include its restriction to European ancestry participants and a lack of health economic evaluation.

Conclusions

Our results suggest that addition of PRSs to conventional risk factors can modestly enhance prediction of first-onset CVD and could translate into population health benefits if used at scale.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003498&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003498; html:https://europepmc.org/articles/PMC7808664; pdf:https://europepmc.org/articles/PMC7808664?pdf=render -38428419,https://doi.org/10.1016/j.xgen.2024.100511,Genomic evolution shapes prostate cancer disease type.,"Woodcock DJ, Sahli A, Teslo R, Bhandari V, Gruber AJ, Ziubroniewicz A, Gundem G, Xu Y, Butler A, Anokian E, Pope BJ, Jung CH, Tarabichi M, Dentro SC, Farmery JHR, CRUK ICGC Prostate Group, Van Loo P, Warren AY, Gnanapragasam V, Hamdy FC, Bova GS, Foster CS, Neal DE, Lu YJ, Kote-Jarai Z, Fraser M, Bristow RG, Boutros PC, Costello AJ, Corcoran NM, Hovens CM, Massie CE, Lynch AG, Brewer DS, Eeles RA, Cooper CS, Wedge DC.",,Cell genomics,2024,2024-02-29,Y,prostate cancer; Ordering; Cancer Evolution; Ar Binding; Evotype Model; Evotypes,,,"The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype tumors diverge from those of the Canonical-evotype through the stochastic accumulation of genetic alterations associated with disruptions to androgen receptor DNA binding. Our model unifies many previous molecular observations, providing a powerful new framework to investigate prostate cancer disease progression.",,doi:https://doi.org/10.1016/j.xgen.2024.100511; html:https://europepmc.org/articles/PMC10943594; pdf:https://europepmc.org/articles/PMC10943594?pdf=render 32979922,https://doi.org/10.1186/s12933-020-01130-4,Diabetes as a risk factor for incident peripheral arterial disease in women compared to men: a systematic review and meta-analysis.,"Chase-Vilchez AZ, Chan IHY, Peters SAE, Woodward M.",,Cardiovascular diabetology,2020,2020-09-26,Y,Sex difference; Diabetes; Cardiovascular disease; Peripheral Arterial Disease; Peripheral Vascular Disease,,,"

Aims/hypothesis

Previous meta-analyses have suggested that diabetes confers a greater excess risk of coronary heart disease, stroke, vascular dementia, and heart failure in women compared to men. While the underlying mechanism that explains such greater excess risk is unknown, in the current meta-analysis we hypothesized that we would find a similar sex difference in the relationship between diabetes and peripheral arterial disease (PAD).

Methods

PubMed MEDLINE, the Cochrane Database of Systematic Reviews, and Embase were systematically searched for prospective population-based cohort studies, with no restriction on publication date, language, or country. We included studies that reported the relative risk (RR), and its variability, for incident PAD associated with diabetes in both sexes. We excluded studies that did not adjust at least for age, and in which participants had pre-existing PAD. In cases where sex-specific results were not reported, study authors were contacted. Random-effects meta-analyses with inverse variance weighting were used to obtain summary sex-specific RRs and the women: men ratio of RRs for PAD. The Newcastle-Ottawa scale was used to assess study quality.

Results

Data from seven cohorts, totalling 2071,260 participants (49.8% women), were included. The relative risk for incident PAD associated with diabetes compared with no diabetes was 1.96 (95% CI 1.29-2.63) in women and 1.84 (95% CI 1.29-2.86) in men, after adjusting for potential confounders. The multiple-adjusted RR ratio was 1.05 (95% CI 0.90-1.22), with virtually no heterogeneity between studies (I2 = 0%). All studies scored 6-8, on the Newcastle-Ottawa scale of 0-9, indicating good quality. Eleven of the 12 studies that met review inclusion criteria did not report sex-specific relative risk, and these data were collected through direct correspondence with the study authors.

Conclusion/interpretation

Consistent with other studies, we found evidence that diabetes is an independent risk factor for PAD. However, in contrast to similar studies of other types of cardiovascular disease, we did not find evidence that diabetes confers a greater excess risk in women compared to men for PAD. More research is needed to explain this sex differential between PAD and other forms of CVD, in the sequelae of diabetes. In addition, we found that very few studies reported the sex-specific relative risk for the association between diabetes and PAD, adding to existing evidence for the need for improved reporting of sex-disaggregated results in cardiovascular disease research.",,pdf:https://cardiab.biomedcentral.com/track/pdf/10.1186/s12933-020-01130-4; doi:https://doi.org/10.1186/s12933-020-01130-4; html:https://europepmc.org/articles/PMC7520021; pdf:https://europepmc.org/articles/PMC7520021?pdf=render +38428419,https://doi.org/10.1016/j.xgen.2024.100511,Genomic evolution shapes prostate cancer disease type.,"Woodcock DJ, Sahli A, Teslo R, Bhandari V, Gruber AJ, Ziubroniewicz A, Gundem G, Xu Y, Butler A, Anokian E, Pope BJ, Jung CH, Tarabichi M, Dentro SC, Farmery JHR, CRUK ICGC Prostate Group, Van Loo P, Warren AY, Gnanapragasam V, Hamdy FC, Bova GS, Foster CS, Neal DE, Lu YJ, Kote-Jarai Z, Fraser M, Bristow RG, Boutros PC, Costello AJ, Corcoran NM, Hovens CM, Massie CE, Lynch AG, Brewer DS, Eeles RA, Cooper CS, Wedge DC.",,Cell genomics,2024,2024-02-29,Y,prostate cancer; Ordering; Cancer Evolution; Ar Binding; Evotype Model; Evotypes,,,"The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype tumors diverge from those of the Canonical-evotype through the stochastic accumulation of genetic alterations associated with disruptions to androgen receptor DNA binding. Our model unifies many previous molecular observations, providing a powerful new framework to investigate prostate cancer disease progression.",,doi:https://doi.org/10.1016/j.xgen.2024.100511; html:https://europepmc.org/articles/PMC10943594; pdf:https://europepmc.org/articles/PMC10943594?pdf=render 33442528,https://doi.org/10.1140/epjds/s13688-020-00257-4,Privacy preserving data visualizations.,"Avraam D, Wilson R, Butters O, Burton T, Nicolaides C, Jones E, Boyd A, Burton P.",,EPJ data science,2021,2021-01-07,Y,Privacy Protection; Anonymization; Sensitive Data; Data Visualizations; Disclosure Control,,,"Data visualizations are a valuable tool used during both statistical analysis and the interpretation of results as they graphically reveal useful information about the structure, properties and relationships between variables, which may otherwise be concealed in tabulated data. In disciplines like medicine and the social sciences, where collected data include sensitive information about study participants, the sharing and publication of individual-level records is controlled by data protection laws and ethico-legal norms. Thus, as data visualizations - such as graphs and plots - may be linked to other released information and used to identify study participants and their personal attributes, their creation is often prohibited by the terms of data use. These restrictions are enforced to reduce the risk of breaching data subject confidentiality, however they limit analysts from displaying useful descriptive plots for their research features and findings. Here we propose the use of anonymization techniques to generate privacy-preserving visualizations that retain the statistical properties of the underlying data while still adhering to strict data disclosure rules. We demonstrate the use of (i) the well-known k-anonymization process which preserves privacy by reducing the granularity of the data using suppression and generalization, (ii) a novel deterministic approach that replaces individual-level observations with the centroids of each k nearest neighbours, and (iii) a probabilistic procedure that perturbs individual attributes with the addition of random stochastic noise. We apply the proposed methods to generate privacy-preserving data visualizations for exploratory data analysis and inferential regression plot diagnostics, and we discuss their strengths and limitations.",,pdf:https://epjdatascience.springeropen.com/track/pdf/10.1140/epjds/s13688-020-00257-4; doi:https://doi.org/10.1140/epjds/s13688-020-00257-4; html:https://europepmc.org/articles/PMC7790778; pdf:https://europepmc.org/articles/PMC7790778?pdf=render 32956399,https://doi.org/10.1371/journal.pmed.1003336,Antibiotic prescribing for lower UTI in elderly patients in primary care and risk of bloodstream infection: A cohort study using electronic health records in England.,"Shallcross L, Rockenschaub P, Blackburn R, Nazareth I, Freemantle N, Hayward A.",,PLoS medicine,2020,2020-09-21,Y,,,,"

Background

Research has questioned the safety of delaying or withholding antibiotics for suspected urinary tract infection (UTI) in older patients. We evaluated the association between antibiotic treatment for lower UTI and risk of bloodstream infection (BSI) in adults aged ≥65 years in primary care.

Methods and findings

We analyzed primary care records from patients aged ≥65 years in England with community-onset UTI using the Clinical Practice Research Datalink (2007-2015) linked to Hospital Episode Statistics and census data. The primary outcome was BSI within 60 days, comparing patients treated immediately with antibiotics and those not treated immediately. Crude and adjusted associations between exposure and outcome were estimated using generalized estimating equations. A total of 147,334 patients were included representing 280,462 episodes of lower UTI. BSI occurred in 0.4% (1,025/244,963) of UTI episodes with immediate antibiotics versus 0.6% (228/35,499) of episodes without immediate antibiotics. After adjusting for patient demographics, year of consultation, comorbidities, smoking status, recent hospitalizations, recent accident and emergency (A&E) attendances, recent antibiotic prescribing, and home visits, the odds of BSI were equivalent in patients who were not treated with antibiotics immediately and those who were treated on the date of their UTI consultation (adjusted odds ratio [aOR] 1.13, 95% CI 0.97-1.32, p-value = 0.105). Delaying or withholding antibiotics was associated with increased odds of death in the subsequent 60 days (aOR 1.17, 95% CI 1.09-1.26, p-value < 0.001), but there was limited evidence that increased deaths were attributable to urinary-source BSI. Limitations include overlap between the categories of immediate and delayed antibiotic prescribing, residual confounding underlying differences between patients who were/were not treated with antibiotics, and lack of microbiological diagnosis for BSI.

Conclusions

In this study, we observed that delaying or withholding antibiotics in older adults with suspected UTI did not increase patients' risk of BSI, in contrast with a previous study that analyzed the same dataset, but mortality was increased. Our findings highlight uncertainty around the risks of delaying or withholding antibiotic treatment, which is exacerbated by systematic differences between patients who were and were not treated immediately with antibiotics. Overall, our findings emphasize the need for improved diagnostic/risk prediction strategies to guide antibiotic prescribing for suspected UTI in older adults.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003336&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003336; html:https://europepmc.org/articles/PMC7505443; pdf:https://europepmc.org/articles/PMC7505443?pdf=render 33385551,https://doi.org/10.1016/j.neuroimage.2020.117689,Deep learning-based unlearning of dataset bias for MRI harmonisation and confound removal.,"Dinsdale NK, Jenkinson M, Namburete AIL.",,NeuroImage,2021,2020-12-30,Y,MRI; Harmonization; Joint Domain Adaptation,,,"Increasingly large MRI neuroimaging datasets are becoming available, including many highly multi-site multi-scanner datasets. Combining the data from the different scanners is vital for increased statistical power; however, this leads to an increase in variance due to nonbiological factors such as the differences in acquisition protocols and hardware, which can mask signals of interest. We propose a deep learning based training scheme, inspired by domain adaptation techniques, which uses an iterative update approach to aim to create scanner-invariant features while simultaneously maintaining performance on the main task of interest, thus reducing the influence of scanner on network predictions. We demonstrate the framework for regression, classification and segmentation tasks with two different network architectures. We show that not only can the framework harmonise many-site datasets but it can also adapt to many data scenarios, including biased datasets and limited training labels. Finally, we show that the framework can be extended for the removal of other known confounds in addition to scanner. The overall framework is therefore flexible and should be applicable to a wide range of neuroimaging studies.",,doi:https://doi.org/10.1016/j.neuroimage.2020.117689; doi:https://doi.org/10.1016/j.neuroimage.2020.117689; html:https://europepmc.org/articles/PMC7903160; pdf:https://europepmc.org/articles/PMC7903160?pdf=render @@ -2523,9 +2523,9 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 33495597,https://doi.org/10.1038/s41588-020-00764-0,Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity.,"Harper AR, Goel A, Grace C, Thomson KL, Petersen SE, Xu X, Waring A, Ormondroyd E, Kramer CM, Ho CY, Neubauer S, HCMR Investigators, Tadros R, Ware JS, Bezzina CR, Farrall M, Watkins H.",,Nature genetics,2021,2021-01-25,N,,,,"Hypertrophic cardiomyopathy (HCM) is a common, serious, genetic heart disorder. Rare pathogenic variants in sarcomere genes cause HCM, but with unexplained phenotypic heterogeneity. Moreover, most patients do not carry such variants. We report a genome-wide association study of 2,780 cases and 47,486 controls that identified 12 genome-wide-significant susceptibility loci for HCM. Single-nucleotide polymorphism heritability indicated a strong polygenic influence, especially for sarcomere-negative HCM (64% of cases; h2g = 0.34 ± 0.02). A genetic risk score showed substantial influence on the odds of HCM in a validation study, halving the odds in the lowest quintile and doubling them in the highest quintile, and also influenced phenotypic severity in sarcomere variant carriers. Mendelian randomization identified diastolic blood pressure (DBP) as a key modifiable risk factor for sarcomere-negative HCM, with a one standard deviation increase in DBP increasing the HCM risk fourfold. Common variants and modifiable risk factors have important roles in HCM that we suggest will be clinically actionable.",,pdf:https://openaccess.sgul.ac.uk/id/eprint/113790/1/EMS128763.pdf; doi:https://doi.org/10.1038/s41588-020-00764-0; html:https://europepmc.org/articles/PMC8240954; pdf:https://europepmc.org/articles/PMC8240954?pdf=render; doi:https://doi.org/10.1038/s41588-020-00764-0 33050951,https://doi.org/10.1186/s12916-020-01789-2,Response strategies for COVID-19 epidemics in African settings: a mathematical modelling study.,"van Zandvoort K, Jarvis CI, Pearson CAB, Davies NG, CMMID COVID-19 working group, Ratnayake R, Russell TW, Kucharski AJ, Jit M, Flasche S, Eggo RM, Checchi F.",,BMC medicine,2020,2020-10-14,Y,Control; Response; Africa; Coronavirus; mathematical model; Low-income; Covid-19; Sars-cov-2,,,"

Background

The health impact of COVID-19 may differ in African settings as compared to countries in Europe or China due to demographic, epidemiological, environmental and socio-economic factors. We evaluated strategies to reduce SARS-CoV-2 burden in African countries, so as to support decisions that balance minimising mortality, protecting health services and safeguarding livelihoods.

Methods

We used a Susceptible-Exposed-Infectious-Recovered mathematical model, stratified by age, to predict the evolution of COVID-19 epidemics in three countries representing a range of age distributions in Africa (from oldest to youngest average age: Mauritius, Nigeria and Niger), under various effectiveness assumptions for combinations of different non-pharmaceutical interventions: self-isolation of symptomatic people, physical distancing and 'shielding' (physical isolation) of the high-risk population. We adapted model parameters to better represent uncertainty about what might be expected in African populations, in particular by shifting the distribution of severity risk towards younger ages and increasing the case-fatality ratio. We also present sensitivity analyses for key model parameters subject to uncertainty.

Results

We predicted median symptomatic attack rates over the first 12 months of 23% (Niger) to 42% (Mauritius), peaking at 2-4 months, if epidemics were unmitigated. Self-isolation while symptomatic had a maximum impact of about 30% on reducing severe cases, while the impact of physical distancing varied widely depending on percent contact reduction and R0. The effect of shielding high-risk people, e.g. by rehousing them in physical isolation, was sensitive mainly to residual contact with low-risk people, and to a lesser extent to contact among shielded individuals. Mitigation strategies incorporating self-isolation of symptomatic individuals, moderate physical distancing and high uptake of shielding reduced predicted peak bed demand and mortality by around 50%. Lockdowns delayed epidemics by about 3 months. Estimates were sensitive to differences in age-specific social mixing patterns, as published in the literature, and assumptions on transmissibility, infectiousness of asymptomatic cases and risk of severe disease or death by age.

Conclusions

In African settings, as elsewhere, current evidence suggests large COVID-19 epidemics are expected. However, African countries have fewer means to suppress transmission and manage cases. We found that self-isolation of symptomatic persons and general physical distancing are unlikely to avert very large epidemics, unless distancing takes the form of stringent lockdown measures. However, both interventions help to mitigate the epidemic. Shielding of high-risk individuals can reduce health service demand and, even more markedly, mortality if it features high uptake and low contact of shielded and unshielded people, with no increase in contact among shielded people. Strategies combining self-isolation, moderate physical distancing and shielding could achieve substantial reductions in mortality in African countries. Temporary lockdowns, where socioeconomically acceptable, can help gain crucial time for planning and expanding health service capacity.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01789-2; doi:https://doi.org/10.1186/s12916-020-01789-2; html:https://europepmc.org/articles/PMC7553800; pdf:https://europepmc.org/articles/PMC7553800?pdf=render 33031764,https://doi.org/10.1016/s0140-6736(20)32013-4,"Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2020,2020-10-05,Y,,,,"

Background

Lopinavir-ritonavir has been proposed as a treatment for COVID-19 on the basis of in vitro activity, preclinical studies, and observational studies. Here, we report the results of a randomised trial to assess whether lopinavir-ritonavir improves outcomes in patients admitted to hospital with COVID-19.

Methods

In this randomised, controlled, open-label, platform trial, a range of possible treatments was compared with usual care in patients admitted to hospital with COVID-19. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus lopinavir-ritonavir (400 mg and 100 mg, respectively) by mouth for 10 days or until discharge (or one of the other RECOVERY treatment groups: hydroxychloroquine, dexamethasone, or azithromycin) using web-based simple (unstratified) randomisation with allocation concealment. Randomisation to usual care was twice that of any of the active treatment groups (eg, 2:1 in favour of usual care if the patient was eligible for only one active group, 2:1:1 if the patient was eligible for two active groups). The primary outcome was 28-day all-cause mortality. Analyses were done on an intention-to-treat basis in all randomly assigned participants. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.

Findings

Between March 19, 2020, and June 29, 2020, 1616 patients were randomly allocated to receive lopinavir-ritonavir and 3424 patients to receive usual care. Overall, 374 (23%) patients allocated to lopinavir-ritonavir and 767 (22%) patients allocated to usual care died within 28 days (rate ratio 1·03, 95% CI 0·91-1·17; p=0·60). Results were consistent across all prespecified subgroups of patients. We observed no significant difference in time until discharge alive from hospital (median 11 days [IQR 5 to >28] in both groups) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 0·98, 95% CI 0·91-1·05; p=0·53). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion who met the composite endpoint of invasive mechanical ventilation or death (risk ratio 1·09, 95% CI 0·99-1·20; p=0·092).

Interpretation

In patients admitted to hospital with COVID-19, lopinavir-ritonavir was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death. These findings do not support the use of lopinavir-ritonavir for treatment of patients admitted to hospital with COVID-19.

Funding

Medical Research Council and National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S0140673620320134/pdf; doi:https://doi.org/10.1016/S0140-6736(20)32013-4; html:https://europepmc.org/articles/PMC7535623 -37681566,https://doi.org/10.1161/jaha.123.030280,Age at Menopause and the Risk of Stroke: Observational and Mendelian Randomization Analysis in 204 244 Postmenopausal Women.,"Tschiderer L, Peters SAE, van der Schouw YT, van Westing AC, Tong TYN, Willeit P, Seekircher L, Moreno-Iribas C, Huerta JM, Crous-Bou M, Söderholm M, Schulze MB, Johansson C, Själander S, Heath AK, Macciotta A, Dahm CC, Ibsen DB, Pala V, Mellemkjær L, Burgess S, Wood A, Kaaks R, Katzke V, Amiano P, Rodriguez-Barranco M, Engström G, Weiderpass E, Tjønneland A, Halkjær J, Panico S, Danesh J, Butterworth A, Onland-Moret NC.",,Journal of the American Heart Association,2023,2023-09-08,Y,Stroke; Age At Menopause; Mendelian Randomization Analysis; Observational Analysis,,,"Background Observational studies have shown that women with an early menopause are at higher risk of stroke compared with women with a later menopause. However, associations with stroke subtypes are inconsistent, and the causality is unclear. Methods and Results We analyzed data of the UK Biobank and EPIC-CVD (European Prospective Investigation Into Cancer and Nutrition-Cardiovascular Diseases) study. A total of 204 244 postmenopausal women without a history of stroke at baseline were included (7883 from EPIC-CVD [5292 from the subcohort], 196 361 from the UK Biobank). Pooled mean baseline age was 58.9 years (SD, 5.8), and pooled mean age at menopause was 47.8 years (SD, 6.2). Over a median follow-up of 12.6 years (interquartile range, 11.8-13.3), 6770 women experienced a stroke (5155 ischemic strokes, 1615 hemorrhagic strokes, 976 intracerebral hemorrhages, and 639 subarachnoid hemorrhages). In multivariable adjusted observational Cox regression analyses, the pooled hazard ratios per 5 years younger age at menopause were 1.09 (95% CI, 1.07-1.12) for stroke, 1.09 (95% CI, 1.06-1.13) for ischemic stroke, 1.10 (95% CI, 1.04-1.16) for hemorrhagic stroke, 1.14 (95% CI, 1.08-1.20) for intracerebral hemorrhage, and 1.00 (95% CI, 0.84-1.20) for subarachnoid hemorrhage. When using 2-sample Mendelian randomization analysis, we found no statistically significant association between genetically proxied age at menopause and risk of any type of stroke. Conclusions In our study, earlier age at menopause was related to a higher risk of stroke. We found no statistically significant association between genetically proxied age at menopause and risk of stroke, suggesting no causal relationship.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.030280; doi:https://doi.org/10.1161/JAHA.123.030280; html:https://europepmc.org/articles/PMC10547274; pdf:https://europepmc.org/articles/PMC10547274?pdf=render 33421867,https://doi.org/10.1016/j.jad.2020.12.053,Comorbidity of self-harm and disordered eating in young people: Evidence from a UK population-based cohort.,"Warne N, Heron J, Mars B, Moran P, Stewart A, Munafò M, Biddle L, Skinner A, Gunnell D, Bould H.",,Journal of affective disorders,2021,2021-01-07,Y,epidemiology; Self-harm; Comorbidity; Alspac; Disordered Eating,,,"

Background

Self-harm and eating disorders are often comorbid in clinical samples but their co-occurrence in the general population is unclear. Given that only a small proportion of individuals who self-harm or have disordered eating present to clinical services, and that both self-harm and eating disorders are associated with substantial morbidity and mortality, it is important to study these behaviours at a population level.

Methods

We assessed the co-occurrence of self-harm and disordered eating behaviours in 3384 females and 2326 males from a UK population-based cohort: the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants reported on their self-harm and disordered eating behaviours (fasting, purging, binge-eating and excessive exercise) in the last year via questionnaire at 16 and 24 years. At each age we assessed how many individuals who self-harm also reported disordered eating, and how many individuals with disordered eating also reported self-harm.

Results

We found high comorbidity of self-harm and disordered eating. Almost two-thirds of 16-year-old females, and two-in-five 24-year old males who self-harmed also reported some form of disordered eating. Young people with disordered eating reported higher levels of self-harm at both ages compared to those without disordered eating.

Limitations

We were not able to measure whether participants identified their disordered eating as a method of self-harm.

Conclusions

Self-harm and disordered eating commonly co-occur in young people in the general population. It is important to screen for both sets of difficulties to provide appropriate treatment.",,doi:https://doi.org/10.1016/j.jad.2020.12.053; doi:https://doi.org/10.1016/j.jad.2020.12.053; html:https://europepmc.org/articles/PMC8150329 33420068,https://doi.org/10.1038/s41541-020-00267-3,Mammalian expression of virus-like particles as a proof of principle for next generation polio vaccines.,"Bahar MW, Porta C, Fox H, Macadam AJ, Fry EE, Stuart DI.",,NPJ vaccines,2021,2021-01-08,Y,,,,"Global vaccination programs using live-attenuated oral and inactivated polio vaccine (OPV and IPV) have almost eradicated poliovirus (PV) but these vaccines or their production pose significant risk in a polio-free world. Recombinant PV virus-like particles (VLPs), lacking the viral genome, represent safe next-generation vaccines, however their production requires optimisation. Here we present an efficient mammalian expression strategy producing good yields of wild-type PV VLPs for all three serotypes and a thermostabilised variant for PV3. Whilst the wild-type VLPs were predominantly in the non-native C-antigenic form, the thermostabilised PV3 VLPs adopted the native D-antigenic conformation eliciting neutralising antibody titres equivalent to the current IPV and were indistinguishable from natural empty particles by cryo-electron microscopy with a similar stabilising lipidic pocket-factor in the VP1 β-barrel. This factor may not be available in alternative expression systems, which may require synthetic pocket-binding factors. VLPs equivalent to these mammalian expressed thermostabilized particles, represent safer non-infectious vaccine candidates for the post-eradication era.",,pdf:https://www.nature.com/articles/s41541-020-00267-3.pdf; doi:https://doi.org/10.1038/s41541-020-00267-3; html:https://europepmc.org/articles/PMC7794334; pdf:https://europepmc.org/articles/PMC7794334?pdf=render +37681566,https://doi.org/10.1161/jaha.123.030280,Age at Menopause and the Risk of Stroke: Observational and Mendelian Randomization Analysis in 204 244 Postmenopausal Women.,"Tschiderer L, Peters SAE, van der Schouw YT, van Westing AC, Tong TYN, Willeit P, Seekircher L, Moreno-Iribas C, Huerta JM, Crous-Bou M, Söderholm M, Schulze MB, Johansson C, Själander S, Heath AK, Macciotta A, Dahm CC, Ibsen DB, Pala V, Mellemkjær L, Burgess S, Wood A, Kaaks R, Katzke V, Amiano P, Rodriguez-Barranco M, Engström G, Weiderpass E, Tjønneland A, Halkjær J, Panico S, Danesh J, Butterworth A, Onland-Moret NC.",,Journal of the American Heart Association,2023,2023-09-08,Y,Stroke; Age At Menopause; Mendelian Randomization Analysis; Observational Analysis,,,"Background Observational studies have shown that women with an early menopause are at higher risk of stroke compared with women with a later menopause. However, associations with stroke subtypes are inconsistent, and the causality is unclear. Methods and Results We analyzed data of the UK Biobank and EPIC-CVD (European Prospective Investigation Into Cancer and Nutrition-Cardiovascular Diseases) study. A total of 204 244 postmenopausal women without a history of stroke at baseline were included (7883 from EPIC-CVD [5292 from the subcohort], 196 361 from the UK Biobank). Pooled mean baseline age was 58.9 years (SD, 5.8), and pooled mean age at menopause was 47.8 years (SD, 6.2). Over a median follow-up of 12.6 years (interquartile range, 11.8-13.3), 6770 women experienced a stroke (5155 ischemic strokes, 1615 hemorrhagic strokes, 976 intracerebral hemorrhages, and 639 subarachnoid hemorrhages). In multivariable adjusted observational Cox regression analyses, the pooled hazard ratios per 5 years younger age at menopause were 1.09 (95% CI, 1.07-1.12) for stroke, 1.09 (95% CI, 1.06-1.13) for ischemic stroke, 1.10 (95% CI, 1.04-1.16) for hemorrhagic stroke, 1.14 (95% CI, 1.08-1.20) for intracerebral hemorrhage, and 1.00 (95% CI, 0.84-1.20) for subarachnoid hemorrhage. When using 2-sample Mendelian randomization analysis, we found no statistically significant association between genetically proxied age at menopause and risk of any type of stroke. Conclusions In our study, earlier age at menopause was related to a higher risk of stroke. We found no statistically significant association between genetically proxied age at menopause and risk of stroke, suggesting no causal relationship.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.030280; doi:https://doi.org/10.1161/JAHA.123.030280; html:https://europepmc.org/articles/PMC10547274; pdf:https://europepmc.org/articles/PMC10547274?pdf=render 32877352,https://doi.org/10.2196/19992,Using Smartphones and Wearable Devices to Monitor Behavioral Changes During COVID-19.,"Sun S, Folarin AA, Ranjan Y, Rashid Z, Conde P, Stewart C, Cummins N, Matcham F, Dalla Costa G, Simblett S, Leocani L, Lamers F, Sørensen PS, Buron M, Zabalza A, Guerrero Pérez AI, Penninx BW, Siddi S, Haro JM, Myin-Germeys I, Rintala A, Wykes T, Narayan VA, Comi G, Hotopf M, Dobson RJ, RADAR-CNS Consortium.",,Journal of medical Internet research,2020,2020-09-25,Y,Mobility; Smartphones; Mobile Health; Behavioral Monitoring; Wearable Devices; Phone Use; Covid-19,,,"

Background

In the absence of a vaccine or effective treatment for COVID-19, countries have adopted nonpharmaceutical interventions (NPIs) such as social distancing and full lockdown. An objective and quantitative means of passively monitoring the impact and response of these interventions at a local level is needed.

Objective

We aim to explore the utility of the recently developed open-source mobile health platform Remote Assessment of Disease and Relapse (RADAR)-base as a toolbox to rapidly test the effect and response to NPIs intended to limit the spread of COVID-19.

Methods

We analyzed data extracted from smartphone and wearable devices, and managed by the RADAR-base from 1062 participants recruited in Italy, Spain, Denmark, the United Kingdom, and the Netherlands. We derived nine features on a daily basis including time spent at home, maximum distance travelled from home, the maximum number of Bluetooth-enabled nearby devices (as a proxy for physical distancing), step count, average heart rate, sleep duration, bedtime, phone unlock duration, and social app use duration. We performed Kruskal-Wallis tests followed by post hoc Dunn tests to assess differences in these features among baseline, prelockdown, and during lockdown periods. We also studied behavioral differences by age, gender, BMI, and educational background.

Results

We were able to quantify expected changes in time spent at home, distance travelled, and the number of nearby Bluetooth-enabled devices between prelockdown and during lockdown periods (P<.001 for all five countries). We saw reduced sociality as measured through mobility features and increased virtual sociality through phone use. People were more active on their phones (P<.001 for Italy, Spain, and the United Kingdom), spending more time using social media apps (P<.001 for Italy, Spain, the United Kingdom, and the Netherlands), particularly around major news events. Furthermore, participants had a lower heart rate (P<.001 for Italy and Spain; P=.02 for Denmark), went to bed later (P<.001 for Italy, Spain, the United Kingdom, and the Netherlands), and slept more (P<.001 for Italy, Spain, and the United Kingdom). We also found that young people had longer homestay than older people during the lockdown and fewer daily steps. Although there was no significant difference between the high and low BMI groups in time spent at home, the low BMI group walked more.

Conclusions

RADAR-base, a freely deployable data collection platform leveraging data from wearables and mobile technologies, can be used to rapidly quantify and provide a holistic view of behavioral changes in response to public health interventions as a result of infectious outbreaks such as COVID-19. RADAR-base may be a viable approach to implementing an early warning system for passively assessing the local compliance to interventions in epidemics and pandemics, and could help countries ease out of lockdown.",,pdf:https://www.jmir.org/2020/9/e19992/PDF; doi:https://doi.org/10.2196/19992; html:https://europepmc.org/articles/PMC7527031 32488134,https://doi.org/10.1038/s41598-020-65855-8,The Human Leukocyte Antigen Locus and Rheumatic Heart Disease Susceptibility in South Asians and Europeans.,"Auckland K, Mittal B, Cairns BJ, Garg N, Kumar S, Mentzer AJ, Kado J, Perman ML, Steer AC, Hill AVS, Parks T.",,Scientific reports,2020,2020-06-02,Y,,,,"Rheumatic heart disease (RHD), an autoinflammatory heart disease, was recently declared a global health priority by the World Health Organization. Here we report a genome-wide association study (GWAS) of RHD susceptibility in 1,163 South Asians (672 cases; 491 controls) recruited in India and Fiji. We analysed directly obtained and imputed genotypes, and followed-up associated loci in 1,459 Europeans (150 cases; 1,309 controls) from the UK Biobank study. We identify a novel susceptibility signal in the class III region of the human leukocyte antigen (HLA) complex in the South Asian dataset that clearly replicates in the Europeans (rs201026476; combined odds ratio 1.81, 95% confidence intervals 1.51-2.18, P = 3.48×10-10). Importantly, this signal remains despite conditioning on the lead class I and class II variants (P = 0.00033). These findings suggest the class III region is a key determinant of RHD susceptibility offering important new insight into pathogenesis while partly explaining the inconsistency of earlier reports.",,pdf:https://www.nature.com/articles/s41598-020-65855-8.pdf; doi:https://doi.org/10.1038/s41598-020-65855-8; html:https://europepmc.org/articles/PMC7265443; pdf:https://europepmc.org/articles/PMC7265443?pdf=render 34800427,https://doi.org/10.1016/s0140-6736(21)01825-0,"Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2022,2021-11-17,Y,,,,"

Background

Aspirin has been proposed as a treatment for COVID-19 on the basis of its anti-thrombotic properties. We aimed to evaluate the efficacy and safety of aspirin in patients admitted to hospital with COVID-19.

Methods

In this randomised, controlled, open-label, platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. The trial took place at 177 hospitals in the UK, two hospitals in Indonesia, and two hospitals in Nepal. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care plus 150 mg aspirin once per day until discharge or usual standard of care alone using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28 day mortality. All analyses were done by intention to treat. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between Nov 1, 2020, and March 21, 2021, 14 892 (66%) of 22 560 patients enrolled into the RECOVERY trial were eligible to be randomly allocated to aspirin. 7351 patients were randomly allocated (1:1) to receive aspirin and 7541 patients to receive usual care alone. Overall, 1222 (17%) of 7351 patients allocated to aspirin and 1299 (17%) of 7541 patients allocated to usual care died within 28 days (rate ratio 0·96, 95% CI 0·89-1·04; p=0·35). Consistent results were seen in all prespecified subgroups of patients. Patients allocated to aspirin had a slightly shorter duration of hospitalisation (median 8 days, IQR 5 to >28, vs 9 days, IQR 5 to >28) and a higher proportion were discharged from hospital alive within 28 days (75% vs 74%; rate ratio 1·06, 95% CI 1·02-1·10; p=0·0062). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs 22%; risk ratio 0·96, 95% CI 0·90-1·03; p=0·23). Aspirin use was associated with a reduction in thrombotic events (4·6% vs 5·3%; absolute reduction 0·6%, SE 0·4%) and an increase in major bleeding events (1·6% vs 1·0%; absolute increase 0·6%, SE 0·2%).

Interpretation

In patients hospitalised with COVID-19, aspirin was not associated with reductions in 28 day mortality or in the risk of progressing to invasive mechanical ventilation or death, but was associated with a small increase in the rate of being discharged alive within 28 days.

Funding

UK Research and Innovation (Medical Research Council), National Institute of Health Research, and the Wellcome Trust through the COVID-19 Therapeutics Accelerator.",,doi:https://doi.org/10.1016/s0140-6736(21)01825-0; doi:https://doi.org/10.1016/S0140-6736(21)01825-0; html:https://europepmc.org/articles/PMC8598213 @@ -2535,8 +2535,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 35609980,https://doi.org/10.1093/nar/gkac364,GEOexplorer: a webserver for gene expression analysis and visualisation.,"Hunt GP, Grassi L, Henkin R, Smeraldi F, Spargo TP, Kabiljo R, Koks S, Ibrahim Z, Dobson RJB, Al-Chalabi A, Barnes MR, Iacoangeli A.",,Nucleic acids research,2022,2022-07-01,Y,,,,"Gene Expression Omnibus (GEO) is a database repository hosting a substantial proportion of publicly available high throughput gene expression data. Gene expression analysis is a powerful tool to gain insight into the mechanisms and processes underlying the biological and phenotypic differences between sample groups. Despite the wide availability of gene expression datasets, their access, analysis, and integration are not trivial and require specific expertise and programming proficiency. We developed the GEOexplorer webserver to allow scientists to access, integrate and analyse gene expression datasets without requiring programming proficiency. Via its user-friendly graphic interface, users can easily apply GEOexplorer to perform interactive and reproducible gene expression analysis of microarray and RNA-seq datasets, while producing a wealth of interactive visualisations to facilitate data exploration and interpretation, and generating a range of publication ready figures. The webserver allows users to search and retrieve datasets from GEO as well as to upload user-generated data and combine and harmonise two datasets to perform joint analyses. GEOexplorer, available at https://geoexplorer.rosalind.kcl.ac.uk, provides a solution for performing interactive and reproducible analyses of microarray and RNA-seq gene expression data, empowering life scientists to perform exploratory data analysis and differential gene expression analysis on-the-fly without informatics proficiency.",,pdf:https://researchrepository.murdoch.edu.au/id/eprint/64965/1/geneexpression.pdf; doi:https://doi.org/10.1093/nar/gkac364; html:https://europepmc.org/articles/PMC9252785; pdf:https://europepmc.org/articles/PMC9252785?pdf=render 36113526,https://doi.org/10.1016/s2214-109x(22)00332-1,"Mapping development and health effects of cooking with solid fuels in low-income and middle-income countries, 2000-18: a geospatial modelling study.",Local Burden of Disease Household Air Pollution Collaborators.,,The Lancet. Global health,2022,2022-10-01,Y,,,,"

Background

More than 3 billion people do not have access to clean energy and primarily use solid fuels to cook. Use of solid fuels generates household air pollution, which was associated with more than 2 million deaths in 2019. Although local patterns in cooking vary systematically, subnational trends in use of solid fuels have yet to be comprehensively analysed. We estimated the prevalence of solid-fuel use with high spatial resolution to explore subnational inequalities, assess local progress, and assess the effects on health in low-income and middle-income countries (LMICs) without universal access to clean fuels.

Methods

We did a geospatial modelling study to map the prevalence of solid-fuel use for cooking at a 5 km × 5 km resolution in 98 LMICs based on 2·1 million household observations of the primary cooking fuel used from 663 population-based household surveys over the years 2000 to 2018. We use observed temporal patterns to forecast household air pollution in 2030 and to assess the probability of attaining the Sustainable Development Goal (SDG) target indicator for clean cooking. We aligned our estimates of household air pollution to geospatial estimates of ambient air pollution to establish the risk transition occurring in LMICs. Finally, we quantified the effect of residual primary solid-fuel use for cooking on child health by doing a counterfactual risk assessment to estimate the proportion of deaths from lower respiratory tract infections in children younger than 5 years that could be associated with household air pollution.

Findings

Although primary reliance on solid-fuel use for cooking has declined globally, it remains widespread. 593 million people live in districts where the prevalence of solid-fuel use for cooking exceeds 95%. 66% of people in LMICs live in districts that are not on track to meet the SDG target for universal access to clean energy by 2030. Household air pollution continues to be a major contributor to particulate exposure in LMICs, and rising ambient air pollution is undermining potential gains from reductions in the prevalence of solid-fuel use for cooking in many countries. We estimated that, in 2018, 205 000 (95% uncertainty interval 147 000-257 000) children younger than 5 years died from lower respiratory tract infections that could be attributed to household air pollution.

Interpretation

Efforts to accelerate the adoption of clean cooking fuels need to be substantially increased and recalibrated to account for subnational inequalities, because there are substantial opportunities to improve air quality and avert child mortality associated with household air pollution.

Funding

Bill & Melinda Gates Foundation.",,pdf:https://repository.kaust.edu.sa/bitstream/10754/686177/1/1-s2.0-S2214109X22003321-main.pdf; doi:https://doi.org/10.1016/S2214-109X(22)00332-1; html:https://europepmc.org/articles/PMC9638039 32384159,https://doi.org/10.1093/jtm/taaa068,Effectiveness of interventions targeting air travellers for delaying local outbreaks of SARS-CoV-2.,"Clifford S, Pearson CAB, Klepac P, Van Zandvoort K, Quilty BJ, CMMID COVID-19 working group, Eggo RM, Flasche S.",,Journal of travel medicine,2020,2020-08-01,Y,Coronavirus; Public Health Emergency Of International Concern; Covid-19; Travel Screening,,,"

Background

We evaluated if interventions aimed at air travellers can delay local severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) community transmission in a previously unaffected country.

Methods

We simulated infected air travellers arriving into countries with no sustained SARS-CoV-2 transmission or other introduction routes from affected regions. We assessed the effectiveness of syndromic screening at departure and/or arrival and traveller sensitisation to the COVID-2019-like symptoms with the aim to trigger rapid self-isolation and reporting on symptom onset to enable contact tracing. We assumed that syndromic screening would reduce the number of infected arrivals and that traveller sensitisation reduces the average number of secondary cases. We use stochastic simulations to account for uncertainty in both arrival and secondary infections rates, and present sensitivity analyses on arrival rates of infected travellers and the effectiveness of traveller sensitisation. We report the median expected delay achievable in each scenario and an inner 50% interval.

Results

Under baseline assumptions, introducing exit and entry screening in combination with traveller sensitisation can delay a local SARS-CoV-2 outbreak by 8 days (50% interval: 3-14 days) when the rate of importation is 1 infected traveller per week at time of introduction. The additional benefit of entry screening is small if exit screening is effective: the combination of only exit screening and traveller sensitisation can delay an outbreak by 7 days (50% interval: 2-13 days). In the absence of screening, with less effective sensitisation, or a higher rate of importation, these delays shrink rapidly to <4 days.

Conclusion

Syndromic screening and traveller sensitisation in combination may have marginally delayed SARS-CoV-2 outbreaks in unaffected countries.",,pdf:https://academic.oup.com/jtm/article-pdf/27/5/taaa068/33666000/taaa068.pdf; doi:https://doi.org/10.1093/jtm/taaa068; html:https://europepmc.org/articles/PMC7239177; pdf:https://europepmc.org/articles/PMC7239177?pdf=render -34090494,https://doi.org/10.1186/s13063-021-05284-8,A framework for handling missing accelerometer outcome data in trials.,"Tackney MS, Cook DG, Stahl D, Ismail K, Williamson E, Carpenter J.",,Trials,2021,2021-06-05,Y,Clinical Trial; Missing Data; Accelerometer; Multiple Imputation; Wearables,,,"Accelerometers and other wearable devices are increasingly being used in clinical trials to provide an objective measure of the impact of an intervention on physical activity. Missing data are ubiquitous in this setting, typically for one of two reasons: patients may not wear the device as per protocol, and/or the device may fail to collect data (e.g. flat battery, water damage). However, it is not always possible to distinguish whether the participant stopped wearing the device, or if the participant is wearing the device but staying still. Further, a lack of consensus in the literature on how to aggregate the data before analysis (hourly, daily, weekly) leads to a lack of consensus in how to define a ""missing"" outcome. Different trials have adopted different definitions (ranging from having insufficient step counts in a day, through to missing a certain number of days in a week). We propose an analysis framework that uses wear time to define missingness on the epoch and day level, and propose a multiple imputation approach, at the day level, which treats partially observed daily step counts as right censored. This flexible approach allows the inclusion of auxiliary variables, and is consistent with almost all the primary analysis models described in the literature, and readily allows sensitivity analysis (to the missing at random assumption) to be performed. Having presented our framework, we illustrate its application to the analysis of the 2019 MOVE-IT trial of motivational interviewing to increase exercise.",,pdf:https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-021-05284-8; doi:https://doi.org/10.1186/s13063-021-05284-8; html:https://europepmc.org/articles/PMC8178870; pdf:https://europepmc.org/articles/PMC8178870?pdf=render 32543438,https://doi.org/10.1016/j.healthplace.2020.102355,Impact of air pollution on educational attainment for respiratory health treated students: A cross sectional data linkage study.,"Mizen A, Lyons J, Milojevic A, Doherty R, Wilkinson P, Carruthers D, Akbari A, Lake I, Davies GA, Al Sallakh M, Fry R, Dearden L, Rodgers SE.",,Health & place,2020,2020-05-12,Y,Air pollution; Asthma; poLLen; Data Linkage; Seasonal Allergic Rhinitis; Educational Attainment,,,"

Introduction

There is some evidence that exam results are worse when students are acutely exposed to air pollution. Studies investigating the association between air pollution and academic attainment have been constrained by small sample sizes.

Methods

Cross sectional educational attainment data (2009-2015) from students aged 15-16 years in Cardiff, Wales were linked to primary health care data, modelled air pollution and measured pollen data, and analysed using multilevel linear regression models. Annual cohort, school and individual level confounders were adjusted for in single and multi-pollutant/pollen models. We stratified by treatment of asthma and/or Seasonal Allergic Rhinitis (SAR).

Results

A unit (10μg/m3) increase of short-term exposure to NO2 was associated with 0.044 (95% CI: -0.079, -0.008) reduction of standardised Capped Point Score (CPS) after adjusting for individual and household risk factors for 18,241 students. This association remained statistically significant after controlling for other pollutants and pollen. There was no association of PM2.5, O3, or Pollen with standardised CPS remaining after adjustment. We found no evidence that treatment for asthma or SAR modified the observed NO2 effect on educational attainment.

Conclusion

Our study showed that short-term exposure to traffic-related air pollution, specifically NO2, was associated with detrimental educational attainment for students aged 15-16. Longitudinal investigations in different settings are required to confirm this possible impact and further work may uncover the long-term economic implications, and degree to which impacts are cumulative and permanent.",,doi:https://doi.org/10.1016/j.healthplace.2020.102355; doi:https://doi.org/10.1016/j.healthplace.2020.102355; html:https://europepmc.org/articles/PMC7214342 +34090494,https://doi.org/10.1186/s13063-021-05284-8,A framework for handling missing accelerometer outcome data in trials.,"Tackney MS, Cook DG, Stahl D, Ismail K, Williamson E, Carpenter J.",,Trials,2021,2021-06-05,Y,Clinical Trial; Missing Data; Accelerometer; Multiple Imputation; Wearables,,,"Accelerometers and other wearable devices are increasingly being used in clinical trials to provide an objective measure of the impact of an intervention on physical activity. Missing data are ubiquitous in this setting, typically for one of two reasons: patients may not wear the device as per protocol, and/or the device may fail to collect data (e.g. flat battery, water damage). However, it is not always possible to distinguish whether the participant stopped wearing the device, or if the participant is wearing the device but staying still. Further, a lack of consensus in the literature on how to aggregate the data before analysis (hourly, daily, weekly) leads to a lack of consensus in how to define a ""missing"" outcome. Different trials have adopted different definitions (ranging from having insufficient step counts in a day, through to missing a certain number of days in a week). We propose an analysis framework that uses wear time to define missingness on the epoch and day level, and propose a multiple imputation approach, at the day level, which treats partially observed daily step counts as right censored. This flexible approach allows the inclusion of auxiliary variables, and is consistent with almost all the primary analysis models described in the literature, and readily allows sensitivity analysis (to the missing at random assumption) to be performed. Having presented our framework, we illustrate its application to the analysis of the 2019 MOVE-IT trial of motivational interviewing to increase exercise.",,pdf:https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-021-05284-8; doi:https://doi.org/10.1186/s13063-021-05284-8; html:https://europepmc.org/articles/PMC8178870; pdf:https://europepmc.org/articles/PMC8178870?pdf=render 32855398,https://doi.org/10.1038/s41467-020-18060-0,Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases.,"Rabbie R, Ansari-Pour N, Cast O, Lau D, Scott F, Welsh SJ, Parkinson C, Khoja L, Moore L, Tullett M, Wong K, Ferreira I, Gómez JMM, Levesque M, Gallagher FA, Jiménez-Sánchez A, Riva L, Miller ML, Allinson K, Campbell PJ, Corrie P, Wedge DC, Adams DJ.",,Nature communications,2020,2020-08-27,Y,,,,"Metastatic melanoma carries a poor prognosis despite modern systemic therapies. Understanding the evolution of the disease could help inform patient management. Through whole-genome sequencing of 13 melanoma metastases sampled at autopsy from a treatment naïve patient and by leveraging the analytical power of multi-sample analyses, we reveal evidence of diversification among metastatic lineages. UV-induced mutations dominate the trunk, whereas APOBEC-associated mutations are found in the branches of the evolutionary tree. Multi-sample analyses from a further seven patients confirmed that lineage diversification was pervasive, representing an important mode of melanoma dissemination. Our analyses demonstrate that joint analysis of cancer cell fraction estimates across multiple metastases can uncover previously unrecognised levels of tumour heterogeneity and highlight the limitations of inferring heterogeneity from a single biopsy.",,pdf:https://www.nature.com/articles/s41467-020-18060-0.pdf; doi:https://doi.org/10.1038/s41467-020-18060-0; html:https://europepmc.org/articles/PMC7453196; pdf:https://europepmc.org/articles/PMC7453196?pdf=render 32376654,https://doi.org/10.1136/bmj.m1203,Use of genetic variation to separate the effects of early and later life adiposity on disease risk: mendelian randomisation study.,"Richardson TG, Sanderson E, Elsworth B, Tilling K, Davey Smith G.",,BMJ (Clinical research ed.),2020,2020-05-06,Y,,,,"

Objective

To evaluate whether body size in early life has an independent effect on risk of disease in later life or whether its influence is mediated by body size in adulthood.

Design

Two sample univariable and multivariable mendelian randomisation.

Setting

The UK Biobank prospective cohort study and four large scale genome-wide association studies (GWAS) consortiums.

Participants

453 169 participants enrolled in UK Biobank and a combined total of more than 700 000 people from different GWAS consortiums.

Exposures

Measured body mass index during adulthood (mean age 56.5) and self-reported perceived body size at age 10.

Main outcome measures

Coronary artery disease, type 2 diabetes, breast cancer, and prostate cancer.

Results

Having a larger genetically predicted body size in early life was associated with an increased odds of coronary artery disease (odds ratio 1.49 for each change in body size category unless stated otherwise, 95% confidence interval 1.33 to 1.68) and type 2 diabetes (2.32, 1.76 to 3.05) based on univariable mendelian randomisation analyses. However, little evidence was found of a direct effect (ie, not through adult body size) based on multivariable mendelian randomisation estimates (coronary artery disease: 1.02, 0.86 to 1.22; type 2 diabetes:1.16, 0.74 to 1.82). In the multivariable mendelian randomisation analysis of breast cancer risk, strong evidence was found of a protective direct effect for larger body size in early life (0.59, 0.50 to 0.71), with less evidence of a direct effect of adult body size on this outcome (1.08, 0.93 to 1.27). Including age at menarche as an additional exposure provided weak evidence of a total causal effect (univariable mendelian randomisation odds ratio 0.98, 95% confidence interval 0.91 to 1.06) but strong evidence of a direct causal effect, independent of early life and adult body size (multivariable mendelian randomisation odds ratio 0.90, 0.85 to 0.95). No strong evidence was found of a causal effect of either early or later life measures on prostate cancer (early life body size odds ratio 1.06, 95% confidence interval 0.81 to 1.40; adult body size 0.87, 0.70 to 1.08).

Conclusions

The findings suggest that the positive association between body size in childhood and risk of coronary artery disease and type 2 diabetes in adulthood can be attributed to individuals remaining large into later life. However, having a smaller body size during childhood might increase the risk of breast cancer regardless of body size in adulthood, with timing of puberty also putatively playing a role.",,pdf:https://www.bmj.com/content/bmj/369/bmj.m1203.full.pdf; doi:https://doi.org/10.1136/bmj.m1203; html:https://europepmc.org/articles/PMC7201936 31666367,https://doi.org/10.1128/jcm.01037-19,Hash-Based Core Genome Multilocus Sequence Typing for Clostridium difficile.,"Eyre DW, Peto TEA, Crook DW, Walker AS, Wilcox MH.",,Journal of clinical microbiology,2019,2019-12-23,Y,Quality assurance; Clostridium Difficile; Whole-genome Sequencing; Core Genome Mlst,The Human Phenome,,"Pathogen whole-genome sequencing has huge potential as a tool to better understand infection transmission. However, rapidly identifying closely related genomes among a background of thousands of other genomes is challenging. Here, we describe a refinement to core genome multilocus sequence typing (cgMLST) in which alleles at each gene are reproducibly converted to a unique hash, or short string of letters (hash-cgMLST). This avoids the resource-intensive need for a single centralized database of sequentially numbered alleles. We test the reproducibility and discriminatory power of cgMLST/hash-cgMLST compared to those of mapping-based approaches in Clostridium difficile, using repeated sequencing of the same isolates (replicates) and data from consecutive infection isolates from six English hospitals. Hash-cgMLST provided the same results as standard cgMLST, with minimal performance penalty. Comparing 272 replicate sequence pairs using reference-based mapping, there were 0, 1, or 2 single-nucleotide polymorphisms (SNPs) between 262 (96%), 5 (2%), and 1 (<1%) of the pairs, respectively. Using hash-cgMLST, 218 (80%) of replicate pairs assembled with SPAdes had zero gene differences, and 31 (11%), 5 (2%), and 18 (7%) pairs had 1, 2, and >2 differences, respectively. False gene differences were clustered in specific genes and associated with fragmented assemblies, but were reduced using the SKESA assembler. Considering 412 pairs of infections with ≤2 SNPS, i.e., consistent with recent transmission, 376 (91%) had ≤2 gene differences and 16 (4%) had ≥4. Comparing a genome to 100,000 others took <1 min using hash-cgMLST. Hash-cgMLST is an effective surveillance tool for rapidly identifying clusters of related genomes. However, cgMLST/hash-cgMLST generate more false variants than mapping-based approaches. Follow-up mapping-based analyses are likely required to precisely define close genetic relationships.",,pdf:https://jcm.asm.org/content/jcm/58/1/e01037-19.full.pdf; doi:https://doi.org/10.1128/JCM.01037-19; html:https://europepmc.org/articles/PMC6935933; pdf:https://europepmc.org/articles/PMC6935933?pdf=render @@ -2548,8 +2548,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 31122927,https://doi.org/10.1136/bmj.l1778,Determinants of the decline in mortality from acute stroke in England: linked national database study of 795 869 adults.,"Seminog OO, Scarborough P, Wright FL, Rayner M, Goldacre MJ.",,BMJ (Clinical research ed.),2019,2019-05-22,Y,,Improving Public Health,,"

Objectives

To study trends in stroke mortality rates, event rates, and case fatality, and to explain the extent to which the reduction in stroke mortality rates was influenced by changes in stroke event rates or case fatality.

Design

Population based study.

Setting

Person linked routine hospital and mortality data, England.

Participants

795 869 adults aged 20 and older who were admitted to hospital with acute stroke or died from stroke.

Main outcome measures

Stroke mortality rates, stroke event rates (stroke admission or stroke death without admission), and case fatality within 30 days after stroke.

Results

Between 2001 and 2010 stroke mortality rates decreased by 55%, stroke event rates by 20%, and case fatality by 40%. The study population included 358 599 (45%) men and 437 270 (55%) women. Average annual change in mortality rate was -6.0% (95% confidence interval -6.2% to -5.8%) in men and -6.1% (-6.3% to -6.0%) in women, in stroke event rate was -1.3% (-1.4% to -1.2%) in men and -2.1% (-2.2 to -2.0) in women, and in case fatality was -4.7% (-4.9% to -4.5%) in men and -4.4% (-4.5% to -4.2%) in women. Mortality and case fatality but not event rate declined in all age groups: the stroke event rate decreased in older people but increased by 2% each year in adults aged 35 to 54 years. Of the total decline in mortality rates, 71% was attributed to the decline in case fatality (78% in men and 66% in women) and the remainder to the reduction in stroke event rates. The contribution of the two factors varied between age groups. Whereas the reduction in mortality rates in people younger than 55 years was due to the reduction in case fatality, in the oldest age group (≥85 years) reductions in case fatality and event rates contributed nearly equally.

Conclusions

Declines in case fatality, probably driven by improvements in stroke care, contributed more than declines in event rates to the overall reduction in stroke mortality. Mortality reduction in men and women younger than 55 was solely a result of a decrease in case fatality, whereas stroke event rates increased in the age group 35 to 54 years. The increase in stroke event rates in young adults is a concern. This suggests that stroke prevention needs to be strengthened to reduce the occurrence of stroke in people younger than 55 years.",,pdf:https://www.bmj.com/content/bmj/365/bmj.l1778.full.pdf; doi:https://doi.org/10.1136/bmj.l1778; html:https://europepmc.org/articles/PMC6529851 35027740,https://doi.org/10.1038/s41588-021-00996-8,Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-19.,"Huffman JE, Butler-Laporte G, Khan A, Pairo-Castineira E, Drivas TG, Peloso GM, Nakanishi T, COVID-19 Host Genetics Initiative, Ganna A, Verma A, Baillie JK, Kiryluk K, Richards JB, Zeberg H.",,Nature genetics,2022,2022-01-13,Y,,,,"The OAS1/2/3 cluster has been identified as a risk locus for severe COVID-19 among individuals of European ancestry, with a protective haplotype of approximately 75 kilobases (kb) derived from Neanderthals in the chromosomal region 12q24.13. This haplotype contains a splice variant of OAS1, which occurs in people of African ancestry independently of gene flow from Neanderthals. Using trans-ancestry fine-mapping approaches in 20,779 hospitalized cases, we demonstrate that this splice variant is likely to be the SNP responsible for the association at this locus, thus strongly implicating OAS1 as an effector gene influencing COVID-19 severity.",,pdf:https://www.nature.com/articles/s41588-021-00996-8.pdf; doi:https://doi.org/10.1038/s41588-021-00996-8; html:https://europepmc.org/articles/PMC8837537; pdf:https://europepmc.org/articles/PMC8837537?pdf=render 37221040,https://doi.org/10.1136/oemed-2022-108700,"Coverage, completion and outcomes of COVID-19 risk assessments in a multi-ethnic nationwide cohort of UK healthcare workers: a cross-sectional analysis from the UK-REACH Study.","Martin CA, Woolf K, Bryant L, Goss C, Gogoi M, Lagrata S, Papineni P, Qureshi I, Wobi F, Nellums L, Khunti K, Pareek M, UK-REACH Study Collaborative Group.",,Occupational and environmental medicine,2023,2023-05-23,Y,Ethnic Groups; risk assessment; Health Personnel; Covid-19,,,"

Introduction

There are limited data on the outcomes of COVID-19 risk assessment in healthcare workers (HCWs) or the association of ethnicity, other sociodemographic and occupational factors with risk assessment outcomes.

Methods

We used questionnaire data from UK-REACH (UK Research study into Ethnicity And COVID-19 outcomes in Healthcare workers), an ethnically diverse, nationwide cohort of UK HCWs. We derived four binary outcomes: (1) offered a risk assessment; (2) completed a risk assessment; (3) working practices changed as a result of the risk assessment; (4) wanted changes to working practices after risk assessment but working practices did not change.We examined the association of ethnicity, other sociodemographic/occupational factors and actual/perceived COVID-19 risk variables on our outcomes using multivariable logistic regression.

Results

8649 HCWs were included in total. HCWs from ethnic minority groups were more likely to report being offered a risk assessment than white HCWs, and those from Asian and black ethnic groups were more likely to report having completed an assessment if offered. Ethnic minority HCWs had lower odds of reporting having their work change as a result of risk assessment. Those from Asian and black ethnic groups were more likely to report no changes to their working practices despite wanting them.Previous SARS-CoV-2 infection was associated with lower odds of being offered a risk assessment and having adjustments made to working practices.

Discussion

We found differences in risk assessment outcomes by ethnicity, other sociodemographic/occupational factors and actual/perceived COVID-19 risk factors. These findings are concerning and warrant further research using actual (rather than reported) risk assessment outcomes in an unselected cohort.",,pdf:https://oem.bmj.com/content/oemed/80/7/399.full.pdf; doi:https://doi.org/10.1136/oemed-2022-108700; html:https://europepmc.org/articles/PMC10314065; pdf:https://europepmc.org/articles/PMC10314065?pdf=render -33203707,https://doi.org/10.2337/dc20-1328,Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations.,"Zheng JS, Luan J, Sofianopoulou E, Imamura F, Stewart ID, Day FR, Pietzner M, Wheeler E, Lotta LA, Gundersen TE, Amiano P, Ardanaz E, Chirlaque MD, Fagherazzi G, Franks PW, Kaaks R, Laouali N, Mancini FR, Nilsson PM, Onland-Moret NC, Olsen A, Overvad K, Panico S, Palli D, Ricceri F, Rolandsson O, Spijkerman AMW, Sánchez MJ, Schulze MB, Sala N, Sieri S, Tjønneland A, Tumino R, van der Schouw YT, Weiderpass E, Riboli E, Danesh J, Butterworth AS, Sharp SJ, Langenberg C, Forouhi NG, Wareham NJ.",,Diabetes care,2021,2020-11-17,Y,,,,"

Objective

Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes.

Research design and methods

We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants.

Results

We identified 11 genomic regions associated with plasma vitamin C (P < 5 × 10-8), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10).

Conclusions

These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.",,pdf:https://diabetesjournals.org/care/article-pdf/44/1/98/532486/dc201328.pdf; doi:https://doi.org/10.2337/dc20-1328; html:https://europepmc.org/articles/PMC7783939; pdf:https://europepmc.org/articles/PMC7783939?pdf=render 32062083,https://doi.org/10.1016/j.neuroimage.2020.116604,Optimising network modelling methods for fMRI.,"Pervaiz U, Vidaurre D, Woolrich MW, Smith SM.",,NeuroImage,2020,2020-02-13,Y,Functional Connectivity; Connectome; Deep Learning; Riemannian Geometry; Convolutional Neural Networks; Netmat,,,"A major goal of neuroimaging studies is to develop predictive models to analyze the relationship between whole brain functional connectivity patterns and behavioural traits. However, there is no single widely-accepted standard pipeline for analyzing functional connectivity. The common procedure for designing functional connectivity based predictive models entails three main steps: parcellating the brain, estimating the interaction between defined parcels, and lastly, using these integrated associations between brain parcels as features fed to a classifier for predicting non-imaging variables e.g., behavioural traits, demographics, emotional measures, etc. There are also additional considerations when using correlation-based measures of functional connectivity, resulting in three supplementary steps: utilising Riemannian geometry tangent space parameterization to preserve the geometry of functional connectivity; penalizing the connectivity estimates with shrinkage approaches to handle challenges related to short time-series (and noisy) data; and removing confounding variables from brain-behaviour data. These six steps are contingent on each-other, and to optimise a general framework one should ideally examine these various methods simultaneously. In this paper, we investigated strengths and short-comings, both independently and jointly, of the following measures: parcellation techniques of four kinds (categorized further depending upon number of parcels), five measures of functional connectivity, the decision of staying in the ambient space of connectivity matrices or in tangent space, the choice of applying shrinkage estimators, six alternative techniques for handling confounds and finally four novel classifiers/predictors. For performance evaluation, we have selected two of the largest datasets, UK Biobank and the Human Connectome Project resting state fMRI data, and have run more than 9000 different pipeline variants on a total of ∼14000 individuals to determine the optimum pipeline. For independent performance validation, we have run some best-performing pipeline variants on ABIDE and ACPI datasets (∼1000 subjects) to evaluate the generalisability of proposed network modelling methods.",,doi:https://doi.org/10.1016/j.neuroimage.2020.116604; doi:https://doi.org/10.1016/j.neuroimage.2020.116604; html:https://europepmc.org/articles/PMC7086233 +33203707,https://doi.org/10.2337/dc20-1328,Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations.,"Zheng JS, Luan J, Sofianopoulou E, Imamura F, Stewart ID, Day FR, Pietzner M, Wheeler E, Lotta LA, Gundersen TE, Amiano P, Ardanaz E, Chirlaque MD, Fagherazzi G, Franks PW, Kaaks R, Laouali N, Mancini FR, Nilsson PM, Onland-Moret NC, Olsen A, Overvad K, Panico S, Palli D, Ricceri F, Rolandsson O, Spijkerman AMW, Sánchez MJ, Schulze MB, Sala N, Sieri S, Tjønneland A, Tumino R, van der Schouw YT, Weiderpass E, Riboli E, Danesh J, Butterworth AS, Sharp SJ, Langenberg C, Forouhi NG, Wareham NJ.",,Diabetes care,2021,2020-11-17,Y,,,,"

Objective

Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes.

Research design and methods

We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants.

Results

We identified 11 genomic regions associated with plasma vitamin C (P < 5 × 10-8), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10).

Conclusions

These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.",,pdf:https://diabetesjournals.org/care/article-pdf/44/1/98/532486/dc201328.pdf; doi:https://doi.org/10.2337/dc20-1328; html:https://europepmc.org/articles/PMC7783939; pdf:https://europepmc.org/articles/PMC7783939?pdf=render 31005938,https://doi.org/10.1136/bmjopen-2018-027289,"Longitudinal access and exposure to green-blue spaces and individual-level mental health and well-being: protocol for a longitudinal, population-wide record-linked natural experiment.","Mizen A, Song J, Fry R, Akbari A, Berridge D, Parker SC, Johnson R, Lovell R, Lyons RA, Nieuwenhuijsen M, Stratton G, Wheeler BW, White J, White M, Rodgers SE.",,BMJ open,2019,2019-04-20,Y,Geographic information systems; Mental health; Environmental exposure; Longitudinal; Wellbeing; Routine Linked Data,Improving Public Health,,"

Introduction

Studies suggest that access and exposure to green-blue spaces (GBS) have beneficial impacts on mental health. However, the evidence base is limited with respect to longitudinal studies. The main aim of this longitudinal, population-wide, record-linked natural experiment, is to model the daily lived experience by linking GBS accessibility indices, residential GBS exposure and health data; to enable quantification of the impact of GBS on well-being and common mental health disorders, for a national population.

Methods and analysis

This research will estimate the impact of neighbourhood GBS access, GBS exposure and visits to GBS on the risk of common mental health conditions and the opportunity for promoting subjective well-being (SWB); both key priorities for public health. We will use a Geographic Information System (GIS) to create quarterly household GBS accessibility indices and GBS exposure using digital map and satellite data for 1.4 million homes in Wales, UK (2008-2018). We will link the GBS accessibility indices and GBS exposures to individual-level mental health outcomes for 1.7 million people with general practitioner (GP) data and data from the National Survey for Wales (n=~12 000) on well-being in the Secure Anonymised Information Linkage (SAIL) Databank. We will examine if these associations are modified by multiple sociophysical variables, migration and socioeconomic disadvantage. Subgroup analyses will examine associations by different types of GBS. This longitudinal study will be augmented by cross-sectional research using survey data on self-reported visits to GBS and SWB.

Ethics and dissemination

All data will be anonymised and linked within the privacy protecting SAIL Databank. We will be using anonymised data and therefore we are exempt from National Research Ethics Committee (NREC). An Information Governance Review Panel (IGRP) application (Project ID: 0562) to link these data has been approved.The research programme will be undertaken in close collaboration with public/patient involvement groups. A multistrategy programme of dissemination is planned with the academic community, policy-makers, practitioners and the public.",,pdf:https://bmjopen.bmj.com/content/bmjopen/9/4/e027289.full.pdf; doi:https://doi.org/10.1136/bmjopen-2018-027289; html:https://europepmc.org/articles/PMC6528002; pdf:https://europepmc.org/articles/PMC6528002?pdf=render 30524708,https://doi.org/10.1093/ckj/sfy090,The potential for improving cardio-renal outcomes by sodium-glucose co-transporter-2 inhibition in people with chronic kidney disease: a rationale for the EMPA-KIDNEY study.,"Herrington WG, Preiss D, Haynes R, von Eynatten M, Staplin N, Hauske SJ, George JT, Green JB, Landray MJ, Baigent C, Wanner C.",,Clinical kidney journal,2018,2018-10-25,Y,Clinical Trial; cardiovascular; Ckd; Diabetic Kidney Disease; Sglt-2 Inhibitor,"Better, Faster and More Efficient Clinical Trials",,"Diabetes is a common cause of chronic kidney disease (CKD), but in aggregate, non-diabetic diseases account for a higher proportion of cases of CKD than diabetes in many parts of the world. Inhibition of the renin-angiotensin system reduces the risk of kidney disease progression and treatments that lower blood pressure (BP) or low-density lipoprotein cholesterol reduce cardiovascular (CV) risk in this population. Nevertheless, despite such interventions, considerable risks for kidney and CV complications remain. Recently, large placebo-controlled outcome trials have shown that sodium-glucose co-transporter-2 (SGLT-2) inhibitors reduce the risk of CV disease (including CV death and hospitalization for heart failure) in people with type 2 diabetes who are at high risk of atherosclerotic disease, and these effects were largely independent of improvements in hyperglycaemia, BP and body weight. In the kidney, increased sodium delivery to the macula densa mediated by SGLT-2 inhibition has the potential to reduce intraglomerular pressure, which may explain why SGLT-2 inhibitors reduce albuminuria and appear to slow kidney function decline in people with diabetes. Importantly, in the trials completed to date, these benefits appeared to be maintained at lower levels of kidney function, despite attenuation of glycosuric effects, and did not appear to be dependent on ambient hyperglycaemia. There is therefore a rationale for studying the cardio-renal effects of SGLT-2 inhibition in people at risk of CV disease and hyperfiltration (i.e. those with substantially reduced nephron mass and/or albuminuria), irrespective of whether they have diabetes.",,pdf:https://academic.oup.com/ckj/article-pdf/11/6/749/27765283/sfy090.pdf; doi:https://doi.org/10.1093/ckj/sfy090; html:https://europepmc.org/articles/PMC6275453; pdf:https://europepmc.org/articles/PMC6275453?pdf=render 35187482,https://doi.org/10.1093/braincomms/fcab291,Metabolic correlates of late midlife cognitive outcomes: findings from the 1946 British Birth Cohort.,"Green R, Lord J, Xu J, Maddock J, Kim M, Dobson R, Legido-Quigley C, Wong A, Richards M, Proitsi P.",,Brain communications,2022,2021-12-15,Y,Cognition; Dementia; Metabolomics; epidemiology; Network Analysis,,,"Investigating associations between metabolites and late midlife cognitive function could reveal potential markers and mechanisms relevant to early dementia. Here, we systematically explored the metabolic correlates of cognitive outcomes measured across the seventh decade of life, while untangling influencing life course factors. Using levels of 1019 metabolites profiled by liquid chromatography-mass spectrometry (age 60-64), we evaluated relationships between metabolites and cognitive outcomes in the British 1946 Birth Cohort (N = 1740). We additionally conducted pathway and network analyses to allow for greater insight into potential mechanisms, and sequentially adjusted for life course factors across four models, including sex and blood collection (Model 1), Model 1 + body mass index and lipid medication (Model 2), Model 2 + social factors and childhood cognition (Model 3) and Model 3 + lifestyle influences (Model 4). After adjusting for multiple tests, 155 metabolites, 10 pathways and 5 network modules were associated with cognitive outcomes. Of the 155, 35 metabolites were highly connected in their network module (termed 'hub' metabolites), presenting as promising marker candidates. Notably, we report relationships between a module comprised of acylcarnitines and processing speed which remained robust to life course adjustment, revealing palmitoylcarnitine (C16) as a hub (Model 4: β = -0.10, 95% confidence interval = -0.15 to -0.052, P = 5.99 × 10-5). Most associations were sensitive to adjustment for social factors and childhood cognition; in the final model, four metabolites remained after multiple testing correction, and 80 at P < 0.05. Two modules demonstrated associations that were partly or largely attenuated by life course factors: one enriched in modified nucleosides and amino acids (overall attenuation = 39.2-55.5%), and another in vitamin A and C metabolites (overall attenuation = 68.6-92.6%). Our other findings, including a module enriched in sphingolipid pathways, were entirely explained by life course factors, particularly childhood cognition and education. Using a large birth cohort study with information across the life course, we highlighted potential metabolic mechanisms associated with cognitive function in late midlife, suggesting marker candidates and life course relationships for further study.",,pdf:https://academic.oup.com/braincomms/article-pdf/4/1/fcab291/42546494/fcab291.pdf; doi:https://doi.org/10.1093/braincomms/fcab291; html:https://europepmc.org/articles/PMC8853724; pdf:https://europepmc.org/articles/PMC8853724?pdf=render @@ -2565,12 +2565,12 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 31243008,https://doi.org/10.1136/archdischild-2018-316693,Origins of disparities in preventable child mortality in England and Sweden: a birth cohort study.,"Zylbersztejn A, Gilbert R, Hjern A, Hardelid P.",,Archives of disease in childhood,2020,2019-06-26,Y,Respiratory tract infection; Sweden; England; Child Mortality; Sudden Unexpected Death In Infancy,Improving Public Health,,"

Objective

To compare mortality in children aged <5 years from two causes amenable to healthcare prevention in England and Sweden: respiratory tract infection (RTI) and sudden unexpected death in infancy (SUDI).

Design

Birth cohort study using linked administrative health databases from England and Sweden.

Setting and participants

Singleton live births between 2003 and 2012 in England and Sweden, followed up from age 31 days until the fifth birthday, death or 31 December 2013.

Main outcome measures

The main outcome measures were HR for RTI-related mortality at 31-364 days and at 1-4 years and SUDI mortality at 31-364 days in England versus Sweden estimated using Cox proportional hazards models. We calculated unadjusted HRs and HRs adjusted for birth characteristics (gestational age, birth weight, sex and congenital anomalies) and socioeconomic factors (maternal age and socioeconomic status).

Results

The English cohort comprised 3 928 483 births, 768 RTI-related deaths at 31-364 days, 691 RTI-related deaths at 1-4 years and 1166 SUDIs; the corresponding figures for the Swedish cohort were 1 012 682, 131, 118 and 189. At 31-364 days, unadjusted HR for RTI-related death in England versus Sweden was 1.52 (95% CI 1.26 to 1.82). After adjusting for birth characteristics, the HR reduced to 1.16 (95% CI 0.96 to 1.40) and for socioeconomic factors to 1.11 (95% CI 0.92 to 1.34). At 1-4 years, unadjusted HR was 1.58 (95% CI 1.30 to 1.92) and decreased to 1.32 (95% CI 1.09 to 1.61) after adjusting for birth characteristics and to 1.30 (95% CI 1.07 to 1.59) after further adjustment for socioeconomic factors. For SUDI, the respective HRs were 1.59 (95% CI 1.36 to 1.85) in the unadjusted model, and 1.40 (95% CI 1.20 to 1.63) after accounting for birth characteristics and 1.19 (95% CI 1.02 to 1.39) in the fully adjusted model.

Conclusion

Interventions that improve maternal health before and during pregnancy to reduce the prevalence of adverse birth characteristics and address poverty could reduce child mortality due to RTIs and SUDIs in England.","Zylbersztejn et al. shown that helping mothers to have a healthier pregnancy: better mental health before and during pregnancy, reducing birth complications and addressing poverty are the potential areas which can affect reduction of child mortality at birth. ",pdf:https://adc.bmj.com/content/archdischild/105/1/53.full.pdf; doi:https://doi.org/10.1136/archdischild-2018-316693; html:https://europepmc.org/articles/PMC6951233; pdf:https://europepmc.org/articles/PMC6951233?pdf=render 33822969,https://doi.org/10.1210/clinem/dgab219,Plasma Cortisol and Risk of Atrial Fibrillation: A Mendelian Randomization Study.,"Larsson SC, Lee WH, Burgess S, Allara E.",,The Journal of clinical endocrinology and metabolism,2021,2021-06-01,Y,Cortisol; Atrial fibrillation; Mendelian Randomization; Cushing’s Syndrome,,,"

Context

Atrial fibrillation (AF), cardiac arrhythmias, and related risk factors are common in patients with Cushing's syndrome, or clinical chronic hypercortisolism. While hypercortisolism may be associated with AF, this association has not yet been ascertained causally.

Objective

To determine whether plasma cortisol is causally associated with AF using a 2-sample Mendelian randomization (MR) design.

Methods

Three genetic variants in the SERPINA1/SERPINA6 locus and functionally associated with plasma cortisol were identified in the CORtisol NETwork consortium (12 597 participants). Summary-level genome-wide association study (GWAS) data for the associations between the cortisol-associated variants and AF were obtained from a GWAS meta-analysis of 6 studies (60 620 AF cases and 970 216 noncases) and the FinnGen consortium (17 325 AF cases and 97 214 noncases). The fixed-effects inverse-variance weighted approach accounting for genetic correlations between variants was used for analysis. Multivariable MR analyses were conducted to assess potential mediating effects of systolic blood pressure (SBP) and waist circumference (WC). Summary-level GWAS data for SBP and WC were obtained respectively from the International Consortium of Blood Pressure (757 601 participants) and the Genetic Investigation of ANthropometric Traits consortium (232 101 participants).

Results

One standard deviation increase in genetically predicted plasma cortisol was associated with greater risk of AF (odds ratio [OR] 1.20, 95% CI 1.06-1.35). The association attenuated when adjusting for genetically predicted SBP and WC (OR 0.99, 95% CI 0.72-1.38).

Conclusion

Evidence derived from the MR study suggests a positive association between plasma cortisol and risk of AF, likely mediated through SBP and WC.",,pdf:https://academic.oup.com/jcem/article-pdf/106/7/e2521/38663107/dgab219.pdf; doi:https://doi.org/10.1210/clinem/dgab219; html:https://europepmc.org/articles/PMC8208666 32502668,https://doi.org/10.1016/j.neuroimage.2020.117002,Confound modelling in UK Biobank brain imaging.,"Alfaro-Almagro F, McCarthy P, Afyouni S, Andersson JLR, Bastiani M, Miller KL, Nichols TE, Smith SM.",,NeuroImage,2021,2020-06-02,Y,Image analysis; Machine Learning; Epidemiological Studies; Multi-modal Data Integration; Data Modelling; Confounds; Big Data Imaging; Statistica L Modelling,,,"Dealing with confounds is an essential step in large cohort studies to address problems such as unexplained variance and spurious correlations. UK Biobank is a powerful resource for studying associations between imaging and non-imaging measures such as lifestyle factors and health outcomes, in part because of the large subject numbers. However, the resulting high statistical power also raises the sensitivity to confound effects, which therefore have to be carefully considered. In this work we describe a set of possible confounds (including non-linear effects and interactions that researchers may wish to consider for their studies using such data). We include descriptions of how we can estimate the confounds, and study the extent to which each of these confounds affects the data, and the spurious correlations that may arise if they are not controlled. Finally, we discuss several issues that future studies should consider when dealing with confounds.",,doi:https://doi.org/10.1016/j.neuroimage.2020.117002; doi:https://doi.org/10.1016/j.neuroimage.2020.117002; html:https://europepmc.org/articles/PMC7610719; pdf:https://europepmc.org/articles/PMC7610719?pdf=render -33595074,https://doi.org/10.1093/aje/kwab031,Prediction of Cardiovascular Disease Risk Accounting for Future Initiation of Statin Treatment.,"Xu Z, Arnold M, Stevens D, Kaptoge S, Pennells L, Sweeting MJ, Barrett J, Di Angelantonio E, Wood AM.",,American journal of epidemiology,2021,2021-10-01,Y,Longitudinal data; Cardiovascular disease; Risk Prediction; Electronic Health Records; Treatment Drop-in; Future Statin Initiation,,,"Cardiovascular disease (CVD) risk-prediction models are used to identify high-risk individuals and guide statin initiation. However, these models are usually derived from individuals who might initiate statins during follow-up. We present a simple approach to address statin initiation to predict ""statin-naive"" CVD risk. We analyzed primary care data (2004-2017) from the UK Clinical Practice Research Datalink for 1,678,727 individuals (aged 40-85 years) without CVD or statin treatment history at study entry. We derived age- and sex-specific prediction models including conventional risk factors and a time-dependent effect of statin initiation constrained to 25% risk reduction (from trial results). We compared predictive performance and measures of public-health impact (e.g., number needed to screen to prevent 1 event) against models ignoring statin initiation. During a median follow-up of 8.9 years, 103,163 individuals developed CVD. In models accounting for (versus ignoring) statin initiation, 10-year CVD risk predictions were slightly higher; predictive performance was moderately improved. However, few individuals were reclassified to a high-risk threshold, resulting in negligible improvements in number needed to screen to prevent 1 event. In conclusion, incorporating statin effects from trial results into risk-prediction models enables statin-naive CVD risk estimation and provides moderate gains in predictive ability but had a limited impact on treatment decision-making under current guidelines in this population.",,pdf:https://academic.oup.com/aje/article-pdf/190/10/2000/40491073/kwab031.pdf; doi:https://doi.org/10.1093/aje/kwab031; html:https://europepmc.org/articles/PMC8485151; pdf:https://europepmc.org/articles/PMC8485151?pdf=render 32025702,https://doi.org/10.1093/gigascience/giaa007,Genomic diversity affects the accuracy of bacterial single-nucleotide polymorphism-calling pipelines.,"Bush SJ, Foster D, Eyre DW, Clark EL, De Maio N, Shaw LP, Stoesser N, Peto TEA, Crook DW, Walker AS.",,GigaScience,2020,2020-02-01,Y,Bacteria; Evaluation; Benchmarking; Variant Calling; Snp Calling,The Human Phenome,,"

Background

Accurately identifying single-nucleotide polymorphisms (SNPs) from bacterial sequencing data is an essential requirement for using genomics to track transmission and predict important phenotypes such as antimicrobial resistance. However, most previous performance evaluations of SNP calling have been restricted to eukaryotic (human) data. Additionally, bacterial SNP calling requires choosing an appropriate reference genome to align reads to, which, together with the bioinformatic pipeline, affects the accuracy and completeness of a set of SNP calls obtained. This study evaluates the performance of 209 SNP-calling pipelines using a combination of simulated data from 254 strains of 10 clinically common bacteria and real data from environmentally sourced and genomically diverse isolates within the genera Citrobacter, Enterobacter, Escherichia, and Klebsiella.

Results

We evaluated the performance of 209 SNP-calling pipelines, aligning reads to genomes of the same or a divergent strain. Irrespective of pipeline, a principal determinant of reliable SNP calling was reference genome selection. Across multiple taxa, there was a strong inverse relationship between pipeline sensitivity and precision, and the Mash distance (a proxy for average nucleotide divergence) between reads and reference genome. The effect was especially pronounced for diverse, recombinogenic bacteria such as Escherichia coli but less dominant for clonal species such as Mycobacterium tuberculosis.

Conclusions

The accuracy of SNP calling for a given species is compromised by increasing intra-species diversity. When reads were aligned to the same genome from which they were sequenced, among the highest-performing pipelines was Novoalign/GATK. By contrast, when reads were aligned to particularly divergent genomes, the highest-performing pipelines often used the aligners NextGenMap or SMALT, and/or the variant callers LoFreq, mpileup, or Strelka.","The authors compared the accuracy of data processing steps (called bioinformatics pipelines) for identifying different types of bacteria, and which antibiotics they are resistant to. They identified which processes were most likely to introduce errors for different bacteria, and make recommendations about which pipelines should be used.",pdf:https://watermark.silverchair.com/giaa007.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAArgwggK0BgkqhkiG9w0BBwagggKlMIICoQIBADCCApoGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM317Vywl4J0MoRskUAgEQgIICa7pwfJ56Mly4Anv1BPEAmwtKXOLcmFeMLRa66xhgPdK6Ci4Aw3rp4lJMizin326QALNQsODRERKONUxtXgEWVQAk130Fd7XbP6mDWd-0WqGT3cSidkfYveDUH3QNU5fMzLfCj598hrJEAk1z7LTkxKHEy9DQWfFNTCjY53IC7QawbMnwVvVq_lpTKlRP8_qZiTe8qiEKqWNVZ6woCjOc2Rro01EG5_atdzA8zpmJq2R4tx28FbVmIM7dsgYcT7L9DYQIcPQwJxaZSleSNtEyNXeo-WcHn_ezUiaRb0lthzfWPPdge5nY3tlFAelL_HeYo6jn4CkFdniFC28Gr7TuFnrJyj28_OsKYJICwvgwmNPj-T5rf9MGAMgBV3SLK6l87grZuO1r4Q8AfpvbJY9vHrDDayBzhuXMW_g2CFpQDYzMp4tGX8Yu3uS5qDWR81xG0Xqf5p0i0wsw1ZD1ZDA8tla87WrJCjbGwWjoXx2ihhyp6aXc4DC_8FCavms7sXqxQEsoVtDp6hvmpDsPPSvdGRAOjKeaQD2mWFi_3U7ndjd2_0dGVvsD5zDl0_GrRV8QEGNDocCzvibp-DyCby-tfRS4UsoqVA96Gs3ZgVtZzcQbcDt3C069xpbFOJD2rqJ4oyiGdUUh9uWDxgQFKiRvQZbblRH-htJ8tPKjv371GO1Wm6E-asCRSjCkT4vRP3lzDlab36iWZVp5vS5XoumjEnV9wxKBEqkYGywEdZUlG57ygWi11YTdMK3EYXbFqU0xFXvw34Sdl47d5bUDjYEEcxBciYLJqWhQKY9opr4bt5T3SCS107QDE4VOmd4; doi:https://doi.org/10.1093/gigascience/giaa007; html:https://europepmc.org/articles/PMC7002876; pdf:https://europepmc.org/articles/PMC7002876?pdf=render +33595074,https://doi.org/10.1093/aje/kwab031,Prediction of Cardiovascular Disease Risk Accounting for Future Initiation of Statin Treatment.,"Xu Z, Arnold M, Stevens D, Kaptoge S, Pennells L, Sweeting MJ, Barrett J, Di Angelantonio E, Wood AM.",,American journal of epidemiology,2021,2021-10-01,Y,Longitudinal data; Cardiovascular disease; Risk Prediction; Electronic Health Records; Treatment Drop-in; Future Statin Initiation,,,"Cardiovascular disease (CVD) risk-prediction models are used to identify high-risk individuals and guide statin initiation. However, these models are usually derived from individuals who might initiate statins during follow-up. We present a simple approach to address statin initiation to predict ""statin-naive"" CVD risk. We analyzed primary care data (2004-2017) from the UK Clinical Practice Research Datalink for 1,678,727 individuals (aged 40-85 years) without CVD or statin treatment history at study entry. We derived age- and sex-specific prediction models including conventional risk factors and a time-dependent effect of statin initiation constrained to 25% risk reduction (from trial results). We compared predictive performance and measures of public-health impact (e.g., number needed to screen to prevent 1 event) against models ignoring statin initiation. During a median follow-up of 8.9 years, 103,163 individuals developed CVD. In models accounting for (versus ignoring) statin initiation, 10-year CVD risk predictions were slightly higher; predictive performance was moderately improved. However, few individuals were reclassified to a high-risk threshold, resulting in negligible improvements in number needed to screen to prevent 1 event. In conclusion, incorporating statin effects from trial results into risk-prediction models enables statin-naive CVD risk estimation and provides moderate gains in predictive ability but had a limited impact on treatment decision-making under current guidelines in this population.",,pdf:https://academic.oup.com/aje/article-pdf/190/10/2000/40491073/kwab031.pdf; doi:https://doi.org/10.1093/aje/kwab031; html:https://europepmc.org/articles/PMC8485151; pdf:https://europepmc.org/articles/PMC8485151?pdf=render 36982069,https://doi.org/10.3390/ijerph20065161,The Impact of COVID-19 Lockdown on Adults with Major Depressive Disorder from Catalonia: A Decentralized Longitudinal Study.,"Lavalle R, Condominas E, Haro JM, Giné-Vázquez I, Bailon R, Laporta E, Garcia E, Kontaxis S, Alacid GR, Lombardini F, Preti A, Peñarrubia-Maria MT, Coromina M, Arranz B, Vilella E, Rubio-Alacid E, Radar-Mdd Spain, Matcham F, Lamers F, Hotopf M, Penninx BWJH, Annas P, Narayan V, Simblett SK, Siddi S, The Radar-Cns Consortium.",,International journal of environmental research and public health,2023,2023-03-15,Y,Quarantine; Depression; Anxiety; Spain; Lockdown; Remote Measurement Technology; Sars-cov-2; Decentralized Study,,,"The present study analyzes the effects of each containment phase of the first COVID-19 wave on depression levels in a cohort of 121 adults with a history of major depressive disorder (MDD) from Catalonia recruited from 1 November 2019, to 16 October 2020. This analysis is part of the Remote Assessment of Disease and Relapse-MDD (RADAR-MDD) study. Depression was evaluated with the Patient Health Questionnaire-8 (PHQ-8), and anxiety was evaluated with the Generalized Anxiety Disorder-7 (GAD-7). Depression's levels were explored across the phases (pre-lockdown, lockdown, and four post-lockdown phases) according to the restrictions of Spanish/Catalan governments. Then, a mixed model was fitted to estimate how depression varied over the phases. A significant rise in depression severity was found during the lockdown and phase 0 (early post-lockdown), compared with the pre-lockdown. Those with low pre-lockdown depression experienced an increase in depression severity during the ""new normality"", while those with high pre-lockdown depression decreased compared with the pre-lockdown. These findings suggest that COVID-19 restrictions affected the depression level depending on their pre-lockdown depression severity. Individuals with low levels of depression are more reactive to external stimuli than those with more severe depression, so the lockdown may have worse detrimental effects on them.",,pdf:https://www.mdpi.com/1660-4601/20/6/5161/pdf?version=1678866764; doi:https://doi.org/10.3390/ijerph20065161; html:https://europepmc.org/articles/PMC10048808; pdf:https://europepmc.org/articles/PMC10048808?pdf=render 33757590,https://doi.org/10.1186/s13148-021-01043-3,Multi-omics integration identifies key upstream regulators of pathomechanisms in hypertrophic cardiomyopathy due to truncating MYBPC3 mutations.,"Pei J, Schuldt M, Nagyova E, Gu Z, El Bouhaddani S, Yiangou L, Jansen M, Calis JJA, Dorsch LM, Blok CS, van den Dungen NAM, Lansu N, Boukens BJ, Efimov IR, Michels M, Verhaar MC, de Weger R, Vink A, van Steenbeek FG, Baas AF, Davis RP, Uh HW, Kuster DWD, Cheng C, Mokry M, van der Velden J, Asselbergs FW, Harakalova M.",,Clinical epigenetics,2021,2021-03-23,Y,Transcription factors; Proteome; Transcriptome; Hcm; Mybpc3; Histone Acetylome,,,"

Background

Hypertrophic cardiomyopathy (HCM) is the most common genetic disease of the cardiac muscle, frequently caused by mutations in MYBPC3. However, little is known about the upstream pathways and key regulators causing the disease. Therefore, we employed a multi-omics approach to study the pathomechanisms underlying HCM comparing patient hearts harboring MYBPC3 mutations to control hearts.

Results

Using H3K27ac ChIP-seq and RNA-seq we obtained 9310 differentially acetylated regions and 2033 differentially expressed genes, respectively, between 13 HCM and 10 control hearts. We obtained 441 differentially expressed proteins between 11 HCM and 8 control hearts using proteomics. By integrating multi-omics datasets, we identified a set of DNA regions and genes that differentiate HCM from control hearts and 53 protein-coding genes as the major contributors. This comprehensive analysis consistently points toward altered extracellular matrix formation, muscle contraction, and metabolism. Therefore, we studied enriched transcription factor (TF) binding motifs and identified 9 motif-encoded TFs, including KLF15, ETV4, AR, CLOCK, ETS2, GATA5, MEIS1, RXRA, and ZFX. Selected candidates were examined in stem cell-derived cardiomyocytes with and without mutated MYBPC3. Furthermore, we observed an abundance of acetylation signals and transcripts derived from cardiomyocytes compared to non-myocyte populations.

Conclusions

By integrating histone acetylome, transcriptome, and proteome profiles, we identified major effector genes and protein networks that drive the pathological changes in HCM with mutated MYBPC3. Our work identifies 38 highly affected protein-coding genes as potential plasma HCM biomarkers and 9 TFs as potential upstream regulators of these pathomechanisms that may serve as possible therapeutic targets.",,pdf:https://clinicalepigeneticsjournal.biomedcentral.com/counter/pdf/10.1186/s13148-021-01043-3; doi:https://doi.org/10.1186/s13148-021-01043-3; html:https://europepmc.org/articles/PMC7989210; pdf:https://europepmc.org/articles/PMC7989210?pdf=render -35908040,https://doi.org/10.1038/s41597-022-01534-9,"ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19.","ISARIC Clinical Characterization Group, Garcia-Gallo E, Merson L, Kennon K, Kelly S, Citarella BW, Fryer DV, Shrapnel S, Lee J, Duque S, Fuentes YV, Balan V, Smith S, Wei J, Gonçalves BP, Russell CD, Sigfrid L, Dagens A, Olliaro PL, Baruch J, Kartsonaki C, Dunning J, Rojek A, Rashan A, Beane A, Murthy S, Reyes LF.",,Scientific data,2022,2022-07-30,Y,,,,"The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.",,pdf:https://www.nature.com/articles/s41597-022-01534-9.pdf; doi:https://doi.org/10.1038/s41597-022-01534-9; html:https://europepmc.org/articles/PMC9339000; pdf:https://europepmc.org/articles/PMC9339000?pdf=render 31485076,https://doi.org/10.1038/s41586-019-1530-7,Structures of influenza A virus RNA polymerase offer insight into viral genome replication.,"Fan H, Walker AP, Carrique L, Keown JR, Serna Martin I, Karia D, Sharps J, Hengrung N, Pardon E, Steyaert J, Grimes JM, Fodor E.",,Nature,2019,2019-09-04,Y,,,,"Influenza A viruses are responsible for seasonal epidemics, and pandemics can arise from the transmission of novel zoonotic influenza A viruses to humans1,2. Influenza A viruses contain a segmented negative-sense RNA genome, which is transcribed and replicated by the viral-RNA-dependent RNA polymerase (FluPolA) composed of PB1, PB2 and PA subunits3-5. Although the high-resolution crystal structure of FluPolA of bat influenza A virus has previously been reported6, there are no complete structures available for human and avian FluPolA. Furthermore, the molecular mechanisms of genomic viral RNA (vRNA) replication-which proceeds through a complementary RNA (cRNA) replicative intermediate, and requires oligomerization of the polymerase7-10-remain largely unknown. Here, using crystallography and cryo-electron microscopy, we determine the structures of FluPolA from human influenza A/NT/60/1968 (H3N2) and avian influenza A/duck/Fujian/01/2002 (H5N1) viruses at a resolution of 3.0-4.3 Å, in the presence or absence of a cRNA or vRNA template. In solution, FluPolA forms dimers of heterotrimers through the C-terminal domain of the PA subunit, the thumb subdomain of PB1 and the N1 subdomain of PB2. The cryo-electron microscopy structure of monomeric FluPolA bound to the cRNA template reveals a binding site for the 3' cRNA at the dimer interface. We use a combination of cell-based and in vitro assays to show that the interface of the FluPolA dimer is required for vRNA synthesis during replication of the viral genome. We also show that a nanobody (a single-domain antibody) that interferes with FluPolA dimerization inhibits the synthesis of vRNA and, consequently, inhibits virus replication in infected cells. Our study provides high-resolution structures of medically relevant FluPolA, as well as insights into the replication mechanisms of the viral RNA genome. In addition, our work identifies sites in FluPolA that could be targeted in the development of antiviral drugs.",,pdf:https://europepmc.org/articles/pmc6795553?pdf=render; doi:https://doi.org/10.1038/s41586-019-1530-7; html:https://europepmc.org/articles/PMC6795553; pdf:https://europepmc.org/articles/PMC6795553?pdf=render +35908040,https://doi.org/10.1038/s41597-022-01534-9,"ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19.","ISARIC Clinical Characterization Group, Garcia-Gallo E, Merson L, Kennon K, Kelly S, Citarella BW, Fryer DV, Shrapnel S, Lee J, Duque S, Fuentes YV, Balan V, Smith S, Wei J, Gonçalves BP, Russell CD, Sigfrid L, Dagens A, Olliaro PL, Baruch J, Kartsonaki C, Dunning J, Rojek A, Rashan A, Beane A, Murthy S, Reyes LF.",,Scientific data,2022,2022-07-30,Y,,,,"The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.",,pdf:https://www.nature.com/articles/s41597-022-01534-9.pdf; doi:https://doi.org/10.1038/s41597-022-01534-9; html:https://europepmc.org/articles/PMC9339000; pdf:https://europepmc.org/articles/PMC9339000?pdf=render 36210437,https://doi.org/10.1186/s12916-022-02588-7,Hesitancy for receiving regular SARS-CoV-2 vaccination in UK healthcare workers: a cross-sectional analysis from the UK-REACH study.,"Veli N, Martin CA, Woolf K, Nazareth J, Pan D, Al-Oraibi A, Baggaley RF, Bryant L, Nellums LB, Gray LJ, Khunti K, Pareek M, UK-REACH Study Collaborative Group.",,BMC medicine,2022,2022-10-10,Y,Vaccination; Ethnicity; Healthcare; Hesitancy; Covid-19; Sars-cov-2,,,"

Background

Regular vaccination against SARS-CoV-2 may be needed to maintain immunity in 'at-risk' populations, which include healthcare workers (HCWs). However, little is known about the proportion of HCWs who might be hesitant about receiving a hypothetical regular SARS-CoV-2 vaccination or the factors associated with this hesitancy.

Methods

Cross-sectional analysis of questionnaire data collected as part of UK-REACH, a nationwide, longitudinal cohort study of HCWs. The outcome measure was binary, either a participant indicated they would definitely accept regular SARS-CoV-2 vaccination if recommended or they indicated some degree of hesitancy regarding acceptance (probably accept or less likely). We used logistic regression to identify factors associated with hesitancy for receiving regular vaccination.

Results

A total of 5454 HCWs were included in the analysed cohort, 23.5% of whom were hesitant about regular SARS-CoV-2 vaccination. Black HCWs were more likely to be hesitant than White HCWs (aOR 2.60, 95%CI 1.80-3.72) as were those who reported a previous episode of COVID-19 (1.33, 1.13-1.57 [vs those who tested negative]). Those who received influenza vaccination in the previous two seasons were over five times less likely to report hesitancy for regular SARS-CoV-2 vaccination than those not vaccinated against influenza in either season (0.18, 0.14-0.21). HCWs who trusted official sources of vaccine information (such as NHS or government adverts or websites) were less likely to report hesitancy for a regular vaccination programme. Those who had been exposed to information advocating against vaccination from friends and family were more likely to be hesitant.

Conclusions

In this study, nearly a quarter of UK HCWs were hesitant about receiving a regular SARS-CoV-2 vaccination. We have identified key factors associated with hesitancy for regular SARS-CoV-2 vaccination, which can be used to identify groups of HCWs at the highest risk of vaccine hesitancy and tailor interventions accordingly. Family and friends of HCWs may influence decisions about regular vaccination. This implies that working with HCWs and their social networks to allay concerns about SARS-CoV-2 vaccination could improve uptake in a regular vaccination programme.

Trial registration

ISRCTN Registry, ISRCTN11811602.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02588-7; doi:https://doi.org/10.1186/s12916-022-02588-7; html:https://europepmc.org/articles/PMC9548389; pdf:https://europepmc.org/articles/PMC9548389?pdf=render 32690604,https://doi.org/10.1136/gutjnl-2019-319866,Image-based consensus molecular subtype (imCMS) classification of colorectal cancer using deep learning.,"Sirinukunwattana K, Domingo E, Richman SD, Redmond KL, Blake A, Verrill C, Leedham SJ, Chatzipli A, Hardy C, Whalley CM, Wu CH, Beggs AD, McDermott U, Dunne PD, Meade A, Walker SM, Murray GI, Samuel L, Seymour M, Tomlinson I, Quirke P, Maughan T, Rittscher J, Koelzer VH, S:CORT consortium.",,Gut,2021,2020-07-20,Y,Molecular Pathology; Computerised Image Analysis; Colorectal Pathology,,,"

Objective

Complex phenotypes captured on histological slides represent the biological processes at play in individual cancers, but the link to underlying molecular classification has not been clarified or systematised. In colorectal cancer (CRC), histological grading is a poor predictor of disease progression, and consensus molecular subtypes (CMSs) cannot be distinguished without gene expression profiling. We hypothesise that image analysis is a cost-effective tool to associate complex features of tissue organisation with molecular and outcome data and to resolve unclassifiable or heterogeneous cases. In this study, we present an image-based approach to predict CRC CMS from standard H&E sections using deep learning.

Design

Training and evaluation of a neural network were performed using a total of n=1206 tissue sections with comprehensive multi-omic data from three independent datasets (training on FOCUS trial, n=278 patients; test on rectal cancer biopsies, GRAMPIAN cohort, n=144 patients; and The Cancer Genome Atlas (TCGA), n=430 patients). Ground truth CMS calls were ascertained by matching random forest and single sample predictions from CMS classifier.

Results

Image-based CMS (imCMS) accurately classified slides in unseen datasets from TCGA (n=431 slides, AUC)=0.84) and rectal cancer biopsies (n=265 slides, AUC=0.85). imCMS spatially resolved intratumoural heterogeneity and provided secondary calls correlating with bioinformatic prediction from molecular data. imCMS classified samples previously unclassifiable by RNA expression profiling, reproduced the expected correlations with genomic and epigenetic alterations and showed similar prognostic associations as transcriptomic CMS.

Conclusion

This study shows that a prediction of RNA expression classifiers can be made from H&E images, opening the door to simple, cheap and reliable biological stratification within routine workflows.",,pdf:https://gut.bmj.com/content/gutjnl/70/3/544.full.pdf; doi:https://doi.org/10.1136/gutjnl-2019-319866; html:https://europepmc.org/articles/PMC7873419; pdf:https://europepmc.org/articles/PMC7873419?pdf=render 31607442,https://doi.org/10.1016/j.injury.2019.09.036,Over view of major traumatic injury in Australia--Implications for trauma system design.,"Cameron PA, Fitzgerald MC, Curtis K, McKie E, Gabbe B, Earnest A, Christey G, Clarke C, Crozier J, Dinh M, Ellis DY, Howard T, Joseph AP, McDermott K, Matthew J, Ogilvie R, Pollard C, Rao S, Reade M, Rushworth N, Zalstein S, Australian Trauma Quality Improvement Program (AusTQIP) collaboration.",,Injury,2020,2019-10-03,N,Quality improvement; epidemiology; Older Adults; Risk Adjustment; Trauma System; Major Trauma; System Of Care; Trauma Registries; Injury Burden,Improving Public Health,,"

Background

Trauma registries are known to drive improvements and optimise trauma systems worldwide. This is the first reported comparison of the epidemiology and outcomes at major centres across Australia.

Methods

The Australian Trauma Registry was a collaboration of 26 major trauma centres across Australia at the time of this study and currently collects information on patients admitted to these centres who die after injury and/or sustain major trauma (Injury Severity Score (ISS) > 12). Data from 1 July 2016 to 30 June 2017 were analysed. Primary endpoints were risk adjusted length of stay and mortality (adjusted for age, cause of injury, arrival Glasgow coma scale (GCS), shock-index grouped in quartiles and ISS).

Results

There were 8423 patients from 24 centres included. The median age (IQR) was 48 (28-68) years. Median (IQR) ISS was 17 (14-25). There was a predominance of males (72%) apart from the extremes of age. Transport-related cases accounted for 45% of major trauma, followed by falls (35.1%). Patients took 1.42 (1.03-2.12) h to reach hospital and spent 7.10 (3.64-15.00) days in hospital. Risk adjusted length of stay and mortality did not differ significantly across sites. Primary endpoints across sites were also similar in paediatric and older adult (>65) age groups.

Conclusion

Australia has the capability to identify national injury trends to target prevention and reduce the burden of injury. Quality of care following injury can now be benchmarked across Australia and with the planned enhancements to data collection and reporting, this will enable improved management of trauma victims.","This paper looks at the implications for trauma system design based on major traumatic injuries in Australia and aims to describe the current epidemiology of major trauma across the country, identifying improvements and future directions in the system of trauma care in Australia. This is the first reported comparison of the epidemiology and outcomes at major centres across Australia. They concluded that Australia now has the capability to identify national injury trends in patients admitted to major trauma services, optimising prevention and treamtnet strategies, thereby potentially reducing the burden of injury.",doi:https://doi.org/10.1016/j.injury.2019.09.036 @@ -2615,8 +2615,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 36314129,https://doi.org/10.1161/circulationaha.122.060700,Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.,"Gaziano L, Sun L, Arnold M, Bell S, Cho K, Kaptoge SK, Song RJ, Burgess S, Posner DC, Mosconi K, Robinson-Cohen C, Mason AM, Bolton TR, Tao R, Allara E, Schubert P, Chen L, Staley JR, Staplin N, Altay S, Amiano P, Arndt V, Ärnlöv J, Barr ELM, Björkelund C, Boer JMA, Brenner H, Casiglia E, Chiodini P, Cooper JA, Coresh J, Cushman M, Dankner R, Davidson KW, de Jongh RT, Donfrancesco C, Engström G, Freisling H, de la Cámara AG, Gudnason V, Hankey GJ, Hansson PO, Heath AK, Hoorn EJ, Imano H, Jassal SK, Kaaks R, Katzke V, Kauhanen J, Kiechl S, Koenig W, Kronmal RA, Kyrø C, Lawlor DA, Ljungberg B, MacDonald C, Masala G, Meisinger C, Melander O, Moreno Iribas C, Ninomiya T, Nitsch D, Nordestgaard BG, Onland-Moret C, Palmieri L, Petrova D, Garcia JRQ, Rosengren A, Sacerdote C, Sakurai M, Santiuste C, Schulze MB, Sieri S, Sundström J, Tikhonoff V, Tjønneland A, Tong T, Tumino R, Tzoulaki I, van der Schouw YT, Monique Verschuren WM, Völzke H, Wallace RB, Wannamethee SG, Weiderpass E, Willeit P, Woodward M, Yamagishi K, Zamora-Ros R, Akwo EA, Pyarajan S, Gagnon DR, Tsao PS, Muralidhar S, Edwards TL, Damrauer SM, Joseph J, Pennells L, Wilson PWF, Harrison S, Gaziano TA, Inouye M, Baigent C, Casas JP, Langenberg C, Wareham N, Riboli E, Gaziano JM, Danesh J, Hung AM, Butterworth AS, Wood AM, Di Angelantonio E, Emerging Risk Factors Collaboration/EPIC-CVD/Million Veteran Program.",,Circulation,2022,2022-10-31,Y,Kidney diseases; Cardiovascular diseases; Coronary disease; Stroke,,,"

Background

End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.

Methods

Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.

Results

There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD.

Conclusions

In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.122.060700; doi:https://doi.org/10.1161/CIRCULATIONAHA.122.060700; html:https://europepmc.org/articles/PMC9662821; pdf:https://europepmc.org/articles/PMC9662821?pdf=render 33990564,https://doi.org/10.1038/s41467-021-22752-6,Epigenome-wide association meta-analysis of DNA methylation with coffee and tea consumption.,"Karabegović I, Portilla-Fernandez E, Li Y, Ma J, Maas SCE, Sun D, Hu EA, Kühnel B, Zhang Y, Ambatipudi S, Fiorito G, Huang J, Castillo-Fernandez JE, Wiggins KL, de Klein N, Grioni S, Swenson BR, Polidoro S, Treur JL, Cuenin C, Tsai PC, Costeira R, Chajes V, Braun K, Verweij N, Kretschmer A, Franke L, van Meurs JBJ, Uitterlinden AG, de Knegt RJ, Ikram MA, Dehghan A, Peters A, Schöttker B, Gharib SA, Sotoodehnia N, Bell JT, Elliott P, Vineis P, Relton C, Herceg Z, Brenner H, Waldenberger M, Rebholz CM, Voortman T, Pan Q, Fornage M, Levy D, Kayser M, Ghanbari M.",,Nature communications,2021,2021-05-14,Y,,,,"Coffee and tea are extensively consumed beverages worldwide which have received considerable attention regarding health. Intake of these beverages is consistently linked to, among others, reduced risk of diabetes and liver diseases; however, the mechanisms of action remain elusive. Epigenetics is suggested as a mechanism mediating the effects of dietary and lifestyle factors on disease onset. Here we report the results from epigenome-wide association studies (EWAS) on coffee and tea consumption in 15,789 participants of European and African-American ancestries from 15 cohorts. EWAS meta-analysis of coffee consumption reveals 11 CpGs surpassing the epigenome-wide significance threshold (P-value <1.1×10-7), which annotated to the AHRR, F2RL3, FLJ43663, HDAC4, GFI1 and PHGDH genes. Among them, cg14476101 is significantly associated with expression of the PHGDH and risk of fatty liver disease. Knockdown of PHGDH expression in liver cells shows a correlation with expression levels of genes associated with circulating lipids, suggesting a role of PHGDH in hepatic-lipid metabolism. EWAS meta-analysis on tea consumption reveals no significant association, only two CpGs annotated to CACNA1A and PRDM16 genes show suggestive association (P-value <5.0×10-6). These findings indicate that coffee-associated changes in DNA methylation levels may explain the mechanism of action of coffee consumption in conferring risk of diseases.",,pdf:https://www.nature.com/articles/s41467-021-22752-6.pdf; doi:https://doi.org/10.1038/s41467-021-22752-6; html:https://europepmc.org/articles/PMC8121846; pdf:https://europepmc.org/articles/PMC8121846?pdf=render 35387486,https://doi.org/10.1161/circulationaha.121.057888,Genetic Landscape of the ACE2 Coronavirus Receptor.,"Yang Z, Macdonald-Dunlop E, Chen J, Zhai R, Li T, Richmond A, Klarić L, Pirastu N, Ning Z, Zheng C, Wang Y, Huang T, He Y, Guo H, Ying K, Gustafsson S, Prins B, Ramisch A, Dermitzakis ET, Png G, Eriksson N, Haessler J, Hu X, Zanetti D, Boutin T, Hwang SJ, Wheeler E, Pietzner M, Raffield LM, Kalnapenkis A, Peters JE, Viñuela A, Gilly A, Elmståhl S, Dedoussis G, Petrie JR, Polašek O, Folkersen L, Chen Y, Yao C, Võsa U, Pairo-Castineira E, Clohisey S, Bretherick AD, Rawlik K, GenOMICC Consortium†, IMI-DIRECT Consortium†, Esko T, Enroth S, Johansson Å, Gyllensten U, Langenberg C, Levy D, Hayward C, Assimes TL, Kooperberg C, Manichaikul AW, Siegbahn A, Wallentin L, Lind L, Zeggini E, Schwenk JM, Butterworth AS, Michaëlsson K, Pawitan Y, Joshi PK, Baillie JK, Mälarstig A, Reiner AP, Wilson JF, Shen X.",,Circulation,2022,2022-04-07,Y,Cardiovascular diseases; Angiotensin-converting Enzyme 2; Genome-wide Association Study; Covid-19; Sars-cov-2,,,"

Background

SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood.

Methods

We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data.

Results

We identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis-protein quantitative trait loci-based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10-2.42]; P=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; P=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; P=0.02). Tissue- and cell type-specific transcriptomic and epigenomic analysis revealed that the ACE2 regulatory variants were enriched for DNA methylation sites in blood immune cells.

Conclusions

Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.057888; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.057888; html:https://europepmc.org/articles/PMC9047645; pdf:https://europepmc.org/articles/PMC9047645?pdf=render -34516908,https://doi.org/10.1126/sciadv.abh0534,Cell-free DNA TAPS provides multimodal information for early cancer detection.,"Siejka-Zielińska P, Cheng J, Jackson F, Liu Y, Soonawalla Z, Reddy S, Silva M, Puta L, McCain MV, Culver EL, Bekkali N, Schuster-Böckler B, Palamara PF, Mann D, Reeves H, Barnes E, Sivakumar S, Song CX.",,Science advances,2021,2021-09-01,Y,,,,"Multimodal, genome-wide characterization of epigenetic and genetic information in circulating cell-free DNA (cfDNA) could enable more sensitive early cancer detection, but it is technologically challenging. Recently, we developed TET-assisted pyridine borane sequencing (TAPS), which is a mild, bisulfite-free method for base-resolution direct DNA methylation sequencing. Here, we optimized TAPS for cfDNA (cfTAPS) to provide high-quality and high-depth whole-genome cell-free methylomes. We applied cfTAPS to 85 cfDNA samples from patients with hepatocellular carcinoma (HCC) or pancreatic ductal adenocarcinoma (PDAC) and noncancer controls. From only 10 ng of cfDNA (1 to 3 ml of plasma), we generated the most comprehensive cfDNA methylome to date. We demonstrated that cfTAPS provides multimodal information about cfDNA characteristics, including DNA methylation, tissue of origin, and DNA fragmentation. Integrated analysis of these epigenetic and genetic features enables accurate identification of early HCC and PDAC.",,pdf:https://www.science.org/doi/pdf/10.1126/sciadv.abh0534?download=true; doi:https://doi.org/10.1126/sciadv.abh0534; html:https://europepmc.org/articles/PMC8442905; pdf:https://europepmc.org/articles/PMC8442905?pdf=render 30498058,https://doi.org/10.1136/archdischild-2018-315866,Risk factors for permanent childhood hearing impairment.,"Butcher E, Dezateux C, Knowles RL.",,Archives of disease in childhood,2020,2018-11-28,Y,Deafness; epidemiology,Improving Public Health,,"

Objective

While several perinatal risk factors for permanent childhood hearing impairment (PCHI) are known, association with gestational length remains unclear. We hypothesised that shorter gestational length predicts higher PCHI risk.

Design

19 504 participants from the UK Millennium Cohort Study (born 2000-2002, prior to newborn screening).

Methods

Multivariable discrete-time survival analysis to examine associations between parent-reported PCHI by age 11 years and gestational length, plus other prespecified factors.

Results

PCHI affected 2.1 per 1000 children (95% CI 1.5 to 3.0) by age 11; however, gestational length did not predict PCHI risk (HR, 95% CI 1.00, 0.98 to 1.03 per day increase). Risk was increased in those with neonatal illness, with or without admission to neonatal care (6.33, 2.27 to 17.63 and 2.62, 1.15 to 5.97, respectively), of Bangladeshi or Pakistani ethnicity (2.78, 1.06 to 7.31) or born to younger mothers (0.92, 0.87 to 0.97 per year).

Conclusion

Neonatal illness, rather than gestational length, predicts PCHI risk. Further research should explore associations with ethnicity.","This study looked at whether there is a link between gestational length of a child (the length of time of pregnancy) and the likelihood of permanent hearing impairment. The authors looked at data from over 19000 children from a study called the Millenium Cohort Study. They found that shorter gestational length did not increase the likelihood of childhood permanent hearting impairment. However, they found that children who had neonatal illness (illness in the immediate days after birth), if they were Bangladeshi or Pakistani in ethnicity, or if they were born to younger mothers.",pdf:https://adc.bmj.com/content/archdischild/105/2/187.full.pdf; doi:https://doi.org/10.1136/archdischild-2018-315866; html:https://europepmc.org/articles/PMC7025723; pdf:https://europepmc.org/articles/PMC7025723?pdf=render +34516908,https://doi.org/10.1126/sciadv.abh0534,Cell-free DNA TAPS provides multimodal information for early cancer detection.,"Siejka-Zielińska P, Cheng J, Jackson F, Liu Y, Soonawalla Z, Reddy S, Silva M, Puta L, McCain MV, Culver EL, Bekkali N, Schuster-Böckler B, Palamara PF, Mann D, Reeves H, Barnes E, Sivakumar S, Song CX.",,Science advances,2021,2021-09-01,Y,,,,"Multimodal, genome-wide characterization of epigenetic and genetic information in circulating cell-free DNA (cfDNA) could enable more sensitive early cancer detection, but it is technologically challenging. Recently, we developed TET-assisted pyridine borane sequencing (TAPS), which is a mild, bisulfite-free method for base-resolution direct DNA methylation sequencing. Here, we optimized TAPS for cfDNA (cfTAPS) to provide high-quality and high-depth whole-genome cell-free methylomes. We applied cfTAPS to 85 cfDNA samples from patients with hepatocellular carcinoma (HCC) or pancreatic ductal adenocarcinoma (PDAC) and noncancer controls. From only 10 ng of cfDNA (1 to 3 ml of plasma), we generated the most comprehensive cfDNA methylome to date. We demonstrated that cfTAPS provides multimodal information about cfDNA characteristics, including DNA methylation, tissue of origin, and DNA fragmentation. Integrated analysis of these epigenetic and genetic features enables accurate identification of early HCC and PDAC.",,pdf:https://www.science.org/doi/pdf/10.1126/sciadv.abh0534?download=true; doi:https://doi.org/10.1126/sciadv.abh0534; html:https://europepmc.org/articles/PMC8442905; pdf:https://europepmc.org/articles/PMC8442905?pdf=render 34857774,https://doi.org/10.1038/s41598-021-00854-x,Application of information theoretic feature selection and machine learning methods for the development of genetic risk prediction models.,"Jalali-Najafabadi F, Stadler M, Dand N, Jadon D, Soomro M, Ho P, Marzo-Ortega H, Helliwell P, Korendowych E, Simpson MA, Packham J, Smith CH, Barker JN, McHugh N, Warren RB, Barton A, Bowes J, BADBIR Study Group, BSTOP Study Group.",,Scientific reports,2021,2021-12-02,Y,,,,"In view of the growth of clinical risk prediction models using genetic data, there is an increasing need for studies that use appropriate methods to select the optimum number of features from a large number of genetic variants with a high degree of redundancy between features due to linkage disequilibrium (LD). Filter feature selection methods based on information theoretic criteria, are well suited to this challenge and will identify a subset of the original variables that should result in more accurate prediction. However, data collected from cohort studies are often high-dimensional genetic data with potential confounders presenting challenges to feature selection and risk prediction machine learning models. Patients with psoriasis are at high risk of developing a chronic arthritis known as psoriatic arthritis (PsA). The prevalence of PsA in this patient group can be up to 30% and the identification of high risk patients represents an important clinical research which would allow early intervention and a reduction of disability. This also provides us with an ideal scenario for the development of clinical risk prediction models and an opportunity to explore the application of information theoretic criteria methods. In this study, we developed the feature selection and psoriatic arthritis (PsA) risk prediction models that were applied to a cross-sectional genetic dataset of 1462 PsA cases and 1132 cutaneous-only psoriasis (PsC) cases using 2-digit HLA alleles imputed using the SNP2HLA algorithm. We also developed stratification method to mitigate the impact of potential confounder features and illustrate that confounding features impact the feature selection. The mitigated dataset was used in training of seven supervised algorithms. 80% of data was randomly used for training of seven supervised machine learning methods using stratified nested cross validation and 20% was selected randomly as a holdout set for internal validation. The risk prediction models were then further validated in UK Biobank dataset containing data on 1187 participants and a set of features overlapping with the training dataset.Performance of these methods has been evaluated using the area under the curve (AUC), accuracy, precision, recall, F1 score and decision curve analysis(net benefit). The best model is selected based on three criteria: the 'lowest number of feature subset' with the 'maximal average AUC over the nested cross validation' and good generalisability to the UK Biobank dataset. In the original dataset, with over 100 different bootstraps and seven feature selection (FS) methods, HLA_C_*06 was selected as the most informative genetic variant. When the dataset is mitigated the single most important genetic features based on rank was identified as HLA_B_*27 by the seven different feature selection methods, consistent with previous analyses of this data using regression based methods. However, the predictive accuracy of these single features in post mitigation was found to be moderate (AUC= 0.54 (internal cross validation), AUC=0.53 (internal hold out set), AUC=0.55(external data set)). Sequentially adding additional HLA features based on rank improved the performance of the Random Forest classification model where 20 2-digit features selected by Interaction Capping (ICAP) demonstrated (AUC= 0.61 (internal cross validation), AUC=0.57 (internal hold out set), AUC=0.58 (external dataset)). The stratification method for mitigation of confounding features and filter information theoretic feature selection can be applied to a high dimensional dataset with the potential confounders.",,pdf:https://www.nature.com/articles/s41598-021-00854-x.pdf; doi:https://doi.org/10.1038/s41598-021-00854-x; html:https://europepmc.org/articles/PMC8640070; pdf:https://europepmc.org/articles/PMC8640070?pdf=render 32328990,https://doi.org/10.1007/s10654-020-00633-4,The Dementias Platform UK (DPUK) Data Portal.,"Bauermeister S, Orton C, Thompson S, Barker RA, Bauermeister JR, Ben-Shlomo Y, Brayne C, Burn D, Campbell A, Calvin C, Chandran S, Chaturvedi N, Chêne G, Chessell IP, Corbett A, Davis DHJ, Denis M, Dufouil C, Elliott P, Fox N, Hill D, Hofer SM, Hu MT, Jindra C, Kee F, Kim CH, Kim C, Kivimaki M, Koychev I, Lawson RA, Linden GJ, Lyons RA, Mackay C, Matthews PM, McGuiness B, Middleton L, Moody C, Moore K, Na DL, O'Brien JT, Ourselin S, Paranjothy S, Park KS, Porteous DJ, Richards M, Ritchie CW, Rohrer JD, Rossor MN, Rowe JB, Scahill R, Schnier C, Schott JM, Seo SW, South M, Steptoe M, Tabrizi SJ, Tales A, Tillin T, Timpson NJ, Toga AW, Visser PJ, Wade-Martins R, Wilkinson T, Williams J, Wong A, Gallacher JEJ.",,European journal of epidemiology,2020,2020-04-23,Y,Cohorts; epidemiology; data management; Data Access; Data Repository; Data Platform,,,"The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure 'lab' using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.",,pdf:https://link.springer.com/content/pdf/10.1007/s10654-020-00633-4.pdf; doi:https://doi.org/10.1007/s10654-020-00633-4; html:https://europepmc.org/articles/PMC7320955; pdf:https://europepmc.org/articles/PMC7320955?pdf=render 33837077,https://doi.org/10.1126/sciadv.abe3868,Niche and local geography shape the pangenome of wastewater- and livestock-associated Enterobacteriaceae.,"Shaw LP, Chau KK, Kavanagh J, AbuOun M, Stubberfield E, Gweon HS, Barker L, Rodger G, Bowes MJ, Hubbard ATM, Pickford H, Swann J, Gilson D, Smith RP, Hoosdally SJ, Sebra R, Brett H, Peto TEA, Bailey MJ, Crook DW, Read DS, Anjum MF, Walker AS, Stoesser N, REHAB consortium.",,Science advances,2021,2021-04-09,Y,,,,"Escherichia coli and other Enterobacteriaceae are diverse species with ""open"" pangenomes, where genes move intra- and interspecies via horizontal gene transfer. However, most analyses focus on clinical isolates. The pangenome dynamics of natural populations remain understudied, despite their suggested role as reservoirs for antimicrobial resistance (AMR) genes. Here, we analyze near-complete genomes for 827 Enterobacteriaceae (553 Escherichia and 274 non-Escherichia spp.) with 2292 circularized plasmids in total, collected from 19 locations (livestock farms and wastewater treatment works in the United Kingdom) within a 30-km radius at three time points over a year. We find different dynamics for chromosomal and plasmid-borne genes. Plasmids have a higher burden of AMR genes and insertion sequences, and AMR-gene-carrying plasmids show evidence of being under stronger selective pressure. Environmental niche and local geography both play a role in shaping plasmid dynamics. Our results highlight the importance of local strategies for controlling the spread of AMR.",,pdf:https://discovery.ucl.ac.uk/10126288/1/eabe3868.full.pdf; doi:https://doi.org/10.1126/sciadv.abe3868; html:https://europepmc.org/articles/PMC8034854; pdf:https://europepmc.org/articles/PMC8034854?pdf=render @@ -2679,8 +2679,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 35617423,https://doi.org/10.1371/journal.pmed.1004015,Risk factors associated with SARS-CoV-2 infection in a multiethnic cohort of United Kingdom healthcare workers (UK-REACH): A cross-sectional analysis.,"Martin CA, Pan D, Melbourne C, Teece L, Aujayeb A, Baggaley RF, Bryant L, Carr S, Gregary B, Gupta A, Guyatt AL, John C, McManus IC, Nazareth J, Nellums LB, Reza R, Simpson S, Tobin MD, Woolf K, Zingwe S, Khunti K, Abrams KR, Gray LJ, Pareek M, UK-REACH Study Collaborative Group.",,PLoS medicine,2022,2022-05-26,Y,,,,"

Background

Healthcare workers (HCWs), particularly those from ethnic minority groups, have been shown to be at disproportionately higher risk of infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) compared to the general population. However, there is insufficient evidence on how demographic and occupational factors influence infection risk among ethnic minority HCWs.

Methods and findings

We conducted a cross-sectional analysis using data from the baseline questionnaire of the United Kingdom Research study into Ethnicity and Coronavirus Disease 2019 (COVID-19) Outcomes in Healthcare workers (UK-REACH) cohort study, administered between December 2020 and March 2021. We used logistic regression to examine associations of demographic, household, and occupational risk factors with SARS-CoV-2 infection (defined by polymerase chain reaction (PCR), serology, or suspected COVID-19) in a diverse group of HCWs. The primary exposure of interest was self-reported ethnicity. Among 10,772 HCWs who worked during the first UK national lockdown in March 2020, the median age was 45 (interquartile range [IQR] 35 to 54), 75.1% were female and 29.6% were from ethnic minority groups. A total of 2,496 (23.2%) reported previous SARS-CoV-2 infection. The fully adjusted model contained the following dependent variables: demographic factors (age, sex, ethnicity, migration status, deprivation, religiosity), household factors (living with key workers, shared spaces in accommodation, number of people in household), health factors (presence/absence of diabetes or immunosuppression, smoking history, shielding status, SARS-CoV-2 vaccination status), the extent of social mixing outside of the household, and occupational factors (job role, the area in which a participant worked, use of public transport to work, exposure to confirmed suspected COVID-19 patients, personal protective equipment [PPE] access, aerosol generating procedure exposure, night shift pattern, and the UK region of workplace). After adjustment, demographic and household factors associated with increased odds of infection included younger age, living with other key workers, and higher religiosity. Important occupational risk factors associated with increased odds of infection included attending to a higher number of COVID-19 positive patients (aOR 2.59, 95% CI 2.11 to 3.18 for ≥21 patients per week versus none), working in a nursing or midwifery role (1.30, 1.11 to 1.53, compared to doctors), reporting a lack of access to PPE (1.29, 1.17 to 1.43), and working in an ambulance (2.00, 1.56 to 2.58) or hospital inpatient setting (1.55, 1.38 to 1.75). Those who worked in intensive care units were less likely to have been infected (0.76, 0.64 to 0.92) than those who did not. Black HCWs were more likely to have been infected than their White colleagues, an effect which attenuated after adjustment for other known risk factors. This study is limited by self-selection bias and the cross sectional nature of the study means we cannot infer the direction of causality.

Conclusions

We identified key sociodemographic and occupational risk factors associated with SARS-CoV-2 infection among UK HCWs, and have determined factors that might contribute to a disproportionate odds of infection in HCWs from Black ethnic groups. These findings demonstrate the importance of social and occupational factors in driving ethnic disparities in COVID-19 outcomes, and should inform policies, including targeted vaccination strategies and risk assessments aimed at protecting HCWs in future waves of the COVID-19 pandemic.

Trial registration

The study was prospectively registered at ISRCTN (reference number: ISRCTN11811602).",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004015&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004015; html:https://europepmc.org/articles/PMC9187071; pdf:https://europepmc.org/articles/PMC9187071?pdf=render 32827479,https://doi.org/10.1016/s2214-109x(20)30278-3,"Mapping geographical inequalities in access to drinking water and sanitation facilities in low-income and middle-income countries, 2000-17.",Local Burden of Disease WaSH Collaborators.,,The Lancet. Global health,2020,2020-09-01,Y,,,,"

Background

Universal access to safe drinking water and sanitation facilities is an essential human right, recognised in the Sustainable Development Goals as crucial for preventing disease and improving human wellbeing. Comprehensive, high-resolution estimates are important to inform progress towards achieving this goal. We aimed to produce high-resolution geospatial estimates of access to drinking water and sanitation facilities.

Methods

We used a Bayesian geostatistical model and data from 600 sources across more than 88 low-income and middle-income countries (LMICs) to estimate access to drinking water and sanitation facilities on continuous continent-wide surfaces from 2000 to 2017, and aggregated results to policy-relevant administrative units. We estimated mutually exclusive and collectively exhaustive subcategories of facilities for drinking water (piped water on or off premises, other improved facilities, unimproved, and surface water) and sanitation facilities (septic or sewer sanitation, other improved, unimproved, and open defecation) with use of ordinal regression. We also estimated the number of diarrhoeal deaths in children younger than 5 years attributed to unsafe facilities and estimated deaths that were averted by increased access to safe facilities in 2017, and analysed geographical inequality in access within LMICs.

Findings

Across LMICs, access to both piped water and improved water overall increased between 2000 and 2017, with progress varying spatially. For piped water, the safest water facility type, access increased from 40·0% (95% uncertainty interval [UI] 39·4-40·7) to 50·3% (50·0-50·5), but was lowest in sub-Saharan Africa, where access to piped water was mostly concentrated in urban centres. Access to both sewer or septic sanitation and improved sanitation overall also increased across all LMICs during the study period. For sewer or septic sanitation, access was 46·3% (95% UI 46·1-46·5) in 2017, compared with 28·7% (28·5-29·0) in 2000. Although some units improved access to the safest drinking water or sanitation facilities since 2000, a large absolute number of people continued to not have access in several units with high access to such facilities (>80%) in 2017. More than 253 000 people did not have access to sewer or septic sanitation facilities in the city of Harare, Zimbabwe, despite 88·6% (95% UI 87·2-89·7) access overall. Many units were able to transition from the least safe facilities in 2000 to safe facilities by 2017; for units in which populations primarily practised open defecation in 2000, 686 (95% UI 664-711) of the 1830 (1797-1863) units transitioned to the use of improved sanitation. Geographical disparities in access to improved water across units decreased in 76·1% (95% UI 71·6-80·7) of countries from 2000 to 2017, and in 53·9% (50·6-59·6) of countries for access to improved sanitation, but remained evident subnationally in most countries in 2017.

Interpretation

Our estimates, combined with geospatial trends in diarrhoeal burden, identify where efforts to increase access to safe drinking water and sanitation facilities are most needed. By highlighting areas with successful approaches or in need of targeted interventions, our estimates can enable precision public health to effectively progress towards universal access to safe water and sanitation.

Funding

Bill & Melinda Gates Foundation.",,pdf:http://www.thelancet.com/article/S2214109X20302783/pdf; doi:https://doi.org/10.1016/S2214-109X(20)30278-3; html:https://europepmc.org/articles/PMC7443708 34377737,https://doi.org/10.1016/j.omtm.2021.06.012,Evidence generation and reproducibility in cell and gene therapy research: A call to action.,"Abou-El-Enein M, Angelis A, Appelbaum FR, Andrews NC, Bates SE, Bierman AS, Brenner MK, Cavazzana M, Caligiuri MA, Clevers H, Cooke E, Daley GQ, Dzau VJ, Ellis LM, Fineberg HV, Goldstein LSB, Gottschalk S, Hamburg MA, Ingber DE, Kohn DB, Krainer AR, Maus MV, Marks P, Mummery CL, Pettigrew RI, Rutter JL, Teichmann SA, Terzic A, Urnov FD, Williams DA, Wolchok JD, Lawler M, Turtle CJ, Bauer G, Ioannidis JPA.",,Molecular therapy. Methods & clinical development,2021,2021-07-21,Y,,,,,,doi:https://doi.org/10.1016/j.omtm.2021.06.012; doi:https://doi.org/10.1016/j.omtm.2021.06.012; html:https://europepmc.org/articles/PMC8322039; pdf:https://europepmc.org/articles/PMC8322039?pdf=render -38177345,https://doi.org/10.1038/s41588-023-01596-4,"Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference.","Meng X, Navoly G, Giannakopoulou O, Levey DF, Koller D, Pathak GA, Koen N, Lin K, Adams MJ, Rentería ME, Feng Y, Gaziano JM, Stein DJ, Zar HJ, Campbell ML, van Heel DA, Trivedi B, Finer S, McQuillin A, Bass N, Chundru VK, Martin HC, Huang QQ, Valkovskaya M, Chu CY, Kanjira S, Kuo PH, Chen HC, Tsai SJ, Liu YL, Kendler KS, Peterson RE, Cai N, Fang Y, Sen S, Scott LJ, Burmeister M, Loos RJF, Preuss MH, Actkins KV, Davis LK, Uddin M, Wani AH, Wildman DE, Aiello AE, Ursano RJ, Kessler RC, Kanai M, Okada Y, Sakaue S, Rabinowitz JA, Maher BS, Uhl G, Eaton W, Cruz-Fuentes CS, Martinez-Levy GA, Campos AI, Millwood IY, Chen Z, Li L, Wassertheil-Smoller S, Jiang Y, Tian C, Martin NG, Mitchell BL, Byrne EM, Awasthi S, Coleman JRI, Ripke S, PGC-MDD Working Group, China Kadoorie Biobank Collaborative Group, 23andMe Research Team, Genes and Health Research Team, BioBank Japan Project, Sofer T, Walters RG, McIntosh AM, Polimanti R, Dunn EC, Stein MB, Gelernter J, Lewis CM, Kuchenbaecker K.",,Nature genetics,2024,2024-01-04,Y,,,,"Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.",,pdf:https://www.nature.com/articles/s41588-023-01596-4.pdf; doi:https://doi.org/10.1038/s41588-023-01596-4; html:https://europepmc.org/articles/PMC10864182; pdf:https://europepmc.org/articles/PMC10864182?pdf=render 34193486,https://doi.org/10.1136/bmjopen-2020-045105,SPIRIT-PRO Extension explanation and elaboration: guidelines for inclusion of patient-reported outcomes in protocols of clinical trials.,"Calvert M, King M, Mercieca-Bebber R, Aiyegbusi O, Kyte D, Slade A, Chan AW, Basch E, Bell J, Bennett A, Bhatnagar V, Blazeby J, Bottomley A, Brown J, Brundage M, Campbell L, Cappelleri JC, Draper H, Dueck AC, Ells C, Frank L, Golub RM, Griebsch I, Haywood K, Hunn A, King-Kallimanis B, Martin L, Mitchell S, Morel T, Nelson L, Norquist J, O'Connor D, Palmer M, Patrick D, Price G, Regnault A, Retzer A, Revicki D, Scott J, Stephens R, Turner G, Valakas A, Velikova G, von Hildebrand M, Walker A, Wenzel L.",,BMJ open,2021,2021-06-30,Y,Clinical Trials; Protocols & Guidelines; Statistics & Research Methods; Education & Training (See Medical Education & Training),,,"Patient-reported outcomes (PROs) are used in clinical trials to provide valuable evidence on the impact of disease and treatment on patients' symptoms, function and quality of life. High-quality PRO data from trials can inform shared decision-making, regulatory and economic analyses and health policy. Recent evidence suggests the PRO content of past trial protocols was often incomplete or unclear, leading to research waste. To address this issue, international, consensus-based, PRO-specific guidelines were developed: the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)-PRO Extension. The SPIRIT-PRO Extension is a 16-item checklist which aims to improve the content and quality of aspects of clinical trial protocols relating to PRO data collection to minimise research waste, and ultimately better inform patient-centred care. This SPIRIT-PRO explanation and elaboration (E&E) paper provides information to promote understanding and facilitate uptake of the recommended checklist items, including a comprehensive protocol template. For each SPIRIT-PRO item, we provide a detailed description, one or more examples from existing trial protocols and supporting empirical evidence of the item's importance. We recommend this paper and protocol template be used alongside the SPIRIT 2013 and SPIRIT-PRO Extension paper to optimise the transparent development and review of trial protocols with PROs.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e045105.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-045105; html:https://europepmc.org/articles/PMC8246371; pdf:https://europepmc.org/articles/PMC8246371?pdf=render +38177345,https://doi.org/10.1038/s41588-023-01596-4,"Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference.","Meng X, Navoly G, Giannakopoulou O, Levey DF, Koller D, Pathak GA, Koen N, Lin K, Adams MJ, Rentería ME, Feng Y, Gaziano JM, Stein DJ, Zar HJ, Campbell ML, van Heel DA, Trivedi B, Finer S, McQuillin A, Bass N, Chundru VK, Martin HC, Huang QQ, Valkovskaya M, Chu CY, Kanjira S, Kuo PH, Chen HC, Tsai SJ, Liu YL, Kendler KS, Peterson RE, Cai N, Fang Y, Sen S, Scott LJ, Burmeister M, Loos RJF, Preuss MH, Actkins KV, Davis LK, Uddin M, Wani AH, Wildman DE, Aiello AE, Ursano RJ, Kessler RC, Kanai M, Okada Y, Sakaue S, Rabinowitz JA, Maher BS, Uhl G, Eaton W, Cruz-Fuentes CS, Martinez-Levy GA, Campos AI, Millwood IY, Chen Z, Li L, Wassertheil-Smoller S, Jiang Y, Tian C, Martin NG, Mitchell BL, Byrne EM, Awasthi S, Coleman JRI, Ripke S, PGC-MDD Working Group, China Kadoorie Biobank Collaborative Group, 23andMe Research Team, Genes and Health Research Team, BioBank Japan Project, Sofer T, Walters RG, McIntosh AM, Polimanti R, Dunn EC, Stein MB, Gelernter J, Lewis CM, Kuchenbaecker K.",,Nature genetics,2024,2024-01-04,Y,,,,"Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.",,pdf:https://www.nature.com/articles/s41588-023-01596-4.pdf; doi:https://doi.org/10.1038/s41588-023-01596-4; html:https://europepmc.org/articles/PMC10864182; pdf:https://europepmc.org/articles/PMC10864182?pdf=render 32492392,https://doi.org/10.1016/j.cmet.2020.05.007,"Exome Sequencing Identifies Genes and Gene Sets Contributing to Severe Childhood Obesity, Linking PHIP Variants to Repressed POMC Transcription.","Marenne G, Hendricks AE, Perdikari A, Bounds R, Payne F, Keogh JM, Lelliott CJ, Henning E, Pathan S, Ashford S, Bochukova EG, Mistry V, Daly A, Hayward C, INTERVAL, UK10K Consortium, Wareham NJ, O'Rahilly S, Langenberg C, Wheeler E, Zeggini E, Farooqi IS, Barroso I.",,Cell metabolism,2020,2020-06-01,Y,Genetics; Function; Association; Pomc; Gene Set; Severe Childhood Obesity,,,"Obesity is genetically heterogeneous with monogenic and complex polygenic forms. Using exome and targeted sequencing in 2,737 severely obese cases and 6,704 controls, we identified three genes (PHIP, DGKI, and ZMYM4) with an excess burden of very rare predicted deleterious variants in cases. In cells, we found that nuclear PHIP (pleckstrin homology domain interacting protein) directly enhances transcription of pro-opiomelanocortin (POMC), a neuropeptide that suppresses appetite. Obesity-associated PHIP variants repressed POMC transcription. Our demonstration that PHIP is involved in human energy homeostasis through transcriptional regulation of central melanocortin signaling has potential diagnostic and therapeutic implications for patients with obesity and developmental delay. Additionally, we found an excess burden of predicted deleterious variants involving genes nearest to loci from obesity genome-wide association studies. Genes and gene sets influencing obesity with variable penetrance provide compelling evidence for a continuum of causality in the genetic architecture of obesity, and explain some of its missing heritability.",,pdf:http://www.cell.com/article/S1550413120302461/pdf; doi:https://doi.org/10.1016/j.cmet.2020.05.007; html:https://europepmc.org/articles/PMC7267775 33607016,https://doi.org/10.1016/s2214-109x(20)30488-5,The Lancet Global Health Commission on Global Eye Health: vision beyond 2020.,"Burton MJ, Ramke J, Marques AP, Bourne RRA, Congdon N, Jones I, Ah Tong BAM, Arunga S, Bachani D, Bascaran C, Bastawrous A, Blanchet K, Braithwaite T, Buchan JC, Cairns J, Cama A, Chagunda M, Chuluunkhuu C, Cooper A, Crofts-Lawrence J, Dean WH, Denniston AK, Ehrlich JR, Emerson PM, Evans JR, Frick KD, Friedman DS, Furtado JM, Gichangi MM, Gichuhi S, Gilbert SS, Gurung R, Habtamu E, Holland P, Jonas JB, Keane PA, Keay L, Khanna RC, Khaw PT, Kuper H, Kyari F, Lansingh VC, Mactaggart I, Mafwiri MM, Mathenge W, McCormick I, Morjaria P, Mowatt L, Muirhead D, Murthy GVS, Mwangi N, Patel DB, Peto T, Qureshi BM, Salomão SR, Sarah V, Shilio BR, Solomon AW, Swenor BK, Taylor HR, Wang N, Webson A, West SK, Wong TY, Wormald R, Yasmin S, Yusufu M, Silva JC, Resnikoff S, Ravilla T, Gilbert CE, Foster A, Faal HB.",,The Lancet. Global health,2021,2021-02-16,Y,,,,,,pdf:http://www.thelancet.com/article/S2214109X20304885/pdf; doi:https://doi.org/10.1016/S2214-109X(20)30488-5; html:https://europepmc.org/articles/PMC7966694 33532862,https://doi.org/10.1093/eurheartj/ehaa1040,Genome-wide analysis identifies novel susceptibility loci for myocardial infarction.,"Hartiala JA, Han Y, Jia Q, Hilser JR, Huang P, Gukasyan J, Schwartzman WS, Cai Z, Biswas S, Trégouët DA, Smith NL, INVENT Consortium, CHARGE Consortium Hemostasis Working Group, GENIUS-CHD Consortium, Seldin M, Pan C, Mehrabian M, Lusis AJ, Bazeley P, Sun YV, Liu C, Quyyumi AA, Scholz M, Thiery J, Delgado GE, Kleber ME, März W, Howe LJ, Asselbergs FW, van Vugt M, Vlachojannis GJ, Patel RS, Lyytikäinen LP, Kähönen M, Lehtimäki T, Nieminen TVM, Kuukasjärvi P, Laurikka JO, Chang X, Heng CK, Jiang R, Kraus WE, Hauser ER, Ferguson JF, Reilly MP, Ito K, Koyama S, Kamatani Y, Komuro I, Biobank Japan, Stolze LK, Romanoski CE, Khan MD, Turner AW, Miller CL, Aherrahrou R, Civelek M, Ma L, Björkegren JLM, Kumar SR, Tang WHW, Hazen SL, Allayee H.",,European heart journal,2021,2021-03-01,N,Myocardial infarction; Meta-analysis; genetic factors; Genome-wide Association Study; Slc44a3,,,"

Aims

While most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation.

Methods and results

We carried out a genome-wide association study for MI in the UK Biobank (n∼472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n∼167 000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (n∼165 000) and 16 independent angiography-based cohorts (n∼27 000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1β (vs. vehicle), and associated with smooth muscle cell migration in vitro.

Conclusions

A large-scale analysis comprising ∼831 000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques.",,pdf:https://academic.oup.com/eurheartj/article-pdf/42/9/919/36429038/ehaa1040.pdf; doi:https://doi.org/10.1093/eurheartj/ehaa1040; html:https://europepmc.org/articles/PMC7936531; pdf:https://europepmc.org/articles/PMC7936531?pdf=render; doi:https://doi.org/10.1093/eurheartj/ehaa1040 diff --git a/data/papers.json b/data/papers.json index de2d8e74..5d23bc93 100644 --- a/data/papers.json +++ b/data/papers.json @@ -2039,23 +2039,6 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/5/e066398.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-066398; html:https://europepmc.org/articles/PMC10193088; pdf:https://europepmc.org/articles/PMC10193088?pdf=render" }, - { - "id": "34817387", - "doi": "https://doi.org/10.2196/29532", - "title": "Introduction of Systematized Nomenclature of Medicine-Clinical Terms Coding Into an Electronic Health Record and Evaluation of its Impact: Qualitative and Quantitative Study.", - "authorString": "Pankhurst T, Evison F, Atia J, Gallier S, Coleman J, Ball S, McKee D, Ryan S, Black R.", - "authorAffiliations": "", - "journalTitle": "JMIR medical informatics", - "pubYear": "2021", - "date": "2021-11-23", - "isOpenAccess": "Y", - "keywords": "Research; Diagnoses; data sharing; Clinical Decision Support; Population Health; Electronic Health Records; Coding Standards; Problem List; Health Data Exchange; Clinician Led Design; International Classification Of Diseases Version 10 (Icd-10); National Health Service Blueprint; Systematized Nomenclature Of Medicine\u2013clinical Terms (Snomed-ct); Clinician Reported Experience; Electronic Health Record Standards; Patient Diagnoses; Use Of Electronic Health Data; User-led Design; Clinical Usability; Health Data Research", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

This study describes the conversion within an existing electronic health record (EHR) from the International Classification of Diseases, Tenth Revision coding system to the SNOMED-CT (Systematized Nomenclature of Medicine-Clinical Terms) for the collection of patient histories and diagnoses. The setting is a large acute hospital that is designing and building its own EHR. Well-designed EHRs create opportunities for continuous data collection, which can be used in clinical decision support rules to drive patient safety. Collected data can be exchanged across health care systems to support patients in all health care settings. Data can be used for research to prevent diseases and protect future populations.

Objective

The aim of this study was to migrate a current EHR, with all relevant patient data, to the SNOMED-CT coding system to optimize clinical use and clinical decision support, facilitate data sharing across organizational boundaries for national programs, and enable remodeling of medical pathways.

Methods

The study used qualitative and quantitative data to understand the successes and gaps in the project, clinician attitudes toward the new tool, and the future use of the tool.

Results

The new coding system (tool) was well received and immediately widely used in all specialties. This resulted in increased, accurate, and clinically relevant data collection. Clinicians appreciated the increased depth and detail of the new coding, welcomed the potential for both data sharing and research, and provided extensive feedback for further development.

Conclusions

Successful implementation of the new system aligned the University Hospitals Birmingham NHS Foundation Trust with national strategy and can be used as a blueprint for similar projects in other health care settings.", - "laySummary": "", - "urls": "pdf:https://medinform.jmir.org/2021/11/e29532/PDF; doi:https://doi.org/10.2196/29532; html:https://europepmc.org/articles/PMC8663536" - }, { "id": "36216011", "doi": "https://doi.org/10.1016/s2213-2600(22)00360-5", @@ -2073,6 +2056,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/s2213-2600(22)00360-5; doi:https://doi.org/10.1016/S2213-2600(22)00360-5; html:https://europepmc.org/articles/PMC9708088; pdf:https://europepmc.org/articles/PMC9708088?pdf=render" }, + { + "id": "34817387", + "doi": "https://doi.org/10.2196/29532", + "title": "Introduction of Systematized Nomenclature of Medicine-Clinical Terms Coding Into an Electronic Health Record and Evaluation of its Impact: Qualitative and Quantitative Study.", + "authorString": "Pankhurst T, Evison F, Atia J, Gallier S, Coleman J, Ball S, McKee D, Ryan S, Black R.", + "authorAffiliations": "", + "journalTitle": "JMIR medical informatics", + "pubYear": "2021", + "date": "2021-11-23", + "isOpenAccess": "Y", + "keywords": "Research; Diagnoses; data sharing; Clinical Decision Support; Population Health; Electronic Health Records; Coding Standards; Problem List; Health Data Exchange; Clinician Led Design; International Classification Of Diseases Version 10 (Icd-10); National Health Service Blueprint; Systematized Nomenclature Of Medicine\u2013clinical Terms (Snomed-ct); Clinician Reported Experience; Electronic Health Record Standards; Patient Diagnoses; Use Of Electronic Health Data; User-led Design; Clinical Usability; Health Data Research", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

This study describes the conversion within an existing electronic health record (EHR) from the International Classification of Diseases, Tenth Revision coding system to the SNOMED-CT (Systematized Nomenclature of Medicine-Clinical Terms) for the collection of patient histories and diagnoses. The setting is a large acute hospital that is designing and building its own EHR. Well-designed EHRs create opportunities for continuous data collection, which can be used in clinical decision support rules to drive patient safety. Collected data can be exchanged across health care systems to support patients in all health care settings. Data can be used for research to prevent diseases and protect future populations.

Objective

The aim of this study was to migrate a current EHR, with all relevant patient data, to the SNOMED-CT coding system to optimize clinical use and clinical decision support, facilitate data sharing across organizational boundaries for national programs, and enable remodeling of medical pathways.

Methods

The study used qualitative and quantitative data to understand the successes and gaps in the project, clinician attitudes toward the new tool, and the future use of the tool.

Results

The new coding system (tool) was well received and immediately widely used in all specialties. This resulted in increased, accurate, and clinically relevant data collection. Clinicians appreciated the increased depth and detail of the new coding, welcomed the potential for both data sharing and research, and provided extensive feedback for further development.

Conclusions

Successful implementation of the new system aligned the University Hospitals Birmingham NHS Foundation Trust with national strategy and can be used as a blueprint for similar projects in other health care settings.", + "laySummary": "", + "urls": "pdf:https://medinform.jmir.org/2021/11/e29532/PDF; doi:https://doi.org/10.2196/29532; html:https://europepmc.org/articles/PMC8663536" + }, { "id": "35918098", "doi": "https://doi.org/10.1136/bmj-2022-070695", @@ -2583,23 +2583,6 @@ "laySummary": "", "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4669009/1/Russell_etal_2022_Incidence-and-management-of-inflammatory.pdf; doi:https://doi.org/10.1016/S2665-9913(22)00305-8; html:https://europepmc.org/articles/PMC9691150; pdf:https://europepmc.org/articles/PMC9691150?pdf=render" }, - { - "id": "35909577", - "doi": "https://doi.org/10.23889/ijpds.v7i1.1725", - "title": "Educational achievements of children aged 10-11 years with cystic fibrosis. A data linkage study in Wales.", - "authorString": "Schl\u00fcter DK, Griffiths R, Akbari A, Taylor-Robinson D.", - "authorAffiliations": "", - "journalTitle": "International journal of population data science", - "pubYear": "2022", - "date": "2022-06-27", - "isOpenAccess": "Y", - "keywords": "Education; Cystic Fibrosis; Data Linkage; Sail Databank", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

As people with cystic fibrosis (CF) lead longer, healthier lives, educational qualifications and employment prospects are increasingly important. However, little is known about the social consequences of CF, in particular, any impact on educational achievements and the support children with CF receive in schools.

Objectives

To assess the educational achievements of children with CF in Wales compared to the general Welsh population, and the additional learning support children with CF receive in schools.

Methods

We conducted a population-scale data linkage study of all children born in Wales using the Secure Anonymised Information Linkage (SAIL) Databank. We used anonymised individual-level population-scale health and administrative data sources to identify children with CF born between 2000 - 2015, linked to educational attainment records. We calculated the percentage of children that reached expected levels in statutory assessment at age 10-11, Key Stage 2 (KS2), and compared this to educational outcomes in the general population. We also assessed the percentage of children with CF that received extra learning support.

Results

Out of 150 eligible children, 119 had KS2 results. 77% (95% CI: 69%-84%) of children achieved expected levels in English, 81% (95% CI: 73% -87%) in Mathematics and 82% (95% CI: 75% - 88%) in Science. In the comparable general Welsh population, 83.4% to 91.1% achieved the expected level in English, 84.9% to 91.6% in Maths, and 87.1% to 92.2% in Science across the years of the study. 70% of children with CF received extra learning support.

Conclusions

Children with CF in Wales may have worse educational achievements than the general population. More research is needed to inform policies and interventions to better support children with CF to reach their full educational potential and employment opportunities.", - "laySummary": "", - "urls": "pdf:https://ijpds.org/article/download/1725/3455; doi:https://doi.org/10.23889/ijpds.v7i1.1725; html:https://europepmc.org/articles/PMC9284509; pdf:https://europepmc.org/articles/PMC9284509?pdf=render" - }, { "id": "34148733", "doi": "https://doi.org/10.1016/j.bja.2021.05.018", @@ -2617,6 +2600,23 @@ "laySummary": "", "urls": "pdf:http://www.bjanaesthesia.org/article/S0007091221003123/pdf; doi:https://doi.org/10.1016/j.bja.2021.05.018; html:https://europepmc.org/articles/PMC8192173; pdf:https://europepmc.org/articles/PMC8192173?pdf=render" }, + { + "id": "35909577", + "doi": "https://doi.org/10.23889/ijpds.v7i1.1725", + "title": "Educational achievements of children aged 10-11 years with cystic fibrosis. A data linkage study in Wales.", + "authorString": "Schl\u00fcter DK, Griffiths R, Akbari A, Taylor-Robinson D.", + "authorAffiliations": "", + "journalTitle": "International journal of population data science", + "pubYear": "2022", + "date": "2022-06-27", + "isOpenAccess": "Y", + "keywords": "Education; Cystic Fibrosis; Data Linkage; Sail Databank", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

As people with cystic fibrosis (CF) lead longer, healthier lives, educational qualifications and employment prospects are increasingly important. However, little is known about the social consequences of CF, in particular, any impact on educational achievements and the support children with CF receive in schools.

Objectives

To assess the educational achievements of children with CF in Wales compared to the general Welsh population, and the additional learning support children with CF receive in schools.

Methods

We conducted a population-scale data linkage study of all children born in Wales using the Secure Anonymised Information Linkage (SAIL) Databank. We used anonymised individual-level population-scale health and administrative data sources to identify children with CF born between 2000 - 2015, linked to educational attainment records. We calculated the percentage of children that reached expected levels in statutory assessment at age 10-11, Key Stage 2 (KS2), and compared this to educational outcomes in the general population. We also assessed the percentage of children with CF that received extra learning support.

Results

Out of 150 eligible children, 119 had KS2 results. 77% (95% CI: 69%-84%) of children achieved expected levels in English, 81% (95% CI: 73% -87%) in Mathematics and 82% (95% CI: 75% - 88%) in Science. In the comparable general Welsh population, 83.4% to 91.1% achieved the expected level in English, 84.9% to 91.6% in Maths, and 87.1% to 92.2% in Science across the years of the study. 70% of children with CF received extra learning support.

Conclusions

Children with CF in Wales may have worse educational achievements than the general population. More research is needed to inform policies and interventions to better support children with CF to reach their full educational potential and employment opportunities.", + "laySummary": "", + "urls": "pdf:https://ijpds.org/article/download/1725/3455; doi:https://doi.org/10.23889/ijpds.v7i1.1725; html:https://europepmc.org/articles/PMC9284509; pdf:https://europepmc.org/articles/PMC9284509?pdf=render" + }, { "id": "33319712", "doi": "https://doi.org/10.1186/s12911-020-01336-2", @@ -3637,23 +3637,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/cardiovascres/advance-article-pdf/doi/10.1093/cvr/cvad106/50910161/cvad106.pdf; doi:https://doi.org/10.1093/cvr/cvad106; html:https://europepmc.org/articles/PMC10730242; pdf:https://europepmc.org/articles/PMC10730242?pdf=render" }, - { - "id": "36769519", - "doi": "https://doi.org/10.3390/jcm12030872", - "title": "Patterns of Healthcare Resource Utilisation of Critical Care Survivors between 2006 and 2017 in Wales: A Population-Based Study.", - "authorString": "Alsallakh M, Tan L, Pugh R, Akbari A, Bailey R, Griffiths R, Lyons RA, Szakmany T.", - "authorAffiliations": "", - "journalTitle": "Journal of clinical medicine", - "pubYear": "2023", - "date": "2023-01-21", - "isOpenAccess": "Y", - "keywords": "Wales; Healthcare Resource Utilisation; Critical Care Survivorship", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "In this retrospective cohort study, we used the Secure Anonymised Information Linkage (SAIL) Databank to characterise and identify predictors of the one-year post-discharge healthcare resource utilisation (HRU) of adults who were admitted to critical care units in Wales between 1 April 2006 and 31 December 2017. We modelled one-year post-critical-care HRU using negative binomial models and used linear models for the difference from one-year pre-critical-care HRU. We estimated the association between critical illness and post-hospitalisation HRU using multilevel negative binomial models among people hospitalised in 2015. We studied 55,151 patients. Post-critical-care HRU was 11-87% greater than pre-critical-care levels, whereas emergency department (ED) attendances decreased by 30%. Age \u226550 years was generally associated with greater post-critical-care HRU; those over 80 had three times longer hospital readmissions than those younger than 50 (incidence rate ratio (IRR): 2.96, 95% CI: 2.84, 3.09). However, ED attendances were higher in those younger than 50. High comorbidity was associated with 22-62% greater post-critical-care HRU than no or low comorbidity. The most socioeconomically deprived quintile was associated with 24% more ED attendances (IRR: 1.24 [1.16, 1.32]) and 13% longer hospital stays (IRR: 1.13 [1.09, 1.17]) than the least deprived quintile. Critical care survivors had greater 1-year post-discharge HRU than non-critical inpatients, including 68% longer hospital stays (IRR: 1.68 [1.63, 1.74]). Critical care survivors, particularly those with older ages, high comorbidity, and socioeconomic deprivation, used significantly more primary and secondary care resources after discharge compared with their baseline and non-critical inpatients. Interventions are needed to ensure that key subgroups are identified and adequately supported.", - "laySummary": "", - "urls": "pdf:https://www.mdpi.com/2077-0383/12/3/872/pdf?version=1674984751; doi:https://doi.org/10.3390/jcm12030872; html:https://europepmc.org/articles/PMC9917699; pdf:https://europepmc.org/articles/PMC9917699?pdf=render" - }, { "id": "36035235", "doi": "https://doi.org/10.1212/nxg.0000000000200015", @@ -3671,6 +3654,23 @@ "laySummary": "", "urls": "pdf:https://ng.neurology.org/content/nng/8/5/e200015.full.pdf; doi:https://doi.org/10.1212/NXG.0000000000200015; html:https://europepmc.org/articles/PMC9403885; pdf:https://europepmc.org/articles/PMC9403885?pdf=render" }, + { + "id": "36769519", + "doi": "https://doi.org/10.3390/jcm12030872", + "title": "Patterns of Healthcare Resource Utilisation of Critical Care Survivors between 2006 and 2017 in Wales: A Population-Based Study.", + "authorString": "Alsallakh M, Tan L, Pugh R, Akbari A, Bailey R, Griffiths R, Lyons RA, Szakmany T.", + "authorAffiliations": "", + "journalTitle": "Journal of clinical medicine", + "pubYear": "2023", + "date": "2023-01-21", + "isOpenAccess": "Y", + "keywords": "Wales; Healthcare Resource Utilisation; Critical Care Survivorship", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "In this retrospective cohort study, we used the Secure Anonymised Information Linkage (SAIL) Databank to characterise and identify predictors of the one-year post-discharge healthcare resource utilisation (HRU) of adults who were admitted to critical care units in Wales between 1 April 2006 and 31 December 2017. We modelled one-year post-critical-care HRU using negative binomial models and used linear models for the difference from one-year pre-critical-care HRU. We estimated the association between critical illness and post-hospitalisation HRU using multilevel negative binomial models among people hospitalised in 2015. We studied 55,151 patients. Post-critical-care HRU was 11-87% greater than pre-critical-care levels, whereas emergency department (ED) attendances decreased by 30%. Age \u226550 years was generally associated with greater post-critical-care HRU; those over 80 had three times longer hospital readmissions than those younger than 50 (incidence rate ratio (IRR): 2.96, 95% CI: 2.84, 3.09). However, ED attendances were higher in those younger than 50. High comorbidity was associated with 22-62% greater post-critical-care HRU than no or low comorbidity. The most socioeconomically deprived quintile was associated with 24% more ED attendances (IRR: 1.24 [1.16, 1.32]) and 13% longer hospital stays (IRR: 1.13 [1.09, 1.17]) than the least deprived quintile. Critical care survivors had greater 1-year post-discharge HRU than non-critical inpatients, including 68% longer hospital stays (IRR: 1.68 [1.63, 1.74]). Critical care survivors, particularly those with older ages, high comorbidity, and socioeconomic deprivation, used significantly more primary and secondary care resources after discharge compared with their baseline and non-critical inpatients. Interventions are needed to ensure that key subgroups are identified and adequately supported.", + "laySummary": "", + "urls": "pdf:https://www.mdpi.com/2077-0383/12/3/872/pdf?version=1674984751; doi:https://doi.org/10.3390/jcm12030872; html:https://europepmc.org/articles/PMC9917699; pdf:https://europepmc.org/articles/PMC9917699?pdf=render" + }, { "id": "36609574", "doi": "https://doi.org/10.1038/s41467-022-35771-8", @@ -4487,23 +4487,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/acel.13808; doi:https://doi.org/10.1111/acel.13808; html:https://europepmc.org/articles/PMC10352557; pdf:https://europepmc.org/articles/PMC10352557?pdf=render" }, - { - "id": "38751343", - "doi": "https://doi.org/10.1093/ced/llae196", - "title": "Disagreement concerning atopic dermatitis subtypes between an English prospective cohort (ALSPAC) and linked electronic health records.", - "authorString": "Matthewman J, Mulick A, Dand N, Major-Smith D, Henderson A, Pearce N, Denaxas S, Iskandar R, Roberts A, Cornish RP, Brown SJ, Paternoster L, Langan SM.", - "authorAffiliations": "", - "journalTitle": "Clinical and experimental dermatology", - "pubYear": "2024", - "date": "2024-05-16", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Subtypes of atopic dermatitis (AD) have been derived from the Avon Longitudinal Study of Parents and Children (ALSPAC) based on presence and severity of symptoms reported in questionnaires (Severe-Frequent, Moderate-Frequent, Moderate-Declining, Mild-Intermittent, Unaffected/Rare). Good agreement between ALSPAC and linked electronic health records (EHRs) would increase trust in the clinical validity of these subtypes and allow inferring subtypes from EHRs alone, which would enable their study in large primary care databases.

Objectives

1. Explore if presence and number of AD records in EHRs agrees with AD symptom and severity reports from ALSPAC; 2. Explore if EHRs agree with ALSPAC-derived AD subtypes; 3. Construct models to classify ALSPAC-derived AD subtype using EHRs.

Methods

We used data from the ALSPAC prospective cohort study from 11 timepoints until age 14 years (1991-2008), linked to local general practice EHRs. We assessed how far ALSPAC questionnaire responses and derived subtypes agreed with AD as established in EHRs using different AD definitions (e.g., diagnosis and/or prescription) and other AD-related records. We classified AD subtypes using EHRs, fitting multinomial logistic regression models tuning hyperparameters and evaluating performance in the testing set (ROC AUC, accuracy, sensitivity, and specificity).

Results

8,828 individuals out of a total 13,898 had both been assigned an AD subtype and had linked EHRs. The number of AD-related codes in EHRs generally increased with severity of AD subtype, however not all with the Severe-Frequent subtypes had AD in EHRs, and many with the Unaffected/Rare subtype did have AD in EHRs. When predicting ALSPAC AD subtype using EHRs, the best tuned model had ROC AUC of 0.65, sensitivity of 0.29 and specificity of 0.83 (both macro averaged); when different sets of predictors were used, individuals with missing EHR coverage excluded, and subtypes combined, sensitivity was not considerably improved.

Conclusions

ALSPAC and EHRs disagreed not just on AD subtypes, but also on whether children had AD or not. Researchers should be aware that individuals considered as having AD in one source may not be considered as having AD in another.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/ced/llae196; doi:https://doi.org/10.1093/ced/llae196" - }, { "id": "31783849", "doi": "https://doi.org/10.1186/s12911-019-0953-2", @@ -4521,6 +4504,23 @@ "laySummary": "Rees et al used a Welsh database to examine inpatient episode/transfer coding coding for psychiatric patients. They identified deficiencies in the existing coding system for psychitatrics transfers and unexplained coding mistakes/problems, then they presesnt several different methods for constructing the inpatient spell to improve coding and avoid misclassification.", "urls": "pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-019-0953-2; doi:https://doi.org/10.1186/s12911-019-0953-2; html:https://europepmc.org/articles/PMC6884917; pdf:https://europepmc.org/articles/PMC6884917?pdf=render" }, + { + "id": "38751343", + "doi": "https://doi.org/10.1093/ced/llae196", + "title": "Disagreement concerning atopic dermatitis subtypes between an English prospective cohort (ALSPAC) and linked electronic health records.", + "authorString": "Matthewman J, Mulick A, Dand N, Major-Smith D, Henderson A, Pearce N, Denaxas S, Iskandar R, Roberts A, Cornish RP, Brown SJ, Paternoster L, Langan SM.", + "authorAffiliations": "", + "journalTitle": "Clinical and experimental dermatology", + "pubYear": "2024", + "date": "2024-05-16", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Subtypes of atopic dermatitis (AD) have been derived from the Avon Longitudinal Study of Parents and Children (ALSPAC) based on presence and severity of symptoms reported in questionnaires (Severe-Frequent, Moderate-Frequent, Moderate-Declining, Mild-Intermittent, Unaffected/Rare). Good agreement between ALSPAC and linked electronic health records (EHRs) would increase trust in the clinical validity of these subtypes and allow inferring subtypes from EHRs alone, which would enable their study in large primary care databases.

Objectives

1. Explore if presence and number of AD records in EHRs agrees with AD symptom and severity reports from ALSPAC; 2. Explore if EHRs agree with ALSPAC-derived AD subtypes; 3. Construct models to classify ALSPAC-derived AD subtype using EHRs.

Methods

We used data from the ALSPAC prospective cohort study from 11 timepoints until age 14 years (1991-2008), linked to local general practice EHRs. We assessed how far ALSPAC questionnaire responses and derived subtypes agreed with AD as established in EHRs using different AD definitions (e.g., diagnosis and/or prescription) and other AD-related records. We classified AD subtypes using EHRs, fitting multinomial logistic regression models tuning hyperparameters and evaluating performance in the testing set (ROC AUC, accuracy, sensitivity, and specificity).

Results

8,828 individuals out of a total 13,898 had both been assigned an AD subtype and had linked EHRs. The number of AD-related codes in EHRs generally increased with severity of AD subtype, however not all with the Severe-Frequent subtypes had AD in EHRs, and many with the Unaffected/Rare subtype did have AD in EHRs. When predicting ALSPAC AD subtype using EHRs, the best tuned model had ROC AUC of 0.65, sensitivity of 0.29 and specificity of 0.83 (both macro averaged); when different sets of predictors were used, individuals with missing EHR coverage excluded, and subtypes combined, sensitivity was not considerably improved.

Conclusions

ALSPAC and EHRs disagreed not just on AD subtypes, but also on whether children had AD or not. Researchers should be aware that individuals considered as having AD in one source may not be considered as having AD in another.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/ced/llae196; doi:https://doi.org/10.1093/ced/llae196" + }, { "id": "36997856", "doi": "https://doi.org/10.1186/s12882-023-03126-0", @@ -4742,23 +4742,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/ageing/afad077; doi:https://doi.org/10.1093/ageing/afad077; html:https://europepmc.org/articles/PMC10226747; pdf:https://europepmc.org/articles/PMC10226747?pdf=render" }, - { - "id": "37789603", - "doi": "https://doi.org/10.1002/pon.6225", - "title": "Prognostic factors for mental wellbeing in prostate cancer: A\u00a0systematic review and meta-analysis.", - "authorString": "Vyas N, Brunckhorst O, Fanshawe JB, Stewart R, Dasgupta P, Ahmed K.", - "authorAffiliations": "", - "journalTitle": "Psycho-oncology", - "pubYear": "2023", - "date": "2023-10-03", - "isOpenAccess": "Y", - "keywords": "Cancer; Depression; Quality of life; Anxiety; Oncology; prostate cancer; Body Image; Masculinity; Mental Wellbeing; Fear Of Cancer Recurrence", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

To evaluate the evidence base for patient, oncological, and treatment prognostic factors associated with multiple mental wellbeing outcomes in prostate cancer patients.

Methods

We performed a literature search of MEDLINE, EMBASE, and CINAHL databases including studies evaluating patient, oncological, or treatment factors against one of five mental wellbeing outcomes; depression, anxiety, fear of cancer recurrence, masculinity, and body image perception. Data synthesis included a random effects meta-analysis for the prognostic effect of individual factors if sufficient homogenous data was available, with a structured narrative synthesis where this was not possible.

Results

A final 62 articles were included. Older age was associated with a reducing odds of depression (OR 0.97, p\u00a0=\u00a00.04), with little evidence of effect for other outcomes. Additionally, baseline mental health status was related to depression and increasing time since diagnosis was associated with reducing fear of recurrence, albeith with low certainty of evidence. However, few other patient or oncological factors demonstrated any coherent relationship with any wellbeing outcome. Androgen deprivation therapy was associated with increased depression (HR 1.65, 95% CI 1.41-1.92, p\u00a0<\u00a00.01) and anxiety, however, little difference was seen between other treatment options. Overall, whilst numerous factors were identified, most were evaluated by single studies with few evaluating masculinity and body image outcomes.

Conclusion

We highlight the existing evidence for prognostic factors in mental wellbeing outcomes in prostate cancer, allowing us to consider high-risk groups of patients for preventative and treatment measures. However, the current evidence is heterogenous with further work required exploring less conclusive factors and outcomes.", - "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pon.6225; doi:https://doi.org/10.1002/pon.6225; html:https://europepmc.org/articles/PMC10946963; pdf:https://europepmc.org/articles/PMC10946963?pdf=render" - }, { "id": "36322788", "doi": "https://doi.org/10.2196/40035", @@ -4776,6 +4759,23 @@ "laySummary": "", "urls": "pdf:https://www.jmir.org/2022/12/e40035/PDF; doi:https://doi.org/10.2196/40035; html:https://europepmc.org/articles/PMC9822177" }, + { + "id": "37789603", + "doi": "https://doi.org/10.1002/pon.6225", + "title": "Prognostic factors for mental wellbeing in prostate cancer: A\u00a0systematic review and meta-analysis.", + "authorString": "Vyas N, Brunckhorst O, Fanshawe JB, Stewart R, Dasgupta P, Ahmed K.", + "authorAffiliations": "", + "journalTitle": "Psycho-oncology", + "pubYear": "2023", + "date": "2023-10-03", + "isOpenAccess": "Y", + "keywords": "Cancer; Depression; Quality of life; Anxiety; Oncology; prostate cancer; Body Image; Masculinity; Mental Wellbeing; Fear Of Cancer Recurrence", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

To evaluate the evidence base for patient, oncological, and treatment prognostic factors associated with multiple mental wellbeing outcomes in prostate cancer patients.

Methods

We performed a literature search of MEDLINE, EMBASE, and CINAHL databases including studies evaluating patient, oncological, or treatment factors against one of five mental wellbeing outcomes; depression, anxiety, fear of cancer recurrence, masculinity, and body image perception. Data synthesis included a random effects meta-analysis for the prognostic effect of individual factors if sufficient homogenous data was available, with a structured narrative synthesis where this was not possible.

Results

A final 62 articles were included. Older age was associated with a reducing odds of depression (OR 0.97, p\u00a0=\u00a00.04), with little evidence of effect for other outcomes. Additionally, baseline mental health status was related to depression and increasing time since diagnosis was associated with reducing fear of recurrence, albeith with low certainty of evidence. However, few other patient or oncological factors demonstrated any coherent relationship with any wellbeing outcome. Androgen deprivation therapy was associated with increased depression (HR 1.65, 95% CI 1.41-1.92, p\u00a0<\u00a00.01) and anxiety, however, little difference was seen between other treatment options. Overall, whilst numerous factors were identified, most were evaluated by single studies with few evaluating masculinity and body image outcomes.

Conclusion

We highlight the existing evidence for prognostic factors in mental wellbeing outcomes in prostate cancer, allowing us to consider high-risk groups of patients for preventative and treatment measures. However, the current evidence is heterogenous with further work required exploring less conclusive factors and outcomes.", + "laySummary": "", + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pon.6225; doi:https://doi.org/10.1002/pon.6225; html:https://europepmc.org/articles/PMC10946963; pdf:https://europepmc.org/articles/PMC10946963?pdf=render" + }, { "id": "37765085", "doi": "https://doi.org/10.3390/ph16091277", @@ -5286,23 +5286,6 @@ "laySummary": "", "urls": "pdf:https://bmcmedgenomics.biomedcentral.com/track/pdf/10.1186/s12920-020-00826-6; doi:https://doi.org/10.1186/s12920-020-00826-6; html:https://europepmc.org/articles/PMC7685541; pdf:https://europepmc.org/articles/PMC7685541?pdf=render" }, - { - "id": "37949372", - "doi": "https://doi.org/10.1016/j.jhin.2023.10.021", - "title": "COVID-19-related mortality and hospital admissions in the VIVALDI study cohort: October 2020 to March 2023.", - "authorString": "Stirrup O, Krutikov M, Azmi B, Monakhov I, Hayward A, Copas A, Shallcross L.", - "authorAffiliations": "", - "journalTitle": "The Journal of hospital infection", - "pubYear": "2024", - "date": "2023-11-08", - "isOpenAccess": "Y", - "keywords": "Care Homes; Covid-19; Sars-cov-2; Infection Fatality Ratio; Infection Hospitalization Ratio", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Long-term-care facilities (LTCFs) were heavily affected by COVID-19 early in the pandemic, but the impact of the virus has reduced over time with vaccination campaigns and build-up of immunity from prior infection.

Objectives

To evaluate the mortality and hospital admissions associated with SARS-CoV-2 in LTCFs in England over the course of the VIVALDI study, from October 2020 to March 2023.

Methods

We included residents aged \u226565 years from participating LTCFs who had available follow-up time within the analysis period. We calculated incidence rates (IRs) of COVID-19-linked mortality and hospital admissions per calendar quarter, along with infection fatality ratios (IFRs, within 28 days) and infection hospitalization ratios (IHRs, within 14 days) following positive SARS-CoV-2 test.

Results

A total of 26,286 residents were included, with at least one positive test for SARS-CoV-2 in 8513 (32.4%). The IR of COVID-19-related mortality peaked in the first quarter (Q1) of 2021\u00a0at 0.47 per 1000 person-days (1 kpd) (around a third of all deaths), in comparison with 0.10 per 1 kpd for Q1 2023 which had a similar IR of SARS-CoV-2 infections. There was a fall in observed IFR for SARS-CoV-2 infections from 24.9% to 6.7% between these periods, with a fall in IHR from 12.1% to 8.8%. The population had high overall IRs for mortality for each quarter evaluated, corresponding to annual mortality probability of 28.8-41.3%.

Conclusions

Standardized real-time monitoring of hospitalization and mortality following infection in LTCFs could inform policy on the need for non-pharmaceutical interventions to prevent transmission.", - "laySummary": "", - "urls": "pdf:http://www.journalofhospitalinfection.com/article/S0195670123003572/pdf; doi:https://doi.org/10.1016/j.jhin.2023.10.021; html:https://europepmc.org/articles/PMC10927615; pdf:https://europepmc.org/articles/PMC10927615?pdf=render" - }, { "id": "31469943", "doi": "https://doi.org/10.1002/cnm.3255", @@ -5320,6 +5303,23 @@ "laySummary": "This study aimed to measure how well an algorithm using data from non-invasive tests was able to predict early signs of heart disease.", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cnm.3255; doi:https://doi.org/10.1002/cnm.3255; html:https://europepmc.org/articles/PMC7003475; pdf:https://europepmc.org/articles/PMC7003475?pdf=render" }, + { + "id": "37949372", + "doi": "https://doi.org/10.1016/j.jhin.2023.10.021", + "title": "COVID-19-related mortality and hospital admissions in the VIVALDI study cohort: October 2020 to March 2023.", + "authorString": "Stirrup O, Krutikov M, Azmi B, Monakhov I, Hayward A, Copas A, Shallcross L.", + "authorAffiliations": "", + "journalTitle": "The Journal of hospital infection", + "pubYear": "2024", + "date": "2023-11-08", + "isOpenAccess": "Y", + "keywords": "Care Homes; Covid-19; Sars-cov-2; Infection Fatality Ratio; Infection Hospitalization Ratio", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Long-term-care facilities (LTCFs) were heavily affected by COVID-19 early in the pandemic, but the impact of the virus has reduced over time with vaccination campaigns and build-up of immunity from prior infection.

Objectives

To evaluate the mortality and hospital admissions associated with SARS-CoV-2 in LTCFs in England over the course of the VIVALDI study, from October 2020 to March 2023.

Methods

We included residents aged \u226565 years from participating LTCFs who had available follow-up time within the analysis period. We calculated incidence rates (IRs) of COVID-19-linked mortality and hospital admissions per calendar quarter, along with infection fatality ratios (IFRs, within 28 days) and infection hospitalization ratios (IHRs, within 14 days) following positive SARS-CoV-2 test.

Results

A total of 26,286 residents were included, with at least one positive test for SARS-CoV-2 in 8513 (32.4%). The IR of COVID-19-related mortality peaked in the first quarter (Q1) of 2021\u00a0at 0.47 per 1000 person-days (1 kpd) (around a third of all deaths), in comparison with 0.10 per 1 kpd for Q1 2023 which had a similar IR of SARS-CoV-2 infections. There was a fall in observed IFR for SARS-CoV-2 infections from 24.9% to 6.7% between these periods, with a fall in IHR from 12.1% to 8.8%. The population had high overall IRs for mortality for each quarter evaluated, corresponding to annual mortality probability of 28.8-41.3%.

Conclusions

Standardized real-time monitoring of hospitalization and mortality following infection in LTCFs could inform policy on the need for non-pharmaceutical interventions to prevent transmission.", + "laySummary": "", + "urls": "pdf:http://www.journalofhospitalinfection.com/article/S0195670123003572/pdf; doi:https://doi.org/10.1016/j.jhin.2023.10.021; html:https://europepmc.org/articles/PMC10927615; pdf:https://europepmc.org/articles/PMC10927615?pdf=render" + }, { "id": "37120260", "doi": "https://doi.org/10.1016/s2468-2667(23)00079-8", @@ -5422,23 +5422,6 @@ "laySummary": "", "urls": "pdf:https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.200121; doi:https://doi.org/10.1098/rsob.200121; html:https://europepmc.org/articles/PMC7574545; pdf:https://europepmc.org/articles/PMC7574545?pdf=render" }, - { - "id": "37147628", - "doi": "https://doi.org/10.1186/s12911-023-02181-9", - "title": "Ontology-driven and weakly supervised rare disease identification from clinical notes.", - "authorString": "Dong H, Su\u00e1rez-Paniagua V, Zhang H, Wang M, Casey A, Davidson E, Chen J, Alex B, Whiteley W, Wu H.", - "authorAffiliations": "", - "journalTitle": "BMC medical informatics and decision making", - "pubYear": "2023", - "date": "2023-05-05", - "isOpenAccess": "Y", - "keywords": "Phenotyping; Natural Language Processing; Rare Diseases; Ontology Matching; Clinical Notes; Weak Supervision", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Computational text phenotyping is the practice of identifying patients with certain disorders and traits from clinical notes. Rare diseases are challenging to be identified due to few cases available for machine learning and the need for data annotation from domain experts.

Methods

We propose a method using ontologies and weak supervision, with recent pre-trained contextual representations from Bi-directional Transformers (e.g. BERT). The ontology-driven framework includes two steps: (i) Text-to-UMLS, extracting phenotypes by contextually linking mentions to concepts in Unified Medical Language System (UMLS), with a Named Entity Recognition and Linking (NER+L) tool, SemEHR, and weak supervision with customised rules and contextual mention representation; (ii) UMLS-to-ORDO, matching UMLS concepts to rare diseases in Orphanet Rare Disease Ontology (ORDO). The weakly supervised approach is proposed to learn a phenotype confirmation model to improve Text-to-UMLS linking, without annotated data from domain experts. We evaluated the approach on three clinical datasets, MIMIC-III discharge summaries, MIMIC-III radiology reports, and NHS Tayside brain imaging reports from two institutions in the US and the UK, with annotations.

Results

The improvements in the precision were pronounced (by over 30% to 50% absolute score for Text-to-UMLS linking), with almost no loss of recall compared to the existing NER+L tool, SemEHR. Results on radiology reports from MIMIC-III and NHS Tayside were consistent with the discharge summaries. The overall pipeline processing clinical notes can extract rare disease cases, mostly uncaptured in structured data (manually assigned ICD codes).

Conclusion

The study provides empirical evidence for the task by applying a weakly supervised NLP pipeline on clinical notes. The proposed weak supervised deep learning approach requires no human annotation except for validation and testing, by leveraging ontologies, NER+L tools, and contextual representations. The study also demonstrates that Natural Language Processing (NLP) can complement traditional ICD-based approaches to better estimate rare diseases in clinical notes. We discuss the usefulness and limitations of the weak supervision approach and propose directions for future studies.", - "laySummary": "", - "urls": "pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-023-02181-9; doi:https://doi.org/10.1186/s12911-023-02181-9; html:https://europepmc.org/articles/PMC10162001; pdf:https://europepmc.org/articles/PMC10162001?pdf=render" - }, { "id": "35354646", "doi": "https://doi.org/10.1136/thoraxjnl-2021-218629", @@ -5456,6 +5439,23 @@ "laySummary": "", "urls": "pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/03/29/thoraxjnl-2021-218629.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2021-218629; html:https://europepmc.org/articles/PMC8983409; pdf:https://europepmc.org/articles/PMC8983409?pdf=render" }, + { + "id": "37147628", + "doi": "https://doi.org/10.1186/s12911-023-02181-9", + "title": "Ontology-driven and weakly supervised rare disease identification from clinical notes.", + "authorString": "Dong H, Su\u00e1rez-Paniagua V, Zhang H, Wang M, Casey A, Davidson E, Chen J, Alex B, Whiteley W, Wu H.", + "authorAffiliations": "", + "journalTitle": "BMC medical informatics and decision making", + "pubYear": "2023", + "date": "2023-05-05", + "isOpenAccess": "Y", + "keywords": "Phenotyping; Natural Language Processing; Rare Diseases; Ontology Matching; Clinical Notes; Weak Supervision", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Computational text phenotyping is the practice of identifying patients with certain disorders and traits from clinical notes. Rare diseases are challenging to be identified due to few cases available for machine learning and the need for data annotation from domain experts.

Methods

We propose a method using ontologies and weak supervision, with recent pre-trained contextual representations from Bi-directional Transformers (e.g. BERT). The ontology-driven framework includes two steps: (i) Text-to-UMLS, extracting phenotypes by contextually linking mentions to concepts in Unified Medical Language System (UMLS), with a Named Entity Recognition and Linking (NER+L) tool, SemEHR, and weak supervision with customised rules and contextual mention representation; (ii) UMLS-to-ORDO, matching UMLS concepts to rare diseases in Orphanet Rare Disease Ontology (ORDO). The weakly supervised approach is proposed to learn a phenotype confirmation model to improve Text-to-UMLS linking, without annotated data from domain experts. We evaluated the approach on three clinical datasets, MIMIC-III discharge summaries, MIMIC-III radiology reports, and NHS Tayside brain imaging reports from two institutions in the US and the UK, with annotations.

Results

The improvements in the precision were pronounced (by over 30% to 50% absolute score for Text-to-UMLS linking), with almost no loss of recall compared to the existing NER+L tool, SemEHR. Results on radiology reports from MIMIC-III and NHS Tayside were consistent with the discharge summaries. The overall pipeline processing clinical notes can extract rare disease cases, mostly uncaptured in structured data (manually assigned ICD codes).

Conclusion

The study provides empirical evidence for the task by applying a weakly supervised NLP pipeline on clinical notes. The proposed weak supervised deep learning approach requires no human annotation except for validation and testing, by leveraging ontologies, NER+L tools, and contextual representations. The study also demonstrates that Natural Language Processing (NLP) can complement traditional ICD-based approaches to better estimate rare diseases in clinical notes. We discuss the usefulness and limitations of the weak supervision approach and propose directions for future studies.", + "laySummary": "", + "urls": "pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-023-02181-9; doi:https://doi.org/10.1186/s12911-023-02181-9; html:https://europepmc.org/articles/PMC10162001; pdf:https://europepmc.org/articles/PMC10162001?pdf=render" + }, { "id": "33683514", "doi": "https://doi.org/10.1007/s10237-021-01437-5", @@ -5677,23 +5677,6 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/1422-0067/22/16/8527/pdf?version=1628431894; doi:https://doi.org/10.3390/ijms22168527; html:https://europepmc.org/articles/PMC8395220; pdf:https://europepmc.org/articles/PMC8395220?pdf=render" }, - { - "id": "34829865", - "doi": "https://doi.org/10.3390/biomedicines9111636", - "title": "Machine Learning-Based Identification of Potentially Novel Non-Alcoholic Fatty Liver Disease Biomarkers.", - "authorString": "Shafiha R, Bahcivanci B, Gkoutos GV, Acharjee A.", - "authorAffiliations": "", - "journalTitle": "Biomedicines", - "pubYear": "2021", - "date": "2021-11-07", - "isOpenAccess": "Y", - "keywords": "Biomarker; Machine Learning; Lipidomics; Transcriptomics; Nafld", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that presents a great challenge for treatment and prevention.. This study aims to implement a machine learning approach that employs such datasets to identify potential biomarker targets. We developed a pipeline to identify potential biomarkers for NAFLD that includes five major processes, namely, a pre-processing step, a feature selection and a generation of a random forest model and, finally, a downstream feature analysis and a provision of a potential biological interpretation. The pre-processing step includes data normalising and variable extraction accompanied by appropriate annotations. A feature selection based on a differential gene expression analysis is then conducted to identify significant features and then employ them to generate a random forest model whose performance is assessed based on a receiver operating characteristic curve. Next, the features are subjected to a downstream analysis, such as univariate analysis, a pathway enrichment analysis, a network analysis and a generation of correlation plots, boxplots and heatmaps. Once the results are obtained, the biological interpretation and the literature validation is conducted over the identified features and results. We applied this pipeline to transcriptomics and lipidomic datasets and concluded that the C4BPA gene could play a role in the development of NAFLD. The activation of the complement pathway, due to the downregulation of the C4BPA gene, leads to an increase in triglyceride content, which might further render the lipid metabolism. This approach identified the C4BPA gene, an inhibitor of the complement pathway, as a potential biomarker for the development of NAFLD.", - "laySummary": "", - "urls": "pdf:https://www.mdpi.com/2227-9059/9/11/1636/pdf?version=1637024773; doi:https://doi.org/10.3390/biomedicines9111636; html:https://europepmc.org/articles/PMC8615894; pdf:https://europepmc.org/articles/PMC8615894?pdf=render" - }, { "id": "35165107", "doi": "https://doi.org/10.1136/bmjopen-2021-050062", @@ -5712,21 +5695,21 @@ "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e050062.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-050062; html:https://europepmc.org/articles/PMC8844955; pdf:https://europepmc.org/articles/PMC8844955?pdf=render" }, { - "id": "37463814", - "doi": "https://doi.org/10.1136/bmjopen-2022-069635", - "title": "HbA1c recording in patients following a first diagnosis of serious mental illness: the South London and Maudsley Biomedical Research Centre case register.", - "authorString": "Bell N, Perera G, Chandran D, Stubbs B, Gaughran F, Stewart R.", + "id": "34829865", + "doi": "https://doi.org/10.3390/biomedicines9111636", + "title": "Machine Learning-Based Identification of Potentially Novel Non-Alcoholic Fatty Liver Disease Biomarkers.", + "authorString": "Shafiha R, Bahcivanci B, Gkoutos GV, Acharjee A.", "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2023", - "date": "2023-07-18", + "journalTitle": "Biomedicines", + "pubYear": "2021", + "date": "2021-11-07", "isOpenAccess": "Y", - "keywords": "Psychiatry; Mental health; epidemiology; Health Informatics; General Diabetes; Quality In Health Care", + "keywords": "Biomarker; Machine Learning; Lipidomics; Transcriptomics; Nafld", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Objectives

To investigate factors associated with the recording of glycated haemoglobin (HbA1c) in people with first diagnoses of serious mental illness (SMI) in a large mental healthcare provider, and factors associated with HbA1c levels, when recorded. To our knowledge this is the first such investigation, although attention to dysglycaemia in SMI is an increasing priority in mental healthcare.

Design

The study was primarily descriptive in nature, seeking to ascertain the frequency of HbA1c recording in the mental healthcare sector for people following first SMI diagnosis.

Settings

A large mental healthcare provider, the South London and Maudsley National Health Service Trust.

Participants

Using electronic mental health records data, we ascertained patients with first SMI diagnoses (schizophrenia, schizoaffective disorder, bipolar disorder) from 2008 to 2018.

Outcome measures

Recording or not of HbA1c level was ascertained from routine local laboratory data and supplemented by a natural language processing (NLP) algorithm for extracting recorded values in text fields (precision 0.89%, recall 0.93%). Age, gender, ethnic group, year of diagnosis, and SMI diagnosis were investigated as covariates in relation to recording or not of HbA1c and first recorded levels.

Results

Of 21 462 patients in the sample (6546 bipolar disorder; 14 916 schizophrenia or schizoaffective disorder; mean age 38.8 years, 49% female), 4106 (19.1%) had at least one HbA1c result recorded from laboratory data, increasing to 6901 (32.2%) following NLP. HbA1c recording was independently more likely in non-white ethnic groups (black compared with white: OR 2.45, 95% CI 2.29 to 2.62), and was negatively associated with age (OR per year increase 0.93, 0.92-0.95), female gender (0.83, 0.78-0.88) and bipolar disorder (0.49, 0.45-0.52).

Conclusions

Over a 10-year period, relatively low level of recording of HbA1c was observed, although this has increased over time and ascertainment was increased with text extraction. It remains important to improve the routine monitoring of dysglycaemia in these at-risk disorders.", + "abstract": "Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that presents a great challenge for treatment and prevention.. This study aims to implement a machine learning approach that employs such datasets to identify potential biomarker targets. We developed a pipeline to identify potential biomarkers for NAFLD that includes five major processes, namely, a pre-processing step, a feature selection and a generation of a random forest model and, finally, a downstream feature analysis and a provision of a potential biological interpretation. The pre-processing step includes data normalising and variable extraction accompanied by appropriate annotations. A feature selection based on a differential gene expression analysis is then conducted to identify significant features and then employ them to generate a random forest model whose performance is assessed based on a receiver operating characteristic curve. Next, the features are subjected to a downstream analysis, such as univariate analysis, a pathway enrichment analysis, a network analysis and a generation of correlation plots, boxplots and heatmaps. Once the results are obtained, the biological interpretation and the literature validation is conducted over the identified features and results. We applied this pipeline to transcriptomics and lipidomic datasets and concluded that the C4BPA gene could play a role in the development of NAFLD. The activation of the complement pathway, due to the downregulation of the C4BPA gene, leads to an increase in triglyceride content, which might further render the lipid metabolism. This approach identified the C4BPA gene, an inhibitor of the complement pathway, as a potential biomarker for the development of NAFLD.", "laySummary": "", - "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/7/e069635.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-069635; html:https://europepmc.org/articles/PMC10357777; pdf:https://europepmc.org/articles/PMC10357777?pdf=render" + "urls": "pdf:https://www.mdpi.com/2227-9059/9/11/1636/pdf?version=1637024773; doi:https://doi.org/10.3390/biomedicines9111636; html:https://europepmc.org/articles/PMC8615894; pdf:https://europepmc.org/articles/PMC8615894?pdf=render" }, { "id": "34879829", @@ -5745,6 +5728,23 @@ "laySummary": "", "urls": "pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-021-01693-6; doi:https://doi.org/10.1186/s12911-021-01693-6; html:https://europepmc.org/articles/PMC8653614; pdf:https://europepmc.org/articles/PMC8653614?pdf=render" }, + { + "id": "37463814", + "doi": "https://doi.org/10.1136/bmjopen-2022-069635", + "title": "HbA1c recording in patients following a first diagnosis of serious mental illness: the South London and Maudsley Biomedical Research Centre case register.", + "authorString": "Bell N, Perera G, Chandran D, Stubbs B, Gaughran F, Stewart R.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2023", + "date": "2023-07-18", + "isOpenAccess": "Y", + "keywords": "Psychiatry; Mental health; epidemiology; Health Informatics; General Diabetes; Quality In Health Care", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

To investigate factors associated with the recording of glycated haemoglobin (HbA1c) in people with first diagnoses of serious mental illness (SMI) in a large mental healthcare provider, and factors associated with HbA1c levels, when recorded. To our knowledge this is the first such investigation, although attention to dysglycaemia in SMI is an increasing priority in mental healthcare.

Design

The study was primarily descriptive in nature, seeking to ascertain the frequency of HbA1c recording in the mental healthcare sector for people following first SMI diagnosis.

Settings

A large mental healthcare provider, the South London and Maudsley National Health Service Trust.

Participants

Using electronic mental health records data, we ascertained patients with first SMI diagnoses (schizophrenia, schizoaffective disorder, bipolar disorder) from 2008 to 2018.

Outcome measures

Recording or not of HbA1c level was ascertained from routine local laboratory data and supplemented by a natural language processing (NLP) algorithm for extracting recorded values in text fields (precision 0.89%, recall 0.93%). Age, gender, ethnic group, year of diagnosis, and SMI diagnosis were investigated as covariates in relation to recording or not of HbA1c and first recorded levels.

Results

Of 21 462 patients in the sample (6546 bipolar disorder; 14 916 schizophrenia or schizoaffective disorder; mean age 38.8 years, 49% female), 4106 (19.1%) had at least one HbA1c result recorded from laboratory data, increasing to 6901 (32.2%) following NLP. HbA1c recording was independently more likely in non-white ethnic groups (black compared with white: OR 2.45, 95% CI 2.29 to 2.62), and was negatively associated with age (OR per year increase 0.93, 0.92-0.95), female gender (0.83, 0.78-0.88) and bipolar disorder (0.49, 0.45-0.52).

Conclusions

Over a 10-year period, relatively low level of recording of HbA1c was observed, although this has increased over time and ascertainment was increased with text extraction. It remains important to improve the routine monitoring of dysglycaemia in these at-risk disorders.", + "laySummary": "", + "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/7/e069635.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-069635; html:https://europepmc.org/articles/PMC10357777; pdf:https://europepmc.org/articles/PMC10357777?pdf=render" + }, { "id": "38177425", "doi": "https://doi.org/10.1038/s43588-023-00461-y", @@ -6119,23 +6119,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.ssmph.2023.101592; html:https://europepmc.org/articles/PMC10821139; pdf:https://europepmc.org/articles/PMC10821139?pdf=render" }, - { - "id": "37180154", - "doi": "https://doi.org/10.3389/fimmu.2023.1083072", - "title": "Real-time assessment of neutrophil metabolism and oxidative burst using extracellular flux analysis.", - "authorString": "Grudzinska FS, Jasper A, Sapey E, Thickett DR, Mauro C, Scott A, Barlow J.", - "authorAffiliations": "", - "journalTitle": "Frontiers in immunology", - "pubYear": "2023", - "date": "2023-04-25", - "isOpenAccess": "Y", - "keywords": "Neutrophils; Oxidative burst; glycolysis; Immunometabolism; Extracellular Flux Analysis", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Neutrophil responses are critical during inflammatory and infective events, and neutrophil dysregulation has been associated with poor patient outcomes. Immunometabolism is a rapidly growing field that has provided insights into cellular functions in health and disease. Neutrophils are highly glycolytic when activated, with inhibition of glycolysis associated with functional deficits. There is currently very limited data available assessing metabolism in neutrophils. Extracellular flux (XF) analysis assesses real time oxygen consumption and the rate of proton efflux in cells. This technology allows for the automated addition of inhibitors and stimulants to visualise the effect on metabolism. We describe optimised protocols for an XFe96 XF Analyser to (i) probe glycolysis in neutrophils under basal and stimulated conditions, (ii) probe phorbol 12-myristate 13-acetate induced oxidative burst, and (iii) highlight challenges of using XF technology to examine mitochondrial function in neutrophils. We provide an overview of how to analyze XF data and identify pitfalls of probing neutrophil metabolism with XF analysis. In summary we describe robust methods for assessing glycolysis and oxidative burst in human neutrophils and discuss the challenges around using this technique to assess mitochondrial respiration. XF technology is a powerful platform with a user-friendly interface and data analysis templates, however we suggest caution when assessing neutrophil mitochondrial respiration.", - "laySummary": "", - "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1083072/pdf; doi:https://doi.org/10.3389/fimmu.2023.1083072; html:https://europepmc.org/articles/PMC10166867; pdf:https://europepmc.org/articles/PMC10166867?pdf=render" - }, { "id": "37358897", "doi": "https://doi.org/10.2196/45849", @@ -6153,6 +6136,23 @@ "laySummary": "", "urls": "pdf:https://formative.jmir.org/2023/1/e45849/PDF; doi:https://doi.org/10.2196/45849; html:https://europepmc.org/articles/PMC10337440; pdf:https://europepmc.org/articles/PMC10337440?pdf=render" }, + { + "id": "37180154", + "doi": "https://doi.org/10.3389/fimmu.2023.1083072", + "title": "Real-time assessment of neutrophil metabolism and oxidative burst using extracellular flux analysis.", + "authorString": "Grudzinska FS, Jasper A, Sapey E, Thickett DR, Mauro C, Scott A, Barlow J.", + "authorAffiliations": "", + "journalTitle": "Frontiers in immunology", + "pubYear": "2023", + "date": "2023-04-25", + "isOpenAccess": "Y", + "keywords": "Neutrophils; Oxidative burst; glycolysis; Immunometabolism; Extracellular Flux Analysis", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Neutrophil responses are critical during inflammatory and infective events, and neutrophil dysregulation has been associated with poor patient outcomes. Immunometabolism is a rapidly growing field that has provided insights into cellular functions in health and disease. Neutrophils are highly glycolytic when activated, with inhibition of glycolysis associated with functional deficits. There is currently very limited data available assessing metabolism in neutrophils. Extracellular flux (XF) analysis assesses real time oxygen consumption and the rate of proton efflux in cells. This technology allows for the automated addition of inhibitors and stimulants to visualise the effect on metabolism. We describe optimised protocols for an XFe96 XF Analyser to (i) probe glycolysis in neutrophils under basal and stimulated conditions, (ii) probe phorbol 12-myristate 13-acetate induced oxidative burst, and (iii) highlight challenges of using XF technology to examine mitochondrial function in neutrophils. We provide an overview of how to analyze XF data and identify pitfalls of probing neutrophil metabolism with XF analysis. In summary we describe robust methods for assessing glycolysis and oxidative burst in human neutrophils and discuss the challenges around using this technique to assess mitochondrial respiration. XF technology is a powerful platform with a user-friendly interface and data analysis templates, however we suggest caution when assessing neutrophil mitochondrial respiration.", + "laySummary": "", + "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1083072/pdf; doi:https://doi.org/10.3389/fimmu.2023.1083072; html:https://europepmc.org/articles/PMC10166867; pdf:https://europepmc.org/articles/PMC10166867?pdf=render" + }, { "id": "37650027", "doi": "https://doi.org/10.23889/ijpds.v7i1.1724", @@ -6171,21 +6171,21 @@ "urls": "doi:https://doi.org/10.23889/ijpds.v7i1.1724; html:https://europepmc.org/articles/PMC10464871; pdf:https://europepmc.org/articles/PMC10464871?pdf=render" }, { - "id": "38192590", - "doi": "https://doi.org/10.1016/j.eclinm.2023.102321", - "title": "Clinical and health inequality risk factors for non-COVID-related sepsis during the global COVID-19 pandemic: a national case-control and cohort study.", - "authorString": "Zhong X, Ashiru-Oredope D, Pate A, Martin GP, Sharma A, Dark P, Felton T, Lake C, MacKenna B, Mehrkar A, Bacon SCJ, Massey J, Inglesby P, Goldacre B, OpenSAFELY Collaborative, Hand K, Bladon S, Cunningham N, Gilham E, Brown CS, Mirfenderesky M, Palin V, van Staa TP.", + "id": "35572721", + "doi": "https://doi.org/10.1016/j.eclinm.2022.101419", + "title": "Breakthrough SARS-CoV-2 infections in double and triple vaccinated adults and single dose vaccine effectiveness among children in Autumn 2021 in England: REACT-1 study.", + "authorString": "Chadeau-Hyam M, Eales O, Bodinier B, Wang H, Haw D, Whitaker M, Elliott J, Walters CE, Jonnerby J, Atchison C, Diggle PJ, Page AJ, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly CA, Elliott P.", "authorAffiliations": "", "journalTitle": "EClinicalMedicine", - "pubYear": "2023", - "date": "2023-11-23", + "pubYear": "2022", + "date": "2022-05-06", "isOpenAccess": "Y", - "keywords": "Sepsis; Morbidity; Primary Care; Deprivation; Health Inequality; Covid-19 Pandemic", + "keywords": "School-aged children; Vaccine Effectiveness; Booster Dose; Children Vaccination; Sars-cov-2 Prevalence", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Sepsis, characterised by significant morbidity and mortality, is intricately linked to socioeconomic disparities and pre-admission clinical histories. This study aspires to elucidate the association between non-COVID-19 related sepsis and health inequality risk factors amidst the pandemic in England, with a secondary focus on their association with 30-day sepsis mortality.

Methods

With the approval of NHS England, we harnessed the OpenSAFELY platform to execute a cohort study and a 1:6 matched case-control study. A sepsis diagnosis was identified from the incident hospital admissions record using ICD-10 codes. This encompassed 248,767 cases with non-COVID-19 sepsis from a cohort of 22.0 million individuals spanning January 1, 2019, to June 31, 2022. Socioeconomic deprivation was gauged using the Index of Multiple Deprivation score, reflecting indicators like income, employment, and education. Hospitalisation-related sepsis diagnoses were categorised as community-acquired or hospital-acquired. Cases were matched to controls who had no recorded diagnosis of sepsis, based on age (stepwise), sex, and calendar month. The eligibility criteria for controls were established primarily on the absence of a recorded sepsis diagnosis. Associations between potential predictors and odds of developing non-COVID-19 sepsis underwent assessment through conditional logistic regression models, with multivariable regression determining odds ratios (ORs) for 30-day mortality.

Findings

The study included 224,361 (10.2%) cases with non-COVID-19 sepsis and 1,346,166 matched controls. The most socioeconomic deprived quintile was associated with higher odds of developing non-COVID-19 sepsis than the least deprived quintile (crude OR 1.80 [95% CI 1.77-1.83]). Other risk factors (after adjusting comorbidities) such as learning disability (adjusted OR 3.53 [3.35-3.73]), chronic liver disease (adjusted OR 3.08 [2.97-3.19]), chronic kidney disease (stage 4: adjusted OR 2.62 [2.55-2.70], stage 5: adjusted OR 6.23 [5.81-6.69]), cancer, neurological disease, immunosuppressive conditions were also associated with developing non-COVID-19 sepsis. The incidence rate of non-COVID-19 sepsis decreased during the COVID-19 pandemic and rebounded to pre-pandemic levels (April 2021) after national lockdowns had been lifted. The 30-day mortality risk in cases with non-COVID-19 sepsis was higher for the most deprived quintile across all periods.

Interpretation

Socioeconomic deprivation, comorbidity and learning disabilities were associated with an increased odds of developing non-COVID-19 related sepsis and 30-day mortality in England. This study highlights the need to improve the prevention of sepsis, including more precise targeting of antimicrobials to higher-risk patients.

Funding

The UK Health Security Agency, Health Data Research UK, and National Institute for Health Research.", + "abstract": "

Background

Prevalence of SARS-CoV-2 infection with Delta variant was increasing in England in late summer 2021 among children aged 5 to 17 years, and adults who had received two vaccine doses. In September 2021, a third (booster) dose was offered to vaccinated adults aged 50 years and over, vulnerable adults and healthcare/care-home workers, and a single vaccine dose already offered to 16 and 17 year-olds was extended to children aged 12 to 15 years.

Methods

SARS-CoV-2 community prevalence in England was available from self-administered throat and nose swabs using reverse transcriptase polymerase chain reaction (RT-PCR) in round 13 (24 June to 12 July 2021, N = 98,233), round 14 (9 to 27 September 2021, N\u00a0=\u00a0100,527) and round 15 (19 October to 5 November 2021, N\u00a0=\u00a0100,112) from the REACT-1 study randomised community surveys. Linking to National Health Service (NHS) vaccination data for consenting participants, we estimated vaccine effectiveness in children aged 12 to 17 years and compared swab-positivity rates in adults who received a third dose with those who received two doses.

Findings

Weighted SARS-CoV-2 prevalence was 1.57% (1.48%, 1.66%) in round 15 compared with 0.83% (0.76%, 0.89%) in round 14, and the previously observed link between infections and hospitalisations and deaths had weakened. Vaccine effectiveness against infection in children aged 12 to 17 years was estimated (round 15) at 64.0% (50.9%, 70.6%) and 67.7% (53.8%, 77.5%) for symptomatic infections. Adults who received a third vaccine dose were less likely to test positive compared to those who received two doses, with adjusted OR of 0.36 (0.25, 0.53).

Interpretation

Vaccination of children aged 12 to 17 years and third (booster) doses in adults were effective at reducing infection risk. High rates of vaccination, including booster doses, are a key part of the strategy to reduce infection rates in the community.

Funding

Department of Health and Social Care, England.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.eclinm.2023.102321; html:https://europepmc.org/articles/PMC10772239; pdf:https://europepmc.org/articles/PMC10772239?pdf=render" + "urls": "pdf:http://www.thelancet.com/article/S2589537022001493/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101419; html:https://europepmc.org/articles/PMC9076030; pdf:https://europepmc.org/articles/PMC9076030?pdf=render" }, { "id": "36219788", @@ -6205,21 +6205,21 @@ "urls": "pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac185/47708280/dyac185.pdf; doi:https://doi.org/10.1093/ije/dyac185; html:https://europepmc.org/articles/PMC10244047; pdf:https://europepmc.org/articles/PMC10244047?pdf=render" }, { - "id": "35572721", - "doi": "https://doi.org/10.1016/j.eclinm.2022.101419", - "title": "Breakthrough SARS-CoV-2 infections in double and triple vaccinated adults and single dose vaccine effectiveness among children in Autumn 2021 in England: REACT-1 study.", - "authorString": "Chadeau-Hyam M, Eales O, Bodinier B, Wang H, Haw D, Whitaker M, Elliott J, Walters CE, Jonnerby J, Atchison C, Diggle PJ, Page AJ, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly CA, Elliott P.", + "id": "38192590", + "doi": "https://doi.org/10.1016/j.eclinm.2023.102321", + "title": "Clinical and health inequality risk factors for non-COVID-related sepsis during the global COVID-19 pandemic: a national case-control and cohort study.", + "authorString": "Zhong X, Ashiru-Oredope D, Pate A, Martin GP, Sharma A, Dark P, Felton T, Lake C, MacKenna B, Mehrkar A, Bacon SCJ, Massey J, Inglesby P, Goldacre B, OpenSAFELY Collaborative, Hand K, Bladon S, Cunningham N, Gilham E, Brown CS, Mirfenderesky M, Palin V, van Staa TP.", "authorAffiliations": "", "journalTitle": "EClinicalMedicine", - "pubYear": "2022", - "date": "2022-05-06", + "pubYear": "2023", + "date": "2023-11-23", "isOpenAccess": "Y", - "keywords": "School-aged children; Vaccine Effectiveness; Booster Dose; Children Vaccination; Sars-cov-2 Prevalence", + "keywords": "Sepsis; Morbidity; Primary Care; Deprivation; Health Inequality; Covid-19 Pandemic", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Prevalence of SARS-CoV-2 infection with Delta variant was increasing in England in late summer 2021 among children aged 5 to 17 years, and adults who had received two vaccine doses. In September 2021, a third (booster) dose was offered to vaccinated adults aged 50 years and over, vulnerable adults and healthcare/care-home workers, and a single vaccine dose already offered to 16 and 17 year-olds was extended to children aged 12 to 15 years.

Methods

SARS-CoV-2 community prevalence in England was available from self-administered throat and nose swabs using reverse transcriptase polymerase chain reaction (RT-PCR) in round 13 (24 June to 12 July 2021, N = 98,233), round 14 (9 to 27 September 2021, N\u00a0=\u00a0100,527) and round 15 (19 October to 5 November 2021, N\u00a0=\u00a0100,112) from the REACT-1 study randomised community surveys. Linking to National Health Service (NHS) vaccination data for consenting participants, we estimated vaccine effectiveness in children aged 12 to 17 years and compared swab-positivity rates in adults who received a third dose with those who received two doses.

Findings

Weighted SARS-CoV-2 prevalence was 1.57% (1.48%, 1.66%) in round 15 compared with 0.83% (0.76%, 0.89%) in round 14, and the previously observed link between infections and hospitalisations and deaths had weakened. Vaccine effectiveness against infection in children aged 12 to 17 years was estimated (round 15) at 64.0% (50.9%, 70.6%) and 67.7% (53.8%, 77.5%) for symptomatic infections. Adults who received a third vaccine dose were less likely to test positive compared to those who received two doses, with adjusted OR of 0.36 (0.25, 0.53).

Interpretation

Vaccination of children aged 12 to 17 years and third (booster) doses in adults were effective at reducing infection risk. High rates of vaccination, including booster doses, are a key part of the strategy to reduce infection rates in the community.

Funding

Department of Health and Social Care, England.", + "abstract": "

Background

Sepsis, characterised by significant morbidity and mortality, is intricately linked to socioeconomic disparities and pre-admission clinical histories. This study aspires to elucidate the association between non-COVID-19 related sepsis and health inequality risk factors amidst the pandemic in England, with a secondary focus on their association with 30-day sepsis mortality.

Methods

With the approval of NHS England, we harnessed the OpenSAFELY platform to execute a cohort study and a 1:6 matched case-control study. A sepsis diagnosis was identified from the incident hospital admissions record using ICD-10 codes. This encompassed 248,767 cases with non-COVID-19 sepsis from a cohort of 22.0 million individuals spanning January 1, 2019, to June 31, 2022. Socioeconomic deprivation was gauged using the Index of Multiple Deprivation score, reflecting indicators like income, employment, and education. Hospitalisation-related sepsis diagnoses were categorised as community-acquired or hospital-acquired. Cases were matched to controls who had no recorded diagnosis of sepsis, based on age (stepwise), sex, and calendar month. The eligibility criteria for controls were established primarily on the absence of a recorded sepsis diagnosis. Associations between potential predictors and odds of developing non-COVID-19 sepsis underwent assessment through conditional logistic regression models, with multivariable regression determining odds ratios (ORs) for 30-day mortality.

Findings

The study included 224,361 (10.2%) cases with non-COVID-19 sepsis and 1,346,166 matched controls. The most socioeconomic deprived quintile was associated with higher odds of developing non-COVID-19 sepsis than the least deprived quintile (crude OR 1.80 [95% CI 1.77-1.83]). Other risk factors (after adjusting comorbidities) such as learning disability (adjusted OR 3.53 [3.35-3.73]), chronic liver disease (adjusted OR 3.08 [2.97-3.19]), chronic kidney disease (stage 4: adjusted OR 2.62 [2.55-2.70], stage 5: adjusted OR 6.23 [5.81-6.69]), cancer, neurological disease, immunosuppressive conditions were also associated with developing non-COVID-19 sepsis. The incidence rate of non-COVID-19 sepsis decreased during the COVID-19 pandemic and rebounded to pre-pandemic levels (April 2021) after national lockdowns had been lifted. The 30-day mortality risk in cases with non-COVID-19 sepsis was higher for the most deprived quintile across all periods.

Interpretation

Socioeconomic deprivation, comorbidity and learning disabilities were associated with an increased odds of developing non-COVID-19 related sepsis and 30-day mortality in England. This study highlights the need to improve the prevention of sepsis, including more precise targeting of antimicrobials to higher-risk patients.

Funding

The UK Health Security Agency, Health Data Research UK, and National Institute for Health Research.", "laySummary": "", - "urls": "pdf:http://www.thelancet.com/article/S2589537022001493/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101419; html:https://europepmc.org/articles/PMC9076030; pdf:https://europepmc.org/articles/PMC9076030?pdf=render" + "urls": "doi:https://doi.org/10.1016/j.eclinm.2023.102321; html:https://europepmc.org/articles/PMC10772239; pdf:https://europepmc.org/articles/PMC10772239?pdf=render" }, { "id": "35296643", @@ -6663,23 +6663,6 @@ "laySummary": "", "urls": "pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-020-01169-z; doi:https://doi.org/10.1186/s12911-020-01169-z; html:https://europepmc.org/articles/PMC7339522; pdf:https://europepmc.org/articles/PMC7339522?pdf=render" }, - { - "id": "38269898", - "doi": "https://doi.org/10.3233/shti231054", - "title": "Identifying Mentions of Pain in Mental Health Records Text: A Natural Language Processing Approach.", - "authorString": "Chaturvedi J, Velupillai S, Stewart R, Roberts A.", - "authorAffiliations": "", - "journalTitle": "Studies in health technology and informatics", - "pubYear": "2024", - "date": "2024-01-01", - "isOpenAccess": "N", - "keywords": "Pain; Mental health; Electronic Health Records; Natural Language Processing; Transformers", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Pain is a common reason for accessing healthcare resources and is a growing area of research, especially in its overlap with mental health. Mental health electronic health records are a good data source to study this overlap. However, much information on pain is held in the free text of these records, where mentions of pain present a unique natural language processing problem due to its ambiguous nature. This project uses data from an anonymised mental health electronic health records database. A machine learning based classification algorithm is trained to classify sentences as discussing patient pain or not. This will facilitate the extraction of relevant pain information from large databases. 1,985 documents were manually triple-annotated for creation of gold standard training data, which was used to train four classification algorithms. The best performing model achieved an F1-score of 0.98 (95% CI 0.98-0.99).", - "laySummary": "", - "urls": "pdf:https://ebooks.iospress.nl/pdf/doi/10.3233/SHTI231054; doi:https://doi.org/10.3233/SHTI231054" - }, { "id": "35050151", "doi": "https://doi.org/10.3390/metabo12010029", @@ -6697,6 +6680,23 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/2218-1989/12/1/29/pdf?version=1642410547; doi:https://doi.org/10.3390/metabo12010029; html:https://europepmc.org/articles/PMC8780653; pdf:https://europepmc.org/articles/PMC8780653?pdf=render" }, + { + "id": "38269898", + "doi": "https://doi.org/10.3233/shti231054", + "title": "Identifying Mentions of Pain in Mental Health Records Text: A Natural Language Processing Approach.", + "authorString": "Chaturvedi J, Velupillai S, Stewart R, Roberts A.", + "authorAffiliations": "", + "journalTitle": "Studies in health technology and informatics", + "pubYear": "2024", + "date": "2024-01-01", + "isOpenAccess": "N", + "keywords": "Pain; Mental health; Electronic Health Records; Natural Language Processing; Transformers", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Pain is a common reason for accessing healthcare resources and is a growing area of research, especially in its overlap with mental health. Mental health electronic health records are a good data source to study this overlap. However, much information on pain is held in the free text of these records, where mentions of pain present a unique natural language processing problem due to its ambiguous nature. This project uses data from an anonymised mental health electronic health records database. A machine learning based classification algorithm is trained to classify sentences as discussing patient pain or not. This will facilitate the extraction of relevant pain information from large databases. 1,985 documents were manually triple-annotated for creation of gold standard training data, which was used to train four classification algorithms. The best performing model achieved an F1-score of 0.98 (95% CI 0.98-0.99).", + "laySummary": "", + "urls": "pdf:https://ebooks.iospress.nl/pdf/doi/10.3233/SHTI231054; doi:https://doi.org/10.3233/SHTI231054" + }, { "id": "36217535", "doi": "https://doi.org/10.1038/s43856-022-00185-6", @@ -6748,23 +6748,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/s2589-7500(22)00123-6; doi:https://doi.org/10.1016/S2589-7500(22)00123-6; html:https://europepmc.org/articles/PMC9333950; pdf:https://europepmc.org/articles/PMC9333950?pdf=render" }, - { - "id": "37678881", - "doi": "https://doi.org/10.1093/ageing/afad157", - "title": "Survival and critical care use among people with dementia in a large English cohort.", - "authorString": "Yorganci E, Sleeman KE, Sampson EL, Stewart R, EMBED-Care Programme.", - "authorAffiliations": "", - "journalTitle": "Age and ageing", - "pubYear": "2023", - "date": "2023-09-01", - "isOpenAccess": "Y", - "keywords": "Survival; Dementia; Intensive Care; Older People; Critical Care; Routine Data", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Admitting people with dementia to critical care units may not always lead to a clear survival benefit. Critical care admissions of people with dementia vary across countries. Little is known about the use and trends of critical care admissions of people with dementia in England.

Objective

To investigate critical care use and survival among people with dementia in a large London catchment area.

Methods

A retrospective cohort study using data from dementia assessment services in south London, UK (2007-20) linked with national hospitalisation data to ascertain critical care admissions. Outcomes included age-sex-standardised critical care use and 1-year post-critical care admission survival by dementia severity (binary: mild versus moderate/severe). We used logistic regression and Kaplan-Meier survival plots for investigating 1-year survival following a critical care admission and linear regressions for time trends.

Results

Of 19,787 people diagnosed with dementia, 726 (3.7%) had \u22651 critical care admission at any time after receiving their dementia diagnosis. The overall 1-year survival of people with dementia, who had a CCA, was 47.5% (n\u2009=\u2009345). Dementia severity was not associated with 1-year survival following a critical care admission (mild dementia versus moderate-severe dementia odds of 1-year mortality OR: 0.90, 95% CI [0.66-1.22]). Over the 12-year period from 2008 to 2019, overall critical care use decreased (\u03b2\u2009=\u2009-0.05; 95% CI = -0.01, -0.0003; P\u2009=\u20090.03), while critical care admissions occurring during the last year of life increased (\u03b2\u2009=\u20090.11, 95% CI = 0.01, 0.20, P\u2009=\u20090.03).

Conclusions

In this cohort, while critical care use among people with dementia declined overall, its use increased among those in their last year of life. Survival remains comparable to that observed in general older populations.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/ageing/afad157; html:https://europepmc.org/articles/PMC10484725; pdf:https://europepmc.org/articles/PMC10484725?pdf=render" - }, { "id": "31878916", "doi": "https://doi.org/10.1186/s12889-019-7919-2", @@ -6782,6 +6765,23 @@ "laySummary": "This study aimed to calculate the proportion of deaths that could be prevented over a 14 year period through making long-term changes in lifestyle (diet and physical activity). Over 22K people were included in the study and filled out questionnaires about their lifestyle at three different time points. The authors used statistical methods that take into account how lifestyle measurements change over time and estimated the relative impact that different lifestyle factors have on death. The study suggests that being more physically active in middle age is more likely to reduce mortality than maintaining a Mediterranean-style diet.", "urls": "pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-019-7919-2; doi:https://doi.org/10.1186/s12889-019-7919-2; html:https://europepmc.org/articles/PMC6933918; pdf:https://europepmc.org/articles/PMC6933918?pdf=render" }, + { + "id": "37678881", + "doi": "https://doi.org/10.1093/ageing/afad157", + "title": "Survival and critical care use among people with dementia in a large English cohort.", + "authorString": "Yorganci E, Sleeman KE, Sampson EL, Stewart R, EMBED-Care Programme.", + "authorAffiliations": "", + "journalTitle": "Age and ageing", + "pubYear": "2023", + "date": "2023-09-01", + "isOpenAccess": "Y", + "keywords": "Survival; Dementia; Intensive Care; Older People; Critical Care; Routine Data", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Admitting people with dementia to critical care units may not always lead to a clear survival benefit. Critical care admissions of people with dementia vary across countries. Little is known about the use and trends of critical care admissions of people with dementia in England.

Objective

To investigate critical care use and survival among people with dementia in a large London catchment area.

Methods

A retrospective cohort study using data from dementia assessment services in south London, UK (2007-20) linked with national hospitalisation data to ascertain critical care admissions. Outcomes included age-sex-standardised critical care use and 1-year post-critical care admission survival by dementia severity (binary: mild versus moderate/severe). We used logistic regression and Kaplan-Meier survival plots for investigating 1-year survival following a critical care admission and linear regressions for time trends.

Results

Of 19,787 people diagnosed with dementia, 726 (3.7%) had \u22651 critical care admission at any time after receiving their dementia diagnosis. The overall 1-year survival of people with dementia, who had a CCA, was 47.5% (n\u2009=\u2009345). Dementia severity was not associated with 1-year survival following a critical care admission (mild dementia versus moderate-severe dementia odds of 1-year mortality OR: 0.90, 95% CI [0.66-1.22]). Over the 12-year period from 2008 to 2019, overall critical care use decreased (\u03b2\u2009=\u2009-0.05; 95% CI = -0.01, -0.0003; P\u2009=\u20090.03), while critical care admissions occurring during the last year of life increased (\u03b2\u2009=\u20090.11, 95% CI = 0.01, 0.20, P\u2009=\u20090.03).

Conclusions

In this cohort, while critical care use among people with dementia declined overall, its use increased among those in their last year of life. Survival remains comparable to that observed in general older populations.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/ageing/afad157; html:https://europepmc.org/articles/PMC10484725; pdf:https://europepmc.org/articles/PMC10484725?pdf=render" + }, { "id": "33780469", "doi": "https://doi.org/10.1371/journal.pone.0248195", @@ -6935,23 +6935,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.lanepe.2023.100653; doi:https://doi.org/10.1016/j.lanepe.2023.100653; html:https://europepmc.org/articles/PMC10186397; pdf:https://europepmc.org/articles/PMC10186397?pdf=render" }, - { - "id": "36544046", - "doi": "https://doi.org/10.1038/s41746-022-00730-6", - "title": "A survey on clinical natural language processing in the United Kingdom from 2007 to 2022.", - "authorString": "Wu H, Wang M, Wu J, Francis F, Chang YH, Shavick A, Dong H, Poon MTC, Fitzpatrick N, Levine AP, Slater LT, Handy A, Karwath A, Gkoutos GV, Chelala C, Shah AD, Stewart R, Collier N, Alex B, Whiteley W, Sudlow C, Roberts A, Dobson RJB.", - "authorAffiliations": "", - "journalTitle": "NPJ digital medicine", - "pubYear": "2022", - "date": "2022-12-21", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Much of the knowledge and information needed for enabling high-quality clinical research is stored in free-text format. Natural language processing (NLP) has been used to extract information from these sources at scale for several decades. This paper aims to present a comprehensive review of clinical NLP for the past 15 years in the UK to identify the community, depict its evolution, analyse methodologies and applications, and identify the main barriers. We collect a dataset of clinical NLP projects (n\u2009=\u200994; \u00a3\u2009=\u200941.97\u2009m) funded by UK funders or the European Union's funding programmes. Additionally, we extract details on 9 funders, 137 organisations, 139 persons and 431 research papers. Networks are created from timestamped data interlinking all entities, and network analysis is subsequently applied to generate insights. 431 publications are identified as part of a literature review, of which 107 are eligible for final analysis. Results show, not surprisingly, clinical NLP in the UK has increased substantially in the last 15 years: the total budget in the period of 2019-2022 was 80 times that of 2007-2010. However, the effort is required to deepen areas such as disease (sub-)phenotyping and broaden application domains. There is also a need to improve links between academia and industry and enable deployments in real-world settings for the realisation of clinical NLP's great potential in care delivery. The major barriers include research and development access to hospital data, lack of capable computational resources in the right places, the scarcity of labelled data and barriers to sharing of pretrained models.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41746-022-00730-6.pdf; doi:https://doi.org/10.1038/s41746-022-00730-6; html:https://europepmc.org/articles/PMC9770568; pdf:https://europepmc.org/articles/PMC9770568?pdf=render" - }, { "id": "34598993", "doi": "https://doi.org/10.1136/bmjopen-2021-054410", @@ -6969,6 +6952,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/10/e054410.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054410; html:https://europepmc.org/articles/PMC8488283; pdf:https://europepmc.org/articles/PMC8488283?pdf=render" }, + { + "id": "36544046", + "doi": "https://doi.org/10.1038/s41746-022-00730-6", + "title": "A survey on clinical natural language processing in the United Kingdom from 2007 to 2022.", + "authorString": "Wu H, Wang M, Wu J, Francis F, Chang YH, Shavick A, Dong H, Poon MTC, Fitzpatrick N, Levine AP, Slater LT, Handy A, Karwath A, Gkoutos GV, Chelala C, Shah AD, Stewart R, Collier N, Alex B, Whiteley W, Sudlow C, Roberts A, Dobson RJB.", + "authorAffiliations": "", + "journalTitle": "NPJ digital medicine", + "pubYear": "2022", + "date": "2022-12-21", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Much of the knowledge and information needed for enabling high-quality clinical research is stored in free-text format. Natural language processing (NLP) has been used to extract information from these sources at scale for several decades. This paper aims to present a comprehensive review of clinical NLP for the past 15 years in the UK to identify the community, depict its evolution, analyse methodologies and applications, and identify the main barriers. We collect a dataset of clinical NLP projects (n\u2009=\u200994; \u00a3\u2009=\u200941.97\u2009m) funded by UK funders or the European Union's funding programmes. Additionally, we extract details on 9 funders, 137 organisations, 139 persons and 431 research papers. Networks are created from timestamped data interlinking all entities, and network analysis is subsequently applied to generate insights. 431 publications are identified as part of a literature review, of which 107 are eligible for final analysis. Results show, not surprisingly, clinical NLP in the UK has increased substantially in the last 15 years: the total budget in the period of 2019-2022 was 80 times that of 2007-2010. However, the effort is required to deepen areas such as disease (sub-)phenotyping and broaden application domains. There is also a need to improve links between academia and industry and enable deployments in real-world settings for the realisation of clinical NLP's great potential in care delivery. The major barriers include research and development access to hospital data, lack of capable computational resources in the right places, the scarcity of labelled data and barriers to sharing of pretrained models.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41746-022-00730-6.pdf; doi:https://doi.org/10.1038/s41746-022-00730-6; html:https://europepmc.org/articles/PMC9770568; pdf:https://europepmc.org/articles/PMC9770568?pdf=render" + }, { "id": "37400731", "doi": "https://doi.org/10.1007/s10802-023-01086-5", @@ -7156,23 +7156,6 @@ "laySummary": "", "urls": "pdf:https://www.rcpjournals.org/content/clinmedicine/21/6/e620.full.pdf; doi:https://doi.org/10.7861/clinmed.2021-0386; html:https://europepmc.org/articles/PMC8806292; pdf:https://europepmc.org/articles/PMC8806292?pdf=render; doi:https://doi.org/10.7861/clinmed.2021-0386" }, - { - "id": "38769347", - "doi": "https://doi.org/10.1038/s41746-024-01065-0", - "title": "Self-supervised learning of accelerometer data provides new insights for sleep and its association with mortality.", - "authorString": "Yuan H, Plekhanova T, Walmsley R, Reynolds AC, Maddison KJ, Bucan M, Gehrman P, Rowlands A, Ray DW, Bennett D, McVeigh J, Straker L, Eastwood P, Kyle SD, Doherty A.", - "authorAffiliations": "", - "journalTitle": "NPJ digital medicine", - "pubYear": "2024", - "date": "2024-05-20", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Sleep is essential to life. Accurate measurement and classification of sleep/wake and sleep stages is important in clinical studies for sleep disorder diagnoses and in the interpretation of data from consumer devices for monitoring physical and mental well-being. Existing non-polysomnography sleep classification techniques mainly rely on heuristic methods developed in relatively small cohorts. Thus, we aimed to establish the accuracy of wrist-worn accelerometers for sleep stage classification and subsequently describe the association between sleep duration and efficiency (proportion of total time asleep when in bed) with mortality outcomes. We developed a self-supervised deep neural network for sleep stage classification using concurrent laboratory-based polysomnography and accelerometry. After exclusion, 1448 participant nights of data were used for training. The difference between polysomnography and the model classifications on the external validation was 34.7\u2009min (95% limits of agreement (LoA): -37.8-107.2\u2009min) for total sleep duration, 2.6\u2009min for REM duration (95% LoA: -68.4-73.4\u2009min) and 32.1\u2009min (95% LoA: -54.4-118.5\u2009min) for NREM duration. The sleep classifier was deployed in the UK Biobank with 100,000 participants to study the association of sleep duration and sleep efficiency with all-cause mortality. Among 66,214 UK Biobank participants, 1642 mortality events were observed. Short sleepers (<6\u2009h) had a higher risk of mortality compared to participants with normal sleep duration of 6-7.9\u2009h, regardless of whether they had low sleep efficiency (Hazard ratios (HRs): 1.58; 95% confidence intervals (CIs): 1.19-2.11) or high sleep efficiency (HRs: 1.45; 95% CIs: 1.16-1.81). Deep-learning-based sleep classification using accelerometers has a fair to moderate agreement with polysomnography. Our findings suggest that having short overnight sleep confers mortality risk irrespective of sleep continuity.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41746-024-01065-0.pdf; doi:https://doi.org/10.1038/s41746-024-01065-0; html:https://europepmc.org/articles/PMC11106264; pdf:https://europepmc.org/articles/PMC11106264?pdf=render" - }, { "id": "34232969", "doi": "https://doi.org/10.23889/ijpds.v5i1.1151", @@ -7190,6 +7173,23 @@ "laySummary": "", "urls": "pdf:https://ijpds.org/article/download/1151/2553; doi:https://doi.org/10.23889/ijpds.v5i1.1151; html:https://europepmc.org/articles/PMC7473295; pdf:https://europepmc.org/articles/PMC7473295?pdf=render" }, + { + "id": "38769347", + "doi": "https://doi.org/10.1038/s41746-024-01065-0", + "title": "Self-supervised learning of accelerometer data provides new insights for sleep and its association with mortality.", + "authorString": "Yuan H, Plekhanova T, Walmsley R, Reynolds AC, Maddison KJ, Bucan M, Gehrman P, Rowlands A, Ray DW, Bennett D, McVeigh J, Straker L, Eastwood P, Kyle SD, Doherty A.", + "authorAffiliations": "", + "journalTitle": "NPJ digital medicine", + "pubYear": "2024", + "date": "2024-05-20", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Sleep is essential to life. Accurate measurement and classification of sleep/wake and sleep stages is important in clinical studies for sleep disorder diagnoses and in the interpretation of data from consumer devices for monitoring physical and mental well-being. Existing non-polysomnography sleep classification techniques mainly rely on heuristic methods developed in relatively small cohorts. Thus, we aimed to establish the accuracy of wrist-worn accelerometers for sleep stage classification and subsequently describe the association between sleep duration and efficiency (proportion of total time asleep when in bed) with mortality outcomes. We developed a self-supervised deep neural network for sleep stage classification using concurrent laboratory-based polysomnography and accelerometry. After exclusion, 1448 participant nights of data were used for training. The difference between polysomnography and the model classifications on the external validation was 34.7\u2009min (95% limits of agreement (LoA): -37.8-107.2\u2009min) for total sleep duration, 2.6\u2009min for REM duration (95% LoA: -68.4-73.4\u2009min) and 32.1\u2009min (95% LoA: -54.4-118.5\u2009min) for NREM duration. The sleep classifier was deployed in the UK Biobank with 100,000 participants to study the association of sleep duration and sleep efficiency with all-cause mortality. Among 66,214 UK Biobank participants, 1642 mortality events were observed. Short sleepers (<6\u2009h) had a higher risk of mortality compared to participants with normal sleep duration of 6-7.9\u2009h, regardless of whether they had low sleep efficiency (Hazard ratios (HRs): 1.58; 95% confidence intervals (CIs): 1.19-2.11) or high sleep efficiency (HRs: 1.45; 95% CIs: 1.16-1.81). Deep-learning-based sleep classification using accelerometers has a fair to moderate agreement with polysomnography. Our findings suggest that having short overnight sleep confers mortality risk irrespective of sleep continuity.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41746-024-01065-0.pdf; doi:https://doi.org/10.1038/s41746-024-01065-0; html:https://europepmc.org/articles/PMC11106264; pdf:https://europepmc.org/articles/PMC11106264?pdf=render" + }, { "id": "34746717", "doi": "https://doi.org/10.1016/j.eclinm.2021.101100", @@ -7343,23 +7343,6 @@ "laySummary": "", "urls": "pdf:http://www.cell.com/article/S2666389922000514/pdf; doi:https://doi.org/10.1016/j.patter.2022.100471; html:https://europepmc.org/articles/PMC9122960; pdf:https://europepmc.org/articles/PMC9122960?pdf=render" }, - { - "id": "38806176", - "doi": "https://doi.org/10.1177/00045632241261274", - "title": "A SARS-CoV-2 minimum data standard to support national serology reporting.", - "authorString": "Urwin EN, Martin J, Sebire N, Harris A, Johnston J, Masood E, Milligan G, Mairs L, Chuter A, Ferguson M, Quinlan P, Jefferson E.", - "authorAffiliations": "", - "journalTitle": "Annals of clinical biochemistry", - "pubYear": "2024", - "date": "2024-05-28", - "isOpenAccess": "N", - "keywords": "Computers; Laboratory Management; Laboratory Methods; Analytical Systems", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Healthcare laboratory systems produce and capture a vast array of information, yet do not always report all of this to the national infrastructure within the United Kingdom. The global COVID-19 pandemic brought about a much greater need for detailed healthcare data, one such instance being laboratory testing data. The reporting of qualitative laboratory test results (e.g., positive, negative or indeterminate) provides a basic understanding of levels of seropositivity. However, to better understand and interpret seropositivity, how it is determined and other factors that affect its calculation (i.e., levels of antibodies), quantitative laboratory test data are needed.

Method

36 data attributes were collected from 3 NHS laboratories and 20 CO-CONNECT project partner organisations. These were assessed against the need for a minimum dataset to determine data attribute importance. An NHS laboratory feasibility study was undertaken to assess the minimum data standard, together with a literature review of national and international data standards and healthcare reports.

Results

A COVID serology minimum data standard (CSMDS) comprising 12 data attributes was created and verified by 3 NHS laboratories to allow national granular reporting of COVID serology results. To support this, a standardised set of vocabulary terms was developed to represent laboratory analyser systems and laboratory information management systems.

Conclusions

This paper puts forward a minimum viable standard for COVID-19 serology data attributes to enhance its granularity and augment the national reporting of COVID-19 serology laboratory results, with implications for future pandemics.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1177/00045632241261274" - }, { "id": "37006328", "doi": "https://doi.org/10.1093/braincomms/fcad065", @@ -7377,6 +7360,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/braincomms/advance-article-pdf/doi/10.1093/braincomms/fcad065/49588224/fcad065.pdf; doi:https://doi.org/10.1093/braincomms/fcad065; html:https://europepmc.org/articles/PMC10053639; pdf:https://europepmc.org/articles/PMC10053639?pdf=render" }, + { + "id": "38806176", + "doi": "https://doi.org/10.1177/00045632241261274", + "title": "A SARS-CoV-2 minimum data standard to support national serology reporting.", + "authorString": "Urwin EN, Martin J, Sebire N, Harris A, Johnston J, Masood E, Milligan G, Mairs L, Chuter A, Ferguson M, Quinlan P, Jefferson E.", + "authorAffiliations": "", + "journalTitle": "Annals of clinical biochemistry", + "pubYear": "2024", + "date": "2024-05-28", + "isOpenAccess": "N", + "keywords": "Computers; Laboratory Management; Laboratory Methods; Analytical Systems", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Healthcare laboratory systems produce and capture a vast array of information, yet do not always report all of this to the national infrastructure within the United Kingdom. The global COVID-19 pandemic brought about a much greater need for detailed healthcare data, one such instance being laboratory testing data. The reporting of qualitative laboratory test results (e.g., positive, negative or indeterminate) provides a basic understanding of levels of seropositivity. However, to better understand and interpret seropositivity, how it is determined and other factors that affect its calculation (i.e., levels of antibodies), quantitative laboratory test data are needed.

Method

36 data attributes were collected from 3 NHS laboratories and 20 CO-CONNECT project partner organisations. These were assessed against the need for a minimum dataset to determine data attribute importance. An NHS laboratory feasibility study was undertaken to assess the minimum data standard, together with a literature review of national and international data standards and healthcare reports.

Results

A COVID serology minimum data standard (CSMDS) comprising 12 data attributes was created and verified by 3 NHS laboratories to allow national granular reporting of COVID serology results. To support this, a standardised set of vocabulary terms was developed to represent laboratory analyser systems and laboratory information management systems.

Conclusions

This paper puts forward a minimum viable standard for COVID-19 serology data attributes to enhance its granularity and augment the national reporting of COVID-19 serology laboratory results, with implications for future pandemics.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1177/00045632241261274" + }, { "id": "36992188", "doi": "https://doi.org/10.3390/vaccines11030604", @@ -7530,23 +7530,6 @@ "laySummary": "", "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4668507/1/Hollestein_etal_2023_The-association-between-atopic-eczema.pdf; doi:https://doi.org/10.1111/jdv.18841; html:https://europepmc.org/articles/PMC10947025; pdf:https://europepmc.org/articles/PMC10947025?pdf=render" }, - { - "id": "37536152", - "doi": "https://doi.org/10.1016/j.seizure.2023.07.016", - "title": "Association of comorbid-socioeconomic clusters with mortality in late onset epilepsy derived through unsupervised machine learning.", - "authorString": "Josephson CB, Gonzalez-Izquierdo A, Engbers JDT, Denaxas S, Delgado-Garcia G, Sajobi TT, Wang M, Keezer MR, Wiebe S.", - "authorAffiliations": "", - "journalTitle": "Seizure", - "pubYear": "2023", - "date": "2023-07-29", - "isOpenAccess": "N", - "keywords": "Epilepsy; Elderly; Cohort study; Electronic Health Records; Unsupervised Machine Learning; Late-onset Epilepsy", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background and objectives

Late-onset epilepsy is a heterogenous entity associated with specific aetiologies and an elevated risk of premature mortality. Specific multimorbid-socioeconomic profiles and their unique prognostic trajectories have not been described. We sought to determine if specific clusters of late onset epilepsy exist, and whether they have unique hazards of premature mortality.

Methods

We performed a retrospective observational cohort study linking primary and hospital-based UK electronic health records with vital statistics data (covering years 1998-2019) to identify all cases of incident late onset epilepsy (from people aged \u226565) and 1:10 age, sex, and GP practice-matched controls. We applied hierarchical agglomerative clustering using common aetiologies identified at baseline to define multimorbid-socioeconomic profiles, compare hazards of early mortality, and tabulating causes of death stratified by cluster.

Results

From 1,032,129 people aged \u226565, we identified 1048 cases of late onset epilepsy who were matched to 10,259 controls. Median age at epilepsy diagnosis was 68 (interquartile range: 66-72) and 474 (45%) were female. The hazard of premature mortality related to late-onset epilepsy was higher than matched controls (hazard ratio [HR] 1.73; 95% confidence interval [95%CI] 1.51-1.99). Ten unique phenotypic clusters were identified, defined by 'healthy' males and females, ischaemic stroke, intracerebral haemorrhage (ICH), ICH and alcohol misuse, dementia and anxiety, anxiety, depression in males and females, and brain tumours. Cluster-specific hazards were often similar to that derived for late-onset epilepsy as a whole. Clusters that differed significantly from the base late-onset epilepsy hazard were 'dementia and anxiety' (HR 5.36; 95%CI 3.31-8.68), 'brain tumour' (HR 4.97; 95%CI 2.89-8.56), 'ICH and alcohol misuse' (HR 2.91; 95%CI 1.76-4.81), and 'ischaemic stroke' (HR 2.83; 95%CI 1.83-4.04). These cluster-specific risks were also elevated compared to those derived for tumours, dementia, ischaemic stroke, and ICH in the whole population. Seizure-related cause of death was uncommon and restricted to the ICH, ICH and alcohol misuse, and healthy female clusters.

Significance

Late-onset epilepsy is an amalgam of unique phenotypic clusters that can be quantitatively defined. Late-onset epilepsy and cluster-specific comorbid profiles have complex effects on premature mortality above and beyond the base rates attributed to epilepsy and cluster-defining comorbidities alone.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.seizure.2023.07.016" - }, { "id": "32946449", "doi": "https://doi.org/10.1371/journal.pone.0237676", @@ -7564,6 +7547,23 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0237676&type=printable; doi:https://doi.org/10.1371/journal.pone.0237676; html:https://europepmc.org/articles/PMC7500586; pdf:https://europepmc.org/articles/PMC7500586?pdf=render" }, + { + "id": "37536152", + "doi": "https://doi.org/10.1016/j.seizure.2023.07.016", + "title": "Association of comorbid-socioeconomic clusters with mortality in late onset epilepsy derived through unsupervised machine learning.", + "authorString": "Josephson CB, Gonzalez-Izquierdo A, Engbers JDT, Denaxas S, Delgado-Garcia G, Sajobi TT, Wang M, Keezer MR, Wiebe S.", + "authorAffiliations": "", + "journalTitle": "Seizure", + "pubYear": "2023", + "date": "2023-07-29", + "isOpenAccess": "N", + "keywords": "Epilepsy; Elderly; Cohort study; Electronic Health Records; Unsupervised Machine Learning; Late-onset Epilepsy", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background and objectives

Late-onset epilepsy is a heterogenous entity associated with specific aetiologies and an elevated risk of premature mortality. Specific multimorbid-socioeconomic profiles and their unique prognostic trajectories have not been described. We sought to determine if specific clusters of late onset epilepsy exist, and whether they have unique hazards of premature mortality.

Methods

We performed a retrospective observational cohort study linking primary and hospital-based UK electronic health records with vital statistics data (covering years 1998-2019) to identify all cases of incident late onset epilepsy (from people aged \u226565) and 1:10 age, sex, and GP practice-matched controls. We applied hierarchical agglomerative clustering using common aetiologies identified at baseline to define multimorbid-socioeconomic profiles, compare hazards of early mortality, and tabulating causes of death stratified by cluster.

Results

From 1,032,129 people aged \u226565, we identified 1048 cases of late onset epilepsy who were matched to 10,259 controls. Median age at epilepsy diagnosis was 68 (interquartile range: 66-72) and 474 (45%) were female. The hazard of premature mortality related to late-onset epilepsy was higher than matched controls (hazard ratio [HR] 1.73; 95% confidence interval [95%CI] 1.51-1.99). Ten unique phenotypic clusters were identified, defined by 'healthy' males and females, ischaemic stroke, intracerebral haemorrhage (ICH), ICH and alcohol misuse, dementia and anxiety, anxiety, depression in males and females, and brain tumours. Cluster-specific hazards were often similar to that derived for late-onset epilepsy as a whole. Clusters that differed significantly from the base late-onset epilepsy hazard were 'dementia and anxiety' (HR 5.36; 95%CI 3.31-8.68), 'brain tumour' (HR 4.97; 95%CI 2.89-8.56), 'ICH and alcohol misuse' (HR 2.91; 95%CI 1.76-4.81), and 'ischaemic stroke' (HR 2.83; 95%CI 1.83-4.04). These cluster-specific risks were also elevated compared to those derived for tumours, dementia, ischaemic stroke, and ICH in the whole population. Seizure-related cause of death was uncommon and restricted to the ICH, ICH and alcohol misuse, and healthy female clusters.

Significance

Late-onset epilepsy is an amalgam of unique phenotypic clusters that can be quantitatively defined. Late-onset epilepsy and cluster-specific comorbid profiles have complex effects on premature mortality above and beyond the base rates attributed to epilepsy and cluster-defining comorbidities alone.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.seizure.2023.07.016" + }, { "id": "36882868", "doi": "https://doi.org/10.1186/s12916-023-02784-z", @@ -7615,23 +7615,6 @@ "laySummary": "", "urls": "pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-023-16202-9; doi:https://doi.org/10.1186/s12889-023-16202-9; html:https://europepmc.org/articles/PMC10326925; pdf:https://europepmc.org/articles/PMC10326925?pdf=render" }, - { - "id": "37018139", - "doi": "https://doi.org/10.1093/rheumatology/kead150", - "title": "COVID-19 infection, admission and death and the impact of corticosteroids among people with rare autoimmune rheumatic disease during the second wave of COVID-19 in England: results from the RECORDER Project.", - "authorString": "Rutter M, Lanyon PC, Grainge MJ, Hubbard R, Bythell M, Stilwell P, Aston J, McPhail S, Stevens S, Pearce FA.", - "authorAffiliations": "", - "journalTitle": "Rheumatology (Oxford, England)", - "pubYear": "2023", - "date": "2023-12-01", - "isOpenAccess": "Y", - "keywords": "Infection; Mortality; Coronavirus; epidemiology; Shielding; Covid-19; Rare Autoimmune Rheumatic Diseases", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the second wave of the COVID-19 pandemic in England, and describe the impact of corticosteroids on outcomes.

Methods

Hospital Episode Statistics data were used to identify people alive on 1 August 2020 with ICD-10 codes for RAIRD from the whole population of England. Linked national health records were used to calculate rates and rate ratios of COVID-19 infection and death up to 30 April 2021. Primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. NHS Digital and Office for National Statistics general population data were used for comparison. The association between 30-day corticosteroid usage and COVID-19-related death, COVID-19-related hospital admissions and all-cause deaths was also described.

Results

Of 168\u2009330 people with RAIRD, 9961 (5.92%) had a positive COVID-19 PCR test. The age-standardized infection rate ratio between RAIRD and the general population was 0.99 (95% CI: 0.97, 1.00). 1342 (0.80%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardized mortality rate for COVID-19-related death was 2.76 (95% CI: 2.63, 2.89) times higher than in the general population. There was a dose-dependent relationship between 30-day corticosteroid usage and COVID-19-related death. There was no increase in deaths due to other causes.

Conclusions

During the second wave of COVID-19 in England, people with RAIRD had the same risk of COVID-19 infection but a 2.76-fold increased risk of COVID-19-related death compared with the general population, with corticosteroids associated with increased risk.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/kead150/49769320/kead150.pdf; doi:https://doi.org/10.1093/rheumatology/kead150; html:https://europepmc.org/articles/PMC10691923; pdf:https://europepmc.org/articles/PMC10691923?pdf=render" - }, { "id": "34582457", "doi": "https://doi.org/10.1371/journal.pmed.1003777", @@ -7649,6 +7632,23 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003777&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003777; html:https://europepmc.org/articles/PMC8478234; pdf:https://europepmc.org/articles/PMC8478234?pdf=render" }, + { + "id": "37018139", + "doi": "https://doi.org/10.1093/rheumatology/kead150", + "title": "COVID-19 infection, admission and death and the impact of corticosteroids among people with rare autoimmune rheumatic disease during the second wave of COVID-19 in England: results from the RECORDER Project.", + "authorString": "Rutter M, Lanyon PC, Grainge MJ, Hubbard R, Bythell M, Stilwell P, Aston J, McPhail S, Stevens S, Pearce FA.", + "authorAffiliations": "", + "journalTitle": "Rheumatology (Oxford, England)", + "pubYear": "2023", + "date": "2023-12-01", + "isOpenAccess": "Y", + "keywords": "Infection; Mortality; Coronavirus; epidemiology; Shielding; Covid-19; Rare Autoimmune Rheumatic Diseases", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the second wave of the COVID-19 pandemic in England, and describe the impact of corticosteroids on outcomes.

Methods

Hospital Episode Statistics data were used to identify people alive on 1 August 2020 with ICD-10 codes for RAIRD from the whole population of England. Linked national health records were used to calculate rates and rate ratios of COVID-19 infection and death up to 30 April 2021. Primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. NHS Digital and Office for National Statistics general population data were used for comparison. The association between 30-day corticosteroid usage and COVID-19-related death, COVID-19-related hospital admissions and all-cause deaths was also described.

Results

Of 168\u2009330 people with RAIRD, 9961 (5.92%) had a positive COVID-19 PCR test. The age-standardized infection rate ratio between RAIRD and the general population was 0.99 (95% CI: 0.97, 1.00). 1342 (0.80%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardized mortality rate for COVID-19-related death was 2.76 (95% CI: 2.63, 2.89) times higher than in the general population. There was a dose-dependent relationship between 30-day corticosteroid usage and COVID-19-related death. There was no increase in deaths due to other causes.

Conclusions

During the second wave of COVID-19 in England, people with RAIRD had the same risk of COVID-19 infection but a 2.76-fold increased risk of COVID-19-related death compared with the general population, with corticosteroids associated with increased risk.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/kead150/49769320/kead150.pdf; doi:https://doi.org/10.1093/rheumatology/kead150; html:https://europepmc.org/articles/PMC10691923; pdf:https://europepmc.org/articles/PMC10691923?pdf=render" + }, { "id": "36755846", "doi": "https://doi.org/10.1093/ckj/sfac241", @@ -7972,6 +7972,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/aje/advance-article-pdf/doi/10.1093/aje/kwad179/51329819/kwad179.pdf; doi:https://doi.org/10.1093/aje/kwad179; html:https://europepmc.org/articles/PMC10773473; pdf:https://europepmc.org/articles/PMC10773473?pdf=render" }, + { + "id": "32723851", + "doi": "https://doi.org/10.1136/bmjhci-2019-100122", + "title": "HDR UK supporting mobilising computable biomedical knowledge in the UK.", + "authorString": "Sebire NJ, Cake C, Morris AD.", + "authorAffiliations": "", + "journalTitle": "BMJ health & care informatics", + "pubYear": "2020", + "date": "2020-07-01", + "isOpenAccess": "Y", + "keywords": "Health care; Medical Informatics; Information Systems", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Computable biomedical knowledge (CBK) represents an evolving area of health informatics, with potential for rapid translational patient benefit. Health Data Research UK (HDR UK) is the national Institute for Health Data Science, whose aim is to unite the UK's health data to enable discoveries that improve people's lives. The three main components include the UK HDR Alliance of data custodians, committed to making health data available for research and innovation purposes for public benefit while ensuring safe use of data and building public trust, the HDR Hubs, as centres of expertise for curating data and providing expert domain-specific services, and the HDR Innovation Gateway ('Gateway'), providing discovery, accessibility, security and interoperability services. To support CBK developments, HDR UK is encouraging use of open data standards for research purposes, with guidance around areas in which standards are emerging, aims to work closely with the international CBK community to support initiatives and aid with evaluation and collaboration, and has established a phenomics workstream to create a national platform for dissemination of machine readable and computable phenotypical algorithms to reduce duplication of effort and improve reproducibility in clinical studies.", + "laySummary": "", + "urls": "pdf:https://informatics.bmj.com/content/bmjhci/27/2/e100122.full.pdf; doi:https://doi.org/10.1136/bmjhci-2019-100122; html:https://europepmc.org/articles/PMC7388881; pdf:https://europepmc.org/articles/PMC7388881?pdf=render" + }, { "id": "38191614", "doi": "https://doi.org/10.1038/s41591-023-02686-w", @@ -7990,21 +8007,21 @@ "urls": "doi:https://doi.org/10.1038/s41591-023-02686-w" }, { - "id": "32723851", - "doi": "https://doi.org/10.1136/bmjhci-2019-100122", - "title": "HDR UK supporting mobilising computable biomedical knowledge in the UK.", - "authorString": "Sebire NJ, Cake C, Morris AD.", + "id": "32935048", + "doi": "https://doi.org/10.23889/ijpds.v5i1.1121", + "title": "The Secure Anonymised Information Linkage databank Dementia e-cohort (SAIL-DeC).", + "authorString": "Schnier C, Wilkinson T, Akbari A, Orton C, Sleegers K, Gallacher J, Lyons RA, Sudlow C.", "authorAffiliations": "", - "journalTitle": "BMJ health & care informatics", + "journalTitle": "International journal of population data science", "pubYear": "2020", - "date": "2020-07-01", + "date": "2020-02-25", "isOpenAccess": "Y", - "keywords": "Health care; Medical Informatics; Information Systems", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "Computable biomedical knowledge (CBK) represents an evolving area of health informatics, with potential for rapid translational patient benefit. Health Data Research UK (HDR UK) is the national Institute for Health Data Science, whose aim is to unite the UK's health data to enable discoveries that improve people's lives. The three main components include the UK HDR Alliance of data custodians, committed to making health data available for research and innovation purposes for public benefit while ensuring safe use of data and building public trust, the HDR Hubs, as centres of expertise for curating data and providing expert domain-specific services, and the HDR Innovation Gateway ('Gateway'), providing discovery, accessibility, security and interoperability services. To support CBK developments, HDR UK is encouraging use of open data standards for research purposes, with guidance around areas in which standards are emerging, aims to work closely with the international CBK community to support initiatives and aid with evaluation and collaboration, and has established a phenomics workstream to create a national platform for dissemination of machine readable and computable phenotypical algorithms to reduce duplication of effort and improve reproducibility in clinical studies.", + "abstract": "

Introduction

The rising burden of dementia is a global concern, and there is a need to study its causes, natural history and outcomes. The Secure Anonymised Information Linkage (SAIL) Databank contains anonymised, routinely-collected healthcare data for the population of Wales, UK. It has potential to be a valuable resource for dementia research owing to its size, long follow-up time and prospective collection of data during clinical care.

Objectives

We aimed to apply reproducible methods to create the SAIL dementia e-cohort (SAIL-DeC). We created SAIL-DeC with a view to maximising its utility for a broad range of research questions whilst minimising duplication of effort for researchers.

Methods

SAIL contains individual-level, linked primary care, hospital admission, mortality and demographic data. Data are currently available until 2018 and future updates will extend participant follow-up time. We included participants who were born between 1st January 1900 and 1st January 1958 and for whom primary care data were available. We applied algorithms consisting of International Classification of Diseases (versions 9 and 10) and Read (version 2) codes to identify participants with and without all-cause dementia and dementia subtypes. We also created derived variables for comorbidities and risk factors.

Results

From 4.4 million unique participants in SAIL, 1.2 million met the cohort inclusion criteria, resulting in 18.8 million person-years of follow-up. Of these, 129,650 (10%) developed all-cause dementia, with 77,978 (60%) having dementia subtype codes. Alzheimer's disease was the most common subtype diagnosis (62%). Among the dementia cases, the median duration of observation time was 14 years.

Conclusion

We have created a generalisable, national dementia e-cohort, aimed at facilitating epidemiological dementia research.", "laySummary": "", - "urls": "pdf:https://informatics.bmj.com/content/bmjhci/27/2/e100122.full.pdf; doi:https://doi.org/10.1136/bmjhci-2019-100122; html:https://europepmc.org/articles/PMC7388881; pdf:https://europepmc.org/articles/PMC7388881?pdf=render" + "urls": "pdf:https://ijpds.org/article/download/1121/2984; doi:https://doi.org/10.23889/ijpds.v5i1.1121; html:https://europepmc.org/articles/PMC7473277; pdf:https://europepmc.org/articles/PMC7473277?pdf=render" }, { "id": "35534084", @@ -8023,23 +8040,6 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/5/e054186.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054186; html:https://europepmc.org/articles/PMC9086620; pdf:https://europepmc.org/articles/PMC9086620?pdf=render" }, - { - "id": "32935048", - "doi": "https://doi.org/10.23889/ijpds.v5i1.1121", - "title": "The Secure Anonymised Information Linkage databank Dementia e-cohort (SAIL-DeC).", - "authorString": "Schnier C, Wilkinson T, Akbari A, Orton C, Sleegers K, Gallacher J, Lyons RA, Sudlow C.", - "authorAffiliations": "", - "journalTitle": "International journal of population data science", - "pubYear": "2020", - "date": "2020-02-25", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

The rising burden of dementia is a global concern, and there is a need to study its causes, natural history and outcomes. The Secure Anonymised Information Linkage (SAIL) Databank contains anonymised, routinely-collected healthcare data for the population of Wales, UK. It has potential to be a valuable resource for dementia research owing to its size, long follow-up time and prospective collection of data during clinical care.

Objectives

We aimed to apply reproducible methods to create the SAIL dementia e-cohort (SAIL-DeC). We created SAIL-DeC with a view to maximising its utility for a broad range of research questions whilst minimising duplication of effort for researchers.

Methods

SAIL contains individual-level, linked primary care, hospital admission, mortality and demographic data. Data are currently available until 2018 and future updates will extend participant follow-up time. We included participants who were born between 1st January 1900 and 1st January 1958 and for whom primary care data were available. We applied algorithms consisting of International Classification of Diseases (versions 9 and 10) and Read (version 2) codes to identify participants with and without all-cause dementia and dementia subtypes. We also created derived variables for comorbidities and risk factors.

Results

From 4.4 million unique participants in SAIL, 1.2 million met the cohort inclusion criteria, resulting in 18.8 million person-years of follow-up. Of these, 129,650 (10%) developed all-cause dementia, with 77,978 (60%) having dementia subtype codes. Alzheimer's disease was the most common subtype diagnosis (62%). Among the dementia cases, the median duration of observation time was 14 years.

Conclusion

We have created a generalisable, national dementia e-cohort, aimed at facilitating epidemiological dementia research.", - "laySummary": "", - "urls": "pdf:https://ijpds.org/article/download/1121/2984; doi:https://doi.org/10.23889/ijpds.v5i1.1121; html:https://europepmc.org/articles/PMC7473277; pdf:https://europepmc.org/articles/PMC7473277?pdf=render" - }, { "id": "35922409", "doi": "https://doi.org/10.1038/s41467-022-32121-6", @@ -8074,23 +8074,6 @@ "laySummary": "", "urls": "pdf:https://bmcbioinformatics.biomedcentral.com/track/pdf/10.1186/s12859-022-04641-x; doi:https://doi.org/10.1186/s12859-022-04641-x; html:https://europepmc.org/articles/PMC8974006; pdf:https://europepmc.org/articles/PMC8974006?pdf=render" }, - { - "id": "37408471", - "doi": "https://doi.org/10.1093/eurheartj/ehad424", - "title": "The CODE-EHR global framework: lifting the veil on health record data.", - "authorString": "Asselbergs FW, Kotecha D.", - "authorAffiliations": "", - "journalTitle": "European heart journal", - "pubYear": "2023", - "date": "2023-09-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad424/50827856/ehad424.pdf; doi:https://doi.org/10.1093/eurheartj/ehad424" - }, { "id": "32499256", "doi": "https://doi.org/10.1136/bmjopen-2019-033424", @@ -8108,6 +8091,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/10/6/e033424.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-033424; html:https://europepmc.org/articles/PMC7282288; pdf:https://europepmc.org/articles/PMC7282288?pdf=render" }, + { + "id": "37408471", + "doi": "https://doi.org/10.1093/eurheartj/ehad424", + "title": "The CODE-EHR global framework: lifting the veil on health record data.", + "authorString": "Asselbergs FW, Kotecha D.", + "authorAffiliations": "", + "journalTitle": "European heart journal", + "pubYear": "2023", + "date": "2023-09-01", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad424/50827856/ehad424.pdf; doi:https://doi.org/10.1093/eurheartj/ehad424" + }, { "id": "36536453", "doi": "https://doi.org/10.1186/s41512-022-00137-7", @@ -8499,23 +8499,6 @@ "laySummary": "", "urls": "pdf:https://bmcnephrol.biomedcentral.com/counter/pdf/10.1186/s12882-022-02902-8; doi:https://doi.org/10.1186/s12882-022-02902-8; html:https://europepmc.org/articles/PMC9351155; pdf:https://europepmc.org/articles/PMC9351155?pdf=render" }, - { - "id": "37927438", - "doi": "https://doi.org/10.1016/j.lanepe.2023.100741", - "title": "Comparative effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised high-risk patients during Omicron waves: observational cohort study using the OpenSAFELY platform.", - "authorString": "Zheng B, Tazare J, Nab L, Green AC, Curtis HJ, Mahalingasivam V, Herrett EL, Costello RE, Eggo RM, Speed V, Bacon SC, Bates C, Parry J, Cockburn J, Hester F, Harper S, Schaffer AL, Hulme WJ, Mehrkar A, Evans SJ, MacKenna B, Goldacre B, Douglas IJ, Tomlinson LA, OpenSAFELY Collaborative.", - "authorAffiliations": "", - "journalTitle": "The Lancet regional health. Europe", - "pubYear": "2023", - "date": "2023-10-08", - "isOpenAccess": "Y", - "keywords": "Comparative Effectiveness; Real-world Data; Covid-19; Sotrovimab; Paxlovid", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Timely evidence of the comparative effectiveness between COVID-19 therapies in real-world settings is needed to inform clinical care. This study aimed to compare the effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir in preventing severe COVID-19 outcomes in non-hospitalised high-risk COVID-19 adult patients during Omicron waves.

Methods

With the approval of NHS England, we conducted a real-world cohort study using the OpenSAFELY-TPP platform. Patient-level primary care data were obtained from 24 million people in England and were securely linked with data on COVID-19 infection and therapeutics, hospital admission, and death, covering a period where both nirmatrelvir/ritonavir and sotrovimab were first-line treatment options in community settings (February 10, 2022-November 27, 2022). Molnupiravir (third-line option) was used as an exploratory comparator to nirmatrelvir/ritonavir, both of which were antivirals. Cox proportional hazards model stratified by area was used to compare the risk of 28-day COVID-19 related hospitalisation/death across treatment groups.

Findings

A total of 9026 eligible patients treated with nirmatrelvir/ritonavir (n\u00a0=\u00a05704) and sotrovimab (n\u00a0=\u00a03322) were included in the main analysis. The mean age was 52.7 (SD\u00a0=\u00a014.9) years and 93% (8436/9026) had three or more COVID-19 vaccinations. Within 28 days after treatment initiation, 55/9026 (0.61%) COVID-19 related hospitalisations/deaths were observed (34/5704 [0.60%] treated with nirmatrelvir/ritonavir and 21/3322 [0.63%] with sotrovimab). After adjusting for demographics, high-risk cohort categories, vaccination status, calendar time, body mass index and other comorbidities, we observed no significant difference in outcome risk between nirmatrelvir/ritonavir and sotrovimab users (HR\u00a0=\u00a00.89, 95% CI: 0.48-1.63; P\u00a0=\u00a00.698). Results from propensity score weighted model also showed non-significant difference between treatment groups (HR\u00a0=\u00a00.82, 95% CI: 0.45-1.52; P\u00a0=\u00a00.535). The exploratory analysis comparing nirmatrelvir/ritonavir users with 1041 molnupiravir users (13/1041 [1.25%] COVID-19 related hospitalisations/deaths) showed an association in favour of nirmatrelvir/ritonavir (HR\u00a0=\u00a00.45, 95% CI: 0.22-0.94; P\u00a0=\u00a00.033).

Interpretation

In routine care of non-hospitalised high-risk adult patients with COVID-19 in England, no substantial difference in the risk of severe COVID-19 outcomes was observed between those who received nirmatrelvir/ritonavir and sotrovimab between February and November 2022, when Omicron subvariants BA.2, BA.5, or BQ.1 were dominant.

Funding

UK Research and Innovation, Wellcome Trust, UK Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.lanepe.2023.100741; doi:https://doi.org/10.1016/j.lanepe.2023.100741; html:https://europepmc.org/articles/PMC10624988; pdf:https://europepmc.org/articles/PMC10624988?pdf=render" - }, { "id": "37248229", "doi": "https://doi.org/10.1038/s41467-023-38756-3", @@ -8533,6 +8516,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41467-023-38756-3; doi:https://doi.org/10.1038/s41467-023-38756-3; html:https://europepmc.org/articles/PMC10226446; pdf:https://europepmc.org/articles/PMC10226446?pdf=render" }, + { + "id": "37927438", + "doi": "https://doi.org/10.1016/j.lanepe.2023.100741", + "title": "Comparative effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised high-risk patients during Omicron waves: observational cohort study using the OpenSAFELY platform.", + "authorString": "Zheng B, Tazare J, Nab L, Green AC, Curtis HJ, Mahalingasivam V, Herrett EL, Costello RE, Eggo RM, Speed V, Bacon SC, Bates C, Parry J, Cockburn J, Hester F, Harper S, Schaffer AL, Hulme WJ, Mehrkar A, Evans SJ, MacKenna B, Goldacre B, Douglas IJ, Tomlinson LA, OpenSAFELY Collaborative.", + "authorAffiliations": "", + "journalTitle": "The Lancet regional health. Europe", + "pubYear": "2023", + "date": "2023-10-08", + "isOpenAccess": "Y", + "keywords": "Comparative Effectiveness; Real-world Data; Covid-19; Sotrovimab; Paxlovid", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Timely evidence of the comparative effectiveness between COVID-19 therapies in real-world settings is needed to inform clinical care. This study aimed to compare the effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir in preventing severe COVID-19 outcomes in non-hospitalised high-risk COVID-19 adult patients during Omicron waves.

Methods

With the approval of NHS England, we conducted a real-world cohort study using the OpenSAFELY-TPP platform. Patient-level primary care data were obtained from 24 million people in England and were securely linked with data on COVID-19 infection and therapeutics, hospital admission, and death, covering a period where both nirmatrelvir/ritonavir and sotrovimab were first-line treatment options in community settings (February 10, 2022-November 27, 2022). Molnupiravir (third-line option) was used as an exploratory comparator to nirmatrelvir/ritonavir, both of which were antivirals. Cox proportional hazards model stratified by area was used to compare the risk of 28-day COVID-19 related hospitalisation/death across treatment groups.

Findings

A total of 9026 eligible patients treated with nirmatrelvir/ritonavir (n\u00a0=\u00a05704) and sotrovimab (n\u00a0=\u00a03322) were included in the main analysis. The mean age was 52.7 (SD\u00a0=\u00a014.9) years and 93% (8436/9026) had three or more COVID-19 vaccinations. Within 28 days after treatment initiation, 55/9026 (0.61%) COVID-19 related hospitalisations/deaths were observed (34/5704 [0.60%] treated with nirmatrelvir/ritonavir and 21/3322 [0.63%] with sotrovimab). After adjusting for demographics, high-risk cohort categories, vaccination status, calendar time, body mass index and other comorbidities, we observed no significant difference in outcome risk between nirmatrelvir/ritonavir and sotrovimab users (HR\u00a0=\u00a00.89, 95% CI: 0.48-1.63; P\u00a0=\u00a00.698). Results from propensity score weighted model also showed non-significant difference between treatment groups (HR\u00a0=\u00a00.82, 95% CI: 0.45-1.52; P\u00a0=\u00a00.535). The exploratory analysis comparing nirmatrelvir/ritonavir users with 1041 molnupiravir users (13/1041 [1.25%] COVID-19 related hospitalisations/deaths) showed an association in favour of nirmatrelvir/ritonavir (HR\u00a0=\u00a00.45, 95% CI: 0.22-0.94; P\u00a0=\u00a00.033).

Interpretation

In routine care of non-hospitalised high-risk adult patients with COVID-19 in England, no substantial difference in the risk of severe COVID-19 outcomes was observed between those who received nirmatrelvir/ritonavir and sotrovimab between February and November 2022, when Omicron subvariants BA.2, BA.5, or BQ.1 were dominant.

Funding

UK Research and Innovation, Wellcome Trust, UK Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.lanepe.2023.100741; doi:https://doi.org/10.1016/j.lanepe.2023.100741; html:https://europepmc.org/articles/PMC10624988; pdf:https://europepmc.org/articles/PMC10624988?pdf=render" + }, { "id": "37311808", "doi": "https://doi.org/10.1038/s41467-023-39193-y", @@ -8856,23 +8856,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac233/48422792/dyac233.pdf; doi:https://doi.org/10.1093/ije/dyac233; html:https://europepmc.org/articles/PMC10396423; pdf:https://europepmc.org/articles/PMC10396423?pdf=render" }, - { - "id": "38569874", - "doi": "https://doi.org/10.1136/jnnp-2024-333530", - "title": "Trends in the prevalence and pharmacological management of migraine during pregnancy in the UK, 2000-2018.", - "authorString": "Phillips K, Nirantharakumar K, Wakerley BR, Crowe FL.", - "authorAffiliations": "", - "journalTitle": "Journal of neurology, neurosurgery, and psychiatry", - "pubYear": "2024", - "date": "2024-04-03", - "isOpenAccess": "N", - "keywords": "Migraine", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Migraine is common in women of reproductive age. This study aimed to (1) describe the prevalence of migraine in pregnant women in the UK, (2) identify drugs commonly prescribed for migraine during pregnancy and (3) identify characteristics associated with being prescribed medication for migraine during pregnancy.

Methods

The Clinical Practice Research Datalink pregnancy register, a database of pregnancy episodes identified in anonymised primary care health records, was used.Crude and age-standardised prevalence of migraine during pregnancy and the proportion of women with migraine prescribed drugs used for migraine management were calculated for each year between 2000 and 2018.Logistic regression was used to describe the relationship between patient characteristics and being prescribed migraine medication during pregnancy.

Results

1\u2009377\u2009053 pregnancies were included, of which 187\u2009328 were in women with a history of migraine. The age-adjusted prevalence increased from 11.4% in 2000 to 17.2% in 2018. There was an increase in the rates of prescription for numerous medications for the management of migraine.Older women (adjusted OR (aOR) 1.41 (1.20 to 1.66)), women of black (aOR 1.40 (1.32 to 1.48)) and South Asian ethnicity (aOR 1.48 (1.38 to 1.59)), those living in the most deprived areas (aOR 1.60 (1.54 to 1.66)), women who were obese (aOR 1.39 (1.35 to 1.43)), smokers (aOR 1.15 (1.12 to 1.18)) and those with comorbid conditions were more likely to receive a prescription during pregnancy.

Conclusions

Rates of recorded migraine have increased over the past two decades as well as rates of prescribing in women with migraine. Higher prescribing rates are seen in certain groups, which has the potential to exacerbate health inequalities.", - "laySummary": "", - "urls": "pdf:https://jnnp.bmj.com/content/jnnp/early/2024/04/03/jnnp-2024-333530.full.pdf; doi:https://doi.org/10.1136/jnnp-2024-333530" - }, { "id": "36716318", "doi": "https://doi.org/10.1371/journal.pmed.1004174", @@ -8907,6 +8890,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41588-023-01585-7.pdf; doi:https://doi.org/10.1038/s41588-023-01585-7; html:https://europepmc.org/articles/PMC10786720; pdf:https://europepmc.org/articles/PMC10786720?pdf=render" }, + { + "id": "38569874", + "doi": "https://doi.org/10.1136/jnnp-2024-333530", + "title": "Trends in the prevalence and pharmacological management of migraine during pregnancy in the UK, 2000-2018.", + "authorString": "Phillips K, Nirantharakumar K, Wakerley BR, Crowe FL.", + "authorAffiliations": "", + "journalTitle": "Journal of neurology, neurosurgery, and psychiatry", + "pubYear": "2024", + "date": "2024-04-03", + "isOpenAccess": "N", + "keywords": "Migraine", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Migraine is common in women of reproductive age. This study aimed to (1) describe the prevalence of migraine in pregnant women in the UK, (2) identify drugs commonly prescribed for migraine during pregnancy and (3) identify characteristics associated with being prescribed medication for migraine during pregnancy.

Methods

The Clinical Practice Research Datalink pregnancy register, a database of pregnancy episodes identified in anonymised primary care health records, was used.Crude and age-standardised prevalence of migraine during pregnancy and the proportion of women with migraine prescribed drugs used for migraine management were calculated for each year between 2000 and 2018.Logistic regression was used to describe the relationship between patient characteristics and being prescribed migraine medication during pregnancy.

Results

1\u2009377\u2009053 pregnancies were included, of which 187\u2009328 were in women with a history of migraine. The age-adjusted prevalence increased from 11.4% in 2000 to 17.2% in 2018. There was an increase in the rates of prescription for numerous medications for the management of migraine.Older women (adjusted OR (aOR) 1.41 (1.20 to 1.66)), women of black (aOR 1.40 (1.32 to 1.48)) and South Asian ethnicity (aOR 1.48 (1.38 to 1.59)), those living in the most deprived areas (aOR 1.60 (1.54 to 1.66)), women who were obese (aOR 1.39 (1.35 to 1.43)), smokers (aOR 1.15 (1.12 to 1.18)) and those with comorbid conditions were more likely to receive a prescription during pregnancy.

Conclusions

Rates of recorded migraine have increased over the past two decades as well as rates of prescribing in women with migraine. Higher prescribing rates are seen in certain groups, which has the potential to exacerbate health inequalities.", + "laySummary": "", + "urls": "pdf:https://jnnp.bmj.com/content/jnnp/early/2024/04/03/jnnp-2024-333530.full.pdf; doi:https://doi.org/10.1136/jnnp-2024-333530" + }, { "id": "37159441", "doi": "https://doi.org/10.1371/journal.pdig.0000218", @@ -9842,23 +9842,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.ijmedinf.2021.104400; doi:https://doi.org/10.1016/j.ijmedinf.2021.104400; html:https://europepmc.org/articles/PMC7843148" }, - { - "id": "37996473", - "doi": "https://doi.org/10.1038/s41598-023-47371-7", - "title": "Evidence for involvement of the alcohol consumption WDPCP gene in lipid metabolism, and liver cirrhosis.", - "authorString": "O'Farrell F, Aleyakpo B, Mustafa R, Jiang X, Pinto RC, Elliott P, Tzoulaki I, Dehghan A, Loh SHY, Barclay JW, Martins LM, Pazoki R.", - "authorAffiliations": "", - "journalTitle": "Scientific reports", - "pubYear": "2023", - "date": "2023-11-23", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Biological pathways between alcohol consumption and alcohol liver disease (ALD) are not fully understood. We selected genes with known effect on (1) alcohol consumption, (2) liver function, and (3) gene expression. Expression of the orthologs of these genes in Caenorhabditis elegans and Drosophila melanogaster was suppressed using mutations and/or RNA interference (RNAi). In humans, association analysis, pathway analysis, and Mendelian randomization analysis were performed to identify metabolic changes due to alcohol consumption. In C. elegans, we found a reduction in locomotion rate after exposure to ethanol for RNAi knockdown of ACTR1B and MAPT. In Drosophila, we observed (1) a change in sedative effect of ethanol for RNAi knockdown of WDPCP, TENM2, GPN1, ARPC1B, and SCN8A, (2) a reduction in ethanol consumption for RNAi knockdown of TENM2, (3) a reduction in triradylglycerols (TAG) levels for RNAi knockdown of WDPCP, TENM2, and GPN1. In human, we observed (1) a link between alcohol consumption and several metabolites including TAG, (2) an enrichment of the candidate (alcohol-associated) metabolites within the linoleic acid (LNA) and alpha-linolenic acid (ALA) metabolism pathways, (3) a causal link between gene expression of WDPCP to liver fibrosis and liver cirrhosis. Our results imply that WDPCP might be involved in ALD.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41598-023-47371-7.pdf; doi:https://doi.org/10.1038/s41598-023-47371-7; html:https://europepmc.org/articles/PMC10667215; pdf:https://europepmc.org/articles/PMC10667215?pdf=render" - }, { "id": "33965593", "doi": "https://doi.org/10.1016/j.jaip.2021.04.055", @@ -9876,6 +9859,23 @@ "laySummary": "", "urls": "pdf:https://europepmc.org/articles/pmc8443840?pdf=render; doi:https://doi.org/10.1016/j.jaip.2021.04.055; html:https://europepmc.org/articles/PMC8443840; pdf:https://europepmc.org/articles/PMC8443840?pdf=render" }, + { + "id": "37996473", + "doi": "https://doi.org/10.1038/s41598-023-47371-7", + "title": "Evidence for involvement of the alcohol consumption WDPCP gene in lipid metabolism, and liver cirrhosis.", + "authorString": "O'Farrell F, Aleyakpo B, Mustafa R, Jiang X, Pinto RC, Elliott P, Tzoulaki I, Dehghan A, Loh SHY, Barclay JW, Martins LM, Pazoki R.", + "authorAffiliations": "", + "journalTitle": "Scientific reports", + "pubYear": "2023", + "date": "2023-11-23", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Biological pathways between alcohol consumption and alcohol liver disease (ALD) are not fully understood. We selected genes with known effect on (1) alcohol consumption, (2) liver function, and (3) gene expression. Expression of the orthologs of these genes in Caenorhabditis elegans and Drosophila melanogaster was suppressed using mutations and/or RNA interference (RNAi). In humans, association analysis, pathway analysis, and Mendelian randomization analysis were performed to identify metabolic changes due to alcohol consumption. In C. elegans, we found a reduction in locomotion rate after exposure to ethanol for RNAi knockdown of ACTR1B and MAPT. In Drosophila, we observed (1) a change in sedative effect of ethanol for RNAi knockdown of WDPCP, TENM2, GPN1, ARPC1B, and SCN8A, (2) a reduction in ethanol consumption for RNAi knockdown of TENM2, (3) a reduction in triradylglycerols (TAG) levels for RNAi knockdown of WDPCP, TENM2, and GPN1. In human, we observed (1) a link between alcohol consumption and several metabolites including TAG, (2) an enrichment of the candidate (alcohol-associated) metabolites within the linoleic acid (LNA) and alpha-linolenic acid (ALA) metabolism pathways, (3) a causal link between gene expression of WDPCP to liver fibrosis and liver cirrhosis. Our results imply that WDPCP might be involved in ALD.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41598-023-47371-7.pdf; doi:https://doi.org/10.1038/s41598-023-47371-7; html:https://europepmc.org/articles/PMC10667215; pdf:https://europepmc.org/articles/PMC10667215?pdf=render" + }, { "id": "31462651", "doi": "https://doi.org/10.1038/s41598-019-48927-2", @@ -10131,23 +10131,6 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/1424-8220/21/6/2190/pdf?version=1616388230; doi:https://doi.org/10.3390/s21062190; html:https://europepmc.org/articles/PMC8003942; pdf:https://europepmc.org/articles/PMC8003942?pdf=render" }, - { - "id": "37935836", - "doi": "https://doi.org/10.1093/eurheartj/ehad736", - "title": "Mendelian randomization for cardiovascular diseases: principles and applications.", - "authorString": "Larsson SC, Butterworth AS, Burgess S.", - "authorAffiliations": "", - "journalTitle": "European heart journal", - "pubYear": "2023", - "date": "2023-12-01", - "isOpenAccess": "Y", - "keywords": "Genetics; Cardiovascular disease; Single Nucleotide Polymorphisms; Mendelian Randomization", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Large-scale genome-wide association studies conducted over the last decade have uncovered numerous genetic variants associated with cardiometabolic traits and risk factors. These discoveries have enabled the Mendelian randomization (MR) design, which uses genetic variation as a natural experiment to improve causal inferences from observational data. By analogy with the random assignment of treatment in randomized controlled trials, the random segregation of genetic alleles when DNA is transmitted from parents to offspring at gamete formation is expected to reduce confounding in genetic associations. Mendelian randomization analyses make a set of assumptions that must hold for valid results. Provided that the assumptions are well justified for the genetic variants that are employed as instrumental variables, MR studies can inform on whether a putative risk factor likely has a causal effect on the disease or not. Mendelian randomization has been increasingly applied over recent years to predict the efficacy and safety of existing and novel drugs targeting cardiovascular risk factors and to explore the repurposing potential of available drugs. This review article describes the principles of the MR design and some applications in cardiovascular epidemiology.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad736/52829421/ehad736.pdf; doi:https://doi.org/10.1093/eurheartj/ehad736; html:https://europepmc.org/articles/PMC10719501; pdf:https://europepmc.org/articles/PMC10719501?pdf=render" - }, { "id": "35997000", "doi": "https://doi.org/10.1111/ene.15530", @@ -10165,6 +10148,23 @@ "laySummary": "", "urls": "pdf:https://cronfa.swan.ac.uk/Record/cronfa62203/Download/62203__26254__0c88bfc9ff7e4fe2acaea5e2a2d74058.pdf; doi:https://doi.org/10.1111/ene.15530; html:https://europepmc.org/articles/PMC9826317; pdf:https://europepmc.org/articles/PMC9826317?pdf=render" }, + { + "id": "37935836", + "doi": "https://doi.org/10.1093/eurheartj/ehad736", + "title": "Mendelian randomization for cardiovascular diseases: principles and applications.", + "authorString": "Larsson SC, Butterworth AS, Burgess S.", + "authorAffiliations": "", + "journalTitle": "European heart journal", + "pubYear": "2023", + "date": "2023-12-01", + "isOpenAccess": "Y", + "keywords": "Genetics; Cardiovascular disease; Single Nucleotide Polymorphisms; Mendelian Randomization", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Large-scale genome-wide association studies conducted over the last decade have uncovered numerous genetic variants associated with cardiometabolic traits and risk factors. These discoveries have enabled the Mendelian randomization (MR) design, which uses genetic variation as a natural experiment to improve causal inferences from observational data. By analogy with the random assignment of treatment in randomized controlled trials, the random segregation of genetic alleles when DNA is transmitted from parents to offspring at gamete formation is expected to reduce confounding in genetic associations. Mendelian randomization analyses make a set of assumptions that must hold for valid results. Provided that the assumptions are well justified for the genetic variants that are employed as instrumental variables, MR studies can inform on whether a putative risk factor likely has a causal effect on the disease or not. Mendelian randomization has been increasingly applied over recent years to predict the efficacy and safety of existing and novel drugs targeting cardiovascular risk factors and to explore the repurposing potential of available drugs. This review article describes the principles of the MR design and some applications in cardiovascular epidemiology.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad736/52829421/ehad736.pdf; doi:https://doi.org/10.1093/eurheartj/ehad736; html:https://europepmc.org/articles/PMC10719501; pdf:https://europepmc.org/articles/PMC10719501?pdf=render" + }, { "id": "33495722", "doi": "https://doi.org/10.1109/access.2021.3050524", @@ -10284,23 +10284,6 @@ "laySummary": "", "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4659476/13/PIIS0140673621006346.pdf; doi:https://doi.org/10.1016/S0140-6736(21)00634-6; html:https://europepmc.org/articles/PMC8087292; pdf:https://europepmc.org/articles/PMC8087292?pdf=render" }, - { - "id": "38662697", - "doi": "https://doi.org/10.1093/cid/ciae108", - "title": "Reducing the Antigen Prevalence Target Threshold for Stopping and Restarting Mass Drug Administration for Lymphatic Filariasis Elimination: A Model-Based Cost-effectiveness Simulation in Tanzania, India and Haiti.", - "authorString": "Antony Oliver MC, Graham M, Gass KM, Medley GF, Clark J, Davis EL, Reimer LJ, King JD, Pouwels KB, Hollingsworth TD.", - "authorAffiliations": "", - "journalTitle": "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America", - "pubYear": "2024", - "date": "2024-04-01", - "isOpenAccess": "Y", - "keywords": "Threshold; Modeling; Elimination; Health Economics; Lymphatic Filariasis", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

The Global Programme to Eliminate Lymphatic Filariasis (GPELF) aims to reduce and maintain infection levels through mass drug administration (MDA), but there is evidence of ongoing transmission after MDA in areas where Culex mosquitoes are the main transmission vector, suggesting that a more stringent criterion is required for MDA decision making in these settings.

Methods

We use a transmission model to investigate how a lower prevalence threshold (<1% antigenemia [Ag] prevalence compared with <2% Ag prevalence) for MDA decision making would affect the probability of local elimination, health outcomes, the number of MDA rounds, including restarts, and program costs associated with MDA and surveys across different scenarios. To determine the cost-effectiveness of switching to a lower threshold, we simulated 65% and 80% MDA coverage of the total population for different willingness to pay per disability-adjusted life-year averted for India ($446.07), Tanzania ($389.83), and Haiti ($219.84).

Results

Our results suggest that with a lower Ag threshold, there is a small proportion of simulations where extra rounds are required to reach the target, but this also reduces the need to restart MDA later in the program. For 80% coverage, the lower threshold is cost-effective across all baseline prevalences for India, Tanzania, and Haiti. For 65% MDA coverage, the lower threshold is not cost-effective due to additional MDA rounds, although it increases the probability of local elimination. Valuing the benefits of elimination to align with the GPELF goals, we find that a willingness to pay per capita government expenditure of approximately $1000-$4000 for 1% increase in the probability of local elimination would be required to make a lower threshold cost-effective.

Conclusions

Lower Ag thresholds for stopping MDAs generally mean a higher probability of local elimination, reducing long-term costs and health impacts. However, they may also lead to an increased number of MDA rounds required to reach the lower threshold and, therefore, increased short-term costs. Collectively, our analyses highlight that lower target Ag thresholds have the potential to assist programs in achieving lymphatic filariasis goals.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/cid/ciae108; html:https://europepmc.org/articles/PMC11045020; pdf:https://europepmc.org/articles/PMC11045020?pdf=render" - }, { "id": "37158960", "doi": "https://doi.org/10.1186/s40168-023-01518-w", @@ -10318,6 +10301,23 @@ "laySummary": "", "urls": "pdf:https://microbiomejournal.biomedcentral.com/counter/pdf/10.1186/s40168-023-01518-w; doi:https://doi.org/10.1186/s40168-023-01518-w; html:https://europepmc.org/articles/PMC10165813; pdf:https://europepmc.org/articles/PMC10165813?pdf=render" }, + { + "id": "38662697", + "doi": "https://doi.org/10.1093/cid/ciae108", + "title": "Reducing the Antigen Prevalence Target Threshold for Stopping and Restarting Mass Drug Administration for Lymphatic Filariasis Elimination: A Model-Based Cost-effectiveness Simulation in Tanzania, India and Haiti.", + "authorString": "Antony Oliver MC, Graham M, Gass KM, Medley GF, Clark J, Davis EL, Reimer LJ, King JD, Pouwels KB, Hollingsworth TD.", + "authorAffiliations": "", + "journalTitle": "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America", + "pubYear": "2024", + "date": "2024-04-01", + "isOpenAccess": "Y", + "keywords": "Threshold; Modeling; Elimination; Health Economics; Lymphatic Filariasis", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

The Global Programme to Eliminate Lymphatic Filariasis (GPELF) aims to reduce and maintain infection levels through mass drug administration (MDA), but there is evidence of ongoing transmission after MDA in areas where Culex mosquitoes are the main transmission vector, suggesting that a more stringent criterion is required for MDA decision making in these settings.

Methods

We use a transmission model to investigate how a lower prevalence threshold (<1% antigenemia [Ag] prevalence compared with <2% Ag prevalence) for MDA decision making would affect the probability of local elimination, health outcomes, the number of MDA rounds, including restarts, and program costs associated with MDA and surveys across different scenarios. To determine the cost-effectiveness of switching to a lower threshold, we simulated 65% and 80% MDA coverage of the total population for different willingness to pay per disability-adjusted life-year averted for India ($446.07), Tanzania ($389.83), and Haiti ($219.84).

Results

Our results suggest that with a lower Ag threshold, there is a small proportion of simulations where extra rounds are required to reach the target, but this also reduces the need to restart MDA later in the program. For 80% coverage, the lower threshold is cost-effective across all baseline prevalences for India, Tanzania, and Haiti. For 65% MDA coverage, the lower threshold is not cost-effective due to additional MDA rounds, although it increases the probability of local elimination. Valuing the benefits of elimination to align with the GPELF goals, we find that a willingness to pay per capita government expenditure of approximately $1000-$4000 for 1% increase in the probability of local elimination would be required to make a lower threshold cost-effective.

Conclusions

Lower Ag thresholds for stopping MDAs generally mean a higher probability of local elimination, reducing long-term costs and health impacts. However, they may also lead to an increased number of MDA rounds required to reach the lower threshold and, therefore, increased short-term costs. Collectively, our analyses highlight that lower target Ag thresholds have the potential to assist programs in achieving lymphatic filariasis goals.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/cid/ciae108; html:https://europepmc.org/articles/PMC11045020; pdf:https://europepmc.org/articles/PMC11045020?pdf=render" + }, { "id": "33623985", "doi": "https://doi.org/10.1093/cid/ciab159", @@ -10386,23 +10386,6 @@ "laySummary": "", "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02190-3; doi:https://doi.org/10.1186/s12916-021-02190-3; html:https://europepmc.org/articles/PMC8632563; pdf:https://europepmc.org/articles/PMC8632563?pdf=render" }, - { - "id": "37185641", - "doi": "https://doi.org/10.1136/bmjopen-2022-070022", - "title": "EXAcerbations of COPD and their OutcomeS on CardioVascular diseases (EXACOS-CV) Programme: protocol of multicountry observational cohort studies.", - "authorString": "Nordon C, Rhodes K, Quint JK, Vogelmeier CF, Simons SO, Hawkins NM, Marshall J, Ouwens M, Garbe E, M\u00fcllerov\u00e1 H.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2023", - "date": "2023-04-26", - "isOpenAccess": "Y", - "keywords": "epidemiology; Cardiology; Vascular Medicine; Chronic Airways Disease", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

In patients with chronic obstructive pulmonary disease (COPD), the risk of certain cardiovascular (CV) events is increased by threefold to fivefold in the year following acute exacerbation of COPD (AECOPD), compared with a non-exacerbation period. While the effect of severe AECOPD is well established, the relationship of moderate exacerbation or prior exacerbation to elevated risk of CV events is less clear. We will conduct cohort studies in multiple countries to further characterise the association between AECOPD and CV events.

Methods and analysis

Retrospective longitudinal cohort studies will be conducted within routinely collected electronic healthcare records or claims databases. The study cohorts will include patients meeting inclusion criteria for COPD between 1 January 2014 and 31 December 2018. Moderate exacerbation is defined as an outpatient visit and/or medication dispensation/prescription for exacerbation; severe exacerbation is defined as hospitalisation for COPD. The primary outcomes of interest are the time to (1) first hospitalisation for a CV event (including acute coronary syndrome, heart failure, arrhythmias or cerebral ischaemia) since cohort entry or (2) death. Time-dependent Cox proportional hazards models will compare the hazard of a CV event between exposed periods following exacerbation (split into these periods: 1-7, 8-14, 15-30, 31-180 and 181-365 days) and the unexposed reference time period, adjusted on time-fixed and time-varying confounders.

Ethics and dissemination

Studies have been approved in Canada, Japan, the Netherlands, Spain and the UK, where an institutional review board is mandated. For each study, the results will be published in peer-reviewed journals.", - "laySummary": "", - "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e070022.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-070022; html:https://europepmc.org/articles/PMC10151875; pdf:https://europepmc.org/articles/PMC10151875?pdf=render" - }, { "id": "30928998", "doi": "https://doi.org/10.4193/rhin18.237", @@ -10420,6 +10403,23 @@ "laySummary": "", "urls": "pdf:https://www.rhinologyjournal.com/download.php?id=1882; doi:https://doi.org/10.4193/Rhin18.237" }, + { + "id": "37185641", + "doi": "https://doi.org/10.1136/bmjopen-2022-070022", + "title": "EXAcerbations of COPD and their OutcomeS on CardioVascular diseases (EXACOS-CV) Programme: protocol of multicountry observational cohort studies.", + "authorString": "Nordon C, Rhodes K, Quint JK, Vogelmeier CF, Simons SO, Hawkins NM, Marshall J, Ouwens M, Garbe E, M\u00fcllerov\u00e1 H.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2023", + "date": "2023-04-26", + "isOpenAccess": "Y", + "keywords": "epidemiology; Cardiology; Vascular Medicine; Chronic Airways Disease", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

In patients with chronic obstructive pulmonary disease (COPD), the risk of certain cardiovascular (CV) events is increased by threefold to fivefold in the year following acute exacerbation of COPD (AECOPD), compared with a non-exacerbation period. While the effect of severe AECOPD is well established, the relationship of moderate exacerbation or prior exacerbation to elevated risk of CV events is less clear. We will conduct cohort studies in multiple countries to further characterise the association between AECOPD and CV events.

Methods and analysis

Retrospective longitudinal cohort studies will be conducted within routinely collected electronic healthcare records or claims databases. The study cohorts will include patients meeting inclusion criteria for COPD between 1 January 2014 and 31 December 2018. Moderate exacerbation is defined as an outpatient visit and/or medication dispensation/prescription for exacerbation; severe exacerbation is defined as hospitalisation for COPD. The primary outcomes of interest are the time to (1) first hospitalisation for a CV event (including acute coronary syndrome, heart failure, arrhythmias or cerebral ischaemia) since cohort entry or (2) death. Time-dependent Cox proportional hazards models will compare the hazard of a CV event between exposed periods following exacerbation (split into these periods: 1-7, 8-14, 15-30, 31-180 and 181-365 days) and the unexposed reference time period, adjusted on time-fixed and time-varying confounders.

Ethics and dissemination

Studies have been approved in Canada, Japan, the Netherlands, Spain and the UK, where an institutional review board is mandated. For each study, the results will be published in peer-reviewed journals.", + "laySummary": "", + "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e070022.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-070022; html:https://europepmc.org/articles/PMC10151875; pdf:https://europepmc.org/articles/PMC10151875?pdf=render" + }, { "id": "35151397", "doi": "https://doi.org/10.1016/s0140-6736(22)00163-5", @@ -10794,23 +10794,6 @@ "laySummary": "", "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00127-022-02393-w.pdf; doi:https://doi.org/10.1007/s00127-022-02393-w; html:https://europepmc.org/articles/PMC9702612; pdf:https://europepmc.org/articles/PMC9702612?pdf=render" }, - { - "id": "35836669", - "doi": "https://doi.org/10.1097/txd.0000000000001188", - "title": "HLA Alleles Cw12 and DQ4 in Kidney Transplant Recipients Are Independent Risk Factors for the Development of Posttransplantation Diabetes.", - "authorString": "Phagura N, Hussain A, Culliford A, Hodson J, Evison F, Gallier S, Borrows R, Lane HA, Briggs D, Sharif A.", - "authorAffiliations": "", - "journalTitle": "Transplantation direct", - "pubYear": "2021", - "date": "2021-07-23", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The association between specific HLA alleles and risk for posttransplantation diabetes (PTDM) in a contemporary and multiethnic kidney transplant recipient cohort is not clear.

Methods

In this single-center analysis, data were retrospectively analyzed for 1560 nondiabetic kidney transplant recipients at a single center between 2007 and 2018, with median follow-up of 33 mo (interquartile range 8-73). HLA typing methodology was by DNA analysis and reported at the resolution required for the national allocation scheme. Diagnosis of PTDM was aligned with International Consensus recommendations.

Results

PTDM developed in 231 kidney transplant recipients. Exploring 99 HLA alleles, the presence of Cw12, B52, B38, B58, DQ4, A80, and DR13 and the absence of DQ3 and DR04 were associated with significant increases in PTDM risk. In a multivariable Cox regression model, adjusting for other clinical risk factors for PTDM, the presence of Cw12 (hazard ratio [HR], 1.57; 95% CI, 1.08-2.27; P\u2009=\u20090.017) and DQ4 (HR, 1.78; 95% CI, 1.07-2.96; P\u2009=\u20090.026) were found to be independent risk factors for PTDM. There was also evidence that the presence of B58 increases PTDM risk within the subgroup of recipients of White ethnicity (HR, 5.01; 95% CI, 2.20-11.42; P\u2009<\u20090.001).

Conclusion

Our data suggest that specific HLA alleles can be associated with PTDM risk, which can be used pretransplantation for PTDM risk stratification. However, association is not causality, and this work requires replication and further investigation to understand underlying biological mechanisms.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1097/txd.0000000000001188; doi:https://doi.org/10.1097/TXD.0000000000001188; html:https://europepmc.org/articles/PMC9276282; pdf:https://europepmc.org/articles/PMC9276282?pdf=render" - }, { "id": "31818272", "doi": "https://doi.org/10.1186/s12889-019-8015-3", @@ -10828,6 +10811,23 @@ "laySummary": "This longitudinal study investigated whether and to what extent consumption by beverage type, BMI, smoking and other factors explained inequalities in alcohol-related hospital admission (ARHA). Using statistical analysis methods, it was found that people living in more deprived areas had a higher risk of ARHA compared to less deprived. Smokers and people currently being treated for mental illness had higher risk of ARHA, while BMI appeared to be slightly protective. ", "urls": "pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-019-8015-3; doi:https://doi.org/10.1186/s12889-019-8015-3; html:https://europepmc.org/articles/PMC6902530; pdf:https://europepmc.org/articles/PMC6902530?pdf=render" }, + { + "id": "35836669", + "doi": "https://doi.org/10.1097/txd.0000000000001188", + "title": "HLA Alleles Cw12 and DQ4 in Kidney Transplant Recipients Are Independent Risk Factors for the Development of Posttransplantation Diabetes.", + "authorString": "Phagura N, Hussain A, Culliford A, Hodson J, Evison F, Gallier S, Borrows R, Lane HA, Briggs D, Sharif A.", + "authorAffiliations": "", + "journalTitle": "Transplantation direct", + "pubYear": "2021", + "date": "2021-07-23", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The association between specific HLA alleles and risk for posttransplantation diabetes (PTDM) in a contemporary and multiethnic kidney transplant recipient cohort is not clear.

Methods

In this single-center analysis, data were retrospectively analyzed for 1560 nondiabetic kidney transplant recipients at a single center between 2007 and 2018, with median follow-up of 33 mo (interquartile range 8-73). HLA typing methodology was by DNA analysis and reported at the resolution required for the national allocation scheme. Diagnosis of PTDM was aligned with International Consensus recommendations.

Results

PTDM developed in 231 kidney transplant recipients. Exploring 99 HLA alleles, the presence of Cw12, B52, B38, B58, DQ4, A80, and DR13 and the absence of DQ3 and DR04 were associated with significant increases in PTDM risk. In a multivariable Cox regression model, adjusting for other clinical risk factors for PTDM, the presence of Cw12 (hazard ratio [HR], 1.57; 95% CI, 1.08-2.27; P\u2009=\u20090.017) and DQ4 (HR, 1.78; 95% CI, 1.07-2.96; P\u2009=\u20090.026) were found to be independent risk factors for PTDM. There was also evidence that the presence of B58 increases PTDM risk within the subgroup of recipients of White ethnicity (HR, 5.01; 95% CI, 2.20-11.42; P\u2009<\u20090.001).

Conclusion

Our data suggest that specific HLA alleles can be associated with PTDM risk, which can be used pretransplantation for PTDM risk stratification. However, association is not causality, and this work requires replication and further investigation to understand underlying biological mechanisms.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1097/txd.0000000000001188; doi:https://doi.org/10.1097/TXD.0000000000001188; html:https://europepmc.org/articles/PMC9276282; pdf:https://europepmc.org/articles/PMC9276282?pdf=render" + }, { "id": "31612961", "doi": "https://doi.org/10.1093/nar/gkz895", @@ -11100,23 +11100,6 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0241800&type=printable; doi:https://doi.org/10.1371/journal.pone.0241800; html:https://europepmc.org/articles/PMC7644261; pdf:https://europepmc.org/articles/PMC7644261?pdf=render" }, - { - "id": "36713473", - "doi": "https://doi.org/10.1093/ofid/ofac694", - "title": "Clinical Effectiveness of SARS-CoV-2 Booster Vaccine Against Omicron Infection in Residents and Staff of Long-term Care Facilities: A Prospective Cohort Study (VIVALDI).", - "authorString": "Stirrup O, Shrotri M, Adams NL, Krutikov M, Nacer-Laidi H, Azmi B, Palmer T, Fuller C, Irwin-Singer A, Baynton V, Tut G, Moss P, Hayward A, Copas A, Shallcross L.", - "authorAffiliations": "", - "journalTitle": "Open forum infectious diseases", - "pubYear": "2023", - "date": "2022-12-29", - "isOpenAccess": "Y", - "keywords": "Vaccine Effectiveness; Long-term Care Facilities; Covid-19; Sars-cov-2; Omicron", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Successive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have caused severe disease in long-term care facility (LTCF) residents. Primary vaccination provides strong short-term protection, but data are limited on duration of protection following booster vaccines, particularly against the Omicron variant. We investigated the effectiveness of booster vaccination against infections, hospitalizations, and deaths among LTCF residents and staff in England.

Methods

We included residents and staff of LTCFs within the VIVALDI study (ISRCTN 14447421) who underwent routine, asymptomatic testing (December 12, 2021-March 31, 2022). Cox regression was used to estimate relative hazards of SARS-CoV-2 infection, and associated hospitalization and death at 0-13, 14-48, 49-83, 84-111, 112-139, and 140+ days after dose 3 of SARS-CoV-2 vaccination compared with 2 doses (after 84+ days), stratified by previous SARS-CoV-2 infection and adjusting for age, sex, LTCF capacity, and local SARS-CoV-2 incidence.

Results

A total of 14 175 residents and 19 793 staff were included. In residents without prior SARS-CoV-2 infection, infection risk was reduced 0-111 days after the first booster, but no protection was apparent after 112 days. Additional protection following booster vaccination waned but was still present at 140+ days for COVID-associated hospitalization (adjusted hazard ratio [aHR], 0.20; 95% CI, 0.06-0.63) and death (aHR, 0.50; 95% CI, 0.20-1.27). Most residents (64.4%) had received primary course vaccine of AstraZeneca, but this did not impact pre- or postbooster risk. Staff showed a similar pattern of waning booster effectiveness against infection, with few hospitalizations and no deaths.

Conclusions

Our findings suggest that booster vaccination provided sustained protection against severe outcomes following infection with the Omicron variant, but no protection against infection from 4 months onwards. Ongoing surveillance for SARS-CoV-2 in LTCFs is crucial.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/ofid/article-pdf/10/1/ofac694/48846221/ofac694.pdf; doi:https://doi.org/10.1093/ofid/ofac694; html:https://europepmc.org/articles/PMC9874026; pdf:https://europepmc.org/articles/PMC9874026?pdf=render" - }, { "id": "33185672", "doi": "https://doi.org/10.1093/jamia/ocaa295", @@ -11134,6 +11117,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/jamia/article-pdf/28/4/791/41182395/ocaa295.pdf; doi:https://doi.org/10.1093/jamia/ocaa295; html:https://europepmc.org/articles/PMC7717299; pdf:https://europepmc.org/articles/PMC7717299?pdf=render" }, + { + "id": "36713473", + "doi": "https://doi.org/10.1093/ofid/ofac694", + "title": "Clinical Effectiveness of SARS-CoV-2 Booster Vaccine Against Omicron Infection in Residents and Staff of Long-term Care Facilities: A Prospective Cohort Study (VIVALDI).", + "authorString": "Stirrup O, Shrotri M, Adams NL, Krutikov M, Nacer-Laidi H, Azmi B, Palmer T, Fuller C, Irwin-Singer A, Baynton V, Tut G, Moss P, Hayward A, Copas A, Shallcross L.", + "authorAffiliations": "", + "journalTitle": "Open forum infectious diseases", + "pubYear": "2023", + "date": "2022-12-29", + "isOpenAccess": "Y", + "keywords": "Vaccine Effectiveness; Long-term Care Facilities; Covid-19; Sars-cov-2; Omicron", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Successive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have caused severe disease in long-term care facility (LTCF) residents. Primary vaccination provides strong short-term protection, but data are limited on duration of protection following booster vaccines, particularly against the Omicron variant. We investigated the effectiveness of booster vaccination against infections, hospitalizations, and deaths among LTCF residents and staff in England.

Methods

We included residents and staff of LTCFs within the VIVALDI study (ISRCTN 14447421) who underwent routine, asymptomatic testing (December 12, 2021-March 31, 2022). Cox regression was used to estimate relative hazards of SARS-CoV-2 infection, and associated hospitalization and death at 0-13, 14-48, 49-83, 84-111, 112-139, and 140+ days after dose 3 of SARS-CoV-2 vaccination compared with 2 doses (after 84+ days), stratified by previous SARS-CoV-2 infection and adjusting for age, sex, LTCF capacity, and local SARS-CoV-2 incidence.

Results

A total of 14 175 residents and 19 793 staff were included. In residents without prior SARS-CoV-2 infection, infection risk was reduced 0-111 days after the first booster, but no protection was apparent after 112 days. Additional protection following booster vaccination waned but was still present at 140+ days for COVID-associated hospitalization (adjusted hazard ratio [aHR], 0.20; 95% CI, 0.06-0.63) and death (aHR, 0.50; 95% CI, 0.20-1.27). Most residents (64.4%) had received primary course vaccine of AstraZeneca, but this did not impact pre- or postbooster risk. Staff showed a similar pattern of waning booster effectiveness against infection, with few hospitalizations and no deaths.

Conclusions

Our findings suggest that booster vaccination provided sustained protection against severe outcomes following infection with the Omicron variant, but no protection against infection from 4 months onwards. Ongoing surveillance for SARS-CoV-2 in LTCFs is crucial.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/ofid/article-pdf/10/1/ofac694/48846221/ofac694.pdf; doi:https://doi.org/10.1093/ofid/ofac694; html:https://europepmc.org/articles/PMC9874026; pdf:https://europepmc.org/articles/PMC9874026?pdf=render" + }, { "id": "33728401", "doi": "https://doi.org/10.1038/s42254-020-0178-4", @@ -11525,23 +11525,6 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jmri.28675; doi:https://doi.org/10.1002/jmri.28675; html:https://europepmc.org/articles/PMC10947470; pdf:https://europepmc.org/articles/PMC10947470?pdf=render" }, - { - "id": "38849195", - "doi": "https://doi.org/10.1136/archdischild-2023-326756", - "title": "Utility and acceptability of remote 6-lead electrocardiographic monitoring in children with inherited cardiac conditions.", - "authorString": "Lawley CM, Luczak-Wozniak K, Chung SC, Field E, Barnes A, Starling L, Cervi E, Kaski JP.", - "authorAffiliations": "", - "journalTitle": "Archives of disease in childhood", - "pubYear": "2024", - "date": "2024-06-07", - "isOpenAccess": "N", - "keywords": "Cardiology; Paediatrics", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

This pilot study sought to investigate the utility and acceptability of the KardiaMobile 6-lead ECG (KM6LECG) as a tool for remote monitoring in children with inherited cardiac conditions.

Design

A single-centre prospective cohort study. Children underwent standard clinical evaluation including a 12-lead ECG and a KM6LECG in the clinic. Participants recorded KM6LECGs monthly at home for 3 months. Families completed a questionnaire on their experience.

Setting

Great Ormond Street Hospital Centre for Inherited Cardiovascular Diseases.

Participants

64 children: 22 with hypertrophic cardiomyopathy (HCM); 22 with long QT syndrome and 20 unaffected siblings (controls).

Main outcome measures

Comparison of data extracted from the clinic 12-lead ECG and supervised KM6LECG, and the supervised and unsupervised KM6LECG recording.

Results

Of 64 children (35% female, mean age 12 years), 58 had a baseline 12-lead ECG and appropriate baseline KM6LECG. In children with HCM, abnormalities in ventricular depolarisation/repolarisation in the limb leads of the 12-lead ECG were reliably reproduced. From the whole cohort, there was a strong positive correlation between the corrected QT interval from the 12-lead ECG and baseline KM6LECG (intraclass correlation coefficient=0.839) and baseline KM6LECG with an unsupervised KM6LECG (intraclass correlation coefficient=0.736). Suspected 'lead' misplacement impacted 18% of unsupervised recordings. Overall, the acceptability of the KM6LECG to families was good.

Conclusions

The KM6LECG provides an accurate tool for assessing some ECG abnormalities associated with paediatric inherited cardiovascular disease and may provide a useful at-home adjunct to face-to-face clinical care of children requiring ECG assessment.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/archdischild-2023-326756" - }, { "id": "37650026", "doi": "https://doi.org/10.23889/ijpds.v7i1.1727", @@ -11559,6 +11542,23 @@ "laySummary": "", "urls": "pdf:https://ijpds.org/article/download/1727/3395; doi:https://doi.org/10.23889/ijpds.v7i1.1727; html:https://europepmc.org/articles/PMC10464868; pdf:https://europepmc.org/articles/PMC10464868?pdf=render" }, + { + "id": "38849195", + "doi": "https://doi.org/10.1136/archdischild-2023-326756", + "title": "Utility and acceptability of remote 6-lead electrocardiographic monitoring in children with inherited cardiac conditions.", + "authorString": "Lawley CM, Luczak-Wozniak K, Chung SC, Field E, Barnes A, Starling L, Cervi E, Kaski JP.", + "authorAffiliations": "", + "journalTitle": "Archives of disease in childhood", + "pubYear": "2024", + "date": "2024-06-07", + "isOpenAccess": "N", + "keywords": "Cardiology; Paediatrics", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

This pilot study sought to investigate the utility and acceptability of the KardiaMobile 6-lead ECG (KM6LECG) as a tool for remote monitoring in children with inherited cardiac conditions.

Design

A single-centre prospective cohort study. Children underwent standard clinical evaluation including a 12-lead ECG and a KM6LECG in the clinic. Participants recorded KM6LECGs monthly at home for 3 months. Families completed a questionnaire on their experience.

Setting

Great Ormond Street Hospital Centre for Inherited Cardiovascular Diseases.

Participants

64 children: 22 with hypertrophic cardiomyopathy (HCM); 22 with long QT syndrome and 20 unaffected siblings (controls).

Main outcome measures

Comparison of data extracted from the clinic 12-lead ECG and supervised KM6LECG, and the supervised and unsupervised KM6LECG recording.

Results

Of 64 children (35% female, mean age 12 years), 58 had a baseline 12-lead ECG and appropriate baseline KM6LECG. In children with HCM, abnormalities in ventricular depolarisation/repolarisation in the limb leads of the 12-lead ECG were reliably reproduced. From the whole cohort, there was a strong positive correlation between the corrected QT interval from the 12-lead ECG and baseline KM6LECG (intraclass correlation coefficient=0.839) and baseline KM6LECG with an unsupervised KM6LECG (intraclass correlation coefficient=0.736). Suspected 'lead' misplacement impacted 18% of unsupervised recordings. Overall, the acceptability of the KM6LECG to families was good.

Conclusions

The KM6LECG provides an accurate tool for assessing some ECG abnormalities associated with paediatric inherited cardiovascular disease and may provide a useful at-home adjunct to face-to-face clinical care of children requiring ECG assessment.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/archdischild-2023-326756" + }, { "id": "33632765", "doi": "https://doi.org/10.1136/thoraxjnl-2020-215986", @@ -11763,23 +11763,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/S0140-6736(24)00537-3" }, - { - "id": "37678576", - "doi": "https://doi.org/10.1016/j.jaci.2023.08.025", - "title": "E-cigarette vapor renders neutrophils dysfunctional due to filamentous actin accumulation.", - "authorString": "Jasper AE, Faniyi AA, Davis LC, Grudzinska FS, Halston R, Hazeldine J, Parekh D, Sapey E, Thickett DR, Scott A.", - "authorAffiliations": "", - "journalTitle": "The Journal of allergy and clinical immunology", - "pubYear": "2024", - "date": "2023-09-05", - "isOpenAccess": "N", - "keywords": "Neutrophils; Phagocytosis; Oxidative burst; Nicotine; Netosis; E-cigarettes", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Electronic cigarette (e-cigarette) use continues to rise despite concerns of long-term effects, especially the risk of developing lung diseases such as chronic obstructive pulmonary disease. Neutrophils are central to the pathogenesis of chronic obstructive pulmonary disease, with changes in phenotype and function implicated in tissue damage.

Objective

We sought to measure the impact of direct exposure to nicotine-containing and nicotine-free e-cigarette vapor on human neutrophil function and phenotype.

Methods

Neutrophils were isolated from the whole blood of self-reported nonsmoking, nonvaping healthy volunteers. Neutrophils were exposed to 40 puffs of e-cigarette vapor generated from e-cigarette devices using flavorless e-cigarette liquids with and without nicotine before functions, deformability, and phenotype were assessed.

Results

Neutrophil surface marker expression was altered, with CD62L and CXCR2 expression significantly reduced in neutrophils treated with e-cigarette vapor containing nicotine. Neutrophil migration to IL-8, phagocytosis of Escherichia coli and Staphylococcus aureus pHrodo bioparticles, oxidative burst response, and phorbol 12-myristate 13-acetate-stimulated neutrophil extracellular trap formation were all significantly reduced by e-cigarette vapor treatments, independent of nicotine content. E-cigarette vapor induced increased levels of baseline polymerized filamentous actin levels in the cytoplasm, compared with untreated controls.

Conclusions

The significant reduction in effector neutrophil functions after exposure to high-power e-cigarette devices, even in the absence of nicotine, is associated with excessive filamentous actin polymerization. This highlights the potentially damaging impact of vaping on respiratory health and reinforces the urgency of research to uncover the long-term health implications of e-cigarettes.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jaci.2023.08.025" - }, { "id": "35443953", "doi": "https://doi.org/10.1136/bmjopen-2021-056523", @@ -11797,6 +11780,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e056523.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-056523; html:https://europepmc.org/articles/PMC9021768; pdf:https://europepmc.org/articles/PMC9021768?pdf=render" }, + { + "id": "37678576", + "doi": "https://doi.org/10.1016/j.jaci.2023.08.025", + "title": "E-cigarette vapor renders neutrophils dysfunctional due to filamentous actin accumulation.", + "authorString": "Jasper AE, Faniyi AA, Davis LC, Grudzinska FS, Halston R, Hazeldine J, Parekh D, Sapey E, Thickett DR, Scott A.", + "authorAffiliations": "", + "journalTitle": "The Journal of allergy and clinical immunology", + "pubYear": "2024", + "date": "2023-09-05", + "isOpenAccess": "N", + "keywords": "Neutrophils; Phagocytosis; Oxidative burst; Nicotine; Netosis; E-cigarettes", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Electronic cigarette (e-cigarette) use continues to rise despite concerns of long-term effects, especially the risk of developing lung diseases such as chronic obstructive pulmonary disease. Neutrophils are central to the pathogenesis of chronic obstructive pulmonary disease, with changes in phenotype and function implicated in tissue damage.

Objective

We sought to measure the impact of direct exposure to nicotine-containing and nicotine-free e-cigarette vapor on human neutrophil function and phenotype.

Methods

Neutrophils were isolated from the whole blood of self-reported nonsmoking, nonvaping healthy volunteers. Neutrophils were exposed to 40 puffs of e-cigarette vapor generated from e-cigarette devices using flavorless e-cigarette liquids with and without nicotine before functions, deformability, and phenotype were assessed.

Results

Neutrophil surface marker expression was altered, with CD62L and CXCR2 expression significantly reduced in neutrophils treated with e-cigarette vapor containing nicotine. Neutrophil migration to IL-8, phagocytosis of Escherichia coli and Staphylococcus aureus pHrodo bioparticles, oxidative burst response, and phorbol 12-myristate 13-acetate-stimulated neutrophil extracellular trap formation were all significantly reduced by e-cigarette vapor treatments, independent of nicotine content. E-cigarette vapor induced increased levels of baseline polymerized filamentous actin levels in the cytoplasm, compared with untreated controls.

Conclusions

The significant reduction in effector neutrophil functions after exposure to high-power e-cigarette devices, even in the absence of nicotine, is associated with excessive filamentous actin polymerization. This highlights the potentially damaging impact of vaping on respiratory health and reinforces the urgency of research to uncover the long-term health implications of e-cigarettes.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.jaci.2023.08.025" + }, { "id": "35383067", "doi": "https://doi.org/10.1136/bmjopen-2021-055447", @@ -11815,38 +11815,38 @@ "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e055447.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055447; html:https://europepmc.org/articles/PMC8984034; pdf:https://europepmc.org/articles/PMC8984034?pdf=render" }, { - "id": "38689316", - "doi": "https://doi.org/10.1186/s13643-024-02540-1", - "title": "Correction: Patient\u2011reported outcome (PRO) instruments used in patients undergoing adoptive cell therapy (ACT) for the treatment of cancer: a systematic review.", - "authorString": "Taylor S, Law K, Coomber-Moore J, Davies M, Thistlethwaite F, Calvert M, Aiyegbusi O, Yorke J.", + "id": "37398988", + "doi": "https://doi.org/10.1007/s40258-023-00821-9", + "title": "Correction to: The False Economy of Seeking to Eliminate Delayed Transfers of Care: Some Lessons from Queueing Theory.", + "authorString": "Wood RM, Harper AL, Onen-Dumlu Z, Forte PG, Pitt M, Vasilakis C.", "authorAffiliations": "", - "journalTitle": "Systematic reviews", - "pubYear": "2024", - "date": "2024-04-30", + "journalTitle": "Applied health economics and health policy", + "pubYear": "2023", + "date": "2023-09-01", "isOpenAccess": "Y", "keywords": "", "nationalPriorities": "", "healthCategories": "", "abstract": "", "laySummary": "", - "urls": "pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-024-02540-1; doi:https://doi.org/10.1186/s13643-024-02540-1; html:https://europepmc.org/articles/PMC11059719; pdf:https://europepmc.org/articles/PMC11059719?pdf=render" + "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s40258-023-00821-9.pdf; doi:https://doi.org/10.1007/s40258-023-00821-9; html:https://europepmc.org/articles/PMC10403424; pdf:https://europepmc.org/articles/PMC10403424?pdf=render" }, { - "id": "37398988", - "doi": "https://doi.org/10.1007/s40258-023-00821-9", - "title": "Correction to: The False Economy of Seeking to Eliminate Delayed Transfers of Care: Some Lessons from Queueing Theory.", - "authorString": "Wood RM, Harper AL, Onen-Dumlu Z, Forte PG, Pitt M, Vasilakis C.", + "id": "38689316", + "doi": "https://doi.org/10.1186/s13643-024-02540-1", + "title": "Correction: Patient\u2011reported outcome (PRO) instruments used in patients undergoing adoptive cell therapy (ACT) for the treatment of cancer: a systematic review.", + "authorString": "Taylor S, Law K, Coomber-Moore J, Davies M, Thistlethwaite F, Calvert M, Aiyegbusi O, Yorke J.", "authorAffiliations": "", - "journalTitle": "Applied health economics and health policy", - "pubYear": "2023", - "date": "2023-09-01", + "journalTitle": "Systematic reviews", + "pubYear": "2024", + "date": "2024-04-30", "isOpenAccess": "Y", "keywords": "", "nationalPriorities": "", "healthCategories": "", "abstract": "", "laySummary": "", - "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s40258-023-00821-9.pdf; doi:https://doi.org/10.1007/s40258-023-00821-9; html:https://europepmc.org/articles/PMC10403424; pdf:https://europepmc.org/articles/PMC10403424?pdf=render" + "urls": "pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-024-02540-1; doi:https://doi.org/10.1186/s13643-024-02540-1; html:https://europepmc.org/articles/PMC11059719; pdf:https://europepmc.org/articles/PMC11059719?pdf=render" }, { "id": "PMC9645061", @@ -12035,23 +12035,6 @@ "laySummary": "", "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/F22DF5FD826B1626B9873013DBAFF82B/S0924933821022550a.pdf/div-class-title-investigating-the-association-between-physical-health-comorbidities-and-disability-in-individuals-with-severe-mental-illness-div.pdf; doi:https://doi.org/10.1192/j.eurpsy.2021.2255; html:https://europepmc.org/articles/PMC8727716; pdf:https://europepmc.org/articles/PMC8727716?pdf=render" }, - { - "id": "38216198", - "doi": "https://doi.org/10.1136/bmjopen-2023-080410", - "title": "Rationale and design of the THIRST Alert feasibility study: a pragmatic, single-centre, parallel-group randomised controlled trial of an interruptive alert for oral fluid restriction in patients treated with intravenous furosemide.", - "authorString": "Chen Y, Shah A, Jani Y, Higgins D, Saleem N, Chafer K, Sydes MR, Asselbergs FW, Lumbers RT.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2024", - "date": "2024-01-11", - "isOpenAccess": "Y", - "keywords": "Randomized controlled trial; Heart Failure; Electronic Health Records; Feasibility Studies", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

Acute heart failure (HF) is a major cause of unplanned hospitalisation characterised by excess body water. A restriction in oral fluid intake is commonly imposed on patients as an adjunct to pharmacological therapy with loop diuretics, but there is a lack of evidence from traditional randomised controlled trials (RCTs) to support the safety and effectiveness of this intervention in the acute setting.This study aims to explore the feasibility of using computer alerts within the electronic health record (EHR) system to invite clinical care teams to enrol patients into a pragmatic RCT at the time of clinical decision-making. It will additionally assess the effectiveness of using an alert to help address the clinical research question of whether oral fluid restriction is a safe and effective adjunct to pharmacological therapy for patients admitted with fluid overload.

Methods and analysis

THIRST (Randomised Controlled Trial within the electronic Health record of an Interruptive alert displaying a fluid Restriction Suggestion in patients with the treatable Trait of congestion) Alert is a single-centre, parallel-group, open-label pragmatic RCT embedded in the EHR system that will be conducted as a feasibility study at an National Health Service (NHS) hospital in London. The clinical care team will be invited to enrol suitable patients in the study using a point-of-care alert with a target sample size of 50 patients. Enrolled patients will then be randomised to either restricted or unrestricted oral fluid intake. Two primary outcomes will be explored (1) the proportion of eligible patients enrolled in the study and (2) the mean difference in oral fluid intake between randomised groups. A series of secondary outcomes are specified to evaluate the effectiveness of the alert, adherence to the randomised treatment allocation and the quality of data generated from routine care, relevant to the outcomes of interest.

Ethics and dissemination

This study was approved by Riverside Research Ethics Committee (Ref: 22/LO/0889) and will be published on completion.

Trial registration number

NCT05869656.", - "laySummary": "", - "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/14/1/e080410.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-080410; html:https://europepmc.org/articles/PMC10806795; pdf:https://europepmc.org/articles/PMC10806795?pdf=render" - }, { "id": "37667866", "doi": "https://doi.org/10.1111/cen.14966", @@ -12069,6 +12052,23 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cen.14966; doi:https://doi.org/10.1111/cen.14966; html:https://europepmc.org/articles/PMC7615603; pdf:https://europepmc.org/articles/PMC7615603?pdf=render" }, + { + "id": "38216198", + "doi": "https://doi.org/10.1136/bmjopen-2023-080410", + "title": "Rationale and design of the THIRST Alert feasibility study: a pragmatic, single-centre, parallel-group randomised controlled trial of an interruptive alert for oral fluid restriction in patients treated with intravenous furosemide.", + "authorString": "Chen Y, Shah A, Jani Y, Higgins D, Saleem N, Chafer K, Sydes MR, Asselbergs FW, Lumbers RT.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2024", + "date": "2024-01-11", + "isOpenAccess": "Y", + "keywords": "Randomized controlled trial; Heart Failure; Electronic Health Records; Feasibility Studies", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

Acute heart failure (HF) is a major cause of unplanned hospitalisation characterised by excess body water. A restriction in oral fluid intake is commonly imposed on patients as an adjunct to pharmacological therapy with loop diuretics, but there is a lack of evidence from traditional randomised controlled trials (RCTs) to support the safety and effectiveness of this intervention in the acute setting.This study aims to explore the feasibility of using computer alerts within the electronic health record (EHR) system to invite clinical care teams to enrol patients into a pragmatic RCT at the time of clinical decision-making. It will additionally assess the effectiveness of using an alert to help address the clinical research question of whether oral fluid restriction is a safe and effective adjunct to pharmacological therapy for patients admitted with fluid overload.

Methods and analysis

THIRST (Randomised Controlled Trial within the electronic Health record of an Interruptive alert displaying a fluid Restriction Suggestion in patients with the treatable Trait of congestion) Alert is a single-centre, parallel-group, open-label pragmatic RCT embedded in the EHR system that will be conducted as a feasibility study at an National Health Service (NHS) hospital in London. The clinical care team will be invited to enrol suitable patients in the study using a point-of-care alert with a target sample size of 50 patients. Enrolled patients will then be randomised to either restricted or unrestricted oral fluid intake. Two primary outcomes will be explored (1) the proportion of eligible patients enrolled in the study and (2) the mean difference in oral fluid intake between randomised groups. A series of secondary outcomes are specified to evaluate the effectiveness of the alert, adherence to the randomised treatment allocation and the quality of data generated from routine care, relevant to the outcomes of interest.

Ethics and dissemination

This study was approved by Riverside Research Ethics Committee (Ref: 22/LO/0889) and will be published on completion.

Trial registration number

NCT05869656.", + "laySummary": "", + "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/14/1/e080410.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-080410; html:https://europepmc.org/articles/PMC10806795; pdf:https://europepmc.org/articles/PMC10806795?pdf=render" + }, { "id": "38434152", "doi": "https://doi.org/10.5334/gh.1298", @@ -12256,23 +12256,6 @@ "laySummary": "", "urls": "pdf:https://discovery.ucl.ac.uk/10133388/1/1-s2.0-S2666756821001689-main.pdf; doi:https://doi.org/10.1016/S2666-7568(21)00168-9; html:https://europepmc.org/articles/PMC8376213" }, - { - "id": "36994768", - "doi": "https://doi.org/10.1002/cphy.c210037", - "title": "Autonomic Cardiovascular Control in Health and Disease.", - "authorString": "Karim S, Chahal A, Khanji MY, Petersen SE, Somers VK.", - "authorAffiliations": "", - "journalTitle": "Comprehensive Physiology", - "pubYear": "2023", - "date": "2023-03-30", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Autonomic neural control of the cardiovascular system is formed of complex and dynamic processes able to adjust rapidly to mitigate perturbations in hemodynamics and maintain homeostasis. Alterations in autonomic control feature in the development or progression of a multitude of diseases with wide-ranging physiological implications given the neural system's responsibility for controlling inotropy, chronotropy, lusitropy, and dromotropy. Imbalances in sympathetic and parasympathetic neural control are also implicated in the development of arrhythmia in several cardiovascular conditions sparking interest in autonomic modulation as a form of treatment. A number of measures of autonomic function have shown prognostic significance in health and in pathological states and have undergone varying degrees of refinement, yet adoption into clinical practice remains extremely limited. The focus of this contemporary narrative review is to summarize the anatomy, physiology, and pathophysiology of the cardiovascular autonomic nervous system and describe the merits and shortfalls of testing modalities available. \u00a9 2023 American Physiological Society. Compr Physiol 13:4493-4511, 2023.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1002/cphy.c210037; html:https://europepmc.org/articles/PMC10406398; pdf:https://europepmc.org/articles/PMC10406398?pdf=render; doi:https://doi.org/10.1002/cphy.c210037" - }, { "id": "34556677", "doi": "https://doi.org/10.1038/s41598-021-96189-8", @@ -12290,6 +12273,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41598-021-96189-8.pdf; doi:https://doi.org/10.1038/s41598-021-96189-8; html:https://europepmc.org/articles/PMC8460620; pdf:https://europepmc.org/articles/PMC8460620?pdf=render" }, + { + "id": "36994768", + "doi": "https://doi.org/10.1002/cphy.c210037", + "title": "Autonomic Cardiovascular Control in Health and Disease.", + "authorString": "Karim S, Chahal A, Khanji MY, Petersen SE, Somers VK.", + "authorAffiliations": "", + "journalTitle": "Comprehensive Physiology", + "pubYear": "2023", + "date": "2023-03-30", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Autonomic neural control of the cardiovascular system is formed of complex and dynamic processes able to adjust rapidly to mitigate perturbations in hemodynamics and maintain homeostasis. Alterations in autonomic control feature in the development or progression of a multitude of diseases with wide-ranging physiological implications given the neural system's responsibility for controlling inotropy, chronotropy, lusitropy, and dromotropy. Imbalances in sympathetic and parasympathetic neural control are also implicated in the development of arrhythmia in several cardiovascular conditions sparking interest in autonomic modulation as a form of treatment. A number of measures of autonomic function have shown prognostic significance in health and in pathological states and have undergone varying degrees of refinement, yet adoption into clinical practice remains extremely limited. The focus of this contemporary narrative review is to summarize the anatomy, physiology, and pathophysiology of the cardiovascular autonomic nervous system and describe the merits and shortfalls of testing modalities available. \u00a9 2023 American Physiological Society. Compr Physiol 13:4493-4511, 2023.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1002/cphy.c210037; html:https://europepmc.org/articles/PMC10406398; pdf:https://europepmc.org/articles/PMC10406398?pdf=render; doi:https://doi.org/10.1002/cphy.c210037" + }, { "id": "34894331", "doi": "https://doi.org/10.1007/s10461-021-03551-y", @@ -12358,23 +12358,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41467-022-35017-7.pdf; doi:https://doi.org/10.1038/s41467-022-35017-7; html:https://europepmc.org/articles/PMC9708841; pdf:https://europepmc.org/articles/PMC9708841?pdf=render" }, - { - "id": "37080566", - "doi": "https://doi.org/10.1183/13993003.01720-2022", - "title": "Collaboration between explainable artificial intelligence and pulmonologists improves the accuracy of pulmonary function test interpretation.", - "authorString": "Das N, Happaerts S, Gyselinck I, Staes M, Derom E, Brusselle G, Burgos F, Contoli M, Dinh-Xuan AT, Franssen FME, Gonem S, Greening N, Haenebalcke C, Man WD, Mois\u00e9s J, Pech\u00e9 R, Poberezhets V, Quint JK, Steiner MC, Vanderhelst E, Abdo M, Topalovic M, Janssens W.", - "authorAffiliations": "", - "journalTitle": "The European respiratory journal", - "pubYear": "2023", - "date": "2023-05-18", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Few studies have investigated the collaborative potential between artificial intelligence (AI) and pulmonologists for diagnosing pulmonary disease. We hypothesised that the collaboration between a pulmonologist and AI with explanations (explainable AI (XAI)) is superior in diagnostic interpretation of pulmonary function tests (PFTs) than the pulmonologist without support.

Methods

The study was conducted in two phases, a monocentre study (phase 1) and a multicentre intervention study (phase 2). Each phase utilised two different sets of 24 PFT reports of patients with a clinically validated gold standard diagnosis. Each PFT was interpreted without (control) and with XAI's suggestions (intervention). Pulmonologists provided a differential diagnosis consisting of a preferential diagnosis and optionally up to three additional diagnoses. The primary end-point compared accuracy of preferential and additional diagnoses between control and intervention. Secondary end-points were the number of diagnoses in differential diagnosis, diagnostic confidence and inter-rater agreement. We also analysed how XAI influenced pulmonologists' decisions.

Results

In phase 1 (n=16 pulmonologists), mean preferential and differential diagnostic accuracy significantly increased by 10.4% and 9.4%, respectively, between control and intervention (p<0.001). Improvements were somewhat lower but highly significant (p<0.0001) in phase 2 (5.4% and 8.7%, respectively; n=62 pulmonologists). In both phases, the number of diagnoses in the differential diagnosis did not reduce, but diagnostic confidence and inter-rater agreement significantly increased during intervention. Pulmonologists updated their decisions with XAI's feedback and consistently improved their baseline performance if AI provided correct predictions.

Conclusion

A collaboration between a pulmonologist and XAI is better at interpreting PFTs than individual pulmonologists reading without XAI support or XAI alone.", - "laySummary": "", - "urls": "pdf:https://erj.ersjournals.com/content/erj/early/2023/03/15/13993003.01720-2022.full.pdf; doi:https://doi.org/10.1183/13993003.01720-2022; html:https://europepmc.org/articles/PMC10196345; pdf:https://europepmc.org/articles/PMC10196345?pdf=render" - }, { "id": "35176022", "doi": "https://doi.org/10.1371/journal.pmed.1003915", @@ -12393,21 +12376,21 @@ "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003915&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003915; html:https://europepmc.org/articles/PMC8853584; pdf:https://europepmc.org/articles/PMC8853584?pdf=render" }, { - "id": "35879616", - "doi": "https://doi.org/10.1038/s41591-022-01909-w", - "title": "Symptoms and risk factors for long COVID in non-hospitalized adults.", - "authorString": "Subramanian A, Nirantharakumar K, Hughes S, Myles P, Williams T, Gokhale KM, Taverner T, Chandan JS, Brown K, Simms-Williams N, Shah AD, Singh M, Kidy F, Okoth K, Hotham R, Bashir N, Cockburn N, Lee SI, Turner GM, Gkoutos GV, Aiyegbusi OL, McMullan C, Denniston AK, Sapey E, Lord JM, Wraith DC, Leggett E, Iles C, Marshall T, Price MJ, Marwaha S, Davies EH, Jackson LJ, Matthews KL, Camaradou J, Calvert M, Haroon S.", + "id": "37080566", + "doi": "https://doi.org/10.1183/13993003.01720-2022", + "title": "Collaboration between explainable artificial intelligence and pulmonologists improves the accuracy of pulmonary function test interpretation.", + "authorString": "Das N, Happaerts S, Gyselinck I, Staes M, Derom E, Brusselle G, Burgos F, Contoli M, Dinh-Xuan AT, Franssen FME, Gonem S, Greening N, Haenebalcke C, Man WD, Mois\u00e9s J, Pech\u00e9 R, Poberezhets V, Quint JK, Steiner MC, Vanderhelst E, Abdo M, Topalovic M, Janssens W.", "authorAffiliations": "", - "journalTitle": "Nature medicine", - "pubYear": "2022", - "date": "2022-07-25", + "journalTitle": "The European respiratory journal", + "pubYear": "2023", + "date": "2023-05-18", "isOpenAccess": "Y", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02-8.39), hair loss (3.99, 3.63-4.39), sneezing (2.77, 1.40-5.50), ejaculation difficulty (2.63, 1.61-4.28) and reduced libido (2.36, 1.61-3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.", + "abstract": "

Background

Few studies have investigated the collaborative potential between artificial intelligence (AI) and pulmonologists for diagnosing pulmonary disease. We hypothesised that the collaboration between a pulmonologist and AI with explanations (explainable AI (XAI)) is superior in diagnostic interpretation of pulmonary function tests (PFTs) than the pulmonologist without support.

Methods

The study was conducted in two phases, a monocentre study (phase 1) and a multicentre intervention study (phase 2). Each phase utilised two different sets of 24 PFT reports of patients with a clinically validated gold standard diagnosis. Each PFT was interpreted without (control) and with XAI's suggestions (intervention). Pulmonologists provided a differential diagnosis consisting of a preferential diagnosis and optionally up to three additional diagnoses. The primary end-point compared accuracy of preferential and additional diagnoses between control and intervention. Secondary end-points were the number of diagnoses in differential diagnosis, diagnostic confidence and inter-rater agreement. We also analysed how XAI influenced pulmonologists' decisions.

Results

In phase 1 (n=16 pulmonologists), mean preferential and differential diagnostic accuracy significantly increased by 10.4% and 9.4%, respectively, between control and intervention (p<0.001). Improvements were somewhat lower but highly significant (p<0.0001) in phase 2 (5.4% and 8.7%, respectively; n=62 pulmonologists). In both phases, the number of diagnoses in the differential diagnosis did not reduce, but diagnostic confidence and inter-rater agreement significantly increased during intervention. Pulmonologists updated their decisions with XAI's feedback and consistently improved their baseline performance if AI provided correct predictions.

Conclusion

A collaboration between a pulmonologist and XAI is better at interpreting PFTs than individual pulmonologists reading without XAI support or XAI alone.", "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41591-022-01909-w.pdf; doi:https://doi.org/10.1038/s41591-022-01909-w; html:https://europepmc.org/articles/PMC9388369; pdf:https://europepmc.org/articles/PMC9388369?pdf=render" + "urls": "pdf:https://erj.ersjournals.com/content/erj/early/2023/03/15/13993003.01720-2022.full.pdf; doi:https://doi.org/10.1183/13993003.01720-2022; html:https://europepmc.org/articles/PMC10196345; pdf:https://europepmc.org/articles/PMC10196345?pdf=render" }, { "id": "33971933", @@ -12426,6 +12409,23 @@ "laySummary": "", "urls": "pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-021-05295-5; doi:https://doi.org/10.1186/s13063-021-05295-5; html:https://europepmc.org/articles/PMC8108438; pdf:https://europepmc.org/articles/PMC8108438?pdf=render" }, + { + "id": "35879616", + "doi": "https://doi.org/10.1038/s41591-022-01909-w", + "title": "Symptoms and risk factors for long COVID in non-hospitalized adults.", + "authorString": "Subramanian A, Nirantharakumar K, Hughes S, Myles P, Williams T, Gokhale KM, Taverner T, Chandan JS, Brown K, Simms-Williams N, Shah AD, Singh M, Kidy F, Okoth K, Hotham R, Bashir N, Cockburn N, Lee SI, Turner GM, Gkoutos GV, Aiyegbusi OL, McMullan C, Denniston AK, Sapey E, Lord JM, Wraith DC, Leggett E, Iles C, Marshall T, Price MJ, Marwaha S, Davies EH, Jackson LJ, Matthews KL, Camaradou J, Calvert M, Haroon S.", + "authorAffiliations": "", + "journalTitle": "Nature medicine", + "pubYear": "2022", + "date": "2022-07-25", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02-8.39), hair loss (3.99, 3.63-4.39), sneezing (2.77, 1.40-5.50), ejaculation difficulty (2.63, 1.61-4.28) and reduced libido (2.36, 1.61-3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41591-022-01909-w.pdf; doi:https://doi.org/10.1038/s41591-022-01909-w; html:https://europepmc.org/articles/PMC9388369; pdf:https://europepmc.org/articles/PMC9388369?pdf=render" + }, { "id": "36384749", "doi": "https://doi.org/10.1136/heartjnl-2022-321733", @@ -12460,23 +12460,6 @@ "laySummary": "", "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s10654-020-00677-6.pdf; doi:https://doi.org/10.1007/s10654-020-00677-6; html:https://europepmc.org/articles/PMC7987616; pdf:https://europepmc.org/articles/PMC7987616?pdf=render" }, - { - "id": "36541282", - "doi": "https://doi.org/10.14814/phy2.15546", - "title": "Reduced oxygen saturation entropy is associated with poor prognosis in critically ill patients with sepsis.", - "authorString": "Gheorghita M, Wikner M, Cawthorn A, Oyelade T, Nemeth K, Rockenschaub P, Gonzalez Hernandez F, Swanepoel N, Lilaonitkul W, Mani AR.", - "authorAffiliations": "", - "journalTitle": "Physiological reports", - "pubYear": "2022", - "date": "2022-12-01", - "isOpenAccess": "Y", - "keywords": "Variability; Survival; Sepsis; Entropy; Oxygen saturation; Spo2", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Recent studies have found that oxygen saturation (SpO2 ) variability analysis has potential for noninvasive assessment of the functional connectivity of cardiorespiratory control systems during hypoxia. Patients with sepsis have suboptimal tissue oxygenation and impaired organ system connectivity. Our objective with this report was to highlight the potential use for SpO2 variability analysis in predicting intensive care survival in patients with sepsis. MIMIC-III clinical data of 164 adults meeting Sepsis-3 criteria and with 30\u2009min of SpO2 and respiratory rate data were analyzed. The complexity of SpO2 signals was measured through various entropy calculations such as sample entropy and multiscale entropy analysis. The sequential organ failure assessment (SOFA) score was calculated to assess the severity of sepsis and multiorgan failure. While the standard deviation of SpO2 signals was comparable in the non-survivor and survivor groups, non-survivors had significantly lower SpO2 entropy than those who survived their ICU stay (0.107\u2009\u00b1\u20090.084 vs. 0.070\u2009\u00b1\u20090.083, p\u00a0<\u20090.05). According to Cox regression analysis, higher SpO2 entropy was a predictor of survival in patients with sepsis. Multivariate analysis also showed that the prognostic value of SpO2 entropy was independent of other covariates such as age, SOFA score, mean SpO2 , and ventilation status. When SpO2 entropy was combined with mean SpO2 , the composite had a significantly higher performance in prediction of survival. Analysis of SpO2 entropy can predict patient outcome, and when combined with SpO2 mean, can provide improved prognostic information. The prognostic power is on par with the SOFA score. This analysis can easily be incorporated into current ICU practice and has potential for noninvasive assessment of critically ill patients.", - "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.14814/phy2.15546; doi:https://doi.org/10.14814/phy2.15546; html:https://europepmc.org/articles/PMC9768724; pdf:https://europepmc.org/articles/PMC9768724?pdf=render" - }, { "id": "34007896", "doi": "https://doi.org/10.23889/ijpds.v6i1.1387", @@ -12494,6 +12477,23 @@ "laySummary": "", "urls": "pdf:https://ijpds.org/article/download/1387/3155; doi:https://doi.org/10.23889/ijpds.v6i1.1387; html:https://europepmc.org/articles/PMC8103995; pdf:https://europepmc.org/articles/PMC8103995?pdf=render" }, + { + "id": "36541282", + "doi": "https://doi.org/10.14814/phy2.15546", + "title": "Reduced oxygen saturation entropy is associated with poor prognosis in critically ill patients with sepsis.", + "authorString": "Gheorghita M, Wikner M, Cawthorn A, Oyelade T, Nemeth K, Rockenschaub P, Gonzalez Hernandez F, Swanepoel N, Lilaonitkul W, Mani AR.", + "authorAffiliations": "", + "journalTitle": "Physiological reports", + "pubYear": "2022", + "date": "2022-12-01", + "isOpenAccess": "Y", + "keywords": "Variability; Survival; Sepsis; Entropy; Oxygen saturation; Spo2", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Recent studies have found that oxygen saturation (SpO2 ) variability analysis has potential for noninvasive assessment of the functional connectivity of cardiorespiratory control systems during hypoxia. Patients with sepsis have suboptimal tissue oxygenation and impaired organ system connectivity. Our objective with this report was to highlight the potential use for SpO2 variability analysis in predicting intensive care survival in patients with sepsis. MIMIC-III clinical data of 164 adults meeting Sepsis-3 criteria and with 30\u2009min of SpO2 and respiratory rate data were analyzed. The complexity of SpO2 signals was measured through various entropy calculations such as sample entropy and multiscale entropy analysis. The sequential organ failure assessment (SOFA) score was calculated to assess the severity of sepsis and multiorgan failure. While the standard deviation of SpO2 signals was comparable in the non-survivor and survivor groups, non-survivors had significantly lower SpO2 entropy than those who survived their ICU stay (0.107\u2009\u00b1\u20090.084 vs. 0.070\u2009\u00b1\u20090.083, p\u00a0<\u20090.05). According to Cox regression analysis, higher SpO2 entropy was a predictor of survival in patients with sepsis. Multivariate analysis also showed that the prognostic value of SpO2 entropy was independent of other covariates such as age, SOFA score, mean SpO2 , and ventilation status. When SpO2 entropy was combined with mean SpO2 , the composite had a significantly higher performance in prediction of survival. Analysis of SpO2 entropy can predict patient outcome, and when combined with SpO2 mean, can provide improved prognostic information. The prognostic power is on par with the SOFA score. This analysis can easily be incorporated into current ICU practice and has potential for noninvasive assessment of critically ill patients.", + "laySummary": "", + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.14814/phy2.15546; doi:https://doi.org/10.14814/phy2.15546; html:https://europepmc.org/articles/PMC9768724; pdf:https://europepmc.org/articles/PMC9768724?pdf=render" + }, { "id": "33875444", "doi": "https://doi.org/10.1136/bmjopen-2020-045077", @@ -12630,23 +12630,6 @@ "laySummary": "", "urls": "pdf:http://www.journalofinfection.com/article/S0163445321001158/pdf; doi:https://doi.org/10.1016/j.jinf.2021.03.002; html:https://europepmc.org/articles/PMC7948670; pdf:https://europepmc.org/articles/PMC7948670?pdf=render" }, - { - "id": "36350656", - "doi": "https://doi.org/10.1093/nar/gkac1010", - "title": "The NHGRI-EBI GWAS Catalog: knowledgebase and deposition resource.", - "authorString": "Sollis E, Mosaku A, Abid A, Buniello A, Cerezo M, Gil L, Groza T, G\u00fcne\u015f O, Hall P, Hayhurst J, Ibrahim A, Ji Y, John S, Lewis E, MacArthur JAL, McMahon A, Osumi-Sutherland D, Panoutsopoulou K, Pendlington Z, Ramachandran S, Stefancsik R, Stewart J, Whetzel P, Wilson R, Hindorff L, Cunningham F, Lambert SA, Inouye M, Parkinson H, Harris LW.", - "authorAffiliations": "", - "journalTitle": "Nucleic acids research", - "pubYear": "2023", - "date": "2023-01-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The NHGRI-EBI GWAS Catalog (www.ebi.ac.uk/gwas) is a FAIR knowledgebase providing detailed, structured, standardised and interoperable genome-wide association study (GWAS) data to\u00a0>200 000 users per year from academic research, healthcare and industry. The Catalog contains variant-trait associations and supporting metadata for\u00a0>45 000 published GWAS across\u00a0>5000 human traits, and\u00a0>40 000 full P-value summary statistics datasets. Content is curated from publications or acquired via author submission of prepublication summary statistics through a new submission portal and validation tool. GWAS data volume has vastly increased in recent years. We have updated our software to meet this scaling challenge and to enable rapid release of submitted summary statistics. The scope of the repository has expanded to include additional data types of high interest to the community, including sequencing-based GWAS, gene-based analyses and copy number variation analyses. Community outreach has increased the number of shared datasets from under-represented traits, e.g. cancer, and we continue to contribute to awareness of the lack of population diversity in GWAS. Interoperability of the Catalog has been enhanced through links to other resources including the Polygenic Score Catalog and the International Mouse Phenotyping Consortium, refinements to GWAS trait annotation, and the development of a standard format for GWAS data.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/nar/article-pdf/51/D1/D977/48440802/gkac1010.pdf; doi:https://doi.org/10.1093/nar/gkac1010; html:https://europepmc.org/articles/PMC9825413; pdf:https://europepmc.org/articles/PMC9825413?pdf=render" - }, { "id": "34265229", "doi": "https://doi.org/10.1177/01410768211032850", @@ -12664,6 +12647,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1177/01410768211032850; doi:https://doi.org/10.1177/01410768211032850; html:https://europepmc.org/articles/PMC8450986; pdf:https://europepmc.org/articles/PMC8450986?pdf=render" }, + { + "id": "36350656", + "doi": "https://doi.org/10.1093/nar/gkac1010", + "title": "The NHGRI-EBI GWAS Catalog: knowledgebase and deposition resource.", + "authorString": "Sollis E, Mosaku A, Abid A, Buniello A, Cerezo M, Gil L, Groza T, G\u00fcne\u015f O, Hall P, Hayhurst J, Ibrahim A, Ji Y, John S, Lewis E, MacArthur JAL, McMahon A, Osumi-Sutherland D, Panoutsopoulou K, Pendlington Z, Ramachandran S, Stefancsik R, Stewart J, Whetzel P, Wilson R, Hindorff L, Cunningham F, Lambert SA, Inouye M, Parkinson H, Harris LW.", + "authorAffiliations": "", + "journalTitle": "Nucleic acids research", + "pubYear": "2023", + "date": "2023-01-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The NHGRI-EBI GWAS Catalog (www.ebi.ac.uk/gwas) is a FAIR knowledgebase providing detailed, structured, standardised and interoperable genome-wide association study (GWAS) data to\u00a0>200 000 users per year from academic research, healthcare and industry. The Catalog contains variant-trait associations and supporting metadata for\u00a0>45 000 published GWAS across\u00a0>5000 human traits, and\u00a0>40 000 full P-value summary statistics datasets. Content is curated from publications or acquired via author submission of prepublication summary statistics through a new submission portal and validation tool. GWAS data volume has vastly increased in recent years. We have updated our software to meet this scaling challenge and to enable rapid release of submitted summary statistics. The scope of the repository has expanded to include additional data types of high interest to the community, including sequencing-based GWAS, gene-based analyses and copy number variation analyses. Community outreach has increased the number of shared datasets from under-represented traits, e.g. cancer, and we continue to contribute to awareness of the lack of population diversity in GWAS. Interoperability of the Catalog has been enhanced through links to other resources including the Polygenic Score Catalog and the International Mouse Phenotyping Consortium, refinements to GWAS trait annotation, and the development of a standard format for GWAS data.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/nar/article-pdf/51/D1/D977/48440802/gkac1010.pdf; doi:https://doi.org/10.1093/nar/gkac1010; html:https://europepmc.org/articles/PMC9825413; pdf:https://europepmc.org/articles/PMC9825413?pdf=render" + }, { "id": "31315158", "doi": "https://doi.org/10.1002/cnm.3235", @@ -12732,23 +12732,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/mbe/article-pdf/38/3/1122/36533820/msaa279.pdf; doi:https://doi.org/10.1093/molbev/msaa279; html:https://europepmc.org/articles/PMC7947781; pdf:https://europepmc.org/articles/PMC7947781?pdf=render" }, - { - "id": "38837310", - "doi": "https://doi.org/10.1002/ejhf.3306", - "title": "A nationwide, population-based study on specialized care for acute heart failure throughout the COVID-19 pandemic.", - "authorString": "Cannata A, Mizani MA, Bromage DI, Piper SE, Hardman SMC, Sudlow C, de Belder M, Deanfield J, Gardner RS, Clark AL, Cleland JGF, McDonagh TA, \u2009on behalf of the CVD\u2010COVID\u2010UK/COVID\u2010IMPACT Consortium.", - "authorAffiliations": "", - "journalTitle": "European journal of heart failure", - "pubYear": "2024", - "date": "2024-06-04", - "isOpenAccess": "N", - "keywords": "Heart Failure; Specialist Care; Covid\u201019; National Heart Failure Audit", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

The COVID-19 pandemic disrupted the delivery of care for patients with heart failure (HF), leading to fewer HF hospitalizations and increased mortality. However, nationwide data on quality of care and long-term outcomes across the pandemic are scarce.

Methods and results

We used data from the National Heart Failure Audit (NHFA) linked to national records for hospitalization and deaths. We compared pre-COVID (2018-2019), COVID (2020), and late/post-COVID (2021-2022) periods. Data for 227\u2009250 patients admitted to hospital with HF were analysed and grouped according to the admission year and the presence of HF with (HFrEF) or without reduced ejection fraction (non-HFrEF). The median age at admission was 81\u2009years (interquartile range 72-88), 55% were men (n\u2009=\u2009125\u2009975), 87% were of white ethnicity (n\u2009=\u2009102\u2009805), and 51% had HFrEF (n\u2009=\u2009116\u2009990). In-hospital management and specialized cardiology care were maintained throughout the pandemic with an increasing percentage of patients discharged on disease-modifying medications over time (p\u2009<\u20090.001). Long-term outcomes improved over time (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.90-0.95, p\u2009<\u20090.001), mainly driven by a reduction in cardiovascular death. Receiving specialized cardiology care was associated with better long-term outcomes both for those who had HFrEF (HR 0.79, 95% CI 0.77-0.82, p\u2009<\u20090.001) and for those who had non-HFrEF (HR 0.87, 95% CI 0.85-0.90, p\u2009<\u20090.001).

Conclusions

Despite the disruption of healthcare systems, the clinical characteristics of patients admitted with HF were similar and the overall standard of care was maintained throughout the pandemic. Long-term survival of patients hospitalized with HF continued to improve after COVID-19, especially for HFrEF.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1002/ejhf.3306; doi:https://doi.org/10.1002/ejhf.3306" - }, { "id": "34534697", "doi": "https://doi.org/10.1016/j.jbi.2021.103916", @@ -12767,21 +12750,21 @@ "urls": "doi:https://doi.org/10.1016/j.jbi.2021.103916; doi:https://doi.org/10.1016/j.jbi.2021.103916; html:https://europepmc.org/articles/PMC8524321" }, { - "id": "38833617", - "doi": "https://doi.org/10.1093/cvr/cvae123", - "title": "Sex inequalities in cardiovascular risk prediction.", - "authorString": "Elliott J, Bodinier B, Whitaker M, Wada R, Cooke G, Ward H, Tzoulaki I, Elliott P, Chadeau-Hyam M.", + "id": "38837310", + "doi": "https://doi.org/10.1002/ejhf.3306", + "title": "A nationwide, population-based study on specialized care for acute heart failure throughout the COVID-19 pandemic.", + "authorString": "Cannata A, Mizani MA, Bromage DI, Piper SE, Hardman SMC, Sudlow C, de Belder M, Deanfield J, Gardner RS, Clark AL, Cleland JGF, McDonagh TA, \u2009on behalf of the CVD\u2010COVID\u2010UK/COVID\u2010IMPACT Consortium.", "authorAffiliations": "", - "journalTitle": "Cardiovascular research", + "journalTitle": "European journal of heart failure", "pubYear": "2024", "date": "2024-06-04", "isOpenAccess": "N", - "keywords": "Biomarkers; Cvd Risk Prediction; Pooled Cohort Equations; Qrisk3; Sparse Variable Selection", + "keywords": "Heart Failure; Specialist Care; Covid\u201019; National Heart Failure Audit", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Aims

Evaluate sex differences in cardiovascular disease (CVD) risk prediction, including use of i) optimal sex-specific risk predictors and ii) sex-specific risk thresholds.

Methods and results

Prospective cohort study using UK Biobank, including 121,724 and 182,632 healthy men and women, respectively, aged 38-73 years at baseline. There were 11,899 (men) and 9,110 (women) incident CVD cases (hospitalization or mortality) with median 12.1 years follow-up. We used recalibrated Pooled Cohort Equations (PCE, 7.5% 10-year risk threshold as per US guidelines), QRISK3 (10% 10-year risk threshold as per UK guidelines) and Cox survival models using sparse sex-specific variable sets (via LASSO stability selection) to predict CVD risk separately in men and women. LASSO stability selection included 12 variables in common between men and women, with three additional variables selected for men and one for women. C-statistics were slightly lower for PCE than QRISK3 and models using stably-selected variables, but were similar between men and women: 0.67 [0.66-0.68], 0.70 [0.69-0.71], and 0.71 [0.70-0.72] in men and 0.69 [0.68-0.70], 0.72 [0.71-0.73], and 0.72 [0.71-0.73] in women for PCE, QRISK3 and models using stably-selected variables, respectively. At current clinically implemented risk thresholds, test sensitivity was markedly lower in women than men for all models: at 7.5% 10-year risk, sensitivity was 65.1% and 68.2% in men and 24.0% and 33.4% in women for PCE and models using stably-selected variables, respectively; at 10% 10-year risk, sensitivity was 53.7% and 52.3% in men and 16.8% and 20.2% in women for QRISK3 and models using stably-selected variables, respectively. Specificity was correspondingly higher in women than men. However, the sensitivity in women at 5% 10-year risk threshold increased to 50.1%, 58.5% and 55.7% for PCE, QRISK3 and models using stably-selected variables, respectively.

Conclusions

Use of sparse sex-specific variables improved CVD risk prediction compared with PCE but not QRISK3. At current risk thresholds, PCE and QRISK3 work less well for women than men but sensitivity was improved in women using a 5% 10-year risk threshold. Use of sex-specific risk thresholds should be considered in any re-evaluation of CVD risk calculators.

Translational perspective

Cardiovascular disease (CVD) risk prediction is an important component of clinical risk management and disease prevention. We find that at risk prediction thresholds used by currently applied risk prediction algorithms (PCE 7.5% 10-year risk threshold in the US and QRISK3 10% risk threshold in the UK), sensitivity of these risk prediction tools is markedly lower in women than in men. This sex inequality implies that women are proportionately less likely to receive appropriate clinical management including lipid-lowering therapy. If the risk prediction threshold is lowered to 5% 10-year risk in women, then sensitivity in women is substantially increased.", + "abstract": "

Aims

The COVID-19 pandemic disrupted the delivery of care for patients with heart failure (HF), leading to fewer HF hospitalizations and increased mortality. However, nationwide data on quality of care and long-term outcomes across the pandemic are scarce.

Methods and results

We used data from the National Heart Failure Audit (NHFA) linked to national records for hospitalization and deaths. We compared pre-COVID (2018-2019), COVID (2020), and late/post-COVID (2021-2022) periods. Data for 227\u2009250 patients admitted to hospital with HF were analysed and grouped according to the admission year and the presence of HF with (HFrEF) or without reduced ejection fraction (non-HFrEF). The median age at admission was 81\u2009years (interquartile range 72-88), 55% were men (n\u2009=\u2009125\u2009975), 87% were of white ethnicity (n\u2009=\u2009102\u2009805), and 51% had HFrEF (n\u2009=\u2009116\u2009990). In-hospital management and specialized cardiology care were maintained throughout the pandemic with an increasing percentage of patients discharged on disease-modifying medications over time (p\u2009<\u20090.001). Long-term outcomes improved over time (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.90-0.95, p\u2009<\u20090.001), mainly driven by a reduction in cardiovascular death. Receiving specialized cardiology care was associated with better long-term outcomes both for those who had HFrEF (HR 0.79, 95% CI 0.77-0.82, p\u2009<\u20090.001) and for those who had non-HFrEF (HR 0.87, 95% CI 0.85-0.90, p\u2009<\u20090.001).

Conclusions

Despite the disruption of healthcare systems, the clinical characteristics of patients admitted with HF were similar and the overall standard of care was maintained throughout the pandemic. Long-term survival of patients hospitalized with HF continued to improve after COVID-19, especially for HFrEF.", "laySummary": "", - "urls": "doi:https://doi.org/10.1093/cvr/cvae123" + "urls": "doi:https://doi.org/10.1002/ejhf.3306; doi:https://doi.org/10.1002/ejhf.3306" }, { "id": "37272361", @@ -12800,6 +12783,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.2340/actadv.v103.5268; html:https://europepmc.org/articles/PMC10259463; pdf:https://europepmc.org/articles/PMC10259463?pdf=render" }, + { + "id": "38833617", + "doi": "https://doi.org/10.1093/cvr/cvae123", + "title": "Sex inequalities in cardiovascular risk prediction.", + "authorString": "Elliott J, Bodinier B, Whitaker M, Wada R, Cooke G, Ward H, Tzoulaki I, Elliott P, Chadeau-Hyam M.", + "authorAffiliations": "", + "journalTitle": "Cardiovascular research", + "pubYear": "2024", + "date": "2024-06-04", + "isOpenAccess": "N", + "keywords": "Biomarkers; Cvd Risk Prediction; Pooled Cohort Equations; Qrisk3; Sparse Variable Selection", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

Evaluate sex differences in cardiovascular disease (CVD) risk prediction, including use of i) optimal sex-specific risk predictors and ii) sex-specific risk thresholds.

Methods and results

Prospective cohort study using UK Biobank, including 121,724 and 182,632 healthy men and women, respectively, aged 38-73 years at baseline. There were 11,899 (men) and 9,110 (women) incident CVD cases (hospitalization or mortality) with median 12.1 years follow-up. We used recalibrated Pooled Cohort Equations (PCE, 7.5% 10-year risk threshold as per US guidelines), QRISK3 (10% 10-year risk threshold as per UK guidelines) and Cox survival models using sparse sex-specific variable sets (via LASSO stability selection) to predict CVD risk separately in men and women. LASSO stability selection included 12 variables in common between men and women, with three additional variables selected for men and one for women. C-statistics were slightly lower for PCE than QRISK3 and models using stably-selected variables, but were similar between men and women: 0.67 [0.66-0.68], 0.70 [0.69-0.71], and 0.71 [0.70-0.72] in men and 0.69 [0.68-0.70], 0.72 [0.71-0.73], and 0.72 [0.71-0.73] in women for PCE, QRISK3 and models using stably-selected variables, respectively. At current clinically implemented risk thresholds, test sensitivity was markedly lower in women than men for all models: at 7.5% 10-year risk, sensitivity was 65.1% and 68.2% in men and 24.0% and 33.4% in women for PCE and models using stably-selected variables, respectively; at 10% 10-year risk, sensitivity was 53.7% and 52.3% in men and 16.8% and 20.2% in women for QRISK3 and models using stably-selected variables, respectively. Specificity was correspondingly higher in women than men. However, the sensitivity in women at 5% 10-year risk threshold increased to 50.1%, 58.5% and 55.7% for PCE, QRISK3 and models using stably-selected variables, respectively.

Conclusions

Use of sparse sex-specific variables improved CVD risk prediction compared with PCE but not QRISK3. At current risk thresholds, PCE and QRISK3 work less well for women than men but sensitivity was improved in women using a 5% 10-year risk threshold. Use of sex-specific risk thresholds should be considered in any re-evaluation of CVD risk calculators.

Translational perspective

Cardiovascular disease (CVD) risk prediction is an important component of clinical risk management and disease prevention. We find that at risk prediction thresholds used by currently applied risk prediction algorithms (PCE 7.5% 10-year risk threshold in the US and QRISK3 10% risk threshold in the UK), sensitivity of these risk prediction tools is markedly lower in women than in men. This sex inequality implies that women are proportionately less likely to receive appropriate clinical management including lipid-lowering therapy. If the risk prediction threshold is lowered to 5% 10-year risk in women, then sensitivity in women is substantially increased.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/cvr/cvae123" + }, { "id": "36921925", "doi": "https://doi.org/10.1136/bmj-2022-072808", @@ -12919,23 +12919,6 @@ "laySummary": "", "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220254; doi:https://doi.org/10.1016/j.epidem.2022.100604; html:https://europepmc.org/articles/PMC9220254; pdf:https://europepmc.org/articles/PMC9220254?pdf=render" }, - { - "id": "33634312", - "doi": "https://doi.org/10.1093/bib/bbab006", - "title": "Benchmarking network-based gene prioritization methods for cerebral small vessel disease.", - "authorString": "Zhang H, Ferguson A, Robertson G, Jiang M, Zhang T, Sudlow C, Smith K, Rannikmae K, Wu H.", - "authorAffiliations": "", - "journalTitle": "Briefings in bioinformatics", - "pubYear": "2021", - "date": "2021-09-01", - "isOpenAccess": "Y", - "keywords": "Cerebral Small Vessel Disease; Protein\u2013protein Interaction; Benchmarking; Disease Gene Association; Network-based Gene Prioritization", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Network-based gene prioritization algorithms are designed to prioritize disease-associated genes based on known ones using biological networks of protein interactions, gene-disease associations (GDAs) and other relationships between biological entities. Various algorithms have been developed based on different mechanisms, but it is not obvious which algorithm is optimal for a specific disease. To address this issue, we benchmarked multiple algorithms for their application in cerebral small vessel disease (cSVD). We curated protein-gene interactions (PGIs) and GDAs from databases and assembled PGI networks and disease-gene heterogeneous networks. A screening of algorithms resulted in seven representative algorithms to be benchmarked. Performance of algorithms was assessed using both leave-one-out cross-validation (LOOCV) and external validation with MEGASTROKE genome-wide association study (GWAS). We found that random walk with restart on the heterogeneous network (RWRH) showed best LOOCV performance, with median LOOCV rediscovery rank of 185.5 (out of 19\u00a0463 genes). The GenePanda algorithm had most GWAS-confirmable genes in top 200 predictions, while RWRH had best ranks for small vessel stroke-associated genes confirmed in GWAS. In conclusion, RWRH has overall better performance for application in cSVD despite its susceptibility to bias caused by degree centrality. Choice of algorithms should be determined before applying to specific disease. Current pure network-based gene prioritization algorithms are unlikely to find novel disease-associated genes that are not associated with known ones. The tools for implementing and benchmarking algorithms have been made available and can be generalized for other diseases.", - "laySummary": "", - "urls": "pdf:https://www.pure.ed.ac.uk/ws/files/198917679/bbab006.pdf; doi:https://doi.org/10.1093/bib/bbab006; html:https://europepmc.org/articles/PMC8425308; pdf:https://europepmc.org/articles/PMC8425308?pdf=render" - }, { "id": "35611160", "doi": "https://doi.org/10.1016/j.eclinm.2022.101462", @@ -12953,6 +12936,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S2589537022001924/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101462; html:https://europepmc.org/articles/PMC9121886; pdf:https://europepmc.org/articles/PMC9121886?pdf=render" }, + { + "id": "33634312", + "doi": "https://doi.org/10.1093/bib/bbab006", + "title": "Benchmarking network-based gene prioritization methods for cerebral small vessel disease.", + "authorString": "Zhang H, Ferguson A, Robertson G, Jiang M, Zhang T, Sudlow C, Smith K, Rannikmae K, Wu H.", + "authorAffiliations": "", + "journalTitle": "Briefings in bioinformatics", + "pubYear": "2021", + "date": "2021-09-01", + "isOpenAccess": "Y", + "keywords": "Cerebral Small Vessel Disease; Protein\u2013protein Interaction; Benchmarking; Disease Gene Association; Network-based Gene Prioritization", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Network-based gene prioritization algorithms are designed to prioritize disease-associated genes based on known ones using biological networks of protein interactions, gene-disease associations (GDAs) and other relationships between biological entities. Various algorithms have been developed based on different mechanisms, but it is not obvious which algorithm is optimal for a specific disease. To address this issue, we benchmarked multiple algorithms for their application in cerebral small vessel disease (cSVD). We curated protein-gene interactions (PGIs) and GDAs from databases and assembled PGI networks and disease-gene heterogeneous networks. A screening of algorithms resulted in seven representative algorithms to be benchmarked. Performance of algorithms was assessed using both leave-one-out cross-validation (LOOCV) and external validation with MEGASTROKE genome-wide association study (GWAS). We found that random walk with restart on the heterogeneous network (RWRH) showed best LOOCV performance, with median LOOCV rediscovery rank of 185.5 (out of 19\u00a0463 genes). The GenePanda algorithm had most GWAS-confirmable genes in top 200 predictions, while RWRH had best ranks for small vessel stroke-associated genes confirmed in GWAS. In conclusion, RWRH has overall better performance for application in cSVD despite its susceptibility to bias caused by degree centrality. Choice of algorithms should be determined before applying to specific disease. Current pure network-based gene prioritization algorithms are unlikely to find novel disease-associated genes that are not associated with known ones. The tools for implementing and benchmarking algorithms have been made available and can be generalized for other diseases.", + "laySummary": "", + "urls": "pdf:https://www.pure.ed.ac.uk/ws/files/198917679/bbab006.pdf; doi:https://doi.org/10.1093/bib/bbab006; html:https://europepmc.org/articles/PMC8425308; pdf:https://europepmc.org/articles/PMC8425308?pdf=render" + }, { "id": "33587202", "doi": "https://doi.org/10.1007/s10654-021-00722-y", @@ -13242,23 +13242,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/ageing/afac176; doi:https://doi.org/10.1093/ageing/afac176; html:https://europepmc.org/articles/PMC9356534; pdf:https://europepmc.org/articles/PMC9356534?pdf=render" }, - { - "id": "38528230", - "doi": "https://doi.org/10.1038/s43587-024-00590-7", - "title": "Integration of polygenic and gut metagenomic risk prediction for common diseases.", - "authorString": "Liu Y, Ritchie SC, Teo SM, Ruuskanen MO, Kambur O, Zhu Q, Sanders J, V\u00e1zquez-Baeza Y, Verspoor K, Jousilahti P, Lahti L, Niiranen T, Salomaa V, Havulinna AS, Knight R, M\u00e9ric G, Inouye M.", - "authorAffiliations": "", - "journalTitle": "Nature aging", - "pubYear": "2024", - "date": "2024-03-25", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Multiomics has shown promise in noninvasive risk profiling and early detection of various common diseases. In the present study, in a prospective population-based cohort with ~18\u2009years of e-health record follow-up, we investigated the incremental and combined value of genomic and gut metagenomic risk assessment compared with conventional risk factors for predicting incident coronary artery disease (CAD), type 2 diabetes (T2D), Alzheimer disease and prostate cancer. We found that polygenic risk scores (PRSs) improved prediction over conventional risk factors for all diseases. Gut microbiome scores improved predictive capacity over baseline age for CAD, T2D and prostate cancer. Integrated risk models of PRSs, gut microbiome scores and conventional risk factors achieved the highest predictive performance for all diseases studied compared with models based on conventional risk factors alone. The present study demonstrates that integrated PRSs and gut metagenomic risk models improve the predictive value over conventional risk factors for common chronic diseases.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s43587-024-00590-7.pdf; doi:https://doi.org/10.1038/s43587-024-00590-7; html:https://europepmc.org/articles/PMC11031402; pdf:https://europepmc.org/articles/PMC11031402?pdf=render" - }, { "id": "35802764", "doi": "https://doi.org/10.7189/jogh.12.05025", @@ -13276,6 +13259,23 @@ "laySummary": "", "urls": "pdf:https://jogh.org/wp-content/uploads/2022/07/jogh-12-05025.pdf; doi:https://doi.org/10.7189/jogh.12.05025; html:https://europepmc.org/articles/PMC9269984; pdf:https://europepmc.org/articles/PMC9269984?pdf=render" }, + { + "id": "38528230", + "doi": "https://doi.org/10.1038/s43587-024-00590-7", + "title": "Integration of polygenic and gut metagenomic risk prediction for common diseases.", + "authorString": "Liu Y, Ritchie SC, Teo SM, Ruuskanen MO, Kambur O, Zhu Q, Sanders J, V\u00e1zquez-Baeza Y, Verspoor K, Jousilahti P, Lahti L, Niiranen T, Salomaa V, Havulinna AS, Knight R, M\u00e9ric G, Inouye M.", + "authorAffiliations": "", + "journalTitle": "Nature aging", + "pubYear": "2024", + "date": "2024-03-25", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Multiomics has shown promise in noninvasive risk profiling and early detection of various common diseases. In the present study, in a prospective population-based cohort with ~18\u2009years of e-health record follow-up, we investigated the incremental and combined value of genomic and gut metagenomic risk assessment compared with conventional risk factors for predicting incident coronary artery disease (CAD), type 2 diabetes (T2D), Alzheimer disease and prostate cancer. We found that polygenic risk scores (PRSs) improved prediction over conventional risk factors for all diseases. Gut microbiome scores improved predictive capacity over baseline age for CAD, T2D and prostate cancer. Integrated risk models of PRSs, gut microbiome scores and conventional risk factors achieved the highest predictive performance for all diseases studied compared with models based on conventional risk factors alone. The present study demonstrates that integrated PRSs and gut metagenomic risk models improve the predictive value over conventional risk factors for common chronic diseases.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s43587-024-00590-7.pdf; doi:https://doi.org/10.1038/s43587-024-00590-7; html:https://europepmc.org/articles/PMC11031402; pdf:https://europepmc.org/articles/PMC11031402?pdf=render" + }, { "id": "35105585", "doi": "https://doi.org/10.1136/bmjopen-2021-054376", @@ -13497,23 +13497,6 @@ "laySummary": "", "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/1460458220977579; doi:https://doi.org/10.1177/1460458220977579" }, - { - "id": "38304287", - "doi": "https://doi.org/10.3389/fpsyt.2024.1347358", - "title": "How will AI make sense of our messy lives and improve our mental health?", - "authorString": "Speechley J, McTernan M.", - "authorAffiliations": "", - "journalTitle": "Frontiers in psychiatry", - "pubYear": "2024", - "date": "2024-01-18", - "isOpenAccess": "Y", - "keywords": "Artificial intelligence; Data; Mental health; TRUST; Patient And Public Engagement", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "doi:https://doi.org/10.3389/fpsyt.2024.1347358; html:https://europepmc.org/articles/PMC10832992; pdf:https://europepmc.org/articles/PMC10832992?pdf=render" - }, { "id": "33469151", "doi": "https://doi.org/10.1038/s42003-020-01613-w", @@ -13531,6 +13514,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s42003-020-01613-w.pdf; doi:https://doi.org/10.1038/s42003-020-01613-w; html:https://europepmc.org/articles/PMC7815736; pdf:https://europepmc.org/articles/PMC7815736?pdf=render" }, + { + "id": "38304287", + "doi": "https://doi.org/10.3389/fpsyt.2024.1347358", + "title": "How will AI make sense of our messy lives and improve our mental health?", + "authorString": "Speechley J, McTernan M.", + "authorAffiliations": "", + "journalTitle": "Frontiers in psychiatry", + "pubYear": "2024", + "date": "2024-01-18", + "isOpenAccess": "Y", + "keywords": "Artificial intelligence; Data; Mental health; TRUST; Patient And Public Engagement", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "doi:https://doi.org/10.3389/fpsyt.2024.1347358; html:https://europepmc.org/articles/PMC10832992; pdf:https://europepmc.org/articles/PMC10832992?pdf=render" + }, { "id": "36377225", "doi": "https://doi.org/10.1177/18333583221135710", @@ -13599,40 +13599,6 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/1/e054414.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054414; html:https://europepmc.org/articles/PMC8788233; pdf:https://europepmc.org/articles/PMC8788233?pdf=render" }, - { - "id": "37432340", - "doi": "https://doi.org/10.1093/rheumatology/kead346", - "title": "Trends for opioid prescribing and the impact of the COVID-19 pandemic in patients with rheumatic and musculoskeletal diseases between 2006 and 2021.", - "authorString": "Huang YT, Jenkins DA, Yimer BB, Benitez-Aurioles J, Peek N, Lunt M, Dixon WG, Jani M.", - "authorAffiliations": "", - "journalTitle": "Rheumatology (Oxford, England)", - "pubYear": "2024", - "date": "2024-04-01", - "isOpenAccess": "Y", - "keywords": "RA; SLE; Trend; PSA; Opioids; Oa; Axial Spondyloarthritis; Fm; Covid-19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

To investigate opioid prescribing trends and assess the impact of the COVID-19 pandemic on opioid prescribing in rheumatic and musculoskeletal diseases (RMDs).

Methods

Adult patients with RA, PsA, axial spondyloarthritis (AxSpA), SLE, OA and FM with opioid prescriptions between 1 January 2006 and 31 August 2021 without cancer in UK primary care were included. Age- and gender-standardized yearly rates of new and prevalent opioid users were calculated between 2006 and 2021. For prevalent users, monthly measures of mean morphine milligram equivalents (MME)/day were calculated between 2006 and 2021. To assess the impact of the pandemic, we fitted regression models to the monthly number of prevalent opioid users between January 2015 and August 2021. The time coefficient reflects the trend pre-pandemic and the interaction term coefficient represents the change in the trend during the pandemic.

Results

The study included 1\u200a313\u200a519 RMD patients. New opioid users for RA, PsA and FM increased from 2.6, 1.0 and 3.4/10\u2009000 persons in 2006 to 4.5, 1.8 and 8.7, respectively, in 2018 or 2019. This was followed by a fall to 2.4, 1.2 and 5.9, respectively, in 2021. Prevalent opioid users for all RMDs increased from 2006 but plateaued or dropped beyond 2018, with a 4.5-fold increase in FM between 2006 and 2021. In this period, MME/day increased for all RMDs, with the highest for FM (\u226535). During COVID-19 lockdowns, RA, PsA and FM showed significant changes in the trend of prevalent opioid users. The trend for FM increased pre-pandemic and started decreasing during the pandemic.

Conclusion

The plateauing or decreasing trend of opioid users for RMDs after 2018 may reflect the efforts to tackle rising opioid prescribing in the UK. The pandemic led to fewer people on opioids for most RMDs, providing reassurance that there was no sudden increase in opioid prescribing during the pandemic.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/kead346/50930066/kead346.pdf; doi:https://doi.org/10.1093/rheumatology/kead346; html:https://europepmc.org/articles/PMC10986805; pdf:https://europepmc.org/articles/PMC10986805?pdf=render" - }, - { - "id": "38578666", - "doi": "https://doi.org/10.2196/49548", - "title": "Implementation of an Electronic Clinical Decision Support System for the Early Recognition and Management of Dysglycemia in an Inpatient Mental Health Setting Using CogStack: Protocol for a Pilot Hybrid Type 3 Effectiveness-Implementation Randomized Controlled Cluster Trial.", - "authorString": "Patel D, Msosa YJ, Wang T, Williams J, Mustafa OG, Gee S, Arroyo B, Larkin D, Tiedt T, Roberts A, Dobson RJB, Gaughran F.", - "authorAffiliations": "", - "journalTitle": "JMIR research protocols", - "pubYear": "2024", - "date": "2024-04-05", - "isOpenAccess": "Y", - "keywords": "Blood sugar; Diabetes; Diabetic; Implementation; Mental health; Randomized controlled trial; hyperglycemia; Hypoglycemia; Mental Illness; Clinical Decision Support System; Decision Support; Medical Informatics; Rct; Cdss; Metabolic Health; Mental Healthcare; Electronic Clinical Decision Support; Dysglycemia", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Severe mental illnesses (SMIs), including schizophrenia, bipolar affective disorder, and major depressive disorder, are associated with an increased risk of physical health comorbidities and premature mortality from conditions including cardiovascular disease and diabetes. Digital technologies such as electronic clinical decision support systems (eCDSSs) could play a crucial role in improving the clinician-led management of conditions such as dysglycemia (deranged blood sugar levels) and associated conditions such as diabetes in people with a diagnosis of SMI in mental health settings.

Objective

We have developed a real-time eCDSS using CogStack, an information retrieval and extraction platform, to automatically alert clinicians with National Health Service Trust-approved, guideline-based recommendations for dysglycemia monitoring and management in secondary mental health care. This novel system aims to improve the management of dysglycemia and associated conditions, such as diabetes, in SMI. This protocol describes a pilot study to explore the acceptability, feasibility, and evaluation of its implementation in a mental health inpatient setting.

Methods

This will be a pilot hybrid type 3 effectiveness-implementation randomized controlled cluster trial in inpatient mental health wards. A ward will be the unit of recruitment, where it will be randomly allocated to receive either access to the eCDSS plus usual care or usual care alone over a 4-month period. We will measure implementation outcomes, including the feasibility and acceptability of the eCDSS to clinicians, as primary outcomes, alongside secondary outcomes relating to the process of care measures such as dysglycemia screening rates. An evaluation of other implementation outcomes relating to the eCDSS will be conducted, identifying facilitators and barriers based on established implementation science frameworks.

Results

Enrollment of wards began in April 2022, after which clinical staff were recruited to take part in surveys and interviews. The intervention period of the trial began in February 2023, and subsequent data collection was completed in August 2023. Data are currently being analyzed, and results are expected to be available in June 2024.

Conclusions

An eCDSS can have the potential to improve clinician-led management of dysglycemia in inpatient mental health settings. If found to be feasible and acceptable, then, in combination with the results of the implementation evaluation, the system can be refined and improved to support future successful implementation. A larger and more definitive effectiveness trial should then be conducted to assess its impact on clinical outcomes and to inform scalability and application to other conditions in wider mental health care settings.

Trial registration

ClinicalTrials.gov NCT04792268; https://clinicaltrials.gov/study/NCT04792268.

International registered report identifier (irrid)

DERR1-10.2196/49548.", - "laySummary": "", - "urls": "pdf:https://www.researchprotocols.org/2024/1/e49548/PDF; doi:https://doi.org/10.2196/49548; html:https://europepmc.org/articles/PMC11031689" - }, { "id": "31971603", "doi": "https://doi.org/10.2340/00015555-3384", @@ -13667,6 +13633,23 @@ "laySummary": "", "urls": "pdf:https://bmcmedresmethodol.biomedcentral.com/track/pdf/10.1186/s12874-020-01025-8; doi:https://doi.org/10.1186/s12874-020-01025-8; html:https://europepmc.org/articles/PMC7341581; pdf:https://europepmc.org/articles/PMC7341581?pdf=render" }, + { + "id": "37432340", + "doi": "https://doi.org/10.1093/rheumatology/kead346", + "title": "Trends for opioid prescribing and the impact of the COVID-19 pandemic in patients with rheumatic and musculoskeletal diseases between 2006 and 2021.", + "authorString": "Huang YT, Jenkins DA, Yimer BB, Benitez-Aurioles J, Peek N, Lunt M, Dixon WG, Jani M.", + "authorAffiliations": "", + "journalTitle": "Rheumatology (Oxford, England)", + "pubYear": "2024", + "date": "2024-04-01", + "isOpenAccess": "Y", + "keywords": "RA; SLE; Trend; PSA; Opioids; Oa; Axial Spondyloarthritis; Fm; Covid-19", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

To investigate opioid prescribing trends and assess the impact of the COVID-19 pandemic on opioid prescribing in rheumatic and musculoskeletal diseases (RMDs).

Methods

Adult patients with RA, PsA, axial spondyloarthritis (AxSpA), SLE, OA and FM with opioid prescriptions between 1 January 2006 and 31 August 2021 without cancer in UK primary care were included. Age- and gender-standardized yearly rates of new and prevalent opioid users were calculated between 2006 and 2021. For prevalent users, monthly measures of mean morphine milligram equivalents (MME)/day were calculated between 2006 and 2021. To assess the impact of the pandemic, we fitted regression models to the monthly number of prevalent opioid users between January 2015 and August 2021. The time coefficient reflects the trend pre-pandemic and the interaction term coefficient represents the change in the trend during the pandemic.

Results

The study included 1\u200a313\u200a519 RMD patients. New opioid users for RA, PsA and FM increased from 2.6, 1.0 and 3.4/10\u2009000 persons in 2006 to 4.5, 1.8 and 8.7, respectively, in 2018 or 2019. This was followed by a fall to 2.4, 1.2 and 5.9, respectively, in 2021. Prevalent opioid users for all RMDs increased from 2006 but plateaued or dropped beyond 2018, with a 4.5-fold increase in FM between 2006 and 2021. In this period, MME/day increased for all RMDs, with the highest for FM (\u226535). During COVID-19 lockdowns, RA, PsA and FM showed significant changes in the trend of prevalent opioid users. The trend for FM increased pre-pandemic and started decreasing during the pandemic.

Conclusion

The plateauing or decreasing trend of opioid users for RMDs after 2018 may reflect the efforts to tackle rising opioid prescribing in the UK. The pandemic led to fewer people on opioids for most RMDs, providing reassurance that there was no sudden increase in opioid prescribing during the pandemic.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/kead346/50930066/kead346.pdf; doi:https://doi.org/10.1093/rheumatology/kead346; html:https://europepmc.org/articles/PMC10986805; pdf:https://europepmc.org/articles/PMC10986805?pdf=render" + }, { "id": "35216844", "doi": "https://doi.org/10.1016/j.vaccine.2022.02.056", @@ -13684,6 +13667,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.vaccine.2022.02.056; doi:https://doi.org/10.1016/j.vaccine.2022.02.056; html:https://europepmc.org/articles/PMC8849863" }, + { + "id": "38578666", + "doi": "https://doi.org/10.2196/49548", + "title": "Implementation of an Electronic Clinical Decision Support System for the Early Recognition and Management of Dysglycemia in an Inpatient Mental Health Setting Using CogStack: Protocol for a Pilot Hybrid Type 3 Effectiveness-Implementation Randomized Controlled Cluster Trial.", + "authorString": "Patel D, Msosa YJ, Wang T, Williams J, Mustafa OG, Gee S, Arroyo B, Larkin D, Tiedt T, Roberts A, Dobson RJB, Gaughran F.", + "authorAffiliations": "", + "journalTitle": "JMIR research protocols", + "pubYear": "2024", + "date": "2024-04-05", + "isOpenAccess": "Y", + "keywords": "Blood sugar; Diabetes; Diabetic; Implementation; Mental health; Randomized controlled trial; hyperglycemia; Hypoglycemia; Mental Illness; Clinical Decision Support System; Decision Support; Medical Informatics; Rct; Cdss; Metabolic Health; Mental Healthcare; Electronic Clinical Decision Support; Dysglycemia", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Severe mental illnesses (SMIs), including schizophrenia, bipolar affective disorder, and major depressive disorder, are associated with an increased risk of physical health comorbidities and premature mortality from conditions including cardiovascular disease and diabetes. Digital technologies such as electronic clinical decision support systems (eCDSSs) could play a crucial role in improving the clinician-led management of conditions such as dysglycemia (deranged blood sugar levels) and associated conditions such as diabetes in people with a diagnosis of SMI in mental health settings.

Objective

We have developed a real-time eCDSS using CogStack, an information retrieval and extraction platform, to automatically alert clinicians with National Health Service Trust-approved, guideline-based recommendations for dysglycemia monitoring and management in secondary mental health care. This novel system aims to improve the management of dysglycemia and associated conditions, such as diabetes, in SMI. This protocol describes a pilot study to explore the acceptability, feasibility, and evaluation of its implementation in a mental health inpatient setting.

Methods

This will be a pilot hybrid type 3 effectiveness-implementation randomized controlled cluster trial in inpatient mental health wards. A ward will be the unit of recruitment, where it will be randomly allocated to receive either access to the eCDSS plus usual care or usual care alone over a 4-month period. We will measure implementation outcomes, including the feasibility and acceptability of the eCDSS to clinicians, as primary outcomes, alongside secondary outcomes relating to the process of care measures such as dysglycemia screening rates. An evaluation of other implementation outcomes relating to the eCDSS will be conducted, identifying facilitators and barriers based on established implementation science frameworks.

Results

Enrollment of wards began in April 2022, after which clinical staff were recruited to take part in surveys and interviews. The intervention period of the trial began in February 2023, and subsequent data collection was completed in August 2023. Data are currently being analyzed, and results are expected to be available in June 2024.

Conclusions

An eCDSS can have the potential to improve clinician-led management of dysglycemia in inpatient mental health settings. If found to be feasible and acceptable, then, in combination with the results of the implementation evaluation, the system can be refined and improved to support future successful implementation. A larger and more definitive effectiveness trial should then be conducted to assess its impact on clinical outcomes and to inform scalability and application to other conditions in wider mental health care settings.

Trial registration

ClinicalTrials.gov NCT04792268; https://clinicaltrials.gov/study/NCT04792268.

International registered report identifier (irrid)

DERR1-10.2196/49548.", + "laySummary": "", + "urls": "pdf:https://www.researchprotocols.org/2024/1/e49548/PDF; doi:https://doi.org/10.2196/49548; html:https://europepmc.org/articles/PMC11031689" + }, { "id": "37139857", "doi": "https://doi.org/10.1111/dom.15102", @@ -13837,23 +13837,6 @@ "laySummary": "", "urls": "pdf:https://pn.bmj.com/content/practneurol/early/2023/02/19/pn-2021-003286.full.pdf; doi:https://doi.org/10.1136/pn-2021-003286; html:https://europepmc.org/articles/PMC10423506; pdf:https://europepmc.org/articles/PMC10423506?pdf=render" }, - { - "id": "36895179", - "doi": "https://doi.org/10.1093/eurjpc/zwad055", - "title": "Determining cardiovascular risk in patients with unattributed chest pain in UK primary care: an electronic health record study.", - "authorString": "Jordan KP, Rathod-Mistry T, van der Windt DA, Bailey J, Chen Y, Clarson L, Denaxas S, Hayward RA, Hemingway H, Kyriacou T, Mamas MA.", - "authorAffiliations": "", - "journalTitle": "European journal of preventive cardiology", - "pubYear": "2023", - "date": "2023-08-01", - "isOpenAccess": "Y", - "keywords": "Cardiovascular disease; Chest pain; epidemiology; Primary Health Care; risk; Electronic Health Records", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

Most adults presenting in primary care with chest pain symptoms will not receive a diagnosis ('unattributed' chest pain) but are at increased risk of cardiovascular events. To assess within patients with unattributed chest pain, risk factors for cardiovascular events and whether those at greatest risk of cardiovascular disease can be ascertained by an existing general population risk prediction model or by development of a new model.

Methods and results

The study used UK primary care electronic health records from the Clinical Practice Research Datalink linked to admitted hospitalizations. Study population was patients aged 18 plus with recorded unattributed chest pain 2002-2018. Cardiovascular risk prediction models were developed with external validation and comparison of performance to QRISK3, a general population risk prediction model. There were 374 917 patients with unattributed chest pain in the development data set. The strongest risk factors for cardiovascular disease included diabetes, atrial fibrillation, and hypertension. Risk was increased in males, patients of Asian ethnicity, those in more deprived areas, obese patients, and smokers. The final developed model had good predictive performance (external validation c-statistic 0.81, calibration slope 1.02). A model using a subset of key risk factors for cardiovascular disease gave nearly identical performance. QRISK3 underestimated cardiovascular risk.

Conclusion

Patients presenting with unattributed chest pain are at increased risk of cardiovascular events. It is feasible to accurately estimate individual risk using routinely recorded information in the primary care record, focusing on a small number of risk factors. Patients at highest risk could be targeted for preventative measures.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/eurjpc/advance-article-pdf/doi/10.1093/eurjpc/zwad055/49604587/zwad055.pdf; doi:https://doi.org/10.1093/eurjpc/zwad055; html:https://europepmc.org/articles/PMC10442054; pdf:https://europepmc.org/articles/PMC10442054?pdf=render" - }, { "id": "34649997", "doi": "https://doi.org/10.2337/dc21-0437", @@ -13871,6 +13854,23 @@ "laySummary": "", "urls": "pdf:https://diabetesjournals.org/care/article-pdf/44/12/2758/631597/dc210437.pdf; doi:https://doi.org/10.2337/dc21-0437; html:https://europepmc.org/articles/PMC8669537; pdf:https://europepmc.org/articles/PMC8669537?pdf=render" }, + { + "id": "36895179", + "doi": "https://doi.org/10.1093/eurjpc/zwad055", + "title": "Determining cardiovascular risk in patients with unattributed chest pain in UK primary care: an electronic health record study.", + "authorString": "Jordan KP, Rathod-Mistry T, van der Windt DA, Bailey J, Chen Y, Clarson L, Denaxas S, Hayward RA, Hemingway H, Kyriacou T, Mamas MA.", + "authorAffiliations": "", + "journalTitle": "European journal of preventive cardiology", + "pubYear": "2023", + "date": "2023-08-01", + "isOpenAccess": "Y", + "keywords": "Cardiovascular disease; Chest pain; epidemiology; Primary Health Care; risk; Electronic Health Records", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

Most adults presenting in primary care with chest pain symptoms will not receive a diagnosis ('unattributed' chest pain) but are at increased risk of cardiovascular events. To assess within patients with unattributed chest pain, risk factors for cardiovascular events and whether those at greatest risk of cardiovascular disease can be ascertained by an existing general population risk prediction model or by development of a new model.

Methods and results

The study used UK primary care electronic health records from the Clinical Practice Research Datalink linked to admitted hospitalizations. Study population was patients aged 18 plus with recorded unattributed chest pain 2002-2018. Cardiovascular risk prediction models were developed with external validation and comparison of performance to QRISK3, a general population risk prediction model. There were 374 917 patients with unattributed chest pain in the development data set. The strongest risk factors for cardiovascular disease included diabetes, atrial fibrillation, and hypertension. Risk was increased in males, patients of Asian ethnicity, those in more deprived areas, obese patients, and smokers. The final developed model had good predictive performance (external validation c-statistic 0.81, calibration slope 1.02). A model using a subset of key risk factors for cardiovascular disease gave nearly identical performance. QRISK3 underestimated cardiovascular risk.

Conclusion

Patients presenting with unattributed chest pain are at increased risk of cardiovascular events. It is feasible to accurately estimate individual risk using routinely recorded information in the primary care record, focusing on a small number of risk factors. Patients at highest risk could be targeted for preventative measures.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/eurjpc/advance-article-pdf/doi/10.1093/eurjpc/zwad055/49604587/zwad055.pdf; doi:https://doi.org/10.1093/eurjpc/zwad055; html:https://europepmc.org/articles/PMC10442054; pdf:https://europepmc.org/articles/PMC10442054?pdf=render" + }, { "id": "36447757", "doi": "https://doi.org/10.1136/gpsych-2022-100819", @@ -13888,23 +13888,6 @@ "laySummary": "", "urls": "pdf:https://gpsych.bmj.com/content/gpsych/35/5/e100819.full.pdf; doi:https://doi.org/10.1136/gpsych-2022-100819; html:https://europepmc.org/articles/PMC9639123; pdf:https://europepmc.org/articles/PMC9639123?pdf=render" }, - { - "id": "38036971", - "doi": "https://doi.org/10.1186/s12859-023-05576-7", - "title": "Completing a genomic characterisation of microscopic tumour samples with copy number.", - "authorString": "Nulsen J, Hussain N, Al-Deka A, Yap J, Uddin K, Yau C, Ahmed AA.", - "authorAffiliations": "", - "journalTitle": "BMC bioinformatics", - "pubYear": "2023", - "date": "2023-11-30", - "isOpenAccess": "Y", - "keywords": "Copy number; Microscopic Samples; Cancer Genomics", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Genomic insights in settings where tumour sample sizes are limited to just hundreds or even tens of cells hold great clinical potential, but also present significant technical challenges. We previously developed the DigiPico sequencing platform to accurately identify somatic mutations from such samples.

Results

Here, we complete this genomic characterisation with copy number. We present a novel protocol, PicoCNV, to call allele-specific somatic copy number alterations from picogram quantities of tumour DNA. We find that PicoCNV provides exactly accurate copy number in 84% of the genome for even the smallest samples, and demonstrate its clinical potential in maintenance therapy.

Conclusions

PicoCNV complements our existing platform, allowing for accurate and comprehensive genomic characterisations of cancers in settings where only microscopic samples are available.", - "laySummary": "", - "urls": "pdf:https://bmcbioinformatics.biomedcentral.com/counter/pdf/10.1186/s12859-023-05576-7; doi:https://doi.org/10.1186/s12859-023-05576-7; html:https://europepmc.org/articles/PMC10688092; pdf:https://europepmc.org/articles/PMC10688092?pdf=render" - }, { "id": "33123364", "doi": "https://doi.org/10.1093/ckj/sfaa192", @@ -13922,6 +13905,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ckj/article-pdf/13/5/889/33980535/sfaa192.pdf; doi:https://doi.org/10.1093/ckj/sfaa192; html:https://europepmc.org/articles/PMC7577776; pdf:https://europepmc.org/articles/PMC7577776?pdf=render" }, + { + "id": "38036971", + "doi": "https://doi.org/10.1186/s12859-023-05576-7", + "title": "Completing a genomic characterisation of microscopic tumour samples with copy number.", + "authorString": "Nulsen J, Hussain N, Al-Deka A, Yap J, Uddin K, Yau C, Ahmed AA.", + "authorAffiliations": "", + "journalTitle": "BMC bioinformatics", + "pubYear": "2023", + "date": "2023-11-30", + "isOpenAccess": "Y", + "keywords": "Copy number; Microscopic Samples; Cancer Genomics", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Genomic insights in settings where tumour sample sizes are limited to just hundreds or even tens of cells hold great clinical potential, but also present significant technical challenges. We previously developed the DigiPico sequencing platform to accurately identify somatic mutations from such samples.

Results

Here, we complete this genomic characterisation with copy number. We present a novel protocol, PicoCNV, to call allele-specific somatic copy number alterations from picogram quantities of tumour DNA. We find that PicoCNV provides exactly accurate copy number in 84% of the genome for even the smallest samples, and demonstrate its clinical potential in maintenance therapy.

Conclusions

PicoCNV complements our existing platform, allowing for accurate and comprehensive genomic characterisations of cancers in settings where only microscopic samples are available.", + "laySummary": "", + "urls": "pdf:https://bmcbioinformatics.biomedcentral.com/counter/pdf/10.1186/s12859-023-05576-7; doi:https://doi.org/10.1186/s12859-023-05576-7; html:https://europepmc.org/articles/PMC10688092; pdf:https://europepmc.org/articles/PMC10688092?pdf=render" + }, { "id": "38018286", "doi": "https://doi.org/10.1111/vox.13564", @@ -13939,23 +13939,6 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/vox.13564; doi:https://doi.org/10.1111/vox.13564" }, - { - "id": "36280346", - "doi": "https://doi.org/10.1136/heartjnl-2022-321492", - "title": "Cardiovascular disease and mortality sequelae of COVID-19 in the UK Biobank.", - "authorString": "Raisi-Estabragh Z, Cooper J, Salih A, Raman B, Lee AM, Neubauer S, Harvey NC, Petersen SE.", - "authorAffiliations": "", - "journalTitle": "Heart (British Cardiac Society)", - "pubYear": "2022", - "date": "2022-12-22", - "isOpenAccess": "Y", - "keywords": "epidemiology; Covid-19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

To examine association of COVID-19 with incident cardiovascular events in 17\u2009871 UK Biobank cases between March 2020 and 2021.

Methods

COVID-19 cases were defined using health record linkage. Each case was propensity score-matched to two uninfected controls on age, sex, deprivation, body mass index, ethnicity, diabetes, prevalent ischaemic heart disease (IHD), smoking, hypertension and high cholesterol. We included the following incident outcomes: myocardial infarction, stroke, heart failure, atrial fibrillation, venous thromboembolism (VTE), pericarditis, all-cause death, cardiovascular death, IHD death. Cox proportional hazards regression was used to estimate associations of COVID-19 with each outcome over an average of 141 days (range 32-395) of prospective follow-up.

Results

Non-hospitalised cases (n=14\u2009304) had increased risk of incident VTE (HR 2.74 (95% CI 1.38 to 5.45), p=0.004) and death (HR 10.23 (95% CI 7.63 to 13.70), p<0.0001). Individuals with primary COVID-19 hospitalisation (n=2701) had increased risk of all outcomes considered. The largest effect sizes were with VTE (HR 27.6 (95% CI 14.5 to 52.3); p<0.0001), heart failure (HR 21.6 (95% CI 10.9 to 42.9); p<0.0001) and stroke (HR 17.5 (95% CI 5.26 to 57.9); p<0.0001). Those hospitalised with COVID-19 as a secondary diagnosis (n=866) had similarly increased cardiovascular risk. The associated risks were greatest in the first 30 days after infection but remained higher than controls even after this period.

Conclusions

Individuals hospitalised with COVID-19 have increased risk of incident cardiovascular events across a range of disease and mortality outcomes. The risk of most events is highest in the early postinfection period. Individuals not requiring hospitalisation have increased risk of VTE, but not of other cardiovascular-specific outcomes.", - "laySummary": "", - "urls": "pdf:https://heart.bmj.com/content/heartjnl/109/2/119.full.pdf; doi:https://doi.org/10.1136/heartjnl-2022-321492; html:https://europepmc.org/articles/PMC9811071; pdf:https://europepmc.org/articles/PMC9811071?pdf=render" - }, { "id": "33436761", "doi": "https://doi.org/10.1038/s41598-020-79964-x", @@ -13973,6 +13956,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41598-020-79964-x.pdf; doi:https://doi.org/10.1038/s41598-020-79964-x; html:https://europepmc.org/articles/PMC7804422; pdf:https://europepmc.org/articles/PMC7804422?pdf=render" }, + { + "id": "36280346", + "doi": "https://doi.org/10.1136/heartjnl-2022-321492", + "title": "Cardiovascular disease and mortality sequelae of COVID-19 in the UK Biobank.", + "authorString": "Raisi-Estabragh Z, Cooper J, Salih A, Raman B, Lee AM, Neubauer S, Harvey NC, Petersen SE.", + "authorAffiliations": "", + "journalTitle": "Heart (British Cardiac Society)", + "pubYear": "2022", + "date": "2022-12-22", + "isOpenAccess": "Y", + "keywords": "epidemiology; Covid-19", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

To examine association of COVID-19 with incident cardiovascular events in 17\u2009871 UK Biobank cases between March 2020 and 2021.

Methods

COVID-19 cases were defined using health record linkage. Each case was propensity score-matched to two uninfected controls on age, sex, deprivation, body mass index, ethnicity, diabetes, prevalent ischaemic heart disease (IHD), smoking, hypertension and high cholesterol. We included the following incident outcomes: myocardial infarction, stroke, heart failure, atrial fibrillation, venous thromboembolism (VTE), pericarditis, all-cause death, cardiovascular death, IHD death. Cox proportional hazards regression was used to estimate associations of COVID-19 with each outcome over an average of 141 days (range 32-395) of prospective follow-up.

Results

Non-hospitalised cases (n=14\u2009304) had increased risk of incident VTE (HR 2.74 (95% CI 1.38 to 5.45), p=0.004) and death (HR 10.23 (95% CI 7.63 to 13.70), p<0.0001). Individuals with primary COVID-19 hospitalisation (n=2701) had increased risk of all outcomes considered. The largest effect sizes were with VTE (HR 27.6 (95% CI 14.5 to 52.3); p<0.0001), heart failure (HR 21.6 (95% CI 10.9 to 42.9); p<0.0001) and stroke (HR 17.5 (95% CI 5.26 to 57.9); p<0.0001). Those hospitalised with COVID-19 as a secondary diagnosis (n=866) had similarly increased cardiovascular risk. The associated risks were greatest in the first 30 days after infection but remained higher than controls even after this period.

Conclusions

Individuals hospitalised with COVID-19 have increased risk of incident cardiovascular events across a range of disease and mortality outcomes. The risk of most events is highest in the early postinfection period. Individuals not requiring hospitalisation have increased risk of VTE, but not of other cardiovascular-specific outcomes.", + "laySummary": "", + "urls": "pdf:https://heart.bmj.com/content/heartjnl/109/2/119.full.pdf; doi:https://doi.org/10.1136/heartjnl-2022-321492; html:https://europepmc.org/articles/PMC9811071; pdf:https://europepmc.org/articles/PMC9811071?pdf=render" + }, { "id": "35301875", "doi": "https://doi.org/10.1161/jaha.121.023146", @@ -14024,6 +14024,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.eclinm.2021.101163; doi:https://doi.org/10.1016/j.eclinm.2021.101163; html:https://europepmc.org/articles/PMC8571171; pdf:https://europepmc.org/articles/PMC8571171?pdf=render" }, + { + "id": "34298561", + "doi": "https://doi.org/10.1177/2047487320914115", + "title": "Achievement of European guideline-recommended lipid levels post-percutaneous coronary intervention: A population-level observational cohort study.", + "authorString": "Harris DE, Lacey A, Akbari A, Torabi F, Smith D, Jenkins G, Obaid D, Chase A, Gravenor M, Halcox J.", + "authorAffiliations": "", + "journalTitle": "European journal of preventive cardiology", + "pubYear": "2021", + "date": "2021-07-01", + "isOpenAccess": "N", + "keywords": "Lipids; Cholesterol; Percutaneous coronary intervention; Secondary Prevention; Pharmacoepidemiology; statins", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

European Society of Cardiology/European Atherosclerosis Society 2019 guidelines recommend more aggressive lipid targets in high- and very high-risk patients and the addition of adjuvant treatments to statins in uncontrolled patients. We aimed to assess (a) achievement of prior and new European Society of Cardiology/European Atherosclerosis Society lipid targets and (b) lipid-lowering therapy prescribing in a nationwide cohort of very high-risk patients.

Methods

We conducted a retrospective observational population study using linked health data in patients undergoing percutaneous coronary intervention (2012-2017). Follow-up was for one-year post-discharge.

Results

Altogether, 10,071 patients had a documented LDL-C level, of whom 48% had low-density lipoprotein cholesterol (LDL-C)<1.8\u2009mmol/l (2016 target) and (23%) <1.4\u2009mmol/l (2019 target). Five thousand three hundred and forty patients had non-high-density lipoprotein cholesterol (non-HDL-C) documented with 57% <2.6\u2009mmol/l (2016) and 37% <2.2\u2009mmol/l (2019). In patients with recurrent vascular events, fewer than 6% of the patients achieved the 2019 LDL-C target of <1.0\u2009mmol/l. A total of 10,592 patients had triglyceride (TG) levels documented, of whom 14% were \u22652.3\u2009mmol/l and 41% \u22651.5\u2009mmol/l (2019). High-intensity statins were prescribed in 56.4% of the cohort, only 3% were prescribed ezetimibe, fibrates or prescription-grade N-3 fatty acids. Prescribing of these agents was lower amongst patients above target LDL-C, non-HDL-C and triglyceride levels. Females were more likely to have LDL-C, non-HDL-C and triglyceride levels above target.

Conclusion

There was a low rate of achievement of the new European Society of Cardiology/European Atherosclerosis Society lipid targets in this large post-percutaneous coronary intervention population and relatively low rates of intensive lipid-lowering therapy prescribing in those with uncontrolled lipids. There is considerable potential to optimise lipid-lowering therapy further through statin intensification and appropriate use of novel lipid-lowering therapy, especially in women.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/eurjpc/article-pdf/28/8/854/39301721/zwaa298.pdf; doi:https://doi.org/10.1177/2047487320914115" + }, { "id": "PMC10686417", "doi": "https://doi.org/", @@ -14058,23 +14075,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/jcem/advance-article-pdf/doi/10.1210/clinem/dgad201/50034331/dgad201.pdf; doi:https://doi.org/10.1210/clinem/dgad201; html:https://europepmc.org/articles/PMC10505547" }, - { - "id": "34298561", - "doi": "https://doi.org/10.1177/2047487320914115", - "title": "Achievement of European guideline-recommended lipid levels post-percutaneous coronary intervention: A population-level observational cohort study.", - "authorString": "Harris DE, Lacey A, Akbari A, Torabi F, Smith D, Jenkins G, Obaid D, Chase A, Gravenor M, Halcox J.", - "authorAffiliations": "", - "journalTitle": "European journal of preventive cardiology", - "pubYear": "2021", - "date": "2021-07-01", - "isOpenAccess": "N", - "keywords": "Lipids; Cholesterol; Percutaneous coronary intervention; Secondary Prevention; Pharmacoepidemiology; statins", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

European Society of Cardiology/European Atherosclerosis Society 2019 guidelines recommend more aggressive lipid targets in high- and very high-risk patients and the addition of adjuvant treatments to statins in uncontrolled patients. We aimed to assess (a) achievement of prior and new European Society of Cardiology/European Atherosclerosis Society lipid targets and (b) lipid-lowering therapy prescribing in a nationwide cohort of very high-risk patients.

Methods

We conducted a retrospective observational population study using linked health data in patients undergoing percutaneous coronary intervention (2012-2017). Follow-up was for one-year post-discharge.

Results

Altogether, 10,071 patients had a documented LDL-C level, of whom 48% had low-density lipoprotein cholesterol (LDL-C)<1.8\u2009mmol/l (2016 target) and (23%) <1.4\u2009mmol/l (2019 target). Five thousand three hundred and forty patients had non-high-density lipoprotein cholesterol (non-HDL-C) documented with 57% <2.6\u2009mmol/l (2016) and 37% <2.2\u2009mmol/l (2019). In patients with recurrent vascular events, fewer than 6% of the patients achieved the 2019 LDL-C target of <1.0\u2009mmol/l. A total of 10,592 patients had triglyceride (TG) levels documented, of whom 14% were \u22652.3\u2009mmol/l and 41% \u22651.5\u2009mmol/l (2019). High-intensity statins were prescribed in 56.4% of the cohort, only 3% were prescribed ezetimibe, fibrates or prescription-grade N-3 fatty acids. Prescribing of these agents was lower amongst patients above target LDL-C, non-HDL-C and triglyceride levels. Females were more likely to have LDL-C, non-HDL-C and triglyceride levels above target.

Conclusion

There was a low rate of achievement of the new European Society of Cardiology/European Atherosclerosis Society lipid targets in this large post-percutaneous coronary intervention population and relatively low rates of intensive lipid-lowering therapy prescribing in those with uncontrolled lipids. There is considerable potential to optimise lipid-lowering therapy further through statin intensification and appropriate use of novel lipid-lowering therapy, especially in women.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/eurjpc/article-pdf/28/8/854/39301721/zwaa298.pdf; doi:https://doi.org/10.1177/2047487320914115" - }, { "id": "35365351", "doi": "https://doi.org/10.1016/j.injury.2022.03.039", @@ -14381,23 +14381,6 @@ "laySummary": "", "urls": "pdf:https://publichealth.jmir.org/2023/1/e43419/PDF; doi:https://doi.org/10.2196/43419; html:https://europepmc.org/articles/PMC9989910" }, - { - "id": "36773891", - "doi": "https://doi.org/10.1016/j.jinf.2023.02.012", - "title": "Real-world effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab on preventing hospital admission among higher-risk patients with COVID-19 in Wales: A retrospective cohort study.", - "authorString": "Evans A, Qi C, Adebayo JO, Underwood J, Coulson J, Bailey R, Lyons R, Edwards A, Cooper A, John G, Akbari A.", - "authorAffiliations": "", - "journalTitle": "The Journal of infection", - "pubYear": "2023", - "date": "2023-02-10", - "isOpenAccess": "Y", - "keywords": "Health protection; Public Health; Covid-19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

To compare the effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab with no treatment in preventing hospital admission or death in higher-risk patients infected with SARS-CoV-2 in the community.

Design

Retrospective cohort study of non-hospitalized adult patients with COVID-19 using the Secure Anonymised Information Linkage (SAIL) Databank.

Setting

A real-world cohort study was conducted within the SAIL Databank (a secure trusted research environment containing anonymised, individual, population-scale electronic health record (EHR) data) for the population of Wales, UK.

Participants

Adult patients with COVID-19 in the community, at higher risk of hospitalization and death, testing positive for SARS-CoV-2 between 16th December 2021 and 22nd April 2022.

Interventions

Molnupiravir, nirmatrelvir-ritonavir, and sotrovimab given in the community by local health boards and the National Antiviral Service in Wales.

Main outcome measures

All-cause admission to hospital or death within 28 days of a positive test for SARS-CoV-2.

Statistical analysis

Cox proportional hazard model with treatment status (treated/untreated) as a time-dependent covariate and adjusted for age, sex, number of comorbidities, Welsh Index of Multiple Deprivation, and vaccination status. Secondary subgroup analyses were by treatment type, number of comorbidities, and before and on or after 20th February 2022, when omicron BA.1 and omicron BA.2 were the dominant subvariants in Wales.

Results

Between 16th December 2021 and 22nd April 2022, 7013 higher-risk patients were eligible for inclusion in the study. Of these, 2040 received treatment with molnupiravir (359, 17.6%), nirmatrelvir-ritonavir (602, 29.5%), or sotrovimab (1079, 52.9%). Patients in the treatment group were younger (mean age 53 vs 57 years), had fewer comorbidities, and a higher proportion had received four or more doses of the COVID-19 vaccine (36.3% vs 17.6%). Within 28 days of a positive test, 628 (9.0%) patients were admitted to hospital or died (84 treated and 544 untreated). The primary analysis indicated a lower risk of hospitalization or death at any point within 28 days in treated participants compared to those not receiving treatment. The adjusted hazard rate was 35% (95% CI: 18-49%) lower in treated than untreated participants. There was no indication of the superiority of one treatment over another and no evidence of a reduction in risk of hospitalization or death within 28 days for patients with no or only one comorbidity. In patients treated with sotrovimab, the event rates before and on or after 20th February 2022 were similar (5.0% vs 4.9%) with no significant difference in the hazard ratios for sotrovimab between the time periods.

Conclusions

In higher-risk adult patients in the community with COVID-19, those who received treatment with molnupiravir, nirmatrelvir-ritonavir, or sotrovimab were at lower risk of hospitalization or death than those not receiving treatment.", - "laySummary": "", - "urls": "pdf:http://www.journalofinfection.com/article/S0163445323000828/pdf; doi:https://doi.org/10.1016/j.jinf.2023.02.012; html:https://europepmc.org/articles/PMC9911979; pdf:https://europepmc.org/articles/PMC9911979?pdf=render" - }, { "id": "29938349", "doi": "https://doi.org/10.1007/s11892-018-1021-5", @@ -14415,6 +14398,23 @@ "laySummary": "", "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s11892-018-1021-5.pdf; doi:https://doi.org/10.1007/s11892-018-1021-5; html:https://europepmc.org/articles/PMC6015804; pdf:https://europepmc.org/articles/PMC6015804?pdf=render" }, + { + "id": "36773891", + "doi": "https://doi.org/10.1016/j.jinf.2023.02.012", + "title": "Real-world effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab on preventing hospital admission among higher-risk patients with COVID-19 in Wales: A retrospective cohort study.", + "authorString": "Evans A, Qi C, Adebayo JO, Underwood J, Coulson J, Bailey R, Lyons R, Edwards A, Cooper A, John G, Akbari A.", + "authorAffiliations": "", + "journalTitle": "The Journal of infection", + "pubYear": "2023", + "date": "2023-02-10", + "isOpenAccess": "Y", + "keywords": "Health protection; Public Health; Covid-19", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

To compare the effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab with no treatment in preventing hospital admission or death in higher-risk patients infected with SARS-CoV-2 in the community.

Design

Retrospective cohort study of non-hospitalized adult patients with COVID-19 using the Secure Anonymised Information Linkage (SAIL) Databank.

Setting

A real-world cohort study was conducted within the SAIL Databank (a secure trusted research environment containing anonymised, individual, population-scale electronic health record (EHR) data) for the population of Wales, UK.

Participants

Adult patients with COVID-19 in the community, at higher risk of hospitalization and death, testing positive for SARS-CoV-2 between 16th December 2021 and 22nd April 2022.

Interventions

Molnupiravir, nirmatrelvir-ritonavir, and sotrovimab given in the community by local health boards and the National Antiviral Service in Wales.

Main outcome measures

All-cause admission to hospital or death within 28 days of a positive test for SARS-CoV-2.

Statistical analysis

Cox proportional hazard model with treatment status (treated/untreated) as a time-dependent covariate and adjusted for age, sex, number of comorbidities, Welsh Index of Multiple Deprivation, and vaccination status. Secondary subgroup analyses were by treatment type, number of comorbidities, and before and on or after 20th February 2022, when omicron BA.1 and omicron BA.2 were the dominant subvariants in Wales.

Results

Between 16th December 2021 and 22nd April 2022, 7013 higher-risk patients were eligible for inclusion in the study. Of these, 2040 received treatment with molnupiravir (359, 17.6%), nirmatrelvir-ritonavir (602, 29.5%), or sotrovimab (1079, 52.9%). Patients in the treatment group were younger (mean age 53 vs 57 years), had fewer comorbidities, and a higher proportion had received four or more doses of the COVID-19 vaccine (36.3% vs 17.6%). Within 28 days of a positive test, 628 (9.0%) patients were admitted to hospital or died (84 treated and 544 untreated). The primary analysis indicated a lower risk of hospitalization or death at any point within 28 days in treated participants compared to those not receiving treatment. The adjusted hazard rate was 35% (95% CI: 18-49%) lower in treated than untreated participants. There was no indication of the superiority of one treatment over another and no evidence of a reduction in risk of hospitalization or death within 28 days for patients with no or only one comorbidity. In patients treated with sotrovimab, the event rates before and on or after 20th February 2022 were similar (5.0% vs 4.9%) with no significant difference in the hazard ratios for sotrovimab between the time periods.

Conclusions

In higher-risk adult patients in the community with COVID-19, those who received treatment with molnupiravir, nirmatrelvir-ritonavir, or sotrovimab were at lower risk of hospitalization or death than those not receiving treatment.", + "laySummary": "", + "urls": "pdf:http://www.journalofinfection.com/article/S0163445323000828/pdf; doi:https://doi.org/10.1016/j.jinf.2023.02.012; html:https://europepmc.org/articles/PMC9911979; pdf:https://europepmc.org/articles/PMC9911979?pdf=render" + }, { "id": "36112916", "doi": "https://doi.org/10.1177/09622802211055853", @@ -14432,23 +14432,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1177/09622802211055853; doi:https://doi.org/10.1177/09622802211055853; html:https://europepmc.org/articles/PMC9465559; pdf:https://europepmc.org/articles/PMC9465559?pdf=render" }, - { - "id": "38765656", - "doi": "https://doi.org/10.1016/j.jacasi.2024.01.005", - "title": "The Prognostic Value of Left Ventricular Entropy From T1 Mapping in Patients With Hypertrophic Cardiomyopathy.", - "authorString": "Wang J, Zhang J, Pu L, Qi W, Xu Y, Wan K, Zhu Y, Gkoutos GV, Han Y, Chen Y.", - "authorAffiliations": "", - "journalTitle": "JACC. Asia", - "pubYear": "2024", - "date": "2024-03-26", - "isOpenAccess": "Y", - "keywords": "Entropy; hypertrophic cardiomyopathy; Sudden Cardiac Death; Cardiac Magnetic Resonance; T1 Mapping", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

The prognostic value of left ventricular (LV) entropy in hypertrophic cardiomyopathy (HCM) is unclear.

Objectives

This study aimed to assess the prognostic value of LV entropy from T1 mapping in HCM.

Methods

A total of 748 participants with HCM, who underwent cardiovascular magnetic resonance (CMR), were consecutively enrolled. LV entropy was quantified by native T1 mapping. A competing risk analysis and a Cox proportional hazards regression analysis were performed to identify potential associations of LV entropy with sudden cardiac death (SCD) and cardiovascular death (CVD), respectively.

Results

A total of 40 patients with HCM experienced SCD, and 65 experienced CVD during a median follow-up of 43\u00a0months. Participants with increased LV entropy (\u22654.06) were more likely to experience SCD and CVD (all P\u00a0< 0.05) in the entire study cohort or the subgroup with low late gadolinium enhancement (LGE) extent (<15%). After adjustment for the European Society of Cardiology predictors and the presence of high LGE extent (\u226515%), LV mean entropy was an independent predictor for SCD (HR: 1.03; all P\u00a0< 0.05) by the multivariable competing risk analysis and CVD (HR: 1.06; 95%\u00a0CI: 1.03-1.09; P\u00a0< 0.001) by multivariable Cox regression analysis.

Conclusions

LV mean entropy derived from native T1 mapping, reflecting myocardial tissue heterogeneity, was an independent predictor of SCD and CVD in participants with HCM. (Cardiac Magnetic Resonance Imaging Clinical Application Registration Study; ChiCTR1900024094).", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jacasi.2024.01.005; html:https://europepmc.org/articles/PMC11099820; pdf:https://europepmc.org/articles/PMC11099820?pdf=render" - }, { "id": "33521768", "doi": "https://doi.org/10.1016/s2666-7568(20)30011-8", @@ -14466,6 +14449,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S2666756820300118/pdf; doi:https://doi.org/10.1016/S2666-7568(20)30011-8; html:https://europepmc.org/articles/PMC7834195; pdf:https://europepmc.org/articles/PMC7834195?pdf=render" }, + { + "id": "38765656", + "doi": "https://doi.org/10.1016/j.jacasi.2024.01.005", + "title": "The Prognostic Value of Left Ventricular Entropy From T1 Mapping in Patients With Hypertrophic Cardiomyopathy.", + "authorString": "Wang J, Zhang J, Pu L, Qi W, Xu Y, Wan K, Zhu Y, Gkoutos GV, Han Y, Chen Y.", + "authorAffiliations": "", + "journalTitle": "JACC. Asia", + "pubYear": "2024", + "date": "2024-03-26", + "isOpenAccess": "Y", + "keywords": "Entropy; hypertrophic cardiomyopathy; Sudden Cardiac Death; Cardiac Magnetic Resonance; T1 Mapping", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

The prognostic value of left ventricular (LV) entropy in hypertrophic cardiomyopathy (HCM) is unclear.

Objectives

This study aimed to assess the prognostic value of LV entropy from T1 mapping in HCM.

Methods

A total of 748 participants with HCM, who underwent cardiovascular magnetic resonance (CMR), were consecutively enrolled. LV entropy was quantified by native T1 mapping. A competing risk analysis and a Cox proportional hazards regression analysis were performed to identify potential associations of LV entropy with sudden cardiac death (SCD) and cardiovascular death (CVD), respectively.

Results

A total of 40 patients with HCM experienced SCD, and 65 experienced CVD during a median follow-up of 43\u00a0months. Participants with increased LV entropy (\u22654.06) were more likely to experience SCD and CVD (all P\u00a0< 0.05) in the entire study cohort or the subgroup with low late gadolinium enhancement (LGE) extent (<15%). After adjustment for the European Society of Cardiology predictors and the presence of high LGE extent (\u226515%), LV mean entropy was an independent predictor for SCD (HR: 1.03; all P\u00a0< 0.05) by the multivariable competing risk analysis and CVD (HR: 1.06; 95%\u00a0CI: 1.03-1.09; P\u00a0< 0.001) by multivariable Cox regression analysis.

Conclusions

LV mean entropy derived from native T1 mapping, reflecting myocardial tissue heterogeneity, was an independent predictor of SCD and CVD in participants with HCM. (Cardiac Magnetic Resonance Imaging Clinical Application Registration Study; ChiCTR1900024094).", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.jacasi.2024.01.005; html:https://europepmc.org/articles/PMC11099820; pdf:https://europepmc.org/articles/PMC11099820?pdf=render" + }, { "id": "36806317", "doi": "https://doi.org/10.1038/s41746-023-00749-3", @@ -14653,23 +14653,6 @@ "laySummary": "", "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01893-3; doi:https://doi.org/10.1186/s12916-020-01893-3; html:https://europepmc.org/articles/PMC7817348; pdf:https://europepmc.org/articles/PMC7817348?pdf=render" }, - { - "id": "36543561", - "doi": "https://doi.org/10.3399/bjgp.2022.0156", - "title": "Anticoagulation in older people with atrial fibrillation moving to care homes: a data linkage study.", - "authorString": "Ritchie LA, Harrison SL, Penson PE, Akbari A, Torabi F, Hollinghurst J, Harris D, Oke OB, Akpan A, Halcox JP, Rodgers SE, Lip GY, Lane DA.", - "authorAffiliations": "", - "journalTitle": "The British journal of general practice : the journal of the Royal College of General Practitioners", - "pubYear": "2023", - "date": "2022-12-21", - "isOpenAccess": "Y", - "keywords": "Anticoagulants; Atrial fibrillation; Primary Health Care; Nursing Homes; Long-term Care; Practice Patterns, Physicians\u2019", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Treatment decisions about oral anticoagulants (OACs) for atrial fibrillation (AF) are complex in older care home residents.

Aim

To explore factors associated with OAC prescription.

Design and setting

Retrospective cohort study set in care homes in Wales, UK, listed in the Care Inspectorate Wales Registry 2017/18.

Method

Analysis of anonymised individual-level electronic health and administrative data was carried out on people aged \u226565 years entering a care home between 1 January 2003 and 31 December 2018, provisioned from the Secure Anonymised Information Linkage Databank.

Results

Between 2003 and 2018, 14 493 people with AF aged \u226565 years became new residents in care homes in Wales and 7057 (48.7%) were prescribed OACs (32.7% in 2003 compared with 72.7% in 2018) within 6 months before care home entry. Increasing age and prescription of antiplatelet therapy were associated with lower odds of OAC prescription (adjusted odds ratio [aOR] 0.96 per 1-year age increase, 95% confidence interval [CI] = 0.95 to 0.96 and aOR 0.91, 95% CI = 0.84 to 0.98, respectively). Conversely, prior venous thromboembolism (aOR 4.06, 95% CI = 3.17 to 5.20), advancing frailty (mild: aOR 4.61, 95% CI = 3.95 to 5.38; moderate: aOR 6.69, 95% CI = 5.74 to 7.80; and severe: aOR 8.42, 95% CI = 7.16 to 9.90), and year of care home entry from 2011 onwards (aOR 1.91, 95% CI = 1.76 to 2.06) were associated with higher odds of an OAC prescription.

Conclusion

There has been an increase in OAC prescribing in older people newly admitted to care homes with AF. This study provides an insight into the factors influencing OAC prescribing in this population.", - "laySummary": "", - "urls": "pdf:https://bjgp.org/content/bjgp/73/726/e43.full.pdf; doi:https://doi.org/10.3399/BJGP.2022.0156; html:https://europepmc.org/articles/PMC9799341; pdf:https://europepmc.org/articles/PMC9799341?pdf=render" - }, { "id": "32855306", "doi": "https://doi.org/10.1136/gutjnl-2020-321650", @@ -14688,21 +14671,21 @@ "urls": "pdf:https://gut.bmj.com/content/gutjnl/70/6/1053.full.pdf; doi:https://doi.org/10.1136/gutjnl-2020-321650; html:https://europepmc.org/articles/PMC7447105; pdf:https://europepmc.org/articles/PMC7447105?pdf=render" }, { - "id": "38509467", - "doi": "https://doi.org/10.1186/s12874-024-02175-9", - "title": "Implementation and external validation of the Cambridge Multimorbidity Score in the UK Biobank cohort.", - "authorString": "Harrison H, Ip S, Renzi C, Li Y, Barclay M, Usher-Smith J, Lyratzopoulos G, Wood A, Antoniou AC.", + "id": "36543561", + "doi": "https://doi.org/10.3399/bjgp.2022.0156", + "title": "Anticoagulation in older people with atrial fibrillation moving to care homes: a data linkage study.", + "authorString": "Ritchie LA, Harrison SL, Penson PE, Akbari A, Torabi F, Hollinghurst J, Harris D, Oke OB, Akpan A, Halcox JP, Rodgers SE, Lip GY, Lane DA.", "authorAffiliations": "", - "journalTitle": "BMC medical research methodology", - "pubYear": "2024", - "date": "2024-03-20", + "journalTitle": "The British journal of general practice : the journal of the Royal College of General Practitioners", + "pubYear": "2023", + "date": "2022-12-21", "isOpenAccess": "Y", - "keywords": "Electronic Health Records; Multimorbidity; Uk Biobank; External Validation; Primary Care Records", + "keywords": "Anticoagulants; Atrial fibrillation; Primary Health Care; Nursing Homes; Long-term Care; Practice Patterns, Physicians\u2019", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Patients with multiple conditions present a growing challenge for healthcare provision. Measures of multimorbidity may support clinical management, healthcare resource allocation and accounting for the health of participants in purpose-designed cohorts. The recently developed Cambridge Multimorbidity scores (CMS) have the potential to achieve these aims using primary care records, however, they have not yet been validated outside of their development cohort.

Methods

The CMS, developed in the Clinical Research Practice Dataset (CPRD), were validated in UK Biobank participants whose data is not available in CPRD (the cohort used for CMS development) with available primary care records (n\u2009=\u2009111,898). This required mapping of the 37 pre-existing conditions used in the CMS to the coding frameworks used by UK Biobank data providers. We used calibration plots and measures of discrimination to validate the CMS for two of the three outcomes used in the development study (death and primary care consultation rate) and explored variation by age and sex. We also examined the predictive ability of the CMS for the outcome of cancer diagnosis. The results were compared to an unweighted count score of the 37 pre-existing conditions.

Results

For all three outcomes considered, the CMS were poorly calibrated in UK Biobank. We observed a similar discriminative ability for the outcome of primary care consultation rate to that reported in the development study (C-index: 0.67 (95%CI:0.66-0.68) for both, 5-year follow-up); however, we report lower discrimination for the outcome of death than the development study (0.69 (0.68-0.70) and 0.89 (0.88-0.90) respectively). Discrimination for cancer diagnosis was adequate (0.64 (0.63-0.65)). The CMS performs favourably to the unweighted count score for death, but not for the outcomes of primary care consultation rate or cancer diagnosis.

Conclusions

In the UK Biobank, CMS discriminates reasonably for the outcomes of death, primary care consultation rate and cancer diagnosis and may be a valuable resource for clinicians, public health professionals and data scientists. However, recalibration will be required to make accurate predictions when cohort composition and risk levels differ substantially from the development cohort. The generated resources (including codelists for the conditions and code for CMS implementation in UK Biobank) are available online.", + "abstract": "

Background

Treatment decisions about oral anticoagulants (OACs) for atrial fibrillation (AF) are complex in older care home residents.

Aim

To explore factors associated with OAC prescription.

Design and setting

Retrospective cohort study set in care homes in Wales, UK, listed in the Care Inspectorate Wales Registry 2017/18.

Method

Analysis of anonymised individual-level electronic health and administrative data was carried out on people aged \u226565 years entering a care home between 1 January 2003 and 31 December 2018, provisioned from the Secure Anonymised Information Linkage Databank.

Results

Between 2003 and 2018, 14 493 people with AF aged \u226565 years became new residents in care homes in Wales and 7057 (48.7%) were prescribed OACs (32.7% in 2003 compared with 72.7% in 2018) within 6 months before care home entry. Increasing age and prescription of antiplatelet therapy were associated with lower odds of OAC prescription (adjusted odds ratio [aOR] 0.96 per 1-year age increase, 95% confidence interval [CI] = 0.95 to 0.96 and aOR 0.91, 95% CI = 0.84 to 0.98, respectively). Conversely, prior venous thromboembolism (aOR 4.06, 95% CI = 3.17 to 5.20), advancing frailty (mild: aOR 4.61, 95% CI = 3.95 to 5.38; moderate: aOR 6.69, 95% CI = 5.74 to 7.80; and severe: aOR 8.42, 95% CI = 7.16 to 9.90), and year of care home entry from 2011 onwards (aOR 1.91, 95% CI = 1.76 to 2.06) were associated with higher odds of an OAC prescription.

Conclusion

There has been an increase in OAC prescribing in older people newly admitted to care homes with AF. This study provides an insight into the factors influencing OAC prescribing in this population.", "laySummary": "", - "urls": "pdf:https://bmcmedresmethodol.biomedcentral.com/counter/pdf/10.1186/s12874-024-02175-9; doi:https://doi.org/10.1186/s12874-024-02175-9; html:https://europepmc.org/articles/PMC10953059; pdf:https://europepmc.org/articles/PMC10953059?pdf=render" + "urls": "pdf:https://bjgp.org/content/bjgp/73/726/e43.full.pdf; doi:https://doi.org/10.3399/BJGP.2022.0156; html:https://europepmc.org/articles/PMC9799341; pdf:https://europepmc.org/articles/PMC9799341?pdf=render" }, { "id": "34044910", @@ -14721,6 +14704,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/bs.acc.2020.08.002" }, + { + "id": "38509467", + "doi": "https://doi.org/10.1186/s12874-024-02175-9", + "title": "Implementation and external validation of the Cambridge Multimorbidity Score in the UK Biobank cohort.", + "authorString": "Harrison H, Ip S, Renzi C, Li Y, Barclay M, Usher-Smith J, Lyratzopoulos G, Wood A, Antoniou AC.", + "authorAffiliations": "", + "journalTitle": "BMC medical research methodology", + "pubYear": "2024", + "date": "2024-03-20", + "isOpenAccess": "Y", + "keywords": "Electronic Health Records; Multimorbidity; Uk Biobank; External Validation; Primary Care Records", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Patients with multiple conditions present a growing challenge for healthcare provision. Measures of multimorbidity may support clinical management, healthcare resource allocation and accounting for the health of participants in purpose-designed cohorts. The recently developed Cambridge Multimorbidity scores (CMS) have the potential to achieve these aims using primary care records, however, they have not yet been validated outside of their development cohort.

Methods

The CMS, developed in the Clinical Research Practice Dataset (CPRD), were validated in UK Biobank participants whose data is not available in CPRD (the cohort used for CMS development) with available primary care records (n\u2009=\u2009111,898). This required mapping of the 37 pre-existing conditions used in the CMS to the coding frameworks used by UK Biobank data providers. We used calibration plots and measures of discrimination to validate the CMS for two of the three outcomes used in the development study (death and primary care consultation rate) and explored variation by age and sex. We also examined the predictive ability of the CMS for the outcome of cancer diagnosis. The results were compared to an unweighted count score of the 37 pre-existing conditions.

Results

For all three outcomes considered, the CMS were poorly calibrated in UK Biobank. We observed a similar discriminative ability for the outcome of primary care consultation rate to that reported in the development study (C-index: 0.67 (95%CI:0.66-0.68) for both, 5-year follow-up); however, we report lower discrimination for the outcome of death than the development study (0.69 (0.68-0.70) and 0.89 (0.88-0.90) respectively). Discrimination for cancer diagnosis was adequate (0.64 (0.63-0.65)). The CMS performs favourably to the unweighted count score for death, but not for the outcomes of primary care consultation rate or cancer diagnosis.

Conclusions

In the UK Biobank, CMS discriminates reasonably for the outcomes of death, primary care consultation rate and cancer diagnosis and may be a valuable resource for clinicians, public health professionals and data scientists. However, recalibration will be required to make accurate predictions when cohort composition and risk levels differ substantially from the development cohort. The generated resources (including codelists for the conditions and code for CMS implementation in UK Biobank) are available online.", + "laySummary": "", + "urls": "pdf:https://bmcmedresmethodol.biomedcentral.com/counter/pdf/10.1186/s12874-024-02175-9; doi:https://doi.org/10.1186/s12874-024-02175-9; html:https://europepmc.org/articles/PMC10953059; pdf:https://europepmc.org/articles/PMC10953059?pdf=render" + }, { "id": "36764720", "doi": "https://doi.org/10.1136/bmjopen-2022-063836", @@ -14772,23 +14772,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/jamiaopen/article-pdf/3/4/545/36625793/ooaa047.pdf; doi:https://doi.org/10.1093/jamiaopen/ooaa047; html:https://europepmc.org/articles/PMC7717266; pdf:https://europepmc.org/articles/PMC7717266?pdf=render" }, - { - "id": "37907891", - "doi": "https://doi.org/10.1186/s12888-023-05217-6", - "title": "Association between 5-min Apgar score and attention deficit hyperactivity disorder: a Scotland-wide record linkage study of 758,423 school children.", - "authorString": "Bala JJ, Bala JD, Pell JP, Fleming M.", - "authorAffiliations": "", - "journalTitle": "BMC psychiatry", - "pubYear": "2023", - "date": "2023-10-31", - "isOpenAccess": "Y", - "keywords": "attention deficit disorder with hyperactivity; Cohort studies; Education; Medical Record Linkage; Apgar Score", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Attention-deficit hyperactivity disorder (ADHD) affects around 1 in 20 children and is associated with life-long sequelae. Previous studies of the association between Apgar score and ADHD have reported inconsistent findings.

Methods

Record linkage of maternity, prescribing and school pupil census databases was used to conduct a population e-cohort study of singleton children born in Scotland and attending school in Scotland at any point between 2009 and 2013. Binary logistic regression analysis was used to investigate the association between 5-min Apgar score and treated ADHD adjusting for sociodemographic and maternity confounders.

Results

Of the 758,423 children, 7,292 (0.96%) received ADHD medication. The results suggested a potential dose-response relationship between Apgar score and treated ADHD independent of confounders. Referent to an Apgar score of 10, risk of treated ADHD was higher for scores of 0-3 (adjusted OR 1.76, 95% CI 1.32-2.34), 4-6 (adjusted OR 1.50, 95% CI 1.21-1.86) and even 7-9 (adjusted OR 1.26, 95% CI 1.18-1.36) which are traditionally considered within the normal range.

Conclusions

In addition to reinforcing the need to maximise Apgar score through good obstetric practice, the findings suggest that Apgar score may be useful in predicting future risk of ADHD and therefore facilitating early diagnosis and treatment.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s12888-023-05217-6; html:https://europepmc.org/articles/PMC10619264; pdf:https://europepmc.org/articles/PMC10619264?pdf=render" - }, { "id": "33262478", "doi": "https://doi.org/10.1038/s41433-020-01326-8", @@ -14807,38 +14790,21 @@ "urls": "pdf:https://www.nature.com/articles/s41433-020-01326-8.pdf; doi:https://doi.org/10.1038/s41433-020-01326-8; html:https://europepmc.org/articles/PMC8452782; pdf:https://europepmc.org/articles/PMC8452782?pdf=render; doi:https://doi.org/10.1038/s41433-020-01326-8" }, { - "id": "37657941", - "doi": "https://doi.org/10.1212/wnl.0000000000207777", - "title": "Exploring the Role of Plasma Lipids and Statin Interventions on Multiple Sclerosis Risk and Severity: A Mendelian Randomization Study.", - "authorString": "Almramhi MM, Finan C, Storm CS, Schmidt AF, Kia DA, Coneys R, Chopade S, Hingorani AD, Wood NW.", + "id": "37907891", + "doi": "https://doi.org/10.1186/s12888-023-05217-6", + "title": "Association between 5-min Apgar score and attention deficit hyperactivity disorder: a Scotland-wide record linkage study of 758,423 school children.", + "authorString": "Bala JJ, Bala JD, Pell JP, Fleming M.", "authorAffiliations": "", - "journalTitle": "Neurology", + "journalTitle": "BMC psychiatry", "pubYear": "2023", - "date": "2023-09-01", + "date": "2023-10-31", "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background and objectives

There has been considerable interest in statins because of their pleiotropic effects beyond their lipid-lowering properties. Many of these pleiotropic effects are predominantly ascribed to Rho small guanosine triphosphatases (Rho GTPases) proteins. We aimed to genetically investigate the role of lipids and statin interventions on multiple sclerosis (MS) risk and severity.

Method

We used two-sample Mendelian randomization (MR) to investigate (1) the causal role of genetically mimic both cholesterol-dependent (through low-density lipoprotein cholesterol (LDL-C) and cholesterol biosynthesis pathway) and cholesterol-independent (through Rho GTPases) effects of statins on MS risk and MS severity, (2) the causal link between lipids (high-density lipoprotein cholesterol [HDL-C] and triglycerides [TG]) levels and MS risk and severity, and (3) the reverse causation between lipid fractions and MS risk. We used summary statistics from the Global Lipids Genetics Consortium (GLGC), eQTLGen Consortium, and the International MS Genetics Consortium (IMSGC) for lipids, expression quantitative trait loci, and MS, respectively (GLGC: n = 188,577; eQTLGen: n = 31,684; IMSGC (MS risk): n = 41,505; IMSGC (MS severity): n = 7,069).

Results

The results of MR using the inverse-variance weighted method show that genetically predicted RAC2, a member of cholesterol-independent pathway (OR 0.86 [95% CI 0.78-0.95], p-value 3.80E-03), is implicated causally in reducing MS risk. We found no evidence for the causal role of LDL-C and the member of cholesterol biosynthesis pathway on MS risk. The MR results also show that lifelong higher HDL-C (OR 1.14 [95% CI 1.04-1.26], p-value 7.94E-03) increases MS risk but TG was not. Furthermore, we found no evidence for the causal role of lipids and genetically mimicked statins on MS severity. There is no evidence of reverse causation between MS risk and lipids.

Discussion

Evidence from this study suggests that RAC2 is a genetic modifier of MS risk. Because RAC2 has been reported to mediate some of the pleiotropic effects of statins, we suggest that statins may reduce MS risk through a cholesterol-independent pathway (that is, RAC2-related mechanism(s)). MR analyses also support a causal effect of HDL-C on MS risk.", - "laySummary": "", - "urls": "pdf:https://n.neurology.org/content/neurology/early/2023/09/01/WNL.0000000000207777.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000207777; html:https://europepmc.org/articles/PMC10624499; pdf:https://europepmc.org/articles/PMC10624499?pdf=render" - }, - { - "id": "37042240", - "doi": "https://doi.org/10.1161/circimaging.122.014519", - "title": "Explainable Artificial Intelligence and Cardiac Imaging: Toward More Interpretable Models.", - "authorString": "Salih A, Boscolo Galazzo I, Gkontra P, Lee AM, Lekadir K, Raisi-Estabragh Z, Petersen SE.", - "authorAffiliations": "", - "journalTitle": "Circulation. Cardiovascular imaging", - "pubYear": "2023", - "date": "2023-04-12", - "isOpenAccess": "N", - "keywords": "Artificial intelligence; Diagnostic Imaging; Machine Learning; Cardiac Imaging Techniques", + "keywords": "attention deficit disorder with hyperactivity; Cohort studies; Education; Medical Record Linkage; Apgar Score", "nationalPriorities": "", "healthCategories": "", - "abstract": "Artificial intelligence applications have shown success in different medical and health care domains, and cardiac imaging is no exception. However, some machine learning models, especially deep learning, are considered black box as they do not provide an explanation or rationale for model outcomes. Complexity and vagueness in these models necessitate a transition to explainable artificial intelligence (XAI) methods to ensure that model results are both transparent and understandable to end users. In cardiac imaging studies, there are a limited number of papers that use XAI methodologies. This article provides a comprehensive literature review of state-of-the-art works using XAI methods for cardiac imaging. Moreover, it provides simple and comprehensive guidelines on XAI. Finally, open issues and directions for XAI in cardiac imaging are discussed.", + "abstract": "

Background

Attention-deficit hyperactivity disorder (ADHD) affects around 1 in 20 children and is associated with life-long sequelae. Previous studies of the association between Apgar score and ADHD have reported inconsistent findings.

Methods

Record linkage of maternity, prescribing and school pupil census databases was used to conduct a population e-cohort study of singleton children born in Scotland and attending school in Scotland at any point between 2009 and 2013. Binary logistic regression analysis was used to investigate the association between 5-min Apgar score and treated ADHD adjusting for sociodemographic and maternity confounders.

Results

Of the 758,423 children, 7,292 (0.96%) received ADHD medication. The results suggested a potential dose-response relationship between Apgar score and treated ADHD independent of confounders. Referent to an Apgar score of 10, risk of treated ADHD was higher for scores of 0-3 (adjusted OR 1.76, 95% CI 1.32-2.34), 4-6 (adjusted OR 1.50, 95% CI 1.21-1.86) and even 7-9 (adjusted OR 1.26, 95% CI 1.18-1.36) which are traditionally considered within the normal range.

Conclusions

In addition to reinforcing the need to maximise Apgar score through good obstetric practice, the findings suggest that Apgar score may be useful in predicting future risk of ADHD and therefore facilitating early diagnosis and treatment.", "laySummary": "", - "urls": "doi:https://doi.org/10.1161/CIRCIMAGING.122.014519" + "urls": "doi:https://doi.org/10.1186/s12888-023-05217-6; html:https://europepmc.org/articles/PMC10619264; pdf:https://europepmc.org/articles/PMC10619264?pdf=render" }, { "id": "30423068", @@ -14874,6 +14840,40 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e043906.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-043906; html:https://europepmc.org/articles/PMC8211043; pdf:https://europepmc.org/articles/PMC8211043?pdf=render" }, + { + "id": "37657941", + "doi": "https://doi.org/10.1212/wnl.0000000000207777", + "title": "Exploring the Role of Plasma Lipids and Statin Interventions on Multiple Sclerosis Risk and Severity: A Mendelian Randomization Study.", + "authorString": "Almramhi MM, Finan C, Storm CS, Schmidt AF, Kia DA, Coneys R, Chopade S, Hingorani AD, Wood NW.", + "authorAffiliations": "", + "journalTitle": "Neurology", + "pubYear": "2023", + "date": "2023-09-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background and objectives

There has been considerable interest in statins because of their pleiotropic effects beyond their lipid-lowering properties. Many of these pleiotropic effects are predominantly ascribed to Rho small guanosine triphosphatases (Rho GTPases) proteins. We aimed to genetically investigate the role of lipids and statin interventions on multiple sclerosis (MS) risk and severity.

Method

We used two-sample Mendelian randomization (MR) to investigate (1) the causal role of genetically mimic both cholesterol-dependent (through low-density lipoprotein cholesterol (LDL-C) and cholesterol biosynthesis pathway) and cholesterol-independent (through Rho GTPases) effects of statins on MS risk and MS severity, (2) the causal link between lipids (high-density lipoprotein cholesterol [HDL-C] and triglycerides [TG]) levels and MS risk and severity, and (3) the reverse causation between lipid fractions and MS risk. We used summary statistics from the Global Lipids Genetics Consortium (GLGC), eQTLGen Consortium, and the International MS Genetics Consortium (IMSGC) for lipids, expression quantitative trait loci, and MS, respectively (GLGC: n = 188,577; eQTLGen: n = 31,684; IMSGC (MS risk): n = 41,505; IMSGC (MS severity): n = 7,069).

Results

The results of MR using the inverse-variance weighted method show that genetically predicted RAC2, a member of cholesterol-independent pathway (OR 0.86 [95% CI 0.78-0.95], p-value 3.80E-03), is implicated causally in reducing MS risk. We found no evidence for the causal role of LDL-C and the member of cholesterol biosynthesis pathway on MS risk. The MR results also show that lifelong higher HDL-C (OR 1.14 [95% CI 1.04-1.26], p-value 7.94E-03) increases MS risk but TG was not. Furthermore, we found no evidence for the causal role of lipids and genetically mimicked statins on MS severity. There is no evidence of reverse causation between MS risk and lipids.

Discussion

Evidence from this study suggests that RAC2 is a genetic modifier of MS risk. Because RAC2 has been reported to mediate some of the pleiotropic effects of statins, we suggest that statins may reduce MS risk through a cholesterol-independent pathway (that is, RAC2-related mechanism(s)). MR analyses also support a causal effect of HDL-C on MS risk.", + "laySummary": "", + "urls": "pdf:https://n.neurology.org/content/neurology/early/2023/09/01/WNL.0000000000207777.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000207777; html:https://europepmc.org/articles/PMC10624499; pdf:https://europepmc.org/articles/PMC10624499?pdf=render" + }, + { + "id": "37042240", + "doi": "https://doi.org/10.1161/circimaging.122.014519", + "title": "Explainable Artificial Intelligence and Cardiac Imaging: Toward More Interpretable Models.", + "authorString": "Salih A, Boscolo Galazzo I, Gkontra P, Lee AM, Lekadir K, Raisi-Estabragh Z, Petersen SE.", + "authorAffiliations": "", + "journalTitle": "Circulation. Cardiovascular imaging", + "pubYear": "2023", + "date": "2023-04-12", + "isOpenAccess": "N", + "keywords": "Artificial intelligence; Diagnostic Imaging; Machine Learning; Cardiac Imaging Techniques", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Artificial intelligence applications have shown success in different medical and health care domains, and cardiac imaging is no exception. However, some machine learning models, especially deep learning, are considered black box as they do not provide an explanation or rationale for model outcomes. Complexity and vagueness in these models necessitate a transition to explainable artificial intelligence (XAI) methods to ensure that model results are both transparent and understandable to end users. In cardiac imaging studies, there are a limited number of papers that use XAI methodologies. This article provides a comprehensive literature review of state-of-the-art works using XAI methods for cardiac imaging. Moreover, it provides simple and comprehensive guidelines on XAI. Finally, open issues and directions for XAI in cardiac imaging are discussed.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1161/CIRCIMAGING.122.014519" + }, { "id": "29925668", "doi": "https://doi.org/10.1136/jech-2017-210370", @@ -15061,23 +15061,6 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0243843&type=printable; doi:https://doi.org/10.1371/journal.pone.0243843; html:https://europepmc.org/articles/PMC7737962; pdf:https://europepmc.org/articles/PMC7737962?pdf=render" }, - { - "id": "38740716", - "doi": "https://doi.org/10.1007/s40266-024-01116-x", - "title": "Associations Between Midlife Anticholinergic Medication Use and Subsequent Cognitive Decline: A British Birth Cohort Study.", - "authorString": "Rawle MJ, Lau WCY, Gonzalez-Izquierdo A, Patalay P, Richards M, Davis D.", - "authorAffiliations": "", - "journalTitle": "Drugs & aging", - "pubYear": "2024", - "date": "2024-05-13", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Anticholinergic medication use is associated with cognitive decline and incident dementia. Our study, a prospective birth\u00a0cohort\u00a0analysis, aimed to determine if repeated exposure to anticholinergic medications\u00a0was associated with greater decline, and whether decline was reversed with medication reduction.

Methods

From the Medical Research Council (MRC) National Survey of Health and Development, a British birth cohort with all participants born in a single week of March 1946, we quantified anticholinergic exposure between ages 53 and 69 years using the Anticholinergic Cognitive Burden Scale (ACBS). We used multinomial regression to estimate associations with global cognition, quantified by\u00a0the Addenbrooke's Cognitive Examination, 3rd Edition (ACE-III). Longitudinal associations between ACBS and cognitive test results (Verbal memory quantified\u00a0by the\u00a0Word Learning Test [WLT], and processing speed quantified by the\u00a0Timed Letter Search Task [TLST]) at three time points (age 53, 60-64 and 69) were assessed using mixed and fixed effects linear regression models. Analyses were adjusted for sex, childhood cognition, education, chronic disease count and severity, and mental health symptoms.

Results

Anticholinergic exposure was associated cross-sectionally with lower ACE-III scores at age 69, with the greatest effects in those with high exposure at ages 60-64 (mean difference -\u20092.34, 95% confidence interval [CI] -\u20093.51 to -\u20091.17). Longitudinally, both mild-moderate and high ACBS scores were linked to lower WLT scores, again with high exposure showing larger effects (mean difference with contemporaneous exposure -\u20090.90, 95% CI -\u20091.63 to -\u20090.17; mean difference with lagged exposure -\u20091.53, 95% CI -\u20092.43 to -\u20090.64). Associations remained in fixed effects models (mean difference with contemporaneous exposure -1.78, 95% CI -2.85 to -\u20090.71; mean difference with lagged exposure -\u20092.23, 95% CI -\u20093.33 to -\u20091.13). Associations with TLST were noted only in isolated contemporaneous exposure (mean difference -\u200913.14, 95% CI -\u200919.04 to -\u20097.23; p\u00a0<\u00a00.01).

Conclusions

Anticholinergic exposure throughout mid and later life was associated with lower cognitive function. Reduced processing speed was associated only with contemporaneous anticholinergic medication use, and not historical use. Associations with lower verbal recall were evident with both historical and contemporaneous use of anticholinergic medication, and associations with historical use persisted in individuals even when their anticholinergic medication use decreased over the course of the study.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1007/s40266-024-01116-x" - }, { "id": "35429382", "doi": "https://doi.org/10.1093/infdis/jiac146", @@ -15112,6 +15095,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S1473309921002899/pdf; doi:https://doi.org/10.1016/S1473-3099(21)00289-9; html:https://europepmc.org/articles/PMC8221738" }, + { + "id": "38740716", + "doi": "https://doi.org/10.1007/s40266-024-01116-x", + "title": "Associations Between Midlife Anticholinergic Medication Use and Subsequent Cognitive Decline: A British Birth Cohort Study.", + "authorString": "Rawle MJ, Lau WCY, Gonzalez-Izquierdo A, Patalay P, Richards M, Davis D.", + "authorAffiliations": "", + "journalTitle": "Drugs & aging", + "pubYear": "2024", + "date": "2024-05-13", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Anticholinergic medication use is associated with cognitive decline and incident dementia. Our study, a prospective birth\u00a0cohort\u00a0analysis, aimed to determine if repeated exposure to anticholinergic medications\u00a0was associated with greater decline, and whether decline was reversed with medication reduction.

Methods

From the Medical Research Council (MRC) National Survey of Health and Development, a British birth cohort with all participants born in a single week of March 1946, we quantified anticholinergic exposure between ages 53 and 69 years using the Anticholinergic Cognitive Burden Scale (ACBS). We used multinomial regression to estimate associations with global cognition, quantified by\u00a0the Addenbrooke's Cognitive Examination, 3rd Edition (ACE-III). Longitudinal associations between ACBS and cognitive test results (Verbal memory quantified\u00a0by the\u00a0Word Learning Test [WLT], and processing speed quantified by the\u00a0Timed Letter Search Task [TLST]) at three time points (age 53, 60-64 and 69) were assessed using mixed and fixed effects linear regression models. Analyses were adjusted for sex, childhood cognition, education, chronic disease count and severity, and mental health symptoms.

Results

Anticholinergic exposure was associated cross-sectionally with lower ACE-III scores at age 69, with the greatest effects in those with high exposure at ages 60-64 (mean difference -\u20092.34, 95% confidence interval [CI] -\u20093.51 to -\u20091.17). Longitudinally, both mild-moderate and high ACBS scores were linked to lower WLT scores, again with high exposure showing larger effects (mean difference with contemporaneous exposure -\u20090.90, 95% CI -\u20091.63 to -\u20090.17; mean difference with lagged exposure -\u20091.53, 95% CI -\u20092.43 to -\u20090.64). Associations remained in fixed effects models (mean difference with contemporaneous exposure -1.78, 95% CI -2.85 to -\u20090.71; mean difference with lagged exposure -\u20092.23, 95% CI -\u20093.33 to -\u20091.13). Associations with TLST were noted only in isolated contemporaneous exposure (mean difference -\u200913.14, 95% CI -\u200919.04 to -\u20097.23; p\u00a0<\u00a00.01).

Conclusions

Anticholinergic exposure throughout mid and later life was associated with lower cognitive function. Reduced processing speed was associated only with contemporaneous anticholinergic medication use, and not historical use. Associations with lower verbal recall were evident with both historical and contemporaneous use of anticholinergic medication, and associations with historical use persisted in individuals even when their anticholinergic medication use decreased over the course of the study.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1007/s40266-024-01116-x" + }, { "id": "36763324", "doi": "https://doi.org/10.1007/s12687-023-00635-1", @@ -15129,23 +15129,6 @@ "laySummary": "", "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s12687-023-00635-1.pdf; doi:https://doi.org/10.1007/s12687-023-00635-1; html:https://europepmc.org/articles/PMC10576689; pdf:https://europepmc.org/articles/PMC10576689?pdf=render" }, - { - "id": "36382153", - "doi": "https://doi.org/10.5334/gh.1166", - "title": "Risk Factors and Prevalence of Dilated Cardiomyopathy in Sub-Saharan Africa: A Systematic Review.", - "authorString": "Fundikira LS, Chillo P, Mutagaywa R, Kamuhabwa A, Kwesigabo G, Asselbergs FW, van Laake LW.", - "authorAffiliations": "", - "journalTitle": "Global heart", - "pubYear": "2022", - "date": "2022-10-21", - "isOpenAccess": "Y", - "keywords": "Dilated cardiomyopathy; Sub-Saharan Africa; Cardiovascular risk factors", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Highlights\u00a0 Prevalence of DCM varies widely in SSA.Cardiovascular risk factors are important in patients with DCM.The role of genetics in idiopathic DCM is not studied in major part of SSA.", - "laySummary": "", - "urls": "pdf:http://globalheartjournal.com/articles/10.5334/gh.1166/galley/1329/download/; doi:https://doi.org/10.5334/gh.1166; html:https://europepmc.org/articles/PMC9585983; pdf:https://europepmc.org/articles/PMC9585983?pdf=render" - }, { "id": "34716166", "doi": "https://doi.org/10.1136/bmjopen-2021-053268", @@ -15163,6 +15146,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/10/e053268.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-053268; html:https://europepmc.org/articles/PMC8559117; pdf:https://europepmc.org/articles/PMC8559117?pdf=render" }, + { + "id": "36382153", + "doi": "https://doi.org/10.5334/gh.1166", + "title": "Risk Factors and Prevalence of Dilated Cardiomyopathy in Sub-Saharan Africa: A Systematic Review.", + "authorString": "Fundikira LS, Chillo P, Mutagaywa R, Kamuhabwa A, Kwesigabo G, Asselbergs FW, van Laake LW.", + "authorAffiliations": "", + "journalTitle": "Global heart", + "pubYear": "2022", + "date": "2022-10-21", + "isOpenAccess": "Y", + "keywords": "Dilated cardiomyopathy; Sub-Saharan Africa; Cardiovascular risk factors", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Highlights\u00a0 Prevalence of DCM varies widely in SSA.Cardiovascular risk factors are important in patients with DCM.The role of genetics in idiopathic DCM is not studied in major part of SSA.", + "laySummary": "", + "urls": "pdf:http://globalheartjournal.com/articles/10.5334/gh.1166/galley/1329/download/; doi:https://doi.org/10.5334/gh.1166; html:https://europepmc.org/articles/PMC9585983; pdf:https://europepmc.org/articles/PMC9585983?pdf=render" + }, { "id": "36038914", "doi": "https://doi.org/10.1186/s12916-022-02473-3", @@ -15333,23 +15333,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1148/radiol.232455" }, - { - "id": "37777816", - "doi": "https://doi.org/10.1186/s13643-023-02337-8", - "title": "Patient-reported outcome (PRO) instruments used in patients undergoing adoptive cell therapy (ACT) for the treatment of cancer: a systematic review.", - "authorString": "Taylor S, Law K, Coomber-Moore J, Davies M, Thistlethwaite F, Calvert M, Aiyegbusi O, Yorke J.", - "authorAffiliations": "", - "journalTitle": "Systematic reviews", - "pubYear": "2023", - "date": "2023-09-30", - "isOpenAccess": "Y", - "keywords": "Cancer; Systematic; Review; Quality of life; Patient-reported Outcomes (Pros); Adoptive Cell Therapy (Act)", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

Adoptive cell therapy (ACT) is a rapidly evolving field. Patient-reported outcomes (PROs) allow patients to report the impact of treatment on their quality of life during and after treatment. The systematic review aims to characterise the breadth of PROs utilised in ACT cancer care and provide guidance for the use of PROs in this patient population in the future.

Methods

A systematic search was conducted (MEDLINE, PsycINFO, Embase and CINAHL) in August 2021 by two reviewers. Search terms covered the following: \"adoptive cell therapy\", \"patient-reported outcomes\" and \"cancer\". Studies were included if they used a PRO measure to report the impact of ACT. The methodological quality of PROs was assessed. Forward and backward reference searching was conducted of any relevant papers. A quality grading scale was applied based on Cochrane and Revenson criteria for classification of high-quality studies. Key data from the studies and the included PROs was extracted by two researchers and tabulated.

Results

One-hundred nine papers were identified; 11 papers were included. The majority of studies were single-arm trials or observational studies. Twenty-two different PROs were identified; none was ACT specific. The PROMIS-29 and EQ-5D were most commonly used. Few studies collected PRO data in the first 1-2\u00a0weeks. Four studies followed patients up for over a year, and a further four studies followed patients for approximately 3\u00a0months.

Discussion

None of the PROs identified have been designed specifically for ACT. Appropriateness of existing instruments should be considered. It should be considered whether it is appropriate to collect data more frequently in the acute stage and then less frequently during follow-up. It should be considered if one tool is suitable at all time points or if the tool should be adapted depending on time since treatment. More research is needed to identify the exact timings of PRO assessments, and qualitative work with patients is needed to determine the most important issues for them throughout the treatment and follow-up.", - "laySummary": "", - "urls": "pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02337-8; doi:https://doi.org/10.1186/s13643-023-02337-8; html:https://europepmc.org/articles/PMC10541698; pdf:https://europepmc.org/articles/PMC10541698?pdf=render" - }, { "id": "35776101", "doi": "https://doi.org/10.1093/ije/dyac140", @@ -15367,6 +15350,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac140/45030523/dyac140.pdf; doi:https://doi.org/10.1093/ije/dyac140; html:https://europepmc.org/articles/PMC9749723; pdf:https://europepmc.org/articles/PMC9749723?pdf=render" }, + { + "id": "37777816", + "doi": "https://doi.org/10.1186/s13643-023-02337-8", + "title": "Patient-reported outcome (PRO) instruments used in patients undergoing adoptive cell therapy (ACT) for the treatment of cancer: a systematic review.", + "authorString": "Taylor S, Law K, Coomber-Moore J, Davies M, Thistlethwaite F, Calvert M, Aiyegbusi O, Yorke J.", + "authorAffiliations": "", + "journalTitle": "Systematic reviews", + "pubYear": "2023", + "date": "2023-09-30", + "isOpenAccess": "Y", + "keywords": "Cancer; Systematic; Review; Quality of life; Patient-reported Outcomes (Pros); Adoptive Cell Therapy (Act)", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

Adoptive cell therapy (ACT) is a rapidly evolving field. Patient-reported outcomes (PROs) allow patients to report the impact of treatment on their quality of life during and after treatment. The systematic review aims to characterise the breadth of PROs utilised in ACT cancer care and provide guidance for the use of PROs in this patient population in the future.

Methods

A systematic search was conducted (MEDLINE, PsycINFO, Embase and CINAHL) in August 2021 by two reviewers. Search terms covered the following: \"adoptive cell therapy\", \"patient-reported outcomes\" and \"cancer\". Studies were included if they used a PRO measure to report the impact of ACT. The methodological quality of PROs was assessed. Forward and backward reference searching was conducted of any relevant papers. A quality grading scale was applied based on Cochrane and Revenson criteria for classification of high-quality studies. Key data from the studies and the included PROs was extracted by two researchers and tabulated.

Results

One-hundred nine papers were identified; 11 papers were included. The majority of studies were single-arm trials or observational studies. Twenty-two different PROs were identified; none was ACT specific. The PROMIS-29 and EQ-5D were most commonly used. Few studies collected PRO data in the first 1-2\u00a0weeks. Four studies followed patients up for over a year, and a further four studies followed patients for approximately 3\u00a0months.

Discussion

None of the PROs identified have been designed specifically for ACT. Appropriateness of existing instruments should be considered. It should be considered whether it is appropriate to collect data more frequently in the acute stage and then less frequently during follow-up. It should be considered if one tool is suitable at all time points or if the tool should be adapted depending on time since treatment. More research is needed to identify the exact timings of PRO assessments, and qualitative work with patients is needed to determine the most important issues for them throughout the treatment and follow-up.", + "laySummary": "", + "urls": "pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02337-8; doi:https://doi.org/10.1186/s13643-023-02337-8; html:https://europepmc.org/articles/PMC10541698; pdf:https://europepmc.org/articles/PMC10541698?pdf=render" + }, { "id": "36715329", "doi": "https://doi.org/10.1093/bjd/ljac090", @@ -15520,23 +15520,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad376/50684614/ehad376.pdf; doi:https://doi.org/10.1093/eurheartj/ehad376; html:https://europepmc.org/articles/PMC10406338; pdf:https://europepmc.org/articles/PMC10406338?pdf=render" }, - { - "id": "37294923", - "doi": "https://doi.org/10.1093/eurjpc/zwad192", - "title": "Incidence of 12 common cardiovascular diseases and subsequent mortality risk in the general population.", - "authorString": "Prugger C, Perier MC, Gonzalez-Izquierdo A, Hemingway H, Denaxas S, Empana JP.", - "authorAffiliations": "", - "journalTitle": "European journal of preventive cardiology", - "pubYear": "2023", - "date": "2023-10-01", - "isOpenAccess": "N", - "keywords": "Prevention; Survival analysis; Stroke; epidemiology; Coronary Heart Disease; incidence", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Incident events of cardiovascular diseases (CVDs) are heterogenous and may result in different mortality risks. Such evidence may help inform patient and physician decisions in CVD prevention and risk factor management.

Aims

This study aimed to determine the extent to which incident events of common CVD show heterogeneous associations with subsequent mortality risk in the general population.

Methods and results

Based on England-wide linked electronic health records, we established a cohort of 1 310 518 people \u226530 years of age initially free of CVD and followed up for non-fatal events of 12 common CVD and cause-specific mortality. The 12 CVDs were considered as time-varying exposures in Cox's proportional hazards models to estimate hazard rate ratios (HRRs) with 95% confidence intervals (CIs). Over the median follow-up of 4.2 years (2010-16), 81 516 non-fatal CVD, 10 906 cardiovascular deaths, and 40 843 non-cardiovascular deaths occurred. All 12 CVDs were associated with increased risk of cardiovascular mortality, with HRR (95% CI) ranging from 1.67 (1.47-1.89) for stable angina to 7.85 (6.62-9.31) for haemorrhagic stroke. All 12 CVDs were also associated with increased non-cardiovascular and all-cause mortality risk but to a lesser extent: HRR (95% CI) ranged from 1.10 (1.00-1.22) to 4.55 (4.03-5.13) and from 1.24 (1.13-1.35) to 4.92 (4.44-5.46) for transient ischaemic attack and sudden cardiac arrest, respectively.

Conclusion

Incident events of 12 common CVD show significant adverse and markedly differential associations with subsequent cardiovascular, non-cardiovascular, and all-cause mortality risk in the general population.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/eurjpc/zwad192" - }, { "id": "33413610", "doi": "https://doi.org/10.1186/s13073-020-00822-6", @@ -15554,6 +15537,23 @@ "laySummary": "", "urls": "pdf:https://genomemedicine.biomedcentral.com/counter/pdf/10.1186/s13073-020-00822-6; doi:https://doi.org/10.1186/s13073-020-00822-6; html:https://europepmc.org/articles/PMC7790334; pdf:https://europepmc.org/articles/PMC7790334?pdf=render" }, + { + "id": "37294923", + "doi": "https://doi.org/10.1093/eurjpc/zwad192", + "title": "Incidence of 12 common cardiovascular diseases and subsequent mortality risk in the general population.", + "authorString": "Prugger C, Perier MC, Gonzalez-Izquierdo A, Hemingway H, Denaxas S, Empana JP.", + "authorAffiliations": "", + "journalTitle": "European journal of preventive cardiology", + "pubYear": "2023", + "date": "2023-10-01", + "isOpenAccess": "N", + "keywords": "Prevention; Survival analysis; Stroke; epidemiology; Coronary Heart Disease; incidence", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Incident events of cardiovascular diseases (CVDs) are heterogenous and may result in different mortality risks. Such evidence may help inform patient and physician decisions in CVD prevention and risk factor management.

Aims

This study aimed to determine the extent to which incident events of common CVD show heterogeneous associations with subsequent mortality risk in the general population.

Methods and results

Based on England-wide linked electronic health records, we established a cohort of 1 310 518 people \u226530 years of age initially free of CVD and followed up for non-fatal events of 12 common CVD and cause-specific mortality. The 12 CVDs were considered as time-varying exposures in Cox's proportional hazards models to estimate hazard rate ratios (HRRs) with 95% confidence intervals (CIs). Over the median follow-up of 4.2 years (2010-16), 81 516 non-fatal CVD, 10 906 cardiovascular deaths, and 40 843 non-cardiovascular deaths occurred. All 12 CVDs were associated with increased risk of cardiovascular mortality, with HRR (95% CI) ranging from 1.67 (1.47-1.89) for stable angina to 7.85 (6.62-9.31) for haemorrhagic stroke. All 12 CVDs were also associated with increased non-cardiovascular and all-cause mortality risk but to a lesser extent: HRR (95% CI) ranged from 1.10 (1.00-1.22) to 4.55 (4.03-5.13) and from 1.24 (1.13-1.35) to 4.92 (4.44-5.46) for transient ischaemic attack and sudden cardiac arrest, respectively.

Conclusion

Incident events of 12 common CVD show significant adverse and markedly differential associations with subsequent cardiovascular, non-cardiovascular, and all-cause mortality risk in the general population.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/eurjpc/zwad192" + }, { "id": "37156273", "doi": "https://doi.org/10.1016/j.jad.2023.04.138", @@ -15605,23 +15605,6 @@ "laySummary": "", "urls": "pdf:https://eje.bioscientifica.com/downloadpdf/journals/eje/184/1/EJE-20-0296.pdf; doi:https://doi.org/10.1530/EJE-20-0296; html:https://europepmc.org/articles/PMC7707806; pdf:https://europepmc.org/articles/PMC7707806?pdf=render" }, - { - "id": "33856367", - "doi": "https://doi.org/10.1097/sla.0000000000004904", - "title": "Optimizing Trauma Systems: A Geospatial Analysis of the Victorian State Trauma System.", - "authorString": "Beck B, Tack G, Cameron P, Smith K, Gabbe B.", - "authorAffiliations": "", - "journalTitle": "Annals of surgery", - "pubYear": "2023", - "date": "2023-01-10", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

The aim of this study was to develop a data-driven approach to assessing the influence of trauma system parameters and optimizing the configuration of the Victorian State Trauma System (VSTS).

Summary background data

Regionalized trauma systems have been shown to reduce the risk of mortality and improve patient function and health-related quality of life. However, major trauma case numbers are rapidly increasing and there is a need to evolve the configuration of trauma systems.

Methods

A retrospective review of major trauma patients from 2016 to 2018 in Victoria, Australia. Drive times and flight times were calculated for transport to each of 138 trauma receiving hospitals. Changes to the configuration of the VSTS were modeled using a Mixed Integer Linear Programming algorithm across 156 simulations.

Results

There were 8327 patients included in the study, of which 58% were transported directly to a major trauma service (MTS). For adult patients, the proportion of patients transported directly to an MTS increased with higher transport time limit, greater probability of helicopter emergency medical service utilization, and lower hospital patient threshold numbers. The proportion of adult patients transported directly to an MTS varied from 66% to 90% across simulations. Across all simulations for pediatric patients, only 1 pediatric MTS was assigned.

Conclusions

We have developed a robust and data-driven approach to optimizing trauma systems. Through the use of geospatial and mathematical models, we have modeled how potential future changes to trauma system characteristics may impact on the optimal configuration of the system, which will enable policy makers to make informed decisions about health service planning into the future.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1097/SLA.0000000000004904" - }, { "id": "32226230", "doi": "https://doi.org/10.1016/j.neucom.2018.04.087", @@ -15639,6 +15622,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.neucom.2018.04.087; doi:https://doi.org/10.1016/j.neucom.2018.04.087; html:https://europepmc.org/articles/PMC7086459" }, + { + "id": "33856367", + "doi": "https://doi.org/10.1097/sla.0000000000004904", + "title": "Optimizing Trauma Systems: A Geospatial Analysis of the Victorian State Trauma System.", + "authorString": "Beck B, Tack G, Cameron P, Smith K, Gabbe B.", + "authorAffiliations": "", + "journalTitle": "Annals of surgery", + "pubYear": "2023", + "date": "2023-01-10", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

The aim of this study was to develop a data-driven approach to assessing the influence of trauma system parameters and optimizing the configuration of the Victorian State Trauma System (VSTS).

Summary background data

Regionalized trauma systems have been shown to reduce the risk of mortality and improve patient function and health-related quality of life. However, major trauma case numbers are rapidly increasing and there is a need to evolve the configuration of trauma systems.

Methods

A retrospective review of major trauma patients from 2016 to 2018 in Victoria, Australia. Drive times and flight times were calculated for transport to each of 138 trauma receiving hospitals. Changes to the configuration of the VSTS were modeled using a Mixed Integer Linear Programming algorithm across 156 simulations.

Results

There were 8327 patients included in the study, of which 58% were transported directly to a major trauma service (MTS). For adult patients, the proportion of patients transported directly to an MTS increased with higher transport time limit, greater probability of helicopter emergency medical service utilization, and lower hospital patient threshold numbers. The proportion of adult patients transported directly to an MTS varied from 66% to 90% across simulations. Across all simulations for pediatric patients, only 1 pediatric MTS was assigned.

Conclusions

We have developed a robust and data-driven approach to optimizing trauma systems. Through the use of geospatial and mathematical models, we have modeled how potential future changes to trauma system characteristics may impact on the optimal configuration of the system, which will enable policy makers to make informed decisions about health service planning into the future.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1097/SLA.0000000000004904" + }, { "id": "33052324", "doi": "https://doi.org/10.1016/j.eclinm.2020.100574", @@ -15809,23 +15809,6 @@ "laySummary": "", "urls": "pdf:https://informatics.bmj.com/content/bmjhci/28/1/e100356.full.pdf; doi:https://doi.org/10.1136/bmjhci-2021-100356; html:https://europepmc.org/articles/PMC8286765; pdf:https://europepmc.org/articles/PMC8286765?pdf=render" }, - { - "id": "38655112", - "doi": "https://doi.org/10.1089/neur.2023.0127", - "title": "The Australian Traumatic Brain Injury Initiative: Review and Recommendations for Outcome Measures for Use With Adults and Children After Moderate-to-Severe Traumatic Brain Injury.", - "authorString": "Ponsford JL, Hicks AJ, Bagg MK, Phyland R, Carrier S, James AC, Lannin NA, Rushworth N, O'Brien TJ, Cameron PA, Cooper DJ, Hill R, Gabbe BJ, Fitzgerald M.", - "authorAffiliations": "", - "journalTitle": "Neurotrauma reports", - "pubYear": "2024", - "date": "2024-04-11", - "isOpenAccess": "Y", - "keywords": "Review; Traumatic brain injury; Outcome Measures; Common Data Elements", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to select a set of measures to comprehensively predict and assess outcomes following moderate-to-severe traumatic brain injury (TBI) across Australia. The aim of this article was to report on the implementation and findings of an evidence-based consensus approach to develop AUS-TBI recommendations for outcome measures following adult and pediatric moderate-to-severe TBI. Following consultation with a panel of expert clinicians, Aboriginal and Torres Strait Islander representatives and a Living Experience group, and preliminary literature searches with a broader focus, a decision was made to focus on measures of mortality, everyday functional outcomes, and quality of life. Standardized searches of bibliographic databases were conducted through March 2022. Characteristics of 75 outcome measures were extracted from 1485 primary studies. Consensus meetings among the AUS-TBI Steering Committee, an expert panel of clinicians and researchers and a group of individuals with lived experience of TBI resulted in the production of a final list of 11 core outcome measures: the Functional Independence Measure (FIM); Glasgow Outcome Scale-Extended (GOS-E); Satisfaction With Life Scale (SWLS) (adult); mortality; EuroQol-5 Dimensions (EQ5D); Mayo-Portland Adaptability Inventory (MPAI); Return to Work /Study (adult and pediatric); Functional Independence Measure for Children (WEEFIM); Glasgow Outcome Scale Modified for Children (GOS-E PEDS); Paediatric Quality of Life Scale (PEDS-QL); and Strengths and Difficulties Questionnaire (pediatric). These 11 outcome measures will be included as common data elements in the AUS-TBI data dictionary. Review Registration PROSPERO (CRD42022290954).", - "laySummary": "", - "urls": "doi:https://doi.org/10.1089/neur.2023.0127; html:https://europepmc.org/articles/PMC11035854; pdf:https://europepmc.org/articles/PMC11035854?pdf=render" - }, { "id": "34190735", "doi": "https://doi.org/", @@ -15843,6 +15826,23 @@ "laySummary": "", "urls": "" }, + { + "id": "38655112", + "doi": "https://doi.org/10.1089/neur.2023.0127", + "title": "The Australian Traumatic Brain Injury Initiative: Review and Recommendations for Outcome Measures for Use With Adults and Children After Moderate-to-Severe Traumatic Brain Injury.", + "authorString": "Ponsford JL, Hicks AJ, Bagg MK, Phyland R, Carrier S, James AC, Lannin NA, Rushworth N, O'Brien TJ, Cameron PA, Cooper DJ, Hill R, Gabbe BJ, Fitzgerald M.", + "authorAffiliations": "", + "journalTitle": "Neurotrauma reports", + "pubYear": "2024", + "date": "2024-04-11", + "isOpenAccess": "Y", + "keywords": "Review; Traumatic brain injury; Outcome Measures; Common Data Elements", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to select a set of measures to comprehensively predict and assess outcomes following moderate-to-severe traumatic brain injury (TBI) across Australia. The aim of this article was to report on the implementation and findings of an evidence-based consensus approach to develop AUS-TBI recommendations for outcome measures following adult and pediatric moderate-to-severe TBI. Following consultation with a panel of expert clinicians, Aboriginal and Torres Strait Islander representatives and a Living Experience group, and preliminary literature searches with a broader focus, a decision was made to focus on measures of mortality, everyday functional outcomes, and quality of life. Standardized searches of bibliographic databases were conducted through March 2022. Characteristics of 75 outcome measures were extracted from 1485 primary studies. Consensus meetings among the AUS-TBI Steering Committee, an expert panel of clinicians and researchers and a group of individuals with lived experience of TBI resulted in the production of a final list of 11 core outcome measures: the Functional Independence Measure (FIM); Glasgow Outcome Scale-Extended (GOS-E); Satisfaction With Life Scale (SWLS) (adult); mortality; EuroQol-5 Dimensions (EQ5D); Mayo-Portland Adaptability Inventory (MPAI); Return to Work /Study (adult and pediatric); Functional Independence Measure for Children (WEEFIM); Glasgow Outcome Scale Modified for Children (GOS-E PEDS); Paediatric Quality of Life Scale (PEDS-QL); and Strengths and Difficulties Questionnaire (pediatric). These 11 outcome measures will be included as common data elements in the AUS-TBI data dictionary. Review Registration PROSPERO (CRD42022290954).", + "laySummary": "", + "urls": "doi:https://doi.org/10.1089/neur.2023.0127; html:https://europepmc.org/articles/PMC11035854; pdf:https://europepmc.org/articles/PMC11035854?pdf=render" + }, { "id": "35444210", "doi": "https://doi.org/10.1038/s41698-022-00269-5", @@ -16047,23 +16047,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41588-023-01462-3.pdf; doi:https://doi.org/10.1038/s41588-023-01462-3; html:https://europepmc.org/articles/PMC10484788; pdf:https://europepmc.org/articles/PMC10484788?pdf=render" }, - { - "id": "38811438", - "doi": "https://doi.org/10.1007/s00586-024-08315-5", - "title": "Early evaluation of a natural language processing tool to improve access to educational resources for surgical patients.", - "authorString": "Booker J, Penn J, Noor K, Dobson RJB, Funnell JP, Koh CH, Khan DZ, Newall N, Rowland D, Sinha S, Williams SC, Sayal P, Marcus HJ.", - "authorAffiliations": "", - "journalTitle": "European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society", - "pubYear": "2024", - "date": "2024-05-30", - "isOpenAccess": "N", - "keywords": "Spine; Education; Machine Learning; Natural Language Processing; automation", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Purpose

Accessible patient information sources are vital in educating patients about the benefits and risks of spinal surgery, which is crucial for obtaining informed consent. We aim to assess the effectiveness of a natural language processing (NLP) pipeline in recognizing surgical procedures from clinic letters and linking this with educational resources.

Methods

Retrospective examination of letters from patients seeking surgery for degenerative spinal disease at a single neurosurgical center. We utilized MedCAT, a named entity recognition and linking NLP, integrated into the electronic health record (EHR), which extracts concepts and links them to systematized nomenclature of medicine-clinical terms (SNOMED-CT). Investigators reviewed clinic letters, identifying words or phrases that described or identified operations and recording the SNOMED-CT terms as ground truth. This was compared to SNOMED-CT terms identified by the model, untrained on our dataset. A pipeline linking clinic letters to patient-specific educational resources was established, and precision, recall, and F1 scores were calculated.

Results

Across 199 letters the model identified 582 surgical procedures, and the overall pipeline after adding rules a total of 784 procedures (precision\u2009=\u20090.94, recall\u2009=\u20090.86, F1\u2009=\u20090.91). Across 187 letters with identified SNOMED-CT terms the integrated pipeline linking education resources directly to the EHR was successful in 157 (78%) patients (precision\u2009=\u20090.99, recall\u2009=\u20090.87, F1\u2009=\u20090.92).

Conclusions

NLP accurately identifies surgical procedures in pre-operative clinic letters within an untrained subspecialty. Performance varies among letter authors and depends on the language used by clinicians. The identified procedures can be linked to patient education resources, potentially improving patients' understanding of surgical procedures.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1007/s00586-024-08315-5; doi:https://doi.org/10.1007/s00586-024-08315-5" - }, { "id": "34481555", "doi": "https://doi.org/10.1016/s2213-8587(21)00207-2", @@ -16098,6 +16081,23 @@ "laySummary": "", "urls": "pdf:https://appliednetsci.springeropen.com/track/pdf/10.1007/s41109-020-00273-3; doi:https://doi.org/10.1007/s41109-020-00273-3; html:https://europepmc.org/articles/PMC7319291; pdf:https://europepmc.org/articles/PMC7319291?pdf=render" }, + { + "id": "38811438", + "doi": "https://doi.org/10.1007/s00586-024-08315-5", + "title": "Early evaluation of a natural language processing tool to improve access to educational resources for surgical patients.", + "authorString": "Booker J, Penn J, Noor K, Dobson RJB, Funnell JP, Koh CH, Khan DZ, Newall N, Rowland D, Sinha S, Williams SC, Sayal P, Marcus HJ.", + "authorAffiliations": "", + "journalTitle": "European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society", + "pubYear": "2024", + "date": "2024-05-30", + "isOpenAccess": "N", + "keywords": "Spine; Education; Machine Learning; Natural Language Processing; automation", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Purpose

Accessible patient information sources are vital in educating patients about the benefits and risks of spinal surgery, which is crucial for obtaining informed consent. We aim to assess the effectiveness of a natural language processing (NLP) pipeline in recognizing surgical procedures from clinic letters and linking this with educational resources.

Methods

Retrospective examination of letters from patients seeking surgery for degenerative spinal disease at a single neurosurgical center. We utilized MedCAT, a named entity recognition and linking NLP, integrated into the electronic health record (EHR), which extracts concepts and links them to systematized nomenclature of medicine-clinical terms (SNOMED-CT). Investigators reviewed clinic letters, identifying words or phrases that described or identified operations and recording the SNOMED-CT terms as ground truth. This was compared to SNOMED-CT terms identified by the model, untrained on our dataset. A pipeline linking clinic letters to patient-specific educational resources was established, and precision, recall, and F1 scores were calculated.

Results

Across 199 letters the model identified 582 surgical procedures, and the overall pipeline after adding rules a total of 784 procedures (precision\u2009=\u20090.94, recall\u2009=\u20090.86, F1\u2009=\u20090.91). Across 187 letters with identified SNOMED-CT terms the integrated pipeline linking education resources directly to the EHR was successful in 157 (78%) patients (precision\u2009=\u20090.99, recall\u2009=\u20090.87, F1\u2009=\u20090.92).

Conclusions

NLP accurately identifies surgical procedures in pre-operative clinic letters within an untrained subspecialty. Performance varies among letter authors and depends on the language used by clinicians. The identified procedures can be linked to patient education resources, potentially improving patients' understanding of surgical procedures.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1007/s00586-024-08315-5; doi:https://doi.org/10.1007/s00586-024-08315-5" + }, { "id": "37578823", "doi": "https://doi.org/10.2196/45233", @@ -16234,6 +16234,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41467-023-41876-5.pdf; doi:https://doi.org/10.1038/s41467-023-41876-5; html:https://europepmc.org/articles/PMC10570309; pdf:https://europepmc.org/articles/PMC10570309?pdf=render" }, + { + "id": "33813844", + "doi": "https://doi.org/10.1161/hypertensionaha.120.16534", + "title": "Relationship Between Blood Pressure and Incident Cardiovascular Disease: Linear and Nonlinear Mendelian Randomization Analyses.", + "authorString": "Malik R, Georgakis MK, Vujkovic M, Damrauer SM, Elliott P, Karhunen V, Giontella A, Fava C, Hellwege JN, Shuey MM, Edwards TL, Rogne T, \u00c5svold BO, Brumpton BM, Burgess S, Dichgans M, Gill D.", + "authorAffiliations": "", + "journalTitle": "Hypertension (Dallas, Tex. : 1979)", + "pubYear": "2021", + "date": "2021-04-05", + "isOpenAccess": "Y", + "keywords": "Hypertension; Blood pressure; Stroke; coronary artery disease; Primary Prevention", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "[Figure: see text].", + "laySummary": "", + "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/HYPERTENSIONAHA.120.16534; doi:https://doi.org/10.1161/HYPERTENSIONAHA.120.16534; html:https://europepmc.org/articles/PMC8115430; pdf:https://europepmc.org/articles/PMC8115430?pdf=render" + }, { "id": "37773956", "doi": "https://doi.org/10.1371/journal.pone.0292240", @@ -16268,23 +16285,6 @@ "laySummary": "", "urls": "pdf:https://openres.ersjournals.com/content/erjor/8/4/00211-2022.full.pdf; doi:https://doi.org/10.1183/23120541.00211-2022; html:https://europepmc.org/articles/PMC9589337; pdf:https://europepmc.org/articles/PMC9589337?pdf=render" }, - { - "id": "33813844", - "doi": "https://doi.org/10.1161/hypertensionaha.120.16534", - "title": "Relationship Between Blood Pressure and Incident Cardiovascular Disease: Linear and Nonlinear Mendelian Randomization Analyses.", - "authorString": "Malik R, Georgakis MK, Vujkovic M, Damrauer SM, Elliott P, Karhunen V, Giontella A, Fava C, Hellwege JN, Shuey MM, Edwards TL, Rogne T, \u00c5svold BO, Brumpton BM, Burgess S, Dichgans M, Gill D.", - "authorAffiliations": "", - "journalTitle": "Hypertension (Dallas, Tex. : 1979)", - "pubYear": "2021", - "date": "2021-04-05", - "isOpenAccess": "Y", - "keywords": "Hypertension; Blood pressure; Stroke; coronary artery disease; Primary Prevention", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "[Figure: see text].", - "laySummary": "", - "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/HYPERTENSIONAHA.120.16534; doi:https://doi.org/10.1161/HYPERTENSIONAHA.120.16534; html:https://europepmc.org/articles/PMC8115430; pdf:https://europepmc.org/articles/PMC8115430?pdf=render" - }, { "id": "32997638", "doi": "https://doi.org/10.1109/jbhi.2020.3027987", @@ -16302,23 +16302,6 @@ "laySummary": "", "urls": "pdf:https://ieeexplore.ieee.org/ielx7/6221020/9281055/09210178.pdf; doi:https://doi.org/10.1109/JBHI.2020.3027987; html:https://europepmc.org/articles/PMC8545177; pdf:https://europepmc.org/articles/PMC8545177?pdf=render" }, - { - "id": "37667806", - "doi": "https://doi.org/10.1177/17562848231193211", - "title": "Planning to conceive within a year is associated with better pregnancy-specific disease-related patient knowledge and better medication adherence in women of childbearing age with inflammatory bowel disease.", - "authorString": "Selinger CP, Laube R, Steed H, Brookes M, BioResource N, Leong RWL.", - "authorAffiliations": "", - "journalTitle": "Therapeutic advances in gastroenterology", - "pubYear": "2023", - "date": "2023-08-30", - "isOpenAccess": "Y", - "keywords": "Pregnancy; Inflammatory Bowel Disease; Patient Knowledge; Medication Adherence", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Adherence to inflammatory bowel disease (IBD) medication is crucial to maintain remission, especially during pregnancy.

Objective

To examine the influence of family planning and pregnancy-related patient knowledge regarding IBD and pregnancy on adherence.

Design

Cross-sectional survey study.

Methods

We surveyed female patients with IBD aged 18-35\u2009years, who at recruitment to the UK IBD BioResource had not had children. We elicited disease and treatment history, demographics and family planning status via an online questionnaire. Patient knowledge as assessed by the validated Crohn's and Colitis Pregnancy Knowledge Score (CCPKnow) and adherence by visual analogue scale (VAS).

Results

In 326 responders (13.8% response rate), good adherence (VAS\u2009\u2a7e\u200980) was found in only 38.35%. Disease- and treatment-related factors were not significantly associated with good adherence, except for methotrexate (70.0% adherent of 10 exposed patients versus 37.2% non-exposed; p\u2009=\u20090.036). Patients planning pregnancy for the next year were more often adherent (59.0% versus 35.5%; p\u2009=\u20090.019) and knowledgeable (median CCPKnow 8 versus 7; p\u2009=\u20090.035) compared to those in other family planning categories. Pregnancy-related patient knowledge was significantly associated with adherence (Pearson correlation 0.141; p\u2009=\u20090.015). Adherent patients had significantly higher CCPKnow scores than non-adherent patients (median 8 versus 6; p\u2009=\u20090.009). On binary regression analysis, only planning to conceive within 12\u2009months was independently associated with better adherence (p\u2009=\u20090.016), but not methotrexate exposure (p\u2009=\u20090.076) and CCPKnow (p\u2009=\u20090.056).

Conclusions

In a cohort of women of childbearing age with IBD overall medication, adherence was low. Planning to conceive within the next year was associated with better adherence and greater patient knowledge.", - "laySummary": "", - "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/17562848231193211; doi:https://doi.org/10.1177/17562848231193211; html:https://europepmc.org/articles/PMC10475232; pdf:https://europepmc.org/articles/PMC10475232?pdf=render" - }, { "id": "31607513", "doi": "https://doi.org/10.1016/j.cell.2019.08.051", @@ -16336,6 +16319,23 @@ "laySummary": "", "urls": "pdf:http://www.cell.com/article/S0092867419310025/pdf; doi:https://doi.org/10.1016/j.cell.2019.08.051; html:https://europepmc.org/articles/PMC6939869; pdf:https://europepmc.org/articles/PMC6939869?pdf=render; doi:https://doi.org/10.1016/j.cell.2019.08.051" }, + { + "id": "37667806", + "doi": "https://doi.org/10.1177/17562848231193211", + "title": "Planning to conceive within a year is associated with better pregnancy-specific disease-related patient knowledge and better medication adherence in women of childbearing age with inflammatory bowel disease.", + "authorString": "Selinger CP, Laube R, Steed H, Brookes M, BioResource N, Leong RWL.", + "authorAffiliations": "", + "journalTitle": "Therapeutic advances in gastroenterology", + "pubYear": "2023", + "date": "2023-08-30", + "isOpenAccess": "Y", + "keywords": "Pregnancy; Inflammatory Bowel Disease; Patient Knowledge; Medication Adherence", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Adherence to inflammatory bowel disease (IBD) medication is crucial to maintain remission, especially during pregnancy.

Objective

To examine the influence of family planning and pregnancy-related patient knowledge regarding IBD and pregnancy on adherence.

Design

Cross-sectional survey study.

Methods

We surveyed female patients with IBD aged 18-35\u2009years, who at recruitment to the UK IBD BioResource had not had children. We elicited disease and treatment history, demographics and family planning status via an online questionnaire. Patient knowledge as assessed by the validated Crohn's and Colitis Pregnancy Knowledge Score (CCPKnow) and adherence by visual analogue scale (VAS).

Results

In 326 responders (13.8% response rate), good adherence (VAS\u2009\u2a7e\u200980) was found in only 38.35%. Disease- and treatment-related factors were not significantly associated with good adherence, except for methotrexate (70.0% adherent of 10 exposed patients versus 37.2% non-exposed; p\u2009=\u20090.036). Patients planning pregnancy for the next year were more often adherent (59.0% versus 35.5%; p\u2009=\u20090.019) and knowledgeable (median CCPKnow 8 versus 7; p\u2009=\u20090.035) compared to those in other family planning categories. Pregnancy-related patient knowledge was significantly associated with adherence (Pearson correlation 0.141; p\u2009=\u20090.015). Adherent patients had significantly higher CCPKnow scores than non-adherent patients (median 8 versus 6; p\u2009=\u20090.009). On binary regression analysis, only planning to conceive within 12\u2009months was independently associated with better adherence (p\u2009=\u20090.016), but not methotrexate exposure (p\u2009=\u20090.076) and CCPKnow (p\u2009=\u20090.056).

Conclusions

In a cohort of women of childbearing age with IBD overall medication, adherence was low. Planning to conceive within the next year was associated with better adherence and greater patient knowledge.", + "laySummary": "", + "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/17562848231193211; doi:https://doi.org/10.1177/17562848231193211; html:https://europepmc.org/articles/PMC10475232; pdf:https://europepmc.org/articles/PMC10475232?pdf=render" + }, { "id": "37794871", "doi": "https://doi.org/10.1093/ehjdh/ztad044", @@ -16387,23 +16387,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/cercor/article-pdf/31/4/2071/36458400/bhaa345.pdf; doi:https://doi.org/10.1093/cercor/bhaa345; html:https://europepmc.org/articles/PMC7945030; pdf:https://europepmc.org/articles/PMC7945030?pdf=render" }, - { - "id": "37562944", - "doi": "https://doi.org/10.1136/emermed-2023-213186", - "title": "Biases in the collection of blood alcohol data for adult major trauma patients in Victoria, Australia.", - "authorString": "Lau G, Gabbe B, Mitra B, Dietze P, Reeder S, Cameron P, Read DJ, Symons E, Beck B.", - "authorAffiliations": "", - "journalTitle": "Emergency medicine journal : EMJ", - "pubYear": "2023", - "date": "2023-08-10", - "isOpenAccess": "N", - "keywords": "epidemiology; wounds and injuries; toxicology; Alcohol Abuse", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

In-hospital alcohol testing provides an opportunity to implement prevention strategies for patients with high risk of experiencing repeated alcohol-related injuries. However, barriers to alcohol testing in emergency settings can prevent patients from being tested. In this study, we aimed to understand potential biases in current data on the completion of blood alcohol tests for major trauma patients at hospitals in Victoria, Australia.

Methods

Victorian State Trauma Registry data on all adult major trauma patients from 1 January 2018 to 31 December 2021 were used. Characteristics associated with having a blood alcohol test recorded in the registry were assessed using logistic regression models.

Results

This study included 14\u2009221 major trauma patients, of which 4563 (32.1%) had a blood alcohol test recorded. Having a blood alcohol test completed was significantly associated with age, socioeconomic disadvantage level, preferred language, having pre-existing mental health or substance use conditions, smoking status, presenting during times associated with heavy community alcohol consumption, injury cause and intent, and Glasgow Coma Scale scores (p<0.05). Restricting analyses to patients from a trauma centre where blood alcohol testing was part of routine clinical care mitigated most biases. However, relative to patients injured while driving a motor vehicle/motorcycle, lower odds of testing were still observed for patients with injuries from flames/scalds/contact burns (adjusted OR (aOR)=0.33, 95%\u2009CI 0.18 to 0.61) and low falls (aOR=0.17, 95% CI 0.12 to 0.25). Higher odds of testing were associated with pre-existing mental health (aOR=1.39, 95% CI 1.02 to 1.89) or substance use conditions (aOR=2.33, 95% CI to 1.47-3.70), and living in a more disadvantaged area (most disadvantaged quintile relative to least disadvantaged quintile: aOR=2.30, 95% CI 1.52 to 3.48).

Conclusion

Biases in the collection of blood alcohol data likely impact the surveillance of alcohol-related injuries. Routine alcohol testing after major trauma is needed to accurately inform epidemiology and the subsequent implementation of strategies for reducing alcohol-related injuries.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/emermed-2023-213186" - }, { "id": "36564466", "doi": "https://doi.org/10.1038/s41598-022-26141-x", @@ -16421,6 +16404,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41598-022-26141-x.pdf; doi:https://doi.org/10.1038/s41598-022-26141-x; html:https://europepmc.org/articles/PMC9789116; pdf:https://europepmc.org/articles/PMC9789116?pdf=render" }, + { + "id": "37562944", + "doi": "https://doi.org/10.1136/emermed-2023-213186", + "title": "Biases in the collection of blood alcohol data for adult major trauma patients in Victoria, Australia.", + "authorString": "Lau G, Gabbe B, Mitra B, Dietze P, Reeder S, Cameron P, Read DJ, Symons E, Beck B.", + "authorAffiliations": "", + "journalTitle": "Emergency medicine journal : EMJ", + "pubYear": "2023", + "date": "2023-08-10", + "isOpenAccess": "N", + "keywords": "epidemiology; wounds and injuries; toxicology; Alcohol Abuse", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

In-hospital alcohol testing provides an opportunity to implement prevention strategies for patients with high risk of experiencing repeated alcohol-related injuries. However, barriers to alcohol testing in emergency settings can prevent patients from being tested. In this study, we aimed to understand potential biases in current data on the completion of blood alcohol tests for major trauma patients at hospitals in Victoria, Australia.

Methods

Victorian State Trauma Registry data on all adult major trauma patients from 1 January 2018 to 31 December 2021 were used. Characteristics associated with having a blood alcohol test recorded in the registry were assessed using logistic regression models.

Results

This study included 14\u2009221 major trauma patients, of which 4563 (32.1%) had a blood alcohol test recorded. Having a blood alcohol test completed was significantly associated with age, socioeconomic disadvantage level, preferred language, having pre-existing mental health or substance use conditions, smoking status, presenting during times associated with heavy community alcohol consumption, injury cause and intent, and Glasgow Coma Scale scores (p<0.05). Restricting analyses to patients from a trauma centre where blood alcohol testing was part of routine clinical care mitigated most biases. However, relative to patients injured while driving a motor vehicle/motorcycle, lower odds of testing were still observed for patients with injuries from flames/scalds/contact burns (adjusted OR (aOR)=0.33, 95%\u2009CI 0.18 to 0.61) and low falls (aOR=0.17, 95% CI 0.12 to 0.25). Higher odds of testing were associated with pre-existing mental health (aOR=1.39, 95% CI 1.02 to 1.89) or substance use conditions (aOR=2.33, 95% CI to 1.47-3.70), and living in a more disadvantaged area (most disadvantaged quintile relative to least disadvantaged quintile: aOR=2.30, 95% CI 1.52 to 3.48).

Conclusion

Biases in the collection of blood alcohol data likely impact the surveillance of alcohol-related injuries. Routine alcohol testing after major trauma is needed to accurately inform epidemiology and the subsequent implementation of strategies for reducing alcohol-related injuries.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/emermed-2023-213186" + }, { "id": "36571960", "doi": "https://doi.org/10.1016/j.bjps.2022.11.049", @@ -16472,23 +16472,6 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279250&type=printable; doi:https://doi.org/10.1371/journal.pone.0279250; html:https://europepmc.org/articles/PMC9757548; pdf:https://europepmc.org/articles/PMC9757548?pdf=render" }, - { - "id": "38660461", - "doi": "https://doi.org/10.1089/neur.2023.0116", - "title": "The Australian Traumatic Brain Injury Initiative: Statement of Working Principles and Rapid Review of Methods to Define Data Dictionaries for Neurological Conditions.", - "authorString": "Bagg MK, Hicks AJ, Hellewell SC, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Gabbe BJ, Fitzgerald M.", - "authorAffiliations": "", - "journalTitle": "Neurotrauma reports", - "pubYear": "2024", - "date": "2024-04-11", - "isOpenAccess": "Y", - "keywords": "Brain injuries; Traumatic; Neurology; Common Data Elements; Systematic Review [Publication Type]", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to develop a health informatics approach to collect data predictive of outcomes for persons with moderate-severe TBI across Australia. Central to this approach is a data dictionary; however, no systematic reviews of methods to define and develop data dictionaries exist to-date. This rapid systematic review aimed to identify and characterize methods for designing data dictionaries to collect outcomes or variables in persons with neurological conditions. Database searches were conducted from inception through October 2021. Records were screened in two stages against set criteria to identify methods to define data dictionaries for neurological conditions (International Classification of Diseases, 11th Revision: 08, 22, and 23). Standardized data were extracted. Processes were checked at each stage by independent review of a random 25% of records. Consensus was reached through discussion where necessary. Thirty-nine initiatives were identified across 29 neurological conditions. No single established or recommended method for defining a data dictionary was identified. Nine initiatives conducted systematic reviews to collate information before implementing a consensus process. Thirty-seven initiatives consulted with end-users. Methods of consultation were \"roundtable\" discussion (n\u2009=\u200930); with facilitation (n\u2009=\u200916); that was iterative (n\u2009=\u200927); and frequently conducted in-person (n\u2009=\u200927). Researcher stakeholders were involved in all initiatives and clinicians in 25. Importantly, only six initiatives involved persons with lived experience of TBI and four involved carers. Methods for defining data dictionaries were variable and reporting is sparse. Our findings are instructive for AUS-TBI and can be used to further development of methods for defining data dictionaries.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1089/neur.2023.0116; html:https://europepmc.org/articles/PMC11040195; pdf:https://europepmc.org/articles/PMC11040195?pdf=render" - }, { "id": "37953241", "doi": "https://doi.org/10.1186/s12916-023-03153-6", @@ -16506,6 +16489,23 @@ "laySummary": "", "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-03153-6; doi:https://doi.org/10.1186/s12916-023-03153-6; html:https://europepmc.org/articles/PMC10641987; pdf:https://europepmc.org/articles/PMC10641987?pdf=render" }, + { + "id": "38660461", + "doi": "https://doi.org/10.1089/neur.2023.0116", + "title": "The Australian Traumatic Brain Injury Initiative: Statement of Working Principles and Rapid Review of Methods to Define Data Dictionaries for Neurological Conditions.", + "authorString": "Bagg MK, Hicks AJ, Hellewell SC, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Gabbe BJ, Fitzgerald M.", + "authorAffiliations": "", + "journalTitle": "Neurotrauma reports", + "pubYear": "2024", + "date": "2024-04-11", + "isOpenAccess": "Y", + "keywords": "Brain injuries; Traumatic; Neurology; Common Data Elements; Systematic Review [Publication Type]", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to develop a health informatics approach to collect data predictive of outcomes for persons with moderate-severe TBI across Australia. Central to this approach is a data dictionary; however, no systematic reviews of methods to define and develop data dictionaries exist to-date. This rapid systematic review aimed to identify and characterize methods for designing data dictionaries to collect outcomes or variables in persons with neurological conditions. Database searches were conducted from inception through October 2021. Records were screened in two stages against set criteria to identify methods to define data dictionaries for neurological conditions (International Classification of Diseases, 11th Revision: 08, 22, and 23). Standardized data were extracted. Processes were checked at each stage by independent review of a random 25% of records. Consensus was reached through discussion where necessary. Thirty-nine initiatives were identified across 29 neurological conditions. No single established or recommended method for defining a data dictionary was identified. Nine initiatives conducted systematic reviews to collate information before implementing a consensus process. Thirty-seven initiatives consulted with end-users. Methods of consultation were \"roundtable\" discussion (n\u2009=\u200930); with facilitation (n\u2009=\u200916); that was iterative (n\u2009=\u200927); and frequently conducted in-person (n\u2009=\u200927). Researcher stakeholders were involved in all initiatives and clinicians in 25. Importantly, only six initiatives involved persons with lived experience of TBI and four involved carers. Methods for defining data dictionaries were variable and reporting is sparse. Our findings are instructive for AUS-TBI and can be used to further development of methods for defining data dictionaries.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1089/neur.2023.0116; html:https://europepmc.org/articles/PMC11040195; pdf:https://europepmc.org/articles/PMC11040195?pdf=render" + }, { "id": "37812323", "doi": "https://doi.org/10.1186/s41687-023-00634-3", @@ -16625,6 +16625,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e061849.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-061849; html:https://europepmc.org/articles/PMC9709811; pdf:https://europepmc.org/articles/PMC9709811?pdf=render" }, + { + "id": "32398093", + "doi": "https://doi.org/10.1186/s13063-020-04329-8", + "title": "Access to routinely collected health data for clinical trials - review of successful data requests to UK registries.", + "authorString": "Lensen S, Macnair A, Love SB, Yorke-Edwards V, Noor NM, Martyn M, Blenkinsop A, Diaz-Montana C, Powell G, Williamson E, Carpenter J, Sydes MR.", + "authorAffiliations": "", + "journalTitle": "Trials", + "pubYear": "2020", + "date": "2020-05-12", + "isOpenAccess": "Y", + "keywords": "Systematic review; Rct; Registry; Routinely Collected Health Data", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Clinical trials generally each collect their own data despite routinely collected health data (RCHD) increasing in quality and breadth. Our aim is to quantify UK-based randomised controlled trials (RCTs) accessing RCHD for participant data, characterise how these data are used and thereby recommend how more trials could use RCHD.

Methods

We conducted a systematic review of RCTs accessing RCHD from at least one registry in the UK between 2013 and 2018 for the purposes of informing or supplementing participant data. A list of all registries holding RCHD in the UK was compiled. In cases where registries published release registers, these were searched for RCTs accessing RCHD. Where no release register was available, registries were contacted to request a list of RCTs. For each identified RCT, information was collected from all publicly available sources (release registers, websites, protocol etc.). The search and data extraction were undertaken between January and May 2019.

Results

We identified 160 RCTs accessing RCHD between 2013 and 2018 from a total of 22 registries; this corresponds to only a very small proportion of all UK RCTs (about 3%). RCTs accessing RCHD were generally large (median sample size 1590), commonly evaluating treatments for cancer or cardiovascular disease. Most of the included RCTs accessed RCHD from NHS Digital (68%), and the most frequently accessed datasets were mortality (76%) and hospital visits (55%). RCHD was used to inform the primary trial (82%) and long-term follow-up (57%). There was substantial variation in how RCTs used RCHD to inform participant outcome measures. A limitation was the lack of information and transparency from registries and RCTs with respect to which datasets have been accessed and for what purposes.

Conclusions

In the last five years, only a small minority of UK-based RCTs have accessed RCHD to inform participant data. We ask for improved accessibility, confirmed data quality and joined-up thinking between the registries and the regulatory authorities.

Trial registration

PROSPERO CRD42019123088.", + "laySummary": "", + "urls": "pdf:https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-020-04329-8; doi:https://doi.org/10.1186/s13063-020-04329-8; html:https://europepmc.org/articles/PMC7218527; pdf:https://europepmc.org/articles/PMC7218527?pdf=render" + }, { "id": "33262239", "doi": "https://doi.org/10.1128/msystems.00677-20", @@ -16659,23 +16676,6 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/1742-6723.14312; doi:https://doi.org/10.1111/1742-6723.14312; html:https://europepmc.org/articles/PMC10952644; pdf:https://europepmc.org/articles/PMC10952644?pdf=render" }, - { - "id": "32398093", - "doi": "https://doi.org/10.1186/s13063-020-04329-8", - "title": "Access to routinely collected health data for clinical trials - review of successful data requests to UK registries.", - "authorString": "Lensen S, Macnair A, Love SB, Yorke-Edwards V, Noor NM, Martyn M, Blenkinsop A, Diaz-Montana C, Powell G, Williamson E, Carpenter J, Sydes MR.", - "authorAffiliations": "", - "journalTitle": "Trials", - "pubYear": "2020", - "date": "2020-05-12", - "isOpenAccess": "Y", - "keywords": "Systematic review; Rct; Registry; Routinely Collected Health Data", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Clinical trials generally each collect their own data despite routinely collected health data (RCHD) increasing in quality and breadth. Our aim is to quantify UK-based randomised controlled trials (RCTs) accessing RCHD for participant data, characterise how these data are used and thereby recommend how more trials could use RCHD.

Methods

We conducted a systematic review of RCTs accessing RCHD from at least one registry in the UK between 2013 and 2018 for the purposes of informing or supplementing participant data. A list of all registries holding RCHD in the UK was compiled. In cases where registries published release registers, these were searched for RCTs accessing RCHD. Where no release register was available, registries were contacted to request a list of RCTs. For each identified RCT, information was collected from all publicly available sources (release registers, websites, protocol etc.). The search and data extraction were undertaken between January and May 2019.

Results

We identified 160 RCTs accessing RCHD between 2013 and 2018 from a total of 22 registries; this corresponds to only a very small proportion of all UK RCTs (about 3%). RCTs accessing RCHD were generally large (median sample size 1590), commonly evaluating treatments for cancer or cardiovascular disease. Most of the included RCTs accessed RCHD from NHS Digital (68%), and the most frequently accessed datasets were mortality (76%) and hospital visits (55%). RCHD was used to inform the primary trial (82%) and long-term follow-up (57%). There was substantial variation in how RCTs used RCHD to inform participant outcome measures. A limitation was the lack of information and transparency from registries and RCTs with respect to which datasets have been accessed and for what purposes.

Conclusions

In the last five years, only a small minority of UK-based RCTs have accessed RCHD to inform participant data. We ask for improved accessibility, confirmed data quality and joined-up thinking between the registries and the regulatory authorities.

Trial registration

PROSPERO CRD42019123088.", - "laySummary": "", - "urls": "pdf:https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-020-04329-8; doi:https://doi.org/10.1186/s13063-020-04329-8; html:https://europepmc.org/articles/PMC7218527; pdf:https://europepmc.org/articles/PMC7218527?pdf=render" - }, { "id": "38581198", "doi": "https://doi.org/10.1001/jama.2024.4011", @@ -16829,23 +16829,6 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/mnfr.202100316; doi:https://doi.org/10.1002/mnfr.202100316" }, - { - "id": "37327673", - "doi": "https://doi.org/10.1016/j.ebiom.2023.104655", - "title": "HFrEF subphenotypes based on 4210 repeatedly measured circulating proteins are driven by different biological mechanisms.", - "authorString": "Petersen TB, de Bakker M, Asselbergs FW, Harakalova M, Akkerhuis KM, Brugts JJ, van Ramshorst J, Lumbers RT, Ostroff RM, Katsikis PD, van der Spek PJ, Umans VA, Boersma E, Rizopoulos D, Kardys I.", - "authorAffiliations": "", - "journalTitle": "EBioMedicine", - "pubYear": "2023", - "date": "2023-06-14", - "isOpenAccess": "Y", - "keywords": "Proteomics; Phenotypes; Biomarkers; Heart Failure; Unsupervised Machine Learning", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

HFrEF is a heterogenous condition with high mortality. We used serial assessments of 4210 circulating proteins to identify distinct novel protein-based HFrEF subphenotypes and to investigate underlying dynamic biological mechanisms. Herewith we aimed to gain pathophysiological insights and fuel opportunities for personalised treatment.

Methods

In 382 patients, we performed trimonthly blood sampling during a median follow-up of 2.1 [IQR:1.1-2.6] years. We selected all baseline samples and two samples closest to the primary endpoint (PEP; composite of cardiovascular mortality, HF hospitalization, LVAD implantation, and heart transplantation) or censoring, and applied an aptamer-based multiplex proteomic approach. Using unsupervised machine learning methods, we derived clusters from 4210 repeatedly measured proteomic biomarkers. Sets of proteins that drove cluster allocation were analysed via an enrichment analysis. Differences in clinical characteristics and PEP occurrence were evaluated.

Findings

We identified four subphenotypes with different protein profiles, prognosis and clinical characteristics, including age (median [IQR] for subphenotypes 1-4, respectively:70 [64, 76], 68 [60, 79], 57 [47, 65], 59 [56, 66]years), EF (30 [26, 36], 26 [20, 38], 26 [22, 32], 33 [28, 37]%), and chronic renal failure (45%, 65%, 36%, 37%). Subphenotype allocation was driven by subsets of proteins associated with various biological functions, such as oxidative stress, inflammation and extracellular matrix organisation. Clinical characteristics of the subphenotypes were aligned with these associations. Subphenotypes 2 and 3 had the worst prognosis compared to subphenotype 1 (adjHR (95%CI):3.43 (1.76-6.69), and 2.88 (1.37-6.03), respectively).

Interpretation

Four circulating-protein based subphenotypes are present in HFrEF, which are driven by varying combinations of protein subsets, and have different clinical characteristics and prognosis.

Clinical trial registration

ClinicalTrials.gov Identifier: NCT01851538https://clinicaltrials.gov/ct2/show/NCT01851538.

Funding

EU/EFPIA IMI2JU BigData@Heart grant n\u00b0116074, Jaap Schouten Foundation and Noordwest Academie.", - "laySummary": "", - "urls": "pdf:http://www.thelancet.com/article/S2352396423002207/pdf; doi:https://doi.org/10.1016/j.ebiom.2023.104655; html:https://europepmc.org/articles/PMC10279550; pdf:https://europepmc.org/articles/PMC10279550?pdf=render" - }, { "id": "35143670", "doi": "https://doi.org/10.1093/molbev/msac034", @@ -16863,6 +16846,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/mbe/article-pdf/39/3/msac034/42692776/msac034.pdf; doi:https://doi.org/10.1093/molbev/msac034; html:https://europepmc.org/articles/PMC8892942; pdf:https://europepmc.org/articles/PMC8892942?pdf=render" }, + { + "id": "37327673", + "doi": "https://doi.org/10.1016/j.ebiom.2023.104655", + "title": "HFrEF subphenotypes based on 4210 repeatedly measured circulating proteins are driven by different biological mechanisms.", + "authorString": "Petersen TB, de Bakker M, Asselbergs FW, Harakalova M, Akkerhuis KM, Brugts JJ, van Ramshorst J, Lumbers RT, Ostroff RM, Katsikis PD, van der Spek PJ, Umans VA, Boersma E, Rizopoulos D, Kardys I.", + "authorAffiliations": "", + "journalTitle": "EBioMedicine", + "pubYear": "2023", + "date": "2023-06-14", + "isOpenAccess": "Y", + "keywords": "Proteomics; Phenotypes; Biomarkers; Heart Failure; Unsupervised Machine Learning", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

HFrEF is a heterogenous condition with high mortality. We used serial assessments of 4210 circulating proteins to identify distinct novel protein-based HFrEF subphenotypes and to investigate underlying dynamic biological mechanisms. Herewith we aimed to gain pathophysiological insights and fuel opportunities for personalised treatment.

Methods

In 382 patients, we performed trimonthly blood sampling during a median follow-up of 2.1 [IQR:1.1-2.6] years. We selected all baseline samples and two samples closest to the primary endpoint (PEP; composite of cardiovascular mortality, HF hospitalization, LVAD implantation, and heart transplantation) or censoring, and applied an aptamer-based multiplex proteomic approach. Using unsupervised machine learning methods, we derived clusters from 4210 repeatedly measured proteomic biomarkers. Sets of proteins that drove cluster allocation were analysed via an enrichment analysis. Differences in clinical characteristics and PEP occurrence were evaluated.

Findings

We identified four subphenotypes with different protein profiles, prognosis and clinical characteristics, including age (median [IQR] for subphenotypes 1-4, respectively:70 [64, 76], 68 [60, 79], 57 [47, 65], 59 [56, 66]years), EF (30 [26, 36], 26 [20, 38], 26 [22, 32], 33 [28, 37]%), and chronic renal failure (45%, 65%, 36%, 37%). Subphenotype allocation was driven by subsets of proteins associated with various biological functions, such as oxidative stress, inflammation and extracellular matrix organisation. Clinical characteristics of the subphenotypes were aligned with these associations. Subphenotypes 2 and 3 had the worst prognosis compared to subphenotype 1 (adjHR (95%CI):3.43 (1.76-6.69), and 2.88 (1.37-6.03), respectively).

Interpretation

Four circulating-protein based subphenotypes are present in HFrEF, which are driven by varying combinations of protein subsets, and have different clinical characteristics and prognosis.

Clinical trial registration

ClinicalTrials.gov Identifier: NCT01851538https://clinicaltrials.gov/ct2/show/NCT01851538.

Funding

EU/EFPIA IMI2JU BigData@Heart grant n\u00b0116074, Jaap Schouten Foundation and Noordwest Academie.", + "laySummary": "", + "urls": "pdf:http://www.thelancet.com/article/S2352396423002207/pdf; doi:https://doi.org/10.1016/j.ebiom.2023.104655; html:https://europepmc.org/articles/PMC10279550; pdf:https://europepmc.org/articles/PMC10279550?pdf=render" + }, { "id": "34571200", "doi": "https://doi.org/10.1016/j.jaip.2021.09.026", @@ -16965,23 +16965,6 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pds.5121; doi:https://doi.org/10.1002/pds.5121" }, - { - "id": "36812613", - "doi": "https://doi.org/10.1371/journal.pdig.0000190", - "title": "Optimizing cardiovascular risk assessment and registration in a developing cardiovascular learning health care system: Women benefit most.", - "authorString": "Groenhof TKJ, Haitjema S, Lely AT, Grobbee DE, Asselbergs FW, Bots ML, UCC-CVRM and UPOD Study groups.", - "authorAffiliations": "", - "journalTitle": "PLOS digital health", - "pubYear": "2023", - "date": "2023-02-08", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Since 2015 we organized a uniform, structured collection of a fixed set of cardiovascular risk factors according the (inter)national guidelines on cardiovascular risk management. We evaluated the current state of a developing cardiovascular towards learning healthcare system-the Utrecht Cardiovascular Cohort Cardiovascular Risk Management (UCC-CVRM)-and its potential effect on guideline adherence in cardiovascular risk management. We conducted a before-after study comparing data from patients included in UCC-CVRM (2015-2018) and patients treated in our center before UCC-CVRM (2013-2015) who would have been eligible for UCC-CVRM using the Utrecht Patient Oriented Database (UPOD). Proportions of cardiovascular risk factor measurement before and after UCC-CVRM initiation were compared, as were proportions of patients that required (change of) blood pressure, lipid, or blood glucose lowering treatment. We estimated the likelihood to miss patients with hypertension, dyslipidemia, and elevated HbA1c before UCC-CVRM for the whole cohort and stratified for sex. In the present study, patients included up to October 2018 (n = 1904) were matched with 7195 UPOD patients with similar age, sex, department of referral and diagnose description. Completeness of risk factor measurement increased, ranging from 0% -77% before to 82%-94% after UCC-CVRM initiation. Before UCC-CVRM, we found more unmeasured risk factors in women compared to men. This sex-gap resolved in UCC-CVRM. The likelihood to miss hypertension, dyslipidemia, and elevated HbA1c was reduced by 67%, 75% and 90%, respectively, after UCC-CVRM initiation. A finding more pronounced in women compared to men. In conclusion, a systematic registration of the cardiovascular risk profile substantially improves guideline adherent assessment and decreases the risk of missing patients with elevated levels with an indication for treatment. The sex-gap disappeared after UCC-CVRM initiation. Thus, an LHS approach contributes to a more inclusive insight into quality of care and prevention of cardiovascular disease (progression).", - "laySummary": "", - "urls": "pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000190&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000190; html:https://europepmc.org/articles/PMC9931327; pdf:https://europepmc.org/articles/PMC9931327?pdf=render" - }, { "id": "35459950", "doi": "https://doi.org/10.1093/intqhc/mzac031", @@ -17000,21 +16983,21 @@ "urls": "pdf:https://academic.oup.com/intqhc/article-pdf/34/2/mzac031/43704475/mzac031.pdf; doi:https://doi.org/10.1093/intqhc/mzac031" }, { - "id": "35898465", - "doi": "https://doi.org/10.3389/fendo.2022.888924", - "title": "Diabetic Foot Risk Classification at the Time of Type 2 Diabetes Diagnosis and Subsequent Risk of Mortality: A Population-Based Cohort Study.", - "authorString": "Wang Z, Hazlehurst J, Subramanian A, Tahrani AA, Hanif W, Thomas N, Singh P, Wang J, Sainsbury C, Nirantharakumar K, Crowe FL.", + "id": "33306026", + "doi": "https://doi.org/10.2196/23369", + "title": "Engagement With a Behavior Change App for Alcohol Reduction: Data Visualization for Longitudinal Observational Study.", + "authorString": "Bell L, Garnett C, Qian T, Perski O, Williamson E, Potts HW.", "authorAffiliations": "", - "journalTitle": "Frontiers in endocrinology", - "pubYear": "2022", - "date": "2022-07-11", + "journalTitle": "Journal of medical Internet research", + "pubYear": "2020", + "date": "2020-12-11", "isOpenAccess": "Y", - "keywords": "Mortality; Type 2 diabetes; Diabetic Foot Disease; Diabetic Foot Risk; Foot Risk Examination", + "keywords": "Engagement; Behavior Change; Apps; Mobile Health; Digital Health; Just-in-time Adaptive Interventions; Push Notifications; Micro-randomized Trial; Data Visualizations", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Aim

We aimed to compare the mortality of individuals at low, moderate, and high risk of diabetic foot disease (DFD) in the context of newly diagnosed type 2 diabetes, before developing active diabetic foot problem.

Methods

This was a population-based cohort study of adults with newly diagnosed type 2 diabetes utilizing IQVIA Medical Research Data. The outcome was all-cause mortality among individuals with low, moderate, and high risk of DFD, and also in those with no record of foot assessment and those who declined foot examination.

Results

Of 225,787 individuals with newly diagnosed type 2 diabetes, 34,061 (15.1%) died during the study period from January 1, 2000 to December 31, 2019. Moderate risk and high risk of DFD were associated with increased mortality risk compared to low risk of DFD (adjusted hazard ratio [aHR] 1.50, 95% CI 1.42, 1.58; aHR 2.01, 95% CI 1.84, 2.20, respectively). Individuals who declined foot examination or who had no record also had increased mortality risk of 75% and 25% vs. those at low risk of DFD, respectively (aHR 1.75, 95% CI 1.51, 2.04; aHR 1.25, 95% CI 1.20, 1.30).

Conclusion

Individuals with new-onset type 2 diabetes who had moderate to high risk of DFD were more likely to die compared to those at low risk of DFD. The associations between declined foot examination and absence of foot examinations, and increased risk of mortality further highlight the importance of assessing foot risk as it identifies not only patients at risk of diabetic foot ulceration but also mortality.", + "abstract": "

Background

Behavior change apps can develop iteratively, where the app evolves into a complex, dynamic, or personalized intervention through cycles of research, development, and implementation. Understanding how existing users engage with an app (eg, frequency, amount, depth, and duration of use) can help guide further incremental improvements. We aim to explore how simple visualizations can provide a good understanding of temporal patterns of engagement, as usage data are often longitudinal and rich.

Objective

This study aims to visualize behavioral engagement with Drink Less, a behavior change app to help reduce hazardous and harmful alcohol consumption in the general adult population of the United Kingdom.

Methods

We explored behavioral engagement among 19,233 existing users of Drink Less. Users were included in the sample if they were from the United Kingdom; were 18 years or older; were interested in reducing their alcohol consumption; had a baseline Alcohol Use Disorders Identification Test score of 8 or above, indicative of excessive drinking; and had downloaded the app between May 17, 2017, and January 22, 2019 (615 days). Measures of when sessions begin, length of sessions, time to disengagement, and patterns of use were visualized with heat maps, timeline plots, k-modes clustering analyses, and Kaplan-Meier plots.

Results

The daily 11 AM notification is strongly associated with a change in engagement in the following hour; reduction in behavioral engagement over time, with 50.00% (9617/19,233) of users disengaging (defined as no use for 7 or more consecutive days) 22 days after download; identification of 3 distinct trajectories of use, namely engagers (4651/19,233, 24.18% of users), slow disengagers (3679/19,233, 19.13% of users), and fast disengagers (10,903/19,233, 56.68% of users); and limited depth of engagement with 85.076% (7,095,348/8,340,005) of screen views occurring within the Self-monitoring and Feedback module. In addition, a peak of both frequency and amount of time spent per session was observed in the evenings.

Conclusions

Visualizations play an important role in understanding engagement with behavior change apps. Here, we discuss how simple visualizations helped identify important patterns of engagement with Drink Less. Our visualizations of behavioral engagement suggest that the daily notification substantially impacts engagement. Furthermore, the visualizations suggest that a fixed notification policy can be effective for maintaining engagement for some users but ineffective for others. We conclude that optimizing the notification policy to target both effectiveness and engagement is a worthwhile investment. Our future goal is to both understand the causal effect of the notification on engagement and further optimize the notification policy within Drink Less by tailoring to contextual circumstances of individuals over time. Such tailoring will be informed from the findings of our micro-randomized trial (MRT), and these visualizations were useful in both gaining a better understanding of engagement and designing the MRT.", "laySummary": "", - "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fendo.2022.888924/pdf; doi:https://doi.org/10.3389/fendo.2022.888924; html:https://europepmc.org/articles/PMC9309507; pdf:https://europepmc.org/articles/PMC9309507?pdf=render" + "urls": "pdf:https://www.jmir.org/2020/12/e23369/PDF; doi:https://doi.org/10.2196/23369; html:https://europepmc.org/articles/PMC7762688" }, { "id": "34543272", @@ -17034,38 +17017,38 @@ "urls": "pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009324&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1009324; html:https://europepmc.org/articles/PMC8452068; pdf:https://europepmc.org/articles/PMC8452068?pdf=render" }, { - "id": "33306026", - "doi": "https://doi.org/10.2196/23369", - "title": "Engagement With a Behavior Change App for Alcohol Reduction: Data Visualization for Longitudinal Observational Study.", - "authorString": "Bell L, Garnett C, Qian T, Perski O, Williamson E, Potts HW.", + "id": "35898465", + "doi": "https://doi.org/10.3389/fendo.2022.888924", + "title": "Diabetic Foot Risk Classification at the Time of Type 2 Diabetes Diagnosis and Subsequent Risk of Mortality: A Population-Based Cohort Study.", + "authorString": "Wang Z, Hazlehurst J, Subramanian A, Tahrani AA, Hanif W, Thomas N, Singh P, Wang J, Sainsbury C, Nirantharakumar K, Crowe FL.", "authorAffiliations": "", - "journalTitle": "Journal of medical Internet research", - "pubYear": "2020", - "date": "2020-12-11", + "journalTitle": "Frontiers in endocrinology", + "pubYear": "2022", + "date": "2022-07-11", "isOpenAccess": "Y", - "keywords": "Engagement; Behavior Change; Apps; Mobile Health; Digital Health; Just-in-time Adaptive Interventions; Push Notifications; Micro-randomized Trial; Data Visualizations", + "keywords": "Mortality; Type 2 diabetes; Diabetic Foot Disease; Diabetic Foot Risk; Foot Risk Examination", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Behavior change apps can develop iteratively, where the app evolves into a complex, dynamic, or personalized intervention through cycles of research, development, and implementation. Understanding how existing users engage with an app (eg, frequency, amount, depth, and duration of use) can help guide further incremental improvements. We aim to explore how simple visualizations can provide a good understanding of temporal patterns of engagement, as usage data are often longitudinal and rich.

Objective

This study aims to visualize behavioral engagement with Drink Less, a behavior change app to help reduce hazardous and harmful alcohol consumption in the general adult population of the United Kingdom.

Methods

We explored behavioral engagement among 19,233 existing users of Drink Less. Users were included in the sample if they were from the United Kingdom; were 18 years or older; were interested in reducing their alcohol consumption; had a baseline Alcohol Use Disorders Identification Test score of 8 or above, indicative of excessive drinking; and had downloaded the app between May 17, 2017, and January 22, 2019 (615 days). Measures of when sessions begin, length of sessions, time to disengagement, and patterns of use were visualized with heat maps, timeline plots, k-modes clustering analyses, and Kaplan-Meier plots.

Results

The daily 11 AM notification is strongly associated with a change in engagement in the following hour; reduction in behavioral engagement over time, with 50.00% (9617/19,233) of users disengaging (defined as no use for 7 or more consecutive days) 22 days after download; identification of 3 distinct trajectories of use, namely engagers (4651/19,233, 24.18% of users), slow disengagers (3679/19,233, 19.13% of users), and fast disengagers (10,903/19,233, 56.68% of users); and limited depth of engagement with 85.076% (7,095,348/8,340,005) of screen views occurring within the Self-monitoring and Feedback module. In addition, a peak of both frequency and amount of time spent per session was observed in the evenings.

Conclusions

Visualizations play an important role in understanding engagement with behavior change apps. Here, we discuss how simple visualizations helped identify important patterns of engagement with Drink Less. Our visualizations of behavioral engagement suggest that the daily notification substantially impacts engagement. Furthermore, the visualizations suggest that a fixed notification policy can be effective for maintaining engagement for some users but ineffective for others. We conclude that optimizing the notification policy to target both effectiveness and engagement is a worthwhile investment. Our future goal is to both understand the causal effect of the notification on engagement and further optimize the notification policy within Drink Less by tailoring to contextual circumstances of individuals over time. Such tailoring will be informed from the findings of our micro-randomized trial (MRT), and these visualizations were useful in both gaining a better understanding of engagement and designing the MRT.", + "abstract": "

Aim

We aimed to compare the mortality of individuals at low, moderate, and high risk of diabetic foot disease (DFD) in the context of newly diagnosed type 2 diabetes, before developing active diabetic foot problem.

Methods

This was a population-based cohort study of adults with newly diagnosed type 2 diabetes utilizing IQVIA Medical Research Data. The outcome was all-cause mortality among individuals with low, moderate, and high risk of DFD, and also in those with no record of foot assessment and those who declined foot examination.

Results

Of 225,787 individuals with newly diagnosed type 2 diabetes, 34,061 (15.1%) died during the study period from January 1, 2000 to December 31, 2019. Moderate risk and high risk of DFD were associated with increased mortality risk compared to low risk of DFD (adjusted hazard ratio [aHR] 1.50, 95% CI 1.42, 1.58; aHR 2.01, 95% CI 1.84, 2.20, respectively). Individuals who declined foot examination or who had no record also had increased mortality risk of 75% and 25% vs. those at low risk of DFD, respectively (aHR 1.75, 95% CI 1.51, 2.04; aHR 1.25, 95% CI 1.20, 1.30).

Conclusion

Individuals with new-onset type 2 diabetes who had moderate to high risk of DFD were more likely to die compared to those at low risk of DFD. The associations between declined foot examination and absence of foot examinations, and increased risk of mortality further highlight the importance of assessing foot risk as it identifies not only patients at risk of diabetic foot ulceration but also mortality.", "laySummary": "", - "urls": "pdf:https://www.jmir.org/2020/12/e23369/PDF; doi:https://doi.org/10.2196/23369; html:https://europepmc.org/articles/PMC7762688" + "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fendo.2022.888924/pdf; doi:https://doi.org/10.3389/fendo.2022.888924; html:https://europepmc.org/articles/PMC9309507; pdf:https://europepmc.org/articles/PMC9309507?pdf=render" }, { - "id": "32788201", - "doi": "https://doi.org/10.1136/archdischild-2020-319027", - "title": "Predictive value of indicators for identifying child maltreatment and intimate partner violence in coded electronic health records: a systematic review and meta-analysis.", - "authorString": "Syed S, Ashwick R, Schlosser M, Gonzalez-Izquierdo A, Li L, Gilbert R.", + "id": "36812613", + "doi": "https://doi.org/10.1371/journal.pdig.0000190", + "title": "Optimizing cardiovascular risk assessment and registration in a developing cardiovascular learning health care system: Women benefit most.", + "authorString": "Groenhof TKJ, Haitjema S, Lely AT, Grobbee DE, Asselbergs FW, Bots ML, UCC-CVRM and UPOD Study groups.", "authorAffiliations": "", - "journalTitle": "Archives of disease in childhood", - "pubYear": "2021", - "date": "2020-08-11", + "journalTitle": "PLOS digital health", + "pubYear": "2023", + "date": "2023-02-08", "isOpenAccess": "Y", - "keywords": "Data collection; epidemiology; Child Abuse; Health Services Research; Drug Withdrawal", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Objective

Electronic health records (EHRs) are routinely used to identify family violence, yet reliable evidence of their validity remains limited. We conducted a systematic review and meta-analysis to evaluate the positive predictive values (PPVs) of coded indicators in EHRs for identifying intimate partner violence (IPV) and child maltreatment (CM), including prenatal neglect.

Methods

We searched 18 electronic databases between January 1980 and May 2020 for studies comparing any coded indicator of IPV or CM including prenatal neglect defined as neonatal abstinence syndrome (NAS) or fetal alcohol syndrome (FAS), against an independent reference standard. We pooled PPVs for each indicator using random effects meta-analyses.

Results

We included 88 studies (3 875 183 individuals) involving 15 indicators for identifying CM in the prenatal period and childhood (0-18 years) and five indicators for IPV among women of reproductive age (12-50 years). Based on the International Classification of Disease system, the pooled PPV was over 80% for NAS (16 studies) but lower for FAS (<40%; seven studies). For young children, primary diagnoses of CM, specific injury presentations (eg, rib fractures and retinal haemorrhages) and assaults showed a high PPV for CM (pooled PPVs: 55.9%-87.8%). Indicators of IPV in women had a high PPV, with primary diagnoses correctly identifying IPV in >85% of cases.

Conclusions

Coded indicators in EHRs have a high likelihood of correctly classifying types of CM and IPV across the life course, providing a useful tool for assessment, support and monitoring of high-risk groups in health services and research.", + "abstract": "Since 2015 we organized a uniform, structured collection of a fixed set of cardiovascular risk factors according the (inter)national guidelines on cardiovascular risk management. We evaluated the current state of a developing cardiovascular towards learning healthcare system-the Utrecht Cardiovascular Cohort Cardiovascular Risk Management (UCC-CVRM)-and its potential effect on guideline adherence in cardiovascular risk management. We conducted a before-after study comparing data from patients included in UCC-CVRM (2015-2018) and patients treated in our center before UCC-CVRM (2013-2015) who would have been eligible for UCC-CVRM using the Utrecht Patient Oriented Database (UPOD). Proportions of cardiovascular risk factor measurement before and after UCC-CVRM initiation were compared, as were proportions of patients that required (change of) blood pressure, lipid, or blood glucose lowering treatment. We estimated the likelihood to miss patients with hypertension, dyslipidemia, and elevated HbA1c before UCC-CVRM for the whole cohort and stratified for sex. In the present study, patients included up to October 2018 (n = 1904) were matched with 7195 UPOD patients with similar age, sex, department of referral and diagnose description. Completeness of risk factor measurement increased, ranging from 0% -77% before to 82%-94% after UCC-CVRM initiation. Before UCC-CVRM, we found more unmeasured risk factors in women compared to men. This sex-gap resolved in UCC-CVRM. The likelihood to miss hypertension, dyslipidemia, and elevated HbA1c was reduced by 67%, 75% and 90%, respectively, after UCC-CVRM initiation. A finding more pronounced in women compared to men. In conclusion, a systematic registration of the cardiovascular risk profile substantially improves guideline adherent assessment and decreases the risk of missing patients with elevated levels with an indication for treatment. The sex-gap disappeared after UCC-CVRM initiation. Thus, an LHS approach contributes to a more inclusive insight into quality of care and prevention of cardiovascular disease (progression).", "laySummary": "", - "urls": "pdf:https://adc.bmj.com/content/archdischild/106/1/44.full.pdf; doi:https://doi.org/10.1136/archdischild-2020-319027; html:https://europepmc.org/articles/PMC7788194; pdf:https://europepmc.org/articles/PMC7788194?pdf=render" + "urls": "pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000190&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000190; html:https://europepmc.org/articles/PMC9931327; pdf:https://europepmc.org/articles/PMC9931327?pdf=render" }, { "id": "32103533", @@ -17085,21 +17068,21 @@ "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4656008/1/manuscript.pdf; doi:https://doi.org/10.1002/sim.8503; html:https://europepmc.org/articles/PMC7612316; pdf:https://europepmc.org/articles/PMC7612316?pdf=render; doi:https://doi.org/10.1002/sim.8503" }, { - "id": "38692281", - "doi": "https://doi.org/10.1016/j.xgen.2024.100544", - "title": "Blood-based epigenome-wide analyses of chronic low-grade inflammation across diverse population cohorts.", - "authorString": "Hillary RF, Ng HK, McCartney DL, Elliott HR, Walker RM, Campbell A, Huang F, Direk K, Welsh P, Sattar N, Corley J, Hayward C, McIntosh AM, Sudlow C, Evans KL, Cox SR, Chambers JC, Loh M, Relton CL, Marioni RE, Yousefi PD, Suderman M.", + "id": "32788201", + "doi": "https://doi.org/10.1136/archdischild-2020-319027", + "title": "Predictive value of indicators for identifying child maltreatment and intimate partner violence in coded electronic health records: a systematic review and meta-analysis.", + "authorString": "Syed S, Ashwick R, Schlosser M, Gonzalez-Izquierdo A, Li L, Gilbert R.", "authorAffiliations": "", - "journalTitle": "Cell genomics", - "pubYear": "2024", - "date": "2024-04-30", + "journalTitle": "Archives of disease in childhood", + "pubYear": "2021", + "date": "2020-08-11", "isOpenAccess": "Y", - "keywords": "Prediction; DNA methylation; C-reactive Protein; Feature Selection; Alspac; Chronic Inflammation; Helios; Sabre; Generation Scotland; Lothian Birth Cohorts", + "keywords": "Data collection; epidemiology; Child Abuse; Health Services Research; Drug Withdrawal", "nationalPriorities": "", "healthCategories": "", - "abstract": "Chronic inflammation is a hallmark of age-related disease states. The effectiveness of inflammatory proteins including C-reactive protein (CRP) in assessing long-term inflammation is hindered by their phasic nature. DNA methylation (DNAm) signatures of CRP may act as more reliable markers of chronic inflammation. We show that inter-individual differences in DNAm capture 50% of the variance in circulating CRP (N\u00a0= 17,936, Generation Scotland). We develop a series of DNAm predictors of CRP using state-of-the-art algorithms. An elastic-net-regression-based predictor outperformed competing methods and explained 18% of phenotypic variance in the Lothian Birth Cohort of 1936 (LBC1936) cohort, doubling that of existing DNAm predictors. DNAm predictors performed comparably in four additional test cohorts (Avon Longitudinal Study of Parents and Children, Health for Life in Singapore, Southall and Brent Revisited, and LBC1921), including for individuals of diverse genetic ancestry and different age groups. The best-performing predictor surpassed assay-measured CRP and a genetic score in its associations with 26 health outcomes. Our findings forge new avenues for assessing chronic low-grade inflammation in diverse populations.", + "abstract": "

Objective

Electronic health records (EHRs) are routinely used to identify family violence, yet reliable evidence of their validity remains limited. We conducted a systematic review and meta-analysis to evaluate the positive predictive values (PPVs) of coded indicators in EHRs for identifying intimate partner violence (IPV) and child maltreatment (CM), including prenatal neglect.

Methods

We searched 18 electronic databases between January 1980 and May 2020 for studies comparing any coded indicator of IPV or CM including prenatal neglect defined as neonatal abstinence syndrome (NAS) or fetal alcohol syndrome (FAS), against an independent reference standard. We pooled PPVs for each indicator using random effects meta-analyses.

Results

We included 88 studies (3 875 183 individuals) involving 15 indicators for identifying CM in the prenatal period and childhood (0-18 years) and five indicators for IPV among women of reproductive age (12-50 years). Based on the International Classification of Disease system, the pooled PPV was over 80% for NAS (16 studies) but lower for FAS (<40%; seven studies). For young children, primary diagnoses of CM, specific injury presentations (eg, rib fractures and retinal haemorrhages) and assaults showed a high PPV for CM (pooled PPVs: 55.9%-87.8%). Indicators of IPV in women had a high PPV, with primary diagnoses correctly identifying IPV in >85% of cases.

Conclusions

Coded indicators in EHRs have a high likelihood of correctly classifying types of CM and IPV across the life course, providing a useful tool for assessment, support and monitoring of high-risk groups in health services and research.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.xgen.2024.100544; html:https://europepmc.org/articles/PMC11099341; pdf:https://europepmc.org/articles/PMC11099341?pdf=render" + "urls": "pdf:https://adc.bmj.com/content/archdischild/106/1/44.full.pdf; doi:https://doi.org/10.1136/archdischild-2020-319027; html:https://europepmc.org/articles/PMC7788194; pdf:https://europepmc.org/articles/PMC7788194?pdf=render" }, { "id": "32657853", @@ -17118,6 +17101,23 @@ "laySummary": "", "urls": "pdf:https://cronfa.swan.ac.uk/Record/cronfa53972/Download/53972__17281__0cb520258c2b49cdb0e751a62be92c5d.pdf; doi:https://doi.org/10.1097/SAP.0000000000002434" }, + { + "id": "38692281", + "doi": "https://doi.org/10.1016/j.xgen.2024.100544", + "title": "Blood-based epigenome-wide analyses of chronic low-grade inflammation across diverse population cohorts.", + "authorString": "Hillary RF, Ng HK, McCartney DL, Elliott HR, Walker RM, Campbell A, Huang F, Direk K, Welsh P, Sattar N, Corley J, Hayward C, McIntosh AM, Sudlow C, Evans KL, Cox SR, Chambers JC, Loh M, Relton CL, Marioni RE, Yousefi PD, Suderman M.", + "authorAffiliations": "", + "journalTitle": "Cell genomics", + "pubYear": "2024", + "date": "2024-04-30", + "isOpenAccess": "Y", + "keywords": "Prediction; DNA methylation; C-reactive Protein; Feature Selection; Alspac; Chronic Inflammation; Helios; Sabre; Generation Scotland; Lothian Birth Cohorts", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Chronic inflammation is a hallmark of age-related disease states. The effectiveness of inflammatory proteins including C-reactive protein (CRP) in assessing long-term inflammation is hindered by their phasic nature. DNA methylation (DNAm) signatures of CRP may act as more reliable markers of chronic inflammation. We show that inter-individual differences in DNAm capture 50% of the variance in circulating CRP (N\u00a0= 17,936, Generation Scotland). We develop a series of DNAm predictors of CRP using state-of-the-art algorithms. An elastic-net-regression-based predictor outperformed competing methods and explained 18% of phenotypic variance in the Lothian Birth Cohort of 1936 (LBC1936) cohort, doubling that of existing DNAm predictors. DNAm predictors performed comparably in four additional test cohorts (Avon Longitudinal Study of Parents and Children, Health for Life in Singapore, Southall and Brent Revisited, and LBC1921), including for individuals of diverse genetic ancestry and different age groups. The best-performing predictor surpassed assay-measured CRP and a genetic score in its associations with 26 health outcomes. Our findings forge new avenues for assessing chronic low-grade inflammation in diverse populations.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.xgen.2024.100544; html:https://europepmc.org/articles/PMC11099341; pdf:https://europepmc.org/articles/PMC11099341?pdf=render" + }, { "id": "35793336", "doi": "https://doi.org/10.1371/journal.pone.0266521", @@ -17390,23 +17390,6 @@ "laySummary": "", "urls": "html:https://europepmc.org/articles/PMC8861682; pdf:https://europepmc.org/articles/PMC8861682?pdf=render" }, - { - "id": "37306981", - "doi": "https://doi.org/10.1001/jamaneurol.2023.1580", - "title": "Independent Associations of Incident Epilepsy and Enzyme-Inducing and Non-Enzyme-Inducing Antiseizure Medications With the Development of Osteoporosis.", - "authorString": "Josephson CB, Gonzalez-Izquierdo A, Denaxas S, Sajobi TT, Klein KM, Wiebe S.", - "authorAffiliations": "", - "journalTitle": "JAMA neurology", - "pubYear": "2023", - "date": "2023-08-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Importance

Both epilepsy and enzyme-inducing antiseizure medications (eiASMs) having varying reports of an association with increased risks for osteoporosis.

Objective

To quantify and model the independent hazards for osteoporosis associated with incident epilepsy and eiASMS and non-eiASMs.

Design, setting, and participants

This open cohort study covered the years 1998 to 2019, with a median (IQR) follow-up of 5 (1.7-11.1) years. Data were collected for 6275 patients enrolled in the Clinical Practice Research Datalink and from hospital electronic health records. No patients who met inclusion criteria (Clinical Practice Research Datalink-acceptable data, aged 18 years or older, follow-up after the Hospital Episode Statistics patient care linkage date of 1998, and free of osteoporosis at baseline) were excluded or declined.

Exposure

Incident adult-onset epilepsy using a 5-year washout and receipt of 4 consecutive ASMs.

Main outcomes and measures

The outcome was incident osteoporosis as determined through Cox proportional hazards or accelerated failure time models where appropriate. Incident epilepsy was treated as a time-varying covariate. Analyses controlled for age, sex, socioeconomic status, cancer, 1 or more years of corticosteroid use, body mass index, bariatric surgery, eating disorders, hyperthyroidism, inflammatory bowel disease, rheumatoid arthritis, smoking status, falls, fragility fractures, and osteoporosis screening tests. Subsequent analyses (1) excluded body mass index, which was missing in 30% of patients; (2) applied propensity score matching for receipt of an eiASM; (3) restricted analyses to only those with incident onset epilepsy; and (4) restricted analyses to patients who developed epilepsy at age 65 years or older. Analyses were performed between July 1 and October 31, 2022, and in February 2023 for revisions.

Results

Of 8\u202f095\u202f441 adults identified, 6275 had incident adult-onset epilepsy (3220 female [51%] and 3055 male [49%]; incidence rate, 62 per 100\u202f000 person-years) with a median (IQR) age of 56 (38-73) years. When controlling for osteoporosis risk factors, incident epilepsy was independently associated with a 41% faster time to incident osteoporosis (time ratio [TR], 0.59; 95% CI, 0.52-0.67; P\u2009<\u2009.001). Both eiASMs (TR, 0.91; 95% CI, 0.87-0.95; P\u2009<\u2009.001) and non-eiASMs (TR, 0.77; 95% CI, 0.76-0.78; P\u2009<\u2009.001) were also associated with significant increased risks independent of epilepsy, accounting for 9% and 23% faster times to development of osteoporosis, respectively. The independent associations among epilepsy, eiASMs, and non-eiASMs remained consistent in propensity score-matched analyses, cohorts restricted to adult-onset epilepsy, and cohorts restricted to late-onset epilepsy.

Conclusions and relevance

These findings suggest that epilepsy is independently associated with a clinically meaningful increase in the risk for osteoporosis, as are both eiASMs and non-eiASMs. Routine screening and prophylaxis should be considered in all people with epilepsy.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1001/jamaneurol.2023.1580" - }, { "id": "31153319", "doi": "https://doi.org/10.1121/1.5100272", @@ -17424,6 +17407,23 @@ "laySummary": "", "urls": "pdf:https://asa.scitation.org/doi/pdf/10.1121/1.5100272; doi:https://doi.org/10.1121/1.5100272; html:https://europepmc.org/articles/PMC6509044; pdf:https://europepmc.org/articles/PMC6509044?pdf=render; doi:https://doi.org/10.1121/1.5100272" }, + { + "id": "37306981", + "doi": "https://doi.org/10.1001/jamaneurol.2023.1580", + "title": "Independent Associations of Incident Epilepsy and Enzyme-Inducing and Non-Enzyme-Inducing Antiseizure Medications With the Development of Osteoporosis.", + "authorString": "Josephson CB, Gonzalez-Izquierdo A, Denaxas S, Sajobi TT, Klein KM, Wiebe S.", + "authorAffiliations": "", + "journalTitle": "JAMA neurology", + "pubYear": "2023", + "date": "2023-08-01", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Importance

Both epilepsy and enzyme-inducing antiseizure medications (eiASMs) having varying reports of an association with increased risks for osteoporosis.

Objective

To quantify and model the independent hazards for osteoporosis associated with incident epilepsy and eiASMS and non-eiASMs.

Design, setting, and participants

This open cohort study covered the years 1998 to 2019, with a median (IQR) follow-up of 5 (1.7-11.1) years. Data were collected for 6275 patients enrolled in the Clinical Practice Research Datalink and from hospital electronic health records. No patients who met inclusion criteria (Clinical Practice Research Datalink-acceptable data, aged 18 years or older, follow-up after the Hospital Episode Statistics patient care linkage date of 1998, and free of osteoporosis at baseline) were excluded or declined.

Exposure

Incident adult-onset epilepsy using a 5-year washout and receipt of 4 consecutive ASMs.

Main outcomes and measures

The outcome was incident osteoporosis as determined through Cox proportional hazards or accelerated failure time models where appropriate. Incident epilepsy was treated as a time-varying covariate. Analyses controlled for age, sex, socioeconomic status, cancer, 1 or more years of corticosteroid use, body mass index, bariatric surgery, eating disorders, hyperthyroidism, inflammatory bowel disease, rheumatoid arthritis, smoking status, falls, fragility fractures, and osteoporosis screening tests. Subsequent analyses (1) excluded body mass index, which was missing in 30% of patients; (2) applied propensity score matching for receipt of an eiASM; (3) restricted analyses to only those with incident onset epilepsy; and (4) restricted analyses to patients who developed epilepsy at age 65 years or older. Analyses were performed between July 1 and October 31, 2022, and in February 2023 for revisions.

Results

Of 8\u202f095\u202f441 adults identified, 6275 had incident adult-onset epilepsy (3220 female [51%] and 3055 male [49%]; incidence rate, 62 per 100\u202f000 person-years) with a median (IQR) age of 56 (38-73) years. When controlling for osteoporosis risk factors, incident epilepsy was independently associated with a 41% faster time to incident osteoporosis (time ratio [TR], 0.59; 95% CI, 0.52-0.67; P\u2009<\u2009.001). Both eiASMs (TR, 0.91; 95% CI, 0.87-0.95; P\u2009<\u2009.001) and non-eiASMs (TR, 0.77; 95% CI, 0.76-0.78; P\u2009<\u2009.001) were also associated with significant increased risks independent of epilepsy, accounting for 9% and 23% faster times to development of osteoporosis, respectively. The independent associations among epilepsy, eiASMs, and non-eiASMs remained consistent in propensity score-matched analyses, cohorts restricted to adult-onset epilepsy, and cohorts restricted to late-onset epilepsy.

Conclusions and relevance

These findings suggest that epilepsy is independently associated with a clinically meaningful increase in the risk for osteoporosis, as are both eiASMs and non-eiASMs. Routine screening and prophylaxis should be considered in all people with epilepsy.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1001/jamaneurol.2023.1580" + }, { "id": "31611193", "doi": "https://doi.org/10.1136/archdischild-2019-317248", @@ -17492,6 +17492,23 @@ "laySummary": "", "urls": "pdf:http://www.aginganddisease.org/EN/PDF/10.14336/AD.2022.1107; doi:https://doi.org/10.14336/AD.2022.1107; html:https://europepmc.org/articles/PMC10187689; pdf:https://europepmc.org/articles/PMC10187689?pdf=render" }, + { + "id": "31765395", + "doi": "https://doi.org/10.1371/journal.pone.0225625", + "title": "Semantic computational analysis of anticoagulation use in atrial fibrillation from real world data.", + "authorString": "Bean DM, Teo J, Wu H, Oliveira R, Patel R, Bendayan R, Shah AM, Dobson RJB, Scott PA.", + "authorAffiliations": "", + "journalTitle": "PloS one", + "pubYear": "2019", + "date": "2019-11-25", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Atrial fibrillation (AF) is the most common arrhythmia and significantly increases stroke risk. This risk is effectively managed by oral anticoagulation. Recent studies using national registry data indicate increased use of anticoagulation resulting from changes in guidelines and the availability of newer drugs. The aim of this study is to develop and validate an open source risk scoring pipeline for free-text electronic health record data using natural language processing. AF patients discharged from 1st January 2011 to 1st October 2017 were identified from discharge summaries (N = 10,030, 64.6% male, average age 75.3 \u00b1 12.3 years). A natural language processing pipeline was developed to identify risk factors in clinical text and calculate risk for ischaemic stroke (CHA2DS2-VASc) and bleeding (HAS-BLED). Scores were validated vs two independent experts for 40 patients. Automatic risk scores were in strong agreement with the two independent experts for CHA2DS2-VASc (average kappa 0.78 vs experts, compared to 0.85 between experts). Agreement was lower for HAS-BLED (average kappa 0.54 vs experts, compared to 0.74 between experts). In high-risk patients (CHA2DS2-VASc \u22652) OAC use has increased significantly over the last 7 years, driven by the availability of DOACs and the transitioning of patients from AP medication alone to OAC. Factors independently associated with OAC use included components of the CHA2DS2-VASc and HAS-BLED scores as well as discharging specialty and frailty. OAC use was highest in patients discharged under cardiology (69%). Electronic health record text can be used for automatic calculation of clinical risk scores at scale. Open source tools are available today for this task but require further validation. Analysis of routinely collected EHR data can replicate findings from large-scale curated registries.", + "laySummary": "Bean et al. looked at using clinical notes to calculate risk scores: CHADSVASC and HASBLED for 10,030 AF patients from 2011 to October 2017), they\u2019ve validated their natural language processing algorithm with getting clinicians to calculate the risk in conventional manner for 40 of cases, the two scores were in higher agreement for stroke risk compared to HAS-BLED They\u2019ve concluded on usefulness of NLP method in risk calculation at the large scale.", + "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0225625&type=printable; doi:https://doi.org/10.1371/journal.pone.0225625; html:https://europepmc.org/articles/PMC6876873; pdf:https://europepmc.org/articles/PMC6876873?pdf=render" + }, { "id": "37717030", "doi": "https://doi.org/10.1186/s13756-023-01280-6", @@ -17526,23 +17543,6 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/acps.13566; doi:https://doi.org/10.1111/acps.13566; html:https://europepmc.org/articles/PMC10953461; pdf:https://europepmc.org/articles/PMC10953461?pdf=render" }, - { - "id": "31765395", - "doi": "https://doi.org/10.1371/journal.pone.0225625", - "title": "Semantic computational analysis of anticoagulation use in atrial fibrillation from real world data.", - "authorString": "Bean DM, Teo J, Wu H, Oliveira R, Patel R, Bendayan R, Shah AM, Dobson RJB, Scott PA.", - "authorAffiliations": "", - "journalTitle": "PloS one", - "pubYear": "2019", - "date": "2019-11-25", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Atrial fibrillation (AF) is the most common arrhythmia and significantly increases stroke risk. This risk is effectively managed by oral anticoagulation. Recent studies using national registry data indicate increased use of anticoagulation resulting from changes in guidelines and the availability of newer drugs. The aim of this study is to develop and validate an open source risk scoring pipeline for free-text electronic health record data using natural language processing. AF patients discharged from 1st January 2011 to 1st October 2017 were identified from discharge summaries (N = 10,030, 64.6% male, average age 75.3 \u00b1 12.3 years). A natural language processing pipeline was developed to identify risk factors in clinical text and calculate risk for ischaemic stroke (CHA2DS2-VASc) and bleeding (HAS-BLED). Scores were validated vs two independent experts for 40 patients. Automatic risk scores were in strong agreement with the two independent experts for CHA2DS2-VASc (average kappa 0.78 vs experts, compared to 0.85 between experts). Agreement was lower for HAS-BLED (average kappa 0.54 vs experts, compared to 0.74 between experts). In high-risk patients (CHA2DS2-VASc \u22652) OAC use has increased significantly over the last 7 years, driven by the availability of DOACs and the transitioning of patients from AP medication alone to OAC. Factors independently associated with OAC use included components of the CHA2DS2-VASc and HAS-BLED scores as well as discharging specialty and frailty. OAC use was highest in patients discharged under cardiology (69%). Electronic health record text can be used for automatic calculation of clinical risk scores at scale. Open source tools are available today for this task but require further validation. Analysis of routinely collected EHR data can replicate findings from large-scale curated registries.", - "laySummary": "Bean et al. looked at using clinical notes to calculate risk scores: CHADSVASC and HASBLED for 10,030 AF patients from 2011 to October 2017), they\u2019ve validated their natural language processing algorithm with getting clinicians to calculate the risk in conventional manner for 40 of cases, the two scores were in higher agreement for stroke risk compared to HAS-BLED They\u2019ve concluded on usefulness of NLP method in risk calculation at the large scale.", - "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0225625&type=printable; doi:https://doi.org/10.1371/journal.pone.0225625; html:https://europepmc.org/articles/PMC6876873; pdf:https://europepmc.org/articles/PMC6876873?pdf=render" - }, { "id": "32790708", "doi": "https://doi.org/10.1371/journal.pone.0237298", @@ -17662,23 +17662,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.5837/bjc.2023.003; html:https://europepmc.org/articles/PMC10495762; pdf:https://europepmc.org/articles/PMC10495762?pdf=render; doi:https://doi.org/10.5837/bjc.2023.003" }, - { - "id": "37897346", - "doi": "https://doi.org/10.1093/eurheartj/ehad727", - "title": "Five critical quality criteria for artificial intelligence-based prediction models.", - "authorString": "van Royen FS, Asselbergs FW, Alfonso F, Vardas P, van Smeden M.", - "authorAffiliations": "", - "journalTitle": "European heart journal", - "pubYear": "2023", - "date": "2023-12-01", - "isOpenAccess": "Y", - "keywords": "Prediction; Artificial intelligence; Diagnosis; Prognosis; Digital Health", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "To raise the quality of clinical artificial intelligence (AI) prediction modelling studies in the cardiovascular health domain and thereby improve their impact and relevancy, the editors for digital health, innovation, and quality standards of the European Heart Journal propose five minimal quality criteria for AI-based prediction model development and validation studies: complete reporting, carefully defined intended use of the model, rigorous validation, large enough sample size, and openness of code and software.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/eurheartj/ehad727; html:https://europepmc.org/articles/PMC10702458; pdf:https://europepmc.org/articles/PMC10702458?pdf=render" - }, { "id": "33851963", "doi": "https://doi.org/10.1001/jamadermatol.2021.0009", @@ -17730,6 +17713,23 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/1660-4601/20/4/3477/pdf?version=1677135187; doi:https://doi.org/10.3390/ijerph20043477; html:https://europepmc.org/articles/PMC9967466; pdf:https://europepmc.org/articles/PMC9967466?pdf=render" }, + { + "id": "37897346", + "doi": "https://doi.org/10.1093/eurheartj/ehad727", + "title": "Five critical quality criteria for artificial intelligence-based prediction models.", + "authorString": "van Royen FS, Asselbergs FW, Alfonso F, Vardas P, van Smeden M.", + "authorAffiliations": "", + "journalTitle": "European heart journal", + "pubYear": "2023", + "date": "2023-12-01", + "isOpenAccess": "Y", + "keywords": "Prediction; Artificial intelligence; Diagnosis; Prognosis; Digital Health", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "To raise the quality of clinical artificial intelligence (AI) prediction modelling studies in the cardiovascular health domain and thereby improve their impact and relevancy, the editors for digital health, innovation, and quality standards of the European Heart Journal propose five minimal quality criteria for AI-based prediction model development and validation studies: complete reporting, carefully defined intended use of the model, rigorous validation, large enough sample size, and openness of code and software.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/eurheartj/ehad727; html:https://europepmc.org/articles/PMC10702458; pdf:https://europepmc.org/articles/PMC10702458?pdf=render" + }, { "id": "33497994", "doi": "https://doi.org/10.1016/j.puhe.2020.12.003", @@ -17764,23 +17764,6 @@ "laySummary": "", "urls": "pdf:http://www.jacionline.org/article/S0091674920317127/pdf; doi:https://doi.org/10.1016/j.jaci.2020.12.001; html:https://europepmc.org/articles/PMC8098860; pdf:https://europepmc.org/articles/PMC8098860?pdf=render" }, - { - "id": "38374065", - "doi": "https://doi.org/10.1038/s41467-024-45779-x", - "title": "Genetic influences on circulating retinol and its relationship to human health.", - "authorString": "Reay WR, Kiltschewskij DJ, Di Biase MA, Gerring ZF, Kundu K, Surendran P, Greco LA, Clarke ED, Collins CE, Mondul AM, Albanes D, Cairns MJ.", - "authorAffiliations": "", - "journalTitle": "Nature communications", - "pubYear": "2024", - "date": "2024-02-19", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Retinol is a fat-soluble vitamin that plays an essential role in many biological processes throughout the human lifespan. Here, we perform the largest genome-wide association study (GWAS) of retinol to date in up to 22,274 participants. We identify eight common variant loci associated with retinol, as well as a rare-variant signal. An integrative gene prioritisation pipeline supports novel retinol-associated genes outside of the main retinol transport complex (RBP4:TTR) related to lipid biology, energy homoeostasis, and endocrine signalling. Genetic proxies of circulating retinol were then used to estimate causal relationships with almost 20,000 clinical phenotypes via a phenome-wide Mendelian randomisation study (MR-pheWAS). The MR-pheWAS suggests that retinol may exert causal effects on inflammation, adiposity, ocular measures, the microbiome, and MRI-derived brain phenotypes, amongst several others. Conversely, circulating retinol may be causally influenced by factors including lipids and serum creatinine. Finally, we demonstrate how a retinol polygenic score could identify individuals more likely to fall outside of the normative range of circulating retinol for a given age. In summary, this study provides a comprehensive evaluation of the genetics of circulating retinol, as well as revealing traits which should be prioritised for further investigation with respect to retinol related therapies or nutritional intervention.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41467-024-45779-x.pdf; doi:https://doi.org/10.1038/s41467-024-45779-x; html:https://europepmc.org/articles/PMC10876955; pdf:https://europepmc.org/articles/PMC10876955?pdf=render" - }, { "id": "37814053", "doi": "https://doi.org/10.1038/s41588-023-01522-8", @@ -17798,6 +17781,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41588-023-01522-8.pdf; doi:https://doi.org/10.1038/s41588-023-01522-8; html:https://europepmc.org/articles/PMC10632146; pdf:https://europepmc.org/articles/PMC10632146?pdf=render" }, + { + "id": "38374065", + "doi": "https://doi.org/10.1038/s41467-024-45779-x", + "title": "Genetic influences on circulating retinol and its relationship to human health.", + "authorString": "Reay WR, Kiltschewskij DJ, Di Biase MA, Gerring ZF, Kundu K, Surendran P, Greco LA, Clarke ED, Collins CE, Mondul AM, Albanes D, Cairns MJ.", + "authorAffiliations": "", + "journalTitle": "Nature communications", + "pubYear": "2024", + "date": "2024-02-19", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Retinol is a fat-soluble vitamin that plays an essential role in many biological processes throughout the human lifespan. Here, we perform the largest genome-wide association study (GWAS) of retinol to date in up to 22,274 participants. We identify eight common variant loci associated with retinol, as well as a rare-variant signal. An integrative gene prioritisation pipeline supports novel retinol-associated genes outside of the main retinol transport complex (RBP4:TTR) related to lipid biology, energy homoeostasis, and endocrine signalling. Genetic proxies of circulating retinol were then used to estimate causal relationships with almost 20,000 clinical phenotypes via a phenome-wide Mendelian randomisation study (MR-pheWAS). The MR-pheWAS suggests that retinol may exert causal effects on inflammation, adiposity, ocular measures, the microbiome, and MRI-derived brain phenotypes, amongst several others. Conversely, circulating retinol may be causally influenced by factors including lipids and serum creatinine. Finally, we demonstrate how a retinol polygenic score could identify individuals more likely to fall outside of the normative range of circulating retinol for a given age. In summary, this study provides a comprehensive evaluation of the genetics of circulating retinol, as well as revealing traits which should be prioritised for further investigation with respect to retinol related therapies or nutritional intervention.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41467-024-45779-x.pdf; doi:https://doi.org/10.1038/s41467-024-45779-x; html:https://europepmc.org/articles/PMC10876955; pdf:https://europepmc.org/articles/PMC10876955?pdf=render" + }, { "id": "37008054", "doi": "https://doi.org/10.14336/ad.2022.0829", @@ -18002,23 +18002,6 @@ "laySummary": "", "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497842; doi:https://doi.org/10.1038/s43016-020-0093-y; html:https://europepmc.org/articles/PMC7497842; pdf:https://europepmc.org/articles/PMC7497842?pdf=render; doi:https://doi.org/10.1038/s43016-020-0093-y" }, - { - "id": "34969173", - "doi": "https://doi.org/10.1002/ejhf.2417", - "title": "A population-based study of 92 clinically recognized risk factors for heart failure: co-occurrence, prognosis and preventive potential.", - "authorString": "Banerjee A, Pasea L, Chung SC, Direk K, Asselbergs FW, Grobbee DE, Kotecha D, Anker SD, Dyszynski T, Tyl B, Denaxas S, Lumbers RT, Hemingway H.", - "authorAffiliations": "", - "journalTitle": "European journal of heart failure", - "pubYear": "2022", - "date": "2022-01-26", - "isOpenAccess": "Y", - "keywords": "Risk factor; epidemiology; Heart Failure; Primary Prevention", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

Primary prevention strategies for heart failure (HF) have had limited success, possibly due to a wide range of underlying risk factors (RFs). Systematic evaluations of the prognostic burden and preventive potential across this wide range of risk factors are lacking. We aimed at estimating evidence, prevalence and co-occurrence for primary prevention and impact on prognosis of RFs for incident HF.

Methods and results

We systematically reviewed trials and observational evidence of primary HF prevention across 92 putative aetiologic RFs for HF identified from US and European clinical practice guidelines. We identified 170\u2009885 individuals aged \u226530\u2009years with incident HF from 1997 to 2017, using linked primary and secondary care UK electronic health records (EHR) and rule-based phenotypes (ICD-10, Read Version 2, OPCS-4 procedure and medication codes) for each of 92 RFs. Only 10/92 factors had high quality observational evidence for association with incident HF; 7 had effective randomized controlled trial (RCT)-based interventions for HF prevention (RCT-HF), and 6 for cardiovascular disease prevention, but not HF (RCT-CVD), and the remainder had no RCT-based preventive interventions (RCT-0). We were able to map 91/92 risk factors to EHR using 5961 terms, and 88/91 factors were represented by at least one patient. In the 5\u2009years prior to HF diagnosis, 44.3% had \u22654 RFs. By RCT evidence, the most common RCT-HF RFs were hypertension (48.5%), stable angina (34.9%), unstable angina (16.8%), myocardial infarction (15.8%), and diabetes (15.1%); RCT-CVD RFs were smoking (46.4%) and obesity (29.9%); and RCT-0 RFs were atrial arrhythmias (17.2%), cancer (16.5%), heavy alcohol intake (14.9%). Mortality at 1\u00a0year varied across all 91 factors (lowest: pregnancy-related hormonal disorder 4.2%; highest: phaeochromocytoma 73.7%). Among new HF cases, 28.5% had no RCT-HF RFs and 38.6% had no RCT-CVD RFs. 15.6% had either no RF or only RCT-0 RFs.

Conclusion

One in six individuals with HF have no recorded RFs or RFs without trials. We provide a systematic map of primary preventive opportunities across a wide range of RFs for HF, demonstrating a high burden of co-occurrence and the need for trials tackling multiple RFs.", - "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejhf.2417; doi:https://doi.org/10.1002/ejhf.2417; html:https://europepmc.org/articles/PMC9305958; pdf:https://europepmc.org/articles/PMC9305958?pdf=render" - }, { "id": "35130878", "doi": "https://doi.org/10.1186/s12916-022-02234-2", @@ -18036,6 +18019,23 @@ "laySummary": "", "urls": "pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-022-02234-2; doi:https://doi.org/10.1186/s12916-022-02234-2; html:https://europepmc.org/articles/PMC8822817; pdf:https://europepmc.org/articles/PMC8822817?pdf=render" }, + { + "id": "34969173", + "doi": "https://doi.org/10.1002/ejhf.2417", + "title": "A population-based study of 92 clinically recognized risk factors for heart failure: co-occurrence, prognosis and preventive potential.", + "authorString": "Banerjee A, Pasea L, Chung SC, Direk K, Asselbergs FW, Grobbee DE, Kotecha D, Anker SD, Dyszynski T, Tyl B, Denaxas S, Lumbers RT, Hemingway H.", + "authorAffiliations": "", + "journalTitle": "European journal of heart failure", + "pubYear": "2022", + "date": "2022-01-26", + "isOpenAccess": "Y", + "keywords": "Risk factor; epidemiology; Heart Failure; Primary Prevention", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

Primary prevention strategies for heart failure (HF) have had limited success, possibly due to a wide range of underlying risk factors (RFs). Systematic evaluations of the prognostic burden and preventive potential across this wide range of risk factors are lacking. We aimed at estimating evidence, prevalence and co-occurrence for primary prevention and impact on prognosis of RFs for incident HF.

Methods and results

We systematically reviewed trials and observational evidence of primary HF prevention across 92 putative aetiologic RFs for HF identified from US and European clinical practice guidelines. We identified 170\u2009885 individuals aged \u226530\u2009years with incident HF from 1997 to 2017, using linked primary and secondary care UK electronic health records (EHR) and rule-based phenotypes (ICD-10, Read Version 2, OPCS-4 procedure and medication codes) for each of 92 RFs. Only 10/92 factors had high quality observational evidence for association with incident HF; 7 had effective randomized controlled trial (RCT)-based interventions for HF prevention (RCT-HF), and 6 for cardiovascular disease prevention, but not HF (RCT-CVD), and the remainder had no RCT-based preventive interventions (RCT-0). We were able to map 91/92 risk factors to EHR using 5961 terms, and 88/91 factors were represented by at least one patient. In the 5\u2009years prior to HF diagnosis, 44.3% had \u22654 RFs. By RCT evidence, the most common RCT-HF RFs were hypertension (48.5%), stable angina (34.9%), unstable angina (16.8%), myocardial infarction (15.8%), and diabetes (15.1%); RCT-CVD RFs were smoking (46.4%) and obesity (29.9%); and RCT-0 RFs were atrial arrhythmias (17.2%), cancer (16.5%), heavy alcohol intake (14.9%). Mortality at 1\u00a0year varied across all 91 factors (lowest: pregnancy-related hormonal disorder 4.2%; highest: phaeochromocytoma 73.7%). Among new HF cases, 28.5% had no RCT-HF RFs and 38.6% had no RCT-CVD RFs. 15.6% had either no RF or only RCT-0 RFs.

Conclusion

One in six individuals with HF have no recorded RFs or RFs without trials. We provide a systematic map of primary preventive opportunities across a wide range of RFs for HF, demonstrating a high burden of co-occurrence and the need for trials tackling multiple RFs.", + "laySummary": "", + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejhf.2417; doi:https://doi.org/10.1002/ejhf.2417; html:https://europepmc.org/articles/PMC9305958; pdf:https://europepmc.org/articles/PMC9305958?pdf=render" + }, { "id": "36439548", "doi": "https://doi.org/10.3389/fsurg.2022.870494", @@ -18053,23 +18053,6 @@ "laySummary": "", "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fsurg.2022.870494/pdf; doi:https://doi.org/10.3389/fsurg.2022.870494; html:https://europepmc.org/articles/PMC9683031; pdf:https://europepmc.org/articles/PMC9683031?pdf=render" }, - { - "id": "38124256", - "doi": "https://doi.org/10.1093/ageing/afad219", - "title": "New Horizons in artificial intelligence in the healthcare of older people.", - "authorString": "Shiwani T, Relton S, Evans R, Kale A, Heaven A, Clegg A, Ageing Data Research Collaborative (Geridata) AI group\n, Todd O.", - "authorAffiliations": "", - "journalTitle": "Age and ageing", - "pubYear": "2023", - "date": "2023-12-01", - "isOpenAccess": "Y", - "keywords": "Artificial intelligence; Technology; Ageing; Health; Older People", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Artificial intelligence (AI) in healthcare describes algorithm-based computational techniques which manage and analyse large datasets to make inferences and predictions. There are many potential applications of AI in the care of older people, from clinical decision support systems that can support identification of delirium from clinical records to wearable devices that can predict the risk of a fall. We held four meetings of older people, clinicians and AI researchers. Three priority areas were identified for AI application in the care of older people. These included: monitoring and early diagnosis of disease, stratified care and care coordination between healthcare providers. However, the meetings also highlighted concerns that AI may exacerbate health inequity for older people through bias within AI models, lack of external validation amongst older people, infringements on privacy and autonomy, insufficient transparency of AI models and lack of safeguarding for errors. Creating effective interventions for older people requires a person-centred approach to account for the needs of older people, as well as sufficient clinical and technological governance to meet standards of generalisability, transparency and effectiveness. Education of clinicians and patients is also needed to ensure appropriate use of AI technologies, with investment in technological infrastructure required to ensure equity of access.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/ageing/afad219; html:https://europepmc.org/articles/PMC10733173; pdf:https://europepmc.org/articles/PMC10733173?pdf=render" - }, { "id": "33890864", "doi": "https://doi.org/10.2196/24728", @@ -18087,6 +18070,23 @@ "laySummary": "", "urls": "pdf:https://aging.jmir.org/2021/2/e24728/PDF; doi:https://doi.org/10.2196/24728; html:https://europepmc.org/articles/PMC8105762; pdf:https://europepmc.org/articles/PMC8105762?pdf=render" }, + { + "id": "38124256", + "doi": "https://doi.org/10.1093/ageing/afad219", + "title": "New Horizons in artificial intelligence in the healthcare of older people.", + "authorString": "Shiwani T, Relton S, Evans R, Kale A, Heaven A, Clegg A, Ageing Data Research Collaborative (Geridata) AI group\n, Todd O.", + "authorAffiliations": "", + "journalTitle": "Age and ageing", + "pubYear": "2023", + "date": "2023-12-01", + "isOpenAccess": "Y", + "keywords": "Artificial intelligence; Technology; Ageing; Health; Older People", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Artificial intelligence (AI) in healthcare describes algorithm-based computational techniques which manage and analyse large datasets to make inferences and predictions. There are many potential applications of AI in the care of older people, from clinical decision support systems that can support identification of delirium from clinical records to wearable devices that can predict the risk of a fall. We held four meetings of older people, clinicians and AI researchers. Three priority areas were identified for AI application in the care of older people. These included: monitoring and early diagnosis of disease, stratified care and care coordination between healthcare providers. However, the meetings also highlighted concerns that AI may exacerbate health inequity for older people through bias within AI models, lack of external validation amongst older people, infringements on privacy and autonomy, insufficient transparency of AI models and lack of safeguarding for errors. Creating effective interventions for older people requires a person-centred approach to account for the needs of older people, as well as sufficient clinical and technological governance to meet standards of generalisability, transparency and effectiveness. Education of clinicians and patients is also needed to ensure appropriate use of AI technologies, with investment in technological infrastructure required to ensure equity of access.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/ageing/afad219; html:https://europepmc.org/articles/PMC10733173; pdf:https://europepmc.org/articles/PMC10733173?pdf=render" + }, { "id": "33414147", "doi": "https://doi.org/10.1136/bmjopen-2020-041536", @@ -18104,23 +18104,6 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e041536.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-041536; html:https://europepmc.org/articles/PMC7797241; pdf:https://europepmc.org/articles/PMC7797241?pdf=render" }, - { - "id": "37032516", - "doi": "https://doi.org/10.1111/aor.14537", - "title": "Incidence and risk factors of late right heart failure in chronic mechanical circulatory support.", - "authorString": "Felix SEA, Numan L, Oerlemans MIF, Aarts E, Ramjankhan FZ, Gianoli M, Asselbergs FW, De Jonge N, Van Laake LW.", - "authorAffiliations": "", - "journalTitle": "Artificial organs", - "pubYear": "2023", - "date": "2023-04-21", - "isOpenAccess": "N", - "keywords": "Risk factor; Mechanical Circulatory Support; Left Ventricular Assist Device; Late Right Heart Failure", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Late right heart failure (LRHF) is a common complication during long-term left ventricular assist device (LVAD) support. We aimed to identify risk factors for LRHF after LVAD implantation.

Methods

Patients undergoing primary LVAD implantation between 2006 and 2019 and surviving the perioperative period were included for this study (n\u2009=\u2009261). Univariate Cox proportional hazards analysis was used to assess the association of clinical covariates and LRHF, stratified for device type. Variables with p <\u20090.10 entered the multivariable model. In a subset of patients with complete echocardiography or right catheterization data, this multivariable model was extended. Postoperative cardiopulmonary exercise test data were compared in patients with and without LRHF.

Results

Nineteen percentage of patients suffered from LRHF after a median of 12\u2009months, of which 67% required hospitalization. A history of atrial fibrillation (AF) (HR: 2.06 [1.08-3.93], p\u2009=\u20090.029), a higher preoperative body mass index (BMI) (HR: 1.07 [1.01-1.13], p\u2009=\u20090.023), and intensive care unit (ICU) duration (HR: 1.03 [1.00-1.06], p\u2009=\u20090.025) were independent predictors of LHRF in the multivariable model. A significant relation between the severity of tricuspid regurgitation (TR) and LRHF (HR: 1.91 [1.13-3.21], p\u2009=\u20090.016) was found in patients with echocardiographic data. Patients with LRHF demonstrated a lower maximal workload and peak VO2 at 6\u2009months postoperatively.

Conclusion

A history of AF, BMI, and longer ICU stay may help identify patients at high risk for LRHF. Severity of TR was significantly related to LRHF in a subset of patients.", - "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/aor.14537; doi:https://doi.org/10.1111/aor.14537" - }, { "id": "34286192", "doi": "https://doi.org/10.7861/fhj.2021-0083", @@ -18138,23 +18121,6 @@ "laySummary": "", "urls": "pdf:https://www.rcpjournals.org/content/futurehosp/8/2/e243.full.pdf; doi:https://doi.org/10.7861/fhj.2021-0083; html:https://europepmc.org/articles/PMC8285150; pdf:https://europepmc.org/articles/PMC8285150?pdf=render; doi:https://doi.org/10.7861/fhj.2021-0083" }, - { - "id": "37549998", - "doi": "https://doi.org/10.1136/bjsports-2022-106460", - "title": "Device-based measurement of physical activity in cardiovascular healthcare: possibilities and challenges.", - "authorString": "Chico TJ, Stamatakis E, Ciravegna F, Dunn J, Redwood S, Al-Lamee R, Sofat R, Gill J.", - "authorAffiliations": "", - "journalTitle": "British journal of sports medicine", - "pubYear": "2023", - "date": "2023-08-07", - "isOpenAccess": "N", - "keywords": "Cardiovascular diseases; Health; Physical Activity", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bjsports-2022-106460" - }, { "id": "32060159", "doi": "https://doi.org/10.1136/bmjopen-2019-034396", @@ -18172,6 +18138,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/10/2/e034396.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-034396; html:https://europepmc.org/articles/PMC7045100; pdf:https://europepmc.org/articles/PMC7045100?pdf=render" }, + { + "id": "37032516", + "doi": "https://doi.org/10.1111/aor.14537", + "title": "Incidence and risk factors of late right heart failure in chronic mechanical circulatory support.", + "authorString": "Felix SEA, Numan L, Oerlemans MIF, Aarts E, Ramjankhan FZ, Gianoli M, Asselbergs FW, De Jonge N, Van Laake LW.", + "authorAffiliations": "", + "journalTitle": "Artificial organs", + "pubYear": "2023", + "date": "2023-04-21", + "isOpenAccess": "N", + "keywords": "Risk factor; Mechanical Circulatory Support; Left Ventricular Assist Device; Late Right Heart Failure", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Late right heart failure (LRHF) is a common complication during long-term left ventricular assist device (LVAD) support. We aimed to identify risk factors for LRHF after LVAD implantation.

Methods

Patients undergoing primary LVAD implantation between 2006 and 2019 and surviving the perioperative period were included for this study (n\u2009=\u2009261). Univariate Cox proportional hazards analysis was used to assess the association of clinical covariates and LRHF, stratified for device type. Variables with p <\u20090.10 entered the multivariable model. In a subset of patients with complete echocardiography or right catheterization data, this multivariable model was extended. Postoperative cardiopulmonary exercise test data were compared in patients with and without LRHF.

Results

Nineteen percentage of patients suffered from LRHF after a median of 12\u2009months, of which 67% required hospitalization. A history of atrial fibrillation (AF) (HR: 2.06 [1.08-3.93], p\u2009=\u20090.029), a higher preoperative body mass index (BMI) (HR: 1.07 [1.01-1.13], p\u2009=\u20090.023), and intensive care unit (ICU) duration (HR: 1.03 [1.00-1.06], p\u2009=\u20090.025) were independent predictors of LHRF in the multivariable model. A significant relation between the severity of tricuspid regurgitation (TR) and LRHF (HR: 1.91 [1.13-3.21], p\u2009=\u20090.016) was found in patients with echocardiographic data. Patients with LRHF demonstrated a lower maximal workload and peak VO2 at 6\u2009months postoperatively.

Conclusion

A history of AF, BMI, and longer ICU stay may help identify patients at high risk for LRHF. Severity of TR was significantly related to LRHF in a subset of patients.", + "laySummary": "", + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/aor.14537; doi:https://doi.org/10.1111/aor.14537" + }, { "id": "33612430", "doi": "https://doi.org/10.1016/s2589-7500(21)00017-0", @@ -18190,21 +18173,21 @@ "urls": "pdf:http://www.thelancet.com/article/S2589750021000170/pdf; doi:https://doi.org/10.1016/S2589-7500(21)00017-0; html:https://europepmc.org/articles/PMC7985613; pdf:https://europepmc.org/articles/PMC7985613?pdf=render" }, { - "id": "34399584", - "doi": "https://doi.org/10.1161/strokeaha.120.032619", - "title": "Risk Prediction Using Polygenic Risk Scores for Prevention of Stroke and Other Cardiovascular Diseases.", - "authorString": "Abraham G, Rutten-Jacobs L, Inouye M.", + "id": "37549998", + "doi": "https://doi.org/10.1136/bjsports-2022-106460", + "title": "Device-based measurement of physical activity in cardiovascular healthcare: possibilities and challenges.", + "authorString": "Chico TJ, Stamatakis E, Ciravegna F, Dunn J, Redwood S, Al-Lamee R, Sofat R, Gill J.", "authorAffiliations": "", - "journalTitle": "Stroke", - "pubYear": "2021", - "date": "2021-08-17", + "journalTitle": "British journal of sports medicine", + "pubYear": "2023", + "date": "2023-08-07", "isOpenAccess": "N", - "keywords": "Genetics; Myocardial infarction; Cardiovascular disease; Stroke; risk assessment", + "keywords": "Cardiovascular diseases; Health; Physical Activity", "nationalPriorities": "", "healthCategories": "", - "abstract": "Early prediction of risk of cardiovascular disease (CVD), including stroke, is a cornerstone of disease prevention. Clinical risk scores have been widely used for predicting CVD risk from known risk factors. Most CVDs have a substantial genetic component, which also has been confirmed for stroke in recent gene discovery efforts. However, the role of genetics in prediction of risk of CVD, including stroke, has been limited to testing for highly penetrant monogenic disorders. In contrast, the importance of polygenic variation, the aggregated effect of many common genetic variants across the genome with individually small effects, has become more apparent in the last 5 to 10 years, and powerful polygenic risk scores for CVD have been developed. Here we review the current state of the field of polygenic risk scores for CVD including stroke, and their potential to improve CVD risk prediction. We present findings and lessons from diseases such as coronary artery disease as these will likely be useful to inform future research in stroke polygenic risk prediction.", + "abstract": "", "laySummary": "", - "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.120.032619; doi:https://doi.org/10.1161/STROKEAHA.120.032619; html:https://europepmc.org/articles/PMC7611731; pdf:https://europepmc.org/articles/PMC7611731?pdf=render; doi:https://doi.org/10.1161/strokeaha.120.032619" + "urls": "doi:https://doi.org/10.1136/bjsports-2022-106460" }, { "id": "33249608", @@ -18223,6 +18206,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/opo.12765" }, + { + "id": "34399584", + "doi": "https://doi.org/10.1161/strokeaha.120.032619", + "title": "Risk Prediction Using Polygenic Risk Scores for Prevention of Stroke and Other Cardiovascular Diseases.", + "authorString": "Abraham G, Rutten-Jacobs L, Inouye M.", + "authorAffiliations": "", + "journalTitle": "Stroke", + "pubYear": "2021", + "date": "2021-08-17", + "isOpenAccess": "N", + "keywords": "Genetics; Myocardial infarction; Cardiovascular disease; Stroke; risk assessment", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Early prediction of risk of cardiovascular disease (CVD), including stroke, is a cornerstone of disease prevention. Clinical risk scores have been widely used for predicting CVD risk from known risk factors. Most CVDs have a substantial genetic component, which also has been confirmed for stroke in recent gene discovery efforts. However, the role of genetics in prediction of risk of CVD, including stroke, has been limited to testing for highly penetrant monogenic disorders. In contrast, the importance of polygenic variation, the aggregated effect of many common genetic variants across the genome with individually small effects, has become more apparent in the last 5 to 10 years, and powerful polygenic risk scores for CVD have been developed. Here we review the current state of the field of polygenic risk scores for CVD including stroke, and their potential to improve CVD risk prediction. We present findings and lessons from diseases such as coronary artery disease as these will likely be useful to inform future research in stroke polygenic risk prediction.", + "laySummary": "", + "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.120.032619; doi:https://doi.org/10.1161/STROKEAHA.120.032619; html:https://europepmc.org/articles/PMC7611731; pdf:https://europepmc.org/articles/PMC7611731?pdf=render; doi:https://doi.org/10.1161/strokeaha.120.032619" + }, { "id": "34169636", "doi": "https://doi.org/10.1002/pst.2148", @@ -18257,23 +18257,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1167/tvst.9.9.38; doi:https://doi.org/10.1167/tvst.9.9.38; html:https://europepmc.org/articles/PMC7453042; pdf:https://europepmc.org/articles/PMC7453042?pdf=render" }, - { - "id": "37140153", - "doi": "https://doi.org/10.1093/ehjci/jead093", - "title": "Determinants of post-operative left ventricular dysfunction in degenerative mitral regurgitation.", - "authorString": "Althunayyan AM, Alborikan S, Badiani S, Wong K, Uppal R, Patel N, Petersen SE, Lloyd G, Bhattacharyya S.", - "authorAffiliations": "", - "journalTitle": "European heart journal. Cardiovascular Imaging", - "pubYear": "2023", - "date": "2023-08-01", - "isOpenAccess": "N", - "keywords": "Surgery; Mitral regurgitation; Mitral Valve Prolapse; Global Longitudinal Strain; Lv Volumes", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

Chronic degenerative mitral regurgitation leads to volume overload causing left ventricular (LV) enlargement and eventually LV impairment. Current guidelines determining thresholds for intervention are based on LV diameters and ejection fraction (LVEF). There are sparse data examining the value of LV volumes and newer markers of LV performance on outcomes of surgery in mitral valve prolapse. The aim of this study is to identify the best marker of LV impairment after mitral valve surgery.

Methods and results

Prospective, observational study of patients with mitral valve prolapse undergoing mitral valve surgery. Pre-operative LV diameters, volumes, LVEF, global longitudinal strain (GLS), and myocardial work measured. Post-operative LV impairment defined as LVEF < 50% at 1 year post-surgery. Eighty-seven patients included. Thirteen percent developed post-operative LV impairment. Patients with post-operative LV dysfunction showed significantly larger indexed LV end-systolic diameters, indexed LV end-systolic volumes (LVESVi), lower LVEF, and more abnormal GLS than patients without post-operative LV dysfunction. In multivariate analysis, LVESVi [odds ratio 1.11 (95% CI 1.01-1.23), P = 0.039] and GLS [odds ratio 1.46 (95% CI 1.00-2.14), P = 0.054] were the only independent predictors of post-operative LV dysfunction. The optimal cut-off of 36.3 mL/m2 for LVESVi had a sensitivity of 82% and specificity of 78% for detection of post-operative LV impairment.

Conclusion

Post-operative LV impairment is common. Indexed LV volumes (36.3 mL/m2) provided the best marker of post-operative LV impairment.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead093/50200028/jead093.pdf; doi:https://doi.org/10.1093/ehjci/jead093" - }, { "id": "33704068", "doi": "https://doi.org/10.7554/elife.64827", @@ -18291,6 +18274,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.7554/elife.64827; doi:https://doi.org/10.7554/eLife.64827; html:https://europepmc.org/articles/PMC8064756; pdf:https://europepmc.org/articles/PMC8064756?pdf=render" }, + { + "id": "37140153", + "doi": "https://doi.org/10.1093/ehjci/jead093", + "title": "Determinants of post-operative left ventricular dysfunction in degenerative mitral regurgitation.", + "authorString": "Althunayyan AM, Alborikan S, Badiani S, Wong K, Uppal R, Patel N, Petersen SE, Lloyd G, Bhattacharyya S.", + "authorAffiliations": "", + "journalTitle": "European heart journal. Cardiovascular Imaging", + "pubYear": "2023", + "date": "2023-08-01", + "isOpenAccess": "N", + "keywords": "Surgery; Mitral regurgitation; Mitral Valve Prolapse; Global Longitudinal Strain; Lv Volumes", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

Chronic degenerative mitral regurgitation leads to volume overload causing left ventricular (LV) enlargement and eventually LV impairment. Current guidelines determining thresholds for intervention are based on LV diameters and ejection fraction (LVEF). There are sparse data examining the value of LV volumes and newer markers of LV performance on outcomes of surgery in mitral valve prolapse. The aim of this study is to identify the best marker of LV impairment after mitral valve surgery.

Methods and results

Prospective, observational study of patients with mitral valve prolapse undergoing mitral valve surgery. Pre-operative LV diameters, volumes, LVEF, global longitudinal strain (GLS), and myocardial work measured. Post-operative LV impairment defined as LVEF < 50% at 1 year post-surgery. Eighty-seven patients included. Thirteen percent developed post-operative LV impairment. Patients with post-operative LV dysfunction showed significantly larger indexed LV end-systolic diameters, indexed LV end-systolic volumes (LVESVi), lower LVEF, and more abnormal GLS than patients without post-operative LV dysfunction. In multivariate analysis, LVESVi [odds ratio 1.11 (95% CI 1.01-1.23), P = 0.039] and GLS [odds ratio 1.46 (95% CI 1.00-2.14), P = 0.054] were the only independent predictors of post-operative LV dysfunction. The optimal cut-off of 36.3 mL/m2 for LVESVi had a sensitivity of 82% and specificity of 78% for detection of post-operative LV impairment.

Conclusion

Post-operative LV impairment is common. Indexed LV volumes (36.3 mL/m2) provided the best marker of post-operative LV impairment.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead093/50200028/jead093.pdf; doi:https://doi.org/10.1093/ehjci/jead093" + }, { "id": "35667411", "doi": "https://doi.org/10.1016/j.jamda.2022.05.003", @@ -18835,23 +18835,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jtha.2023.07.008" }, - { - "id": "37440761", - "doi": "https://doi.org/10.1093/ehjci/jead166", - "title": "Neuroticism personality traits are linked to adverse cardiovascular phenotypes in the UK Biobank.", - "authorString": "Mahmood A, Simon J, Cooper J, Murphy T, McCracken C, Quiroz J, Laranjo L, Aung N, Lee AM, Khanji MY, Neubauer S, Raisi-Estabragh Z, Maurovich-Horvat P, Petersen SE.", - "authorAffiliations": "", - "journalTitle": "European heart journal. Cardiovascular Imaging", - "pubYear": "2023", - "date": "2023-10-01", - "isOpenAccess": "Y", - "keywords": "Cardiac function; Cardiac morphology; Mental health; Cardiovascular Magnetic Resonance; Neuroticism; Cardiovascular Remodelling", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

To evaluate the relationship between neuroticism personality traits and cardiovascular magnetic resonance (CMR) measures of cardiac morphology and function, considering potential differential associations in men and women.

Methods and results

The analysis includes 36 309 UK Biobank participants (average age = 63.9 \u00b1 7.7 years; 47.8% men) with CMR available and neuroticism score assessed by the 12-item Eysenck Personality Questionnaire-Revised Short Form. CMR scans were performed on 1.5 Tesla scanners (MAGNETOM Aera, Siemens Healthcare, Erlangen, Germany) according to pre-defined protocols and analysed using automated pipelines. We considered measures of left ventricular (LV) and right ventricular (RV) structure and function, and indicators of arterial compliance. Multivariable linear regression was used to estimate association of neuroticism score with individual CMR metrics, with adjustment for age, sex, obesity, deprivation, smoking, diabetes, hypertension, hypercholesterolaemia, alcohol use, exercise, and education. Higher neuroticism scores were associated with smaller LV and RV end-diastolic volumes, lower LV mass, greater concentricity (higher LV mass to volume ratio), and higher native T1. Greater neuroticism was also linked to poorer LV and RV function (lower stroke volumes) and greater arterial stiffness. In sex-stratified analyses, the relationships between neuroticism and LV stroke volume, concentricity, and arterial stiffness were attenuated in women. In men, association (with exception of native T1) remained robust.

Conclusion

Greater tendency towards neuroticism personality traits is linked to smaller, poorer functioning ventricles with lower LV mass, higher myocardial fibrosis, and higher arterial stiffness. These relationships are independent of traditional vascular risk factors and are more robust in men than women.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead166/50880139/jead166.pdf; doi:https://doi.org/10.1093/ehjci/jead166; html:https://europepmc.org/articles/PMC10610755; pdf:https://europepmc.org/articles/PMC10610755?pdf=render" - }, { "id": "34088700", "doi": "https://doi.org/10.2337/dc20-2518", @@ -18869,6 +18852,23 @@ "laySummary": "", "urls": "pdf:https://diabetesjournals.org/care/article-pdf/44/7/1699/632992/dc202518.pdf; doi:https://doi.org/10.2337/dc20-2518; html:https://europepmc.org/articles/PMC8323186; pdf:https://europepmc.org/articles/PMC8323186?pdf=render" }, + { + "id": "37440761", + "doi": "https://doi.org/10.1093/ehjci/jead166", + "title": "Neuroticism personality traits are linked to adverse cardiovascular phenotypes in the UK Biobank.", + "authorString": "Mahmood A, Simon J, Cooper J, Murphy T, McCracken C, Quiroz J, Laranjo L, Aung N, Lee AM, Khanji MY, Neubauer S, Raisi-Estabragh Z, Maurovich-Horvat P, Petersen SE.", + "authorAffiliations": "", + "journalTitle": "European heart journal. Cardiovascular Imaging", + "pubYear": "2023", + "date": "2023-10-01", + "isOpenAccess": "Y", + "keywords": "Cardiac function; Cardiac morphology; Mental health; Cardiovascular Magnetic Resonance; Neuroticism; Cardiovascular Remodelling", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

To evaluate the relationship between neuroticism personality traits and cardiovascular magnetic resonance (CMR) measures of cardiac morphology and function, considering potential differential associations in men and women.

Methods and results

The analysis includes 36 309 UK Biobank participants (average age = 63.9 \u00b1 7.7 years; 47.8% men) with CMR available and neuroticism score assessed by the 12-item Eysenck Personality Questionnaire-Revised Short Form. CMR scans were performed on 1.5 Tesla scanners (MAGNETOM Aera, Siemens Healthcare, Erlangen, Germany) according to pre-defined protocols and analysed using automated pipelines. We considered measures of left ventricular (LV) and right ventricular (RV) structure and function, and indicators of arterial compliance. Multivariable linear regression was used to estimate association of neuroticism score with individual CMR metrics, with adjustment for age, sex, obesity, deprivation, smoking, diabetes, hypertension, hypercholesterolaemia, alcohol use, exercise, and education. Higher neuroticism scores were associated with smaller LV and RV end-diastolic volumes, lower LV mass, greater concentricity (higher LV mass to volume ratio), and higher native T1. Greater neuroticism was also linked to poorer LV and RV function (lower stroke volumes) and greater arterial stiffness. In sex-stratified analyses, the relationships between neuroticism and LV stroke volume, concentricity, and arterial stiffness were attenuated in women. In men, association (with exception of native T1) remained robust.

Conclusion

Greater tendency towards neuroticism personality traits is linked to smaller, poorer functioning ventricles with lower LV mass, higher myocardial fibrosis, and higher arterial stiffness. These relationships are independent of traditional vascular risk factors and are more robust in men than women.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead166/50880139/jead166.pdf; doi:https://doi.org/10.1093/ehjci/jead166; html:https://europepmc.org/articles/PMC10610755; pdf:https://europepmc.org/articles/PMC10610755?pdf=render" + }, { "id": "37649471", "doi": "https://doi.org/10.23889/ijpds.v6i3.1705", @@ -19056,23 +19056,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1097/HTR.0000000000000741" }, - { - "id": "37456658", - "doi": "https://doi.org/10.12688/hrbopenres.13667.1", - "title": "Qualitative data sharing practices in clinical trials in the UK and Ireland: towards the production of good practice guidance.", - "authorString": "McCarthy M, Gillies K, Rousseau N, Wade J, Gamble C, Toomey E, Matvienko-Sikar K, Sydes M, Dowling M, Bryant V, Biesty L, Houghton C.", - "authorAffiliations": "", - "journalTitle": "HRB open research", - "pubYear": "2023", - "date": "2023-02-06", - "isOpenAccess": "Y", - "keywords": "data sharing; Qualitative; trials; Focus Groups", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Background: Data sharing enables researchers to conduct novel research with previously collected datasets, thus maximising scientific findings and cost effectiveness, and reducing research waste. The value of sharing, even de-identified, quantitative data from clinical trials is well recognised with a moderated access approach recommended. While substantial challenges to sharing quantitative data remain, there are additional challenges for sharing qualitative data in trials. Incorporating the necessary information about how qualitative data will be shared into already complex trial recruitment and consent processes proves challenging. The aim of this study was to explore whether and how trial teams share qualitative data collected as part of the design, conduct, analysis, or delivery of clinical trials. Methods:\u00a0Phase 1 involved semi-structured, in-depth qualitative interviews and focus groups with key trial stakeholder groups including trial managers and clinical trialists (n=3), qualitative researchers in trials (n=9), members of research funding bodies (n=2) and trial participants (n=1). Data were analysed using thematic analysis. In Phase 2, we conducted a content analysis of 16 participant information leaflets (PIL) and consent forms (CF) for trials that collected qualitative data. Results: Three key themes were identified from our Phase 1 findings: ' Understanding and experiences of the potential benefits of sharing qualitative data from trials', 'Concerns about qualitative data sharing', and ' Future guidance and funding'. In phase 2, the PILs and CFs received revealed that the benefits of data sharing for participants were only explained in two of the study documents. Conclusions: The value of sharing qualitative data was acknowledged, but there are many uncertainties as to how, when, and where to share this data. In addition, there were ethical concerns in relation to the consent process required for qualitative data sharing in trials. This study provides insight into the existing practice of qualitative data sharing in trials.", - "laySummary": "", - "urls": "pdf:https://hrbopenresearch.org/articles/6-10/pdf; doi:https://doi.org/10.12688/hrbopenres.13667.1; html:https://europepmc.org/articles/PMC10345597; pdf:https://europepmc.org/articles/PMC10345597?pdf=render" - }, { "id": "34847088", "doi": "https://doi.org/10.1097/ede.0000000000001429", @@ -19090,6 +19073,23 @@ "laySummary": "", "urls": "html:https://journals.lww.com/epidem/Fulltext/2022/01000/The_Authors_Respond.22.aspx; doi:https://doi.org/10.1097/EDE.0000000000001429" }, + { + "id": "37456658", + "doi": "https://doi.org/10.12688/hrbopenres.13667.1", + "title": "Qualitative data sharing practices in clinical trials in the UK and Ireland: towards the production of good practice guidance.", + "authorString": "McCarthy M, Gillies K, Rousseau N, Wade J, Gamble C, Toomey E, Matvienko-Sikar K, Sydes M, Dowling M, Bryant V, Biesty L, Houghton C.", + "authorAffiliations": "", + "journalTitle": "HRB open research", + "pubYear": "2023", + "date": "2023-02-06", + "isOpenAccess": "Y", + "keywords": "data sharing; Qualitative; trials; Focus Groups", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Background: Data sharing enables researchers to conduct novel research with previously collected datasets, thus maximising scientific findings and cost effectiveness, and reducing research waste. The value of sharing, even de-identified, quantitative data from clinical trials is well recognised with a moderated access approach recommended. While substantial challenges to sharing quantitative data remain, there are additional challenges for sharing qualitative data in trials. Incorporating the necessary information about how qualitative data will be shared into already complex trial recruitment and consent processes proves challenging. The aim of this study was to explore whether and how trial teams share qualitative data collected as part of the design, conduct, analysis, or delivery of clinical trials. Methods:\u00a0Phase 1 involved semi-structured, in-depth qualitative interviews and focus groups with key trial stakeholder groups including trial managers and clinical trialists (n=3), qualitative researchers in trials (n=9), members of research funding bodies (n=2) and trial participants (n=1). Data were analysed using thematic analysis. In Phase 2, we conducted a content analysis of 16 participant information leaflets (PIL) and consent forms (CF) for trials that collected qualitative data. Results: Three key themes were identified from our Phase 1 findings: ' Understanding and experiences of the potential benefits of sharing qualitative data from trials', 'Concerns about qualitative data sharing', and ' Future guidance and funding'. In phase 2, the PILs and CFs received revealed that the benefits of data sharing for participants were only explained in two of the study documents. Conclusions: The value of sharing qualitative data was acknowledged, but there are many uncertainties as to how, when, and where to share this data. In addition, there were ethical concerns in relation to the consent process required for qualitative data sharing in trials. This study provides insight into the existing practice of qualitative data sharing in trials.", + "laySummary": "", + "urls": "pdf:https://hrbopenresearch.org/articles/6-10/pdf; doi:https://doi.org/10.12688/hrbopenres.13667.1; html:https://europepmc.org/articles/PMC10345597; pdf:https://europepmc.org/articles/PMC10345597?pdf=render" + }, { "id": "37293269", "doi": "https://doi.org/10.1140/epjds/s13688-023-00394-6", @@ -19124,23 +19124,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3389/fcvm.2023.1148931; html:https://europepmc.org/articles/PMC10619754; pdf:https://europepmc.org/articles/PMC10619754?pdf=render" }, - { - "id": "34798287", - "doi": "https://doi.org/10.1016/j.jclinepi.2021.11.023", - "title": "Missing data is poorly handled and reported in prediction model studies using machine learning: a literature review.", - "authorString": "Nijman S, Leeuwenberg AM, Beekers I, Verkouter I, Jacobs J, Bots ML, Asselbergs FW, Moons K, Debray T.", - "authorAffiliations": "", - "journalTitle": "Journal of clinical epidemiology", - "pubYear": "2022", - "date": "2021-11-16", - "isOpenAccess": "N", - "keywords": "Prediction; Literature review; Reporting; Missing Data; Machine Learning", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

Missing data is a common problem during the development, evaluation, and implementation of prediction models. Although machine learning (ML) methods are often said to be capable of circumventing missing data, it is unclear how these methods are used in medical research. We aim to find out if and how well prediction model studies using machine learning report on their handling of missing data.

Study design and setting

We systematically searched the literature on published papers between 2018 and 2019 about primary studies developing and/or validating clinical prediction models using any supervised ML methodology across medical fields. From the retrieved studies information about the amount and nature (e.g. missing completely at random, potential reasons for missingness) of missing data and the way they were handled were extracted.

Results

We identified 152 machine learning-based clinical prediction model studies. A substantial amount of these 152 papers did not report anything on missing data (n\u00a0=\u00a056/152). A majority (n\u00a0=\u00a096/152) reported details on the handling of missing data (e.g., methods used), though many of these (n\u00a0=\u00a046/96) did not report the amount of the missingness in the data. In these 96 papers the authors only sometimes reported possible reasons for missingness (n\u00a0=\u00a07/96) and information about missing data mechanisms (n\u00a0=\u00a08/96). The most common approach for handling missing data was deletion (n\u00a0=\u00a065/96), mostly via complete-case analysis (CCA) (n\u00a0=\u00a043/96). Very few studies used multiple imputation (n\u00a0=\u00a08/96) or built-in mechanisms such as surrogate splits (n\u00a0=\u00a07/96) that directly address missing data during the development, validation, or implementation of the prediction model.

Conclusion

Though missing values are highly common in any type of medical research and certainly in the research based on routine healthcare data, a majority of the prediction model studies using machine learning does not report sufficient information on the presence and handling of missing data. Strategies in which patient data are simply omitted are unfortunately the most often used methods, even though it is generally advised against and well known that it likely causes bias and loss of analytical power in prediction model development and in the predictive accuracy estimates. Prediction model researchers should be much more aware of alternative methodologies to address missing data.", - "laySummary": "", - "urls": "pdf:http://www.jclinepi.com/article/S0895435621003759/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.11.023" - }, { "id": "32728709", "doi": "https://doi.org/10.1093/pubmed/fdaa115", @@ -19158,6 +19141,23 @@ "laySummary": "", "urls": "pdf:https://discovery.ucl.ac.uk/10110375/1/Syed%20and%20Gilbert%20%282020%29.%20Are%20children%20who%20are%20home%20from%20school%20at%20an%20increased%20risk%20of%20child%20maltreatment.pdf; doi:https://doi.org/10.1093/pubmed/fdaa115" }, + { + "id": "34798287", + "doi": "https://doi.org/10.1016/j.jclinepi.2021.11.023", + "title": "Missing data is poorly handled and reported in prediction model studies using machine learning: a literature review.", + "authorString": "Nijman S, Leeuwenberg AM, Beekers I, Verkouter I, Jacobs J, Bots ML, Asselbergs FW, Moons K, Debray T.", + "authorAffiliations": "", + "journalTitle": "Journal of clinical epidemiology", + "pubYear": "2022", + "date": "2021-11-16", + "isOpenAccess": "N", + "keywords": "Prediction; Literature review; Reporting; Missing Data; Machine Learning", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

Missing data is a common problem during the development, evaluation, and implementation of prediction models. Although machine learning (ML) methods are often said to be capable of circumventing missing data, it is unclear how these methods are used in medical research. We aim to find out if and how well prediction model studies using machine learning report on their handling of missing data.

Study design and setting

We systematically searched the literature on published papers between 2018 and 2019 about primary studies developing and/or validating clinical prediction models using any supervised ML methodology across medical fields. From the retrieved studies information about the amount and nature (e.g. missing completely at random, potential reasons for missingness) of missing data and the way they were handled were extracted.

Results

We identified 152 machine learning-based clinical prediction model studies. A substantial amount of these 152 papers did not report anything on missing data (n\u00a0=\u00a056/152). A majority (n\u00a0=\u00a096/152) reported details on the handling of missing data (e.g., methods used), though many of these (n\u00a0=\u00a046/96) did not report the amount of the missingness in the data. In these 96 papers the authors only sometimes reported possible reasons for missingness (n\u00a0=\u00a07/96) and information about missing data mechanisms (n\u00a0=\u00a08/96). The most common approach for handling missing data was deletion (n\u00a0=\u00a065/96), mostly via complete-case analysis (CCA) (n\u00a0=\u00a043/96). Very few studies used multiple imputation (n\u00a0=\u00a08/96) or built-in mechanisms such as surrogate splits (n\u00a0=\u00a07/96) that directly address missing data during the development, validation, or implementation of the prediction model.

Conclusion

Though missing values are highly common in any type of medical research and certainly in the research based on routine healthcare data, a majority of the prediction model studies using machine learning does not report sufficient information on the presence and handling of missing data. Strategies in which patient data are simply omitted are unfortunately the most often used methods, even though it is generally advised against and well known that it likely causes bias and loss of analytical power in prediction model development and in the predictive accuracy estimates. Prediction model researchers should be much more aware of alternative methodologies to address missing data.", + "laySummary": "", + "urls": "pdf:http://www.jclinepi.com/article/S0895435621003759/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.11.023" + }, { "id": "36936265", "doi": "https://doi.org/10.1136/bmjmed-2022-000276", @@ -19363,21 +19363,21 @@ "urls": "doi:https://doi.org/10.1684/ejd.2021.4108" }, { - "id": "37218687", - "doi": "https://doi.org/10.1093/ehjqcco/qcad029", - "title": "Sex-based differences in risk factors for incident myocardial infarction and stroke in the UK Biobank.", - "authorString": "Remfry E, Ardissino M, McCracken C, Szabo L, Neubauer S, Harvey NC, Mamas MA, Robson J, Petersen SE, Raisi-Estabragh Z.", + "id": "34939031", + "doi": "https://doi.org/10.1093/braincomms/fcab241", + "title": "Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia.", + "authorString": "Vuksanovi\u0107 V, Staff RT, Morson S, Ahearn T, Bracoud L, Murray AD, Bentham P, Kipps CM, Harrington CR, Wischik CM.", "authorAffiliations": "", - "journalTitle": "European heart journal. Quality of care & clinical outcomes", - "pubYear": "2024", - "date": "2024-03-01", + "journalTitle": "Brain communications", + "pubYear": "2021", + "date": "2021-10-21", "isOpenAccess": "Y", - "keywords": "Myocardial infarction; Stroke; Sex differences; risk factors", + "keywords": "Neurodegeneration; Brain Networks; Behavioural Variant Frontotemporal Dementia; Rich Club; Anatomical Subtypes", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Aim

This study examined sex-based differences in associations of vascular risk factors with incident cardiovascular events in the UK Biobank.

Methods

Baseline participant demographic, clinical, laboratory, anthropometric, and imaging characteristics were collected. Multivariable Cox regression was used to estimate independent associations of vascular risk factors with incident myocardial infarction (MI) and ischaemic stroke for men and women. Women-to-men ratios of hazard ratios (RHRs), and related 95% confidence intervals, represent the relative effect-size magnitude by sex.

Results

Among the 363\u00a0313 participants (53.5% women), 8470 experienced MI (29.9% women) and 7705 experienced stroke (40.1% women) over 12.66 [11.93, 13.38] years of prospective follow-up. Men had greater risk factor burden and higher arterial stiffness index at baseline. Women had greater age-related decline in aortic distensibility. Older age [RHR: 1.02 (1.01-1.03)], greater deprivation [RHR: 1.02 (1.00-1.03)], hypertension [RHR: 1.14 (1.02-1.27)], and current smoking [RHR: 1.45 (1.27-1.66)] were associated with a greater excess risk of MI in women than men. Low-density lipoprotein cholesterol was associated with excess MI risk in men [RHR: 0.90 (0.84-0.95)] and apolipoprotein A (ApoA) was less protective for MI in women [RHR: 1.65 (1.01-2.71)]. Older age was associated with excess risk of stroke [RHR: 1.01 (1.00-1.02)] and ApoA was less protective for stroke in women [RHR: 2.55 (1.58-4.14)].

Conclusion

Older age, hypertension, and smoking appeared stronger drivers of cardiovascular disease in women, whereas lipid metrics appeared stronger risk determinants for men. These findings highlight the importance of sex-specific preventive strategies and suggest priority targets for intervention in men and women.", + "abstract": "The behavioural variant of frontotemporal dementia is a clinical syndrome characterized by changes in behaviour, cognition and functional ability. Although atrophy in frontal and temporal regions would appear to be a defining feature, neuroimaging studies have identified volumetric differences distributed across large parts of the cortex, giving rise to a classification into distinct neuroanatomical subtypes. Here, we extended these neuroimaging studies to examine how distributed patterns of cortical atrophy map onto brain network hubs. We used baseline structural magnetic resonance imaging data collected from 213 behavioural variant of frontotemporal dementia patients meeting consensus diagnostic criteria and having definite evidence of frontal and/or temporal lobe atrophy from a global clinical trial conducted in 70 sites in Canada, United States of America, Australia, Asia and Europe. These were compared with data from 244 healthy elderly subjects from a well-characterized cohort study. We have used statistical methods of hierarchical agglomerative clustering of 68 regional cortical and subcortical volumes (34 in each hemisphere) to determine the reproducibility of previously described neuroanatomical subtypes in a global study. We have also attempted to link the structural findings to clinical features defined systematically using well-validated clinical scales (Addenbrooke's Cognitive Examination Revised, the Mini-Mental Status Examination, the Frontotemporal Dementia Rating Scale and the Functional Assessment Questionnaire) and subscales derived from them. Whilst we can confirm that the subtypes are robust, they have limited value in explaining the clinical heterogeneity of the syndrome. We have found that a common pattern of degeneration affecting a small number of subcortical, limbic and frontal nodes within highly connected networks (most previously identified as rich club members or functional binding nodes) is shared by all the anatomical subtypes. Degeneration in these core regions is correlated with cognitive and functional impairment, but less so with behavioural impairment. These findings suggest that degeneration in highly connected basal, limbic and frontal networks is a core feature of the behavioural variant of frontotemporal dementia phenotype irrespective of neuroanatomical and clinical heterogeneity, and may underly the impairment of integration in cognition, function and behaviour responsible for the loss of insight that characterizes the syndrome.", "laySummary": "", - "urls": "pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcad029/50422842/qcad029.pdf; doi:https://doi.org/10.1093/ehjqcco/qcad029; html:https://europepmc.org/articles/PMC10904726; pdf:https://europepmc.org/articles/PMC10904726?pdf=render" + "urls": "pdf:https://academic.oup.com/braincomms/article-pdf/3/4/fcab241/41829863/fcab241.pdf; doi:https://doi.org/10.1093/braincomms/fcab241; html:https://europepmc.org/articles/PMC8688778; pdf:https://europepmc.org/articles/PMC8688778?pdf=render" }, { "id": "38784722", @@ -19397,38 +19397,21 @@ "urls": "doi:https://doi.org/10.1093/jbmrpl/ziae058; html:https://europepmc.org/articles/PMC11114472; pdf:https://europepmc.org/articles/PMC11114472?pdf=render" }, { - "id": "34939031", - "doi": "https://doi.org/10.1093/braincomms/fcab241", - "title": "Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia.", - "authorString": "Vuksanovi\u0107 V, Staff RT, Morson S, Ahearn T, Bracoud L, Murray AD, Bentham P, Kipps CM, Harrington CR, Wischik CM.", - "authorAffiliations": "", - "journalTitle": "Brain communications", - "pubYear": "2021", - "date": "2021-10-21", - "isOpenAccess": "Y", - "keywords": "Neurodegeneration; Brain Networks; Behavioural Variant Frontotemporal Dementia; Rich Club; Anatomical Subtypes", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The behavioural variant of frontotemporal dementia is a clinical syndrome characterized by changes in behaviour, cognition and functional ability. Although atrophy in frontal and temporal regions would appear to be a defining feature, neuroimaging studies have identified volumetric differences distributed across large parts of the cortex, giving rise to a classification into distinct neuroanatomical subtypes. Here, we extended these neuroimaging studies to examine how distributed patterns of cortical atrophy map onto brain network hubs. We used baseline structural magnetic resonance imaging data collected from 213 behavioural variant of frontotemporal dementia patients meeting consensus diagnostic criteria and having definite evidence of frontal and/or temporal lobe atrophy from a global clinical trial conducted in 70 sites in Canada, United States of America, Australia, Asia and Europe. These were compared with data from 244 healthy elderly subjects from a well-characterized cohort study. We have used statistical methods of hierarchical agglomerative clustering of 68 regional cortical and subcortical volumes (34 in each hemisphere) to determine the reproducibility of previously described neuroanatomical subtypes in a global study. We have also attempted to link the structural findings to clinical features defined systematically using well-validated clinical scales (Addenbrooke's Cognitive Examination Revised, the Mini-Mental Status Examination, the Frontotemporal Dementia Rating Scale and the Functional Assessment Questionnaire) and subscales derived from them. Whilst we can confirm that the subtypes are robust, they have limited value in explaining the clinical heterogeneity of the syndrome. We have found that a common pattern of degeneration affecting a small number of subcortical, limbic and frontal nodes within highly connected networks (most previously identified as rich club members or functional binding nodes) is shared by all the anatomical subtypes. Degeneration in these core regions is correlated with cognitive and functional impairment, but less so with behavioural impairment. These findings suggest that degeneration in highly connected basal, limbic and frontal networks is a core feature of the behavioural variant of frontotemporal dementia phenotype irrespective of neuroanatomical and clinical heterogeneity, and may underly the impairment of integration in cognition, function and behaviour responsible for the loss of insight that characterizes the syndrome.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/braincomms/article-pdf/3/4/fcab241/41829863/fcab241.pdf; doi:https://doi.org/10.1093/braincomms/fcab241; html:https://europepmc.org/articles/PMC8688778; pdf:https://europepmc.org/articles/PMC8688778?pdf=render" - }, - { - "id": "37563310", - "doi": "https://doi.org/10.1038/s41590-023-01588-w", - "title": "Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets.", - "authorString": "Zhao JH, Stacey D, Eriksson N, Macdonald-Dunlop E, Hedman \u00c5K, Kalnapenkis A, Enroth S, Cozzetto D, Digby-Bell J, Marten J, Folkersen L, Herder C, Jonsson L, Bergen SE, Gieger C, Needham EJ, Surendran P, Estonian Biobank Research Team, Paul DS, Polasek O, Thorand B, Grallert H, Roden M, V\u00f5sa U, Esko T, Hayward C, Johansson \u00c5, Gyllensten U, Powell N, Hansson O, Mattsson-Carlgren N, Joshi PK, Danesh J, Padyukov L, Klareskog L, Land\u00e9n M, Wilson JF, Siegbahn A, Wallentin L, M\u00e4larstig A, Butterworth AS, Peters JE.", + "id": "37218687", + "doi": "https://doi.org/10.1093/ehjqcco/qcad029", + "title": "Sex-based differences in risk factors for incident myocardial infarction and stroke in the UK Biobank.", + "authorString": "Remfry E, Ardissino M, McCracken C, Szabo L, Neubauer S, Harvey NC, Mamas MA, Robson J, Petersen SE, Raisi-Estabragh Z.", "authorAffiliations": "", - "journalTitle": "Nature immunology", - "pubYear": "2023", - "date": "2023-08-10", + "journalTitle": "European heart journal. Quality of care & clinical outcomes", + "pubYear": "2024", + "date": "2024-03-01", "isOpenAccess": "Y", - "keywords": "", + "keywords": "Myocardial infarction; Stroke; Sex differences; risk factors", "nationalPriorities": "", "healthCategories": "", - "abstract": "Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted a genome-wide protein quantitative trait locus (pQTL) study of 91 plasma proteins measured using the Olink Target platform in 14,824 participants. We identified 180 pQTLs (59 cis, 121 trans). Integration of pQTL data with eQTL and disease genome-wide association studies provided insight into pathogenesis, implicating lymphotoxin-\u03b1 in multiple sclerosis. Using Mendelian randomization (MR) to assess causality in disease etiology, we identified both shared and distinct effects of specific proteins across immune-mediated diseases, including directionally discordant effects of CD40 on risk of rheumatoid arthritis versus multiple sclerosis and inflammatory bowel disease. MR implicated CXCL5 in the etiology of ulcerative colitis (UC) and we show elevated gut CXCL5 transcript expression in patients with UC. These results identify targets of existing drugs and provide a powerful resource to facilitate future drug target prioritization.", + "abstract": "

Aim

This study examined sex-based differences in associations of vascular risk factors with incident cardiovascular events in the UK Biobank.

Methods

Baseline participant demographic, clinical, laboratory, anthropometric, and imaging characteristics were collected. Multivariable Cox regression was used to estimate independent associations of vascular risk factors with incident myocardial infarction (MI) and ischaemic stroke for men and women. Women-to-men ratios of hazard ratios (RHRs), and related 95% confidence intervals, represent the relative effect-size magnitude by sex.

Results

Among the 363\u00a0313 participants (53.5% women), 8470 experienced MI (29.9% women) and 7705 experienced stroke (40.1% women) over 12.66 [11.93, 13.38] years of prospective follow-up. Men had greater risk factor burden and higher arterial stiffness index at baseline. Women had greater age-related decline in aortic distensibility. Older age [RHR: 1.02 (1.01-1.03)], greater deprivation [RHR: 1.02 (1.00-1.03)], hypertension [RHR: 1.14 (1.02-1.27)], and current smoking [RHR: 1.45 (1.27-1.66)] were associated with a greater excess risk of MI in women than men. Low-density lipoprotein cholesterol was associated with excess MI risk in men [RHR: 0.90 (0.84-0.95)] and apolipoprotein A (ApoA) was less protective for MI in women [RHR: 1.65 (1.01-2.71)]. Older age was associated with excess risk of stroke [RHR: 1.01 (1.00-1.02)] and ApoA was less protective for stroke in women [RHR: 2.55 (1.58-4.14)].

Conclusion

Older age, hypertension, and smoking appeared stronger drivers of cardiovascular disease in women, whereas lipid metrics appeared stronger risk determinants for men. These findings highlight the importance of sex-specific preventive strategies and suggest priority targets for intervention in men and women.", "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41590-023-01588-w.pdf; doi:https://doi.org/10.1038/s41590-023-01588-w; html:https://europepmc.org/articles/PMC10457199; pdf:https://europepmc.org/articles/PMC10457199?pdf=render" + "urls": "pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcad029/50422842/qcad029.pdf; doi:https://doi.org/10.1093/ehjqcco/qcad029; html:https://europepmc.org/articles/PMC10904726; pdf:https://europepmc.org/articles/PMC10904726?pdf=render" }, { "id": "31748543", @@ -19447,6 +19430,23 @@ "laySummary": "This study aimed to identify parts of the genome that cause chronic pain (self-reported as lasting 3+ months), or major depressive disorder (MDD) and to investigate if these two conditions share common genetic causes. They identified 11 different parts of the genome where a specific change (SNP) was linked to chronic pain (6 parts of the genome), MDD (9 parts), or symptoms shared by both conditions (4 parts). The results also suggest that one of parts of the genome that causes chronic pain may influence the development of MDD (but not vice versa), including through lifestyle factors.", "urls": "pdf:https://www.nature.com/articles/s41398-019-0613-4.pdf; doi:https://doi.org/10.1038/s41398-019-0613-4; html:https://europepmc.org/articles/PMC6868167; pdf:https://europepmc.org/articles/PMC6868167?pdf=render" }, + { + "id": "37563310", + "doi": "https://doi.org/10.1038/s41590-023-01588-w", + "title": "Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets.", + "authorString": "Zhao JH, Stacey D, Eriksson N, Macdonald-Dunlop E, Hedman \u00c5K, Kalnapenkis A, Enroth S, Cozzetto D, Digby-Bell J, Marten J, Folkersen L, Herder C, Jonsson L, Bergen SE, Gieger C, Needham EJ, Surendran P, Estonian Biobank Research Team, Paul DS, Polasek O, Thorand B, Grallert H, Roden M, V\u00f5sa U, Esko T, Hayward C, Johansson \u00c5, Gyllensten U, Powell N, Hansson O, Mattsson-Carlgren N, Joshi PK, Danesh J, Padyukov L, Klareskog L, Land\u00e9n M, Wilson JF, Siegbahn A, Wallentin L, M\u00e4larstig A, Butterworth AS, Peters JE.", + "authorAffiliations": "", + "journalTitle": "Nature immunology", + "pubYear": "2023", + "date": "2023-08-10", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted a genome-wide protein quantitative trait locus (pQTL) study of 91 plasma proteins measured using the Olink Target platform in 14,824 participants. We identified 180 pQTLs (59 cis, 121 trans). Integration of pQTL data with eQTL and disease genome-wide association studies provided insight into pathogenesis, implicating lymphotoxin-\u03b1 in multiple sclerosis. Using Mendelian randomization (MR) to assess causality in disease etiology, we identified both shared and distinct effects of specific proteins across immune-mediated diseases, including directionally discordant effects of CD40 on risk of rheumatoid arthritis versus multiple sclerosis and inflammatory bowel disease. MR implicated CXCL5 in the etiology of ulcerative colitis (UC) and we show elevated gut CXCL5 transcript expression in patients with UC. These results identify targets of existing drugs and provide a powerful resource to facilitate future drug target prioritization.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41590-023-01588-w.pdf; doi:https://doi.org/10.1038/s41590-023-01588-w; html:https://europepmc.org/articles/PMC10457199; pdf:https://europepmc.org/articles/PMC10457199?pdf=render" + }, { "id": "37986130", "doi": "https://doi.org/10.1186/s41512-023-00159-9", @@ -19549,23 +19549,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1210/clinem/dgad276; doi:https://doi.org/10.1210/clinem/dgad276; html:https://europepmc.org/articles/PMC10584009" }, - { - "id": "37729117", - "doi": "https://doi.org/10.1371/journal.pdig.0000309", - "title": "Training and testing of a gradient boosted machine learning model to predict adverse outcome in patients presenting to emergency departments with suspected covid-19 infection in a middle-income setting.", - "authorString": "Fuller GW, Hasan M, Hodkinson P, McAlpine D, Goodacre S, Bath PA, Sbaffi L, Omer Y, Wallis L, Marincowitz C.", - "authorAffiliations": "", - "journalTitle": "PLOS digital health", - "pubYear": "2023", - "date": "2023-09-20", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "COVID-19 infection rates remain high in South Africa. Clinical prediction models may be helpful for rapid triage, and supporting clinical decision making, for patients with suspected COVID-19 infection. The Western Cape, South Africa, has integrated electronic health care data facilitating large-scale linked routine datasets. The aim of this study was to develop a machine learning model to predict adverse outcome in patients presenting with suspected COVID-19 suitable for use in a middle-income setting. A retrospective cohort study was conducted using linked, routine data, from patients presenting with suspected COVID-19 infection to public-sector emergency departments (EDs) in the Western Cape, South Africa between 27th August 2020 and 31st October 2021. The primary outcome was death or critical care admission at 30 days. An XGBoost machine learning model was trained and internally tested using split-sample validation. External validation was performed in 3 test cohorts: Western Cape patients presenting during the Omicron COVID-19 wave, a UK cohort during the ancestral COVID-19 wave, and a Sudanese cohort during ancestral and Eta waves. A total of 282,051 cases were included in a complete case training dataset. The prevalence of 30-day adverse outcome was 4.0%. The most important features for predicting adverse outcome were the requirement for supplemental oxygen, peripheral oxygen saturations, level of consciousness and age. Internal validation using split-sample test data revealed excellent discrimination (C-statistic 0.91, 95% CI 0.90 to 0.91) and calibration (CITL of 1.05). The model achieved C-statistics of 0.84 (95% CI 0.84 to 0.85), 0.72 (95% CI 0.71 to 0.73), and 0.62, (95% CI 0.59 to 0.65) in the Omicron, UK, and Sudanese test cohorts. Results were materially unchanged in sensitivity analyses examining missing data. An XGBoost machine learning model achieved good discrimination and calibration in prediction of adverse outcome in patients presenting with suspected COVID19 to Western Cape EDs. Performance was reduced in temporal and geographical external validation.", - "laySummary": "", - "urls": "pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000309&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000309; html:https://europepmc.org/articles/PMC10511129; pdf:https://europepmc.org/articles/PMC10511129?pdf=render" - }, { "id": "35151869", "doi": "https://doi.org/10.1016/j.jbi.2022.104010", @@ -19583,6 +19566,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jbi.2022.104010; doi:https://doi.org/10.1016/j.jbi.2022.104010; html:https://europepmc.org/articles/PMC8894882" }, + { + "id": "37729117", + "doi": "https://doi.org/10.1371/journal.pdig.0000309", + "title": "Training and testing of a gradient boosted machine learning model to predict adverse outcome in patients presenting to emergency departments with suspected covid-19 infection in a middle-income setting.", + "authorString": "Fuller GW, Hasan M, Hodkinson P, McAlpine D, Goodacre S, Bath PA, Sbaffi L, Omer Y, Wallis L, Marincowitz C.", + "authorAffiliations": "", + "journalTitle": "PLOS digital health", + "pubYear": "2023", + "date": "2023-09-20", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "COVID-19 infection rates remain high in South Africa. Clinical prediction models may be helpful for rapid triage, and supporting clinical decision making, for patients with suspected COVID-19 infection. The Western Cape, South Africa, has integrated electronic health care data facilitating large-scale linked routine datasets. The aim of this study was to develop a machine learning model to predict adverse outcome in patients presenting with suspected COVID-19 suitable for use in a middle-income setting. A retrospective cohort study was conducted using linked, routine data, from patients presenting with suspected COVID-19 infection to public-sector emergency departments (EDs) in the Western Cape, South Africa between 27th August 2020 and 31st October 2021. The primary outcome was death or critical care admission at 30 days. An XGBoost machine learning model was trained and internally tested using split-sample validation. External validation was performed in 3 test cohorts: Western Cape patients presenting during the Omicron COVID-19 wave, a UK cohort during the ancestral COVID-19 wave, and a Sudanese cohort during ancestral and Eta waves. A total of 282,051 cases were included in a complete case training dataset. The prevalence of 30-day adverse outcome was 4.0%. The most important features for predicting adverse outcome were the requirement for supplemental oxygen, peripheral oxygen saturations, level of consciousness and age. Internal validation using split-sample test data revealed excellent discrimination (C-statistic 0.91, 95% CI 0.90 to 0.91) and calibration (CITL of 1.05). The model achieved C-statistics of 0.84 (95% CI 0.84 to 0.85), 0.72 (95% CI 0.71 to 0.73), and 0.62, (95% CI 0.59 to 0.65) in the Omicron, UK, and Sudanese test cohorts. Results were materially unchanged in sensitivity analyses examining missing data. An XGBoost machine learning model achieved good discrimination and calibration in prediction of adverse outcome in patients presenting with suspected COVID19 to Western Cape EDs. Performance was reduced in temporal and geographical external validation.", + "laySummary": "", + "urls": "pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000309&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000309; html:https://europepmc.org/articles/PMC10511129; pdf:https://europepmc.org/articles/PMC10511129?pdf=render" + }, { "id": "36644660", "doi": "https://doi.org/10.1177/20552076221128677", @@ -19651,23 +19651,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41598-018-32876-3.pdf; doi:https://doi.org/10.1038/s41598-018-32876-3; html:https://europepmc.org/articles/PMC6168481; pdf:https://europepmc.org/articles/PMC6168481?pdf=render" }, - { - "id": "34506014", - "doi": "https://doi.org/10.1007/s11605-020-04612-8", - "title": "The Impact of a Centralised Pancreatic Cancer Service: a Case Study of Wales, UK.", - "authorString": "Mowbray NG, Griffiths R, Akbari A, Hutchings H, Jenkins G, Al-Sarireh B.", - "authorAffiliations": "", - "journalTitle": "Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract", - "pubYear": "2022", - "date": "2021-09-10", - "isOpenAccess": "N", - "keywords": "Pancreatic cancer; Pancreatic Surgery; Centralisation", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

The centralisation of pancreatic cancer (PC) services still varies worldwide. This study aimed to assess the impact that a centralisation has had on patients in South Wales, UK.

Methods

A retrospective cohort analysis of patients in South Wales, UK, with PC prior to (2004-2009), and after (2010-2014) the formation of a specialist centre. Patients were identified using record linkage of electronic health records.

Results

The overall survival (OS) of all 3413 patients with PC increased from a median (IQR) 10\u00a0weeks (3-31) to 11\u00a0weeks (4-35), p\u2009=\u20090.038, after centralisation. The OS of patients undergoing surgical resection or chemotherapy alone did not improve (93\u00a0weeks (39-203) vs. 90\u00a0weeks (50-95), p\u2009=\u20090.764 and 33\u00a0weeks (20-57) vs. 33\u00a0weeks (19-58), p\u2009=\u20090.793). Surgical resection and chemotherapy rates increased (6.1% vs. 9.2%, p\u2009<\u20090.001 and 19.7% vs. 27.0%, p\u2009<\u20090.001). The 30-day mortality rate trended downwards (7.2% vs. 3.6%, p\u2009=\u20090.186). The percentage of patients who received no treatment reduced (75.2% vs. 69.6%, p\u2009<\u20090.001).

Conclusion

The centralisation of PC services in South Wales is associated with a small increase in OS and a larger increase in PC treatment utilisation. It is concerning that many patients still fail to receive any treatments.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1007/s11605-020-04612-8" - }, { "id": "32575372", "doi": "https://doi.org/10.3390/genes11060668", @@ -19685,6 +19668,23 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/2073-4425/11/6/668/pdf?version=1592549363; doi:https://doi.org/10.3390/genes11060668; html:https://europepmc.org/articles/PMC7349022; pdf:https://europepmc.org/articles/PMC7349022?pdf=render" }, + { + "id": "34506014", + "doi": "https://doi.org/10.1007/s11605-020-04612-8", + "title": "The Impact of a Centralised Pancreatic Cancer Service: a Case Study of Wales, UK.", + "authorString": "Mowbray NG, Griffiths R, Akbari A, Hutchings H, Jenkins G, Al-Sarireh B.", + "authorAffiliations": "", + "journalTitle": "Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract", + "pubYear": "2022", + "date": "2021-09-10", + "isOpenAccess": "N", + "keywords": "Pancreatic cancer; Pancreatic Surgery; Centralisation", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

The centralisation of pancreatic cancer (PC) services still varies worldwide. This study aimed to assess the impact that a centralisation has had on patients in South Wales, UK.

Methods

A retrospective cohort analysis of patients in South Wales, UK, with PC prior to (2004-2009), and after (2010-2014) the formation of a specialist centre. Patients were identified using record linkage of electronic health records.

Results

The overall survival (OS) of all 3413 patients with PC increased from a median (IQR) 10\u00a0weeks (3-31) to 11\u00a0weeks (4-35), p\u2009=\u20090.038, after centralisation. The OS of patients undergoing surgical resection or chemotherapy alone did not improve (93\u00a0weeks (39-203) vs. 90\u00a0weeks (50-95), p\u2009=\u20090.764 and 33\u00a0weeks (20-57) vs. 33\u00a0weeks (19-58), p\u2009=\u20090.793). Surgical resection and chemotherapy rates increased (6.1% vs. 9.2%, p\u2009<\u20090.001 and 19.7% vs. 27.0%, p\u2009<\u20090.001). The 30-day mortality rate trended downwards (7.2% vs. 3.6%, p\u2009=\u20090.186). The percentage of patients who received no treatment reduced (75.2% vs. 69.6%, p\u2009<\u20090.001).

Conclusion

The centralisation of PC services in South Wales is associated with a small increase in OS and a larger increase in PC treatment utilisation. It is concerning that many patients still fail to receive any treatments.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1007/s11605-020-04612-8" + }, { "id": "36581539", "doi": "https://doi.org/10.1016/j.jpsychires.2022.12.015", @@ -19719,6 +19719,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeab178/40357499/jeab178.pdf; doi:https://doi.org/10.1093/ehjci/jeab178; html:https://europepmc.org/articles/PMC9584619; pdf:https://europepmc.org/articles/PMC9584619?pdf=render" }, + { + "id": "36744612", + "doi": "https://doi.org/10.1111/ppe.12959", + "title": "Trends in survival of children with severe congenital heart defects by gestational age at birth: A population-based study using administrative hospital data for England.", + "authorString": "Gimeno L, Brown K, Harron K, Peppa M, Gilbert R, Blackburn R.", + "authorAffiliations": "", + "journalTitle": "Paediatric and perinatal epidemiology", + "pubYear": "2023", + "date": "2023-02-06", + "isOpenAccess": "Y", + "keywords": "Survival analysis; Congenital heart defects; England; trends; Gestational Age; Administrative Data", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Children with congenital heart defects (CHD) are twice as likely as their peers to be born preterm (<37\u2009weeks' gestation), yet descriptions of recent trends in long-term survival by gestational age at birth (GA) are lacking.

Objectives

To quantify changes in survival to age 5\u2009years of children in England with severe CHD by GA.

Methods

We estimated changes in survival to age five of children with severe CHD and all other children born in England between April 2004 and March 2016, overall and by GA-group using linked hospital and mortality records.

Results

Of 5,953,598 livebirths, 5.7% (339,080 of 5,953,598) were born preterm, 0.35% (20,648 of 5,953,598) died before age five and 3.6 per 1000 (21,291 of 5,953,598) had severe CHD. Adjusting for GA, under-five mortality rates fell at a similar rate between 2004-2008 and 2012-2016 for children with severe CHD (adjusted hazard ratio [HR] 0.79, 95% CI 0.71, 0.88) and all other children (HR 0.78, 95% CI 0.76, 0.81). For children with severe CHD, overall survival to age five increased from 87.5% (95% CI 86.6, 88.4) in 2004-2008 to 89.6% (95% CI 88.9, 90.3) in 2012-2016. There was strong evidence for better survival in the \u226539-week group (90.2%, 95% CI 89.1, 91.2 to 93%, 95% CI 92.4, 93.9), weaker evidence at 24-31 and 37-38\u2009weeks and no evidence at 32-36\u2009weeks. We estimate that 51 deaths (95% CI 24, 77) per year in children with severe CHD were averted in 2012-2016 compared to what would have been the case had 2004-2008 mortality rates persisted.

Conclusions

Nine out of 10 children with severe CHD in 2012-2016 survived to age five. The small improvement in survival over the study period was driven by increased survival in term children. Most children with severe CHD are reaching school age and may require additional support by schools and healthcare services.", + "laySummary": "", + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/ppe.12959; doi:https://doi.org/10.1111/ppe.12959; html:https://europepmc.org/articles/PMC10946523; pdf:https://europepmc.org/articles/PMC10946523?pdf=render" + }, { "id": "34631820", "doi": "https://doi.org/10.3389/fcvm.2021.716577", @@ -19737,21 +19754,21 @@ "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.716577/pdf; doi:https://doi.org/10.3389/fcvm.2021.716577; html:https://europepmc.org/articles/PMC8494975; pdf:https://europepmc.org/articles/PMC8494975?pdf=render" }, { - "id": "36744612", - "doi": "https://doi.org/10.1111/ppe.12959", - "title": "Trends in survival of children with severe congenital heart defects by gestational age at birth: A population-based study using administrative hospital data for England.", - "authorString": "Gimeno L, Brown K, Harron K, Peppa M, Gilbert R, Blackburn R.", + "id": "33678589", + "doi": "https://doi.org/10.1016/s2589-7500(20)30317-4", + "title": "Health data poverty: an assailable barrier to equitable digital health care.", + "authorString": "Ibrahim H, Liu X, Zariffa N, Morris AD, Denniston AK.", "authorAffiliations": "", - "journalTitle": "Paediatric and perinatal epidemiology", - "pubYear": "2023", - "date": "2023-02-06", - "isOpenAccess": "Y", - "keywords": "Survival analysis; Congenital heart defects; England; trends; Gestational Age; Administrative Data", + "journalTitle": "The Lancet. Digital health", + "pubYear": "2021", + "date": "2021-03-04", + "isOpenAccess": "N", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Children with congenital heart defects (CHD) are twice as likely as their peers to be born preterm (<37\u2009weeks' gestation), yet descriptions of recent trends in long-term survival by gestational age at birth (GA) are lacking.

Objectives

To quantify changes in survival to age 5\u2009years of children in England with severe CHD by GA.

Methods

We estimated changes in survival to age five of children with severe CHD and all other children born in England between April 2004 and March 2016, overall and by GA-group using linked hospital and mortality records.

Results

Of 5,953,598 livebirths, 5.7% (339,080 of 5,953,598) were born preterm, 0.35% (20,648 of 5,953,598) died before age five and 3.6 per 1000 (21,291 of 5,953,598) had severe CHD. Adjusting for GA, under-five mortality rates fell at a similar rate between 2004-2008 and 2012-2016 for children with severe CHD (adjusted hazard ratio [HR] 0.79, 95% CI 0.71, 0.88) and all other children (HR 0.78, 95% CI 0.76, 0.81). For children with severe CHD, overall survival to age five increased from 87.5% (95% CI 86.6, 88.4) in 2004-2008 to 89.6% (95% CI 88.9, 90.3) in 2012-2016. There was strong evidence for better survival in the \u226539-week group (90.2%, 95% CI 89.1, 91.2 to 93%, 95% CI 92.4, 93.9), weaker evidence at 24-31 and 37-38\u2009weeks and no evidence at 32-36\u2009weeks. We estimate that 51 deaths (95% CI 24, 77) per year in children with severe CHD were averted in 2012-2016 compared to what would have been the case had 2004-2008 mortality rates persisted.

Conclusions

Nine out of 10 children with severe CHD in 2012-2016 survived to age five. The small improvement in survival over the study period was driven by increased survival in term children. Most children with severe CHD are reaching school age and may require additional support by schools and healthcare services.", + "abstract": "Data-driven digital health technologies have the power to transform health care. If these tools could be sustainably delivered at scale, they might have the potential to provide everyone, everywhere, with equitable access to expert-level care, narrowing the global health and wellbeing gap. Conversely, it is highly possible that these transformative technologies could exacerbate existing health-care inequalities instead. In this Viewpoint, we describe the problem of health data poverty: the inability for individuals, groups, or populations to benefit from a discovery or innovation due to a scarcity of data that are adequately representative. We assert that health data poverty is a threat to global health that could prevent the benefits of data-driven digital health technologies from being more widely realised and might even lead to them causing harm. We argue that the time to act is now to avoid creating a digital health divide that exacerbates existing health-care inequalities and to ensure that no one is left behind in the digital era.", "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/ppe.12959; doi:https://doi.org/10.1111/ppe.12959; html:https://europepmc.org/articles/PMC10946523; pdf:https://europepmc.org/articles/PMC10946523?pdf=render" + "urls": "pdf:http://www.thelancet.com/article/S2589750020303174/pdf; doi:https://doi.org/10.1016/S2589-7500(20)30317-4" }, { "id": "32182948", @@ -19770,23 +19787,6 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/2073-4409/9/3/665/pdf?version=1584361130; doi:https://doi.org/10.3390/cells9030665; html:https://europepmc.org/articles/PMC7140647; pdf:https://europepmc.org/articles/PMC7140647?pdf=render" }, - { - "id": "33678589", - "doi": "https://doi.org/10.1016/s2589-7500(20)30317-4", - "title": "Health data poverty: an assailable barrier to equitable digital health care.", - "authorString": "Ibrahim H, Liu X, Zariffa N, Morris AD, Denniston AK.", - "authorAffiliations": "", - "journalTitle": "The Lancet. Digital health", - "pubYear": "2021", - "date": "2021-03-04", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Data-driven digital health technologies have the power to transform health care. If these tools could be sustainably delivered at scale, they might have the potential to provide everyone, everywhere, with equitable access to expert-level care, narrowing the global health and wellbeing gap. Conversely, it is highly possible that these transformative technologies could exacerbate existing health-care inequalities instead. In this Viewpoint, we describe the problem of health data poverty: the inability for individuals, groups, or populations to benefit from a discovery or innovation due to a scarcity of data that are adequately representative. We assert that health data poverty is a threat to global health that could prevent the benefits of data-driven digital health technologies from being more widely realised and might even lead to them causing harm. We argue that the time to act is now to avoid creating a digital health divide that exacerbates existing health-care inequalities and to ensure that no one is left behind in the digital era.", - "laySummary": "", - "urls": "pdf:http://www.thelancet.com/article/S2589750020303174/pdf; doi:https://doi.org/10.1016/S2589-7500(20)30317-4" - }, { "id": "33344049", "doi": "https://doi.org/10.1167/tvst.9.13.5", @@ -19805,21 +19805,21 @@ "urls": "doi:https://doi.org/10.1167/tvst.9.13.5; doi:https://doi.org/10.1167/tvst.9.13.5; html:https://europepmc.org/articles/PMC7718823; pdf:https://europepmc.org/articles/PMC7718823?pdf=render" }, { - "id": "37703231", - "doi": "https://doi.org/10.1371/journal.pdig.0000334", - "title": "A population-based study exploring phenotypic clusters and clinical outcomes in stroke using unsupervised machine learning approach.", - "authorString": "Akyea RK, Ntaios G, Kontopantelis E, Georgiopoulos G, Soria D, Asselbergs FW, Kai J, Weng SF, Qureshi N.", + "id": "33085509", + "doi": "https://doi.org/10.7326/m20-4986", + "title": "COVID-19 Mortality Risk in Down Syndrome: Results From a Cohort Study of 8 Million Adults.", + "authorString": "Clift AK, Coupland CAC, Keogh RH, Hemingway H, Hippisley-Cox J.", "authorAffiliations": "", - "journalTitle": "PLOS digital health", - "pubYear": "2023", - "date": "2023-09-13", + "journalTitle": "Annals of internal medicine", + "pubYear": "2021", + "date": "2020-10-21", "isOpenAccess": "Y", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "Individuals developing stroke have varying clinical characteristics, demographic, and biochemical profiles. This heterogeneity in phenotypic characteristics can impact on cardiovascular disease (CVD) morbidity and mortality outcomes. This study uses a novel clustering approach to stratify individuals with incident stroke into phenotypic clusters and evaluates the differential burden of recurrent stroke and other cardiovascular outcomes. We used linked clinical data from primary care, hospitalisations, and death records in the UK. A data-driven clustering analysis (kamila algorithm) was used in 48,114 patients aged \u2265 18 years with incident stroke, from 1-Jan-1998 to 31-Dec-2017 and no prior history of serious vascular events. Cox proportional hazards regression was used to estimate hazard ratios (HRs) for subsequent adverse outcomes, for each of the generated clusters. Adverse outcomes included coronary heart disease (CHD), recurrent stroke, peripheral vascular disease (PVD), heart failure, CVD-related and all-cause mortality. Four distinct phenotypes with varying underlying clinical characteristics were identified in patients with incident stroke. Compared with cluster 1 (n = 5,201, 10.8%), the risk of composite recurrent stroke and CVD-related mortality was higher in the other 3 clusters (cluster 2 [n = 18,655, 38.8%]: hazard ratio [HR], 1.07; 95% CI, 1.02-1.12; cluster 3 [n = 10,244, 21.3%]: HR, 1.20; 95% CI, 1.14-1.26; and cluster 4 [n = 14,014, 29.1%]: HR, 1.44; 95% CI: 1.37-1.50). Similar trends in risk were observed for composite recurrent stroke and all-cause mortality outcome, and subsequent recurrent stroke outcome. However, results were not consistent for subsequent risk in CHD, PVD, heart failure, CVD-related mortality, and all-cause mortality. In this proof of principle study, we demonstrated how a heterogenous population of patients with incident stroke can be stratified into four relatively homogenous phenotypes with differential risk of recurrent and major cardiovascular outcomes. This offers an opportunity to revisit the stratification of care for patients with incident stroke to improve patient outcomes.", + "abstract": "", "laySummary": "", - "urls": "pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000334&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000334; html:https://europepmc.org/articles/PMC10499205; pdf:https://europepmc.org/articles/PMC10499205?pdf=render" + "urls": "pdf:https://europepmc.org/articles/pmc7592804?pdf=render; doi:https://doi.org/10.7326/M20-4986; html:https://europepmc.org/articles/PMC7592804; pdf:https://europepmc.org/articles/PMC7592804?pdf=render" }, { "id": "34270458", @@ -19839,38 +19839,21 @@ "urls": "pdf:https://www.ajtmh.org/downloadpdf/journals/tpmd/105/3/article-p561.pdf; doi:https://doi.org/10.4269/ajtmh.21-0482; html:https://europepmc.org/articles/PMC8592367; pdf:https://europepmc.org/articles/PMC8592367?pdf=render" }, { - "id": "33085509", - "doi": "https://doi.org/10.7326/m20-4986", - "title": "COVID-19 Mortality Risk in Down Syndrome: Results From a Cohort Study of 8 Million Adults.", - "authorString": "Clift AK, Coupland CAC, Keogh RH, Hemingway H, Hippisley-Cox J.", + "id": "37703231", + "doi": "https://doi.org/10.1371/journal.pdig.0000334", + "title": "A population-based study exploring phenotypic clusters and clinical outcomes in stroke using unsupervised machine learning approach.", + "authorString": "Akyea RK, Ntaios G, Kontopantelis E, Georgiopoulos G, Soria D, Asselbergs FW, Kai J, Weng SF, Qureshi N.", "authorAffiliations": "", - "journalTitle": "Annals of internal medicine", - "pubYear": "2021", - "date": "2020-10-21", + "journalTitle": "PLOS digital health", + "pubYear": "2023", + "date": "2023-09-13", "isOpenAccess": "Y", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "pdf:https://europepmc.org/articles/pmc7592804?pdf=render; doi:https://doi.org/10.7326/M20-4986; html:https://europepmc.org/articles/PMC7592804; pdf:https://europepmc.org/articles/PMC7592804?pdf=render" - }, - { - "id": "33655079", - "doi": "https://doi.org/10.12688/wellcomeopenres.16304.2", - "title": "Impact of baseline cases of cough and fever on UK COVID-19 diagnostic testing rates: estimates from the Bug Watch community cohort study.", - "authorString": "Eyre MT, Burns R, Kirkby V, Smith C, Denaxas S, Nguyen V, Hayward A, Shallcross L, Fragaszy E, Aldridge RW.", - "authorAffiliations": "", - "journalTitle": "Wellcome open research", - "pubYear": "2020", - "date": "2020-01-01", - "isOpenAccess": "Y", - "keywords": "Fever; Cough; United Kingdom; Diagnostic Testing Capacity; Covid-19; Swab Test", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Background: Diagnostic testing forms a major part of the UK's response to the current coronavirus disease 2019 (COVID-19) pandemic with tests offered to anyone with a continuous cough, high temperature or anosmia. Testing capacity must be sufficient during the winter respiratory season when levels of cough and fever are high due to non-COVID-19 causes. This study aims to make predictions about the contribution of baseline cough or fever to future testing demand in the UK. Methods: In this analysis of the Bug Watch community cohort study, we estimated the incidence of cough or fever in England in 2018-2019. We then estimated the COVID-19 diagnostic testing rates required in the UK for baseline cough or fever cases for the period July 2020-June 2021. This was explored for different rates of the population requesting tests, four COVID-19 second wave scenarios and high and low baseline cough or fever incidence scenarios. Results: Under the high baseline cough or fever scenario, incidence in the UK is expected to rise rapidly from 250,708 (95%CI 181,095 - 347,080) cases per day in September to a peak of 444,660 (95%CI 353,084 - 559,988) in December. If 80% of these cases request tests, testing demand would exceed 1.4 million tests per week for five consecutive months. Demand was significantly lower in the low cough or fever incidence scenario, with 129,115 (95%CI 111,596 - 151,679) tests per day in January 2021, compared to 340,921 (95%CI 276,039 - 424,491) tests per day in the higher incidence scenario. Conclusions: Our results show that national COVID-19 testing demand is highly dependent on background cough or fever incidence. This study highlights that the UK's response to the COVID-19 pandemic must ensure that a high proportion of people with symptoms request tests, and that testing capacity is sufficient to meet the high predicted demand.", + "abstract": "Individuals developing stroke have varying clinical characteristics, demographic, and biochemical profiles. This heterogeneity in phenotypic characteristics can impact on cardiovascular disease (CVD) morbidity and mortality outcomes. This study uses a novel clustering approach to stratify individuals with incident stroke into phenotypic clusters and evaluates the differential burden of recurrent stroke and other cardiovascular outcomes. We used linked clinical data from primary care, hospitalisations, and death records in the UK. A data-driven clustering analysis (kamila algorithm) was used in 48,114 patients aged \u2265 18 years with incident stroke, from 1-Jan-1998 to 31-Dec-2017 and no prior history of serious vascular events. Cox proportional hazards regression was used to estimate hazard ratios (HRs) for subsequent adverse outcomes, for each of the generated clusters. Adverse outcomes included coronary heart disease (CHD), recurrent stroke, peripheral vascular disease (PVD), heart failure, CVD-related and all-cause mortality. Four distinct phenotypes with varying underlying clinical characteristics were identified in patients with incident stroke. Compared with cluster 1 (n = 5,201, 10.8%), the risk of composite recurrent stroke and CVD-related mortality was higher in the other 3 clusters (cluster 2 [n = 18,655, 38.8%]: hazard ratio [HR], 1.07; 95% CI, 1.02-1.12; cluster 3 [n = 10,244, 21.3%]: HR, 1.20; 95% CI, 1.14-1.26; and cluster 4 [n = 14,014, 29.1%]: HR, 1.44; 95% CI: 1.37-1.50). Similar trends in risk were observed for composite recurrent stroke and all-cause mortality outcome, and subsequent recurrent stroke outcome. However, results were not consistent for subsequent risk in CHD, PVD, heart failure, CVD-related mortality, and all-cause mortality. In this proof of principle study, we demonstrated how a heterogenous population of patients with incident stroke can be stratified into four relatively homogenous phenotypes with differential risk of recurrent and major cardiovascular outcomes. This offers an opportunity to revisit the stratification of care for patients with incident stroke to improve patient outcomes.", "laySummary": "", - "urls": "doi:https://doi.org/10.12688/wellcomeopenres.16304.2; html:https://europepmc.org/articles/PMC7890379; pdf:https://europepmc.org/articles/PMC7890379?pdf=render" + "urls": "pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000334&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000334; html:https://europepmc.org/articles/PMC10499205; pdf:https://europepmc.org/articles/PMC10499205?pdf=render" }, { "id": "31442537", @@ -19889,6 +19872,23 @@ "laySummary": "", "urls": "pdf:http://www.jaad.org/article/S0190962219326143/pdf; doi:https://doi.org/10.1016/j.jaad.2019.08.039; html:https://europepmc.org/articles/PMC7704103; pdf:https://europepmc.org/articles/PMC7704103?pdf=render" }, + { + "id": "33655079", + "doi": "https://doi.org/10.12688/wellcomeopenres.16304.2", + "title": "Impact of baseline cases of cough and fever on UK COVID-19 diagnostic testing rates: estimates from the Bug Watch community cohort study.", + "authorString": "Eyre MT, Burns R, Kirkby V, Smith C, Denaxas S, Nguyen V, Hayward A, Shallcross L, Fragaszy E, Aldridge RW.", + "authorAffiliations": "", + "journalTitle": "Wellcome open research", + "pubYear": "2020", + "date": "2020-01-01", + "isOpenAccess": "Y", + "keywords": "Fever; Cough; United Kingdom; Diagnostic Testing Capacity; Covid-19; Swab Test", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Background: Diagnostic testing forms a major part of the UK's response to the current coronavirus disease 2019 (COVID-19) pandemic with tests offered to anyone with a continuous cough, high temperature or anosmia. Testing capacity must be sufficient during the winter respiratory season when levels of cough and fever are high due to non-COVID-19 causes. This study aims to make predictions about the contribution of baseline cough or fever to future testing demand in the UK. Methods: In this analysis of the Bug Watch community cohort study, we estimated the incidence of cough or fever in England in 2018-2019. We then estimated the COVID-19 diagnostic testing rates required in the UK for baseline cough or fever cases for the period July 2020-June 2021. This was explored for different rates of the population requesting tests, four COVID-19 second wave scenarios and high and low baseline cough or fever incidence scenarios. Results: Under the high baseline cough or fever scenario, incidence in the UK is expected to rise rapidly from 250,708 (95%CI 181,095 - 347,080) cases per day in September to a peak of 444,660 (95%CI 353,084 - 559,988) in December. If 80% of these cases request tests, testing demand would exceed 1.4 million tests per week for five consecutive months. Demand was significantly lower in the low cough or fever incidence scenario, with 129,115 (95%CI 111,596 - 151,679) tests per day in January 2021, compared to 340,921 (95%CI 276,039 - 424,491) tests per day in the higher incidence scenario. Conclusions: Our results show that national COVID-19 testing demand is highly dependent on background cough or fever incidence. This study highlights that the UK's response to the COVID-19 pandemic must ensure that a high proportion of people with symptoms request tests, and that testing capacity is sufficient to meet the high predicted demand.", + "laySummary": "", + "urls": "doi:https://doi.org/10.12688/wellcomeopenres.16304.2; html:https://europepmc.org/articles/PMC7890379; pdf:https://europepmc.org/articles/PMC7890379?pdf=render" + }, { "id": "35987738", "doi": "https://doi.org/10.1016/j.jcmg.2022.06.017", @@ -19940,23 +19940,6 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004141&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004141; html:https://europepmc.org/articles/PMC9799317; pdf:https://europepmc.org/articles/PMC9799317?pdf=render" }, - { - "id": "35440465", - "doi": "https://doi.org/10.3399/bjgp.2021.0689", - "title": "Association between oral anticoagulants and COVID-19-related outcomes: a population-based cohort study.", - "authorString": "Wong AY, Tomlinson L, Brown JP, Elson W, Walker AJ, Schultze A, Morton CE, Evans D, Inglesby P, MacKenna B, Bhaskaran K, Rentsch CT, Powell E, Williamson E, Croker R, Bacon S, Hulme W, Bates C, Curtis HJ, Mehrkar A, Cockburn J, McDonald HI, Mathur R, Wing K, Forbes H, Eggo RM, Evans SJ, Smeeth L, Goldacre B, Douglas IJ, (The OpenSAFELY Collaborative).", - "authorAffiliations": "", - "journalTitle": "The British journal of general practice : the journal of the Royal College of General Practitioners", - "pubYear": "2022", - "date": "2022-06-30", - "isOpenAccess": "Y", - "keywords": "Warfarin; Factor Xa Inhibitors; Dabigatran; Covid-19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Early evidence has shown that anticoagulant reduces the risk of thrombotic events in those infected with COVID-19. However, evidence of the role of routinely prescribed oral anticoagulants (OACs) in COVID-19 outcomes is limited.

Aim

To investigate the association between OACs and COVID-19 outcomes in those with atrial fibrillation and a CHA2DS2-VASc score of 2.

Design and setting

On behalf of NHS England, a population-based cohort study was conducted.

Method

The study used primary care data and pseudonymously-linked SARS-CoV-2 antigen testing data, hospital admissions, and death records from England. Cox regression was used to estimate hazard ratios (HRs) for COVID-19 outcomes comparing people with current OAC use versus non-use, accounting for age, sex, comorbidities, other medications, deprivation, and general practice.

Results

Of 71 103 people with atrial fibrillation and a CHA2DS2-VASc score of 2, there were 52 832 current OAC users and 18 271 non-users. No difference in risk of being tested for SARS-CoV-2 was associated with current use (adjusted HR [aHR] 0.99, 95% confidence interval [CI] = 0.95 to 1.04) versus non-use. A lower risk of testing positive for SARS-CoV-2 (aHR 0.77, 95% CI = 0.63 to 0.95) and a marginally lower risk of COVID-19-related death (aHR, 0.74, 95% CI = 0.53 to 1.04) were associated with current use versus non-use.

Conclusion

Among those at low baseline stroke risk, people receiving OACs had a lower risk of testing positive for SARS-CoV-2 and severe COVID-19 outcomes than non-users; this might be explained by a causal effect of OACs in preventing severe COVID-19 outcomes or unmeasured confounding, including more cautious behaviours leading to reduced infection risk.", - "laySummary": "", - "urls": "pdf:https://bjgp.org/content/bjgp/early/2022/04/19/BJGP.2021.0689.full.pdf; doi:https://doi.org/10.3399/BJGP.2021.0689; html:https://europepmc.org/articles/PMC9037187; pdf:https://europepmc.org/articles/PMC9037187?pdf=render" - }, { "id": "30532623", "doi": "https://doi.org/10.3897/bdj.6.e29232", @@ -19974,6 +19957,23 @@ "laySummary": "", "urls": "pdf:https://bdj.pensoft.net/article/29232/download/pdf/; doi:https://doi.org/10.3897/BDJ.6.e29232; html:https://europepmc.org/articles/PMC6281706; pdf:https://europepmc.org/articles/PMC6281706?pdf=render" }, + { + "id": "35440465", + "doi": "https://doi.org/10.3399/bjgp.2021.0689", + "title": "Association between oral anticoagulants and COVID-19-related outcomes: a population-based cohort study.", + "authorString": "Wong AY, Tomlinson L, Brown JP, Elson W, Walker AJ, Schultze A, Morton CE, Evans D, Inglesby P, MacKenna B, Bhaskaran K, Rentsch CT, Powell E, Williamson E, Croker R, Bacon S, Hulme W, Bates C, Curtis HJ, Mehrkar A, Cockburn J, McDonald HI, Mathur R, Wing K, Forbes H, Eggo RM, Evans SJ, Smeeth L, Goldacre B, Douglas IJ, (The OpenSAFELY Collaborative).", + "authorAffiliations": "", + "journalTitle": "The British journal of general practice : the journal of the Royal College of General Practitioners", + "pubYear": "2022", + "date": "2022-06-30", + "isOpenAccess": "Y", + "keywords": "Warfarin; Factor Xa Inhibitors; Dabigatran; Covid-19", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Early evidence has shown that anticoagulant reduces the risk of thrombotic events in those infected with COVID-19. However, evidence of the role of routinely prescribed oral anticoagulants (OACs) in COVID-19 outcomes is limited.

Aim

To investigate the association between OACs and COVID-19 outcomes in those with atrial fibrillation and a CHA2DS2-VASc score of 2.

Design and setting

On behalf of NHS England, a population-based cohort study was conducted.

Method

The study used primary care data and pseudonymously-linked SARS-CoV-2 antigen testing data, hospital admissions, and death records from England. Cox regression was used to estimate hazard ratios (HRs) for COVID-19 outcomes comparing people with current OAC use versus non-use, accounting for age, sex, comorbidities, other medications, deprivation, and general practice.

Results

Of 71 103 people with atrial fibrillation and a CHA2DS2-VASc score of 2, there were 52 832 current OAC users and 18 271 non-users. No difference in risk of being tested for SARS-CoV-2 was associated with current use (adjusted HR [aHR] 0.99, 95% confidence interval [CI] = 0.95 to 1.04) versus non-use. A lower risk of testing positive for SARS-CoV-2 (aHR 0.77, 95% CI = 0.63 to 0.95) and a marginally lower risk of COVID-19-related death (aHR, 0.74, 95% CI = 0.53 to 1.04) were associated with current use versus non-use.

Conclusion

Among those at low baseline stroke risk, people receiving OACs had a lower risk of testing positive for SARS-CoV-2 and severe COVID-19 outcomes than non-users; this might be explained by a causal effect of OACs in preventing severe COVID-19 outcomes or unmeasured confounding, including more cautious behaviours leading to reduced infection risk.", + "laySummary": "", + "urls": "pdf:https://bjgp.org/content/bjgp/early/2022/04/19/BJGP.2021.0689.full.pdf; doi:https://doi.org/10.3399/BJGP.2021.0689; html:https://europepmc.org/articles/PMC9037187; pdf:https://europepmc.org/articles/PMC9037187?pdf=render" + }, { "id": "37067859", "doi": "https://doi.org/10.1136/bmjmed-2022-000245", @@ -19991,23 +19991,6 @@ "laySummary": "", "urls": "pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000245.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000245; html:https://europepmc.org/articles/PMC10083523; pdf:https://europepmc.org/articles/PMC10083523?pdf=render" }, - { - "id": "35842339", - "doi": "https://doi.org/10.1016/j.vaccine.2022.06.080", - "title": "Linking cohort data and Welsh routine health records to investigate children at risk of delayed primary vaccination.", - "authorString": "Walton S, Cortina-Borja M, Dezateux C, Griffiths LJ, Tingay K, Akbari A, Bandyopadhyay A, Lyons RA, Roberts R, Bedford H.", - "authorAffiliations": "", - "journalTitle": "Vaccine", - "pubYear": "2022", - "date": "2022-07-13", - "isOpenAccess": "Y", - "keywords": "Child; Vaccination; Dtp Vaccine; Timeliness; Child Health Systems; Millennium Cohort Study (Mcs)", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Delayed primary vaccination is one of the strongest predictors of subsequent incomplete immunisation. Identifying children at risk of such delay may enable targeting of interventions, thus decreasing vaccine-preventable illness.

Objectives

To explore socio-demographic factors associated with delayed receipt of the Diphtheria, Tetanus and Pertussis (DTP) vaccine.

Methods

We included 1,782 children, born between 2000 and 2001, participating in the Millennium Cohort Study (MCS) and resident in Wales, whose parents gave consent for linkage to National Community Child Health Database records at the age seven years contact. We examined child, maternal, family and area characteristics associated with delayed receipt of the first dose of the DTP vaccine.

Results

98.6% received the first dose of DTP. The majority, 79.6% (n\u00a0=\u00a01,429) received it on time (between 8 and 12\u00a0weeks of age), 14.2% (n\u00a0=\u00a0251) received it early (prior to 8\u00a0weeks of age) and 4.8% (n\u00a0=\u00a079) were delayed (after 12\u00a0weeks of age); 1.4% (n\u00a0=\u00a023) never received it. Delayed primary vaccination was more likely among children with older natural siblings (risk ratio 3.82, 95% confidence interval (1.97, 7.38)), children admitted to special/intensive care (3.15, (1.65, 5.99)), those whose birth weight was\u00a0>\u00a04Kg (2.02, (1.09, 3.73)) and boys (1.53, (1.01, 2.31)). There was a reduced risk of delayed vaccination with increasing maternal age (0.73, (0.53, 1.00) per 5\u00a0year increase) and for babies born to graduate mothers (0.27, (0.08, 0.90)).

Conclusions

Although the majority of infants were vaccinated in a timely manner, identification of infants at increased risk of early or delayed vaccination will enable targeting of interventions to facilitate timely immunisation. This is to our knowledge the first study exploring individual level socio-demographic factors associated with delayed primary vaccination in the UK and demonstrates the benefits of linking cohort data to routinely-collected child health data.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.vaccine.2022.06.080; doi:https://doi.org/10.1016/j.vaccine.2022.06.080; html:https://europepmc.org/articles/PMC10499753; pdf:https://europepmc.org/articles/PMC10499753?pdf=render" - }, { "id": "36369983", "doi": "https://doi.org/10.1093/eurheartj/ehac650", @@ -20025,6 +20008,23 @@ "laySummary": "", "urls": "pdf:https://discovery.ucl.ac.uk/10159909/1/Asselbergs_EHJ%20digital%20viewpoint%202022_final%20accepted.pdf; doi:https://doi.org/10.1093/eurheartj/ehac650" }, + { + "id": "35842339", + "doi": "https://doi.org/10.1016/j.vaccine.2022.06.080", + "title": "Linking cohort data and Welsh routine health records to investigate children at risk of delayed primary vaccination.", + "authorString": "Walton S, Cortina-Borja M, Dezateux C, Griffiths LJ, Tingay K, Akbari A, Bandyopadhyay A, Lyons RA, Roberts R, Bedford H.", + "authorAffiliations": "", + "journalTitle": "Vaccine", + "pubYear": "2022", + "date": "2022-07-13", + "isOpenAccess": "Y", + "keywords": "Child; Vaccination; Dtp Vaccine; Timeliness; Child Health Systems; Millennium Cohort Study (Mcs)", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Delayed primary vaccination is one of the strongest predictors of subsequent incomplete immunisation. Identifying children at risk of such delay may enable targeting of interventions, thus decreasing vaccine-preventable illness.

Objectives

To explore socio-demographic factors associated with delayed receipt of the Diphtheria, Tetanus and Pertussis (DTP) vaccine.

Methods

We included 1,782 children, born between 2000 and 2001, participating in the Millennium Cohort Study (MCS) and resident in Wales, whose parents gave consent for linkage to National Community Child Health Database records at the age seven years contact. We examined child, maternal, family and area characteristics associated with delayed receipt of the first dose of the DTP vaccine.

Results

98.6% received the first dose of DTP. The majority, 79.6% (n\u00a0=\u00a01,429) received it on time (between 8 and 12\u00a0weeks of age), 14.2% (n\u00a0=\u00a0251) received it early (prior to 8\u00a0weeks of age) and 4.8% (n\u00a0=\u00a079) were delayed (after 12\u00a0weeks of age); 1.4% (n\u00a0=\u00a023) never received it. Delayed primary vaccination was more likely among children with older natural siblings (risk ratio 3.82, 95% confidence interval (1.97, 7.38)), children admitted to special/intensive care (3.15, (1.65, 5.99)), those whose birth weight was\u00a0>\u00a04Kg (2.02, (1.09, 3.73)) and boys (1.53, (1.01, 2.31)). There was a reduced risk of delayed vaccination with increasing maternal age (0.73, (0.53, 1.00) per 5\u00a0year increase) and for babies born to graduate mothers (0.27, (0.08, 0.90)).

Conclusions

Although the majority of infants were vaccinated in a timely manner, identification of infants at increased risk of early or delayed vaccination will enable targeting of interventions to facilitate timely immunisation. This is to our knowledge the first study exploring individual level socio-demographic factors associated with delayed primary vaccination in the UK and demonstrates the benefits of linking cohort data to routinely-collected child health data.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.vaccine.2022.06.080; doi:https://doi.org/10.1016/j.vaccine.2022.06.080; html:https://europepmc.org/articles/PMC10499753; pdf:https://europepmc.org/articles/PMC10499753?pdf=render" + }, { "id": "37740900", "doi": "https://doi.org/10.1093/ageing/afad176", @@ -20127,23 +20127,6 @@ "laySummary": "", "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861899; doi:https://doi.org/10.1001/jamaneurol.2021.5420; html:https://europepmc.org/articles/PMC8861899; doi:https://doi.org/10.1001/jamaneurol.2021.5420" }, - { - "id": "38091687", - "doi": "https://doi.org/10.1016/j.bjps.2023.10.106", - "title": "Revisiting basal cell carcinoma clinical margins: Leveraging natural language processing and multivariate analysis with updated Royal College of Pathologists histological reporting standards.", - "authorString": "Ali SR, Dobbs TD, Jovic M, Strafford H, Lacey AS, Williams N, Pickrell WO, Hutchings HA, Whitaker IS.", - "authorAffiliations": "", - "journalTitle": "Journal of plastic, reconstructive & aesthetic surgery : JPRAS", - "pubYear": "2024", - "date": "2023-10-20", - "isOpenAccess": "N", - "keywords": "multivariate analysis; Royal College Of Pathologists; Basal Cell Carcinoma; Natural Language Processing; Clinical Margins; Histological Reporting Guidelines", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

Data supporting the current British Association of Dermatologists guidelines for the management of basal cell carcinoma (BCC) are based on historic studies and do not consider the updated Royal College of Pathologists (RCPath) histological reporting standards. The aim of this study was to use natural language processing (NLP)-derived data and undertake a multivariate analysis with updated RCPath standards, providing a contemporary update on the excision margins required to achieve histological clearance in BCC.

Methods

A validated NLP information extraction model was used to perform a rapid multi-centre, pan-specialty, consecutive retrospective analysis of BCCs, managed with surgical excision using a pre-determined clinical margin, over a 17-year period (2004-2021) at Swansea Bay University Health Board. Logistic regression assessed the relationship between the peripheral and deep margins and histological clearance.

Results

We ran our NLP algorithm on 34,955 BCCs. Out of the 1447 BCCs that met the inclusion criteria, the peripheral margin clearance was not influenced by the BCC risk level (p\u00a0=\u00a00.670). A clinical peripheral margin of 6\u00a0mm achieved a 95% histological clearance rate (95% confidence interval [CI], 0.93-0.98). Tumour thickness inversely affected deep-margin histological clearance (OR 0.720, 95% CI, 0.525-0.991, p\u00a0<\u00a00.05). Depth level 2 had a 97% probability of achieving deep-margin histological clearance across all tumour thicknesses.

Conclusion

Updated RCPath reporting standards minimally impact the peripheral margin histological clearance in BCC. Larger clinical peripheral margins than those indicated by current guidelines may be necessary to achieve excision rates of \u226595%. These findings emphasise the need for continuous reassessment of clinical standards to enhance patient care.", - "laySummary": "", - "urls": "pdf:http://www.jprasurg.com/article/S1748681523006769/pdf; doi:https://doi.org/10.1016/j.bjps.2023.10.106" - }, { "id": "37505992", "doi": "https://doi.org/10.1093/ageing/afad136", @@ -20161,6 +20144,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ageing/article-pdf/52/7/afad136/50976589/afad136.pdf; doi:https://doi.org/10.1093/ageing/afad136; html:https://europepmc.org/articles/PMC10378723; pdf:https://europepmc.org/articles/PMC10378723?pdf=render" }, + { + "id": "38091687", + "doi": "https://doi.org/10.1016/j.bjps.2023.10.106", + "title": "Revisiting basal cell carcinoma clinical margins: Leveraging natural language processing and multivariate analysis with updated Royal College of Pathologists histological reporting standards.", + "authorString": "Ali SR, Dobbs TD, Jovic M, Strafford H, Lacey AS, Williams N, Pickrell WO, Hutchings HA, Whitaker IS.", + "authorAffiliations": "", + "journalTitle": "Journal of plastic, reconstructive & aesthetic surgery : JPRAS", + "pubYear": "2024", + "date": "2023-10-20", + "isOpenAccess": "N", + "keywords": "multivariate analysis; Royal College Of Pathologists; Basal Cell Carcinoma; Natural Language Processing; Clinical Margins; Histological Reporting Guidelines", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

Data supporting the current British Association of Dermatologists guidelines for the management of basal cell carcinoma (BCC) are based on historic studies and do not consider the updated Royal College of Pathologists (RCPath) histological reporting standards. The aim of this study was to use natural language processing (NLP)-derived data and undertake a multivariate analysis with updated RCPath standards, providing a contemporary update on the excision margins required to achieve histological clearance in BCC.

Methods

A validated NLP information extraction model was used to perform a rapid multi-centre, pan-specialty, consecutive retrospective analysis of BCCs, managed with surgical excision using a pre-determined clinical margin, over a 17-year period (2004-2021) at Swansea Bay University Health Board. Logistic regression assessed the relationship between the peripheral and deep margins and histological clearance.

Results

We ran our NLP algorithm on 34,955 BCCs. Out of the 1447 BCCs that met the inclusion criteria, the peripheral margin clearance was not influenced by the BCC risk level (p\u00a0=\u00a00.670). A clinical peripheral margin of 6\u00a0mm achieved a 95% histological clearance rate (95% confidence interval [CI], 0.93-0.98). Tumour thickness inversely affected deep-margin histological clearance (OR 0.720, 95% CI, 0.525-0.991, p\u00a0<\u00a00.05). Depth level 2 had a 97% probability of achieving deep-margin histological clearance across all tumour thicknesses.

Conclusion

Updated RCPath reporting standards minimally impact the peripheral margin histological clearance in BCC. Larger clinical peripheral margins than those indicated by current guidelines may be necessary to achieve excision rates of \u226595%. These findings emphasise the need for continuous reassessment of clinical standards to enhance patient care.", + "laySummary": "", + "urls": "pdf:http://www.jprasurg.com/article/S1748681523006769/pdf; doi:https://doi.org/10.1016/j.bjps.2023.10.106" + }, { "id": "36707908", "doi": "https://doi.org/10.1186/s13643-023-02173-w", @@ -20263,23 +20263,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.ijmedinf.2020.104237" }, - { - "id": "38660106", - "doi": "https://doi.org/10.1016/j.jacasi.2024.02.003", - "title": "Depression and Incident Cardiovascular\u00a0Disease.", - "authorString": "Pennells L, Mascie-Taylor CGN.", - "authorAffiliations": "", - "journalTitle": "JACC. Asia", - "pubYear": "2024", - "date": "2024-04-03", - "isOpenAccess": "Y", - "keywords": "Sex difference; Depression; Cardiovascular disease; epidemiology", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jacasi.2024.02.003; html:https://europepmc.org/articles/PMC11035929; pdf:https://europepmc.org/articles/PMC11035929?pdf=render" - }, { "id": "35642867", "doi": "https://doi.org/10.1111/bjhp.12606", @@ -20297,6 +20280,23 @@ "laySummary": "", "urls": "pdf:https://cronfa.swan.ac.uk/Record/cronfa60128/Download/60128__24479__4d74009536e649b0b17180e2bfd80435.pdf; doi:https://doi.org/10.1111/bjhp.12606; html:https://europepmc.org/articles/PMC9347957; pdf:https://europepmc.org/articles/PMC9347957?pdf=render" }, + { + "id": "38660106", + "doi": "https://doi.org/10.1016/j.jacasi.2024.02.003", + "title": "Depression and Incident Cardiovascular\u00a0Disease.", + "authorString": "Pennells L, Mascie-Taylor CGN.", + "authorAffiliations": "", + "journalTitle": "JACC. Asia", + "pubYear": "2024", + "date": "2024-04-03", + "isOpenAccess": "Y", + "keywords": "Sex difference; Depression; Cardiovascular disease; epidemiology", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.jacasi.2024.02.003; html:https://europepmc.org/articles/PMC11035929; pdf:https://europepmc.org/articles/PMC11035929?pdf=render" + }, { "id": "36501061", "doi": "https://doi.org/10.3390/nu14235031", @@ -20314,23 +20314,6 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/2072-6643/14/23/5031/pdf?version=1669449806; doi:https://doi.org/10.3390/nu14235031; html:https://europepmc.org/articles/PMC9740080; pdf:https://europepmc.org/articles/PMC9740080?pdf=render" }, - { - "id": "34859617", - "doi": "https://doi.org/10.1002/edm2.309", - "title": "The clinical profile and associated mortality in people with and without diabetes with Coronavirus disease 2019 on admission to acute hospital services.", - "authorString": "Gokhale K, Mostafa SA, Wang J, Tahrani AA, Sainsbury CA, Toulis KA, Thomas GN, Hassan-Smith Z, Sapey E, Gallier S, Adderley NJ, Narendran P, Bellary S, Taverner T, Ghosh S, Nirantharakumar K, Hanif W.", - "authorAffiliations": "", - "journalTitle": "Endocrinology, diabetes & metabolism", - "pubYear": "2022", - "date": "2021-12-03", - "isOpenAccess": "Y", - "keywords": "Diabetes; Complications; Covid-19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

To assess if in adults with COVID-19, whether those with diabetes and complications (DM+C) present with a more severe clinical profile and if that relates to increased mortality, compared to those with diabetes with no complications (DM-NC) and those without diabetes.

Methods

Service-level data was used from 996 adults with laboratory confirmed COVID-19 who presented to the Queen Elizabeth Hospital Birmingham, UK, from March to June 2020. All individuals were categorized into DM+C, DM-NC, and non-diabetes groups. Physiological and laboratory measurements in the first 5 days after admission were collated and compared among groups. Cox proportional hazards regression models were used to evaluate associations between diabetes status and the risk of mortality.

Results

Among the 996 individuals, 104 (10.4%) were DM+C, 295 (29.6%) DM-NC and 597 (59.9%) non-diabetes. There were 309 (31.0%) in-hospital deaths documented, 40 (4.0% of total cohort) were DM+C, 99 (9.9%) DM-NC and 170 (17.0%) non-diabetes. Individuals with DM+C were more likely to present with high anion gap/metabolic acidosis, features of renal impairment, and low albumin/lymphocyte count than those with DM-NC or those without diabetes. There was no significant difference in mortality rates among the groups: compared to individuals without diabetes, the adjusted HRs were 1.39 (95% CI 0.95-2.03, p\u00a0=\u00a00.093) and 1.18 (95% CI 0.90-1.54, p\u00a0=\u00a00.226) in DM+C and DM-C, respectively.

Conclusions

Those with COVID-19 and DM+C presented with a more severe clinical and biochemical profile, but this did not associate with increased mortality in this study.", - "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/edm2.309; doi:https://doi.org/10.1002/edm2.309; html:https://europepmc.org/articles/PMC8754243; pdf:https://europepmc.org/articles/PMC8754243?pdf=render" - }, { "id": "32046816", "doi": "https://doi.org/10.2807/1560-7917.es.2020.25.5.2000080", @@ -20348,6 +20331,23 @@ "laySummary": "", "urls": "pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/5/eurosurv-25-5-2.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.5.2000080&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2020.25.5.2000080; html:https://europepmc.org/articles/PMC7014668; pdf:https://europepmc.org/articles/PMC7014668?pdf=render" }, + { + "id": "34859617", + "doi": "https://doi.org/10.1002/edm2.309", + "title": "The clinical profile and associated mortality in people with and without diabetes with Coronavirus disease 2019 on admission to acute hospital services.", + "authorString": "Gokhale K, Mostafa SA, Wang J, Tahrani AA, Sainsbury CA, Toulis KA, Thomas GN, Hassan-Smith Z, Sapey E, Gallier S, Adderley NJ, Narendran P, Bellary S, Taverner T, Ghosh S, Nirantharakumar K, Hanif W.", + "authorAffiliations": "", + "journalTitle": "Endocrinology, diabetes & metabolism", + "pubYear": "2022", + "date": "2021-12-03", + "isOpenAccess": "Y", + "keywords": "Diabetes; Complications; Covid-19", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

To assess if in adults with COVID-19, whether those with diabetes and complications (DM+C) present with a more severe clinical profile and if that relates to increased mortality, compared to those with diabetes with no complications (DM-NC) and those without diabetes.

Methods

Service-level data was used from 996 adults with laboratory confirmed COVID-19 who presented to the Queen Elizabeth Hospital Birmingham, UK, from March to June 2020. All individuals were categorized into DM+C, DM-NC, and non-diabetes groups. Physiological and laboratory measurements in the first 5 days after admission were collated and compared among groups. Cox proportional hazards regression models were used to evaluate associations between diabetes status and the risk of mortality.

Results

Among the 996 individuals, 104 (10.4%) were DM+C, 295 (29.6%) DM-NC and 597 (59.9%) non-diabetes. There were 309 (31.0%) in-hospital deaths documented, 40 (4.0% of total cohort) were DM+C, 99 (9.9%) DM-NC and 170 (17.0%) non-diabetes. Individuals with DM+C were more likely to present with high anion gap/metabolic acidosis, features of renal impairment, and low albumin/lymphocyte count than those with DM-NC or those without diabetes. There was no significant difference in mortality rates among the groups: compared to individuals without diabetes, the adjusted HRs were 1.39 (95% CI 0.95-2.03, p\u00a0=\u00a00.093) and 1.18 (95% CI 0.90-1.54, p\u00a0=\u00a00.226) in DM+C and DM-C, respectively.

Conclusions

Those with COVID-19 and DM+C presented with a more severe clinical and biochemical profile, but this did not associate with increased mortality in this study.", + "laySummary": "", + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/edm2.309; doi:https://doi.org/10.1002/edm2.309; html:https://europepmc.org/articles/PMC8754243; pdf:https://europepmc.org/articles/PMC8754243?pdf=render" + }, { "id": "37309807", "doi": "https://doi.org/10.1093/ehjci/jead123", @@ -20416,23 +20416,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1167/tvst.12.7.3; doi:https://doi.org/10.1167/tvst.12.7.3; html:https://europepmc.org/articles/PMC10324418; pdf:https://europepmc.org/articles/PMC10324418?pdf=render" }, - { - "id": "36991119", - "doi": "https://doi.org/10.1038/s41586-023-05844-9", - "title": "An atlas of genetic scores to predict multi-omic traits.", - "authorString": "Xu Y, Ritchie SC, Liang Y, Timmers PRHJ, Pietzner M, Lannelongue L, Lambert SA, Tahir UA, May-Wilson S, Foguet C, Johansson \u00c5, Surendran P, Nath AP, Persyn E, Peters JE, Oliver-Williams C, Deng S, Prins B, Luan J, Bomba L, Soranzo N, Di Angelantonio E, Pirastu N, Tai ES, van Dam RM, Parkinson H, Davenport EE, Paul DS, Yau C, Gerszten RE, M\u00e4larstig A, Danesh J, Sim X, Langenberg C, Wilson JF, Butterworth AS, Inouye M.", - "authorAffiliations": "", - "journalTitle": "Nature", - "pubYear": "2023", - "date": "2023-03-29", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The use of omic modalities to dissect the molecular underpinnings of common diseases and traits is becoming increasingly common. But multi-omic traits can be genetically predicted, which enables highly cost-effective and powerful analyses for studies that do not have multi-omics1. Here we examine a large cohort (the INTERVAL study2; n\u2009=\u200950,000 participants) with extensive multi-omic data for plasma proteomics (SomaScan, n\u2009=\u20093,175; Olink, n\u2009=\u20094,822), plasma metabolomics (Metabolon HD4, n\u2009=\u20098,153), serum metabolomics (Nightingale, n\u2009=\u200937,359) and whole-blood Illumina RNA sequencing (n\u2009=\u20094,136), and use machine learning to train genetic scores for 17,227 molecular traits, including 10,521 that reach Bonferroni-adjusted significance. We evaluate the performance of genetic scores through external validation across cohorts of individuals of European, Asian and African American ancestries. In addition, we show the utility of these multi-omic genetic scores by quantifying the genetic control of biological pathways and by generating a synthetic multi-omic dataset of the UK Biobank3 to identify disease associations using a phenome-wide scan. We highlight a series of biological insights with regard to genetic mechanisms in metabolism and canonical pathway associations with disease; for example, JAK-STAT signalling and coronary atherosclerosis. Finally, we develop a portal ( https://www.omicspred.org/ ) to facilitate public access to all genetic scores and validation results, as well as to serve as a platform for future extensions and enhancements of multi-omic genetic scores.", - "laySummary": "", - "urls": "pdf:https://www.pure.ed.ac.uk/ws/files/337957796/An_atlas_of_genetic_scores_to_predict_multi_omic_traits_s41586_023_05844_9.pdf; doi:https://doi.org/10.1038/s41586-023-05844-9; html:https://europepmc.org/articles/PMC10323211; pdf:https://europepmc.org/articles/PMC10323211?pdf=render; doi:https://doi.org/10.1038/s41586-023-05844-9" - }, { "id": "31666244", "doi": "https://doi.org/10.1136/archdischild-2019-317271", @@ -20450,6 +20433,23 @@ "laySummary": "", "urls": "pdf:https://adc.bmj.com/content/archdischild/105/3/282.full.pdf; doi:https://doi.org/10.1136/archdischild-2019-317271; html:https://europepmc.org/articles/PMC7041499; pdf:https://europepmc.org/articles/PMC7041499?pdf=render" }, + { + "id": "36991119", + "doi": "https://doi.org/10.1038/s41586-023-05844-9", + "title": "An atlas of genetic scores to predict multi-omic traits.", + "authorString": "Xu Y, Ritchie SC, Liang Y, Timmers PRHJ, Pietzner M, Lannelongue L, Lambert SA, Tahir UA, May-Wilson S, Foguet C, Johansson \u00c5, Surendran P, Nath AP, Persyn E, Peters JE, Oliver-Williams C, Deng S, Prins B, Luan J, Bomba L, Soranzo N, Di Angelantonio E, Pirastu N, Tai ES, van Dam RM, Parkinson H, Davenport EE, Paul DS, Yau C, Gerszten RE, M\u00e4larstig A, Danesh J, Sim X, Langenberg C, Wilson JF, Butterworth AS, Inouye M.", + "authorAffiliations": "", + "journalTitle": "Nature", + "pubYear": "2023", + "date": "2023-03-29", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The use of omic modalities to dissect the molecular underpinnings of common diseases and traits is becoming increasingly common. But multi-omic traits can be genetically predicted, which enables highly cost-effective and powerful analyses for studies that do not have multi-omics1. Here we examine a large cohort (the INTERVAL study2; n\u2009=\u200950,000 participants) with extensive multi-omic data for plasma proteomics (SomaScan, n\u2009=\u20093,175; Olink, n\u2009=\u20094,822), plasma metabolomics (Metabolon HD4, n\u2009=\u20098,153), serum metabolomics (Nightingale, n\u2009=\u200937,359) and whole-blood Illumina RNA sequencing (n\u2009=\u20094,136), and use machine learning to train genetic scores for 17,227 molecular traits, including 10,521 that reach Bonferroni-adjusted significance. We evaluate the performance of genetic scores through external validation across cohorts of individuals of European, Asian and African American ancestries. In addition, we show the utility of these multi-omic genetic scores by quantifying the genetic control of biological pathways and by generating a synthetic multi-omic dataset of the UK Biobank3 to identify disease associations using a phenome-wide scan. We highlight a series of biological insights with regard to genetic mechanisms in metabolism and canonical pathway associations with disease; for example, JAK-STAT signalling and coronary atherosclerosis. Finally, we develop a portal ( https://www.omicspred.org/ ) to facilitate public access to all genetic scores and validation results, as well as to serve as a platform for future extensions and enhancements of multi-omic genetic scores.", + "laySummary": "", + "urls": "pdf:https://www.pure.ed.ac.uk/ws/files/337957796/An_atlas_of_genetic_scores_to_predict_multi_omic_traits_s41586_023_05844_9.pdf; doi:https://doi.org/10.1038/s41586-023-05844-9; html:https://europepmc.org/articles/PMC10323211; pdf:https://europepmc.org/articles/PMC10323211?pdf=render; doi:https://doi.org/10.1038/s41586-023-05844-9" + }, { "id": "36426221", "doi": "https://doi.org/10.3389/fcvm.2022.1016032", @@ -20501,23 +20501,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41467-022-35321-2.pdf; doi:https://doi.org/10.1038/s41467-022-35321-2; html:https://europepmc.org/articles/PMC9772225; pdf:https://europepmc.org/articles/PMC9772225?pdf=render" }, - { - "id": "38526449", - "doi": "https://doi.org/10.1002/clt2.12348", - "title": "Ethnic differences in depression and anxiety among adults with atopic eczema: Population-based matched cohort studies within UK primary care.", - "authorString": "Adesanya EI, Henderson A, Hayes JF, Lewin A, Mathur R, Mulick A, Morton C, Smith C, Langan SM, Mansfield KE.", - "authorAffiliations": "", - "journalTitle": "Clinical and translational allergy", - "pubYear": "2024", - "date": "2024-03-01", - "isOpenAccess": "Y", - "keywords": "Depression; Anxiety; epidemiology; Atopic Eczema; Ethnicity", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Evidence demonstrates that individuals with atopic eczema (eczema) have increased depression and anxiety; however, the role of ethnicity in these associations is poorly understood. We aimed to investigate whether associations between eczema and depression or anxiety differed between adults from white and minority ethnic groups in the UK.

Methods

We used UK Clinical Practice Research Datalink GOLD to conduct matched cohort studies of adults (\u226518\u00a0years) with ethnicity recorded in primary care electronic health records (April 2006-January 2020). We matched (age, sex, practice) adults with eczema to up to five adults without. We used stratified Cox regression with an interaction between eczema and ethnicity, to estimate hazard ratios (HRs) for associations between eczema and incident depression and anxiety in individuals from white ethnic groups and a pooled minority ethnic group (adults from Black, South Asian, Mixed and Other groups).

Results

We identified separate cohorts for depression (215,073 with eczema matched to 646,539 without) and anxiety (242,598 with eczema matched to 774,113 without). After adjusting for matching variables and potential confounders (age, sex, practice, deprivation, calendar period), we found strong evidence (p\u00a0<\u00a00.01) of ethnic differences in associations between eczema and depression (minority ethnic groups: HR\u00a0=\u00a01.33, 95% CI\u00a0=\u00a01.22,1.45; white ethnic groups: HR\u00a0=\u00a01.15, 95% CI\u00a0=\u00a01.12,1.17) and anxiety (minority ethnic groups: HR\u00a0=\u00a01.41, 95% CI\u00a0=\u00a01.28,1.55; white ethnic groups: HR\u00a0=\u00a01.17, 95% CI\u00a0=\u00a01.14,1.19).

Conclusions

Adults with eczema from minority ethnic groups appear to be at increased depression and anxiety risk compared with their white counterparts. Culturally adapted mental health promotion and prevention strategies should be considered in individuals with eczema from minority ethnic groups.", - "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/clt2.12348; doi:https://doi.org/10.1002/clt2.12348; html:https://europepmc.org/articles/PMC10962487; pdf:https://europepmc.org/articles/PMC10962487?pdf=render" - }, { "id": "31529485", "doi": "https://doi.org/10.1111/bjd.18526", @@ -20552,6 +20535,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/bjd.18889; doi:https://doi.org/10.1111/bjd.18889; html:https://europepmc.org/articles/PMC7587014; pdf:https://europepmc.org/articles/PMC7587014?pdf=render" }, + { + "id": "38526449", + "doi": "https://doi.org/10.1002/clt2.12348", + "title": "Ethnic differences in depression and anxiety among adults with atopic eczema: Population-based matched cohort studies within UK primary care.", + "authorString": "Adesanya EI, Henderson A, Hayes JF, Lewin A, Mathur R, Mulick A, Morton C, Smith C, Langan SM, Mansfield KE.", + "authorAffiliations": "", + "journalTitle": "Clinical and translational allergy", + "pubYear": "2024", + "date": "2024-03-01", + "isOpenAccess": "Y", + "keywords": "Depression; Anxiety; epidemiology; Atopic Eczema; Ethnicity", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Evidence demonstrates that individuals with atopic eczema (eczema) have increased depression and anxiety; however, the role of ethnicity in these associations is poorly understood. We aimed to investigate whether associations between eczema and depression or anxiety differed between adults from white and minority ethnic groups in the UK.

Methods

We used UK Clinical Practice Research Datalink GOLD to conduct matched cohort studies of adults (\u226518\u00a0years) with ethnicity recorded in primary care electronic health records (April 2006-January 2020). We matched (age, sex, practice) adults with eczema to up to five adults without. We used stratified Cox regression with an interaction between eczema and ethnicity, to estimate hazard ratios (HRs) for associations between eczema and incident depression and anxiety in individuals from white ethnic groups and a pooled minority ethnic group (adults from Black, South Asian, Mixed and Other groups).

Results

We identified separate cohorts for depression (215,073 with eczema matched to 646,539 without) and anxiety (242,598 with eczema matched to 774,113 without). After adjusting for matching variables and potential confounders (age, sex, practice, deprivation, calendar period), we found strong evidence (p\u00a0<\u00a00.01) of ethnic differences in associations between eczema and depression (minority ethnic groups: HR\u00a0=\u00a01.33, 95% CI\u00a0=\u00a01.22,1.45; white ethnic groups: HR\u00a0=\u00a01.15, 95% CI\u00a0=\u00a01.12,1.17) and anxiety (minority ethnic groups: HR\u00a0=\u00a01.41, 95% CI\u00a0=\u00a01.28,1.55; white ethnic groups: HR\u00a0=\u00a01.17, 95% CI\u00a0=\u00a01.14,1.19).

Conclusions

Adults with eczema from minority ethnic groups appear to be at increased depression and anxiety risk compared with their white counterparts. Culturally adapted mental health promotion and prevention strategies should be considered in individuals with eczema from minority ethnic groups.", + "laySummary": "", + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/clt2.12348; doi:https://doi.org/10.1002/clt2.12348; html:https://europepmc.org/articles/PMC10962487; pdf:https://europepmc.org/articles/PMC10962487?pdf=render" + }, { "id": "31504435", "doi": "https://doi.org/10.1093/eurheartj/ehz569", @@ -20620,23 +20620,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1183/20734735.0058-2023; html:https://europepmc.org/articles/PMC10461733; pdf:https://europepmc.org/articles/PMC10461733?pdf=render" }, - { - "id": "38355192", - "doi": "https://doi.org/10.1136/bmjopen-2023-080678", - "title": "How far back do we need to look to capture diagnoses in electronic health records? A retrospective observational study of hospital electronic health record data.", - "authorString": "Lewis J, Evison F, Doal R, Field J, Gallier S, Harris S, le Roux P, Osman M, Plummer C, Sapey E, Singer M, Sayer AA, Witham MD, ADMISSION Research Collaborative.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2024", - "date": "2024-02-13", - "isOpenAccess": "Y", - "keywords": "Hospitals; Electronic Health Records; Information Extraction", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

Analysis of routinely collected electronic health data is a key tool for long-term condition research and practice for hospitalised patients. This requires accurate and complete ascertainment of a broad range of diagnoses, something not always recorded on an admission document at a single point in time. This study aimed to ascertain how far back in time electronic hospital records need to be interrogated to capture long-term condition diagnoses.

Design

Retrospective observational study of routinely collected hospital electronic health record data.

Setting

Queen Elizabeth Hospital Birmingham (UK)-linked data held by the PIONEER acute care data hub.

Participants

Patients whose first recorded admission for chronic obstructive pulmonary disease (COPD) exacerbation (n=560) or acute stroke (n=2142) was between January and December 2018 and who had a minimum of 10 years of data prior to the index date.

Outcome measures

We identified the most common International Classification of Diseases version 10-coded diagnoses received by patients with COPD and acute stroke separately. For each diagnosis, we derived the number of patients with the diagnosis recorded at least once over the full 10-year lookback period, and then compared this with shorter lookback periods from 1 year to 9 years prior to the index admission.

Results

Seven of the top 10 most common diagnoses in the COPD dataset reached >90% completeness by 6 years of lookback. Atrial fibrillation and diabetes were >90% coded with 2-3 years of lookback, but hypertension and asthma completeness continued to rise all the way out to 10 years of lookback. For stroke, 4 of the top 10 reached 90% completeness by 5 years of lookback; angina pectoris was >90% coded at 7 years and previous transient ischaemic attack completeness continued to rise out to 10 years of lookback.

Conclusion

A 7-year lookback captures most, but not all, common diagnoses. Lookback duration should be tailored to the conditions being studied.", - "laySummary": "", - "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/14/2/e080678.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-080678; html:https://europepmc.org/articles/PMC10868273; pdf:https://europepmc.org/articles/PMC10868273?pdf=render" - }, { "id": "35589356", "doi": "https://doi.org/10.1136/bmjopen-2021-057343", @@ -20671,6 +20654,23 @@ "laySummary": "", "urls": "pdf:https://bmjopenrespres.bmj.com/content/bmjresp/8/1/e000967.full.pdf; doi:https://doi.org/10.1136/bmjresp-2021-000967; html:https://europepmc.org/articles/PMC8261886; pdf:https://europepmc.org/articles/PMC8261886?pdf=render" }, + { + "id": "38355192", + "doi": "https://doi.org/10.1136/bmjopen-2023-080678", + "title": "How far back do we need to look to capture diagnoses in electronic health records? A retrospective observational study of hospital electronic health record data.", + "authorString": "Lewis J, Evison F, Doal R, Field J, Gallier S, Harris S, le Roux P, Osman M, Plummer C, Sapey E, Singer M, Sayer AA, Witham MD, ADMISSION Research Collaborative.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2024", + "date": "2024-02-13", + "isOpenAccess": "Y", + "keywords": "Hospitals; Electronic Health Records; Information Extraction", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

Analysis of routinely collected electronic health data is a key tool for long-term condition research and practice for hospitalised patients. This requires accurate and complete ascertainment of a broad range of diagnoses, something not always recorded on an admission document at a single point in time. This study aimed to ascertain how far back in time electronic hospital records need to be interrogated to capture long-term condition diagnoses.

Design

Retrospective observational study of routinely collected hospital electronic health record data.

Setting

Queen Elizabeth Hospital Birmingham (UK)-linked data held by the PIONEER acute care data hub.

Participants

Patients whose first recorded admission for chronic obstructive pulmonary disease (COPD) exacerbation (n=560) or acute stroke (n=2142) was between January and December 2018 and who had a minimum of 10 years of data prior to the index date.

Outcome measures

We identified the most common International Classification of Diseases version 10-coded diagnoses received by patients with COPD and acute stroke separately. For each diagnosis, we derived the number of patients with the diagnosis recorded at least once over the full 10-year lookback period, and then compared this with shorter lookback periods from 1 year to 9 years prior to the index admission.

Results

Seven of the top 10 most common diagnoses in the COPD dataset reached >90% completeness by 6 years of lookback. Atrial fibrillation and diabetes were >90% coded with 2-3 years of lookback, but hypertension and asthma completeness continued to rise all the way out to 10 years of lookback. For stroke, 4 of the top 10 reached 90% completeness by 5 years of lookback; angina pectoris was >90% coded at 7 years and previous transient ischaemic attack completeness continued to rise out to 10 years of lookback.

Conclusion

A 7-year lookback captures most, but not all, common diagnoses. Lookback duration should be tailored to the conditions being studied.", + "laySummary": "", + "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/14/2/e080678.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-080678; html:https://europepmc.org/articles/PMC10868273; pdf:https://europepmc.org/articles/PMC10868273?pdf=render" + }, { "id": "37532769", "doi": "https://doi.org/10.1038/s42003-023-05171-9", @@ -20739,6 +20739,23 @@ "laySummary": "", "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s12471-022-01677-9.pdf; doi:https://doi.org/10.1007/s12471-022-01677-9; html:https://europepmc.org/articles/PMC8906525; pdf:https://europepmc.org/articles/PMC8906525?pdf=render" }, + { + "id": "33168126", + "doi": "https://doi.org/10.1192/bjo.2020.42", + "title": "Impact of schizophrenia genetic liability on the association between schizophrenia and physical illness: data-linkage study.", + "authorString": "Kendall KM, John A, Lee SC, Rees E, Pardi\u00f1as AF, Banos MDP, Owen MJ, O'Donovan MC, Kirov G, Lloyd K, Jones I, Legge SE, Walters JTR.", + "authorAffiliations": "", + "journalTitle": "BJPsych open", + "pubYear": "2020", + "date": "2020-11-10", + "isOpenAccess": "Y", + "keywords": "Genetics; Schizophrenia; Physical Health; Psychotic Disorders", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Individuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia.

Aims

To link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records. To assess (a) rates of physical illness in those with schizophrenia, and (b) whether physical illness in schizophrenia is associated with genetic liability.

Method

We linked genetic data from a clinically ascertained sample of individuals with schizophrenia (Cardiff Cognition in Schizophrenia participants, n = 896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (a) rare copy number variants (CNVs), and (b) polygenic risk scores.

Results

Individuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR) = 5.34), intellectual disability (SRR = 3.11), type 2 diabetes (SRR = 2.45), congenital disorders (SRR = 1.77), ischaemic heart disease (SRR = 1.57) and smoking (SRR = 1.44) in comparison with the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorder-associated CNVs was associated with height (P = 0.015-0.017), with carriers being 7.5-7.7 cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia were associated with genetic liability for the disorder.

Conclusions

This study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased risk for physical illness in schizophrenia is not caused by genetic liability for the disorder.", + "laySummary": "", + "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/A00360A347FCC91E2E9D0B39FBDCE887/S2056472420000423a.pdf/div-class-title-impact-of-schizophrenia-genetic-liability-on-the-association-between-schizophrenia-and-physical-illness-data-linkage-study-div.pdf; doi:https://doi.org/10.1192/bjo.2020.42; html:https://europepmc.org/articles/PMC7745237; pdf:https://europepmc.org/articles/PMC7745237?pdf=render" + }, { "id": "38643104", "doi": "https://doi.org/10.1186/s12891-024-07446-6", @@ -20773,23 +20790,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1097/TA.0000000000003592" }, - { - "id": "33168126", - "doi": "https://doi.org/10.1192/bjo.2020.42", - "title": "Impact of schizophrenia genetic liability on the association between schizophrenia and physical illness: data-linkage study.", - "authorString": "Kendall KM, John A, Lee SC, Rees E, Pardi\u00f1as AF, Banos MDP, Owen MJ, O'Donovan MC, Kirov G, Lloyd K, Jones I, Legge SE, Walters JTR.", - "authorAffiliations": "", - "journalTitle": "BJPsych open", - "pubYear": "2020", - "date": "2020-11-10", - "isOpenAccess": "Y", - "keywords": "Genetics; Schizophrenia; Physical Health; Psychotic Disorders", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Individuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia.

Aims

To link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records. To assess (a) rates of physical illness in those with schizophrenia, and (b) whether physical illness in schizophrenia is associated with genetic liability.

Method

We linked genetic data from a clinically ascertained sample of individuals with schizophrenia (Cardiff Cognition in Schizophrenia participants, n = 896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (a) rare copy number variants (CNVs), and (b) polygenic risk scores.

Results

Individuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR) = 5.34), intellectual disability (SRR = 3.11), type 2 diabetes (SRR = 2.45), congenital disorders (SRR = 1.77), ischaemic heart disease (SRR = 1.57) and smoking (SRR = 1.44) in comparison with the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorder-associated CNVs was associated with height (P = 0.015-0.017), with carriers being 7.5-7.7 cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia were associated with genetic liability for the disorder.

Conclusions

This study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased risk for physical illness in schizophrenia is not caused by genetic liability for the disorder.", - "laySummary": "", - "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/A00360A347FCC91E2E9D0B39FBDCE887/S2056472420000423a.pdf/div-class-title-impact-of-schizophrenia-genetic-liability-on-the-association-between-schizophrenia-and-physical-illness-data-linkage-study-div.pdf; doi:https://doi.org/10.1192/bjo.2020.42; html:https://europepmc.org/articles/PMC7745237; pdf:https://europepmc.org/articles/PMC7745237?pdf=render" - }, { "id": "37516479", "doi": "https://doi.org/10.1016/s2468-2667(23)00126-3", @@ -21062,23 +21062,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.12688/wellcomeopenres.15786.1; html:https://europepmc.org/articles/PMC7255910; pdf:https://europepmc.org/articles/PMC7255910?pdf=render" }, - { - "id": "34304048", - "doi": "https://doi.org/10.1016/j.ebiom.2021.103485", - "title": "Shorter leukocyte telomere length is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank.", - "authorString": "Wang Q, Codd V, Raisi-Estabragh Z, Musicha C, Bountziouka V, Kaptoge S, Allara E, Angelantonio ED, Butterworth AS, Wood AM, Thompson JR, Petersen SE, Harvey NC, Danesh JN, Samani NJ, Nelson CP.", - "authorAffiliations": "", - "journalTitle": "EBioMedicine", - "pubYear": "2021", - "date": "2021-07-23", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Background Older age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain whether leucocyte telomere length (LTL), previously proposed as a marker of biological age, is also associated with COVID-19 outcomes. Methods We associated LTL values obtained from participants recruited into UK Biobank (UKB) during 2006-2010 with adverse COVID-19 outcomes recorded by 30 November 2020, defined as a composite of any of the following: hospital admission, need for critical care, respiratory support, or mortality. Using information on 130 LTL-associated genetic variants, we conducted exploratory Mendelian randomisation (MR) analyses in UKB to evaluate whether observational associations might reflect cause-and-effect relationships. Findings Of 6775 participants in UKB who tested positive for infection with SARS-CoV-2 in the community, there were 914 (13.5%) with adverse COVID-19 outcomes. The odds ratio (OR) for adverse COVID-19 outcomes was 1\u00b717 (95% CI 1\u00b705-1\u00b730; P\u00a0=\u00a00\u00b7004) per 1-SD shorter usual LTL, after adjustment for age, sex and ethnicity. Similar ORs were observed in analyses that: adjusted for additional risk factors; disaggregated the composite outcome and reduced the scope for selection or collider bias. In MR analyses, the OR for adverse COVID-19 outcomes was directionally concordant but non-significant. Interpretation Shorter LTL is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including age. Further data are needed to determine whether this association reflects causality. Funding UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation.", - "laySummary": "", - "urls": "pdf:http://www.thelancet.com/article/S2352396421002784/pdf; doi:https://doi.org/10.1016/j.ebiom.2021.103485; html:https://europepmc.org/articles/PMC8299112; pdf:https://europepmc.org/articles/PMC8299112?pdf=render" - }, { "id": "30969971", "doi": "https://doi.org/10.1371/journal.pone.0213435", @@ -21096,6 +21079,23 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0213435&type=printable; doi:https://doi.org/10.1371/journal.pone.0213435; html:https://europepmc.org/articles/PMC6457613; pdf:https://europepmc.org/articles/PMC6457613?pdf=render" }, + { + "id": "34304048", + "doi": "https://doi.org/10.1016/j.ebiom.2021.103485", + "title": "Shorter leukocyte telomere length is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank.", + "authorString": "Wang Q, Codd V, Raisi-Estabragh Z, Musicha C, Bountziouka V, Kaptoge S, Allara E, Angelantonio ED, Butterworth AS, Wood AM, Thompson JR, Petersen SE, Harvey NC, Danesh JN, Samani NJ, Nelson CP.", + "authorAffiliations": "", + "journalTitle": "EBioMedicine", + "pubYear": "2021", + "date": "2021-07-23", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Background Older age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain whether leucocyte telomere length (LTL), previously proposed as a marker of biological age, is also associated with COVID-19 outcomes. Methods We associated LTL values obtained from participants recruited into UK Biobank (UKB) during 2006-2010 with adverse COVID-19 outcomes recorded by 30 November 2020, defined as a composite of any of the following: hospital admission, need for critical care, respiratory support, or mortality. Using information on 130 LTL-associated genetic variants, we conducted exploratory Mendelian randomisation (MR) analyses in UKB to evaluate whether observational associations might reflect cause-and-effect relationships. Findings Of 6775 participants in UKB who tested positive for infection with SARS-CoV-2 in the community, there were 914 (13.5%) with adverse COVID-19 outcomes. The odds ratio (OR) for adverse COVID-19 outcomes was 1\u00b717 (95% CI 1\u00b705-1\u00b730; P\u00a0=\u00a00\u00b7004) per 1-SD shorter usual LTL, after adjustment for age, sex and ethnicity. Similar ORs were observed in analyses that: adjusted for additional risk factors; disaggregated the composite outcome and reduced the scope for selection or collider bias. In MR analyses, the OR for adverse COVID-19 outcomes was directionally concordant but non-significant. Interpretation Shorter LTL is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including age. Further data are needed to determine whether this association reflects causality. Funding UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation.", + "laySummary": "", + "urls": "pdf:http://www.thelancet.com/article/S2352396421002784/pdf; doi:https://doi.org/10.1016/j.ebiom.2021.103485; html:https://europepmc.org/articles/PMC8299112; pdf:https://europepmc.org/articles/PMC8299112?pdf=render" + }, { "id": "32249120", "doi": "https://doi.org/10.1016/j.schres.2020.03.044", @@ -21147,23 +21147,6 @@ "laySummary": "", "urls": "pdf:https://www.karger.com/Article/Pdf/520674; doi:https://doi.org/10.1159/000520674; html:https://europepmc.org/articles/PMC8985014; doi:https://doi.org/10.1159/000520674" }, - { - "id": "38346686", - "doi": "https://doi.org/10.1093/ageing/afae004", - "title": "The impact of digital technology in care homes on unplanned secondary care usage and associated costs.", - "authorString": "Garner A, Lewis J, Dixon S, Preston N, Caiado CCS, Hanratty B, Jones M, Knight J, Mason SM.", - "authorAffiliations": "", - "journalTitle": "Age and ageing", - "pubYear": "2024", - "date": "2024-02-01", - "isOpenAccess": "Y", - "keywords": "Older People; Emergency Medicine; Care Homes; Long-term Care; Telehealth; Routinely Collected Data", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

A substantial number of Emergency Department (ED) attendances by care home residents are potentially avoidable. Health Call Digital Care Homes is an app-based technology that aims to streamline residents' care by recording their observations such as vital parameters electronically. Observations are triaged by remote clinical staff. This study assessed the effectiveness of the Health Call technology to reduce unplanned secondary care usage and associated costs.

Methods

A retrospective analysis of health outcomes and economic impact based on an intervention. The study involved 118 care homes across the North East of UK from 2018 to 2021. Routinely collected NHS secondary care data from County Durham and Darlington NHS Foundation Trust was linked with data from the Health Call app. Three outcomes were modelled monthly using Generalised Linear Mixed Models: counts of emergency attendances, emergency admissions and length of stay of emergency admissions. A similar approach was taken for costs. The impact of Health Call was tested on each outcome using the models.

Findings

Data from 8,702 residents were used in the analysis. Results show Health Call reduces the number of emergency attendances by 11% [6-15%], emergency admissions by 25% [20-39%] and length of stay by 11% [3-18%] (with an additional month-by-month decrease of 28% [24-34%]). The cost analysis found a cost reduction of \u00a357 per resident in 2018, increasing to \u00a3113 in 2021.

Interpretation

The introduction of a digital technology, such as Health Call, could significantly reduce contacts with and costs resulting from unplanned secondary care usage by care home residents.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/ageing/article-pdf/53/2/afae004/56661196/afae004.pdf; doi:https://doi.org/10.1093/ageing/afae004; html:https://europepmc.org/articles/PMC10861323; pdf:https://europepmc.org/articles/PMC10861323?pdf=render" - }, { "id": "37389932", "doi": "https://doi.org/10.2196/44126", @@ -21182,21 +21165,21 @@ "urls": "pdf:https://formative.jmir.org/2023/1/e44126/PDF; doi:https://doi.org/10.2196/44126; html:https://europepmc.org/articles/PMC10365629; pdf:https://europepmc.org/articles/PMC10365629?pdf=render" }, { - "id": "35471746", - "doi": "https://doi.org/10.1186/s13613-022-01011-x", - "title": "The resilient intensive care unit.", - "authorString": "Salluh JIF, Kurtz P, Bastos LSL, Quintairos A, Zampieri FG, Bozza FA.", + "id": "38346686", + "doi": "https://doi.org/10.1093/ageing/afae004", + "title": "The impact of digital technology in care homes on unplanned secondary care usage and associated costs.", + "authorString": "Garner A, Lewis J, Dixon S, Preston N, Caiado CCS, Hanratty B, Jones M, Knight J, Mason SM.", "authorAffiliations": "", - "journalTitle": "Annals of intensive care", - "pubYear": "2022", - "date": "2022-04-26", + "journalTitle": "Age and ageing", + "pubYear": "2024", + "date": "2024-02-01", "isOpenAccess": "Y", - "keywords": "", + "keywords": "Older People; Emergency Medicine; Care Homes; Long-term Care; Telehealth; Routinely Collected Data", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

The COVID-19 pandemic tested the capacity of intensive care units (ICU) to respond to a crisis and demonstrated their fragility. Unsurprisingly, higher than usual mortality rates, lengths of stay (LOS), and ICU-acquired complications occurred during the pandemic. However, worse outcomes were not universal nor constant across ICUs and significant variation in outcomes was reported, demonstrating that some ICUs could adequately manage the surge of COVID-19.

Methods

In the present editorial, we discuss the concept of a resilient Intensive Care Unit, including which metrics can be used to address the capacity to respond, sustain results and incorporate new practices that lead to improvement.

Results

We believe that a resiliency analysis adds a component of preparedness to the usual ICU performance evaluation and outcomes metrics to be used during the crisis and in regular times.

Conclusions

The COVID-19 pandemic demonstrated the need for a resilient health system. Although this concept has been discussed for health systems, it was not tested in intensive care. Future studies should evaluate this concept to improve ICU organization for standard and pandemic times.", + "abstract": "

Background

A substantial number of Emergency Department (ED) attendances by care home residents are potentially avoidable. Health Call Digital Care Homes is an app-based technology that aims to streamline residents' care by recording their observations such as vital parameters electronically. Observations are triaged by remote clinical staff. This study assessed the effectiveness of the Health Call technology to reduce unplanned secondary care usage and associated costs.

Methods

A retrospective analysis of health outcomes and economic impact based on an intervention. The study involved 118 care homes across the North East of UK from 2018 to 2021. Routinely collected NHS secondary care data from County Durham and Darlington NHS Foundation Trust was linked with data from the Health Call app. Three outcomes were modelled monthly using Generalised Linear Mixed Models: counts of emergency attendances, emergency admissions and length of stay of emergency admissions. A similar approach was taken for costs. The impact of Health Call was tested on each outcome using the models.

Findings

Data from 8,702 residents were used in the analysis. Results show Health Call reduces the number of emergency attendances by 11% [6-15%], emergency admissions by 25% [20-39%] and length of stay by 11% [3-18%] (with an additional month-by-month decrease of 28% [24-34%]). The cost analysis found a cost reduction of \u00a357 per resident in 2018, increasing to \u00a3113 in 2021.

Interpretation

The introduction of a digital technology, such as Health Call, could significantly reduce contacts with and costs resulting from unplanned secondary care usage by care home residents.", "laySummary": "", - "urls": "pdf:https://annalsofintensivecare.springeropen.com/track/pdf/10.1186/s13613-022-01011-x; doi:https://doi.org/10.1186/s13613-022-01011-x; html:https://europepmc.org/articles/PMC9038989; pdf:https://europepmc.org/articles/PMC9038989?pdf=render" + "urls": "pdf:https://academic.oup.com/ageing/article-pdf/53/2/afae004/56661196/afae004.pdf; doi:https://doi.org/10.1093/ageing/afae004; html:https://europepmc.org/articles/PMC10861323; pdf:https://europepmc.org/articles/PMC10861323?pdf=render" }, { "id": "29457906", @@ -21215,6 +21198,23 @@ "laySummary": "", "urls": "pdf:https://pubs.acs.org/doi/pdf/10.1021/acs.jproteome.7b00879; doi:https://doi.org/10.1021/acs.jproteome.7b00879; html:https://europepmc.org/articles/PMC5891819; pdf:https://europepmc.org/articles/PMC5891819?pdf=render" }, + { + "id": "35471746", + "doi": "https://doi.org/10.1186/s13613-022-01011-x", + "title": "The resilient intensive care unit.", + "authorString": "Salluh JIF, Kurtz P, Bastos LSL, Quintairos A, Zampieri FG, Bozza FA.", + "authorAffiliations": "", + "journalTitle": "Annals of intensive care", + "pubYear": "2022", + "date": "2022-04-26", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

The COVID-19 pandemic tested the capacity of intensive care units (ICU) to respond to a crisis and demonstrated their fragility. Unsurprisingly, higher than usual mortality rates, lengths of stay (LOS), and ICU-acquired complications occurred during the pandemic. However, worse outcomes were not universal nor constant across ICUs and significant variation in outcomes was reported, demonstrating that some ICUs could adequately manage the surge of COVID-19.

Methods

In the present editorial, we discuss the concept of a resilient Intensive Care Unit, including which metrics can be used to address the capacity to respond, sustain results and incorporate new practices that lead to improvement.

Results

We believe that a resiliency analysis adds a component of preparedness to the usual ICU performance evaluation and outcomes metrics to be used during the crisis and in regular times.

Conclusions

The COVID-19 pandemic demonstrated the need for a resilient health system. Although this concept has been discussed for health systems, it was not tested in intensive care. Future studies should evaluate this concept to improve ICU organization for standard and pandemic times.", + "laySummary": "", + "urls": "pdf:https://annalsofintensivecare.springeropen.com/track/pdf/10.1186/s13613-022-01011-x; doi:https://doi.org/10.1186/s13613-022-01011-x; html:https://europepmc.org/articles/PMC9038989; pdf:https://europepmc.org/articles/PMC9038989?pdf=render" + }, { "id": "35487738", "doi": "https://doi.org/10.1136/bmjopen-2021-057017", @@ -21232,23 +21232,6 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057017.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057017; html:https://europepmc.org/articles/PMC9058768; pdf:https://europepmc.org/articles/PMC9058768?pdf=render" }, - { - "id": "38388919", - "doi": "https://doi.org/10.1186/s12913-024-10716-7", - "title": "Spatio-temporal modelling of referrals to outpatient respiratory clinics in the integrated care system of the Morecambe Bay area, England.", - "authorString": "Mountain R, Knight J, Heys K, Giorgi E, Gatheral T.", - "authorAffiliations": "", - "journalTitle": "BMC health services research", - "pubYear": "2024", - "date": "2024-02-22", - "isOpenAccess": "Y", - "keywords": "Spatio-temporal; Integrated Care; Chronic Respiratory Disease; Routinely Collected Data; Outpatient Referrals", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Promoting integrated care is a key goal of the NHS Long Term Plan to improve population respiratory health, yet there is limited data-driven evidence of its effectiveness. The Morecambe Bay Respiratory Network is an integrated care initiative operating in the North-West of England since 2017. A key target area has been reducing referrals to outpatient respiratory clinics by upskilling primary care teams. This study aims to explore space-time patterns in referrals from general practice in the Morecambe Bay area to evaluate the impact of the initiative.

Methods

Data on referrals to outpatient clinics and chronic respiratory disease patient counts between 2012-2020 were obtained from the Morecambe Bay Community Data Warehouse, a large store of routinely collected healthcare data. For analysis, the data is aggregated by year and small area geography. The methodology comprises of two parts. The first explores the issues that can arise when using routinely collected primary care data for space-time analysis and applies spatio-temporal conditional autoregressive modelling to adjust for data complexities. The second part models the rate of outpatient referral via a Poisson generalised linear mixed model that adjusts for changes in demographic factors and number of respiratory disease patients.

Results

The first year of the Morecambe Bay Respiratory Network was not associated with a significant difference in referral rate. However, the second and third years saw significant reductions in areas that had received intervention, with full intervention associated with a 31.8% (95% CI 17.0-43.9) and 40.5% (95% CI 27.5-50.9) decrease in referral rate in 2018 and 2019, respectively.

Conclusions

Routinely collected data can be used to robustly evaluate key outcome measures of integrated care. The results demonstrate that effective integrated care has real potential to ease the burden on respiratory outpatient services by reducing the need for an onward referral. This is of great relevance given the current pressure on outpatient services globally, particularly long waiting lists following the COVID-19 pandemic and the need for more innovative models of care.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s12913-024-10716-7; html:https://europepmc.org/articles/PMC10882730; pdf:https://europepmc.org/articles/PMC10882730?pdf=render" - }, { "id": "34459398", "doi": "https://doi.org/10.3233/jad-210462", @@ -21266,6 +21249,23 @@ "laySummary": "", "urls": "pdf:https://content.iospress.com:443/download/journal-of-alzheimers-disease/jad210462?id=journal-of-alzheimers-disease%2Fjad210462; doi:https://doi.org/10.3233/JAD-210462; html:https://europepmc.org/articles/PMC8609677; pdf:https://europepmc.org/articles/PMC8609677?pdf=render" }, + { + "id": "38388919", + "doi": "https://doi.org/10.1186/s12913-024-10716-7", + "title": "Spatio-temporal modelling of referrals to outpatient respiratory clinics in the integrated care system of the Morecambe Bay area, England.", + "authorString": "Mountain R, Knight J, Heys K, Giorgi E, Gatheral T.", + "authorAffiliations": "", + "journalTitle": "BMC health services research", + "pubYear": "2024", + "date": "2024-02-22", + "isOpenAccess": "Y", + "keywords": "Spatio-temporal; Integrated Care; Chronic Respiratory Disease; Routinely Collected Data; Outpatient Referrals", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Promoting integrated care is a key goal of the NHS Long Term Plan to improve population respiratory health, yet there is limited data-driven evidence of its effectiveness. The Morecambe Bay Respiratory Network is an integrated care initiative operating in the North-West of England since 2017. A key target area has been reducing referrals to outpatient respiratory clinics by upskilling primary care teams. This study aims to explore space-time patterns in referrals from general practice in the Morecambe Bay area to evaluate the impact of the initiative.

Methods

Data on referrals to outpatient clinics and chronic respiratory disease patient counts between 2012-2020 were obtained from the Morecambe Bay Community Data Warehouse, a large store of routinely collected healthcare data. For analysis, the data is aggregated by year and small area geography. The methodology comprises of two parts. The first explores the issues that can arise when using routinely collected primary care data for space-time analysis and applies spatio-temporal conditional autoregressive modelling to adjust for data complexities. The second part models the rate of outpatient referral via a Poisson generalised linear mixed model that adjusts for changes in demographic factors and number of respiratory disease patients.

Results

The first year of the Morecambe Bay Respiratory Network was not associated with a significant difference in referral rate. However, the second and third years saw significant reductions in areas that had received intervention, with full intervention associated with a 31.8% (95% CI 17.0-43.9) and 40.5% (95% CI 27.5-50.9) decrease in referral rate in 2018 and 2019, respectively.

Conclusions

Routinely collected data can be used to robustly evaluate key outcome measures of integrated care. The results demonstrate that effective integrated care has real potential to ease the burden on respiratory outpatient services by reducing the need for an onward referral. This is of great relevance given the current pressure on outpatient services globally, particularly long waiting lists following the COVID-19 pandemic and the need for more innovative models of care.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s12913-024-10716-7; html:https://europepmc.org/articles/PMC10882730; pdf:https://europepmc.org/articles/PMC10882730?pdf=render" + }, { "id": "34639458", "doi": "https://doi.org/10.3390/ijerph181910156", @@ -21283,23 +21283,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3390/ijerph181910156; html:https://europepmc.org/articles/PMC8507627; pdf:https://europepmc.org/articles/PMC8507627?pdf=render" }, - { - "id": "36932161", - "doi": "https://doi.org/10.1038/s41433-023-02478-z", - "title": "Evaluating patient-reported outcome measures (PROMs) for future clinical trials in adult patients with optic neuritis.", - "authorString": "Panthagani J, O'Donovan C, Aiyegbusi OL, Liu X, Bayliss S, Calvert M, Pesudovs K, Denniston AK, Moore DJ, Braithwaite T.", - "authorAffiliations": "", - "journalTitle": "Eye (London, England)", - "pubYear": "2023", - "date": "2023-03-17", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

To search for and critically appraise the psychometric quality of patient-reported outcome measures (PROMs) developed or validated in optic neuritis, in order to support high-quality research and care.

Methods

We systematically searched MEDLINE(Ovid), Embase(Ovid), PsycINFO(Ovid) and CINAHLPlus(EBSCO), and additional grey literature to November 2021, to identify PROM development or validation studies applicable to optic neuritis associated with any systemic or neurologic disease in adults. We included instruments developed using classic test theory or Rasch analysis approaches. We used established quality criteria to assess content development, validity, reliability, and responsiveness, grading multiple domains from A (high quality) to C (low quality).

Results

From 3142 screened abstracts we identified five PROM instruments potentially applicable to optic neuritis: three differing versions of the National Eye Institute (NEI)-Visual Function Questionnaire (VFQ): the 51-item VFQ; the 25-item VFQ and a 10-item neuro-ophthalmology supplement; and the Impact of Visual Impairment Scale (IVIS), a constituent of the Multiple Sclerosis Quality of Life Inventory (MSQLI) handbook, derived from the Functional Assessment of Multiple Sclerosis (FAMS). Psychometric appraisal revealed the NEI-VFQ-51 and 10-item neuro module had some relevant content development but weak psychometric development, and the FAMS had stronger psychometric development using Rasch Analysis, but was only somewhat relevant to optic neuritis. We identified no content or psychometric development for IVIS.

Conclusion

There is unmet need for a PROM with strong content and psychometric development applicable to optic neuritis for use in virtual care pathways and clinical trials to support drug marketing authorisation.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41433-023-02478-z.pdf; doi:https://doi.org/10.1038/s41433-023-02478-z; html:https://europepmc.org/articles/PMC10022552; pdf:https://europepmc.org/articles/PMC10022552?pdf=render" - }, { "id": "30999919", "doi": "https://doi.org/10.1186/s12911-019-0805-0", @@ -21317,6 +21300,23 @@ "laySummary": "", "urls": "pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-019-0805-0; doi:https://doi.org/10.1186/s12911-019-0805-0; html:https://europepmc.org/articles/PMC6472089; pdf:https://europepmc.org/articles/PMC6472089?pdf=render" }, + { + "id": "36932161", + "doi": "https://doi.org/10.1038/s41433-023-02478-z", + "title": "Evaluating patient-reported outcome measures (PROMs) for future clinical trials in adult patients with optic neuritis.", + "authorString": "Panthagani J, O'Donovan C, Aiyegbusi OL, Liu X, Bayliss S, Calvert M, Pesudovs K, Denniston AK, Moore DJ, Braithwaite T.", + "authorAffiliations": "", + "journalTitle": "Eye (London, England)", + "pubYear": "2023", + "date": "2023-03-17", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

To search for and critically appraise the psychometric quality of patient-reported outcome measures (PROMs) developed or validated in optic neuritis, in order to support high-quality research and care.

Methods

We systematically searched MEDLINE(Ovid), Embase(Ovid), PsycINFO(Ovid) and CINAHLPlus(EBSCO), and additional grey literature to November 2021, to identify PROM development or validation studies applicable to optic neuritis associated with any systemic or neurologic disease in adults. We included instruments developed using classic test theory or Rasch analysis approaches. We used established quality criteria to assess content development, validity, reliability, and responsiveness, grading multiple domains from A (high quality) to C (low quality).

Results

From 3142 screened abstracts we identified five PROM instruments potentially applicable to optic neuritis: three differing versions of the National Eye Institute (NEI)-Visual Function Questionnaire (VFQ): the 51-item VFQ; the 25-item VFQ and a 10-item neuro-ophthalmology supplement; and the Impact of Visual Impairment Scale (IVIS), a constituent of the Multiple Sclerosis Quality of Life Inventory (MSQLI) handbook, derived from the Functional Assessment of Multiple Sclerosis (FAMS). Psychometric appraisal revealed the NEI-VFQ-51 and 10-item neuro module had some relevant content development but weak psychometric development, and the FAMS had stronger psychometric development using Rasch Analysis, but was only somewhat relevant to optic neuritis. We identified no content or psychometric development for IVIS.

Conclusion

There is unmet need for a PROM with strong content and psychometric development applicable to optic neuritis for use in virtual care pathways and clinical trials to support drug marketing authorisation.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41433-023-02478-z.pdf; doi:https://doi.org/10.1038/s41433-023-02478-z; html:https://europepmc.org/articles/PMC10022552; pdf:https://europepmc.org/articles/PMC10022552?pdf=render" + }, { "id": "37225263", "doi": "https://doi.org/10.1136/bmjgast-2023-001139", @@ -21521,23 +21521,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.eclinm.2021.101212; doi:https://doi.org/10.1016/j.eclinm.2021.101212; html:https://europepmc.org/articles/PMC8635464; pdf:https://europepmc.org/articles/PMC8635464?pdf=render" }, - { - "id": "37658971", - "doi": "https://doi.org/10.1007/s11897-023-00626-w", - "title": "Multimorbidity in Heart Failure: Leveraging Cluster Analysis to Guide Tailored Treatment Strategies.", - "authorString": "van de Veerdonk MC, Savarese G, Handoko ML, Beulens JWJ, Asselbergs F, Uijl A.", - "authorAffiliations": "", - "journalTitle": "Current heart failure reports", - "pubYear": "2023", - "date": "2023-09-02", - "isOpenAccess": "Y", - "keywords": "Clustering; Phenotyping; Heart Failure; Machine Learning; Treatment Response; Precision Medicine", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Review purpose

This review summarises key findings on treatment effects within phenotypical clusters of patients with heart failure (HF), making a distinction between patients with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF).

Findings

Treatment response differed among clusters; ACE inhibitors were beneficial in all HFrEF phenotypes, while only some studies show similar beneficial prognostic effects in HFpEF patients. Beta-blockers had favourable effects in all HFrEF patients but not in HFpEF phenotypes and tended to worsen prognosis in older, cardiorenal patients. Mineralocorticoid receptor antagonists had more favourable prognostic effects in young, obese males and metabolic HFpEF patients. While a phenotype-guided approach is a promising solution for individualised treatment strategies, there are several aspects that still require improvements before such an approach could be implemented in clinical practice. Stronger evidence from clinical trials and real-world data may assist in establishing a phenotype-guided treatment approach for patient with HF in the future.", - "laySummary": "", - "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s11897-023-00626-w.pdf; doi:https://doi.org/10.1007/s11897-023-00626-w; html:https://europepmc.org/articles/PMC10589138; pdf:https://europepmc.org/articles/PMC10589138?pdf=render" - }, { "id": "36137640", "doi": "https://doi.org/10.1136/bmjopen-2022-064586", @@ -21555,6 +21538,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e064586.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-064586; html:https://europepmc.org/articles/PMC9511592; pdf:https://europepmc.org/articles/PMC9511592?pdf=render" }, + { + "id": "37658971", + "doi": "https://doi.org/10.1007/s11897-023-00626-w", + "title": "Multimorbidity in Heart Failure: Leveraging Cluster Analysis to Guide Tailored Treatment Strategies.", + "authorString": "van de Veerdonk MC, Savarese G, Handoko ML, Beulens JWJ, Asselbergs F, Uijl A.", + "authorAffiliations": "", + "journalTitle": "Current heart failure reports", + "pubYear": "2023", + "date": "2023-09-02", + "isOpenAccess": "Y", + "keywords": "Clustering; Phenotyping; Heart Failure; Machine Learning; Treatment Response; Precision Medicine", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Review purpose

This review summarises key findings on treatment effects within phenotypical clusters of patients with heart failure (HF), making a distinction between patients with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF).

Findings

Treatment response differed among clusters; ACE inhibitors were beneficial in all HFrEF phenotypes, while only some studies show similar beneficial prognostic effects in HFpEF patients. Beta-blockers had favourable effects in all HFrEF patients but not in HFpEF phenotypes and tended to worsen prognosis in older, cardiorenal patients. Mineralocorticoid receptor antagonists had more favourable prognostic effects in young, obese males and metabolic HFpEF patients. While a phenotype-guided approach is a promising solution for individualised treatment strategies, there are several aspects that still require improvements before such an approach could be implemented in clinical practice. Stronger evidence from clinical trials and real-world data may assist in establishing a phenotype-guided treatment approach for patient with HF in the future.", + "laySummary": "", + "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s11897-023-00626-w.pdf; doi:https://doi.org/10.1007/s11897-023-00626-w; html:https://europepmc.org/articles/PMC10589138; pdf:https://europepmc.org/articles/PMC10589138?pdf=render" + }, { "id": "32975552", "doi": "https://doi.org/10.1001/jamapediatrics.2020.4573", @@ -21606,23 +21606,6 @@ "laySummary": "", "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/01410768221095245; doi:https://doi.org/10.1177/01410768221095245; html:https://europepmc.org/articles/PMC9234890; pdf:https://europepmc.org/articles/PMC9234890?pdf=render" }, - { - "id": "38778017", - "doi": "https://doi.org/10.1038/s41541-024-00878-0", - "title": "Influence of individuals' determinants including vaccine type on cellular and humoral responses to SARS-CoV-2 vaccination.", - "authorString": "Chambers ES, Cai W, Vivaldi G, Jolliffe DA, Perdek N, Li W, Faustini SE, Gibbons JM, Pade C, Richter AG, Coussens AK, Martineau AR.", - "authorAffiliations": "", - "journalTitle": "NPJ vaccines", - "pubYear": "2024", - "date": "2024-05-22", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Vaccine development targeting SARS-CoV-2 in 2020 was of critical importance in reducing COVID-19 severity and mortality. In the U.K. during the initial roll-out most individuals either received two doses of Pfizer COVID-19 vaccine (BNT162b2) or the adenovirus-based vaccine from Oxford/AstraZeneca (ChAdOx1-nCoV-19). There are conflicting data as to the impact of age, sex and body habitus on cellular and humoral responses to vaccination, and most studies in this area have focused on determinants of mRNA vaccine immunogenicity. Here, we studied a cohort of participants in a population-based longitudinal study (COVIDENCE UK) to determine the influence of age, sex, body mass index (BMI) and pre-vaccination anti-Spike (anti-S) antibody status on vaccine-induced humoral and cellular immune responses to two doses of BNT162b2 or ChAdOx-n-CoV-19 vaccination. Younger age and pre-vaccination anti-S seropositivity were both associated with stronger antibody responses to vaccination. BNT162b2 generated higher neutralising and anti-S antibody titres to vaccination than ChAdOx1-nCoV-19, but cellular responses to the two vaccines were no different. Irrespective of vaccine type, increasing age was also associated with decreased frequency of cytokine double-positive CD4+T cells. Increasing BMI was associated with reduced frequency of SARS-CoV-2-specific TNF+CD8% T cells for both vaccines. Together, our findings demonstrate that increasing age and BMI are associated with attenuated cellular and humoral responses to SARS-CoV-2 vaccination. Whilst both vaccines induced T cell responses, BNT162b2 induced significantly elevated humoral immune response as compared to ChAdOx-n-CoV-19.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41541-024-00878-0.pdf; doi:https://doi.org/10.1038/s41541-024-00878-0; html:https://europepmc.org/articles/PMC11111746; pdf:https://europepmc.org/articles/PMC11111746?pdf=render" - }, { "id": "34125897", "doi": "https://doi.org/10.1093/nar/gkab449", @@ -21640,6 +21623,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/nar/gkab449; doi:https://doi.org/10.1093/nar/gkab449; html:https://europepmc.org/articles/PMC8262728; pdf:https://europepmc.org/articles/PMC8262728?pdf=render" }, + { + "id": "38778017", + "doi": "https://doi.org/10.1038/s41541-024-00878-0", + "title": "Influence of individuals' determinants including vaccine type on cellular and humoral responses to SARS-CoV-2 vaccination.", + "authorString": "Chambers ES, Cai W, Vivaldi G, Jolliffe DA, Perdek N, Li W, Faustini SE, Gibbons JM, Pade C, Richter AG, Coussens AK, Martineau AR.", + "authorAffiliations": "", + "journalTitle": "NPJ vaccines", + "pubYear": "2024", + "date": "2024-05-22", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Vaccine development targeting SARS-CoV-2 in 2020 was of critical importance in reducing COVID-19 severity and mortality. In the U.K. during the initial roll-out most individuals either received two doses of Pfizer COVID-19 vaccine (BNT162b2) or the adenovirus-based vaccine from Oxford/AstraZeneca (ChAdOx1-nCoV-19). There are conflicting data as to the impact of age, sex and body habitus on cellular and humoral responses to vaccination, and most studies in this area have focused on determinants of mRNA vaccine immunogenicity. Here, we studied a cohort of participants in a population-based longitudinal study (COVIDENCE UK) to determine the influence of age, sex, body mass index (BMI) and pre-vaccination anti-Spike (anti-S) antibody status on vaccine-induced humoral and cellular immune responses to two doses of BNT162b2 or ChAdOx-n-CoV-19 vaccination. Younger age and pre-vaccination anti-S seropositivity were both associated with stronger antibody responses to vaccination. BNT162b2 generated higher neutralising and anti-S antibody titres to vaccination than ChAdOx1-nCoV-19, but cellular responses to the two vaccines were no different. Irrespective of vaccine type, increasing age was also associated with decreased frequency of cytokine double-positive CD4+T cells. Increasing BMI was associated with reduced frequency of SARS-CoV-2-specific TNF+CD8% T cells for both vaccines. Together, our findings demonstrate that increasing age and BMI are associated with attenuated cellular and humoral responses to SARS-CoV-2 vaccination. Whilst both vaccines induced T cell responses, BNT162b2 induced significantly elevated humoral immune response as compared to ChAdOx-n-CoV-19.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41541-024-00878-0.pdf; doi:https://doi.org/10.1038/s41541-024-00878-0; html:https://europepmc.org/articles/PMC11111746; pdf:https://europepmc.org/articles/PMC11111746?pdf=render" + }, { "id": "32894757", "doi": "https://doi.org/10.1093/ageing/afaa138", @@ -21691,23 +21691,6 @@ "laySummary": "", "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4660846/7/Mulick_etal_2021_Four-childhood-atopic-dermatitis-subtypes.pdf; doi:https://doi.org/10.1111/bjd.19885; html:https://europepmc.org/articles/PMC8410876; pdf:https://europepmc.org/articles/PMC8410876?pdf=render; doi:https://doi.org/10.1111/bjd.19885" }, - { - "id": "35277454", - "doi": "https://doi.org/10.1136/heartjnl-2021-320417", - "title": "Smartphone detection of atrial fibrillation using photoplethysmography: a systematic review and meta-analysis.", - "authorString": "Gill S, Bunting KV, Sartini C, Cardoso VR, Ghoreishi N, Uh HW, Williams JA, Suzart-Woischnik K, Banerjee A, Asselbergs FW, Eijkemans M, Gkoutos GV, Kotecha D.", - "authorAffiliations": "", - "journalTitle": "Heart (British Cardiac Society)", - "pubYear": "2022", - "date": "2022-09-26", - "isOpenAccess": "Y", - "keywords": "Atrial fibrillation; Photoplethysmography; Smartphone", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

Timely diagnosis of atrial fibrillation (AF) is essential to reduce complications from this increasingly common condition. We sought to assess the diagnostic accuracy of smartphone camera photoplethysmography (PPG) compared with conventional electrocardiogram (ECG) for AF detection.

Methods

This is a systematic review of MEDLINE, EMBASE and Cochrane (1980-December 2020), including any study or abstract, where smartphone PPG was compared with a reference ECG (1, 3 or 12-lead). Random effects meta-analysis was performed to pool sensitivity/specificity and identify publication bias, with study quality assessed using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) risk of bias tool.

Results

28 studies were included (10 full-text publications and 18 abstracts), providing 31 comparisons of smartphone PPG versus ECG for AF detection. 11\u2009404 participants were included (2950 in AF), with most studies being small and based in secondary care. Sensitivity and specificity for AF detection were high, ranging from 81% to 100%, and from 85% to 100%, respectively. 20 comparisons from 17 studies were meta-analysed, including 6891 participants (2299 with AF); the pooled sensitivity was 94% (95% CI 92% to 95%) and specificity 97% (96%-98%), with substantial heterogeneity (p<0.01). Studies were of poor quality overall and none met all the QUADAS-2 criteria, with particular issues regarding selection bias and the potential for publication bias.

Conclusion

PPG provides a non-invasive, patient-led screening tool for AF. However, current evidence is limited to small, biased, low-quality studies with unrealistically high sensitivity and specificity. Further studies are needed, preferably independent from manufacturers, in order to advise clinicians on the true value of PPG technology for AF detection.", - "laySummary": "", - "urls": "pdf:https://heart.bmj.com/content/heartjnl/early/2022/03/10/heartjnl-2021-320417.full.pdf; doi:https://doi.org/10.1136/heartjnl-2021-320417; html:https://europepmc.org/articles/PMC9554073; pdf:https://europepmc.org/articles/PMC9554073?pdf=render" - }, { "id": "35038301", "doi": "https://doi.org/10.2196/30523", @@ -21726,21 +21709,21 @@ "urls": "pdf:https://humanfactors.jmir.org/2022/2/e30523/PDF; doi:https://doi.org/10.2196/30523; html:https://europepmc.org/articles/PMC9009380" }, { - "id": "33634927", - "doi": "https://doi.org/10.1111/ans.16649", - "title": "Risk factors for surgical site infections following spinal column trauma in an Australian trauma hospital.", - "authorString": "Baroun-Agob L, Liew S, Gabbe B.", + "id": "35277454", + "doi": "https://doi.org/10.1136/heartjnl-2021-320417", + "title": "Smartphone detection of atrial fibrillation using photoplethysmography: a systematic review and meta-analysis.", + "authorString": "Gill S, Bunting KV, Sartini C, Cardoso VR, Ghoreishi N, Uh HW, Williams JA, Suzart-Woischnik K, Banerjee A, Asselbergs FW, Eijkemans M, Gkoutos GV, Kotecha D.", "authorAffiliations": "", - "journalTitle": "ANZ journal of surgery", - "pubYear": "2021", - "date": "2021-02-26", - "isOpenAccess": "N", - "keywords": "Spine; Trauma; Risk factor; Surgical Wound Infection; Orthopaedic Surgery", + "journalTitle": "Heart (British Cardiac Society)", + "pubYear": "2022", + "date": "2022-09-26", + "isOpenAccess": "Y", + "keywords": "Atrial fibrillation; Photoplethysmography; Smartphone", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

There is limited, and often conflicting, data in the literature about the prevalence and risk factors for surgical site infections (SSI) in spine surgery patients, with the majority consisting of elective spine surgery cohorts. Furthermore, there is no reported Australian data regarding rates of SSI in a spinal trauma cohort. The aim of this study is to identify factors associated with SSI following spinal column trauma.

Methods

Adult (16+ years) patients that underwent surgery following emergency admission for spinal trauma between January 2010 and December 2016 at a major trauma centre in Melbourne, Australia, were identified through the Victorian Orthopaedic Trauma Outcomes Registry. The presence of an SSI was confirmed from the electronic medical record. Patient and clinical factors were analysed by SSI status. Generalized Estimating Equations were used to model predictors of SSI, with a P-value <0.05 deemed significant.

Results

Data for 458 patients and 520 surgical wounds were collected. Twenty-six (5.7%) patients developed an SSI. Staphylococcus aureus was the most common microorganism with methicillin-sensitive S. aureus found in 46% of SSI cases. A posterior surgical approach and same site reoperation were predictors of SSI with adjusted odds ratios (95% confidence intervals) of 4.26 (1.22-14.80, P = 0.02) and 4.99 (1.10-22.58, P = 0.04), respectively.

Conclusions

A posterior surgical approach and same site reoperation increased the risk of SSI after spinal trauma. Further research into modifiable associations within these and other factors will help mitigate the risk of SSI and hence decrease the personal and financial costs of this potentially devastating complication.", + "abstract": "

Objectives

Timely diagnosis of atrial fibrillation (AF) is essential to reduce complications from this increasingly common condition. We sought to assess the diagnostic accuracy of smartphone camera photoplethysmography (PPG) compared with conventional electrocardiogram (ECG) for AF detection.

Methods

This is a systematic review of MEDLINE, EMBASE and Cochrane (1980-December 2020), including any study or abstract, where smartphone PPG was compared with a reference ECG (1, 3 or 12-lead). Random effects meta-analysis was performed to pool sensitivity/specificity and identify publication bias, with study quality assessed using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) risk of bias tool.

Results

28 studies were included (10 full-text publications and 18 abstracts), providing 31 comparisons of smartphone PPG versus ECG for AF detection. 11\u2009404 participants were included (2950 in AF), with most studies being small and based in secondary care. Sensitivity and specificity for AF detection were high, ranging from 81% to 100%, and from 85% to 100%, respectively. 20 comparisons from 17 studies were meta-analysed, including 6891 participants (2299 with AF); the pooled sensitivity was 94% (95% CI 92% to 95%) and specificity 97% (96%-98%), with substantial heterogeneity (p<0.01). Studies were of poor quality overall and none met all the QUADAS-2 criteria, with particular issues regarding selection bias and the potential for publication bias.

Conclusion

PPG provides a non-invasive, patient-led screening tool for AF. However, current evidence is limited to small, biased, low-quality studies with unrealistically high sensitivity and specificity. Further studies are needed, preferably independent from manufacturers, in order to advise clinicians on the true value of PPG technology for AF detection.", "laySummary": "", - "urls": "doi:https://doi.org/10.1111/ans.16649" + "urls": "pdf:https://heart.bmj.com/content/heartjnl/early/2022/03/10/heartjnl-2021-320417.full.pdf; doi:https://doi.org/10.1136/heartjnl-2021-320417; html:https://europepmc.org/articles/PMC9554073; pdf:https://europepmc.org/articles/PMC9554073?pdf=render" }, { "id": "31194737", @@ -21759,6 +21742,23 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1008164&type=printable; doi:https://doi.org/10.1371/journal.pgen.1008164; html:https://europepmc.org/articles/PMC6592570; pdf:https://europepmc.org/articles/PMC6592570?pdf=render" }, + { + "id": "33634927", + "doi": "https://doi.org/10.1111/ans.16649", + "title": "Risk factors for surgical site infections following spinal column trauma in an Australian trauma hospital.", + "authorString": "Baroun-Agob L, Liew S, Gabbe B.", + "authorAffiliations": "", + "journalTitle": "ANZ journal of surgery", + "pubYear": "2021", + "date": "2021-02-26", + "isOpenAccess": "N", + "keywords": "Spine; Trauma; Risk factor; Surgical Wound Infection; Orthopaedic Surgery", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

There is limited, and often conflicting, data in the literature about the prevalence and risk factors for surgical site infections (SSI) in spine surgery patients, with the majority consisting of elective spine surgery cohorts. Furthermore, there is no reported Australian data regarding rates of SSI in a spinal trauma cohort. The aim of this study is to identify factors associated with SSI following spinal column trauma.

Methods

Adult (16+ years) patients that underwent surgery following emergency admission for spinal trauma between January 2010 and December 2016 at a major trauma centre in Melbourne, Australia, were identified through the Victorian Orthopaedic Trauma Outcomes Registry. The presence of an SSI was confirmed from the electronic medical record. Patient and clinical factors were analysed by SSI status. Generalized Estimating Equations were used to model predictors of SSI, with a P-value <0.05 deemed significant.

Results

Data for 458 patients and 520 surgical wounds were collected. Twenty-six (5.7%) patients developed an SSI. Staphylococcus aureus was the most common microorganism with methicillin-sensitive S. aureus found in 46% of SSI cases. A posterior surgical approach and same site reoperation were predictors of SSI with adjusted odds ratios (95% confidence intervals) of 4.26 (1.22-14.80, P = 0.02) and 4.99 (1.10-22.58, P = 0.04), respectively.

Conclusions

A posterior surgical approach and same site reoperation increased the risk of SSI after spinal trauma. Further research into modifiable associations within these and other factors will help mitigate the risk of SSI and hence decrease the personal and financial costs of this potentially devastating complication.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1111/ans.16649" + }, { "id": "36224187", "doi": "https://doi.org/10.1038/s41467-022-33826-4", @@ -21912,23 +21912,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1097/TA.0000000000003317" }, - { - "id": "37750555", - "doi": "https://doi.org/10.1161/jaha.123.030766", - "title": "Impact of New Cardiovascular Events on Quality of Life and Hospital Costs in People With Cardiovascular Disease in the United Kingdom and United States.", - "authorString": "Lui JNM, Williams C, Keng MJ, Hopewell JC, Sammons E, Chen F, Gray A, Bowman L, Landray SMJ, Mihaylova B, REVEAL Collaborative Group.", - "authorAffiliations": "", - "journalTitle": "Journal of the American Heart Association", - "pubYear": "2023", - "date": "2023-09-26", - "isOpenAccess": "Y", - "keywords": "Cardiovascular diseases; Quality of life; United States; United Kingdom; Secondary Prevention; Health Care Costs", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Despite optimized risk factor control, people with prior cardiovascular disease remain at high cardiovascular disease risk. We assess the immediate- and longer-term impacts of new vascular and nonvascular events on quality of life (QoL) and hospital costs among participants in the REVEAL (Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification) trial in secondary prevention.

Methods and results

Data on demographic and clinical characteristics, health-related quality of life (QoL: EuroQoL 5-Dimension-5-Level), adverse events, and hospital admissions during the 4-year follow-up of the 21\u2009820 participants recruited in Europe and North America informed assessments of the impacts of new adverse events on QoL and hospital costs from the UK and US health systems' perspectives using generalized linear regression models. Reductions in QoL were estimated in the years of event occurrence for nonhemorrhagic stroke (-0.067 [United Kingdom], -0.069 [US]), heart failure admission (-0.072 [United Kingdom], -0.103 [US]), incident cancer (-0.064 [United Kingdom], -0.068 [US]), and noncoronary revascularization (-0.071 [United Kingdom], -0.061 [US]), as well as in subsequent years following these events. Myocardial infarction and coronary revascularization (CRV) procedures were not found to affect QoL. All adverse events were associated with additional hospital costs in the years of events and in subsequent years, with the highest additional costs in the years of noncoronary revascularization (\u00a35830 [United Kingdom], $14\u2009133 [US Medicare]), of myocardial infarction with urgent CRV procedure (\u00a35614, $24722), and of urgent/nonurgent CRV procedure without myocardial infarction (\u00a34674/\u00a34651 and $15\u2009251/$17\u2009539).

Conclusions

Stroke, heart failure, and noncoronary revascularization procedures substantially reduce QoL, and all cardiovascular disease events increase hospital costs. These estimates are useful in informing cost-effectiveness of interventions to reduce cardiovascular disease risk in secondary prevention.

Registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252953; https://www.Isrctn.com. Unique identifier: ISRCTN48678192; https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18.", - "laySummary": "", - "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.030766; doi:https://doi.org/10.1161/JAHA.123.030766; html:https://europepmc.org/articles/PMC7615160; pdf:https://europepmc.org/articles/PMC7615160?pdf=render" - }, { "id": "35025917", "doi": "https://doi.org/10.1371/journal.pone.0261142", @@ -21946,6 +21929,23 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0261142&type=printable; doi:https://doi.org/10.1371/journal.pone.0261142; html:https://europepmc.org/articles/PMC8757902; pdf:https://europepmc.org/articles/PMC8757902?pdf=render" }, + { + "id": "37750555", + "doi": "https://doi.org/10.1161/jaha.123.030766", + "title": "Impact of New Cardiovascular Events on Quality of Life and Hospital Costs in People With Cardiovascular Disease in the United Kingdom and United States.", + "authorString": "Lui JNM, Williams C, Keng MJ, Hopewell JC, Sammons E, Chen F, Gray A, Bowman L, Landray SMJ, Mihaylova B, REVEAL Collaborative Group.", + "authorAffiliations": "", + "journalTitle": "Journal of the American Heart Association", + "pubYear": "2023", + "date": "2023-09-26", + "isOpenAccess": "Y", + "keywords": "Cardiovascular diseases; Quality of life; United States; United Kingdom; Secondary Prevention; Health Care Costs", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Despite optimized risk factor control, people with prior cardiovascular disease remain at high cardiovascular disease risk. We assess the immediate- and longer-term impacts of new vascular and nonvascular events on quality of life (QoL) and hospital costs among participants in the REVEAL (Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification) trial in secondary prevention.

Methods and results

Data on demographic and clinical characteristics, health-related quality of life (QoL: EuroQoL 5-Dimension-5-Level), adverse events, and hospital admissions during the 4-year follow-up of the 21\u2009820 participants recruited in Europe and North America informed assessments of the impacts of new adverse events on QoL and hospital costs from the UK and US health systems' perspectives using generalized linear regression models. Reductions in QoL were estimated in the years of event occurrence for nonhemorrhagic stroke (-0.067 [United Kingdom], -0.069 [US]), heart failure admission (-0.072 [United Kingdom], -0.103 [US]), incident cancer (-0.064 [United Kingdom], -0.068 [US]), and noncoronary revascularization (-0.071 [United Kingdom], -0.061 [US]), as well as in subsequent years following these events. Myocardial infarction and coronary revascularization (CRV) procedures were not found to affect QoL. All adverse events were associated with additional hospital costs in the years of events and in subsequent years, with the highest additional costs in the years of noncoronary revascularization (\u00a35830 [United Kingdom], $14\u2009133 [US Medicare]), of myocardial infarction with urgent CRV procedure (\u00a35614, $24722), and of urgent/nonurgent CRV procedure without myocardial infarction (\u00a34674/\u00a34651 and $15\u2009251/$17\u2009539).

Conclusions

Stroke, heart failure, and noncoronary revascularization procedures substantially reduce QoL, and all cardiovascular disease events increase hospital costs. These estimates are useful in informing cost-effectiveness of interventions to reduce cardiovascular disease risk in secondary prevention.

Registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252953; https://www.Isrctn.com. Unique identifier: ISRCTN48678192; https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18.", + "laySummary": "", + "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.030766; doi:https://doi.org/10.1161/JAHA.123.030766; html:https://europepmc.org/articles/PMC7615160; pdf:https://europepmc.org/articles/PMC7615160?pdf=render" + }, { "id": "37124165", "doi": "https://doi.org/10.1016/j.ufug.2023.127934", @@ -21980,23 +21980,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ehjdh/article-pdf/2/4/635/41972750/ztab082.pdf; doi:https://doi.org/10.1093/ehjdh/ztab082; html:https://europepmc.org/articles/PMC9707970; pdf:https://europepmc.org/articles/PMC9707970?pdf=render" }, - { - "id": "35816976", - "doi": "https://doi.org/10.1016/j.jpsychires.2022.06.044", - "title": "Anticoagulation for atrial fibrillation in people with serious mental illness in the general hospital setting.", - "authorString": "Farran D, Bean D, Wang T, Msosa Y, Casetta C, Dobson R, Teo JT, Scott P, Gaughran F.", - "authorAffiliations": "", - "journalTitle": "Journal of psychiatric research", - "pubYear": "2022", - "date": "2022-06-28", - "isOpenAccess": "N", - "keywords": "Atrial fibrillation; Warfarin; Serious Mental Illness; Oral Anticoagulation; Doacs", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

People with serious mental illnesses (SMI) have an increased risk of stroke compared to the general population. This study aims to evaluate oral anticoagulation prescription trends in atrial fibrillation (AF) patients with and without a comorbid SMI.

Methods

An open-source retrieval system for clinical data (CogStack) was used to identify a cohort of AF patients with SMI who ever had an inpatient admission to King's College Hospital from 2011 to 2020. A Natural Language Processing pipeline was used to calculate CHA2DS2-VASc and HASBLED risk scores from Electronic Health Records free text. Antithrombotic prescriptions of warfarin and Direct acting oral anti-coagulants (DOACs) (apixaban, rivaroxaban, dabigatran, edoxaban) were extracted from discharge summaries.

Results

Among patients included in the study (n\u00a0=\u00a016\u00a0916), 2.7% had a recorded co-morbid SMI diagnosis. Compared to non-SMI patients, those with SMI had significantly higher CHA2DS2-VASc (mean (SD): 5.3 (1.96) vs 4.7 (2.08), p\u00a0<\u00a00.001) and HASBLED scores (mean (SD): 3.2 (1.27) vs 2.5 (1.29), p\u00a0<\u00a00.001). Among AF patients having a CHA2DS2-VASc \u22652, those with co-morbid SMI were less likely than non-SMI patients to be prescribed an OAC (44% vs 54%, p\u00a0<\u00a00.001). However, there was no evidence of a significant difference between the two groups since 2019.

Conclusion

Over recent years, DOAC prescription rates have increased among AF patients with SMI in acute hospitals. More research is needed to confirm whether the introduction of DOACs has reduced OAC treatment gaps in people with serious mental illness and to assess whether the use of DOACs has improved health outcomes in this population.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jpsychires.2022.06.044; doi:https://doi.org/10.1016/j.jpsychires.2022.06.044" - }, { "id": "33543581", "doi": "https://doi.org/10.1111/ans.16578", @@ -22014,6 +21997,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/ans.16578" }, + { + "id": "35816976", + "doi": "https://doi.org/10.1016/j.jpsychires.2022.06.044", + "title": "Anticoagulation for atrial fibrillation in people with serious mental illness in the general hospital setting.", + "authorString": "Farran D, Bean D, Wang T, Msosa Y, Casetta C, Dobson R, Teo JT, Scott P, Gaughran F.", + "authorAffiliations": "", + "journalTitle": "Journal of psychiatric research", + "pubYear": "2022", + "date": "2022-06-28", + "isOpenAccess": "N", + "keywords": "Atrial fibrillation; Warfarin; Serious Mental Illness; Oral Anticoagulation; Doacs", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

People with serious mental illnesses (SMI) have an increased risk of stroke compared to the general population. This study aims to evaluate oral anticoagulation prescription trends in atrial fibrillation (AF) patients with and without a comorbid SMI.

Methods

An open-source retrieval system for clinical data (CogStack) was used to identify a cohort of AF patients with SMI who ever had an inpatient admission to King's College Hospital from 2011 to 2020. A Natural Language Processing pipeline was used to calculate CHA2DS2-VASc and HASBLED risk scores from Electronic Health Records free text. Antithrombotic prescriptions of warfarin and Direct acting oral anti-coagulants (DOACs) (apixaban, rivaroxaban, dabigatran, edoxaban) were extracted from discharge summaries.

Results

Among patients included in the study (n\u00a0=\u00a016\u00a0916), 2.7% had a recorded co-morbid SMI diagnosis. Compared to non-SMI patients, those with SMI had significantly higher CHA2DS2-VASc (mean (SD): 5.3 (1.96) vs 4.7 (2.08), p\u00a0<\u00a00.001) and HASBLED scores (mean (SD): 3.2 (1.27) vs 2.5 (1.29), p\u00a0<\u00a00.001). Among AF patients having a CHA2DS2-VASc \u22652, those with co-morbid SMI were less likely than non-SMI patients to be prescribed an OAC (44% vs 54%, p\u00a0<\u00a00.001). However, there was no evidence of a significant difference between the two groups since 2019.

Conclusion

Over recent years, DOAC prescription rates have increased among AF patients with SMI in acute hospitals. More research is needed to confirm whether the introduction of DOACs has reduced OAC treatment gaps in people with serious mental illness and to assess whether the use of DOACs has improved health outcomes in this population.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.jpsychires.2022.06.044; doi:https://doi.org/10.1016/j.jpsychires.2022.06.044" + }, { "id": "36332947", "doi": "https://doi.org/10.1136/bmjopen-2022-061843", @@ -22320,6 +22320,23 @@ "laySummary": "", "urls": "pdf:https://ijpds.org/article/download/1371/2815; doi:https://doi.org/10.23889/ijpds.v5i3.1371; html:https://europepmc.org/articles/PMC7893854; pdf:https://europepmc.org/articles/PMC7893854?pdf=render" }, + { + "id": "33789468", + "doi": "https://doi.org/10.1302/0301-620x.103b4.bjj-2020-1647.r1", + "title": "Outcomes of severe lower limb injury with Mangled Extremity Severity Score \u2265 7.", + "authorString": "Hoogervorst LA, Hart MJ, Simpson PM, Kimmel LA, Oppy A, Edwards ER, Gabbe BJ.", + "authorAffiliations": "", + "journalTitle": "The bone & joint journal", + "pubYear": "2021", + "date": "2021-04-01", + "isOpenAccess": "N", + "keywords": "Injury; Lower limb; Return To Work; Salvage; Functional Outcomes; Mess; Gos-e; Eq-5d-3l; Surgical Amputation; 2-Year", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

Complex fractures of the femur and tibia with associated severe soft tissue injury are often devastating for the individual. The aim of this study was to describe the two-year patient-reported outcomes of patients in a civilian population who sustained a complex fracture of the femur or tibia with a Mangled Extremity Severity Score (MESS) of \u2265 7, whereby the score ranges from 2 (lowest severity) to 11 (highest severity).

Methods

Patients aged \u2265 16 years with a fractured femur or tibia and a MESS of \u2265 7 were extracted from the Victorian Orthopaedic Trauma Outcomes Registry (January 2007 to December 2018). Cases were grouped into surgical amputation or limb salvage. Descriptive analysis were used to examine return to work rates, three-level EuroQol five-dimension questionnaire (EQ-5D-3L), and Glasgow Outcome Scale-Extended (GOS-E) outcomes at 12 and 24 months post-injury.

Results

In all, 111 patients were included: 90 (81%) patients who underwent salvage and 21 (19%) patients with surgical amputation. The mean age of patients was 45.8 years (SD 15.8), 93 (84%) were male, 37 (33%) were involved in motor vehicle collisions, and the mean MESS score was 8.2 (SD 1.4). Two-year outcomes in the cohort were poor: six (7%) patients achieved a GOS-E good recovery, the mean EQ-5D-3L summary score was 0.52 (SD 0.27), and 17 (20%) patients had returned to work.

Conclusion

A small proportion of patients with severe lower limb injury (MESS \u2265 7) achieved a good level of function 24 months post-injury. Further follow-up is needed to better understand the long-term trajectory of these patients, including delayed amputation, hospital readmissions, and healthcare utilization. Cite this article: Bone Joint J\u00a02021;103-B(4):769-774.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1302/0301-620X.103B4.BJJ-2020-1647.R1" + }, { "id": "37284234", "doi": "https://doi.org/10.1140/epjds/s13688-023-00391-9", @@ -22338,21 +22355,21 @@ "urls": "doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; doi:https://doi.org/10.1140/epjds/s13688-023-00391-9; html:https://europepmc.org/articles/PMC10240109; pdf:https://europepmc.org/articles/PMC10240109?pdf=render" }, { - "id": "33789468", - "doi": "https://doi.org/10.1302/0301-620x.103b4.bjj-2020-1647.r1", - "title": "Outcomes of severe lower limb injury with Mangled Extremity Severity Score \u2265 7.", - "authorString": "Hoogervorst LA, Hart MJ, Simpson PM, Kimmel LA, Oppy A, Edwards ER, Gabbe BJ.", + "id": "32831176", + "doi": "https://doi.org/10.7554/elife.58699", + "title": "The contribution of asymptomatic SARS-CoV-2 infections to transmission on the Diamond Princess cruise ship.", + "authorString": "Emery JC, Russell TW, Liu Y, Hellewell J, Pearson CA, CMMID COVID-19 Working Group, Knight GM, Eggo RM, Kucharski AJ, Kucharski AJ, Funk S, Flasche S, Houben RM.", "authorAffiliations": "", - "journalTitle": "The bone & joint journal", - "pubYear": "2021", - "date": "2021-04-01", - "isOpenAccess": "N", - "keywords": "Injury; Lower limb; Return To Work; Salvage; Functional Outcomes; Mess; Gos-e; Eq-5d-3l; Surgical Amputation; 2-Year", + "journalTitle": "eLife", + "pubYear": "2020", + "date": "2020-08-24", + "isOpenAccess": "Y", + "keywords": "Human; Microbiology; Transmission; Infectious disease; epidemiology; Global Health; Asymptomatic Infections; Subclinical Infections; Covid-19; Sars-cov-2", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Aims

Complex fractures of the femur and tibia with associated severe soft tissue injury are often devastating for the individual. The aim of this study was to describe the two-year patient-reported outcomes of patients in a civilian population who sustained a complex fracture of the femur or tibia with a Mangled Extremity Severity Score (MESS) of \u2265 7, whereby the score ranges from 2 (lowest severity) to 11 (highest severity).

Methods

Patients aged \u2265 16 years with a fractured femur or tibia and a MESS of \u2265 7 were extracted from the Victorian Orthopaedic Trauma Outcomes Registry (January 2007 to December 2018). Cases were grouped into surgical amputation or limb salvage. Descriptive analysis were used to examine return to work rates, three-level EuroQol five-dimension questionnaire (EQ-5D-3L), and Glasgow Outcome Scale-Extended (GOS-E) outcomes at 12 and 24 months post-injury.

Results

In all, 111 patients were included: 90 (81%) patients who underwent salvage and 21 (19%) patients with surgical amputation. The mean age of patients was 45.8 years (SD 15.8), 93 (84%) were male, 37 (33%) were involved in motor vehicle collisions, and the mean MESS score was 8.2 (SD 1.4). Two-year outcomes in the cohort were poor: six (7%) patients achieved a GOS-E good recovery, the mean EQ-5D-3L summary score was 0.52 (SD 0.27), and 17 (20%) patients had returned to work.

Conclusion

A small proportion of patients with severe lower limb injury (MESS \u2265 7) achieved a good level of function 24 months post-injury. Further follow-up is needed to better understand the long-term trajectory of these patients, including delayed amputation, hospital readmissions, and healthcare utilization. Cite this article: Bone Joint J\u00a02021;103-B(4):769-774.", + "abstract": "A key unknown for SARS-CoV-2 is how asymptomatic infections contribute to transmission. We used a transmission model with asymptomatic and presymptomatic states, calibrated to data on disease onset and test frequency from the Diamond Princess cruise ship outbreak, to quantify the contribution of asymptomatic infections to transmission. The model estimated that 74% (70-78%, 95% posterior interval) of infections proceeded asymptomatically. Despite intense testing, 53% (51-56%) of infections remained undetected, most of them asymptomatic. Asymptomatic individuals were the source for 69% (20-85%) of all infections. The data did not allow identification of the infectiousness of asymptomatic infections, however low ranges (0-25%) required a net reproduction number for individuals progressing through presymptomatic and symptomatic stages of at least 15. Asymptomatic SARS-CoV-2 infections may contribute substantially to transmission. Control measures, and models projecting their potential impact, need to look beyond the symptomatic cases if they are to understand and address ongoing transmission.", "laySummary": "", - "urls": "doi:https://doi.org/10.1302/0301-620X.103B4.BJJ-2020-1647.R1" + "urls": "doi:https://doi.org/10.7554/elife.58699; doi:https://doi.org/10.7554/eLife.58699; html:https://europepmc.org/articles/PMC7527238; pdf:https://europepmc.org/articles/PMC7527238?pdf=render" }, { "id": "32616598", @@ -22388,23 +22405,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/ehjqcco/qcac039; html:https://europepmc.org/articles/PMC9442847; pdf:https://europepmc.org/articles/PMC9442847?pdf=render; doi:https://doi.org/10.1093/ehjqcco/qcac039" }, - { - "id": "32831176", - "doi": "https://doi.org/10.7554/elife.58699", - "title": "The contribution of asymptomatic SARS-CoV-2 infections to transmission on the Diamond Princess cruise ship.", - "authorString": "Emery JC, Russell TW, Liu Y, Hellewell J, Pearson CA, CMMID COVID-19 Working Group, Knight GM, Eggo RM, Kucharski AJ, Kucharski AJ, Funk S, Flasche S, Houben RM.", - "authorAffiliations": "", - "journalTitle": "eLife", - "pubYear": "2020", - "date": "2020-08-24", - "isOpenAccess": "Y", - "keywords": "Human; Microbiology; Transmission; Infectious disease; epidemiology; Global Health; Asymptomatic Infections; Subclinical Infections; Covid-19; Sars-cov-2", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "A key unknown for SARS-CoV-2 is how asymptomatic infections contribute to transmission. We used a transmission model with asymptomatic and presymptomatic states, calibrated to data on disease onset and test frequency from the Diamond Princess cruise ship outbreak, to quantify the contribution of asymptomatic infections to transmission. The model estimated that 74% (70-78%, 95% posterior interval) of infections proceeded asymptomatically. Despite intense testing, 53% (51-56%) of infections remained undetected, most of them asymptomatic. Asymptomatic individuals were the source for 69% (20-85%) of all infections. The data did not allow identification of the infectiousness of asymptomatic infections, however low ranges (0-25%) required a net reproduction number for individuals progressing through presymptomatic and symptomatic stages of at least 15. Asymptomatic SARS-CoV-2 infections may contribute substantially to transmission. Control measures, and models projecting their potential impact, need to look beyond the symptomatic cases if they are to understand and address ongoing transmission.", - "laySummary": "", - "urls": "doi:https://doi.org/10.7554/elife.58699; doi:https://doi.org/10.7554/eLife.58699; html:https://europepmc.org/articles/PMC7527238; pdf:https://europepmc.org/articles/PMC7527238?pdf=render" - }, { "id": "36403308", "doi": "https://doi.org/10.1016/j.media.2022.102678", @@ -22542,21 +22542,21 @@ "urls": "pdf:https://www.nature.com/articles/s41467-022-28729-3.pdf; doi:https://doi.org/10.1038/s41467-022-28729-3; html:https://europepmc.org/articles/PMC8907312; pdf:https://europepmc.org/articles/PMC8907312?pdf=render" }, { - "id": "37990330", - "doi": "https://doi.org/10.1186/s13063-023-07763-6", - "title": "Correction: Medicines and Healthcare products Regulatory Agency's \"Consultation on proposals for legislative changes for clinical trials\": a response from the Trials Methodology Research Partnership Adaptive Designs Working Group, with a focus on data sharing.", - "authorString": "Law M, Couturier DL, Choodari-Oskooei B, Crout P, Gamble C, Jacko P, Pallmann P, Pilling M, Robertson DS, Robling M, Sydes MR, Villar SS, Wason J, Wheeler G, Williamson SF, Yap C, Jaki T.", + "id": "29944675", + "doi": "https://doi.org/10.1371/journal.pone.0199026", + "title": "The diagnosis, burden and prognosis of dementia: A record-linkage cohort study in England.", + "authorString": "Pujades-Rodriguez M, Assi V, Gonzalez-Izquierdo A, Wilkinson T, Schnier C, Sudlow C, Hemingway H, Whiteley WN.", "authorAffiliations": "", - "journalTitle": "Trials", - "pubYear": "2023", - "date": "2023-11-21", + "journalTitle": "PloS one", + "pubYear": "2018", + "date": "2018-06-26", "isOpenAccess": "Y", "keywords": "", - "nationalPriorities": "", + "nationalPriorities": "The Human Phenome", "healthCategories": "", - "abstract": "", + "abstract": "

Objectives

Electronic health records (EHR) might be a useful resource to study the risk factors and clinical care of people with dementia. We sought to determine the diagnostic validity of dementia captured in linked EHR.

Methods and findings

A cohort of adults in linked primary care, hospital, disease registry and mortality records in England, [CALIBER (CArdiovascular disease research using LInked Bespoke studies and Electronic health Records)]. The proportion of individuals with dementia, Alzheimer's disease, vascular and rare dementia in each data source was determined. A comparison was made of symptoms and care between people with dementia and age-, sex- and general practice-matched controls, using conditional logistic regression. The lifetime risk and prevalence of dementia and mortality rates in people with and without dementia were estimated with random-effects Poisson models. There were 47,386 people with dementia: 12,633 with Alzheimer's disease, 9540 with vascular and 1539 with rare dementia. Seventy-four percent of cases had corroborating evidence of dementia. People with dementia were more likely to live in a deprived area (conditional OR 1.26;95%CI:1.20-1.31 most vs least deprived), have documented memory impairment (cOR = 11.97;95%CI:11.24-12.75), falls (cOR = 2.36;95%CI:2.31-2.41), depression (cOR = 2.03; 95%CI:1.98-2.09) or anxiety (cOR = 1.27; 95%CI:1.23-1.32). The lifetime risk of dementia at age 65 was 9.2% (95%CI:9.0%-9.4%), in men and 14.9% (95%CI:14.7%-15.1%) in women. The population prevalence of recorded dementia increased from 0.3% in 2000 to 0.7% in 2010. A higher mortality rate was observed in people with than without dementia (IRR = 1.56;95%CI:1.54-1.58).

Conclusions

Most people with a record of dementia in linked UK EHR had some corroborating evidence for diagnosis. The estimated 10-year risk of dementia was higher than published population-based estimations. EHR are therefore a promising source of data for dementia research.", "laySummary": "", - "urls": "pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07763-6; doi:https://doi.org/10.1186/s13063-023-07763-6; html:https://europepmc.org/articles/PMC10664262; pdf:https://europepmc.org/articles/PMC10664262?pdf=render" + "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0199026&type=printable; doi:https://doi.org/10.1371/journal.pone.0199026; html:https://europepmc.org/articles/PMC6019102; pdf:https://europepmc.org/articles/PMC6019102?pdf=render" }, { "id": "37987834", @@ -22575,23 +22575,6 @@ "laySummary": "", "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00330-023-10311-0.pdf; doi:https://doi.org/10.1007/s00330-023-10311-0" }, - { - "id": "29944675", - "doi": "https://doi.org/10.1371/journal.pone.0199026", - "title": "The diagnosis, burden and prognosis of dementia: A record-linkage cohort study in England.", - "authorString": "Pujades-Rodriguez M, Assi V, Gonzalez-Izquierdo A, Wilkinson T, Schnier C, Sudlow C, Hemingway H, Whiteley WN.", - "authorAffiliations": "", - "journalTitle": "PloS one", - "pubYear": "2018", - "date": "2018-06-26", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "The Human Phenome", - "healthCategories": "", - "abstract": "

Objectives

Electronic health records (EHR) might be a useful resource to study the risk factors and clinical care of people with dementia. We sought to determine the diagnostic validity of dementia captured in linked EHR.

Methods and findings

A cohort of adults in linked primary care, hospital, disease registry and mortality records in England, [CALIBER (CArdiovascular disease research using LInked Bespoke studies and Electronic health Records)]. The proportion of individuals with dementia, Alzheimer's disease, vascular and rare dementia in each data source was determined. A comparison was made of symptoms and care between people with dementia and age-, sex- and general practice-matched controls, using conditional logistic regression. The lifetime risk and prevalence of dementia and mortality rates in people with and without dementia were estimated with random-effects Poisson models. There were 47,386 people with dementia: 12,633 with Alzheimer's disease, 9540 with vascular and 1539 with rare dementia. Seventy-four percent of cases had corroborating evidence of dementia. People with dementia were more likely to live in a deprived area (conditional OR 1.26;95%CI:1.20-1.31 most vs least deprived), have documented memory impairment (cOR = 11.97;95%CI:11.24-12.75), falls (cOR = 2.36;95%CI:2.31-2.41), depression (cOR = 2.03; 95%CI:1.98-2.09) or anxiety (cOR = 1.27; 95%CI:1.23-1.32). The lifetime risk of dementia at age 65 was 9.2% (95%CI:9.0%-9.4%), in men and 14.9% (95%CI:14.7%-15.1%) in women. The population prevalence of recorded dementia increased from 0.3% in 2000 to 0.7% in 2010. A higher mortality rate was observed in people with than without dementia (IRR = 1.56;95%CI:1.54-1.58).

Conclusions

Most people with a record of dementia in linked UK EHR had some corroborating evidence for diagnosis. The estimated 10-year risk of dementia was higher than published population-based estimations. EHR are therefore a promising source of data for dementia research.", - "laySummary": "", - "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0199026&type=printable; doi:https://doi.org/10.1371/journal.pone.0199026; html:https://europepmc.org/articles/PMC6019102; pdf:https://europepmc.org/articles/PMC6019102?pdf=render" - }, { "id": "37285143", "doi": "https://doi.org/10.1001/jamacardio.2023.1290", @@ -22627,21 +22610,21 @@ "urls": "doi:https://doi.org/10.1093/ije/dyaa216; doi:https://doi.org/10.1093/ije/dyaa216; html:https://europepmc.org/articles/PMC8271202; pdf:https://europepmc.org/articles/PMC8271202?pdf=render" }, { - "id": "36264615", - "doi": "https://doi.org/10.1161/circgen.122.003704", - "title": "Prevalence and Disease Expression of Pathogenic and Likely Pathogenic Variants Associated With Inherited Cardiomyopathies in the General Population.", - "authorString": "Bourfiss M, van Vugt M, Alasiri AI, Ruijsink B, van Setten J, Schmidt AF, Dooijes D, Puyol-Ant\u00f3n E, Velthuis BK, van Tintelen JP, Te Riele ASJM, Baas AF, Asselbergs FW.", + "id": "37990330", + "doi": "https://doi.org/10.1186/s13063-023-07763-6", + "title": "Correction: Medicines and Healthcare products Regulatory Agency's \"Consultation on proposals for legislative changes for clinical trials\": a response from the Trials Methodology Research Partnership Adaptive Designs Working Group, with a focus on data sharing.", + "authorString": "Law M, Couturier DL, Choodari-Oskooei B, Crout P, Gamble C, Jacko P, Pallmann P, Pilling M, Robertson DS, Robling M, Sydes MR, Villar SS, Wason J, Wheeler G, Williamson SF, Yap C, Jaki T.", "authorAffiliations": "", - "journalTitle": "Circulation. Genomic and precision medicine", - "pubYear": "2022", - "date": "2022-10-20", + "journalTitle": "Trials", + "pubYear": "2023", + "date": "2023-11-21", "isOpenAccess": "Y", - "keywords": "Genetics; Dilated cardiomyopathy; hypertrophic cardiomyopathy; Arrhythmogenic Right Ventricular Cardiomyopathy; Whole Exome Sequencing", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Pathogenic and likely pathogenic variants associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy (DCM), and hypertrophic cardiomyopathy (HCM) are recommended to be reported as secondary findings in genome sequencing studies. This provides opportunities for early diagnosis, but also fuels uncertainty in variant carriers (G+), since disease penetrance is incomplete. We assessed the prevalence and disease expression of G+ in the general population.

Methods

We identified pathogenic and likely pathogenic variants associated with ARVC, DCM and/or HCM in 200 643 UK Biobank individuals, who underwent whole exome sequencing. We calculated the prevalence of G+ and analyzed the frequency of cardiomyopathy/heart failure diagnosis. In undiagnosed individuals, we analyzed early signs of disease expression using available electrocardiography and cardiac magnetic resonance imaging data.

Results

We found a prevalence of 1:578, 1:251, and 1:149 for pathogenic and likely pathogenic variants associated with ARVC, DCM and HCM respectively. Compared with controls, cardiovascular mortality was higher in DCM G+ (odds ratio 1.67 [95% CI 1.04; 2.59], P=0.030), but similar in ARVC and HCM G+ (P\u22650.100). Cardiomyopathy or heart failure diagnosis were more frequent in DCM G+ (odds ratio 3.66 [95% CI 2.24; 5.81], P=4.9\u00d710-7) and HCM G+ (odds ratio 3.03 [95% CI 1.98; 4.56], P=5.8\u00d710-7), but comparable in ARVC G+ (P=0.172). In contrast, ARVC G+ had more ventricular arrhythmias (P=3.3\u00d710-4). In undiagnosed individuals, left ventricular ejection fraction was reduced in DCM G+ (P=0.009).

Conclusions

In the general population, pathogenic and likely pathogenic variants associated with ARVC, DCM, or HCM are not uncommon. Although G+ have increased mortality and morbidity, disease penetrance in these carriers from the general population remains low (1.2-3.1%). Follow-up decisions in case of incidental findings should not be based solely on a variant, but on multiple factors, including family history and disease expression.", + "abstract": "", "laySummary": "", - "urls": "pdf:https://discovery.ucl.ac.uk/10160737/3/Asselbergs_hcg-15-e003704.pdf; doi:https://doi.org/10.1161/CIRCGEN.122.003704; html:https://europepmc.org/articles/PMC9770140; pdf:https://europepmc.org/articles/PMC9770140?pdf=render" + "urls": "pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07763-6; doi:https://doi.org/10.1186/s13063-023-07763-6; html:https://europepmc.org/articles/PMC10664262; pdf:https://europepmc.org/articles/PMC10664262?pdf=render" }, { "id": "35684987", @@ -22660,6 +22643,23 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/camh.12571; doi:https://doi.org/10.1111/camh.12571; html:https://europepmc.org/articles/PMC10083915; pdf:https://europepmc.org/articles/PMC10083915?pdf=render" }, + { + "id": "36264615", + "doi": "https://doi.org/10.1161/circgen.122.003704", + "title": "Prevalence and Disease Expression of Pathogenic and Likely Pathogenic Variants Associated With Inherited Cardiomyopathies in the General Population.", + "authorString": "Bourfiss M, van Vugt M, Alasiri AI, Ruijsink B, van Setten J, Schmidt AF, Dooijes D, Puyol-Ant\u00f3n E, Velthuis BK, van Tintelen JP, Te Riele ASJM, Baas AF, Asselbergs FW.", + "authorAffiliations": "", + "journalTitle": "Circulation. Genomic and precision medicine", + "pubYear": "2022", + "date": "2022-10-20", + "isOpenAccess": "Y", + "keywords": "Genetics; Dilated cardiomyopathy; hypertrophic cardiomyopathy; Arrhythmogenic Right Ventricular Cardiomyopathy; Whole Exome Sequencing", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Pathogenic and likely pathogenic variants associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy (DCM), and hypertrophic cardiomyopathy (HCM) are recommended to be reported as secondary findings in genome sequencing studies. This provides opportunities for early diagnosis, but also fuels uncertainty in variant carriers (G+), since disease penetrance is incomplete. We assessed the prevalence and disease expression of G+ in the general population.

Methods

We identified pathogenic and likely pathogenic variants associated with ARVC, DCM and/or HCM in 200 643 UK Biobank individuals, who underwent whole exome sequencing. We calculated the prevalence of G+ and analyzed the frequency of cardiomyopathy/heart failure diagnosis. In undiagnosed individuals, we analyzed early signs of disease expression using available electrocardiography and cardiac magnetic resonance imaging data.

Results

We found a prevalence of 1:578, 1:251, and 1:149 for pathogenic and likely pathogenic variants associated with ARVC, DCM and HCM respectively. Compared with controls, cardiovascular mortality was higher in DCM G+ (odds ratio 1.67 [95% CI 1.04; 2.59], P=0.030), but similar in ARVC and HCM G+ (P\u22650.100). Cardiomyopathy or heart failure diagnosis were more frequent in DCM G+ (odds ratio 3.66 [95% CI 2.24; 5.81], P=4.9\u00d710-7) and HCM G+ (odds ratio 3.03 [95% CI 1.98; 4.56], P=5.8\u00d710-7), but comparable in ARVC G+ (P=0.172). In contrast, ARVC G+ had more ventricular arrhythmias (P=3.3\u00d710-4). In undiagnosed individuals, left ventricular ejection fraction was reduced in DCM G+ (P=0.009).

Conclusions

In the general population, pathogenic and likely pathogenic variants associated with ARVC, DCM, or HCM are not uncommon. Although G+ have increased mortality and morbidity, disease penetrance in these carriers from the general population remains low (1.2-3.1%). Follow-up decisions in case of incidental findings should not be based solely on a variant, but on multiple factors, including family history and disease expression.", + "laySummary": "", + "urls": "pdf:https://discovery.ucl.ac.uk/10160737/3/Asselbergs_hcg-15-e003704.pdf; doi:https://doi.org/10.1161/CIRCGEN.122.003704; html:https://europepmc.org/articles/PMC9770140; pdf:https://europepmc.org/articles/PMC9770140?pdf=render" + }, { "id": "37706486", "doi": "https://doi.org/10.1080/09638288.2023.2254235", @@ -22966,23 +22966,6 @@ "laySummary": "", "urls": "pdf:https://health-policy-systems.biomedcentral.com/counter/pdf/10.1186/s12961-022-00956-6; doi:https://doi.org/10.1186/s12961-022-00956-6; html:https://europepmc.org/articles/PMC9888332; pdf:https://europepmc.org/articles/PMC9888332?pdf=render" }, - { - "id": "35396183", - "doi": "https://doi.org/10.1016/s2589-7500(22)00003-6", - "title": "The medical algorithmic audit.", - "authorString": "Liu X, Glocker B, McCradden MM, Ghassemi M, Denniston AK, Oakden-Rayner L.", - "authorAffiliations": "", - "journalTitle": "The Lancet. Digital health", - "pubYear": "2022", - "date": "2022-04-05", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Artificial intelligence systems for health care, like any other medical device, have the potential to fail. However, specific qualities of artificial intelligence systems, such as the tendency to learn spurious correlates in training data, poor generalisability to new deployment settings, and a paucity of reliable explainability mechanisms, mean they can yield unpredictable errors that might be entirely missed without proactive investigation. We propose a medical algorithmic audit framework that guides the auditor through a process of considering potential algorithmic errors in the context of a clinical task, mapping the components that might contribute to the occurrence of errors, and anticipating their potential consequences. We suggest several approaches for testing algorithmic errors, including exploratory error analysis, subgroup testing, and adversarial testing, and provide examples from our own work and previous studies. The medical algorithmic audit is a tool that can be used to better understand the weaknesses of an artificial intelligence system and put in place mechanisms to mitigate their impact. We propose that safety monitoring and medical algorithmic auditing should be a joint responsibility between users and developers, and encourage the use of feedback mechanisms between these groups to promote learning and maintain safe deployment of artificial intelligence systems.", - "laySummary": "", - "urls": "pdf:http://www.thelancet.com/article/S2589750022000036/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00003-6" - }, { "id": "31446406", "doi": "https://doi.org/10.1136/bmjopen-2018-027577", @@ -23000,6 +22983,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/9/8/e027577.full.pdf; doi:https://doi.org/10.1136/bmjopen-2018-027577; html:https://europepmc.org/articles/PMC6720244; pdf:https://europepmc.org/articles/PMC6720244?pdf=render" }, + { + "id": "35396183", + "doi": "https://doi.org/10.1016/s2589-7500(22)00003-6", + "title": "The medical algorithmic audit.", + "authorString": "Liu X, Glocker B, McCradden MM, Ghassemi M, Denniston AK, Oakden-Rayner L.", + "authorAffiliations": "", + "journalTitle": "The Lancet. Digital health", + "pubYear": "2022", + "date": "2022-04-05", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Artificial intelligence systems for health care, like any other medical device, have the potential to fail. However, specific qualities of artificial intelligence systems, such as the tendency to learn spurious correlates in training data, poor generalisability to new deployment settings, and a paucity of reliable explainability mechanisms, mean they can yield unpredictable errors that might be entirely missed without proactive investigation. We propose a medical algorithmic audit framework that guides the auditor through a process of considering potential algorithmic errors in the context of a clinical task, mapping the components that might contribute to the occurrence of errors, and anticipating their potential consequences. We suggest several approaches for testing algorithmic errors, including exploratory error analysis, subgroup testing, and adversarial testing, and provide examples from our own work and previous studies. The medical algorithmic audit is a tool that can be used to better understand the weaknesses of an artificial intelligence system and put in place mechanisms to mitigate their impact. We propose that safety monitoring and medical algorithmic auditing should be a joint responsibility between users and developers, and encourage the use of feedback mechanisms between these groups to promote learning and maintain safe deployment of artificial intelligence systems.", + "laySummary": "", + "urls": "pdf:http://www.thelancet.com/article/S2589750022000036/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00003-6" + }, { "id": "34751629", "doi": "https://doi.org/10.1080/09638288.2021.1998671", @@ -23238,23 +23238,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ehjdh/advance-article-pdf/doi/10.1093/ehjdh/ztad037/50634764/ztad037.pdf; doi:https://doi.org/10.1093/ehjdh/ztad037; html:https://europepmc.org/articles/PMC10393938; pdf:https://europepmc.org/articles/PMC10393938?pdf=render" }, - { - "id": "36289925", - "doi": "https://doi.org/10.3390/biomedicines10102662", - "title": "Temporal Evolution of Multiday, Epileptic Functional Networks Prior to Seizure Occurrence.", - "authorString": "Laiou P, Biondi A, Bruno E, Viana PF, Winston JS, Rashid Z, Ranjan Y, Conde P, Stewart C, Sun S, Zhang Y, Folarin A, Dobson RJB, Schulze-Bonhage A, D\u00fcmpelmann M, Richardson MP, Radar-Cns Consortium.", - "authorAffiliations": "", - "journalTitle": "Biomedicines", - "pubYear": "2022", - "date": "2022-10-21", - "isOpenAccess": "Y", - "keywords": "Epilepsy; EEG; Graph theory; ECG; Functional Network; Seizure Lateralization; Evolving Network", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Epilepsy is one of the most common neurological disorders, characterized by the occurrence of repeated seizures. Given that epilepsy is considered a network disorder, tools derived from network neuroscience may confer the valuable ability to quantify the properties of epileptic brain networks. In this study, we use well-established brain network metrics (i.e., mean strength, variance of strength, eigenvector centrality, betweenness centrality) to characterize the temporal evolution of epileptic functional networks over several days prior to seizure occurrence. We infer the networks using long-term electroencephalographic recordings from 12 people with epilepsy. We found that brain network metrics are variable across days and show a circadian periodicity. In addition, we found that in 9 out of 12 patients the distribution of the variance of strength in the day (or even two last days) prior to seizure occurrence is significantly different compared to the corresponding distributions on all previous days. Our results suggest that brain network metrics computed fromelectroencephalographic recordings could potentially be used to characterize brain network changes that occur prior to seizures, and ultimately contribute to seizure warning systems.", - "laySummary": "", - "urls": "pdf:https://www.mdpi.com/2227-9059/10/10/2662/pdf?version=1666684470; doi:https://doi.org/10.3390/biomedicines10102662; html:https://europepmc.org/articles/PMC9599905; pdf:https://europepmc.org/articles/PMC9599905?pdf=render" - }, { "id": "31558464", "doi": "https://doi.org/10.1136/bmjopen-2019-033013", @@ -23272,6 +23255,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/9/9/e033013.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-033013; html:https://europepmc.org/articles/PMC6773283; pdf:https://europepmc.org/articles/PMC6773283?pdf=render" }, + { + "id": "36289925", + "doi": "https://doi.org/10.3390/biomedicines10102662", + "title": "Temporal Evolution of Multiday, Epileptic Functional Networks Prior to Seizure Occurrence.", + "authorString": "Laiou P, Biondi A, Bruno E, Viana PF, Winston JS, Rashid Z, Ranjan Y, Conde P, Stewart C, Sun S, Zhang Y, Folarin A, Dobson RJB, Schulze-Bonhage A, D\u00fcmpelmann M, Richardson MP, Radar-Cns Consortium.", + "authorAffiliations": "", + "journalTitle": "Biomedicines", + "pubYear": "2022", + "date": "2022-10-21", + "isOpenAccess": "Y", + "keywords": "Epilepsy; EEG; Graph theory; ECG; Functional Network; Seizure Lateralization; Evolving Network", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Epilepsy is one of the most common neurological disorders, characterized by the occurrence of repeated seizures. Given that epilepsy is considered a network disorder, tools derived from network neuroscience may confer the valuable ability to quantify the properties of epileptic brain networks. In this study, we use well-established brain network metrics (i.e., mean strength, variance of strength, eigenvector centrality, betweenness centrality) to characterize the temporal evolution of epileptic functional networks over several days prior to seizure occurrence. We infer the networks using long-term electroencephalographic recordings from 12 people with epilepsy. We found that brain network metrics are variable across days and show a circadian periodicity. In addition, we found that in 9 out of 12 patients the distribution of the variance of strength in the day (or even two last days) prior to seizure occurrence is significantly different compared to the corresponding distributions on all previous days. Our results suggest that brain network metrics computed fromelectroencephalographic recordings could potentially be used to characterize brain network changes that occur prior to seizures, and ultimately contribute to seizure warning systems.", + "laySummary": "", + "urls": "pdf:https://www.mdpi.com/2227-9059/10/10/2662/pdf?version=1666684470; doi:https://doi.org/10.3390/biomedicines10102662; html:https://europepmc.org/articles/PMC9599905; pdf:https://europepmc.org/articles/PMC9599905?pdf=render" + }, { "id": "34386668", "doi": "https://doi.org/10.1016/j.ekir.2021.05.031", @@ -23306,23 +23306,6 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e052514.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-052514; html:https://europepmc.org/articles/PMC9019828; pdf:https://europepmc.org/articles/PMC9019828?pdf=render" }, - { - "id": "38692709", - "doi": "https://doi.org/10.1136/bmjresp-2023-001746", - "title": "Risk factors for asthma-related hospital and intensive care admissions in children, adolescents and adults: a cohort study using primary and secondary care data.", - "authorString": "Simms-Williams N, Nagakumar P, Thayakaran R, Adderley NJ, Hotham R, Mansur AH, Nirantharakumar K, Haroon S.", - "authorAffiliations": "", - "journalTitle": "BMJ open respiratory research", - "pubYear": "2024", - "date": "2024-05-01", - "isOpenAccess": "Y", - "keywords": "Asthma; Asthma Epidemiology", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Asthma remains a common cause of hospital admissions across the life course. We estimated the contribution of key risk factors to asthma-related hospital and intensive care unit (ICU) admissions in children, adolescents and adults.

Methods

This was a UK-based cohort study using linked primary care (Clinical Practice Research Datalink Aurum) and secondary care (Hospital Episode Statistics Admitted Patient Care) data. Patients were eligible if they were aged 5 years and older and had been diagnosed with asthma. This included 90\u2009989 children aged 5-11 years, 114\u2009927 adolescents aged 12-17 years and 1\u2009179\u2009410 adults aged 18 years or older. The primary outcome was asthma-related hospital admissions from 1 January 2017 to 31 December 2019. The secondary outcome was asthma-related ICU admissions. Incidence rate ratios adjusted for demographic and clinical risk factors were estimated using negative binomial models. Population attributable fraction (PAF) was estimated for modifiable risk factors.

Results

Younger age groups, females and those from ethnic minority and lower socioeconomic backgrounds had an increased risk of asthma-related hospital admissions. Increasing medication burden, including excessive use of short-acting bronchodilators, was also strongly associated with the primary outcome. Similar risk factors were observed for asthma-related ICU admissions. The key potentially modifiable or treatable risk factors were smoking in adolescents and adults (PAF 6.8%, 95%\u2009CI 0.9% to 12.3% and 4.3%, 95%\u2009CI 3.0% to 5.7%, respectively), and obesity (PAF 23.3%, 95%\u2009CI 20.5% to 26.1%), depression (11.1%, 95% CI 9.1% to 13.1%), gastro-oesophageal reflux disease (2.3%, 95% CI 1.2% to 3.4%), anxiety (2.0%, 95% CI 0.5% to 3.6%) and chronic rhinosinusitis (0.8%, 95% CI 0.3% to 1.3%) in adults.

Conclusions

There are significant sociodemographic inequalities in the rates of asthma-related hospital and ICU admissions. Treating age-specific modifiable risk factors should be considered an integral part of asthma management, which could potentially reduce the rate of avoidable hospital admissions.", - "laySummary": "", - "urls": "pdf:https://bmjopenrespres.bmj.com/content/bmjresp/11/1/e001746.full.pdf; doi:https://doi.org/10.1136/bmjresp-2023-001746; html:https://europepmc.org/articles/PMC11086188; pdf:https://europepmc.org/articles/PMC11086188?pdf=render" - }, { "id": "36285341", "doi": "https://doi.org/10.1080/17434440.2022.2132147", @@ -23357,6 +23340,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S0140673620309302/pdf; doi:https://doi.org/10.1016/S0140-6736(20)30930-2; html:https://europepmc.org/articles/PMC7456783; pdf:https://europepmc.org/articles/PMC7456783?pdf=render" }, + { + "id": "38692709", + "doi": "https://doi.org/10.1136/bmjresp-2023-001746", + "title": "Risk factors for asthma-related hospital and intensive care admissions in children, adolescents and adults: a cohort study using primary and secondary care data.", + "authorString": "Simms-Williams N, Nagakumar P, Thayakaran R, Adderley NJ, Hotham R, Mansur AH, Nirantharakumar K, Haroon S.", + "authorAffiliations": "", + "journalTitle": "BMJ open respiratory research", + "pubYear": "2024", + "date": "2024-05-01", + "isOpenAccess": "Y", + "keywords": "Asthma; Asthma Epidemiology", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Asthma remains a common cause of hospital admissions across the life course. We estimated the contribution of key risk factors to asthma-related hospital and intensive care unit (ICU) admissions in children, adolescents and adults.

Methods

This was a UK-based cohort study using linked primary care (Clinical Practice Research Datalink Aurum) and secondary care (Hospital Episode Statistics Admitted Patient Care) data. Patients were eligible if they were aged 5 years and older and had been diagnosed with asthma. This included 90\u2009989 children aged 5-11 years, 114\u2009927 adolescents aged 12-17 years and 1\u2009179\u2009410 adults aged 18 years or older. The primary outcome was asthma-related hospital admissions from 1 January 2017 to 31 December 2019. The secondary outcome was asthma-related ICU admissions. Incidence rate ratios adjusted for demographic and clinical risk factors were estimated using negative binomial models. Population attributable fraction (PAF) was estimated for modifiable risk factors.

Results

Younger age groups, females and those from ethnic minority and lower socioeconomic backgrounds had an increased risk of asthma-related hospital admissions. Increasing medication burden, including excessive use of short-acting bronchodilators, was also strongly associated with the primary outcome. Similar risk factors were observed for asthma-related ICU admissions. The key potentially modifiable or treatable risk factors were smoking in adolescents and adults (PAF 6.8%, 95%\u2009CI 0.9% to 12.3% and 4.3%, 95%\u2009CI 3.0% to 5.7%, respectively), and obesity (PAF 23.3%, 95%\u2009CI 20.5% to 26.1%), depression (11.1%, 95% CI 9.1% to 13.1%), gastro-oesophageal reflux disease (2.3%, 95% CI 1.2% to 3.4%), anxiety (2.0%, 95% CI 0.5% to 3.6%) and chronic rhinosinusitis (0.8%, 95% CI 0.3% to 1.3%) in adults.

Conclusions

There are significant sociodemographic inequalities in the rates of asthma-related hospital and ICU admissions. Treating age-specific modifiable risk factors should be considered an integral part of asthma management, which could potentially reduce the rate of avoidable hospital admissions.", + "laySummary": "", + "urls": "pdf:https://bmjopenrespres.bmj.com/content/bmjresp/11/1/e001746.full.pdf; doi:https://doi.org/10.1136/bmjresp-2023-001746; html:https://europepmc.org/articles/PMC11086188; pdf:https://europepmc.org/articles/PMC11086188?pdf=render" + }, { "id": "36576811", "doi": "https://doi.org/10.1001/jamacardio.2022.4466", @@ -23629,23 +23629,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeab266/41764801/jeab266.pdf; doi:https://doi.org/10.1093/ehjci/jeab266; html:https://europepmc.org/articles/PMC9365306; pdf:https://europepmc.org/articles/PMC9365306?pdf=render" }, - { - "id": "37319288", - "doi": "https://doi.org/10.1371/journal.pone.0287264", - "title": "Evaluation of data processing pipelines on real-world electronic health records data for the purpose of measuring patient similarity.", - "authorString": "Pikoula M, Kallis C, Madjiheurem S, Quint JK, Bafadhel M, Denaxas S.", - "authorAffiliations": "", - "journalTitle": "PloS one", - "pubYear": "2023", - "date": "2023-06-15", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

The ever-growing size, breadth, and availability of patient data allows for a wide variety of clinical features to serve as inputs for phenotype discovery using cluster analysis. Data of mixed types in particular are not straightforward to combine into a single feature vector, and techniques used to address this can be biased towards certain data types in ways that are not immediately obvious or intended. In this context, the process of constructing clinically meaningful patient representations from complex datasets has not been systematically evaluated.

Aims

Our aim was to a) outline and b) implement an analytical framework to evaluate distinct methods of constructing patient representations from routine electronic health record data for the purpose of measuring patient similarity. We applied the analysis on a patient cohort diagnosed with chronic obstructive pulmonary disease.

Methods

Using data from the CALIBER data resource, we extracted clinically relevant features for a cohort of patients diagnosed with chronic obstructive pulmonary disease. We used four different data processing pipelines to construct lower dimensional patient representations from which we calculated patient similarity scores. We described the resulting representations, ranked the influence of each individual feature on patient similarity and evaluated the effect of different pipelines on clustering outcomes. Experts evaluated the resulting representations by rating the clinical relevance of similar patient suggestions with regard to a reference patient.

Results

Each of the four pipelines resulted in similarity scores primarily driven by a unique set of features. It was demonstrated that data transformations according to each pipeline prior to clustering can result in a variation of clustering results of over 40%. The most appropriate pipeline was selected on the basis of feature ranking and clinical expertise. There was moderate agreement between clinicians as measured by Cohen's kappa coefficient.

Conclusions

Data transformation has downstream and unforeseen consequences in cluster analysis. Rather than viewing this process as a black box, we have shown ways to quantitatively and qualitatively evaluate and select the appropriate preprocessing pipeline.", - "laySummary": "", - "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287264&type=printable; doi:https://doi.org/10.1371/journal.pone.0287264; html:https://europepmc.org/articles/PMC10270623; pdf:https://europepmc.org/articles/PMC10270623?pdf=render" - }, { "id": "32856398", "doi": "https://doi.org/10.1111/1742-6723.13604", @@ -23663,6 +23646,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/1742-6723.13604" }, + { + "id": "37319288", + "doi": "https://doi.org/10.1371/journal.pone.0287264", + "title": "Evaluation of data processing pipelines on real-world electronic health records data for the purpose of measuring patient similarity.", + "authorString": "Pikoula M, Kallis C, Madjiheurem S, Quint JK, Bafadhel M, Denaxas S.", + "authorAffiliations": "", + "journalTitle": "PloS one", + "pubYear": "2023", + "date": "2023-06-15", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

The ever-growing size, breadth, and availability of patient data allows for a wide variety of clinical features to serve as inputs for phenotype discovery using cluster analysis. Data of mixed types in particular are not straightforward to combine into a single feature vector, and techniques used to address this can be biased towards certain data types in ways that are not immediately obvious or intended. In this context, the process of constructing clinically meaningful patient representations from complex datasets has not been systematically evaluated.

Aims

Our aim was to a) outline and b) implement an analytical framework to evaluate distinct methods of constructing patient representations from routine electronic health record data for the purpose of measuring patient similarity. We applied the analysis on a patient cohort diagnosed with chronic obstructive pulmonary disease.

Methods

Using data from the CALIBER data resource, we extracted clinically relevant features for a cohort of patients diagnosed with chronic obstructive pulmonary disease. We used four different data processing pipelines to construct lower dimensional patient representations from which we calculated patient similarity scores. We described the resulting representations, ranked the influence of each individual feature on patient similarity and evaluated the effect of different pipelines on clustering outcomes. Experts evaluated the resulting representations by rating the clinical relevance of similar patient suggestions with regard to a reference patient.

Results

Each of the four pipelines resulted in similarity scores primarily driven by a unique set of features. It was demonstrated that data transformations according to each pipeline prior to clustering can result in a variation of clustering results of over 40%. The most appropriate pipeline was selected on the basis of feature ranking and clinical expertise. There was moderate agreement between clinicians as measured by Cohen's kappa coefficient.

Conclusions

Data transformation has downstream and unforeseen consequences in cluster analysis. Rather than viewing this process as a black box, we have shown ways to quantitatively and qualitatively evaluate and select the appropriate preprocessing pipeline.", + "laySummary": "", + "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287264&type=printable; doi:https://doi.org/10.1371/journal.pone.0287264; html:https://europepmc.org/articles/PMC10270623; pdf:https://europepmc.org/articles/PMC10270623?pdf=render" + }, { "id": "32352158", "doi": "https://doi.org/10.1002/bjs.11580", @@ -23697,23 +23697,6 @@ "laySummary": "This is a summary of new methods for estimating phyiscal distancing and compliance with lockdown. I haven't scored the content because it isn't primary research.", "urls": "doi:https://doi.org/10.7189/jogh.10.010348; doi:https://doi.org/10.7189/jogh.10.010348; html:https://europepmc.org/articles/PMC7211415; pdf:https://europepmc.org/articles/PMC7211415?pdf=render" }, - { - "id": "35202588", - "doi": "https://doi.org/10.1016/s2213-8587(22)00015-8", - "title": "Dose-response relationships for vitamin D and all-cause mortality - Authors' reply.", - "authorString": "Burgess S, Butterworth AS.", - "authorAffiliations": "", - "journalTitle": "The lancet. Diabetes & endocrinology", - "pubYear": "2022", - "date": "2022-03-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "pdf:http://www.thelancet.com/article/S2213858722000158/pdf; doi:https://doi.org/10.1016/S2213-8587(22)00015-8" - }, { "id": "34304930", "doi": "https://doi.org/10.1016/j.burns.2021.06.007", @@ -23731,6 +23714,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.burns.2021.06.007" }, + { + "id": "35202588", + "doi": "https://doi.org/10.1016/s2213-8587(22)00015-8", + "title": "Dose-response relationships for vitamin D and all-cause mortality - Authors' reply.", + "authorString": "Burgess S, Butterworth AS.", + "authorAffiliations": "", + "journalTitle": "The lancet. Diabetes & endocrinology", + "pubYear": "2022", + "date": "2022-03-01", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "pdf:http://www.thelancet.com/article/S2213858722000158/pdf; doi:https://doi.org/10.1016/S2213-8587(22)00015-8" + }, { "id": "37730605", "doi": "https://doi.org/10.1186/s12889-023-16523-9", @@ -23918,23 +23918,6 @@ "laySummary": "", "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/A60E6D761449A937DCE08F3A075B236D/S2045796023000276a.pdf/div-class-title-the-mental-health-of-all-children-in-contact-with-social-services-a-population-wide-record-linkage-study-in-northern-ireland-div.pdf; doi:https://doi.org/10.1017/S2045796023000276; html:https://europepmc.org/articles/PMC10227534; pdf:https://europepmc.org/articles/PMC10227534?pdf=render" }, - { - "id": "38326875", - "doi": "https://doi.org/10.1186/s13059-024-03172-3", - "title": "IDHwt glioblastomas can be stratified by their transcriptional response to standard treatment, with implications for targeted therapy.", - "authorString": "Tanner G, Barrow R, Ajaib S, Al-Jabri M, Ahmed N, Pollock S, Finetti M, Rippaus N, Bruns AF, Syed K, Poulter JA, Matthews L, Hughes T, Wilson E, Johnson C, Varn FS, Br\u00fcning-Richardson A, Hogg C, Droop A, Gusnanto A, Care MA, Cutillo L, Westhead DR, Short SC, Jenkinson MD, Brodbelt A, Chakrabarty A, Ismail A, Verhaak RGW, Stead LF.", - "authorAffiliations": "", - "journalTitle": "Genome biology", - "pubYear": "2024", - "date": "2024-02-07", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Glioblastoma (GBM) brain tumors lacking IDH1 mutations (IDHwt) have the worst prognosis of all brain neoplasms. Patients receive surgery and chemoradiotherapy but tumors almost always fatally recur.

Results

Using RNA sequencing data from 107 pairs of pre- and post-standard treatment locally recurrent IDHwt GBM tumors, we identify two responder subtypes based on longitudinal changes in gene expression. In two thirds of patients, a specific subset of genes is upregulated from primary to recurrence (Up responders), and in one third, the same genes are downregulated (Down responders), specifically in neoplastic cells. Characterization of the responder subtypes indicates subtype-specific adaptive treatment resistance mechanisms that are associated with distinct changes in the tumor microenvironment. In Up responders, recurrent tumors are enriched in quiescent proneural GBM stem cells and differentiated neoplastic cells, with increased interaction with the surrounding normal brain and neurotransmitter signaling, whereas Down responders commonly undergo mesenchymal transition. ChIP-sequencing data from longitudinal GBM tumors suggests that the observed transcriptional reprogramming could be driven by Polycomb-based chromatin remodeling rather than DNA methylation.

Conclusions

We show that the responder subtype is cancer-cell intrinsic, recapitulated in in vitro GBM cell models, and influenced by the presence of the tumor microenvironment. Stratifying GBM tumors by responder subtype may lead to more effective treatment.", - "laySummary": "", - "urls": "pdf:https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-024-03172-3; doi:https://doi.org/10.1186/s13059-024-03172-3; html:https://europepmc.org/articles/PMC10848526; pdf:https://europepmc.org/articles/PMC10848526?pdf=render" - }, { "id": "36198485", "doi": "https://doi.org/10.1136/jech-2021-217986", @@ -23952,6 +23935,23 @@ "laySummary": "", "urls": "pdf:https://jech.bmj.com/content/jech/76/12/991.full.pdf; doi:https://doi.org/10.1136/jech-2021-217986; html:https://europepmc.org/articles/PMC9664100; pdf:https://europepmc.org/articles/PMC9664100?pdf=render" }, + { + "id": "38326875", + "doi": "https://doi.org/10.1186/s13059-024-03172-3", + "title": "IDHwt glioblastomas can be stratified by their transcriptional response to standard treatment, with implications for targeted therapy.", + "authorString": "Tanner G, Barrow R, Ajaib S, Al-Jabri M, Ahmed N, Pollock S, Finetti M, Rippaus N, Bruns AF, Syed K, Poulter JA, Matthews L, Hughes T, Wilson E, Johnson C, Varn FS, Br\u00fcning-Richardson A, Hogg C, Droop A, Gusnanto A, Care MA, Cutillo L, Westhead DR, Short SC, Jenkinson MD, Brodbelt A, Chakrabarty A, Ismail A, Verhaak RGW, Stead LF.", + "authorAffiliations": "", + "journalTitle": "Genome biology", + "pubYear": "2024", + "date": "2024-02-07", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Glioblastoma (GBM) brain tumors lacking IDH1 mutations (IDHwt) have the worst prognosis of all brain neoplasms. Patients receive surgery and chemoradiotherapy but tumors almost always fatally recur.

Results

Using RNA sequencing data from 107 pairs of pre- and post-standard treatment locally recurrent IDHwt GBM tumors, we identify two responder subtypes based on longitudinal changes in gene expression. In two thirds of patients, a specific subset of genes is upregulated from primary to recurrence (Up responders), and in one third, the same genes are downregulated (Down responders), specifically in neoplastic cells. Characterization of the responder subtypes indicates subtype-specific adaptive treatment resistance mechanisms that are associated with distinct changes in the tumor microenvironment. In Up responders, recurrent tumors are enriched in quiescent proneural GBM stem cells and differentiated neoplastic cells, with increased interaction with the surrounding normal brain and neurotransmitter signaling, whereas Down responders commonly undergo mesenchymal transition. ChIP-sequencing data from longitudinal GBM tumors suggests that the observed transcriptional reprogramming could be driven by Polycomb-based chromatin remodeling rather than DNA methylation.

Conclusions

We show that the responder subtype is cancer-cell intrinsic, recapitulated in in vitro GBM cell models, and influenced by the presence of the tumor microenvironment. Stratifying GBM tumors by responder subtype may lead to more effective treatment.", + "laySummary": "", + "urls": "pdf:https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-024-03172-3; doi:https://doi.org/10.1186/s13059-024-03172-3; html:https://europepmc.org/articles/PMC10848526; pdf:https://europepmc.org/articles/PMC10848526?pdf=render" + }, { "id": "33240510", "doi": "https://doi.org/10.15420/aer.2020.26", @@ -24071,23 +24071,6 @@ "laySummary": "", "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/0272989X21994035; doi:https://doi.org/10.1177/0272989X21994035" }, - { - "id": "37217302", - "doi": "https://doi.org/10.1136/emermed-2022-212827", - "title": "External validation of triage tools for adults with suspected COVID-19 in a middle-income setting: an observational cohort study.", - "authorString": "Marincowitz C, Sbaffi L, Hasan M, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Omer Y, Wallis LA.", - "authorAffiliations": "", - "journalTitle": "Emergency medicine journal : EMJ", - "pubYear": "2023", - "date": "2023-05-22", - "isOpenAccess": "Y", - "keywords": "risk management; Triage; Covid-19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Tools proposed to triage ED acuity in suspected COVID-19 were derived and validated in higher income settings during early waves of the pandemic. We estimated the accuracy of seven risk-stratification tools recommended to predict severe illness in the Western Cape, South Africa.

Methods

An observational cohort study using routinely collected data from EDs across the Western Cape, from 27 August 2020 to 11 March 2022, was conducted to assess the performance of the PRIEST (Pandemic Respiratory Infection Emergency System Triage) tool, NEWS2 (National Early Warning Score, version 2), TEWS (Triage Early Warning Score), the WHO algorithm, CRB-65, Quick COVID-19 Severity Index and PMEWS (Pandemic Medical Early Warning Score) in suspected COVID-19. The primary outcome was intubation or non-invasive ventilation, death or intensive care unit admission at 30 days.

Results

Of the 446\u2009084 patients, 15\u2009397 (3.45%, 95% CI 34% to 35.1%) experienced the primary outcome. Clinical decision-making for inpatient admission achieved a sensitivity of 0.77 (95% CI 0.76 to 0.78), specificity of 0.88 (95% CI 0.87 to 0.88) and the negative predictive value (NPV) of 0.99 (95% CI 0.99 to 0.99). NEWS2, PMEWS and PRIEST scores achieved good estimated discrimination (C-statistic 0.79 to 0.82) and identified patients at risk of adverse outcomes at recommended cut-offs with moderate sensitivity (>0.8) and specificity ranging from 0.41 to 0.64. Use of the tools at recommended thresholds would have more than doubled admissions, with only a 0.01% reduction in false negative triage.

Conclusion

No risk score outperformed existing clinical decision-making in determining the need for inpatient admission based on prediction of the primary outcome in this setting. Use of the PRIEST score at a threshold of one point higher than the previously recommended best approximated existing clinical accuracy.", - "laySummary": "", - "urls": "pdf:https://emj.bmj.com/content/emermed/early/2023/05/22/emermed-2022-212827.full.pdf; doi:https://doi.org/10.1136/emermed-2022-212827; html:https://europepmc.org/articles/PMC10359554; pdf:https://europepmc.org/articles/PMC10359554?pdf=render" - }, { "id": "35028631", "doi": "https://doi.org/10.1016/s2666-7568(21)00281-6", @@ -24105,6 +24088,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S2666756821002816/pdf; doi:https://doi.org/10.1016/S2666-7568(21)00281-6; html:https://europepmc.org/articles/PMC8732286" }, + { + "id": "37217302", + "doi": "https://doi.org/10.1136/emermed-2022-212827", + "title": "External validation of triage tools for adults with suspected COVID-19 in a middle-income setting: an observational cohort study.", + "authorString": "Marincowitz C, Sbaffi L, Hasan M, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Omer Y, Wallis LA.", + "authorAffiliations": "", + "journalTitle": "Emergency medicine journal : EMJ", + "pubYear": "2023", + "date": "2023-05-22", + "isOpenAccess": "Y", + "keywords": "risk management; Triage; Covid-19", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Tools proposed to triage ED acuity in suspected COVID-19 were derived and validated in higher income settings during early waves of the pandemic. We estimated the accuracy of seven risk-stratification tools recommended to predict severe illness in the Western Cape, South Africa.

Methods

An observational cohort study using routinely collected data from EDs across the Western Cape, from 27 August 2020 to 11 March 2022, was conducted to assess the performance of the PRIEST (Pandemic Respiratory Infection Emergency System Triage) tool, NEWS2 (National Early Warning Score, version 2), TEWS (Triage Early Warning Score), the WHO algorithm, CRB-65, Quick COVID-19 Severity Index and PMEWS (Pandemic Medical Early Warning Score) in suspected COVID-19. The primary outcome was intubation or non-invasive ventilation, death or intensive care unit admission at 30 days.

Results

Of the 446\u2009084 patients, 15\u2009397 (3.45%, 95% CI 34% to 35.1%) experienced the primary outcome. Clinical decision-making for inpatient admission achieved a sensitivity of 0.77 (95% CI 0.76 to 0.78), specificity of 0.88 (95% CI 0.87 to 0.88) and the negative predictive value (NPV) of 0.99 (95% CI 0.99 to 0.99). NEWS2, PMEWS and PRIEST scores achieved good estimated discrimination (C-statistic 0.79 to 0.82) and identified patients at risk of adverse outcomes at recommended cut-offs with moderate sensitivity (>0.8) and specificity ranging from 0.41 to 0.64. Use of the tools at recommended thresholds would have more than doubled admissions, with only a 0.01% reduction in false negative triage.

Conclusion

No risk score outperformed existing clinical decision-making in determining the need for inpatient admission based on prediction of the primary outcome in this setting. Use of the PRIEST score at a threshold of one point higher than the previously recommended best approximated existing clinical accuracy.", + "laySummary": "", + "urls": "pdf:https://emj.bmj.com/content/emermed/early/2023/05/22/emermed-2022-212827.full.pdf; doi:https://doi.org/10.1136/emermed-2022-212827; html:https://europepmc.org/articles/PMC10359554; pdf:https://europepmc.org/articles/PMC10359554?pdf=render" + }, { "id": "33289226", "doi": "https://doi.org/10.1111/ans.16426", @@ -24156,23 +24156,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1183/23120541.00430-2023; html:https://europepmc.org/articles/PMC11089387; pdf:https://europepmc.org/articles/PMC11089387?pdf=render" }, - { - "id": "38725371", - "doi": "https://doi.org/10.1192/bjo.2024.23", - "title": "Contacts with primary and secondary healthcare before suicide by those under the care of mental health services: case-control, whole-population-based study using person-level linked routine data in Wales, UK during 2000-2015.", - "authorString": "DelPozo-Banos M, Rodway C, Lee SC, Rouquette OY, Ibrahim S, Lloyd K, Appleby L, Kapur N, John A.", - "authorAffiliations": "", - "journalTitle": "BJPsych open", - "pubYear": "2024", - "date": "2024-05-10", - "isOpenAccess": "Y", - "keywords": "Suicide; Mental Health Services; Primary Care; Secondary Care; Electronic Health Records", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

People under the care of mental health services are at increased risk of suicide. Existing studies are small in scale and lack comparisons.

Aims

To identify opportunities for suicide prevention and underpinning data enhancement in people with recent contact with mental health services.

Method

This population-based study includes people who died by suicide in the year following a mental health services contact in Wales, 2001-2015 (cases), paired with similar patients who did not die by suicide (controls). We linked the National Confidential Inquiry into Suicide and Safety in Mental Health and the Suicide Information Database - Cymru with primary and secondary healthcare records. We present results of conditional logistic regression.

Results

We matched 1031 cases with 5155 controls. In the year before their death, 98.3% of cases were in contact with healthcare services, and 28.5% presented with self-harm. Cases had more emergency department contacts (odds ratio 2.4, 95% CI 2.1-2.7) and emergency hospital admissions (odds ratio 1.5, 95% CI 1.4-1.7), but fewer primary care contacts (odds ratio 0.7, 95% CI 0.6-0.9) and out-patient appointments (odds ratio 0.2, 95% CI 0.2-0.3) than controls. Odds ratios were larger in females than males for injury and poisoning (odds ratio: 3.3 (95% CI 2.5-4.5) v. 2.6 (95% CI 2.1-3.1)).

Conclusions

We may be missing existing opportunities to intervene, particularly in emergency departments and hospital admissions with self-harm presentations and with unattributed self-harm, especially in females. Prevention efforts should focus on strengthening routine care contacts, responding to emergency contacts and better self-harm care. There are benefits to enhancing clinical audit systems with routinely collected data.", - "laySummary": "", - "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/4C20CD00C92C75F4F0B4FACD8418B244/S2056472424000231a.pdf/div-class-title-contacts-with-primary-and-secondary-healthcare-before-suicide-by-those-under-the-care-of-mental-health-services-case-control-whole-population-based-study-using-person-level-linked-routine-data-in-wales-uk-during-2000-2015-div.pdf; doi:https://doi.org/10.1192/bjo.2024.23; html:https://europepmc.org/articles/PMC11094447; pdf:https://europepmc.org/articles/PMC11094447?pdf=render" - }, { "id": "33830993", "doi": "https://doi.org/10.1371/journal.pgen.1009428", @@ -24190,6 +24173,23 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009428&type=printable; doi:https://doi.org/10.1371/journal.pgen.1009428; html:https://europepmc.org/articles/PMC8031124; pdf:https://europepmc.org/articles/PMC8031124?pdf=render" }, + { + "id": "38725371", + "doi": "https://doi.org/10.1192/bjo.2024.23", + "title": "Contacts with primary and secondary healthcare before suicide by those under the care of mental health services: case-control, whole-population-based study using person-level linked routine data in Wales, UK during 2000-2015.", + "authorString": "DelPozo-Banos M, Rodway C, Lee SC, Rouquette OY, Ibrahim S, Lloyd K, Appleby L, Kapur N, John A.", + "authorAffiliations": "", + "journalTitle": "BJPsych open", + "pubYear": "2024", + "date": "2024-05-10", + "isOpenAccess": "Y", + "keywords": "Suicide; Mental Health Services; Primary Care; Secondary Care; Electronic Health Records", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

People under the care of mental health services are at increased risk of suicide. Existing studies are small in scale and lack comparisons.

Aims

To identify opportunities for suicide prevention and underpinning data enhancement in people with recent contact with mental health services.

Method

This population-based study includes people who died by suicide in the year following a mental health services contact in Wales, 2001-2015 (cases), paired with similar patients who did not die by suicide (controls). We linked the National Confidential Inquiry into Suicide and Safety in Mental Health and the Suicide Information Database - Cymru with primary and secondary healthcare records. We present results of conditional logistic regression.

Results

We matched 1031 cases with 5155 controls. In the year before their death, 98.3% of cases were in contact with healthcare services, and 28.5% presented with self-harm. Cases had more emergency department contacts (odds ratio 2.4, 95% CI 2.1-2.7) and emergency hospital admissions (odds ratio 1.5, 95% CI 1.4-1.7), but fewer primary care contacts (odds ratio 0.7, 95% CI 0.6-0.9) and out-patient appointments (odds ratio 0.2, 95% CI 0.2-0.3) than controls. Odds ratios were larger in females than males for injury and poisoning (odds ratio: 3.3 (95% CI 2.5-4.5) v. 2.6 (95% CI 2.1-3.1)).

Conclusions

We may be missing existing opportunities to intervene, particularly in emergency departments and hospital admissions with self-harm presentations and with unattributed self-harm, especially in females. Prevention efforts should focus on strengthening routine care contacts, responding to emergency contacts and better self-harm care. There are benefits to enhancing clinical audit systems with routinely collected data.", + "laySummary": "", + "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/4C20CD00C92C75F4F0B4FACD8418B244/S2056472424000231a.pdf/div-class-title-contacts-with-primary-and-secondary-healthcare-before-suicide-by-those-under-the-care-of-mental-health-services-case-control-whole-population-based-study-using-person-level-linked-routine-data-in-wales-uk-during-2000-2015-div.pdf; doi:https://doi.org/10.1192/bjo.2024.23; html:https://europepmc.org/articles/PMC11094447; pdf:https://europepmc.org/articles/PMC11094447?pdf=render" + }, { "id": "35536740", "doi": "https://doi.org/10.1136/bmjopen-2021-052884", @@ -24207,23 +24207,6 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/12/e052884.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-052884; html:https://europepmc.org/articles/PMC8719215; pdf:https://europepmc.org/articles/PMC8719215?pdf=render" }, - { - "id": "38345865", - "doi": "https://doi.org/10.1113/jp284597", - "title": "Reduced plakoglobin increases the risk of sodium current defects and atrial conduction abnormalities in response to androgenic anabolic steroid abuse.", - "authorString": "Sommerfeld LC, Holmes AP, Yu TY, O'Shea C, Kavanagh DM, Pike JM, Wright T, Syeda F, Aljehani A, Kew T, Cardoso VR, Kabir SN, Hepburn C, Menon PR, Broadway-Stringer S, O'Reilly M, Witten A, Fortmueller L, Lutz S, Kulle A, Gkoutos GV, Pavlovic D, Arlt W, Lavery GG, Steeds R, Gehmlich K, Stoll M, Kirchhof P, Fabritz L.", - "authorAffiliations": "", - "journalTitle": "The Journal of physiology", - "pubYear": "2024", - "date": "2024-02-12", - "isOpenAccess": "N", - "keywords": "Testosterone; Conduction velocity; Nav1.5; Desmosome; Arrhythmogenic Right Ventricular Cardiomyopathy; Cardiac Atria", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Androgenic anabolic steroids (AAS) are commonly abused by young men. Male sex and increased AAS levels are associated with earlier and more severe manifestation of common cardiac conditions, such as atrial fibrillation, and rare ones, such as arrhythmogenic right ventricular cardiomyopathy (ARVC). Clinical observations suggest a potential atrial involvement in ARVC. Arrhythmogenic right ventricular cardiomyopathy is caused by desmosomal gene defects, including reduced plakoglobin expression. Here, we analysed clinical records from 146 ARVC patients to identify that ARVC is more common in males than females. Patients with ARVC also had an increased incidence of atrial arrhythmias and P\u00a0wave changes. To study desmosomal vulnerability and the effects of AAS on the atria, young adult male mice, heterozygously deficient for plakoglobin (Plako+/- ), and wild type (WT) littermates were chronically exposed to 5\u03b1-dihydrotestosterone (DHT) or placebo. The DHT increased atrial expression of pro-hypertrophic, fibrotic and inflammatory transcripts. In mice with reduced plakoglobin, DHT exaggerated P\u00a0wave abnormalities, atrial conduction slowing, sodium current depletion, action potential amplitude reduction and the fall in action potential depolarization rate. Super-resolution microscopy revealed a decrease in NaV 1.5\u00a0membrane clustering in Plako+/- atrial cardiomyocytes after DHT exposure. In summary, AAS combined with plakoglobin deficiency cause pathological atrial electrical remodelling in young male hearts. Male sex is likely to increase the risk of atrial arrhythmia, particularly in those with desmosomal gene variants. This risk is likely to be exaggerated further by AAS use. KEY POINTS: Androgenic male sex hormones, such as testosterone,\u00a0might increase the risk of atrial fibrillation in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), which is often caused by desmosomal gene defects (e.g. reduced plakoglobin expression). In this study, we observed a significantly higher proportion of males who had ARVC compared with females, and atrial arrhythmias and P\u00a0wave changes represented a common observation in advanced ARVC stages. In mice with reduced plakoglobin expression, chronic administration of 5\u03b1-dihydrotestosterone led to P\u00a0wave abnormalities, atrial conduction slowing, sodium current depletion and a decrease in membrane-localized NaV 1.5 clusters. 5\u03b1-Dihydrotestosterone, therefore, represents a stimulus aggravating the pro-arrhythmic phenotype in carriers of desmosomal mutations and can affect atrial electrical function.", - "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1113/JP284597; doi:https://doi.org/10.1113/JP284597" - }, { "id": "33531486", "doi": "https://doi.org/10.1038/s41467-021-21370-6", @@ -24241,6 +24224,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41467-021-21370-6.pdf; doi:https://doi.org/10.1038/s41467-021-21370-6; html:https://europepmc.org/articles/PMC7854714; pdf:https://europepmc.org/articles/PMC7854714?pdf=render" }, + { + "id": "38345865", + "doi": "https://doi.org/10.1113/jp284597", + "title": "Reduced plakoglobin increases the risk of sodium current defects and atrial conduction abnormalities in response to androgenic anabolic steroid abuse.", + "authorString": "Sommerfeld LC, Holmes AP, Yu TY, O'Shea C, Kavanagh DM, Pike JM, Wright T, Syeda F, Aljehani A, Kew T, Cardoso VR, Kabir SN, Hepburn C, Menon PR, Broadway-Stringer S, O'Reilly M, Witten A, Fortmueller L, Lutz S, Kulle A, Gkoutos GV, Pavlovic D, Arlt W, Lavery GG, Steeds R, Gehmlich K, Stoll M, Kirchhof P, Fabritz L.", + "authorAffiliations": "", + "journalTitle": "The Journal of physiology", + "pubYear": "2024", + "date": "2024-02-12", + "isOpenAccess": "N", + "keywords": "Testosterone; Conduction velocity; Nav1.5; Desmosome; Arrhythmogenic Right Ventricular Cardiomyopathy; Cardiac Atria", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Androgenic anabolic steroids (AAS) are commonly abused by young men. Male sex and increased AAS levels are associated with earlier and more severe manifestation of common cardiac conditions, such as atrial fibrillation, and rare ones, such as arrhythmogenic right ventricular cardiomyopathy (ARVC). Clinical observations suggest a potential atrial involvement in ARVC. Arrhythmogenic right ventricular cardiomyopathy is caused by desmosomal gene defects, including reduced plakoglobin expression. Here, we analysed clinical records from 146 ARVC patients to identify that ARVC is more common in males than females. Patients with ARVC also had an increased incidence of atrial arrhythmias and P\u00a0wave changes. To study desmosomal vulnerability and the effects of AAS on the atria, young adult male mice, heterozygously deficient for plakoglobin (Plako+/- ), and wild type (WT) littermates were chronically exposed to 5\u03b1-dihydrotestosterone (DHT) or placebo. The DHT increased atrial expression of pro-hypertrophic, fibrotic and inflammatory transcripts. In mice with reduced plakoglobin, DHT exaggerated P\u00a0wave abnormalities, atrial conduction slowing, sodium current depletion, action potential amplitude reduction and the fall in action potential depolarization rate. Super-resolution microscopy revealed a decrease in NaV 1.5\u00a0membrane clustering in Plako+/- atrial cardiomyocytes after DHT exposure. In summary, AAS combined with plakoglobin deficiency cause pathological atrial electrical remodelling in young male hearts. Male sex is likely to increase the risk of atrial arrhythmia, particularly in those with desmosomal gene variants. This risk is likely to be exaggerated further by AAS use. KEY POINTS: Androgenic male sex hormones, such as testosterone,\u00a0might increase the risk of atrial fibrillation in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), which is often caused by desmosomal gene defects (e.g. reduced plakoglobin expression). In this study, we observed a significantly higher proportion of males who had ARVC compared with females, and atrial arrhythmias and P\u00a0wave changes represented a common observation in advanced ARVC stages. In mice with reduced plakoglobin expression, chronic administration of 5\u03b1-dihydrotestosterone led to P\u00a0wave abnormalities, atrial conduction slowing, sodium current depletion and a decrease in membrane-localized NaV 1.5 clusters. 5\u03b1-Dihydrotestosterone, therefore, represents a stimulus aggravating the pro-arrhythmic phenotype in carriers of desmosomal mutations and can affect atrial electrical function.", + "laySummary": "", + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1113/JP284597; doi:https://doi.org/10.1113/JP284597" + }, { "id": "36929968", "doi": "https://doi.org/10.1016/s0140-6736(22)02235-8", @@ -24411,23 +24411,6 @@ "laySummary": "", "urls": "pdf:https://publichealth.jmir.org/2022/5/e32543/PDF; doi:https://doi.org/10.2196/32543; html:https://europepmc.org/articles/PMC9150729" }, - { - "id": "37813531", - "doi": "https://doi.org/10.1136/bmjopen-2023-073162", - "title": "Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.", - "authorString": "Subramanian A, Lee SI, Hemali Sudasinghe SPB, Wambua S, Phillips K, Singh M, Azcoaga-Lorenzo A, Cockburn N, Wang J, Fagbamigbe A, Usman M, Damase-Michel C, Yau C, Kent L, McCowan C, OReilly D, Santorelli G, Hope H, Kennedy J, Mhereeg M, Abel KM, Eastwood KA, Black M, Loane M, Moss N, Brophy S, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2023", - "date": "2023-10-09", - "isOpenAccess": "Y", - "keywords": "Obstetrics; epidemiology; Maternal Medicine", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy.

Methods and analysis

Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3\u2009months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation.

Ethics and dissemination

Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.", - "laySummary": "", - "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/10/e073162.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-073162; html:https://europepmc.org/articles/PMC10565241; pdf:https://europepmc.org/articles/PMC10565241?pdf=render" - }, { "id": "34409990", "doi": "https://doi.org/10.1093/dote/doab058", @@ -24445,6 +24428,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/dote/article-pdf/35/1/doab058/42098674/doab058.pdf; doi:https://doi.org/10.1093/dote/doab058" }, + { + "id": "37813531", + "doi": "https://doi.org/10.1136/bmjopen-2023-073162", + "title": "Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.", + "authorString": "Subramanian A, Lee SI, Hemali Sudasinghe SPB, Wambua S, Phillips K, Singh M, Azcoaga-Lorenzo A, Cockburn N, Wang J, Fagbamigbe A, Usman M, Damase-Michel C, Yau C, Kent L, McCowan C, OReilly D, Santorelli G, Hope H, Kennedy J, Mhereeg M, Abel KM, Eastwood KA, Black M, Loane M, Moss N, Brophy S, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2023", + "date": "2023-10-09", + "isOpenAccess": "Y", + "keywords": "Obstetrics; epidemiology; Maternal Medicine", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy.

Methods and analysis

Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3\u2009months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation.

Ethics and dissemination

Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.", + "laySummary": "", + "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/10/e073162.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-073162; html:https://europepmc.org/articles/PMC10565241; pdf:https://europepmc.org/articles/PMC10565241?pdf=render" + }, { "id": "33500288", "doi": "https://doi.org/10.1136/bmjopen-2020-042945", @@ -24751,23 +24751,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.schres.2020.05.007; doi:https://doi.org/10.1016/j.schres.2020.05.007; html:https://europepmc.org/articles/PMC7875179" }, - { - "id": "35623313", - "doi": "https://doi.org/10.1016/j.ejrad.2022.110366", - "title": "Comparison of state-of-the-art machine and deep learning algorithms to classify proximal humeral fractures using radiology text.", - "authorString": "Dipnall JF, Lu J, Gabbe BJ, Cosic F, Edwards E, Page R, Du L.", - "authorAffiliations": "", - "journalTitle": "European journal of radiology", - "pubYear": "2022", - "date": "2022-05-20", - "isOpenAccess": "N", - "keywords": "Classification; Radiology; Machine Learning; Natural Language Processing; Proximal Humeral Fracture; Deep Learning; Neer; Bert", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

Proximal humeral fractures account for a significant proportion of all fractures. Detailed accurate classification of the type and severity of the fracture is a key component of clinical decision making, treatment and plays an important role in orthopaedic trauma research. This research aimed to assess the performance of Machine Learning (ML) multiclass classification algorithms to classify proximal humeral fractures using radiology text data.

Materials and methods

Data from adult (16\u00a0+\u00a0years) patients admitted to a major trauma centre for management of their proximal humerus fracture from January 2010 to January 2019 were used (1,324). Six input text datasets were used for classification: X-ray and/or CT scan reports (primary) and concatenation of patient age and/or patient sex. One of seven Neer class labels were classified. Models were evaluated using accuracy, recall, precision, F1, and One-versus-rest scores.

Results

A number of statistical ML algorithms performed acceptably and one of the BERT models, exhibiting good accuracy of 61% and an excellent one-versus-rest score above 0.8. The highest precision, recall and F1 scores were 50%, 39% and 39% respectively, being considered reasonable scores with the sparse text data used and in the context of machine learning.

Conclusion

ML and BERT algorithms based on routine unstructured X-ray and CT text reports, combined with the demographics of the patient, show promise in Neer classification of proximal humeral fractures to aid research. Use of these algorithms shows potential to speed up the classification task and assist radiologist, surgeons and researchers.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.ejrad.2022.110366" - }, { "id": "33903145", "doi": "https://doi.org/10.1136/bjophthalmol-2020-318570", @@ -24785,6 +24768,23 @@ "laySummary": "", "urls": "pdf:https://bjo.bmj.com/content/bjophthalmol/early/2021/04/25/bjophthalmol-2020-318570.full.pdf; doi:https://doi.org/10.1136/bjophthalmol-2020-318570; html:https://europepmc.org/articles/PMC9340042; pdf:https://europepmc.org/articles/PMC9340042?pdf=render" }, + { + "id": "35623313", + "doi": "https://doi.org/10.1016/j.ejrad.2022.110366", + "title": "Comparison of state-of-the-art machine and deep learning algorithms to classify proximal humeral fractures using radiology text.", + "authorString": "Dipnall JF, Lu J, Gabbe BJ, Cosic F, Edwards E, Page R, Du L.", + "authorAffiliations": "", + "journalTitle": "European journal of radiology", + "pubYear": "2022", + "date": "2022-05-20", + "isOpenAccess": "N", + "keywords": "Classification; Radiology; Machine Learning; Natural Language Processing; Proximal Humeral Fracture; Deep Learning; Neer; Bert", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

Proximal humeral fractures account for a significant proportion of all fractures. Detailed accurate classification of the type and severity of the fracture is a key component of clinical decision making, treatment and plays an important role in orthopaedic trauma research. This research aimed to assess the performance of Machine Learning (ML) multiclass classification algorithms to classify proximal humeral fractures using radiology text data.

Materials and methods

Data from adult (16\u00a0+\u00a0years) patients admitted to a major trauma centre for management of their proximal humerus fracture from January 2010 to January 2019 were used (1,324). Six input text datasets were used for classification: X-ray and/or CT scan reports (primary) and concatenation of patient age and/or patient sex. One of seven Neer class labels were classified. Models were evaluated using accuracy, recall, precision, F1, and One-versus-rest scores.

Results

A number of statistical ML algorithms performed acceptably and one of the BERT models, exhibiting good accuracy of 61% and an excellent one-versus-rest score above 0.8. The highest precision, recall and F1 scores were 50%, 39% and 39% respectively, being considered reasonable scores with the sparse text data used and in the context of machine learning.

Conclusion

ML and BERT algorithms based on routine unstructured X-ray and CT text reports, combined with the demographics of the patient, show promise in Neer classification of proximal humeral fractures to aid research. Use of these algorithms shows potential to speed up the classification task and assist radiologist, surgeons and researchers.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.ejrad.2022.110366" + }, { "id": "33127858", "doi": "https://doi.org/10.1681/asn.2020050679", @@ -24802,23 +24802,6 @@ "laySummary": "", "urls": "pdf:https://jasn.asnjournals.org/content/jnephrol/32/1/127.full.pdf; doi:https://doi.org/10.1681/ASN.2020050679; html:https://europepmc.org/articles/PMC7894659; doi:https://doi.org/10.1681/asn.2020050679" }, - { - "id": "38170504", - "doi": "https://doi.org/10.1001/jamacardio.2023.4994", - "title": "Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia.", - "authorString": "Schuermans A, Truong B, Ardissino M, Bhukar R, Slob EAW, Nakao T, Dron JS, Small AM, Cho SMJ, Yu Z, Hornsby W, Antoine T, Lannery K, Postupaka D, Gray KJ, Yan Q, Butterworth AS, Burgess S, Wood MJ, Scott NS, Harrington CM, Sarma AA, Lau ES, Roh JD, Januzzi JL, Natarajan P, Honigberg MC.", - "authorAffiliations": "", - "journalTitle": "JAMA cardiology", - "pubYear": "2024", - "date": "2024-03-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Importance

Hypertensive disorders of pregnancy (HDPs), including gestational hypertension and preeclampsia, are important contributors to maternal morbidity and mortality worldwide. In addition, women with HDPs face an elevated long-term risk of cardiovascular disease.

Objective

To identify proteins in the circulation associated with HDPs.

Design, setting, and participants

Two-sample mendelian randomization (MR) tested the associations of genetic instruments for cardiovascular disease-related proteins with gestational hypertension and preeclampsia. In downstream analyses, a systematic review of observational data was conducted to evaluate the identified proteins' dynamics across gestation in hypertensive vs normotensive pregnancies, and phenome-wide MR analyses were performed to identify potential non-HDP-related effects associated with the prioritized proteins. Genetic association data for cardiovascular disease-related proteins were obtained from the Systematic and Combined Analysis of Olink Proteins (SCALLOP) consortium. Genetic association data for the HDPs were obtained from recent European-ancestry genome-wide association study meta-analyses for gestational hypertension and preeclampsia. Study data were analyzed October 2022 to October 2023.

Exposures

Genetic instruments for 90 candidate proteins implicated in cardiovascular diseases, constructed using cis-protein quantitative trait loci (cis-pQTLs).

Main outcomes and measures

Gestational hypertension and preeclampsia.

Results

Genetic association data for cardiovascular disease-related proteins were obtained from 21\u202f758 participants from the SCALLOP consortium. Genetic association data for the HDPs were obtained from 393\u202f238 female individuals (8636 cases and 384\u202f602 controls) for gestational hypertension and 606\u202f903 female individuals (16\u202f032 cases and 590\u202f871 controls) for preeclampsia. Seventy-five of 90 proteins (83.3%) had at least 1 valid cis-pQTL. Of those, 10 proteins (13.3%) were significantly associated with HDPs. Four were robust to sensitivity analyses for gestational hypertension (cluster of differentiation 40, eosinophil cationic protein [ECP], galectin 3, N-terminal pro-brain natriuretic peptide [NT-proBNP]), and 2 were robust for preeclampsia (cystatin B, heat shock protein 27 [HSP27]). Consistent with the MR findings, observational data revealed that lower NT-proBNP (0.76- to 0.88-fold difference vs no HDPs) and higher HSP27 (2.40-fold difference vs no HDPs) levels during the first trimester of pregnancy were associated with increased risk of HDPs, as were higher levels of ECP (1.60-fold difference vs no HDPs). Phenome-wide MR analyses identified 37 unique non-HDP-related protein-disease associations, suggesting potential on-target effects associated with interventions lowering HDP risk through the identified proteins.

Conclusions and relevance

Study findings suggest genetic associations of 4 cardiovascular disease-related proteins with gestational hypertension and 2 associated with preeclampsia. Future studies are required to test the efficacy of targeting the corresponding pathways to reduce HDP risk.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1001/jamacardio.2023.4994; html:https://europepmc.org/articles/PMC10765315; pdf:https://europepmc.org/articles/PMC10765315?pdf=render" - }, { "id": "34761838", "doi": "https://doi.org/10.1002/biof.1801", @@ -24887,6 +24870,23 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/2076-2615/12/13/1679/pdf?version=1656561768; doi:https://doi.org/10.3390/ani12131679; html:https://europepmc.org/articles/PMC9265105; pdf:https://europepmc.org/articles/PMC9265105?pdf=render" }, + { + "id": "38170504", + "doi": "https://doi.org/10.1001/jamacardio.2023.4994", + "title": "Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia.", + "authorString": "Schuermans A, Truong B, Ardissino M, Bhukar R, Slob EAW, Nakao T, Dron JS, Small AM, Cho SMJ, Yu Z, Hornsby W, Antoine T, Lannery K, Postupaka D, Gray KJ, Yan Q, Butterworth AS, Burgess S, Wood MJ, Scott NS, Harrington CM, Sarma AA, Lau ES, Roh JD, Januzzi JL, Natarajan P, Honigberg MC.", + "authorAffiliations": "", + "journalTitle": "JAMA cardiology", + "pubYear": "2024", + "date": "2024-03-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Importance

Hypertensive disorders of pregnancy (HDPs), including gestational hypertension and preeclampsia, are important contributors to maternal morbidity and mortality worldwide. In addition, women with HDPs face an elevated long-term risk of cardiovascular disease.

Objective

To identify proteins in the circulation associated with HDPs.

Design, setting, and participants

Two-sample mendelian randomization (MR) tested the associations of genetic instruments for cardiovascular disease-related proteins with gestational hypertension and preeclampsia. In downstream analyses, a systematic review of observational data was conducted to evaluate the identified proteins' dynamics across gestation in hypertensive vs normotensive pregnancies, and phenome-wide MR analyses were performed to identify potential non-HDP-related effects associated with the prioritized proteins. Genetic association data for cardiovascular disease-related proteins were obtained from the Systematic and Combined Analysis of Olink Proteins (SCALLOP) consortium. Genetic association data for the HDPs were obtained from recent European-ancestry genome-wide association study meta-analyses for gestational hypertension and preeclampsia. Study data were analyzed October 2022 to October 2023.

Exposures

Genetic instruments for 90 candidate proteins implicated in cardiovascular diseases, constructed using cis-protein quantitative trait loci (cis-pQTLs).

Main outcomes and measures

Gestational hypertension and preeclampsia.

Results

Genetic association data for cardiovascular disease-related proteins were obtained from 21\u202f758 participants from the SCALLOP consortium. Genetic association data for the HDPs were obtained from 393\u202f238 female individuals (8636 cases and 384\u202f602 controls) for gestational hypertension and 606\u202f903 female individuals (16\u202f032 cases and 590\u202f871 controls) for preeclampsia. Seventy-five of 90 proteins (83.3%) had at least 1 valid cis-pQTL. Of those, 10 proteins (13.3%) were significantly associated with HDPs. Four were robust to sensitivity analyses for gestational hypertension (cluster of differentiation 40, eosinophil cationic protein [ECP], galectin 3, N-terminal pro-brain natriuretic peptide [NT-proBNP]), and 2 were robust for preeclampsia (cystatin B, heat shock protein 27 [HSP27]). Consistent with the MR findings, observational data revealed that lower NT-proBNP (0.76- to 0.88-fold difference vs no HDPs) and higher HSP27 (2.40-fold difference vs no HDPs) levels during the first trimester of pregnancy were associated with increased risk of HDPs, as were higher levels of ECP (1.60-fold difference vs no HDPs). Phenome-wide MR analyses identified 37 unique non-HDP-related protein-disease associations, suggesting potential on-target effects associated with interventions lowering HDP risk through the identified proteins.

Conclusions and relevance

Study findings suggest genetic associations of 4 cardiovascular disease-related proteins with gestational hypertension and 2 associated with preeclampsia. Future studies are required to test the efficacy of targeting the corresponding pathways to reduce HDP risk.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1001/jamacardio.2023.4994; html:https://europepmc.org/articles/PMC10765315; pdf:https://europepmc.org/articles/PMC10765315?pdf=render" + }, { "id": "34772649", "doi": "https://doi.org/10.1016/s2589-7500(21)00252-1", @@ -24989,23 +24989,6 @@ "laySummary": "", "urls": "pdf:https://discovery.dundee.ac.uk/files/66344502/ejn.15423.pdf; doi:https://doi.org/10.1111/ejn.15423" }, - { - "id": "36344532", - "doi": "https://doi.org/10.1038/s41598-022-21663-w", - "title": "Atrial fibrillation prediction by combining ECG markers and CMR radiomics.", - "authorString": "Pujadas ER, Raisi-Estabragh Z, Szabo L, Morcillo CI, Campello VM, Martin-Isla C, Vago H, Merkely B, Harvey NC, Petersen SE, Lekadir K.", - "authorAffiliations": "", - "journalTitle": "Scientific reports", - "pubYear": "2022", - "date": "2022-11-07", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Atrial fibrillation (AF) is the most common cardiac arrhythmia. It is associated with a higher risk of important adverse health outcomes such as stroke and death. AF is linked to distinct electro-anatomic alterations. The main tool for AF diagnosis is the Electrocardiogram (ECG). However, an ECG recorded at a single time point may not detect individuals with paroxysmal AF. In this study, we developed machine learning models for discrimination of prevalent AF using a combination of image-derived radiomics phenotypes and ECG features. Thus, we characterize the phenotypes of prevalent AF in terms of ECG and imaging alterations. Moreover, we explore sex-differential remodelling by building sex-specific models. Our integrative model including radiomics and ECG together resulted in a better performance than ECG alone, particularly in women. ECG had a lower performance in women than men (AUC: 0.77 vs 0.88, p\u2009<\u20090.05) but adding radiomics features, the accuracy of the model was able to improve significantly. The sensitivity also increased considerably in women by adding the radiomics (0.68 vs 0.79, p\u2009<\u20090.05) having a higher detection of AF events. Our findings provide novel insights into AF-related electro-anatomic remodelling and its variations by sex. The integrative radiomics-ECG model also presents a potential novel approach for earlier detection of AF.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41598-022-21663-w.pdf; doi:https://doi.org/10.1038/s41598-022-21663-w; html:https://europepmc.org/articles/PMC9640662; pdf:https://europepmc.org/articles/PMC9640662?pdf=render" - }, { "id": "34850874", "doi": "https://doi.org/10.1093/gigascience/giab083", @@ -25024,21 +25007,21 @@ "urls": "pdf:https://academic.oup.com/gigascience/article-pdf/10/12/giab083/41395049/giab083.pdf; doi:https://doi.org/10.1093/gigascience/giab083; html:https://europepmc.org/articles/PMC8634578; pdf:https://europepmc.org/articles/PMC8634578?pdf=render" }, { - "id": "36798028", - "doi": "https://doi.org/10.1002/ehf2.14308", - "title": "Identifying patients at risk: multi-centre comparison of HeartMate 3 and HeartWare left ventricular assist devices.", - "authorString": "Numan L, Zimpfer D, Zadok OIB, Aarts E, Morshuis M, Guenther SPW, Riebandt J, Wiedemann D, Ramjankhan FZ, Oppelaar AM, Ben-Gal T, Ben-Avraham B, Asselbergs FW, Schramm R, Van Laake LW.", + "id": "36344532", + "doi": "https://doi.org/10.1038/s41598-022-21663-w", + "title": "Atrial fibrillation prediction by combining ECG markers and CMR radiomics.", + "authorString": "Pujadas ER, Raisi-Estabragh Z, Szabo L, Morcillo CI, Campello VM, Martin-Isla C, Vago H, Merkely B, Harvey NC, Petersen SE, Lekadir K.", "authorAffiliations": "", - "journalTitle": "ESC heart failure", - "pubYear": "2023", - "date": "2023-02-16", + "journalTitle": "Scientific reports", + "pubYear": "2022", + "date": "2022-11-07", "isOpenAccess": "Y", - "keywords": "Mechanical Circulatory Support; Left Ventricular Assist Device; End-stage Heart Failure; Lvad; Centrifugal Continuous Flow Pump", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Aims

Since the withdrawal of HeartWare (HVAD) from the global market, there is an ongoing discussion if and which patients require prophylactically exchange for a HeartMate 3 (HM3). Therefore, it is important to study outcome differences between HVAD and HM3 patients. Because centres differ in patient selection and standard of care, we performed a propensity score (PS)-based study including centres that implanted both devices and aimed to identify which HVAD patients are at highest risk.

Methods and results

We performed an international multi-centre study (n\u00a0=\u00a01021) including centres that implanted HVAD and HM3. PS-matching was performed using clinical variables and the implanting centre. Survival and complications were compared. As a sensitivity analysis, PS-adjusted Cox regression was performed. Landmark analysis with conditional survival >2\u00a0years was conducted to evaluate long-term survival differences. To identify which HVAD patients may benefit from a HM3 upgrade, Cox regression using pre-operative variables and their interaction with device type was performed. Survival was significantly better for HM3 patients (P\u00a0<\u00a00.01) in 458 matched patients, with a median follow-up of 23\u00a0months. Within the matched cohort, HM3 patients had a median age of 58\u00a0years, and 83% were male, 80% of the HVAD patients were male, with a median age of 59\u00a0years. PS-adjusted Cox regression confirmed a significantly better survival for HM3 patients when compared with HVAD, with a HR of 1.46 (95% confidence interval 1.14-1.85, P\u00a0<\u00a00.01). Pump thrombosis (P\u00a0<\u00a00.01) and ischaemic stroke (P\u00a0<\u00a00.01) occurred less in HM3 patients. No difference was found for haemorrhagic stroke, right heart failure, driveline infection, and major bleeding. Landmark-analysis confirmed a significant difference in conditional survival >2\u00a0years after implantation (P\u00a0=\u00a00.03). None of the pre-operative variable interactions in the Cox regression were significant.

Conclusions

HM3 patients have a significantly better survival and a lower incidence of ischaemic strokes and pump thrombosis than HVAD patients. This survival difference persisted after 2\u00a0years of implantation. Additional research using post-operative variables is warranted to identify which HVAD patients need an upgrade to HM3 or expedited transplantation.", + "abstract": "Atrial fibrillation (AF) is the most common cardiac arrhythmia. It is associated with a higher risk of important adverse health outcomes such as stroke and death. AF is linked to distinct electro-anatomic alterations. The main tool for AF diagnosis is the Electrocardiogram (ECG). However, an ECG recorded at a single time point may not detect individuals with paroxysmal AF. In this study, we developed machine learning models for discrimination of prevalent AF using a combination of image-derived radiomics phenotypes and ECG features. Thus, we characterize the phenotypes of prevalent AF in terms of ECG and imaging alterations. Moreover, we explore sex-differential remodelling by building sex-specific models. Our integrative model including radiomics and ECG together resulted in a better performance than ECG alone, particularly in women. ECG had a lower performance in women than men (AUC: 0.77 vs 0.88, p\u2009<\u20090.05) but adding radiomics features, the accuracy of the model was able to improve significantly. The sensitivity also increased considerably in women by adding the radiomics (0.68 vs 0.79, p\u2009<\u20090.05) having a higher detection of AF events. Our findings provide novel insights into AF-related electro-anatomic remodelling and its variations by sex. The integrative radiomics-ECG model also presents a potential novel approach for earlier detection of AF.", "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14308; doi:https://doi.org/10.1002/ehf2.14308; html:https://europepmc.org/articles/PMC10192248; pdf:https://europepmc.org/articles/PMC10192248?pdf=render" + "urls": "pdf:https://www.nature.com/articles/s41598-022-21663-w.pdf; doi:https://doi.org/10.1038/s41598-022-21663-w; html:https://europepmc.org/articles/PMC9640662; pdf:https://europepmc.org/articles/PMC9640662?pdf=render" }, { "id": "PMC9023380", @@ -25057,6 +25040,23 @@ "laySummary": "", "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023380/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023380/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9023380; pdf:https://europepmc.org/articles/PMC9023380?pdf=render" }, + { + "id": "36798028", + "doi": "https://doi.org/10.1002/ehf2.14308", + "title": "Identifying patients at risk: multi-centre comparison of HeartMate 3 and HeartWare left ventricular assist devices.", + "authorString": "Numan L, Zimpfer D, Zadok OIB, Aarts E, Morshuis M, Guenther SPW, Riebandt J, Wiedemann D, Ramjankhan FZ, Oppelaar AM, Ben-Gal T, Ben-Avraham B, Asselbergs FW, Schramm R, Van Laake LW.", + "authorAffiliations": "", + "journalTitle": "ESC heart failure", + "pubYear": "2023", + "date": "2023-02-16", + "isOpenAccess": "Y", + "keywords": "Mechanical Circulatory Support; Left Ventricular Assist Device; End-stage Heart Failure; Lvad; Centrifugal Continuous Flow Pump", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

Since the withdrawal of HeartWare (HVAD) from the global market, there is an ongoing discussion if and which patients require prophylactically exchange for a HeartMate 3 (HM3). Therefore, it is important to study outcome differences between HVAD and HM3 patients. Because centres differ in patient selection and standard of care, we performed a propensity score (PS)-based study including centres that implanted both devices and aimed to identify which HVAD patients are at highest risk.

Methods and results

We performed an international multi-centre study (n\u00a0=\u00a01021) including centres that implanted HVAD and HM3. PS-matching was performed using clinical variables and the implanting centre. Survival and complications were compared. As a sensitivity analysis, PS-adjusted Cox regression was performed. Landmark analysis with conditional survival >2\u00a0years was conducted to evaluate long-term survival differences. To identify which HVAD patients may benefit from a HM3 upgrade, Cox regression using pre-operative variables and their interaction with device type was performed. Survival was significantly better for HM3 patients (P\u00a0<\u00a00.01) in 458 matched patients, with a median follow-up of 23\u00a0months. Within the matched cohort, HM3 patients had a median age of 58\u00a0years, and 83% were male, 80% of the HVAD patients were male, with a median age of 59\u00a0years. PS-adjusted Cox regression confirmed a significantly better survival for HM3 patients when compared with HVAD, with a HR of 1.46 (95% confidence interval 1.14-1.85, P\u00a0<\u00a00.01). Pump thrombosis (P\u00a0<\u00a00.01) and ischaemic stroke (P\u00a0<\u00a00.01) occurred less in HM3 patients. No difference was found for haemorrhagic stroke, right heart failure, driveline infection, and major bleeding. Landmark-analysis confirmed a significant difference in conditional survival >2\u00a0years after implantation (P\u00a0=\u00a00.03). None of the pre-operative variable interactions in the Cox regression were significant.

Conclusions

HM3 patients have a significantly better survival and a lower incidence of ischaemic strokes and pump thrombosis than HVAD patients. This survival difference persisted after 2\u00a0years of implantation. Additional research using post-operative variables is warranted to identify which HVAD patients need an upgrade to HM3 or expedited transplantation.", + "laySummary": "", + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14308; doi:https://doi.org/10.1002/ehf2.14308; html:https://europepmc.org/articles/PMC10192248; pdf:https://europepmc.org/articles/PMC10192248?pdf=render" + }, { "id": "33144367", "doi": "https://doi.org/10.3399/bjgpopen20x101109", @@ -25074,23 +25074,6 @@ "laySummary": "", "urls": "pdf:https://bjgpopen.org/content/bjgpoa/4/5/bjgpopen20X101109.full.pdf; doi:https://doi.org/10.3399/bjgpopen20X101109; html:https://europepmc.org/articles/PMC7880177; pdf:https://europepmc.org/articles/PMC7880177?pdf=render" }, - { - "id": "38763167", - "doi": "https://doi.org/10.1164/rccm.202312-2289oc", - "title": "Impact of High Dose Early Mobilization on Outcomes for Patients with Diabetes: A Secondary Analysis of the TEAM Trial.", - "authorString": "Serpa Neto A, Bailey M, Seller D, Agli A, Bellomo R, Brickell K, Broadley T, Buhr H, Gabbe BJ, Gould DW, Harrold M, Higgins AM, Hurford S, Iwashyna TJ, Nichol AD, Presneill JJ, Schaller SJ, Sivasuthan J, Tipping CJ, Poole A, Parke R, Bradley S, Webb S, Zoungas S, Young PJ, Hodgson CL.", - "authorAffiliations": "", - "journalTitle": "American journal of respiratory and critical care medicine", - "pubYear": "2024", - "date": "2024-05-19", - "isOpenAccess": "N", - "keywords": "Mortality; Mechanical ventilation; Physiotherapy; Clinical Trial", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Rationale

Patients with diabetes represent almost 20% of all ICU admissions and might respond differently to high dose early active mobilization.

Objectives

To assess whether diabetes modified the relationship between the dose of early mobilization on clinical outcomes in the TEAM trial.

Methods

All TEAM trial patients were included. The primary outcome was days alive and out of hospital at day 180. Secondary outcomes included 180-day mortality and long-term functional outcomes at day 180. Logistic and median regression models were used to explore the effect of high dose early mobilization on outcomes by diabetes status.

Measurements and main results

All 741 patients from the original trial were included. Of these, 159 patients (21.4%) had diabetes. Patients with diabetes had a lower number of days alive and out of hospital at day 180 (124 [0-153] vs. 147 [82-164], p = 0.013), and higher 180-day mortality (30% vs. 18%, p = 0.044). In patients receiving high dose early mobilization, days alive and out of hospital at day 180 was 73.0 (0.0 - 144.5) in patients with diabetes and 146.5 (95.8 - 163.0) in patients without diabetes (p for interaction = 0.108). However, in patients with diabetes, high dose early mobilization increased the odds of mortality at 180 days (adjusted odds ratio 3.47; 95% confidence interval [CI], 1.67-7.61, p value for interaction, 0.001).

Conclusions

In this secondary analysis of the TEAM trial, in patients with diabetes, a high dose early mobilization strategy did not significantly decrease the number of days alive and out of hospital at day 180 but it increased 180-day mortality.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1164/rccm.202312-2289OC" - }, { "id": "36082669", "doi": "https://doi.org/10.1161/hypertensionaha.122.19354", @@ -25108,6 +25091,23 @@ "laySummary": "", "urls": "pdf:https://ora.ox.ac.uk/objects/uuid:aefe90da-8a81-4cfa-981a-bb36eca6faa3/files/r6w924c60k; doi:https://doi.org/10.1161/HYPERTENSIONAHA.122.19354; html:https://europepmc.org/articles/PMC9640248; pdf:https://europepmc.org/articles/PMC9640248?pdf=render" }, + { + "id": "38763167", + "doi": "https://doi.org/10.1164/rccm.202312-2289oc", + "title": "Impact of High Dose Early Mobilization on Outcomes for Patients with Diabetes: A Secondary Analysis of the TEAM Trial.", + "authorString": "Serpa Neto A, Bailey M, Seller D, Agli A, Bellomo R, Brickell K, Broadley T, Buhr H, Gabbe BJ, Gould DW, Harrold M, Higgins AM, Hurford S, Iwashyna TJ, Nichol AD, Presneill JJ, Schaller SJ, Sivasuthan J, Tipping CJ, Poole A, Parke R, Bradley S, Webb S, Zoungas S, Young PJ, Hodgson CL.", + "authorAffiliations": "", + "journalTitle": "American journal of respiratory and critical care medicine", + "pubYear": "2024", + "date": "2024-05-19", + "isOpenAccess": "N", + "keywords": "Mortality; Mechanical ventilation; Physiotherapy; Clinical Trial", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Rationale

Patients with diabetes represent almost 20% of all ICU admissions and might respond differently to high dose early active mobilization.

Objectives

To assess whether diabetes modified the relationship between the dose of early mobilization on clinical outcomes in the TEAM trial.

Methods

All TEAM trial patients were included. The primary outcome was days alive and out of hospital at day 180. Secondary outcomes included 180-day mortality and long-term functional outcomes at day 180. Logistic and median regression models were used to explore the effect of high dose early mobilization on outcomes by diabetes status.

Measurements and main results

All 741 patients from the original trial were included. Of these, 159 patients (21.4%) had diabetes. Patients with diabetes had a lower number of days alive and out of hospital at day 180 (124 [0-153] vs. 147 [82-164], p = 0.013), and higher 180-day mortality (30% vs. 18%, p = 0.044). In patients receiving high dose early mobilization, days alive and out of hospital at day 180 was 73.0 (0.0 - 144.5) in patients with diabetes and 146.5 (95.8 - 163.0) in patients without diabetes (p for interaction = 0.108). However, in patients with diabetes, high dose early mobilization increased the odds of mortality at 180 days (adjusted odds ratio 3.47; 95% confidence interval [CI], 1.67-7.61, p value for interaction, 0.001).

Conclusions

In this secondary analysis of the TEAM trial, in patients with diabetes, a high dose early mobilization strategy did not significantly decrease the number of days alive and out of hospital at day 180 but it increased 180-day mortality.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1164/rccm.202312-2289OC" + }, { "id": "30648344", "doi": "https://doi.org/10.1002/cnm.3180", @@ -25159,6 +25159,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.injury.2021.06.037" }, + { + "id": "37477803", + "doi": "https://doi.org/10.1007/s11897-023-00615-z", + "title": "Discovering Distinct Phenotypical Clusters in Heart Failure Across the Ejection Fraction Spectrum: a Systematic Review.", + "authorString": "Meijs C, Handoko ML, Savarese G, Vernooij RWM, Vaartjes I, Banerjee A, Koudstaal S, Brugts JJ, Asselbergs FW, Uijl A.", + "authorAffiliations": "", + "journalTitle": "Current heart failure reports", + "pubYear": "2023", + "date": "2023-07-21", + "isOpenAccess": "Y", + "keywords": "Clustering; Phenotyping; Heart Failure; Machine Learning; Precision Medicine", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Review purpose

This systematic review aims to summarise clustering studies in heart failure (HF) and guide future clinical trial design and implementation in routine clinical practice.

Findings

34 studies were identified (n\u2009=\u200919 in HF with preserved ejection fraction (HFpEF)). There was significant heterogeneity invariables and techniques used. However, 149/165 described clusters could be assigned to one of nine phenotypes: 1) young, low comorbidity burden; 2) metabolic; 3) cardio-renal; 4) atrial fibrillation (AF); 5) elderly female AF; 6) hypertensive-comorbidity; 7) ischaemic-male; 8) valvular disease; and 9) devices. There was room for improvement on important methodological topics for all clustering studies such as external validation and transparency of the modelling process. The large overlap between the phenotypes of the clustering studies shows that clustering is a robust approach for discovering clinically distinct phenotypes. However, future studies should invest in a phenotype model that can be implemented in routine clinical practice and future clinical trial design. HF\u2009=\u2009heart failure, EF\u2009=\u2009ejection fraction, HFpEF\u2009=\u2009heart failure with preserved ejection fraction, HFrEF\u2009=\u2009heart failure with reduced ejection fraction, CKD\u2009=\u2009chronic kidney disease, AF\u2009=\u2009atrial fibrillation, IHD\u2009=\u2009ischaemic heart disease, CAD\u2009=\u2009coronary artery disease, ICD\u2009=\u2009implantable cardioverter-defibrillator, CRT\u2009=\u2009cardiac resynchronization therapy, NT-proBNP\u2009=\u2009N-terminal pro b-type natriuretic peptide, BMI\u2009=\u2009Body Mass Index, COPD\u2009=\u2009Chronic obstructive pulmonary disease.", + "laySummary": "", + "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s11897-023-00615-z.pdf; doi:https://doi.org/10.1007/s11897-023-00615-z; html:https://europepmc.org/articles/PMC10589200; pdf:https://europepmc.org/articles/PMC10589200?pdf=render" + }, { "id": "35796550", "doi": "https://doi.org/10.1093/hmg/ddac153", @@ -25177,21 +25194,21 @@ "urls": "pdf:https://academic.oup.com/hmg/advance-article-pdf/doi/10.1093/hmg/ddac153/45277324/ddac153.pdf; doi:https://doi.org/10.1093/hmg/ddac153" }, { - "id": "37477803", - "doi": "https://doi.org/10.1007/s11897-023-00615-z", - "title": "Discovering Distinct Phenotypical Clusters in Heart Failure Across the Ejection Fraction Spectrum: a Systematic Review.", - "authorString": "Meijs C, Handoko ML, Savarese G, Vernooij RWM, Vaartjes I, Banerjee A, Koudstaal S, Brugts JJ, Asselbergs FW, Uijl A.", + "id": "35089148", + "doi": "https://doi.org/10.2196/28095", + "title": "The Association Between Home Stay and Symptom Severity in Major Depressive Disorder: Preliminary Findings From a Multicenter Observational Study Using Geolocation Data From Smartphones.", + "authorString": "Laiou P, Kaliukhovich DA, Folarin AA, Ranjan Y, Rashid Z, Conde P, Stewart C, Sun S, Zhang Y, Matcham F, Ivan A, Lavelle G, Siddi S, Lamers F, Penninx BW, Haro JM, Annas P, Cummins N, Vairavan S, Manyakov NV, Narayan VA, Dobson RJ, Hotopf M, RADAR-CNS.", "authorAffiliations": "", - "journalTitle": "Current heart failure reports", - "pubYear": "2023", - "date": "2023-07-21", + "journalTitle": "JMIR mHealth and uHealth", + "pubYear": "2022", + "date": "2022-01-28", "isOpenAccess": "Y", - "keywords": "Clustering; Phenotyping; Heart Failure; Machine Learning; Precision Medicine", + "keywords": "GPS; Mobile phone; Major Depressive Disorder; Smartphone; Phq-8; Home Stay", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Review purpose

This systematic review aims to summarise clustering studies in heart failure (HF) and guide future clinical trial design and implementation in routine clinical practice.

Findings

34 studies were identified (n\u2009=\u200919 in HF with preserved ejection fraction (HFpEF)). There was significant heterogeneity invariables and techniques used. However, 149/165 described clusters could be assigned to one of nine phenotypes: 1) young, low comorbidity burden; 2) metabolic; 3) cardio-renal; 4) atrial fibrillation (AF); 5) elderly female AF; 6) hypertensive-comorbidity; 7) ischaemic-male; 8) valvular disease; and 9) devices. There was room for improvement on important methodological topics for all clustering studies such as external validation and transparency of the modelling process. The large overlap between the phenotypes of the clustering studies shows that clustering is a robust approach for discovering clinically distinct phenotypes. However, future studies should invest in a phenotype model that can be implemented in routine clinical practice and future clinical trial design. HF\u2009=\u2009heart failure, EF\u2009=\u2009ejection fraction, HFpEF\u2009=\u2009heart failure with preserved ejection fraction, HFrEF\u2009=\u2009heart failure with reduced ejection fraction, CKD\u2009=\u2009chronic kidney disease, AF\u2009=\u2009atrial fibrillation, IHD\u2009=\u2009ischaemic heart disease, CAD\u2009=\u2009coronary artery disease, ICD\u2009=\u2009implantable cardioverter-defibrillator, CRT\u2009=\u2009cardiac resynchronization therapy, NT-proBNP\u2009=\u2009N-terminal pro b-type natriuretic peptide, BMI\u2009=\u2009Body Mass Index, COPD\u2009=\u2009Chronic obstructive pulmonary disease.", + "abstract": "

Background

Most smartphones and wearables are currently equipped with location sensing (using GPS and mobile network information), which enables continuous location tracking of their users. Several studies have reported that various mobility metrics, as well as home stay, that is, the amount of time an individual spends at home in a day, are associated with symptom severity in people with major depressive disorder (MDD). Owing to the use of small and homogeneous cohorts of participants, it is uncertain whether the findings reported in those studies generalize to a broader population of individuals with MDD symptoms.

Objective

The objective of this study is to examine the relationship between the overall severity of depressive symptoms, as assessed by the 8-item Patient Health Questionnaire, and median daily home stay over the 2 weeks preceding the completion of a questionnaire in individuals with MDD.

Methods

We used questionnaire and geolocation data of 164 participants with MDD collected in the observational Remote Assessment of Disease and Relapse-Major Depressive Disorder study. The participants were recruited from three study sites: King's College London in the United Kingdom (109/164, 66.5%); Vrije Universiteit Medisch Centrum in Amsterdam, the Netherlands (17/164, 10.4%); and Centro de Investigaci\u00f3n Biom\u00e9dica en Red in Barcelona, Spain (38/164, 23.2%). We used a linear regression model and a resampling technique (n=100 draws) to investigate the relationship between home stay and the overall severity of MDD symptoms. Participant age at enrollment, gender, occupational status, and geolocation data quality metrics were included in the model as additional explanatory variables. The 95% 2-sided CIs were used to evaluate the significance of model variables.

Results

Participant age and severity of MDD symptoms were found to be significantly related to home stay, with older (95% CI 0.161-0.325) and more severely affected individuals (95% CI 0.015-0.184) spending more time at home. The association between home stay and symptoms severity appeared to be stronger on weekdays (95% CI 0.023-0.178, median 0.098; home stay: 25th-75th percentiles 17.8-22.8, median 20.9 hours a day) than on weekends (95% CI -0.079 to 0.149, median 0.052; home stay: 25th-75th percentiles 19.7-23.5, median 22.3 hours a day). Furthermore, we found a significant modulation of home stay by occupational status, with employment reducing home stay (employed participants: 25th-75th percentiles 16.1-22.1, median 19.7 hours a day; unemployed participants: 25th-75th percentiles 20.4-23.5, median 22.6 hours a day).

Conclusions

Our findings suggest that home stay is associated with symptom severity in MDD and demonstrate the importance of accounting for confounding factors in future studies. In addition, they illustrate that passive sensing of individuals with depression is feasible and could provide clinically relevant information to monitor the course of illness in patients with MDD.", "laySummary": "", - "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s11897-023-00615-z.pdf; doi:https://doi.org/10.1007/s11897-023-00615-z; html:https://europepmc.org/articles/PMC10589200; pdf:https://europepmc.org/articles/PMC10589200?pdf=render" + "urls": "pdf:https://mhealth.jmir.org/2022/1/e28095/PDF; doi:https://doi.org/10.2196/28095; html:https://europepmc.org/articles/PMC8838593" }, { "id": "36692937", @@ -25227,23 +25244,6 @@ "laySummary": "", "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.031646; doi:https://doi.org/10.1161/JAHA.123.031646; html:https://europepmc.org/articles/PMC10926784; pdf:https://europepmc.org/articles/PMC10926784?pdf=render" }, - { - "id": "35089148", - "doi": "https://doi.org/10.2196/28095", - "title": "The Association Between Home Stay and Symptom Severity in Major Depressive Disorder: Preliminary Findings From a Multicenter Observational Study Using Geolocation Data From Smartphones.", - "authorString": "Laiou P, Kaliukhovich DA, Folarin AA, Ranjan Y, Rashid Z, Conde P, Stewart C, Sun S, Zhang Y, Matcham F, Ivan A, Lavelle G, Siddi S, Lamers F, Penninx BW, Haro JM, Annas P, Cummins N, Vairavan S, Manyakov NV, Narayan VA, Dobson RJ, Hotopf M, RADAR-CNS.", - "authorAffiliations": "", - "journalTitle": "JMIR mHealth and uHealth", - "pubYear": "2022", - "date": "2022-01-28", - "isOpenAccess": "Y", - "keywords": "GPS; Mobile phone; Major Depressive Disorder; Smartphone; Phq-8; Home Stay", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Most smartphones and wearables are currently equipped with location sensing (using GPS and mobile network information), which enables continuous location tracking of their users. Several studies have reported that various mobility metrics, as well as home stay, that is, the amount of time an individual spends at home in a day, are associated with symptom severity in people with major depressive disorder (MDD). Owing to the use of small and homogeneous cohorts of participants, it is uncertain whether the findings reported in those studies generalize to a broader population of individuals with MDD symptoms.

Objective

The objective of this study is to examine the relationship between the overall severity of depressive symptoms, as assessed by the 8-item Patient Health Questionnaire, and median daily home stay over the 2 weeks preceding the completion of a questionnaire in individuals with MDD.

Methods

We used questionnaire and geolocation data of 164 participants with MDD collected in the observational Remote Assessment of Disease and Relapse-Major Depressive Disorder study. The participants were recruited from three study sites: King's College London in the United Kingdom (109/164, 66.5%); Vrije Universiteit Medisch Centrum in Amsterdam, the Netherlands (17/164, 10.4%); and Centro de Investigaci\u00f3n Biom\u00e9dica en Red in Barcelona, Spain (38/164, 23.2%). We used a linear regression model and a resampling technique (n=100 draws) to investigate the relationship between home stay and the overall severity of MDD symptoms. Participant age at enrollment, gender, occupational status, and geolocation data quality metrics were included in the model as additional explanatory variables. The 95% 2-sided CIs were used to evaluate the significance of model variables.

Results

Participant age and severity of MDD symptoms were found to be significantly related to home stay, with older (95% CI 0.161-0.325) and more severely affected individuals (95% CI 0.015-0.184) spending more time at home. The association between home stay and symptoms severity appeared to be stronger on weekdays (95% CI 0.023-0.178, median 0.098; home stay: 25th-75th percentiles 17.8-22.8, median 20.9 hours a day) than on weekends (95% CI -0.079 to 0.149, median 0.052; home stay: 25th-75th percentiles 19.7-23.5, median 22.3 hours a day). Furthermore, we found a significant modulation of home stay by occupational status, with employment reducing home stay (employed participants: 25th-75th percentiles 16.1-22.1, median 19.7 hours a day; unemployed participants: 25th-75th percentiles 20.4-23.5, median 22.6 hours a day).

Conclusions

Our findings suggest that home stay is associated with symptom severity in MDD and demonstrate the importance of accounting for confounding factors in future studies. In addition, they illustrate that passive sensing of individuals with depression is feasible and could provide clinically relevant information to monitor the course of illness in patients with MDD.", - "laySummary": "", - "urls": "pdf:https://mhealth.jmir.org/2022/1/e28095/PDF; doi:https://doi.org/10.2196/28095; html:https://europepmc.org/articles/PMC8838593" - }, { "id": "37993464", "doi": "https://doi.org/10.1038/s41467-023-43434-5", @@ -25295,23 +25295,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/jpubhealth/article-pdf/42/4/e516/34469316/fdz172.pdf; doi:https://doi.org/10.1093/pubmed/fdz172" }, - { - "id": "33866023", - "doi": "https://doi.org/10.1016/j.oret.2021.04.001", - "title": "Evolving Treatment Patterns and Outcomes of Neovascular Age-Related Macular Degeneration Over a Decade.", - "authorString": "Schwartz R, Warwick A, Olvera-Barrios A, Pikoula M, Lee AY, Denaxas S, Taylor P, Egan C, Chakravarthy U, Lip PL, Tufail A, of the UK EMR Users Group.", - "authorAffiliations": "", - "journalTitle": "Ophthalmology. Retina", - "pubYear": "2021", - "date": "2021-04-16", - "isOpenAccess": "N", - "keywords": "AMD; Ranibizumab; Anti-vegf; Aflibercept; Electronic Health Records; Etdrs; Early Treatment Diabetic Retinopathy Study", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Purpose

Management of neovascular age-related macular degeneration (nAMD) has evolved over the last decade with several treatment regimens and medications. This study describes the treatment patterns and visual outcomes over 10 years in a large cohort of patients.

Design

Retrospective analysis of electronic health records from 27 National Health Service secondary care healthcare providers in the UK.

Participants

Treatment-na\u00efve patients receiving at least 3 intravitreal anti-vascular endothelial growth factor (VEGF) injections for nAMD in their first 6 months of follow-up were included. Patients with missing data for age or gender and those aged less than 55 years were excluded.

Methods

Eyes with at least 3 years of follow-up were grouped by years of treatment initiation, and 3-year outcomes were compared between the groups. Data were generated during routine clinical care between September 2008 and December\u00a02018.

Main outcome measures

Visual acuity (VA), number of injections, and number of visits.

Results

A total of 15 810 eyes of 13 705 patients receiving 195 104 injections were included. Visual acuity improved from baseline during the first year, but decreased thereafter, resulting in loss of visual gains. This trend remained consistent throughout the past decade. Although an increasing proportion of eyes remained in the driving standard, this was driven by better presenting VA over the decade. The number of injections decreased substantially between the first and subsequent years, from a mean of 6.25 in year 1 to 3 in year 2 and 2.5 in year 3, without improvement over the decade. In a multivariable regression analysis, final VA improved by 0.24 letters for each year since 2008, and younger age and baseline VA were significantly associated with VA at 3 years.

Conclusions

Our findings show that despite improvement in functional VA over the years, primarily driven by improving baseline VA, patients continue to lose vision after the first year of treatment, with only marginal change over the past decade. The data suggest these results may be related to suboptimal treatment patterns, which have not improved over the years. Rethinking treatment strategies may be warranted, possibly on a national level or through the introduction of longer-acting therapies.", - "laySummary": "", - "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165682; doi:https://doi.org/10.1016/j.oret.2021.04.001; html:https://europepmc.org/articles/PMC9165682; pdf:https://europepmc.org/articles/PMC9165682?pdf=render; doi:https://doi.org/10.1016/j.oret.2021.04.001" - }, { "id": "35748342", "doi": "https://doi.org/10.1093/ije/dyac130", @@ -25329,6 +25312,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac130/44245961/dyac130.pdf; doi:https://doi.org/10.1093/ije/dyac130; html:https://europepmc.org/articles/PMC9908066; pdf:https://europepmc.org/articles/PMC9908066?pdf=render" }, + { + "id": "33866023", + "doi": "https://doi.org/10.1016/j.oret.2021.04.001", + "title": "Evolving Treatment Patterns and Outcomes of Neovascular Age-Related Macular Degeneration Over a Decade.", + "authorString": "Schwartz R, Warwick A, Olvera-Barrios A, Pikoula M, Lee AY, Denaxas S, Taylor P, Egan C, Chakravarthy U, Lip PL, Tufail A, of the UK EMR Users Group.", + "authorAffiliations": "", + "journalTitle": "Ophthalmology. Retina", + "pubYear": "2021", + "date": "2021-04-16", + "isOpenAccess": "N", + "keywords": "AMD; Ranibizumab; Anti-vegf; Aflibercept; Electronic Health Records; Etdrs; Early Treatment Diabetic Retinopathy Study", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Purpose

Management of neovascular age-related macular degeneration (nAMD) has evolved over the last decade with several treatment regimens and medications. This study describes the treatment patterns and visual outcomes over 10 years in a large cohort of patients.

Design

Retrospective analysis of electronic health records from 27 National Health Service secondary care healthcare providers in the UK.

Participants

Treatment-na\u00efve patients receiving at least 3 intravitreal anti-vascular endothelial growth factor (VEGF) injections for nAMD in their first 6 months of follow-up were included. Patients with missing data for age or gender and those aged less than 55 years were excluded.

Methods

Eyes with at least 3 years of follow-up were grouped by years of treatment initiation, and 3-year outcomes were compared between the groups. Data were generated during routine clinical care between September 2008 and December\u00a02018.

Main outcome measures

Visual acuity (VA), number of injections, and number of visits.

Results

A total of 15 810 eyes of 13 705 patients receiving 195 104 injections were included. Visual acuity improved from baseline during the first year, but decreased thereafter, resulting in loss of visual gains. This trend remained consistent throughout the past decade. Although an increasing proportion of eyes remained in the driving standard, this was driven by better presenting VA over the decade. The number of injections decreased substantially between the first and subsequent years, from a mean of 6.25 in year 1 to 3 in year 2 and 2.5 in year 3, without improvement over the decade. In a multivariable regression analysis, final VA improved by 0.24 letters for each year since 2008, and younger age and baseline VA were significantly associated with VA at 3 years.

Conclusions

Our findings show that despite improvement in functional VA over the years, primarily driven by improving baseline VA, patients continue to lose vision after the first year of treatment, with only marginal change over the past decade. The data suggest these results may be related to suboptimal treatment patterns, which have not improved over the years. Rethinking treatment strategies may be warranted, possibly on a national level or through the introduction of longer-acting therapies.", + "laySummary": "", + "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165682; doi:https://doi.org/10.1016/j.oret.2021.04.001; html:https://europepmc.org/articles/PMC9165682; pdf:https://europepmc.org/articles/PMC9165682?pdf=render; doi:https://doi.org/10.1016/j.oret.2021.04.001" + }, { "id": "32651323", "doi": "https://doi.org/10.3233/jad-200338", @@ -25363,23 +25363,6 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004036&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004036; html:https://europepmc.org/articles/PMC9879424; pdf:https://europepmc.org/articles/PMC9879424?pdf=render" }, - { - "id": "37735103", - "doi": "https://doi.org/10.1136/bmjresp-2023-001895", - "title": "Preterm birth, birth weight, infant weight gain and their associations with childhood asthma and spirometry: a cross-sectional observational study in Nairobi, Kenya.", - "authorString": "Meme H, Amukoye E, Bowyer C, Chakaya J, Dobson R, Fuld J, Gray CM, Kiplimo R, Lesosky M, Mortimer K, Ndombi A, Obasi A, Orina F, Quint JK, Semple S, West SE, Zurba L, Devereux G.", - "authorAffiliations": "", - "journalTitle": "BMJ open respiratory research", - "pubYear": "2023", - "date": "2023-09-01", - "isOpenAccess": "Y", - "keywords": "Asthma; Paediatric Lung Disaese; Asthma Epidemiology", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

In sub-Saharan Africa, the origins of asthma and high prevalence of abnormal lung function remain unclear. In high-income countries (HICs), associations between birth measurements and childhood asthma and lung function highlight the importance of antenatal and early life factors in the aetiology of asthma and abnormal lung function in children. We present here the first study in sub-Saharan Africa to relate birth characteristics to both childhood respiratory symptoms and lung function.

Methods

Children attending schools in two socioeconomically contrasting but geographically close areas of Nairobi, Kenya, were recruited to a cross-sectional study of childhood asthma and lung function. Questionnaires quantified respiratory symptoms and preterm birth; lung function was measured by spirometry; and parents were invited to bring the child's immunisation booklet containing records of birth weight and serial weights in the first year.

Results

2373 children participated, 52% girls, median age (IQR), 10 years (8-13). Spirometry data were available for 1622. Child immunisation booklets were available for 500 and birth weight and infant weight gain data were available for 323 and 494 children, respectively. In multivariable analyses, preterm birth was associated with the childhood symptoms 'wheeze in the last 12 months'; OR 1.64, (95% CI 1.03 to 2.62), p=0.038; and 'trouble breathing' 3.18 (95% CI 2.27 to 4.45), p<0.001. Birth weight (kg) was associated with forced expiratory volume in 1 s z-score, regression coefficient (\u03b2) 0.30 (0.08, 0.52), p=0.008, FVC z-score 0.29 (95% CI 0.08 to 0.51); p=0.008\u2009and restricted spirometry, OR 0.11 (95% CI 0.02 to 0.78), p=0.027.

Conclusion

These associations are in keeping with those in HICs and highlight antenatal factors in the aetiology of asthma and lung function abnormalities in sub-Saharan Africa.", - "laySummary": "", - "urls": "pdf:https://bmjopenrespres.bmj.com/content/bmjresp/10/1/e001895.full.pdf; doi:https://doi.org/10.1136/bmjresp-2023-001895; html:https://europepmc.org/articles/PMC10514609; pdf:https://europepmc.org/articles/PMC10514609?pdf=render" - }, { "id": "32142356", "doi": "https://doi.org/10.1164/rccm.201902-0286oc", @@ -25414,6 +25397,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S2352396419300775/pdf; doi:https://doi.org/10.1016/j.ebiom.2019.02.005; html:https://europepmc.org/articles/PMC6442001; pdf:https://europepmc.org/articles/PMC6442001?pdf=render" }, + { + "id": "37735103", + "doi": "https://doi.org/10.1136/bmjresp-2023-001895", + "title": "Preterm birth, birth weight, infant weight gain and their associations with childhood asthma and spirometry: a cross-sectional observational study in Nairobi, Kenya.", + "authorString": "Meme H, Amukoye E, Bowyer C, Chakaya J, Dobson R, Fuld J, Gray CM, Kiplimo R, Lesosky M, Mortimer K, Ndombi A, Obasi A, Orina F, Quint JK, Semple S, West SE, Zurba L, Devereux G.", + "authorAffiliations": "", + "journalTitle": "BMJ open respiratory research", + "pubYear": "2023", + "date": "2023-09-01", + "isOpenAccess": "Y", + "keywords": "Asthma; Paediatric Lung Disaese; Asthma Epidemiology", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

In sub-Saharan Africa, the origins of asthma and high prevalence of abnormal lung function remain unclear. In high-income countries (HICs), associations between birth measurements and childhood asthma and lung function highlight the importance of antenatal and early life factors in the aetiology of asthma and abnormal lung function in children. We present here the first study in sub-Saharan Africa to relate birth characteristics to both childhood respiratory symptoms and lung function.

Methods

Children attending schools in two socioeconomically contrasting but geographically close areas of Nairobi, Kenya, were recruited to a cross-sectional study of childhood asthma and lung function. Questionnaires quantified respiratory symptoms and preterm birth; lung function was measured by spirometry; and parents were invited to bring the child's immunisation booklet containing records of birth weight and serial weights in the first year.

Results

2373 children participated, 52% girls, median age (IQR), 10 years (8-13). Spirometry data were available for 1622. Child immunisation booklets were available for 500 and birth weight and infant weight gain data were available for 323 and 494 children, respectively. In multivariable analyses, preterm birth was associated with the childhood symptoms 'wheeze in the last 12 months'; OR 1.64, (95% CI 1.03 to 2.62), p=0.038; and 'trouble breathing' 3.18 (95% CI 2.27 to 4.45), p<0.001. Birth weight (kg) was associated with forced expiratory volume in 1 s z-score, regression coefficient (\u03b2) 0.30 (0.08, 0.52), p=0.008, FVC z-score 0.29 (95% CI 0.08 to 0.51); p=0.008\u2009and restricted spirometry, OR 0.11 (95% CI 0.02 to 0.78), p=0.027.

Conclusion

These associations are in keeping with those in HICs and highlight antenatal factors in the aetiology of asthma and lung function abnormalities in sub-Saharan Africa.", + "laySummary": "", + "urls": "pdf:https://bmjopenrespres.bmj.com/content/bmjresp/10/1/e001895.full.pdf; doi:https://doi.org/10.1136/bmjresp-2023-001895; html:https://europepmc.org/articles/PMC10514609; pdf:https://europepmc.org/articles/PMC10514609?pdf=render" + }, { "id": "37653496", "doi": "https://doi.org/10.1186/s12933-023-01963-9", @@ -25431,23 +25431,6 @@ "laySummary": "", "urls": "pdf:https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-023-01963-9; doi:https://doi.org/10.1186/s12933-023-01963-9; html:https://europepmc.org/articles/PMC10472675; pdf:https://europepmc.org/articles/PMC10472675?pdf=render" }, - { - "id": "35743743", - "doi": "https://doi.org/10.3390/jpm12060958", - "title": "Immune Cell Networks Uncover Candidate Biomarkers of Melanoma Immunotherapy Response.", - "authorString": "Vo DHT, McGleave G, Overton IM.", - "authorAffiliations": "", - "journalTitle": "Journal of personalized medicine", - "pubYear": "2022", - "date": "2022-06-11", - "isOpenAccess": "Y", - "keywords": "Melanoma; Immunotherapy; Ovarian carcinoma; Biomarker; Network Biology; Systems Immunology; Nivolumab; Systems Medicine; Immune Checkpoint; Precision Oncology", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The therapeutic activation of antitumour immunity by immune checkpoint inhibitors (ICIs) is a significant advance in cancer medicine, not least due to the prospect of long-term remission. However, many patients are unresponsive to ICI therapy and may experience serious side effects; companion biomarkers are urgently needed to help inform ICI prescribing decisions. We present the IMMUNETS networks of gene coregulation in five key immune cell types and their application to interrogate control of nivolumab response in advanced melanoma cohorts. The results evidence a role for each of the IMMUNETS cell types in ICI response and in driving tumour clearance with independent cohorts from TCGA. As expected, 'immune hot' status, including T cell proliferation, correlates with response to first-line ICI therapy. Genes regulated in NK, dendritic, and B cells are the most prominent discriminators of nivolumab response in patients that had previously progressed on another ICI. Multivariate analysis controlling for tumour stage and age highlights CIITA and IKZF3 as candidate prognostic biomarkers. IMMUNETS provide a resource for network biology, enabling context-specific analysis of immune components in orthogonal datasets. Overall, our results illuminate the relationship between the tumour microenvironment and clinical trajectories, with potential implications for precision medicine.", - "laySummary": "", - "urls": "pdf:https://www.mdpi.com/2075-4426/12/6/958/pdf?version=1655284846; doi:https://doi.org/10.3390/jpm12060958; html:https://europepmc.org/articles/PMC9225330; pdf:https://europepmc.org/articles/PMC9225330?pdf=render" - }, { "id": "35004880", "doi": "https://doi.org/10.3389/fcvm.2021.763361", @@ -25465,6 +25448,23 @@ "laySummary": "", "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.763361/pdf; doi:https://doi.org/10.3389/fcvm.2021.763361; html:https://europepmc.org/articles/PMC8727756; pdf:https://europepmc.org/articles/PMC8727756?pdf=render" }, + { + "id": "35743743", + "doi": "https://doi.org/10.3390/jpm12060958", + "title": "Immune Cell Networks Uncover Candidate Biomarkers of Melanoma Immunotherapy Response.", + "authorString": "Vo DHT, McGleave G, Overton IM.", + "authorAffiliations": "", + "journalTitle": "Journal of personalized medicine", + "pubYear": "2022", + "date": "2022-06-11", + "isOpenAccess": "Y", + "keywords": "Melanoma; Immunotherapy; Ovarian carcinoma; Biomarker; Network Biology; Systems Immunology; Nivolumab; Systems Medicine; Immune Checkpoint; Precision Oncology", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The therapeutic activation of antitumour immunity by immune checkpoint inhibitors (ICIs) is a significant advance in cancer medicine, not least due to the prospect of long-term remission. However, many patients are unresponsive to ICI therapy and may experience serious side effects; companion biomarkers are urgently needed to help inform ICI prescribing decisions. We present the IMMUNETS networks of gene coregulation in five key immune cell types and their application to interrogate control of nivolumab response in advanced melanoma cohorts. The results evidence a role for each of the IMMUNETS cell types in ICI response and in driving tumour clearance with independent cohorts from TCGA. As expected, 'immune hot' status, including T cell proliferation, correlates with response to first-line ICI therapy. Genes regulated in NK, dendritic, and B cells are the most prominent discriminators of nivolumab response in patients that had previously progressed on another ICI. Multivariate analysis controlling for tumour stage and age highlights CIITA and IKZF3 as candidate prognostic biomarkers. IMMUNETS provide a resource for network biology, enabling context-specific analysis of immune components in orthogonal datasets. Overall, our results illuminate the relationship between the tumour microenvironment and clinical trajectories, with potential implications for precision medicine.", + "laySummary": "", + "urls": "pdf:https://www.mdpi.com/2075-4426/12/6/958/pdf?version=1655284846; doi:https://doi.org/10.3390/jpm12060958; html:https://europepmc.org/articles/PMC9225330; pdf:https://europepmc.org/articles/PMC9225330?pdf=render" + }, { "id": "36469091", "doi": "https://doi.org/10.1093/ageing/afac252", @@ -25584,23 +25584,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1073/pnas.2108395118; doi:https://doi.org/10.1073/pnas.2108395118; html:https://europepmc.org/articles/PMC8670441; pdf:https://europepmc.org/articles/PMC8670441?pdf=render" }, - { - "id": "37573145", - "doi": "https://doi.org/10.1093/ndt/gfad180", - "title": "Recovery of kidney function after acute kidney disease-a multi-cohort analysis.", - "authorString": "Sawhney S, Ball W, Bell S, Black C, Christiansen CF, Heide-J\u00f8rgensen U, Jensen SK, Lambourg E, Ronksley PE, Tan Z, Tonelli M, James MT.", - "authorAffiliations": "", - "journalTitle": "Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association", - "pubYear": "2024", - "date": "2024-02-01", - "isOpenAccess": "Y", - "keywords": "Recovery; Prognosis; epidemiology; Ckd; Aki", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

There are no consensus definitions for evaluating kidney function recovery after acute kidney injury (AKI) and acute kidney disease (AKD), nor is it clear how recovery varies across populations and clinical subsets. We present a federated analysis of four population-based cohorts from Canada, Denmark and Scotland, 2011-18.

Methods

We identified incident AKD defined by serum creatinine changes within 48\u00a0h, 7\u00a0days and 90\u00a0days based on KDIGO AKI and AKD criteria. Separately, we applied changes up to 365\u00a0days to address widely used e-alert implementations that extend beyond the KDIGO AKI and AKD timeframes. Kidney recovery was based on resolution of AKD and a subsequent creatinine measurement below 1.2\u00d7 baseline. We evaluated transitions between non-recovery, recovery and death up to 1\u00a0year; within age, sex and comorbidity subgroups; between subset AKD definitions; and across cohorts.

Results

There were 464\u00a0868 incident cases, median age 67-75\u00a0years. At 1\u00a0year, results were consistent across cohorts, with pooled mortalities for creatinine changes within 48\u00a0h, 7\u00a0days, 90\u00a0days and 365\u00a0days (and 95% confidence interval) of 40% (34%-45%), 40% (34%-46%), 37% (31%-42%) and 22% (16%-29%) respectively, and non-recovery of kidney function of 19% (15%-23%), 30% (24%-35%), 25% (21%-29%) and 37% (30%-43%), respectively. Recovery by 14 and 90\u00a0days was frequently not sustained at 1\u00a0year. Older males and those with heart failure or cancer were more likely to die than to experience sustained non-recovery, whereas the converse was true for younger females and those with diabetes.

Conclusion

Consistently across multiple cohorts, based on 1-year mortality and non-recovery, KDIGO AKD (up to 90\u00a0days) is at least prognostically similar to KDIGO AKI (7\u00a0days), and covers more people. Outcomes associated with AKD vary by age, sex and comorbidities such that older males are more likely to die, and younger females are less likely to recover.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/ndt/advance-article-pdf/doi/10.1093/ndt/gfad180/51104398/gfad180.pdf; doi:https://doi.org/10.1093/ndt/gfad180; html:https://europepmc.org/articles/PMC10899778; pdf:https://europepmc.org/articles/PMC10899778?pdf=render" - }, { "id": "33735069", "doi": "https://doi.org/10.1016/s2589-7500(20)30240-5", @@ -25618,6 +25601,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S2589750020302405/pdf; doi:https://doi.org/10.1016/S2589-7500(20)30240-5" }, + { + "id": "37573145", + "doi": "https://doi.org/10.1093/ndt/gfad180", + "title": "Recovery of kidney function after acute kidney disease-a multi-cohort analysis.", + "authorString": "Sawhney S, Ball W, Bell S, Black C, Christiansen CF, Heide-J\u00f8rgensen U, Jensen SK, Lambourg E, Ronksley PE, Tan Z, Tonelli M, James MT.", + "authorAffiliations": "", + "journalTitle": "Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association", + "pubYear": "2024", + "date": "2024-02-01", + "isOpenAccess": "Y", + "keywords": "Recovery; Prognosis; epidemiology; Ckd; Aki", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

There are no consensus definitions for evaluating kidney function recovery after acute kidney injury (AKI) and acute kidney disease (AKD), nor is it clear how recovery varies across populations and clinical subsets. We present a federated analysis of four population-based cohorts from Canada, Denmark and Scotland, 2011-18.

Methods

We identified incident AKD defined by serum creatinine changes within 48\u00a0h, 7\u00a0days and 90\u00a0days based on KDIGO AKI and AKD criteria. Separately, we applied changes up to 365\u00a0days to address widely used e-alert implementations that extend beyond the KDIGO AKI and AKD timeframes. Kidney recovery was based on resolution of AKD and a subsequent creatinine measurement below 1.2\u00d7 baseline. We evaluated transitions between non-recovery, recovery and death up to 1\u00a0year; within age, sex and comorbidity subgroups; between subset AKD definitions; and across cohorts.

Results

There were 464\u00a0868 incident cases, median age 67-75\u00a0years. At 1\u00a0year, results were consistent across cohorts, with pooled mortalities for creatinine changes within 48\u00a0h, 7\u00a0days, 90\u00a0days and 365\u00a0days (and 95% confidence interval) of 40% (34%-45%), 40% (34%-46%), 37% (31%-42%) and 22% (16%-29%) respectively, and non-recovery of kidney function of 19% (15%-23%), 30% (24%-35%), 25% (21%-29%) and 37% (30%-43%), respectively. Recovery by 14 and 90\u00a0days was frequently not sustained at 1\u00a0year. Older males and those with heart failure or cancer were more likely to die than to experience sustained non-recovery, whereas the converse was true for younger females and those with diabetes.

Conclusion

Consistently across multiple cohorts, based on 1-year mortality and non-recovery, KDIGO AKD (up to 90\u00a0days) is at least prognostically similar to KDIGO AKI (7\u00a0days), and covers more people. Outcomes associated with AKD vary by age, sex and comorbidities such that older males are more likely to die, and younger females are less likely to recover.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/ndt/advance-article-pdf/doi/10.1093/ndt/gfad180/51104398/gfad180.pdf; doi:https://doi.org/10.1093/ndt/gfad180; html:https://europepmc.org/articles/PMC10899778; pdf:https://europepmc.org/articles/PMC10899778?pdf=render" + }, { "id": "30928915", "doi": "https://doi.org/10.1136/injuryprev-2018-043085", @@ -25652,23 +25652,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.amjcard.2023.05.039" }, - { - "id": "37419925", - "doi": "https://doi.org/10.1038/s41467-023-38930-7", - "title": "Optimal strategies for learning multi-ancestry polygenic scores vary across traits.", - "authorString": "Lehmann B, Mackintosh M, McVean G, Holmes C.", - "authorAffiliations": "", - "journalTitle": "Nature communications", - "pubYear": "2023", - "date": "2023-07-07", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Polygenic scores (PGSs) are individual-level measures that aggregate the genome-wide genetic predisposition to a given trait. As PGS have predominantly been developed using European-ancestry samples, trait prediction using such European ancestry-derived PGS is less accurate in non-European ancestry individuals. Although there has been recent progress in combining multiple PGS trained on distinct populations, the problem of how to maximize performance given a multiple-ancestry cohort is largely unexplored. Here, we investigate the effect of sample size and ancestry composition on PGS performance for fifteen traits in UK Biobank. For some traits, PGS estimated using a relatively small African-ancestry training set outperformed, on an African-ancestry test set, PGS estimated using a much larger European-ancestry only training set. We observe similar, but not identical, results when considering other minority-ancestry groups within UK Biobank. Our results emphasise the importance of targeted data collection from underrepresented groups in order to address existing disparities in PGS performance.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41467-023-38930-7.pdf; doi:https://doi.org/10.1038/s41467-023-38930-7; html:https://europepmc.org/articles/PMC10328935; pdf:https://europepmc.org/articles/PMC10328935?pdf=render" - }, { "id": "33328453", "doi": "https://doi.org/10.1038/s41467-020-19996-z", @@ -25687,21 +25670,21 @@ "urls": "pdf:https://www.nature.com/articles/s41467-020-19996-z.pdf; doi:https://doi.org/10.1038/s41467-020-19996-z; html:https://europepmc.org/articles/PMC7744536; pdf:https://europepmc.org/articles/PMC7744536?pdf=render" }, { - "id": "31413164", - "doi": "https://doi.org/10.1183/13993003.00476-2019", - "title": "Allergic diseases and long-term risk of autoimmune disorders: longitudinal cohort study and cluster analysis.", - "authorString": "Krishna MT, Subramanian A, Adderley NJ, Zemedikun DT, Gkoutos GV, Nirantharakumar K.", + "id": "37419925", + "doi": "https://doi.org/10.1038/s41467-023-38930-7", + "title": "Optimal strategies for learning multi-ancestry polygenic scores vary across traits.", + "authorString": "Lehmann B, Mackintosh M, McVean G, Holmes C.", "authorAffiliations": "", - "journalTitle": "The European respiratory journal", - "pubYear": "2019", - "date": "2019-11-14", - "isOpenAccess": "N", + "journalTitle": "Nature communications", + "pubYear": "2023", + "date": "2023-07-07", + "isOpenAccess": "Y", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Introduction

The association between allergic diseases and autoimmune disorders is not well established. Our objective was to determine incidence rates of autoimmune disorders in allergic rhinitis/conjunctivitis (ARC), atopic eczema and asthma, and to investigate for co-occurring patterns.

Methods

This was a retrospective cohort study (1990-2018) employing data extracted from The Health Improvement Network (UK primary care database). The exposure group comprised ARC, atopic eczema and asthma (all ages). For each exposed patient, up to two randomly selected age- and sex-matched controls with no documented allergic disease were used. Adjusted incidence rate ratios (aIRRs) were calculated using Poisson regression. A cross-sectional study was also conducted employing Association Rule Mining (ARM) to investigate disease clusters.

Results

782\u200a320, 1\u200a393\u200a570 and 1\u200a049\u200a868 patients with ARC, atopic eczema and asthma, respectively, were included. aIRRs of systemic lupus erythematosus (SLE), Sj\u00f6gren's syndrome, vitiligo, rheumatoid arthritis, psoriasis, pernicious anaemia, inflammatory bowel disease, coeliac disease and autoimmune thyroiditis were uniformly higher in the three allergic diseases compared with controls. Specifically, aIRRs of SLE (1.45) and Sj\u00f6gren's syndrome (1.88) were higher in ARC; aIRRs of SLE (1.44), Sj\u00f6gren's syndrome (1.61) and myasthenia (1.56) were higher in asthma; and aIRRs of SLE (1.86), Sj\u00f6gren's syndrome (1.48), vitiligo (1.54) and psoriasis (2.41) were higher in atopic eczema. There was no significant effect of the three allergic diseases on multiple sclerosis or of ARC and atopic eczema on myasthenia. Using ARM, allergic diseases clustered with multiple autoimmune disorders. Three age- and sex-related clusters were identified, with a relatively complex pattern in females \u226555\u2005years old.

Conclusions

The long-term risks of autoimmune disorders are significantly higher in patients with allergic diseases. Allergic diseases and autoimmune disorders show age- and sex-related clustering patterns.", + "abstract": "Polygenic scores (PGSs) are individual-level measures that aggregate the genome-wide genetic predisposition to a given trait. As PGS have predominantly been developed using European-ancestry samples, trait prediction using such European ancestry-derived PGS is less accurate in non-European ancestry individuals. Although there has been recent progress in combining multiple PGS trained on distinct populations, the problem of how to maximize performance given a multiple-ancestry cohort is largely unexplored. Here, we investigate the effect of sample size and ancestry composition on PGS performance for fifteen traits in UK Biobank. For some traits, PGS estimated using a relatively small African-ancestry training set outperformed, on an African-ancestry test set, PGS estimated using a much larger European-ancestry only training set. We observe similar, but not identical, results when considering other minority-ancestry groups within UK Biobank. Our results emphasise the importance of targeted data collection from underrepresented groups in order to address existing disparities in PGS performance.", "laySummary": "", - "urls": "pdf:https://erj.ersjournals.com/content/erj/54/5/1900476.full.pdf; doi:https://doi.org/10.1183/13993003.00476-2019" + "urls": "pdf:https://www.nature.com/articles/s41467-023-38930-7.pdf; doi:https://doi.org/10.1038/s41467-023-38930-7; html:https://europepmc.org/articles/PMC10328935; pdf:https://europepmc.org/articles/PMC10328935?pdf=render" }, { "id": "31711543", @@ -25721,21 +25704,21 @@ "urls": "pdf:https://jbiomedsem.biomedcentral.com/track/pdf/10.1186/s13326-019-0214-4; doi:https://doi.org/10.1186/s13326-019-0214-4; html:https://europepmc.org/articles/PMC6849160; pdf:https://europepmc.org/articles/PMC6849160?pdf=render" }, { - "id": "38416429", - "doi": "https://doi.org/10.1056/nejmoa2311330", - "title": "Cognition and Memory after Covid-19 in a Large Community Sample.", - "authorString": "Hampshire A, Azor A, Atchison C, Trender W, Hellyer PJ, Giunchiglia V, Husain M, Cooke GS, Cooper E, Lound A, Donnelly CA, Chadeau-Hyam M, Ward H, Elliott P.", + "id": "31413164", + "doi": "https://doi.org/10.1183/13993003.00476-2019", + "title": "Allergic diseases and long-term risk of autoimmune disorders: longitudinal cohort study and cluster analysis.", + "authorString": "Krishna MT, Subramanian A, Adderley NJ, Zemedikun DT, Gkoutos GV, Nirantharakumar K.", "authorAffiliations": "", - "journalTitle": "The New England journal of medicine", - "pubYear": "2024", - "date": "2024-02-01", - "isOpenAccess": "Y", + "journalTitle": "The European respiratory journal", + "pubYear": "2019", + "date": "2019-11-14", + "isOpenAccess": "N", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Cognitive symptoms after coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are well-recognized. Whether objectively measurable cognitive deficits exist and how long they persist are unclear.

Methods

We invited 800,000 adults in a study in England to complete an online assessment of cognitive function. We estimated a global cognitive score across eight tasks. We hypothesized that participants with persistent symptoms (lasting \u226512 weeks) after infection onset would have objectively measurable global cognitive deficits and that impairments in executive functioning and memory would be observed in such participants, especially in those who reported recent poor memory or difficulty thinking or concentrating (\"brain fog\").

Results

Of the 141,583 participants who started the online cognitive assessment, 112,964 completed it. In a multiple regression analysis, participants who had recovered from Covid-19 in whom symptoms had resolved in less than 4 weeks or at least 12 weeks had similar small deficits in global cognition as compared with those in the no-Covid-19 group, who had not been infected with SARS-CoV-2 or had unconfirmed infection (-0.23 SD [95% confidence interval {CI}, -0.33 to -0.13] and -0.24 SD [95% CI, -0.36 to -0.12], respectively); larger deficits as compared with the no-Covid-19 group were seen in participants with unresolved persistent symptoms (-0.42 SD; 95% CI, -0.53 to -0.31). Larger deficits were seen in participants who had SARS-CoV-2 infection during periods in which the original virus or the B.1.1.7 variant was predominant than in those infected with later variants (e.g., -0.17 SD for the B.1.1.7 variant vs. the B.1.1.529 variant; 95% CI, -0.20 to -0.13) and in participants who had been hospitalized than in those who had not been hospitalized (e.g., intensive care unit admission, -0.35 SD; 95% CI, -0.49 to -0.20). Results of the analyses were similar to those of propensity-score-matching analyses. In a comparison of the group that had unresolved persistent symptoms with the no-Covid-19 group, memory, reasoning, and executive function tasks were associated with the largest deficits (-0.33 to -0.20 SD); these tasks correlated weakly with recent symptoms, including poor memory and brain fog. No adverse events were reported.

Conclusions

Participants with resolved persistent symptoms after Covid-19 had objectively measured cognitive function similar to that in participants with shorter-duration symptoms, although short-duration Covid-19 was still associated with small cognitive deficits after recovery. Longer-term persistence of cognitive deficits and any clinical implications remain uncertain. (Funded by the National Institute for Health and Care Research and others.).", + "abstract": "

Introduction

The association between allergic diseases and autoimmune disorders is not well established. Our objective was to determine incidence rates of autoimmune disorders in allergic rhinitis/conjunctivitis (ARC), atopic eczema and asthma, and to investigate for co-occurring patterns.

Methods

This was a retrospective cohort study (1990-2018) employing data extracted from The Health Improvement Network (UK primary care database). The exposure group comprised ARC, atopic eczema and asthma (all ages). For each exposed patient, up to two randomly selected age- and sex-matched controls with no documented allergic disease were used. Adjusted incidence rate ratios (aIRRs) were calculated using Poisson regression. A cross-sectional study was also conducted employing Association Rule Mining (ARM) to investigate disease clusters.

Results

782\u200a320, 1\u200a393\u200a570 and 1\u200a049\u200a868 patients with ARC, atopic eczema and asthma, respectively, were included. aIRRs of systemic lupus erythematosus (SLE), Sj\u00f6gren's syndrome, vitiligo, rheumatoid arthritis, psoriasis, pernicious anaemia, inflammatory bowel disease, coeliac disease and autoimmune thyroiditis were uniformly higher in the three allergic diseases compared with controls. Specifically, aIRRs of SLE (1.45) and Sj\u00f6gren's syndrome (1.88) were higher in ARC; aIRRs of SLE (1.44), Sj\u00f6gren's syndrome (1.61) and myasthenia (1.56) were higher in asthma; and aIRRs of SLE (1.86), Sj\u00f6gren's syndrome (1.48), vitiligo (1.54) and psoriasis (2.41) were higher in atopic eczema. There was no significant effect of the three allergic diseases on multiple sclerosis or of ARC and atopic eczema on myasthenia. Using ARM, allergic diseases clustered with multiple autoimmune disorders. Three age- and sex-related clusters were identified, with a relatively complex pattern in females \u226555\u2005years old.

Conclusions

The long-term risks of autoimmune disorders are significantly higher in patients with allergic diseases. Allergic diseases and autoimmune disorders show age- and sex-related clustering patterns.", "laySummary": "", - "urls": "pdf:https://www.nejm.org/doi/pdf/10.1056/NEJMoa2311330?articleTools=true; doi:https://doi.org/10.1056/NEJMoa2311330; html:https://europepmc.org/articles/PMC7615803; pdf:https://europepmc.org/articles/PMC7615803?pdf=render" + "urls": "pdf:https://erj.ersjournals.com/content/erj/54/5/1900476.full.pdf; doi:https://doi.org/10.1183/13993003.00476-2019" }, { "id": "33719753", @@ -25788,6 +25771,23 @@ "laySummary": "", "urls": "pdf:https://n.neurology.org/content/neurology/95/4/e353.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000009814; html:https://europepmc.org/articles/PMC7455321; pdf:https://europepmc.org/articles/PMC7455321?pdf=render" }, + { + "id": "38416429", + "doi": "https://doi.org/10.1056/nejmoa2311330", + "title": "Cognition and Memory after Covid-19 in a Large Community Sample.", + "authorString": "Hampshire A, Azor A, Atchison C, Trender W, Hellyer PJ, Giunchiglia V, Husain M, Cooke GS, Cooper E, Lound A, Donnelly CA, Chadeau-Hyam M, Ward H, Elliott P.", + "authorAffiliations": "", + "journalTitle": "The New England journal of medicine", + "pubYear": "2024", + "date": "2024-02-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Cognitive symptoms after coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are well-recognized. Whether objectively measurable cognitive deficits exist and how long they persist are unclear.

Methods

We invited 800,000 adults in a study in England to complete an online assessment of cognitive function. We estimated a global cognitive score across eight tasks. We hypothesized that participants with persistent symptoms (lasting \u226512 weeks) after infection onset would have objectively measurable global cognitive deficits and that impairments in executive functioning and memory would be observed in such participants, especially in those who reported recent poor memory or difficulty thinking or concentrating (\"brain fog\").

Results

Of the 141,583 participants who started the online cognitive assessment, 112,964 completed it. In a multiple regression analysis, participants who had recovered from Covid-19 in whom symptoms had resolved in less than 4 weeks or at least 12 weeks had similar small deficits in global cognition as compared with those in the no-Covid-19 group, who had not been infected with SARS-CoV-2 or had unconfirmed infection (-0.23 SD [95% confidence interval {CI}, -0.33 to -0.13] and -0.24 SD [95% CI, -0.36 to -0.12], respectively); larger deficits as compared with the no-Covid-19 group were seen in participants with unresolved persistent symptoms (-0.42 SD; 95% CI, -0.53 to -0.31). Larger deficits were seen in participants who had SARS-CoV-2 infection during periods in which the original virus or the B.1.1.7 variant was predominant than in those infected with later variants (e.g., -0.17 SD for the B.1.1.7 variant vs. the B.1.1.529 variant; 95% CI, -0.20 to -0.13) and in participants who had been hospitalized than in those who had not been hospitalized (e.g., intensive care unit admission, -0.35 SD; 95% CI, -0.49 to -0.20). Results of the analyses were similar to those of propensity-score-matching analyses. In a comparison of the group that had unresolved persistent symptoms with the no-Covid-19 group, memory, reasoning, and executive function tasks were associated with the largest deficits (-0.33 to -0.20 SD); these tasks correlated weakly with recent symptoms, including poor memory and brain fog. No adverse events were reported.

Conclusions

Participants with resolved persistent symptoms after Covid-19 had objectively measured cognitive function similar to that in participants with shorter-duration symptoms, although short-duration Covid-19 was still associated with small cognitive deficits after recovery. Longer-term persistence of cognitive deficits and any clinical implications remain uncertain. (Funded by the National Institute for Health and Care Research and others.).", + "laySummary": "", + "urls": "pdf:https://www.nejm.org/doi/pdf/10.1056/NEJMoa2311330?articleTools=true; doi:https://doi.org/10.1056/NEJMoa2311330; html:https://europepmc.org/articles/PMC7615803; pdf:https://europepmc.org/articles/PMC7615803?pdf=render" + }, { "id": "35259281", "doi": "https://doi.org/10.1111/acel.13524", @@ -25822,23 +25822,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.chiabu.2020.104760; doi:https://doi.org/10.1016/j.chiabu.2020.104760; html:https://europepmc.org/articles/PMC7718112" }, - { - "id": "37393610", - "doi": "https://doi.org/10.1016/j.xpro.2023.102392", - "title": "Protocol for the automatic extraction of epidemiological information via a pre-trained language model.", - "authorString": "Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wang Z, Cao Y, Wong ZSY, Xu XK, Sun Y.", - "authorAffiliations": "", - "journalTitle": "STAR protocols", - "pubYear": "2023", - "date": "2023-07-01", - "isOpenAccess": "Y", - "keywords": "Health Sciences; Clinical Protocol; Computer Sciences", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The lack of systems to automatically extract epidemiological fields from open-access COVID-19 cases restricts the timeliness of formulating prevention measures. Here we present a protocol for using CCIE, a COVID-19 Cases Information Extraction system based on the pre-trained language model.1 We describe steps for preparing supervised training data and executing python scripts for named entity recognition and text category classification. We then detail the use of machine evaluation and manual validation to illustrate the effectiveness of CCIE. For complete details on the use and execution of this protocol, please refer to Wang et\u00a0al.2.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.xpro.2023.102392; doi:https://doi.org/10.1016/j.xpro.2023.102392; html:https://europepmc.org/articles/PMC10328978; pdf:https://europepmc.org/articles/PMC10328978?pdf=render" - }, { "id": "33824583", "doi": "https://doi.org/10.2147/copd.s298585", @@ -25856,6 +25839,23 @@ "laySummary": "", "urls": "pdf:https://www.dovepress.com/getfile.php?fileID=68078; doi:https://doi.org/10.2147/COPD.S298585; html:https://europepmc.org/articles/PMC8018552; pdf:https://europepmc.org/articles/PMC8018552?pdf=render" }, + { + "id": "37393610", + "doi": "https://doi.org/10.1016/j.xpro.2023.102392", + "title": "Protocol for the automatic extraction of epidemiological information via a pre-trained language model.", + "authorString": "Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wang Z, Cao Y, Wong ZSY, Xu XK, Sun Y.", + "authorAffiliations": "", + "journalTitle": "STAR protocols", + "pubYear": "2023", + "date": "2023-07-01", + "isOpenAccess": "Y", + "keywords": "Health Sciences; Clinical Protocol; Computer Sciences", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The lack of systems to automatically extract epidemiological fields from open-access COVID-19 cases restricts the timeliness of formulating prevention measures. Here we present a protocol for using CCIE, a COVID-19 Cases Information Extraction system based on the pre-trained language model.1 We describe steps for preparing supervised training data and executing python scripts for named entity recognition and text category classification. We then detail the use of machine evaluation and manual validation to illustrate the effectiveness of CCIE. For complete details on the use and execution of this protocol, please refer to Wang et\u00a0al.2.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.xpro.2023.102392; doi:https://doi.org/10.1016/j.xpro.2023.102392; html:https://europepmc.org/articles/PMC10328978; pdf:https://europepmc.org/articles/PMC10328978?pdf=render" + }, { "id": "35842920", "doi": "https://doi.org/10.1002/ehf2.14073", @@ -25941,23 +25941,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.xgen.2024.100541; html:https://europepmc.org/articles/PMC11099345; pdf:https://europepmc.org/articles/PMC11099345?pdf=render" }, - { - "id": "37563195", - "doi": "https://doi.org/10.1038/s41598-023-38880-6", - "title": "Locational memory of macrovessel vascular cells is transcriptionally imprinted.", - "authorString": "Spanjersberg TCF, Oosterhoff LA, Kruitwagen HS, van den Dungen NAM, Vernooij JCM, Asselbergs FW, Mokry M, Spee B, Harakalova M, van Steenbeek FG.", - "authorAffiliations": "", - "journalTitle": "Scientific reports", - "pubYear": "2023", - "date": "2023-08-10", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Vascular pathologies show locational predisposition throughout the body; further insights into the transcriptomics basis of this vascular heterogeneity are needed. We analyzed transcriptomes from cultured endothelial cells and vascular smooth muscle cells from nine adult canine macrovessels: the aorta, coronary artery, vena cava, portal vein, femoral artery, femoral vein, saphenous vein, pulmonary vein, and pulmonary artery. We observed that organ-specific expression patterns persist in vitro, indicating that these genes are not regulated by blood flow or surrounding cell types but are likely fixed in the epigenetic memory. We further demonstrated the preserved location-specific expression of GATA4 protein in cultured cells and in the primary adult vessel. On a functional level, arterial and venous endothelial cells differed in vascular network morphology as the arterial networks maintained a higher complexity. Our findings prompt the rethinking of the extrapolation of results from single-origin endothelial cell systems.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41598-023-38880-6.pdf; doi:https://doi.org/10.1038/s41598-023-38880-6; html:https://europepmc.org/articles/PMC10415317; pdf:https://europepmc.org/articles/PMC10415317?pdf=render" - }, { "id": "36828609", "doi": "https://doi.org/10.1016/s2589-7500(22)00252-7", @@ -25975,6 +25958,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/s2589-7500(22)00252-7; doi:https://doi.org/10.1016/S2589-7500(22)00252-7" }, + { + "id": "37563195", + "doi": "https://doi.org/10.1038/s41598-023-38880-6", + "title": "Locational memory of macrovessel vascular cells is transcriptionally imprinted.", + "authorString": "Spanjersberg TCF, Oosterhoff LA, Kruitwagen HS, van den Dungen NAM, Vernooij JCM, Asselbergs FW, Mokry M, Spee B, Harakalova M, van Steenbeek FG.", + "authorAffiliations": "", + "journalTitle": "Scientific reports", + "pubYear": "2023", + "date": "2023-08-10", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Vascular pathologies show locational predisposition throughout the body; further insights into the transcriptomics basis of this vascular heterogeneity are needed. We analyzed transcriptomes from cultured endothelial cells and vascular smooth muscle cells from nine adult canine macrovessels: the aorta, coronary artery, vena cava, portal vein, femoral artery, femoral vein, saphenous vein, pulmonary vein, and pulmonary artery. We observed that organ-specific expression patterns persist in vitro, indicating that these genes are not regulated by blood flow or surrounding cell types but are likely fixed in the epigenetic memory. We further demonstrated the preserved location-specific expression of GATA4 protein in cultured cells and in the primary adult vessel. On a functional level, arterial and venous endothelial cells differed in vascular network morphology as the arterial networks maintained a higher complexity. Our findings prompt the rethinking of the extrapolation of results from single-origin endothelial cell systems.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41598-023-38880-6.pdf; doi:https://doi.org/10.1038/s41598-023-38880-6; html:https://europepmc.org/articles/PMC10415317; pdf:https://europepmc.org/articles/PMC10415317?pdf=render" + }, { "id": "35504525", "doi": "https://doi.org/10.1016/j.jclinepi.2022.04.025", @@ -26230,23 +26230,6 @@ "laySummary": "", "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCEP.121.010221; doi:https://doi.org/10.1161/CIRCEP.121.010221" }, - { - "id": "35692035", - "doi": "https://doi.org/10.1186/s12916-022-02399-w", - "title": "Role of circulating polyunsaturated fatty acids on cardiovascular diseases risk: analysis using Mendelian randomization and fatty acid genetic association data from over 114,000 UK Biobank participants.", - "authorString": "Borges MC, Haycock PC, Zheng J, Hemani G, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA.", - "authorAffiliations": "", - "journalTitle": "BMC medicine", - "pubYear": "2022", - "date": "2022-06-13", - "isOpenAccess": "Y", - "keywords": "Fatty acids; Cardiovascular diseases; Mendelian Randomization", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Despite early interest in the health effects of polyunsaturated fatty acids (PUFA), there is still substantial controversy and uncertainty on the evidence linking PUFA to cardiovascular diseases (CVDs). We investigated the effect of plasma concentration of omega-3 PUFA (i.e. docosahexaenoic acid (DHA) and total omega-3 PUFA) and omega-6 PUFA (i.e. linoleic acid and total omega-6 PUFA) on the risk of CVDs using Mendelian randomization.

Methods

We conducted the largest genome-wide association study (GWAS) of circulating PUFA to date including a sample of 114,999 individuals and incorporated these data in a two-sample Mendelian randomization framework to investigate the involvement of circulating PUFA on a wide range of CVDs in up to 1,153,768 individuals of European ancestry (i.e. coronary artery disease, ischemic stroke, haemorrhagic stroke, heart failure, atrial fibrillation, peripheral arterial disease, aortic aneurysm, venous thromboembolism and aortic valve stenosis).

Results

GWAS identified between 46 and 64 SNPs for the four PUFA traits, explaining 4.8-7.9% of circulating PUFA variance and with mean F statistics >100. Higher genetically predicted DHA (and total omega-3 fatty acids) concentration was related to higher risk of some cardiovascular endpoints; however, these findings did not pass our criteria for multiple testing correction and were attenuated when accounting for LDL-cholesterol through multivariable Mendelian randomization or excluding SNPs in the vicinity of the FADS locus. Estimates for the relation between higher genetically predicted linoleic acid (and total omega-6) concentration were inconsistent across different cardiovascular endpoints and Mendelian randomization methods. There was weak evidence of higher genetically predicted linoleic acid being related to lower risk of ischemic stroke and peripheral artery disease when accounting by LDL-cholesterol.

Conclusions

We have conducted the largest GWAS of circulating PUFA to date and the most comprehensive Mendelian randomization analyses. Overall, our Mendelian randomization findings do not support a protective role of circulating PUFA concentration on the risk of CVDs. However, horizontal pleiotropy via lipoprotein-related traits could be a key source of bias in our analyses.", - "laySummary": "", - "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02399-w; doi:https://doi.org/10.1186/s12916-022-02399-w; html:https://europepmc.org/articles/PMC9190170; pdf:https://europepmc.org/articles/PMC9190170?pdf=render" - }, { "id": "33372069", "doi": "https://doi.org/10.1136/bmjopen-2020-038360", @@ -26281,6 +26264,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S0140673621009491/pdf; doi:https://doi.org/10.1016/S0140-6736(21)00949-1; html:https://europepmc.org/articles/PMC9755653; pdf:https://europepmc.org/articles/PMC9755653?pdf=render" }, + { + "id": "35692035", + "doi": "https://doi.org/10.1186/s12916-022-02399-w", + "title": "Role of circulating polyunsaturated fatty acids on cardiovascular diseases risk: analysis using Mendelian randomization and fatty acid genetic association data from over 114,000 UK Biobank participants.", + "authorString": "Borges MC, Haycock PC, Zheng J, Hemani G, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA.", + "authorAffiliations": "", + "journalTitle": "BMC medicine", + "pubYear": "2022", + "date": "2022-06-13", + "isOpenAccess": "Y", + "keywords": "Fatty acids; Cardiovascular diseases; Mendelian Randomization", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Despite early interest in the health effects of polyunsaturated fatty acids (PUFA), there is still substantial controversy and uncertainty on the evidence linking PUFA to cardiovascular diseases (CVDs). We investigated the effect of plasma concentration of omega-3 PUFA (i.e. docosahexaenoic acid (DHA) and total omega-3 PUFA) and omega-6 PUFA (i.e. linoleic acid and total omega-6 PUFA) on the risk of CVDs using Mendelian randomization.

Methods

We conducted the largest genome-wide association study (GWAS) of circulating PUFA to date including a sample of 114,999 individuals and incorporated these data in a two-sample Mendelian randomization framework to investigate the involvement of circulating PUFA on a wide range of CVDs in up to 1,153,768 individuals of European ancestry (i.e. coronary artery disease, ischemic stroke, haemorrhagic stroke, heart failure, atrial fibrillation, peripheral arterial disease, aortic aneurysm, venous thromboembolism and aortic valve stenosis).

Results

GWAS identified between 46 and 64 SNPs for the four PUFA traits, explaining 4.8-7.9% of circulating PUFA variance and with mean F statistics >100. Higher genetically predicted DHA (and total omega-3 fatty acids) concentration was related to higher risk of some cardiovascular endpoints; however, these findings did not pass our criteria for multiple testing correction and were attenuated when accounting for LDL-cholesterol through multivariable Mendelian randomization or excluding SNPs in the vicinity of the FADS locus. Estimates for the relation between higher genetically predicted linoleic acid (and total omega-6) concentration were inconsistent across different cardiovascular endpoints and Mendelian randomization methods. There was weak evidence of higher genetically predicted linoleic acid being related to lower risk of ischemic stroke and peripheral artery disease when accounting by LDL-cholesterol.

Conclusions

We have conducted the largest GWAS of circulating PUFA to date and the most comprehensive Mendelian randomization analyses. Overall, our Mendelian randomization findings do not support a protective role of circulating PUFA concentration on the risk of CVDs. However, horizontal pleiotropy via lipoprotein-related traits could be a key source of bias in our analyses.", + "laySummary": "", + "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02399-w; doi:https://doi.org/10.1186/s12916-022-02399-w; html:https://europepmc.org/articles/PMC9190170; pdf:https://europepmc.org/articles/PMC9190170?pdf=render" + }, { "id": "35072885", "doi": "https://doi.org/10.1007/s10439-022-02905-4", @@ -26400,23 +26400,6 @@ "laySummary": "", "urls": "pdf:https://mental.jmir.org/2022/3/e34898/PDF; doi:https://doi.org/10.2196/34898; html:https://europepmc.org/articles/PMC8957008" }, - { - "id": "35355205", - "doi": "https://doi.org/10.1007/s11897-022-00544-3", - "title": "LVEF by Multigated Acquisition Scan Compared to Other Imaging Modalities in Cardio-Oncology: a Systematic Review.", - "authorString": "Printezi MI, Yousif LIE, Kamphuis JAM, van Laake LW, Cramer MJ, Hobbelink MGG, Asselbergs FW, Teske AJ.", - "authorAffiliations": "", - "journalTitle": "Current heart failure reports", - "pubYear": "2022", - "date": "2022-03-30", - "isOpenAccess": "Y", - "keywords": "Cardiotoxicity; Echocardiography; Left ventricular ejection fraction; Cardiac Magnetic Resonance Imaging; Cardio-oncology; Multigated Acquisition Scan", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Purpose of review

The prevalence of cancer therapy-related cardiac dysfunction (CTRCD) is increasing due to improved cancer survival. Serial monitoring of cardiac function is essential to detect CTRCD, guiding timely intervention strategies. Multigated radionuclide angiography (MUGA) has been the main screening tool using left ventricular ejection fraction (LVEF) to monitor cardiac dysfunction. However, transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) may be more suitable for serial assessment. We aimed to assess the concordance between different non-radiating imaging modalities with MUGA to determine whether they can be used interchangeably.

Recent findings

In order to identify relevant studies, a PubMed search was performed. We included cross-sectional studies comparing MUGA LVEF to that of 2D TTE, 3D TTE, and CMR. From 470 articles, 22 were selected, comprising 1017 patients in total. Among others, this included three 3D TTE, seven 2D harmonic TTE + contrast (2DHC), and seven CMR comparisons. The correlations and Bland-Altman limits of agreement varied for CMR but were stronger for 3D TTE and 2DHC. Our findings suggest that MUGA and CMR should not be used interchangeably whereas 3D TTE and 2DHC are appropriate alternatives following an initial MUGA scan. We propose a multimodality diagnostic imaging strategy for LVEF monitoring in patients undergoing cancer treatment.", - "laySummary": "", - "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s11897-022-00544-3.pdf; doi:https://doi.org/10.1007/s11897-022-00544-3; html:https://europepmc.org/articles/PMC9177497; pdf:https://europepmc.org/articles/PMC9177497?pdf=render" - }, { "id": "32017129", "doi": "https://doi.org/10.5694/mja2.50485", @@ -26434,6 +26417,23 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.5694/mja2.50485; doi:https://doi.org/10.5694/mja2.50485" }, + { + "id": "35355205", + "doi": "https://doi.org/10.1007/s11897-022-00544-3", + "title": "LVEF by Multigated Acquisition Scan Compared to Other Imaging Modalities in Cardio-Oncology: a Systematic Review.", + "authorString": "Printezi MI, Yousif LIE, Kamphuis JAM, van Laake LW, Cramer MJ, Hobbelink MGG, Asselbergs FW, Teske AJ.", + "authorAffiliations": "", + "journalTitle": "Current heart failure reports", + "pubYear": "2022", + "date": "2022-03-30", + "isOpenAccess": "Y", + "keywords": "Cardiotoxicity; Echocardiography; Left ventricular ejection fraction; Cardiac Magnetic Resonance Imaging; Cardio-oncology; Multigated Acquisition Scan", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Purpose of review

The prevalence of cancer therapy-related cardiac dysfunction (CTRCD) is increasing due to improved cancer survival. Serial monitoring of cardiac function is essential to detect CTRCD, guiding timely intervention strategies. Multigated radionuclide angiography (MUGA) has been the main screening tool using left ventricular ejection fraction (LVEF) to monitor cardiac dysfunction. However, transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) may be more suitable for serial assessment. We aimed to assess the concordance between different non-radiating imaging modalities with MUGA to determine whether they can be used interchangeably.

Recent findings

In order to identify relevant studies, a PubMed search was performed. We included cross-sectional studies comparing MUGA LVEF to that of 2D TTE, 3D TTE, and CMR. From 470 articles, 22 were selected, comprising 1017 patients in total. Among others, this included three 3D TTE, seven 2D harmonic TTE + contrast (2DHC), and seven CMR comparisons. The correlations and Bland-Altman limits of agreement varied for CMR but were stronger for 3D TTE and 2DHC. Our findings suggest that MUGA and CMR should not be used interchangeably whereas 3D TTE and 2DHC are appropriate alternatives following an initial MUGA scan. We propose a multimodality diagnostic imaging strategy for LVEF monitoring in patients undergoing cancer treatment.", + "laySummary": "", + "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s11897-022-00544-3.pdf; doi:https://doi.org/10.1007/s11897-022-00544-3; html:https://europepmc.org/articles/PMC9177497; pdf:https://europepmc.org/articles/PMC9177497?pdf=render" + }, { "id": "34019073", "doi": "https://doi.org/10.1093/ibd/izab059", @@ -26876,23 +26876,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41467-022-32219-x.pdf; doi:https://doi.org/10.1038/s41467-022-32219-x; html:https://europepmc.org/articles/PMC9349177; pdf:https://europepmc.org/articles/PMC9349177?pdf=render" }, - { - "id": "35410933", - "doi": "https://doi.org/10.1136/bmjopen-2021-057885", - "title": "Non-pharmacological therapies for postviral syndromes, including Long COVID: a systematic review and meta-analysis protocol.", - "authorString": "Chandan JS, Brown K, Simms-Williams N, Camaradou J, Bashir N, Heining D, Aiyegbusi OL, Turner G, Cruz Rivera S, Hotham R, Nirantharakumar K, Sivan M, Khunti K, Raindi D, Marwaha S, Hughes SE, McMullan C, Calvert M, Haroon S.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2022", - "date": "2022-04-11", - "isOpenAccess": "Y", - "keywords": "Infectious diseases; Rehabilitation Medicine; Covid-19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

Postviral syndromes (PVS) describe the sustained presence of symptoms following an acute viral infection, for months or even years. Exposure to the SARS-CoV-2 virus and subsequent development of COVID-19 has shown to have similar effects with individuals continuing to exhibit symptoms for greater than 12 weeks. The sustained presence of symptoms is variably referred to as 'post COVID-19 syndrome', 'post-COVID condition' or more commonly 'Long COVID'. Knowledge of the long-term health impacts and treatments for Long COVID are evolving. To minimise overlap with existing work in the field exploring treatments of Long COVID, we have only chosen to focus on non-pharmacological treatments.

Aims

This review aims to summarise the effectiveness of non-pharmacological treatments for PVS, including Long COVID. A secondary aim is to summarise the symptoms and health impacts associated with PVS in individuals recruited to treatment studies.

Methods and analysis

Primary electronic searches will be performed in bibliographic databases including: Embase, MEDLINE, PyscINFO, CINAHL and MedRxiv from 1 January 2001 to 29 October 2021. At least two independent reviewers will screen each study for inclusion and data will be extracted from all eligible studies onto a data extraction form. The quality of all included studies will be assessed using Cochrane risk of bias tools and the Newcastle-Ottawa grading system. Non-pharmacological treatments for PVS and Long COVID will be narratively summarised and effect estimates will be pooled using random effects meta-analysis where there is sufficient methodological homogeneity. The symptoms and health impacts reported in the included studies on non-pharmacological interventions will be extracted and narratively reported.

Ethics and dissemination

This systematic review does not require ethical approval. The findings from this study will be submitted for peer-reviewed publication, shared at conference presentations and disseminated to both clinical and patient groups.

Prospero registration number

The review will adhere to this protocol which has also been registered with PROSPERO (CRD42021282074).", - "laySummary": "", - "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057885.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057885; html:https://europepmc.org/articles/PMC9002258; pdf:https://europepmc.org/articles/PMC9002258?pdf=render" - }, { "id": "34606520", "doi": "https://doi.org/10.1371/journal.pmed.1003815", @@ -26910,6 +26893,23 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003815&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003815; html:https://europepmc.org/articles/PMC8523052; pdf:https://europepmc.org/articles/PMC8523052?pdf=render" }, + { + "id": "35410933", + "doi": "https://doi.org/10.1136/bmjopen-2021-057885", + "title": "Non-pharmacological therapies for postviral syndromes, including Long COVID: a systematic review and meta-analysis protocol.", + "authorString": "Chandan JS, Brown K, Simms-Williams N, Camaradou J, Bashir N, Heining D, Aiyegbusi OL, Turner G, Cruz Rivera S, Hotham R, Nirantharakumar K, Sivan M, Khunti K, Raindi D, Marwaha S, Hughes SE, McMullan C, Calvert M, Haroon S.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2022", + "date": "2022-04-11", + "isOpenAccess": "Y", + "keywords": "Infectious diseases; Rehabilitation Medicine; Covid-19", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

Postviral syndromes (PVS) describe the sustained presence of symptoms following an acute viral infection, for months or even years. Exposure to the SARS-CoV-2 virus and subsequent development of COVID-19 has shown to have similar effects with individuals continuing to exhibit symptoms for greater than 12 weeks. The sustained presence of symptoms is variably referred to as 'post COVID-19 syndrome', 'post-COVID condition' or more commonly 'Long COVID'. Knowledge of the long-term health impacts and treatments for Long COVID are evolving. To minimise overlap with existing work in the field exploring treatments of Long COVID, we have only chosen to focus on non-pharmacological treatments.

Aims

This review aims to summarise the effectiveness of non-pharmacological treatments for PVS, including Long COVID. A secondary aim is to summarise the symptoms and health impacts associated with PVS in individuals recruited to treatment studies.

Methods and analysis

Primary electronic searches will be performed in bibliographic databases including: Embase, MEDLINE, PyscINFO, CINAHL and MedRxiv from 1 January 2001 to 29 October 2021. At least two independent reviewers will screen each study for inclusion and data will be extracted from all eligible studies onto a data extraction form. The quality of all included studies will be assessed using Cochrane risk of bias tools and the Newcastle-Ottawa grading system. Non-pharmacological treatments for PVS and Long COVID will be narratively summarised and effect estimates will be pooled using random effects meta-analysis where there is sufficient methodological homogeneity. The symptoms and health impacts reported in the included studies on non-pharmacological interventions will be extracted and narratively reported.

Ethics and dissemination

This systematic review does not require ethical approval. The findings from this study will be submitted for peer-reviewed publication, shared at conference presentations and disseminated to both clinical and patient groups.

Prospero registration number

The review will adhere to this protocol which has also been registered with PROSPERO (CRD42021282074).", + "laySummary": "", + "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057885.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057885; html:https://europepmc.org/articles/PMC9002258; pdf:https://europepmc.org/articles/PMC9002258?pdf=render" + }, { "id": "38106559", "doi": "https://doi.org/10.1016/j.eclinm.2023.102251", @@ -26927,23 +26927,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.eclinm.2023.102251; html:https://europepmc.org/articles/PMC10721552; pdf:https://europepmc.org/articles/PMC10721552?pdf=render" }, - { - "id": "35585575", - "doi": "https://doi.org/10.1186/s12889-022-13219-4", - "title": "The impact of COVID-19 vaccination in prisons in England and Wales: a metapopulation model.", - "authorString": "McCarthy CV, O'Mara O, van Leeuwen E, CMMID COVID-19 Working Group, Jit M, Sandmann F.", - "authorAffiliations": "", - "journalTitle": "BMC public health", - "pubYear": "2022", - "date": "2022-05-18", - "isOpenAccess": "Y", - "keywords": "Vaccination; mathematical model; Public Health; Prisons; Covid-19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

High incidence of cases and deaths due to coronavirus disease 2019 (COVID-19) have been reported in prisons worldwide. This study aimed to evaluate the impact of different COVID-19 vaccination strategies in epidemiologically semi-enclosed settings such as prisons, where staff interact regularly with those incarcerated and the wider community.

Methods

We used a metapopulation transmission-dynamic model of a local prison in England and Wales. Two-dose vaccination strategies included no vaccination, vaccination of all individuals\u00a0who are\u00a0incarcerated and/or staff, and an age-based approach. Outcomes were quantified in terms of COVID-19-related symptomatic cases, losses in quality-adjusted life-years (QALYs), and deaths.

Results

Compared to no vaccination, vaccinating all people living and working in prison reduced cases, QALY loss and deaths over a one-year period by 41%, 32% and 36% respectively. However, if vaccine introduction was delayed until the start of an outbreak, the impact was negligible. Vaccinating individuals who are incarcerated and staff over 50\u00a0years old averted one death for every 104 vaccination\u00a0courses administered. All-staff-only strategies reduced cases by up to 5%. Increasing coverage from 30 to 90% among those who are incarcerated reduced cases by around 30 percentage points.

Conclusions

The impact of vaccination in prison settings was highly dependent on early and rapid vaccine delivery. If administered to both those living and working in prison prior to an outbreak occurring, vaccines could substantially reduce COVID-19-related morbidity and mortality in prison settings.", - "laySummary": "", - "urls": "pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-022-13219-4; doi:https://doi.org/10.1186/s12889-022-13219-4; html:https://europepmc.org/articles/PMC9115545; pdf:https://europepmc.org/articles/PMC9115545?pdf=render" - }, { "id": "31671849", "doi": "https://doi.org/10.3390/ijerph16214178", @@ -26961,6 +26944,23 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/1660-4601/16/21/4178/pdf?version=1573119054; doi:https://doi.org/10.3390/ijerph16214178; html:https://europepmc.org/articles/PMC6862192; pdf:https://europepmc.org/articles/PMC6862192?pdf=render" }, + { + "id": "35585575", + "doi": "https://doi.org/10.1186/s12889-022-13219-4", + "title": "The impact of COVID-19 vaccination in prisons in England and Wales: a metapopulation model.", + "authorString": "McCarthy CV, O'Mara O, van Leeuwen E, CMMID COVID-19 Working Group, Jit M, Sandmann F.", + "authorAffiliations": "", + "journalTitle": "BMC public health", + "pubYear": "2022", + "date": "2022-05-18", + "isOpenAccess": "Y", + "keywords": "Vaccination; mathematical model; Public Health; Prisons; Covid-19", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

High incidence of cases and deaths due to coronavirus disease 2019 (COVID-19) have been reported in prisons worldwide. This study aimed to evaluate the impact of different COVID-19 vaccination strategies in epidemiologically semi-enclosed settings such as prisons, where staff interact regularly with those incarcerated and the wider community.

Methods

We used a metapopulation transmission-dynamic model of a local prison in England and Wales. Two-dose vaccination strategies included no vaccination, vaccination of all individuals\u00a0who are\u00a0incarcerated and/or staff, and an age-based approach. Outcomes were quantified in terms of COVID-19-related symptomatic cases, losses in quality-adjusted life-years (QALYs), and deaths.

Results

Compared to no vaccination, vaccinating all people living and working in prison reduced cases, QALY loss and deaths over a one-year period by 41%, 32% and 36% respectively. However, if vaccine introduction was delayed until the start of an outbreak, the impact was negligible. Vaccinating individuals who are incarcerated and staff over 50\u00a0years old averted one death for every 104 vaccination\u00a0courses administered. All-staff-only strategies reduced cases by up to 5%. Increasing coverage from 30 to 90% among those who are incarcerated reduced cases by around 30 percentage points.

Conclusions

The impact of vaccination in prison settings was highly dependent on early and rapid vaccine delivery. If administered to both those living and working in prison prior to an outbreak occurring, vaccines could substantially reduce COVID-19-related morbidity and mortality in prison settings.", + "laySummary": "", + "urls": "pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-022-13219-4; doi:https://doi.org/10.1186/s12889-022-13219-4; html:https://europepmc.org/articles/PMC9115545; pdf:https://europepmc.org/articles/PMC9115545?pdf=render" + }, { "id": "33588321", "doi": "https://doi.org/10.1016/j.retram.2021.103276", @@ -26978,23 +26978,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.retram.2021.103276; doi:https://doi.org/10.1016/j.retram.2021.103276; html:https://europepmc.org/articles/PMC7857048; pdf:https://europepmc.org/articles/PMC7857048?pdf=render" }, - { - "id": "35381001", - "doi": "https://doi.org/10.1371/journal.pgen.1010093", - "title": "Analyzing human knockouts to validate GPR151 as a therapeutic target for reduction of body mass index.", - "authorString": "Gurtan A, Dominy J, Khalid S, Vong L, Caplan S, Currie T, Richards S, Lamarche L, Denning D, Shpektor D, Gurinovich A, Rasheed A, Hameed S, Saeed S, Saleem I, Jalal A, Abbas S, Sultana R, Rasheed SZ, Memon FU, Shah N, Ishaq M, Khera AV, Danesh J, Frossard P, Saleheen D.", - "authorAffiliations": "", - "journalTitle": "PLoS genetics", - "pubYear": "2022", - "date": "2022-04-05", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Novel drug targets for sustained reduction in body mass index (BMI) are needed to curb the epidemic of obesity, which affects 650 million individuals worldwide and is a causal driver of cardiovascular and metabolic disease and mortality. Previous studies reported that the Arg95Ter nonsense variant of GPR151, an orphan G protein-coupled receptor, is associated with reduced BMI and reduced risk of Type 2 Diabetes (T2D). Here, we further investigate GPR151 with the Pakistan Genome Resource (PGR), which is one of the largest exome biobanks of human homozygous loss-of-function carriers (knockouts) in the world. Among PGR participants, we identify eleven GPR151 putative loss-of-function (plof) variants, three of which are present at homozygosity (Arg95Ter, Tyr99Ter, and Phe175LeufsTer7), with a cumulative allele frequency of 2.2%. We confirm these alleles in vitro as loss-of-function. We test if GPR151 plof is associated with BMI, T2D, or other metabolic traits and find that GPR151 deficiency in complete human knockouts is not associated with clinically significant differences in these traits. Relative to Gpr151+/+ mice, Gpr151-/- animals exhibit no difference in body weight on normal chow and higher body weight on a high-fat diet. Together, our findings indicate that GPR151 antagonism is not a compelling therapeutic approach to treatment of obesity.", - "laySummary": "", - "urls": "pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010093&type=printable; doi:https://doi.org/10.1371/journal.pgen.1010093; html:https://europepmc.org/articles/PMC9022822; pdf:https://europepmc.org/articles/PMC9022822?pdf=render" - }, { "id": "31409800", "doi": "https://doi.org/10.1038/s41467-019-11451-y", @@ -27012,6 +26995,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41467-019-11451-y.pdf; doi:https://doi.org/10.1038/s41467-019-11451-y; html:https://europepmc.org/articles/PMC6692500; pdf:https://europepmc.org/articles/PMC6692500?pdf=render" }, + { + "id": "35381001", + "doi": "https://doi.org/10.1371/journal.pgen.1010093", + "title": "Analyzing human knockouts to validate GPR151 as a therapeutic target for reduction of body mass index.", + "authorString": "Gurtan A, Dominy J, Khalid S, Vong L, Caplan S, Currie T, Richards S, Lamarche L, Denning D, Shpektor D, Gurinovich A, Rasheed A, Hameed S, Saeed S, Saleem I, Jalal A, Abbas S, Sultana R, Rasheed SZ, Memon FU, Shah N, Ishaq M, Khera AV, Danesh J, Frossard P, Saleheen D.", + "authorAffiliations": "", + "journalTitle": "PLoS genetics", + "pubYear": "2022", + "date": "2022-04-05", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Novel drug targets for sustained reduction in body mass index (BMI) are needed to curb the epidemic of obesity, which affects 650 million individuals worldwide and is a causal driver of cardiovascular and metabolic disease and mortality. Previous studies reported that the Arg95Ter nonsense variant of GPR151, an orphan G protein-coupled receptor, is associated with reduced BMI and reduced risk of Type 2 Diabetes (T2D). Here, we further investigate GPR151 with the Pakistan Genome Resource (PGR), which is one of the largest exome biobanks of human homozygous loss-of-function carriers (knockouts) in the world. Among PGR participants, we identify eleven GPR151 putative loss-of-function (plof) variants, three of which are present at homozygosity (Arg95Ter, Tyr99Ter, and Phe175LeufsTer7), with a cumulative allele frequency of 2.2%. We confirm these alleles in vitro as loss-of-function. We test if GPR151 plof is associated with BMI, T2D, or other metabolic traits and find that GPR151 deficiency in complete human knockouts is not associated with clinically significant differences in these traits. Relative to Gpr151+/+ mice, Gpr151-/- animals exhibit no difference in body weight on normal chow and higher body weight on a high-fat diet. Together, our findings indicate that GPR151 antagonism is not a compelling therapeutic approach to treatment of obesity.", + "laySummary": "", + "urls": "pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010093&type=printable; doi:https://doi.org/10.1371/journal.pgen.1010093; html:https://europepmc.org/articles/PMC9022822; pdf:https://europepmc.org/articles/PMC9022822?pdf=render" + }, { "id": "36054463", "doi": "https://doi.org/10.1111/ans.17985", @@ -27029,23 +27029,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/ans.17985; doi:https://doi.org/10.1111/ans.17985; html:https://europepmc.org/articles/PMC9804322; pdf:https://europepmc.org/articles/PMC9804322?pdf=render" }, - { - "id": "36224602", - "doi": "https://doi.org/10.1186/s12916-022-02544-5", - "title": "Early onset of immune-mediated diseases in minority ethnic groups in the UK.", - "authorString": "Sharma-Oates A, Zemedikun DT, Kumar K, Reynolds JA, Jain A, Raza K, Williams JA, Bravo L, Cardoso VR, Gkoutos G, Nirantharakumar K, Lord JM.", - "authorAffiliations": "", - "journalTitle": "BMC medicine", - "pubYear": "2022", - "date": "2022-10-13", - "isOpenAccess": "Y", - "keywords": "Ageing; Diagnosis; Ethnicity; Rheumatic Diseases; South Asian; African-caribbean; Immune-mediated Diseases; Autoimmune Inflammatory Diseases", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

The prevalence of some immune-mediated diseases (IMDs) shows distinct differences between populations of different ethnicities. The aim of this study was to determine if the age at diagnosis of common IMDs also differed between different ethnic groups in the UK, suggestive of distinct influences of ethnicity on disease pathogenesis.

Methods

This was a population-based retrospective primary care study. Linear regression provided unadjusted and adjusted estimates of age at diagnosis for common IMDs within the following ethnic groups: White, South Asian, African-Caribbean and Mixed-race/Other. Potential disease risk confounders in the association between ethnicity and diagnosis age including sex, smoking, body mass index and social deprivation (Townsend quintiles) were adjusted for. The analysis was replicated using data from UK Biobank (UKB).

Results

After adjusting for risk confounders, we observed that individuals from South Asian, African-Caribbean and Mixed-race/Other ethnicities were diagnosed with IMDs at a significantly younger age than their White counterparts for almost all IMDs. The difference in the diagnosis age (ranging from 2 to 30 years earlier) varied for each disease and by ethnicity. For example, rheumatoid arthritis was diagnosed at age 49, 48 and 47 years in individuals of African-Caribbean, South Asian and Mixed-race/Other ethnicities respectively, compared to 56 years in White ethnicities. The earlier diagnosis of most IMDs observed was validated in UKB although with a smaller effect size.

Conclusion

Individuals from non-White ethnic groups in the UK had an earlier age at diagnosis for several IMDs than White adults.", - "laySummary": "", - "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02544-5; doi:https://doi.org/10.1186/s12916-022-02544-5; html:https://europepmc.org/articles/PMC9558944; pdf:https://europepmc.org/articles/PMC9558944?pdf=render" - }, { "id": "31446403", "doi": "https://doi.org/10.1136/bmjopen-2018-026677", @@ -27063,6 +27046,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/9/8/e026677.full.pdf; doi:https://doi.org/10.1136/bmjopen-2018-026677; html:https://europepmc.org/articles/PMC6720466; pdf:https://europepmc.org/articles/PMC6720466?pdf=render" }, + { + "id": "36224602", + "doi": "https://doi.org/10.1186/s12916-022-02544-5", + "title": "Early onset of immune-mediated diseases in minority ethnic groups in the UK.", + "authorString": "Sharma-Oates A, Zemedikun DT, Kumar K, Reynolds JA, Jain A, Raza K, Williams JA, Bravo L, Cardoso VR, Gkoutos G, Nirantharakumar K, Lord JM.", + "authorAffiliations": "", + "journalTitle": "BMC medicine", + "pubYear": "2022", + "date": "2022-10-13", + "isOpenAccess": "Y", + "keywords": "Ageing; Diagnosis; Ethnicity; Rheumatic Diseases; South Asian; African-caribbean; Immune-mediated Diseases; Autoimmune Inflammatory Diseases", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

The prevalence of some immune-mediated diseases (IMDs) shows distinct differences between populations of different ethnicities. The aim of this study was to determine if the age at diagnosis of common IMDs also differed between different ethnic groups in the UK, suggestive of distinct influences of ethnicity on disease pathogenesis.

Methods

This was a population-based retrospective primary care study. Linear regression provided unadjusted and adjusted estimates of age at diagnosis for common IMDs within the following ethnic groups: White, South Asian, African-Caribbean and Mixed-race/Other. Potential disease risk confounders in the association between ethnicity and diagnosis age including sex, smoking, body mass index and social deprivation (Townsend quintiles) were adjusted for. The analysis was replicated using data from UK Biobank (UKB).

Results

After adjusting for risk confounders, we observed that individuals from South Asian, African-Caribbean and Mixed-race/Other ethnicities were diagnosed with IMDs at a significantly younger age than their White counterparts for almost all IMDs. The difference in the diagnosis age (ranging from 2 to 30 years earlier) varied for each disease and by ethnicity. For example, rheumatoid arthritis was diagnosed at age 49, 48 and 47 years in individuals of African-Caribbean, South Asian and Mixed-race/Other ethnicities respectively, compared to 56 years in White ethnicities. The earlier diagnosis of most IMDs observed was validated in UKB although with a smaller effect size.

Conclusion

Individuals from non-White ethnic groups in the UK had an earlier age at diagnosis for several IMDs than White adults.", + "laySummary": "", + "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02544-5; doi:https://doi.org/10.1186/s12916-022-02544-5; html:https://europepmc.org/articles/PMC9558944; pdf:https://europepmc.org/articles/PMC9558944?pdf=render" + }, { "id": "34950917", "doi": "https://doi.org/10.1016/j.lanepe.2021.100248", @@ -27097,23 +27097,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jclinepi.2022.10.011; doi:https://doi.org/10.1016/j.jclinepi.2022.10.011; html:https://europepmc.org/articles/PMC7613854; pdf:https://europepmc.org/articles/PMC7613854?pdf=render" }, - { - "id": "36752447", - "doi": "https://doi.org/10.1016/j.jcmg.2022.11.012", - "title": "Prognostic Value of RV Abnormalities on\u00a0CMR in Patients With Known or Suspected Cardiac Sarcoidosis.", - "authorString": "Wang J, Zhang J, Hosadurg N, Iwanaga Y, Chen Y, Liu W, Wan K, Patel AR, Wicks EC, Gkoutos GV, Han Y, Chen Y.", - "authorAffiliations": "", - "journalTitle": "JACC. Cardiovascular imaging", - "pubYear": "2023", - "date": "2023-01-11", - "isOpenAccess": "N", - "keywords": "Right Ventricle; Sudden Cardiac Death; Cardiac Sarcoidosis; Cardiac Magnetic Resonance; Late Gadolinium Enhancement", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Left ventricular abnormalities in cardiac sarcoidosis (CS) are associated with adverse cardiovascular events, whereas the prognostic value of right ventricular (RV) involvement found on cardiac magnetic resonance is unclear.

Objectives

This study aimed to systematically assess the prognostic value of right ventricular ejection fraction (RVEF) and RV late gadolinium enhancement (LGE) in known or suspected CS.

Methods

This study was prospectively registered in PROSPERO (CRD42022302579). PubMed, Embase, and Web of Science were searched to identify studies that evaluated the association between RVEF or RV LGE on clinical outcomes in CS. A composite endpoint of all-cause death, cardiovascular events, or sudden cardiac death (SCD) was used. A meta-analysis was performed to determine the pooled risk ratio (RR) for these adverse events. The calculated sensitivity, specificity, and area under the curve with 95%\u00a0CIs were weighted and summarized.

Results

Eight studies including a total of 899 patients with a mean follow-up duration of 3.2 \u00b1 0.7 years were included. The pooled RR of RV systolic dysfunction was 3.1 (95%\u00a0CI: 1.7-5.5; P\u00a0< 0.01) for composite events and 3.0 (95%\u00a0CI: 1.3-7.0; P\u00a0< 0.01) for SCD events. In addition, CS patients with RV LGE had a significant risk for composite events (RR: 4.8 [95%\u00a0CI: 2.4-9.6]; P\u00a0< 0.01) and a higher risk for SCD (RR: 9.5 [95%\u00a0CI: 4.4-20.5]; P\u00a0< 0.01) than patients without RV LGE. Furthermore, the pooled area under the curve, sensitivity, and specificity of RV LGE for identifying patients with CS who were at highest SCD risk were 0.8 (95%\u00a0CI: 0.8-0.9), 69% (95%\u00a0CI: 50%-84%), and\u00a090% (95%\u00a0CI: 70%-97%), respectively.

Conclusions

In patients with known or suspected CS, RVEF and RV LGE were both associated with adverse events. Furthermore, RV LGE shows good discrimination in identifying CS patients at high risk of SCD.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jcmg.2022.11.012; doi:https://doi.org/10.1016/j.jcmg.2022.11.012" - }, { "id": "33779119", "doi": "https://doi.org/10.1002/ejhf.2169", @@ -27131,6 +27114,23 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejhf.2169; doi:https://doi.org/10.1002/ejhf.2169; html:https://europepmc.org/articles/PMC8359985; pdf:https://europepmc.org/articles/PMC8359985?pdf=render" }, + { + "id": "36752447", + "doi": "https://doi.org/10.1016/j.jcmg.2022.11.012", + "title": "Prognostic Value of RV Abnormalities on\u00a0CMR in Patients With Known or Suspected Cardiac Sarcoidosis.", + "authorString": "Wang J, Zhang J, Hosadurg N, Iwanaga Y, Chen Y, Liu W, Wan K, Patel AR, Wicks EC, Gkoutos GV, Han Y, Chen Y.", + "authorAffiliations": "", + "journalTitle": "JACC. Cardiovascular imaging", + "pubYear": "2023", + "date": "2023-01-11", + "isOpenAccess": "N", + "keywords": "Right Ventricle; Sudden Cardiac Death; Cardiac Sarcoidosis; Cardiac Magnetic Resonance; Late Gadolinium Enhancement", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Left ventricular abnormalities in cardiac sarcoidosis (CS) are associated with adverse cardiovascular events, whereas the prognostic value of right ventricular (RV) involvement found on cardiac magnetic resonance is unclear.

Objectives

This study aimed to systematically assess the prognostic value of right ventricular ejection fraction (RVEF) and RV late gadolinium enhancement (LGE) in known or suspected CS.

Methods

This study was prospectively registered in PROSPERO (CRD42022302579). PubMed, Embase, and Web of Science were searched to identify studies that evaluated the association between RVEF or RV LGE on clinical outcomes in CS. A composite endpoint of all-cause death, cardiovascular events, or sudden cardiac death (SCD) was used. A meta-analysis was performed to determine the pooled risk ratio (RR) for these adverse events. The calculated sensitivity, specificity, and area under the curve with 95%\u00a0CIs were weighted and summarized.

Results

Eight studies including a total of 899 patients with a mean follow-up duration of 3.2 \u00b1 0.7 years were included. The pooled RR of RV systolic dysfunction was 3.1 (95%\u00a0CI: 1.7-5.5; P\u00a0< 0.01) for composite events and 3.0 (95%\u00a0CI: 1.3-7.0; P\u00a0< 0.01) for SCD events. In addition, CS patients with RV LGE had a significant risk for composite events (RR: 4.8 [95%\u00a0CI: 2.4-9.6]; P\u00a0< 0.01) and a higher risk for SCD (RR: 9.5 [95%\u00a0CI: 4.4-20.5]; P\u00a0< 0.01) than patients without RV LGE. Furthermore, the pooled area under the curve, sensitivity, and specificity of RV LGE for identifying patients with CS who were at highest SCD risk were 0.8 (95%\u00a0CI: 0.8-0.9), 69% (95%\u00a0CI: 50%-84%), and\u00a090% (95%\u00a0CI: 70%-97%), respectively.

Conclusions

In patients with known or suspected CS, RVEF and RV LGE were both associated with adverse events. Furthermore, RV LGE shows good discrimination in identifying CS patients at high risk of SCD.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.jcmg.2022.11.012; doi:https://doi.org/10.1016/j.jcmg.2022.11.012" + }, { "id": "34535484", "doi": "https://doi.org/10.1136/bmjopen-2021-050647", @@ -27268,21 +27268,21 @@ "urls": "doi:https://doi.org/10.1002/hpja.287" }, { - "id": "38642613", - "doi": "https://doi.org/10.1016/j.clinme.2024.100209", - "title": "Addressing ethnic disparities in neurological research in the United Kingdom: An example from the prospective multicentre COVID-19 Clinical Neuroscience Study.", - "authorString": "van Wamelen DJ, Rota S, Hartmann M, Martin NH, Alam AM, Thomas RH, Dodd KC, Jenkins T, Smith CJ, Zandi MS, Easton A, Carr G, Benjamin LA, Lilleker JB, Saucer D, Coles AJ, Wood N, Ray Chaudhuri K, Breen G, Michael BD, COVID-CNS consortium.", + "id": "32685698", + "doi": "https://doi.org/10.12688/wellcomeopenres.15842.3", + "title": "Estimating the overdispersion in COVID-19 transmission using outbreak sizes outside China.", + "authorString": "Endo A, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Abbott S, Kucharski AJ, Funk S.", "authorAffiliations": "", - "journalTitle": "Clinical medicine (London, England)", - "pubYear": "2024", - "date": "2024-04-19", + "journalTitle": "Wellcome open research", + "pubYear": "2020", + "date": "2020-07-10", "isOpenAccess": "Y", - "keywords": "Diversity; Recruitment; Neurology; Ethnicity; Covid-19", + "keywords": "Branching Process; Overdispersion; Novel Coronavirus; Superspreading; Covid-19; Sars-cov-2", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Minority ethnic groups have often been underrepresented in research, posing a problem in relation to external validity and extrapolation of findings. Here, we aimed to assess recruitment and retainment strategies in a large observational study assessing neurological complications following SARS-CoV-2 infection.

Methods

Participants were recruited following confirmed infection with SARS-CoV-2 and hospitalisation. Self-reported ethnicity was recorded alongside other demographic data to identify potential barriers to recruitment.

Results

807 participants were recruited to COVID-CNS, and ethnicity data were available for 93.2%. We identified a proportionate representation of self-reported ethnicity categories, and distribution of broad ethnicity categories mirrored individual centres' catchment areas. White ethnicity within individual centres ranged between 44.5% and 89.1%, with highest percentage of participants with non-White ethnicity in London-based centres. Examples are provided how to reach potentially underrepresented minority ethnic groups.

Conclusions

Recruitment barriers in relation to potentially underrepresented ethnic groups may be overcome with strategies identified here.", + "abstract": "Background: A novel coronavirus disease (COVID-19) outbreak has now spread to a number of countries worldwide. While sustained transmission chains of human-to-human transmission suggest high basic reproduction number R 0, variation in the number of secondary transmissions (often characterised by so-called superspreading events) may be large as some countries have observed fewer local transmissions than others. Methods: We quantified individual-level variation in COVID-19 transmission by applying a mathematical model to observed outbreak sizes in affected countries. We extracted the number of imported and local cases in the affected countries from the\u00a0World Health Organization situation report and applied a branching process model where the number of secondary transmissions was assumed to follow a negative-binomial distribution. Results: Our model suggested a high degree of individual-level variation in the transmission of COVID-19. Within the current consensus range of R 0 (2-3), the overdispersion parameter k of a negative-binomial distribution was estimated to be around 0.1 (median estimate 0.1; 95% CrI: 0.05-0.2 for R0 = 2.5), suggesting that 80% of secondary transmissions may have been caused by a small fraction of infectious individuals (~10%). A joint estimation yielded likely ranges for R 0 and k (95% CrIs: R 0 1.4-12; k 0.04-0.2); however, the upper bound of R 0 was not well informed by the model and data, which did not notably differ from that of the prior distribution. Conclusions: Our finding of a highly-overdispersed offspring distribution highlights a potential benefit to focusing intervention efforts on superspreading. As most infected individuals do not contribute to the expansion of an epidemic, the effective reproduction number could be drastically reduced by preventing relatively rare superspreading events.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.clinme.2024.100209; html:https://europepmc.org/articles/PMC11091497; pdf:https://europepmc.org/articles/PMC11091497?pdf=render" + "urls": "doi:https://doi.org/10.12688/wellcomeopenres.15842.3; html:https://europepmc.org/articles/PMC7338915; pdf:https://europepmc.org/articles/PMC7338915?pdf=render" }, { "id": "35115689", @@ -27302,21 +27302,21 @@ "urls": "pdf:https://www.nature.com/articles/s41588-021-00991-z.pdf; doi:https://doi.org/10.1038/s41588-021-00991-z; html:https://europepmc.org/articles/PMC9883041; pdf:https://europepmc.org/articles/PMC9883041?pdf=render; doi:https://doi.org/10.1038/s41588-021-00991-z" }, { - "id": "32685698", - "doi": "https://doi.org/10.12688/wellcomeopenres.15842.3", - "title": "Estimating the overdispersion in COVID-19 transmission using outbreak sizes outside China.", - "authorString": "Endo A, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Abbott S, Kucharski AJ, Funk S.", + "id": "38642613", + "doi": "https://doi.org/10.1016/j.clinme.2024.100209", + "title": "Addressing ethnic disparities in neurological research in the United Kingdom: An example from the prospective multicentre COVID-19 Clinical Neuroscience Study.", + "authorString": "van Wamelen DJ, Rota S, Hartmann M, Martin NH, Alam AM, Thomas RH, Dodd KC, Jenkins T, Smith CJ, Zandi MS, Easton A, Carr G, Benjamin LA, Lilleker JB, Saucer D, Coles AJ, Wood N, Ray Chaudhuri K, Breen G, Michael BD, COVID-CNS consortium.", "authorAffiliations": "", - "journalTitle": "Wellcome open research", - "pubYear": "2020", - "date": "2020-07-10", + "journalTitle": "Clinical medicine (London, England)", + "pubYear": "2024", + "date": "2024-04-19", "isOpenAccess": "Y", - "keywords": "Branching Process; Overdispersion; Novel Coronavirus; Superspreading; Covid-19; Sars-cov-2", + "keywords": "Diversity; Recruitment; Neurology; Ethnicity; Covid-19", "nationalPriorities": "", "healthCategories": "", - "abstract": "Background: A novel coronavirus disease (COVID-19) outbreak has now spread to a number of countries worldwide. While sustained transmission chains of human-to-human transmission suggest high basic reproduction number R 0, variation in the number of secondary transmissions (often characterised by so-called superspreading events) may be large as some countries have observed fewer local transmissions than others. Methods: We quantified individual-level variation in COVID-19 transmission by applying a mathematical model to observed outbreak sizes in affected countries. We extracted the number of imported and local cases in the affected countries from the\u00a0World Health Organization situation report and applied a branching process model where the number of secondary transmissions was assumed to follow a negative-binomial distribution. Results: Our model suggested a high degree of individual-level variation in the transmission of COVID-19. Within the current consensus range of R 0 (2-3), the overdispersion parameter k of a negative-binomial distribution was estimated to be around 0.1 (median estimate 0.1; 95% CrI: 0.05-0.2 for R0 = 2.5), suggesting that 80% of secondary transmissions may have been caused by a small fraction of infectious individuals (~10%). A joint estimation yielded likely ranges for R 0 and k (95% CrIs: R 0 1.4-12; k 0.04-0.2); however, the upper bound of R 0 was not well informed by the model and data, which did not notably differ from that of the prior distribution. Conclusions: Our finding of a highly-overdispersed offspring distribution highlights a potential benefit to focusing intervention efforts on superspreading. As most infected individuals do not contribute to the expansion of an epidemic, the effective reproduction number could be drastically reduced by preventing relatively rare superspreading events.", + "abstract": "

Background

Minority ethnic groups have often been underrepresented in research, posing a problem in relation to external validity and extrapolation of findings. Here, we aimed to assess recruitment and retainment strategies in a large observational study assessing neurological complications following SARS-CoV-2 infection.

Methods

Participants were recruited following confirmed infection with SARS-CoV-2 and hospitalisation. Self-reported ethnicity was recorded alongside other demographic data to identify potential barriers to recruitment.

Results

807 participants were recruited to COVID-CNS, and ethnicity data were available for 93.2%. We identified a proportionate representation of self-reported ethnicity categories, and distribution of broad ethnicity categories mirrored individual centres' catchment areas. White ethnicity within individual centres ranged between 44.5% and 89.1%, with highest percentage of participants with non-White ethnicity in London-based centres. Examples are provided how to reach potentially underrepresented minority ethnic groups.

Conclusions

Recruitment barriers in relation to potentially underrepresented ethnic groups may be overcome with strategies identified here.", "laySummary": "", - "urls": "doi:https://doi.org/10.12688/wellcomeopenres.15842.3; html:https://europepmc.org/articles/PMC7338915; pdf:https://europepmc.org/articles/PMC7338915?pdf=render" + "urls": "doi:https://doi.org/10.1016/j.clinme.2024.100209; html:https://europepmc.org/articles/PMC11091497; pdf:https://europepmc.org/articles/PMC11091497?pdf=render" }, { "id": "38180742", @@ -27352,23 +27352,6 @@ "laySummary": "", "urls": "pdf:https://jogh.org/wp-content/uploads/2022/07/jogh-12-05033.pdf; doi:https://doi.org/10.7189/jogh.12.05033; html:https://europepmc.org/articles/PMC9304921; pdf:https://europepmc.org/articles/PMC9304921?pdf=render" }, - { - "id": "33372068", - "doi": "https://doi.org/10.1136/bmjopen-2020-038324", - "title": "Risk factors for mental illness in adults with atopic eczema or psoriasis: protocol for a systematic review.", - "authorString": "Adesanya EI, Schonmann Y, Hayes JF, Mathur R, Mulick AR, Rayner L, Smeeth L, Smith CH, Langan SM, Mansfield KE.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2020", - "date": "2020-12-28", - "isOpenAccess": "Y", - "keywords": "Psoriasis; Mental health; Eczema; Anxiety Disorders; Schizophrenia & Psychotic Disorders; Depression & Mood Disorders", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

Evidence indicates that people with the common inflammatory skin diseases atopic eczema or psoriasis are at increased risk of mental illness. However, the reasons for the relationship between skin disease and common mental disorders (ie, depression and anxiety) or severe mental illnesses (ie, schizophrenia, bipolar disorder and other psychoses) are unclear. Therefore, we aim to synthesise the available evidence regarding the risk factors for mental illness in adults with atopic eczema or psoriasis.

Methods and analysis

We will conduct a systematic review of randomised controlled trials, cohort, case-control and cross-sectional studies. We will search the following databases from inception to March 2020: Medline, Embase, Global Health, Scopus, the Cochrane Library, Web of Science, Base, PsycInfo, the Global Resource of Eczema Trials, and the grey literature databases Open Grey, PsycExtra and the New York Academy of Medicine Grey Literature Report. We will also search the bibliographies of eligible studies and relevant systematic reviews to identify additional relevant studies. Citation searching of large summary papers will be used to further identify relevant publications. Two reviewers will initially review study titles and abstracts for eligibility, followed by full text screening. We will extract data using a standardised data extraction form. We will assess the risk of bias of included studies using the Quality in Prognosis Studies tool. We will synthesise data narratively, and if studies are sufficiently homogenous, we will consider a meta-analysis. We will assess the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework.

Ethics and dissemination

Ethical approval is not required for a systematic review. Results of the review will be published in a peer-reviewed journal and disseminated through conferences.

Prospero registration number

CRD42020163941.", - "laySummary": "", - "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/10/12/e038324.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-038324; html:https://europepmc.org/articles/PMC7772326; pdf:https://europepmc.org/articles/PMC7772326?pdf=render" - }, { "id": "31282950", "doi": "https://doi.org/10.1001/jamaneurol.2019.1812", @@ -27386,6 +27369,23 @@ "laySummary": "", "urls": "pdf:https://jamanetwork.com/journals/jamaneurology/articlepdf/2737044/jamaneurology_adderley_2019_oi_190046.pdf; doi:https://doi.org/10.1001/jamaneurol.2019.1812; html:https://europepmc.org/articles/PMC6618853" }, + { + "id": "33372068", + "doi": "https://doi.org/10.1136/bmjopen-2020-038324", + "title": "Risk factors for mental illness in adults with atopic eczema or psoriasis: protocol for a systematic review.", + "authorString": "Adesanya EI, Schonmann Y, Hayes JF, Mathur R, Mulick AR, Rayner L, Smeeth L, Smith CH, Langan SM, Mansfield KE.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2020", + "date": "2020-12-28", + "isOpenAccess": "Y", + "keywords": "Psoriasis; Mental health; Eczema; Anxiety Disorders; Schizophrenia & Psychotic Disorders; Depression & Mood Disorders", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

Evidence indicates that people with the common inflammatory skin diseases atopic eczema or psoriasis are at increased risk of mental illness. However, the reasons for the relationship between skin disease and common mental disorders (ie, depression and anxiety) or severe mental illnesses (ie, schizophrenia, bipolar disorder and other psychoses) are unclear. Therefore, we aim to synthesise the available evidence regarding the risk factors for mental illness in adults with atopic eczema or psoriasis.

Methods and analysis

We will conduct a systematic review of randomised controlled trials, cohort, case-control and cross-sectional studies. We will search the following databases from inception to March 2020: Medline, Embase, Global Health, Scopus, the Cochrane Library, Web of Science, Base, PsycInfo, the Global Resource of Eczema Trials, and the grey literature databases Open Grey, PsycExtra and the New York Academy of Medicine Grey Literature Report. We will also search the bibliographies of eligible studies and relevant systematic reviews to identify additional relevant studies. Citation searching of large summary papers will be used to further identify relevant publications. Two reviewers will initially review study titles and abstracts for eligibility, followed by full text screening. We will extract data using a standardised data extraction form. We will assess the risk of bias of included studies using the Quality in Prognosis Studies tool. We will synthesise data narratively, and if studies are sufficiently homogenous, we will consider a meta-analysis. We will assess the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework.

Ethics and dissemination

Ethical approval is not required for a systematic review. Results of the review will be published in a peer-reviewed journal and disseminated through conferences.

Prospero registration number

CRD42020163941.", + "laySummary": "", + "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/10/12/e038324.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-038324; html:https://europepmc.org/articles/PMC7772326; pdf:https://europepmc.org/articles/PMC7772326?pdf=render" + }, { "id": "34348396", "doi": "https://doi.org/10.1097/ede.0000000000001393", @@ -27471,23 +27471,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/eurjpc/advance-article-pdf/doi/10.1093/eurjpc/zwad187/50506335/zwad187.pdf; doi:https://doi.org/10.1093/eurjpc/zwad187; html:https://europepmc.org/articles/PMC10600319; pdf:https://europepmc.org/articles/PMC10600319?pdf=render" }, - { - "id": "37705296", - "doi": "https://doi.org/10.1002/sim.9898", - "title": "Using temporal recalibration to improve the calibration of risk prediction models in competing risk settings when there are trends in survival over time.", - "authorString": "Booth S, Mozumder SI, Archer L, Ensor J, Riley RD, Lambert PC, Rutherford MJ.", - "authorAffiliations": "", - "journalTitle": "Statistics in medicine", - "pubYear": "2023", - "date": "2023-09-13", - "isOpenAccess": "Y", - "keywords": "calibration; Risk Prediction; Competing Risks; Temporal Recalibration; Prognostic Models", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "We have previously proposed temporal recalibration to account for trends in survival over time to improve the calibration of predictions from prognostic models for new patients. This involves first estimating the predictor effects using data from all individuals (full dataset) and then re-estimating the baseline using a subset of the most recent data whilst constraining the predictor effects to remain the same. In this article, we demonstrate how temporal recalibration can be applied in competing risk settings by recalibrating each cause-specific (or subdistribution) hazard model separately. We illustrate this using an example of colon cancer survival with data from the Surveillance Epidemiology and End Results (SEER) program. Data from patients diagnosed in 1995-2004 were used to fit two models for deaths due to colon cancer and other causes respectively. We discuss considerations that need to be made in order to apply temporal recalibration such as the choice of data used in the recalibration step. We also demonstrate how to assess the calibration of these models in new data for patients diagnosed subsequently in 2005. Comparison was made to a standard analysis (when improvements over time are not taken into account) and a period analysis which is similar to temporal recalibration but differs in the data used to estimate the predictor effects. The 10-year calibration plots demonstrated that using the standard approach over-estimated the risk of death due to colon cancer and the total risk of death and that calibration was improved using temporal recalibration or period analysis.", - "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/sim.9898; doi:https://doi.org/10.1002/sim.9898; html:https://europepmc.org/articles/PMC10946485; pdf:https://europepmc.org/articles/PMC10946485?pdf=render" - }, { "id": "33591280", "doi": "https://doi.org/10.2196/16348", @@ -27506,21 +27489,21 @@ "urls": "pdf:https://www.jmir.org/2021/2/e16348/PDF; doi:https://doi.org/10.2196/16348; html:https://europepmc.org/articles/PMC7925154" }, { - "id": "37984978", - "doi": "https://doi.org/10.1136/bmj-2023-076754", - "title": "ROB-ME: a tool for assessing risk of bias due to missing evidence in systematic reviews with meta-analysis.", - "authorString": "Page MJ, Sterne JAC, Boutron I, Hr\u00f3bjartsson A, Kirkham JJ, Li T, Lundh A, Mayo-Wilson E, McKenzie JE, Stewart LA, Sutton AJ, Bero L, Dunn AG, Dwan K, Elbers RG, Kanukula R, Meerpohl JJ, Turner EH, Higgins JPT.", + "id": "37705296", + "doi": "https://doi.org/10.1002/sim.9898", + "title": "Using temporal recalibration to improve the calibration of risk prediction models in competing risk settings when there are trends in survival over time.", + "authorString": "Booth S, Mozumder SI, Archer L, Ensor J, Riley RD, Lambert PC, Rutherford MJ.", "authorAffiliations": "", - "journalTitle": "BMJ (Clinical research ed.)", + "journalTitle": "Statistics in medicine", "pubYear": "2023", - "date": "2023-11-20", - "isOpenAccess": "N", - "keywords": "", + "date": "2023-09-13", + "isOpenAccess": "Y", + "keywords": "calibration; Risk Prediction; Competing Risks; Temporal Recalibration; Prognostic Models", "nationalPriorities": "", "healthCategories": "", - "abstract": "", + "abstract": "We have previously proposed temporal recalibration to account for trends in survival over time to improve the calibration of predictions from prognostic models for new patients. This involves first estimating the predictor effects using data from all individuals (full dataset) and then re-estimating the baseline using a subset of the most recent data whilst constraining the predictor effects to remain the same. In this article, we demonstrate how temporal recalibration can be applied in competing risk settings by recalibrating each cause-specific (or subdistribution) hazard model separately. We illustrate this using an example of colon cancer survival with data from the Surveillance Epidemiology and End Results (SEER) program. Data from patients diagnosed in 1995-2004 were used to fit two models for deaths due to colon cancer and other causes respectively. We discuss considerations that need to be made in order to apply temporal recalibration such as the choice of data used in the recalibration step. We also demonstrate how to assess the calibration of these models in new data for patients diagnosed subsequently in 2005. Comparison was made to a standard analysis (when improvements over time are not taken into account) and a period analysis which is similar to temporal recalibration but differs in the data used to estimate the predictor effects. The 10-year calibration plots demonstrated that using the standard approach over-estimated the risk of death due to colon cancer and the total risk of death and that calibration was improved using temporal recalibration or period analysis.", "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bmj-2023-076754" + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/sim.9898; doi:https://doi.org/10.1002/sim.9898; html:https://europepmc.org/articles/PMC10946485; pdf:https://europepmc.org/articles/PMC10946485?pdf=render" }, { "id": "32846977", @@ -27539,6 +27522,23 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/1660-4601/17/17/6139/pdf?version=1598511551; doi:https://doi.org/10.3390/ijerph17176139; html:https://europepmc.org/articles/PMC7504024; pdf:https://europepmc.org/articles/PMC7504024?pdf=render" }, + { + "id": "37984978", + "doi": "https://doi.org/10.1136/bmj-2023-076754", + "title": "ROB-ME: a tool for assessing risk of bias due to missing evidence in systematic reviews with meta-analysis.", + "authorString": "Page MJ, Sterne JAC, Boutron I, Hr\u00f3bjartsson A, Kirkham JJ, Li T, Lundh A, Mayo-Wilson E, McKenzie JE, Stewart LA, Sutton AJ, Bero L, Dunn AG, Dwan K, Elbers RG, Kanukula R, Meerpohl JJ, Turner EH, Higgins JPT.", + "authorAffiliations": "", + "journalTitle": "BMJ (Clinical research ed.)", + "pubYear": "2023", + "date": "2023-11-20", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/bmj-2023-076754" + }, { "id": "37994361", "doi": "https://doi.org/10.12688/gatesopenres.13654.1", @@ -27658,23 +27658,6 @@ "laySummary": "", "urls": "pdf:https://qualitysafety.bmj.com/content/qhc/early/2022/03/02/bmjqs-2020-012108.full.pdf; doi:https://doi.org/10.1136/bmjqs-2020-012108; html:https://europepmc.org/articles/PMC9606525; pdf:https://europepmc.org/articles/PMC9606525?pdf=render" }, - { - "id": "37647652", - "doi": "https://doi.org/10.1182/blood.2023021100", - "title": "A signature of platelet reactivity in CBC scattergrams reveals genetic predictors of thrombotic disease risk.", - "authorString": "Verdier H, Thomas P, Batista J, Kempster C, McKinney H, Gleadall N, Danesh J, Mumford A, Heemskerk JWM, Ouwehand WH, Downes K, Astle WJ, Turro E.", - "authorAffiliations": "", - "journalTitle": "Blood", - "pubYear": "2023", - "date": "2023-11-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Genetic studies of platelet reactivity (PR) phenotypes may identify novel antiplatelet drug targets. However, such studies have been limited by small sample sizes (n\u00a0< 5000) because of the complexity of measuring PR. We trained a model to predict PR from complete blood count (CBC) scattergrams. A genome-wide association study of this phenotype in 29 806 blood donors identified 21 distinct associations implicating 20 genes, of which 6 have been identified previously. The effect size estimates were significantly correlated with estimates from a study of flow cytometry-measured PR and a study of a phenotype of in\u00a0vitro thrombus formation. A genetic score of PR built from the 21 variants was associated with the incidence rates of myocardial infarction and pulmonary embolism. Mendelian randomization analyses showed that PR was causally associated with the risks of coronary artery disease, stroke, and venous thromboembolism. Our approach provides a blueprint for\u00a0using phenotype imputation to study the determinants of hard-to-measure but biologically important hematological traits.", - "laySummary": "", - "urls": "pdf:https://ashpublications.org/blood/article-pdf/doi/10.1182/blood.2023021100/2076169/blood.2023021100.pdf; doi:https://doi.org/10.1182/blood.2023021100; html:https://europepmc.org/articles/PMC10733829" - }, { "id": "33836256", "doi": "https://doi.org/10.1016/j.jclinepi.2021.03.025", @@ -27692,6 +27675,23 @@ "laySummary": "", "urls": "pdf:http://www.jclinepi.com/article/S0895435621001074/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.03.025" }, + { + "id": "37647652", + "doi": "https://doi.org/10.1182/blood.2023021100", + "title": "A signature of platelet reactivity in CBC scattergrams reveals genetic predictors of thrombotic disease risk.", + "authorString": "Verdier H, Thomas P, Batista J, Kempster C, McKinney H, Gleadall N, Danesh J, Mumford A, Heemskerk JWM, Ouwehand WH, Downes K, Astle WJ, Turro E.", + "authorAffiliations": "", + "journalTitle": "Blood", + "pubYear": "2023", + "date": "2023-11-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Genetic studies of platelet reactivity (PR) phenotypes may identify novel antiplatelet drug targets. However, such studies have been limited by small sample sizes (n\u00a0< 5000) because of the complexity of measuring PR. We trained a model to predict PR from complete blood count (CBC) scattergrams. A genome-wide association study of this phenotype in 29 806 blood donors identified 21 distinct associations implicating 20 genes, of which 6 have been identified previously. The effect size estimates were significantly correlated with estimates from a study of flow cytometry-measured PR and a study of a phenotype of in\u00a0vitro thrombus formation. A genetic score of PR built from the 21 variants was associated with the incidence rates of myocardial infarction and pulmonary embolism. Mendelian randomization analyses showed that PR was causally associated with the risks of coronary artery disease, stroke, and venous thromboembolism. Our approach provides a blueprint for\u00a0using phenotype imputation to study the determinants of hard-to-measure but biologically important hematological traits.", + "laySummary": "", + "urls": "pdf:https://ashpublications.org/blood/article-pdf/doi/10.1182/blood.2023021100/2076169/blood.2023021100.pdf; doi:https://doi.org/10.1182/blood.2023021100; html:https://europepmc.org/articles/PMC10733829" + }, { "id": "34957541", "doi": "https://doi.org/10.1111/bjh.18013", @@ -27794,23 +27794,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeac030/42506545/jeac030.pdf; doi:https://doi.org/10.1093/ehjci/jeac030; html:https://europepmc.org/articles/PMC9762936; pdf:https://europepmc.org/articles/PMC9762936?pdf=render" }, - { - "id": "36462729", - "doi": "https://doi.org/10.1016/j.neuroimage.2022.119779", - "title": "Amplitudes of resting-state functional networks - investigation into their correlates and biophysical properties.", - "authorString": "Lee S, Bijsterbosch JD, Almagro FA, Elliott L, McCarthy P, Taschler B, Sala-Llonch R, Beckmann CF, Duff EP, Smith SM, Douaud G.", - "authorAffiliations": "", - "journalTitle": "NeuroImage", - "pubYear": "2023", - "date": "2022-12-01", - "isOpenAccess": "Y", - "keywords": "Dual regression; Gwas; Resting-state Fmri; Uk Biobank; Temporal Synchrony; Network Amplitude", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Resting-state fMRI studies have shown that multiple functional networks, which consist of distributed brain regions that share synchronised spontaneous activity, co-exist in the brain. As these resting-state networks (RSNs) have been thought to reflect the brain's intrinsic functional organization, intersubject variability in the networks' spontaneous fluctuations may be associated with individuals' clinical, physiological, cognitive, and genetic traits. Here, we investigated resting-state fMRI data along with extensive clinical, lifestyle, and genetic data collected from 37,842 UK Biobank participants, with the object of elucidating intersubject variability in the fluctuation amplitudes of RSNs. Functional properties of the RSN amplitudes were first examined by analyzing correlations with the well-established between-network functional connectivity. It was found that a network amplitude is highly correlated with the mean strength of the functional connectivity that the network has with the other networks. Intersubject clustering analysis showed the amplitudes are most strongly correlated with age, cardiovascular factors, body composition, blood cell counts, lung function, and sex, with some differences in the correlation strengths between sensory and cognitive RSNs. Genome-wide association studies (GWASs) of RSN amplitudes identified several significant genetic variants reported in previous GWASs for their implications in sleep duration. We provide insight into key factors determining RSN amplitudes and demonstrate that intersubject variability of the amplitudes primarily originates from differences in temporal synchrony between functionally linked brain regions, rather than differences in the magnitude of raw voxelwise BOLD signal changes. This finding additionally revealed intriguing differences between sensory and cognitive RSNs with respect to sex effects on temporal synchrony and provided evidence suggesting that synchronous coactivations of functionally linked brain regions, and magnitudes of BOLD signal changes, may be related to different genetic mechanisms. These results underscore that intersubject variability of the amplitudes in health and disease need to be interpreted largely as a measure of the sum of within-network temporal synchrony and amplitudes of BOLD signals, with a dominant contribution from the former.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.neuroimage.2022.119779; doi:https://doi.org/10.1016/j.neuroimage.2022.119779; html:https://europepmc.org/articles/PMC10933815; pdf:https://europepmc.org/articles/PMC10933815?pdf=render" - }, { "id": "33782427", "doi": "https://doi.org/10.1038/s41598-021-86266-3", @@ -27845,6 +27828,23 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1006785&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1006785; html:https://europepmc.org/articles/PMC6386417; pdf:https://europepmc.org/articles/PMC6386417?pdf=render" }, + { + "id": "36462729", + "doi": "https://doi.org/10.1016/j.neuroimage.2022.119779", + "title": "Amplitudes of resting-state functional networks - investigation into their correlates and biophysical properties.", + "authorString": "Lee S, Bijsterbosch JD, Almagro FA, Elliott L, McCarthy P, Taschler B, Sala-Llonch R, Beckmann CF, Duff EP, Smith SM, Douaud G.", + "authorAffiliations": "", + "journalTitle": "NeuroImage", + "pubYear": "2023", + "date": "2022-12-01", + "isOpenAccess": "Y", + "keywords": "Dual regression; Gwas; Resting-state Fmri; Uk Biobank; Temporal Synchrony; Network Amplitude", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Resting-state fMRI studies have shown that multiple functional networks, which consist of distributed brain regions that share synchronised spontaneous activity, co-exist in the brain. As these resting-state networks (RSNs) have been thought to reflect the brain's intrinsic functional organization, intersubject variability in the networks' spontaneous fluctuations may be associated with individuals' clinical, physiological, cognitive, and genetic traits. Here, we investigated resting-state fMRI data along with extensive clinical, lifestyle, and genetic data collected from 37,842 UK Biobank participants, with the object of elucidating intersubject variability in the fluctuation amplitudes of RSNs. Functional properties of the RSN amplitudes were first examined by analyzing correlations with the well-established between-network functional connectivity. It was found that a network amplitude is highly correlated with the mean strength of the functional connectivity that the network has with the other networks. Intersubject clustering analysis showed the amplitudes are most strongly correlated with age, cardiovascular factors, body composition, blood cell counts, lung function, and sex, with some differences in the correlation strengths between sensory and cognitive RSNs. Genome-wide association studies (GWASs) of RSN amplitudes identified several significant genetic variants reported in previous GWASs for their implications in sleep duration. We provide insight into key factors determining RSN amplitudes and demonstrate that intersubject variability of the amplitudes primarily originates from differences in temporal synchrony between functionally linked brain regions, rather than differences in the magnitude of raw voxelwise BOLD signal changes. This finding additionally revealed intriguing differences between sensory and cognitive RSNs with respect to sex effects on temporal synchrony and provided evidence suggesting that synchronous coactivations of functionally linked brain regions, and magnitudes of BOLD signal changes, may be related to different genetic mechanisms. These results underscore that intersubject variability of the amplitudes in health and disease need to be interpreted largely as a measure of the sum of within-network temporal synchrony and amplitudes of BOLD signals, with a dominant contribution from the former.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.neuroimage.2022.119779; doi:https://doi.org/10.1016/j.neuroimage.2022.119779; html:https://europepmc.org/articles/PMC10933815; pdf:https://europepmc.org/articles/PMC10933815?pdf=render" + }, { "id": "37722858", "doi": "https://doi.org/10.3399/bjgp.2023.0077", @@ -27947,23 +27947,6 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejp.1750; doi:https://doi.org/10.1002/ejp.1750" }, - { - "id": "37751444", - "doi": "https://doi.org/10.1371/journal.pone.0290583", - "title": "Long Covid symptoms and diagnosis in primary care: A cohort study using structured and unstructured data in The Health Improvement Network primary care database.", - "authorString": "Shah AD, Subramanian A, Lewis J, Dhalla S, Ford E, Haroon S, Kuan V, Nirantharakumar K.", - "authorAffiliations": "", - "journalTitle": "PloS one", - "pubYear": "2023", - "date": "2023-09-26", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Long Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes.

Aims

To compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis.

Methods

We used primary care electronic health record data until the end of December 2020 from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and 'Long Covid' diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis.

Results

We compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.46, 95% confidence interval (CI) 2.87, 4.17), shortness of breath (aHR 2.89, 95% CI 2.48, 3.36), palpitations (aHR 2.59, 95% CI 1.86, 3.60), and phlegm (aHR 2.43, 95% CI 1.65, 3.59). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression.

Conclusions

Numerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.", - "laySummary": "", - "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0290583&type=printable; doi:https://doi.org/10.1371/journal.pone.0290583; html:https://europepmc.org/articles/PMC10521988; pdf:https://europepmc.org/articles/PMC10521988?pdf=render" - }, { "id": "32570434", "doi": "https://doi.org/10.3233/shti200210", @@ -27981,6 +27964,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3233/SHTI200210" }, + { + "id": "37751444", + "doi": "https://doi.org/10.1371/journal.pone.0290583", + "title": "Long Covid symptoms and diagnosis in primary care: A cohort study using structured and unstructured data in The Health Improvement Network primary care database.", + "authorString": "Shah AD, Subramanian A, Lewis J, Dhalla S, Ford E, Haroon S, Kuan V, Nirantharakumar K.", + "authorAffiliations": "", + "journalTitle": "PloS one", + "pubYear": "2023", + "date": "2023-09-26", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Long Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes.

Aims

To compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis.

Methods

We used primary care electronic health record data until the end of December 2020 from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and 'Long Covid' diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis.

Results

We compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.46, 95% confidence interval (CI) 2.87, 4.17), shortness of breath (aHR 2.89, 95% CI 2.48, 3.36), palpitations (aHR 2.59, 95% CI 1.86, 3.60), and phlegm (aHR 2.43, 95% CI 1.65, 3.59). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression.

Conclusions

Numerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.", + "laySummary": "", + "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0290583&type=printable; doi:https://doi.org/10.1371/journal.pone.0290583; html:https://europepmc.org/articles/PMC10521988; pdf:https://europepmc.org/articles/PMC10521988?pdf=render" + }, { "id": "36960327", "doi": "https://doi.org/10.2147/clep.s384605", @@ -28049,23 +28049,6 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/1660-4601/17/3/892/pdf?version=1580475934; doi:https://doi.org/10.3390/ijerph17030892; html:https://europepmc.org/articles/PMC7037699; pdf:https://europepmc.org/articles/PMC7037699?pdf=render" }, - { - "id": "37407123", - "doi": "https://doi.org/10.1016/j.jcmg.2023.01.016", - "title": "Ischemic Heart Disease and Vascular\u00a0Risk\u00a0Factors Are Associated With Accelerated Brain Aging.", - "authorString": "Rauseo E, Salih A, Raisi-Estabragh Z, Aung N, Khanderia N, Slabaugh GG, Marshall CR, Neubauer S, Radeva P, Galazzo IB, Menegaz G, Petersen SE.", - "authorAffiliations": "", - "journalTitle": "JACC. Cardiovascular imaging", - "pubYear": "2023", - "date": "2023-04-12", - "isOpenAccess": "Y", - "keywords": "brain aging; ischemic heart disease; Cognitive Decline; Vascular Risk Factors; Brain Health", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Ischemic heart disease (IHD) has been linked with poor brain outcomes. The brain magnetic resonance imaging-derived difference between predicted brain age and actual chronological age (brain-age delta in years, positive for accelerated brain aging) may serve as an effective means of communicating brain health to patients to promote healthier lifestyles.

Objectives

The authors investigated the impact of prevalent IHD on brain aging, potential underlying mechanisms, and its relationship with dementia risk, vascular risk factors, cardiovascular structure, and function.

Methods

Brain age was estimated in subjects with prevalent IHD (n\u00a0=\u00a01,341) using a Bayesian ridge regression model with 25 structural (volumetric) brain magnetic resonance imaging features and built using UK Biobank participants with no prevalent IHD (n\u00a0=\u00a035,237).

Results

Prevalent IHD was linked to significantly accelerated brain aging (P\u00a0< 0.001) that was not fully mediated by microvascular injury. Brain aging (positive brain-age delta) was associated with increased risk of dementia (OR: 1.13\u00a0[95%\u00a0CI: 1.04-1.22]; P = 0.002), vascular risk factors (such as diabetes), and high adiposity. In the absence of IHD, brain aging was also associated with cardiovascular structural and functional changes typically observed in aging hearts. However, such alterations were not linked with risk of dementia.

Conclusions

Prevalent IHD and coexisting vascular risk factors are associated with accelerated brain aging and risk of dementia. Positive brain-age delta representing accelerated brain aging may serve as an effective communication tool to show the impact of modifiable risk factors and disease supporting preventative strategies.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jcmg.2023.01.016; html:https://europepmc.org/articles/PMC10317841; pdf:https://europepmc.org/articles/PMC10317841?pdf=render" - }, { "id": "35115301", "doi": "https://doi.org/10.1136/bjophthalmol-2021-319641", @@ -28083,6 +28066,23 @@ "laySummary": "", "urls": "pdf:https://discovery.ucl.ac.uk/10143945/1/Keane_T2DM%20metformin%20and%20risk%20of%20AMD%20BJO%2020220111%20clean.pdf; doi:https://doi.org/10.1136/bjophthalmol-2021-319641" }, + { + "id": "37407123", + "doi": "https://doi.org/10.1016/j.jcmg.2023.01.016", + "title": "Ischemic Heart Disease and Vascular\u00a0Risk\u00a0Factors Are Associated With Accelerated Brain Aging.", + "authorString": "Rauseo E, Salih A, Raisi-Estabragh Z, Aung N, Khanderia N, Slabaugh GG, Marshall CR, Neubauer S, Radeva P, Galazzo IB, Menegaz G, Petersen SE.", + "authorAffiliations": "", + "journalTitle": "JACC. Cardiovascular imaging", + "pubYear": "2023", + "date": "2023-04-12", + "isOpenAccess": "Y", + "keywords": "brain aging; ischemic heart disease; Cognitive Decline; Vascular Risk Factors; Brain Health", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Ischemic heart disease (IHD) has been linked with poor brain outcomes. The brain magnetic resonance imaging-derived difference between predicted brain age and actual chronological age (brain-age delta in years, positive for accelerated brain aging) may serve as an effective means of communicating brain health to patients to promote healthier lifestyles.

Objectives

The authors investigated the impact of prevalent IHD on brain aging, potential underlying mechanisms, and its relationship with dementia risk, vascular risk factors, cardiovascular structure, and function.

Methods

Brain age was estimated in subjects with prevalent IHD (n\u00a0=\u00a01,341) using a Bayesian ridge regression model with 25 structural (volumetric) brain magnetic resonance imaging features and built using UK Biobank participants with no prevalent IHD (n\u00a0=\u00a035,237).

Results

Prevalent IHD was linked to significantly accelerated brain aging (P\u00a0< 0.001) that was not fully mediated by microvascular injury. Brain aging (positive brain-age delta) was associated with increased risk of dementia (OR: 1.13\u00a0[95%\u00a0CI: 1.04-1.22]; P = 0.002), vascular risk factors (such as diabetes), and high adiposity. In the absence of IHD, brain aging was also associated with cardiovascular structural and functional changes typically observed in aging hearts. However, such alterations were not linked with risk of dementia.

Conclusions

Prevalent IHD and coexisting vascular risk factors are associated with accelerated brain aging and risk of dementia. Positive brain-age delta representing accelerated brain aging may serve as an effective communication tool to show the impact of modifiable risk factors and disease supporting preventative strategies.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.jcmg.2023.01.016; html:https://europepmc.org/articles/PMC10317841; pdf:https://europepmc.org/articles/PMC10317841?pdf=render" + }, { "id": "36456017", "doi": "https://doi.org/10.1136/bmjopen-2022-066288", @@ -28202,40 +28202,6 @@ "laySummary": "", "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.119.002711; doi:https://doi.org/10.1161/CIRCGEN.119.002711; html:https://europepmc.org/articles/PMC6922071; pdf:https://europepmc.org/articles/PMC6922071?pdf=render" }, - { - "id": "38233595", - "doi": "https://doi.org/10.1038/s41588-023-01638-x", - "title": "Inherited polygenic effects on common hematological traits influence clonal selection on JAK2V617F and the development of myeloproliferative neoplasms.", - "authorString": "Guo J, Walter K, Quiros PM, Gu M, Baxter EJ, Danesh J, Di Angelantonio E, Roberts D, Guglielmelli P, Harrison CN, Godfrey AL, Green AR, Vassiliou GS, Vuckovic D, Nangalia J, Soranzo N.", - "authorAffiliations": "", - "journalTitle": "Nature genetics", - "pubYear": "2024", - "date": "2024-01-17", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Myeloproliferative neoplasms (MPNs) are chronic cancers characterized by overproduction of mature blood cells. Their causative somatic mutations, for example, JAK2V617F, are common in the population, yet only a minority of carriers develop MPN. Here we show that the inherited polygenic loci that underlie common hematological traits influence JAK2V617F clonal expansion. We identify polygenic risk scores (PGSs) for monocyte count and plateletcrit as new risk factors for JAK2V617F positivity. PGSs for several hematological traits influenced the risk of different MPN subtypes, with low PGSs for two platelet traits also showing protective effects in JAK2V617F carriers, making them two to three times less likely to have essential thrombocythemia than carriers with high PGSs. We observed that extreme hematological PGSs may contribute to an MPN diagnosis in the absence of somatic driver mutations. Our study showcases how polygenic backgrounds underlying common hematological traits influence both clonal selection on somatic mutations and the subsequent phenotype of cancer.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41588-023-01638-x.pdf; doi:https://doi.org/10.1038/s41588-023-01638-x; html:https://europepmc.org/articles/PMC10864174; pdf:https://europepmc.org/articles/PMC10864174?pdf=render" - }, - { - "id": "36732776", - "doi": "https://doi.org/10.1186/s13040-023-00321-5", - "title": "LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes.", - "authorString": "Alasiri A, Karczewski KJ, Cole B, Loza BL, Moore JH, van der Laan SW, Asselbergs FW, Keating BJ, van Setten J.", - "authorAffiliations": "", - "journalTitle": "BioData mining", - "pubYear": "2023", - "date": "2023-02-02", - "isOpenAccess": "Y", - "keywords": "Human Genetic; Loss-of-function Variants; Compound Heterozygotes; Knockout Genes", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Loss-of-Function (LoF) variants in human genes are important due to their impact on clinical phenotypes and frequent occurrence in the genomes of healthy individuals. The association of LoF variants with complex diseases and traits may lead to the discovery and validation of novel therapeutic targets. Current approaches predict high-confidence LoF variants without identifying the specific genes or the number of copies they affect. Moreover, there is a lack of methods for detecting knockout genes caused by compound heterozygous (CH) LoF variants.

Results

We have developed the Loss-of-Function ToolKit (LoFTK), which allows efficient and automated prediction of LoF variants from genotyped, imputed and sequenced genomes. LoFTK enables the identification of genes that are inactive in one or two copies and provides summary statistics for downstream analyses. LoFTK can identify CH LoF variants, which result in LoF genes with two copies lost. Using data from parents and offspring we show that 96% of CH LoF genes predicted by LoFTK in the offspring have the respective alleles donated by each parent.

Conclusions

LoFTK is a command-line based tool that provides a reliable computational workflow for predicting LoF variants from genotyped and sequenced genomes, identifying genes that are inactive in 1 or 2 copies. LoFTK is an open software and is freely available to non-commercial users at https://github.com/CirculatoryHealth/LoFTK .", - "laySummary": "", - "urls": "pdf:https://biodatamining.biomedcentral.com/counter/pdf/10.1186/s13040-023-00321-5; doi:https://doi.org/10.1186/s13040-023-00321-5; html:https://europepmc.org/articles/PMC9893534; pdf:https://europepmc.org/articles/PMC9893534?pdf=render" - }, { "id": "37671353", "doi": "https://doi.org/10.23889/ijpds.v5i3.2133", @@ -28253,6 +28219,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.23889/ijpds.v5i3.2133; html:https://europepmc.org/articles/PMC10476697; pdf:https://europepmc.org/articles/PMC10476697?pdf=render" }, + { + "id": "38233595", + "doi": "https://doi.org/10.1038/s41588-023-01638-x", + "title": "Inherited polygenic effects on common hematological traits influence clonal selection on JAK2V617F and the development of myeloproliferative neoplasms.", + "authorString": "Guo J, Walter K, Quiros PM, Gu M, Baxter EJ, Danesh J, Di Angelantonio E, Roberts D, Guglielmelli P, Harrison CN, Godfrey AL, Green AR, Vassiliou GS, Vuckovic D, Nangalia J, Soranzo N.", + "authorAffiliations": "", + "journalTitle": "Nature genetics", + "pubYear": "2024", + "date": "2024-01-17", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Myeloproliferative neoplasms (MPNs) are chronic cancers characterized by overproduction of mature blood cells. Their causative somatic mutations, for example, JAK2V617F, are common in the population, yet only a minority of carriers develop MPN. Here we show that the inherited polygenic loci that underlie common hematological traits influence JAK2V617F clonal expansion. We identify polygenic risk scores (PGSs) for monocyte count and plateletcrit as new risk factors for JAK2V617F positivity. PGSs for several hematological traits influenced the risk of different MPN subtypes, with low PGSs for two platelet traits also showing protective effects in JAK2V617F carriers, making them two to three times less likely to have essential thrombocythemia than carriers with high PGSs. We observed that extreme hematological PGSs may contribute to an MPN diagnosis in the absence of somatic driver mutations. Our study showcases how polygenic backgrounds underlying common hematological traits influence both clonal selection on somatic mutations and the subsequent phenotype of cancer.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41588-023-01638-x.pdf; doi:https://doi.org/10.1038/s41588-023-01638-x; html:https://europepmc.org/articles/PMC10864174; pdf:https://europepmc.org/articles/PMC10864174?pdf=render" + }, { "id": "33653287", "doi": "https://doi.org/10.1186/s12875-021-01384-1", @@ -28270,6 +28253,23 @@ "laySummary": "", "urls": "pdf:https://bmcfampract.biomedcentral.com/track/pdf/10.1186/s12875-021-01384-1; doi:https://doi.org/10.1186/s12875-021-01384-1; html:https://europepmc.org/articles/PMC7927406; pdf:https://europepmc.org/articles/PMC7927406?pdf=render" }, + { + "id": "36732776", + "doi": "https://doi.org/10.1186/s13040-023-00321-5", + "title": "LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes.", + "authorString": "Alasiri A, Karczewski KJ, Cole B, Loza BL, Moore JH, van der Laan SW, Asselbergs FW, Keating BJ, van Setten J.", + "authorAffiliations": "", + "journalTitle": "BioData mining", + "pubYear": "2023", + "date": "2023-02-02", + "isOpenAccess": "Y", + "keywords": "Human Genetic; Loss-of-function Variants; Compound Heterozygotes; Knockout Genes", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Loss-of-Function (LoF) variants in human genes are important due to their impact on clinical phenotypes and frequent occurrence in the genomes of healthy individuals. The association of LoF variants with complex diseases and traits may lead to the discovery and validation of novel therapeutic targets. Current approaches predict high-confidence LoF variants without identifying the specific genes or the number of copies they affect. Moreover, there is a lack of methods for detecting knockout genes caused by compound heterozygous (CH) LoF variants.

Results

We have developed the Loss-of-Function ToolKit (LoFTK), which allows efficient and automated prediction of LoF variants from genotyped, imputed and sequenced genomes. LoFTK enables the identification of genes that are inactive in one or two copies and provides summary statistics for downstream analyses. LoFTK can identify CH LoF variants, which result in LoF genes with two copies lost. Using data from parents and offspring we show that 96% of CH LoF genes predicted by LoFTK in the offspring have the respective alleles donated by each parent.

Conclusions

LoFTK is a command-line based tool that provides a reliable computational workflow for predicting LoF variants from genotyped and sequenced genomes, identifying genes that are inactive in 1 or 2 copies. LoFTK is an open software and is freely available to non-commercial users at https://github.com/CirculatoryHealth/LoFTK .", + "laySummary": "", + "urls": "pdf:https://biodatamining.biomedcentral.com/counter/pdf/10.1186/s13040-023-00321-5; doi:https://doi.org/10.1186/s13040-023-00321-5; html:https://europepmc.org/articles/PMC9893534; pdf:https://europepmc.org/articles/PMC9893534?pdf=render" + }, { "id": "38115598", "doi": "https://doi.org/10.1089/neu.2023.0461", @@ -28406,23 +28406,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1308/rcsann.2021.0206; html:https://europepmc.org/articles/PMC9157920; pdf:https://europepmc.org/articles/PMC9157920?pdf=render; doi:https://doi.org/10.1308/rcsann.2021.0206" }, - { - "id": "36814324", - "doi": "https://doi.org/10.1186/s13195-023-01184-y", - "title": "Investigating associations between blood metabolites, later life brain imaging measures, and genetic risk for Alzheimer's disease.", - "authorString": "Green RE, Lord J, Scelsi MA, Xu J, Wong A, Naomi-James S, Handy A, Gilchrist L, Williams DM, Parker TD, Lane CA, Malone IB, Cash DM, Sudre CH, Coath W, Thomas DL, Keuss S, Dobson R, Legido-Quigley C, Fox NC, Schott JM, Richards M, Proitsi P, Insight 46 study team.", - "authorAffiliations": "", - "journalTitle": "Alzheimer's research & therapy", - "pubYear": "2023", - "date": "2023-02-22", - "isOpenAccess": "Y", - "keywords": "Metabolites; Ageing; Brain imaging; Alzheimer\u2019s disease; Dementia; Birth Cohort; Polygenic Scores; Weighted-gene Coexpression Network Analysis", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Identifying blood-based signatures of brain health and preclinical pathology may offer insights into early disease mechanisms and highlight avenues for intervention. Here, we systematically profiled associations between blood metabolites and whole-brain volume, hippocampal volume, and amyloid-\u03b2 status among participants of Insight 46-the neuroscience sub-study of the National Survey of Health and Development (NSHD). We additionally explored whether key metabolites were associated with polygenic risk for Alzheimer's disease (AD).

Methods

Following quality control, levels of 1019 metabolites-detected with liquid chromatography-mass spectrometry-were available for 1740 participants at age 60-64. Metabolite data were subsequently clustered into modules of co-expressed metabolites using weighted coexpression network analysis. Accompanying MRI and amyloid-PET imaging data were present for 437 participants (age 69-71). Regression analyses tested relationships between metabolite measures-modules and hub metabolites-and imaging outcomes. Hub metabolites were defined as metabolites that were highly connected within significant (pFDR\u2009<\u20090.05) modules or were identified as a hub in a previous analysis on cognitive function in the same cohort. Regression models included adjustments for age, sex, APOE genotype, lipid medication use, childhood cognitive ability, and social factors. Finally, associations were tested between AD polygenic risk scores (PRS), including and excluding the APOE region, and metabolites and modules that significantly associated (pFDR\u2009<\u20090.05) with an imaging outcome (N\u2009=\u20091638).

Results

In the fully adjusted model, three lipid modules were associated with a brain volume measure (pFDR\u2009<\u20090.05): one enriched in sphingolipids (hippocampal volume: \u00df\u2009=\u20090.14, 95% CI\u2009=\u2009[0.055,0.23]), one in several fatty acid pathways (whole-brain volume: \u00df\u2009=\u2009\u2009-\u20090.072, 95%CI\u2009=\u2009[-\u20090.12,\u2009-\u20090.026]), and another in diacylglycerols and phosphatidylethanolamines (whole-brain volume: \u00df\u2009=\u2009\u2009-\u20090.066, 95% CI\u2009=\u2009[-\u20090.11,\u2009-\u20090.020]). Twenty-two hub metabolites were associated (pFDR\u2009<\u20090.05) with an imaging outcome (whole-brain volume: 22; hippocampal volume: 4). Some nominal associations were reported for amyloid-\u03b2, and with an AD PRS in our genetic analysis, but none survived multiple testing correction.

Conclusions

Our findings highlight key metabolites, with functions in membrane integrity and cell signalling, that associated with structural brain measures in later life. Future research should focus on replicating this work and interrogating causality.", - "laySummary": "", - "urls": "pdf:https://alzres.biomedcentral.com/counter/pdf/10.1186/s13195-023-01184-y; doi:https://doi.org/10.1186/s13195-023-01184-y; html:https://europepmc.org/articles/PMC9945600; pdf:https://europepmc.org/articles/PMC9945600?pdf=render" - }, { "id": "33174528", "doi": "https://doi.org/10.3310/hta24570", @@ -28457,6 +28440,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1161/CIRCGEN.123.004181" }, + { + "id": "36814324", + "doi": "https://doi.org/10.1186/s13195-023-01184-y", + "title": "Investigating associations between blood metabolites, later life brain imaging measures, and genetic risk for Alzheimer's disease.", + "authorString": "Green RE, Lord J, Scelsi MA, Xu J, Wong A, Naomi-James S, Handy A, Gilchrist L, Williams DM, Parker TD, Lane CA, Malone IB, Cash DM, Sudre CH, Coath W, Thomas DL, Keuss S, Dobson R, Legido-Quigley C, Fox NC, Schott JM, Richards M, Proitsi P, Insight 46 study team.", + "authorAffiliations": "", + "journalTitle": "Alzheimer's research & therapy", + "pubYear": "2023", + "date": "2023-02-22", + "isOpenAccess": "Y", + "keywords": "Metabolites; Ageing; Brain imaging; Alzheimer\u2019s disease; Dementia; Birth Cohort; Polygenic Scores; Weighted-gene Coexpression Network Analysis", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Identifying blood-based signatures of brain health and preclinical pathology may offer insights into early disease mechanisms and highlight avenues for intervention. Here, we systematically profiled associations between blood metabolites and whole-brain volume, hippocampal volume, and amyloid-\u03b2 status among participants of Insight 46-the neuroscience sub-study of the National Survey of Health and Development (NSHD). We additionally explored whether key metabolites were associated with polygenic risk for Alzheimer's disease (AD).

Methods

Following quality control, levels of 1019 metabolites-detected with liquid chromatography-mass spectrometry-were available for 1740 participants at age 60-64. Metabolite data were subsequently clustered into modules of co-expressed metabolites using weighted coexpression network analysis. Accompanying MRI and amyloid-PET imaging data were present for 437 participants (age 69-71). Regression analyses tested relationships between metabolite measures-modules and hub metabolites-and imaging outcomes. Hub metabolites were defined as metabolites that were highly connected within significant (pFDR\u2009<\u20090.05) modules or were identified as a hub in a previous analysis on cognitive function in the same cohort. Regression models included adjustments for age, sex, APOE genotype, lipid medication use, childhood cognitive ability, and social factors. Finally, associations were tested between AD polygenic risk scores (PRS), including and excluding the APOE region, and metabolites and modules that significantly associated (pFDR\u2009<\u20090.05) with an imaging outcome (N\u2009=\u20091638).

Results

In the fully adjusted model, three lipid modules were associated with a brain volume measure (pFDR\u2009<\u20090.05): one enriched in sphingolipids (hippocampal volume: \u00df\u2009=\u20090.14, 95% CI\u2009=\u2009[0.055,0.23]), one in several fatty acid pathways (whole-brain volume: \u00df\u2009=\u2009\u2009-\u20090.072, 95%CI\u2009=\u2009[-\u20090.12,\u2009-\u20090.026]), and another in diacylglycerols and phosphatidylethanolamines (whole-brain volume: \u00df\u2009=\u2009\u2009-\u20090.066, 95% CI\u2009=\u2009[-\u20090.11,\u2009-\u20090.020]). Twenty-two hub metabolites were associated (pFDR\u2009<\u20090.05) with an imaging outcome (whole-brain volume: 22; hippocampal volume: 4). Some nominal associations were reported for amyloid-\u03b2, and with an AD PRS in our genetic analysis, but none survived multiple testing correction.

Conclusions

Our findings highlight key metabolites, with functions in membrane integrity and cell signalling, that associated with structural brain measures in later life. Future research should focus on replicating this work and interrogating causality.", + "laySummary": "", + "urls": "pdf:https://alzres.biomedcentral.com/counter/pdf/10.1186/s13195-023-01184-y; doi:https://doi.org/10.1186/s13195-023-01184-y; html:https://europepmc.org/articles/PMC9945600; pdf:https://europepmc.org/articles/PMC9945600?pdf=render" + }, { "id": "38198570", "doi": "https://doi.org/10.1126/scitranslmed.adf4428", @@ -28474,23 +28474,6 @@ "laySummary": "", "urls": "pdf:https://www.pure.ed.ac.uk/ws/files/405264227/scitranslmed.adf4428.pdf; doi:https://doi.org/10.1126/scitranslmed.adf4428; html:https://europepmc.org/articles/PMC11127744; pdf:https://europepmc.org/articles/PMC11127744?pdf=render; doi:https://doi.org/10.1126/scitranslmed.adf4428" }, - { - "id": "36774358", - "doi": "https://doi.org/10.1038/s41467-023-36439-7", - "title": "Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer.", - "authorString": "Malagoli Tagliazucchi G, Wiecek AJ, Withnell E, Secrier M.", - "authorAffiliations": "", - "journalTitle": "Nature communications", - "pubYear": "2023", - "date": "2023-02-11", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The epithelial to mesenchymal transition (EMT) is a key cellular process underlying cancer progression, with multiple intermediate states whose molecular hallmarks remain poorly characterised. To fill this gap, we present a method to robustly evaluate EMT transformation in individual tumours based on transcriptomic signals. We apply this approach to explore EMT trajectories in 7180 tumours of epithelial origin and identify three macro-states with prognostic and therapeutic value, attributable to epithelial, hybrid E/M and mesenchymal phenotypes. We show that the hybrid state is relatively stable and linked with increased aneuploidy. We further employ spatial transcriptomics and single cell datasets to explore the spatial heterogeneity of EMT transformation and distinct interaction patterns with cytotoxic, NK cells and fibroblasts in the tumour microenvironment. Additionally, we provide a catalogue of genomic events underlying distinct evolutionary constraints on EMT transformation. This study sheds light on the aetiology of distinct stages along the EMT trajectory, and highlights broader genomic and environmental hallmarks shaping the mesenchymal transformation of primary tumours.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41467-023-36439-7.pdf; doi:https://doi.org/10.1038/s41467-023-36439-7; html:https://europepmc.org/articles/PMC9922305; pdf:https://europepmc.org/articles/PMC9922305?pdf=render" - }, { "id": "34750571", "doi": "https://doi.org/10.1038/s42255-021-00478-5", @@ -28508,6 +28491,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s42255-021-00478-5.pdf; doi:https://doi.org/10.1038/s42255-021-00478-5; html:https://europepmc.org/articles/PMC8574944; pdf:https://europepmc.org/articles/PMC8574944?pdf=render" }, + { + "id": "36774358", + "doi": "https://doi.org/10.1038/s41467-023-36439-7", + "title": "Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer.", + "authorString": "Malagoli Tagliazucchi G, Wiecek AJ, Withnell E, Secrier M.", + "authorAffiliations": "", + "journalTitle": "Nature communications", + "pubYear": "2023", + "date": "2023-02-11", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The epithelial to mesenchymal transition (EMT) is a key cellular process underlying cancer progression, with multiple intermediate states whose molecular hallmarks remain poorly characterised. To fill this gap, we present a method to robustly evaluate EMT transformation in individual tumours based on transcriptomic signals. We apply this approach to explore EMT trajectories in 7180 tumours of epithelial origin and identify three macro-states with prognostic and therapeutic value, attributable to epithelial, hybrid E/M and mesenchymal phenotypes. We show that the hybrid state is relatively stable and linked with increased aneuploidy. We further employ spatial transcriptomics and single cell datasets to explore the spatial heterogeneity of EMT transformation and distinct interaction patterns with cytotoxic, NK cells and fibroblasts in the tumour microenvironment. Additionally, we provide a catalogue of genomic events underlying distinct evolutionary constraints on EMT transformation. This study sheds light on the aetiology of distinct stages along the EMT trajectory, and highlights broader genomic and environmental hallmarks shaping the mesenchymal transformation of primary tumours.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41467-023-36439-7.pdf; doi:https://doi.org/10.1038/s41467-023-36439-7; html:https://europepmc.org/articles/PMC9922305; pdf:https://europepmc.org/articles/PMC9922305?pdf=render" + }, { "id": "30554166", "doi": "https://doi.org/10.1136/injuryprev-2018-043019", @@ -28525,6 +28525,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/injuryprev-2018-043019" }, + { + "id": "33654696", + "doi": "https://doi.org/10.1093/burnst/tkaa044", + "title": "Venous thromboembolism prophylaxis practice and its association with outcomes in Australia and New Zealand burns patients.", + "authorString": "Tracy LM, Cameron PA, Singer Y, Earnest A, Wood F, Cleland H, Gabbe BJ.", + "authorAffiliations": "", + "journalTitle": "Burns & trauma", + "pubYear": "2021", + "date": "2021-01-01", + "isOpenAccess": "Y", + "keywords": "Australia; New Zealand; Burn injury; Prophylaxis; Venous Thromboembolism", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Patients with burn injuries are considered to have an increased risk of venous thromboembolism (VTE). While untreated VTEs can be fatal, no studies have examined chemoprophylaxis effectiveness. This study aimed to quantify the variation in prevalence of VTE prophylaxis use in patients in Australian and New Zealand burns units and whether prophylaxis use is associated with in-hospital outcomes following burn injury.

Methods

Admission data for adult burns patients (aged \u226516\u00a0years) admitted between 1 July 2016 and 31 December 2018 were extracted from the Burns Registry of Australia and New Zealand. Mixed effects logistic regression modelling investigated whether VTE prophylaxis use was associated with the primary outcome of in-hospital mortality.

Results

There were 5066 admissions over the study period. Of these patients, 81% (n\u2009=\u20093799) with a valid response to the VTE prophylaxis data field received some form of VTE prophylaxis. Use of VTE prophylaxis ranged from 48.6% to 94.8% of patients between units. In-hospital death was recorded in <1% of patients (n\u2009=\u200933). After adjusting for confounders, receiving VTE prophylaxis was associated with a decrease in the adjusted odds of in-hospital mortality (adjusted odds ratio\u2009=\u20090.21; 95% CI, 0.07-0.63; p\u2009=\u20090.006).

Conclusions

Variation in the use of VTE prophylaxis was observed between the units, and prophylaxis use was associated with a decrease in the odds of mortality. These findings provide an opportunity to engage with units to further explore differences in prophylaxis use and develop future best practice guidelines.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/burnstrauma/article-pdf/doi/10.1093/burnst/tkaa044/37307900/tkaa044.pdf; doi:https://doi.org/10.1093/burnst/tkaa044; html:https://europepmc.org/articles/PMC7901708; pdf:https://europepmc.org/articles/PMC7901708?pdf=render" + }, { "id": "33837377", "doi": "https://doi.org/10.1038/s41591-021-01310-z", @@ -28559,23 +28576,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.xgen.2021.100004; doi:https://doi.org/10.1016/j.xgen.2021.100004; html:https://europepmc.org/articles/PMC9451133; pdf:https://europepmc.org/articles/PMC9451133?pdf=render" }, - { - "id": "33654696", - "doi": "https://doi.org/10.1093/burnst/tkaa044", - "title": "Venous thromboembolism prophylaxis practice and its association with outcomes in Australia and New Zealand burns patients.", - "authorString": "Tracy LM, Cameron PA, Singer Y, Earnest A, Wood F, Cleland H, Gabbe BJ.", - "authorAffiliations": "", - "journalTitle": "Burns & trauma", - "pubYear": "2021", - "date": "2021-01-01", - "isOpenAccess": "Y", - "keywords": "Australia; New Zealand; Burn injury; Prophylaxis; Venous Thromboembolism", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Patients with burn injuries are considered to have an increased risk of venous thromboembolism (VTE). While untreated VTEs can be fatal, no studies have examined chemoprophylaxis effectiveness. This study aimed to quantify the variation in prevalence of VTE prophylaxis use in patients in Australian and New Zealand burns units and whether prophylaxis use is associated with in-hospital outcomes following burn injury.

Methods

Admission data for adult burns patients (aged \u226516\u00a0years) admitted between 1 July 2016 and 31 December 2018 were extracted from the Burns Registry of Australia and New Zealand. Mixed effects logistic regression modelling investigated whether VTE prophylaxis use was associated with the primary outcome of in-hospital mortality.

Results

There were 5066 admissions over the study period. Of these patients, 81% (n\u2009=\u20093799) with a valid response to the VTE prophylaxis data field received some form of VTE prophylaxis. Use of VTE prophylaxis ranged from 48.6% to 94.8% of patients between units. In-hospital death was recorded in <1% of patients (n\u2009=\u200933). After adjusting for confounders, receiving VTE prophylaxis was associated with a decrease in the adjusted odds of in-hospital mortality (adjusted odds ratio\u2009=\u20090.21; 95% CI, 0.07-0.63; p\u2009=\u20090.006).

Conclusions

Variation in the use of VTE prophylaxis was observed between the units, and prophylaxis use was associated with a decrease in the odds of mortality. These findings provide an opportunity to engage with units to further explore differences in prophylaxis use and develop future best practice guidelines.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/burnstrauma/article-pdf/doi/10.1093/burnst/tkaa044/37307900/tkaa044.pdf; doi:https://doi.org/10.1093/burnst/tkaa044; html:https://europepmc.org/articles/PMC7901708; pdf:https://europepmc.org/articles/PMC7901708?pdf=render" - }, { "id": "37477760", "doi": "https://doi.org/10.1007/s10875-023-01547-y", @@ -28661,23 +28661,6 @@ "laySummary": "", "urls": "pdf:http://www.internationaljournalofcardiology.com/article/S0167527320335579/pdf; doi:https://doi.org/10.1016/j.ijcard.2020.08.030" }, - { - "id": "34756707", - "doi": "https://doi.org/10.1016/j.evalprogplan.2021.102019", - "title": "How practitioner, organisational and system-level factors act to influence health promotion evaluation capacity: Validation of a conceptual framework.", - "authorString": "Schwarzman J, Bauman A, Gabbe BJ, Rissel C, Shilton T, Smith BJ.", - "authorAffiliations": "", - "journalTitle": "Evaluation and program planning", - "pubYear": "2022", - "date": "2021-10-20", - "isOpenAccess": "N", - "keywords": "Path analysis; Primary Prevention; Health Promotion; Confirmatory Factor Analysis; Evaluation Capacity", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The need to improve the practice and quality of evaluation in the health promotion and disease prevention field is widely recognised. In order to plan, implement and evaluate health promotion evaluation capacity building efforts, there is a need to better understand the practitioner, organisational and system-level determinants of evaluation capacity and practice. This study aimed to assess the validity Evaluation Practice Analysis Survey (EPAS) constructs using confirmatory factor analysis and validate a conceptual framework of health promotion evaluation capacity using path analysis. Experienced Australian health promotion practitioners completed the survey (n\u00a0=\u00a0219). Twenty-one of the original 23 EPAS scales were assessed as reliable and valid. The final model was found to have good fit (\u03c7214 =\u00a018.72, p\u00a0=\u00a00.18, root mean square error of approximation\u00a0=\u00a00.04, 90% CI 0.00-0.82, Comparative Fit Index\u00a0=\u00a01.00, standardised root mean square residual\u00a0=\u00a00.04). This model supports the role of the organisation in facilitating evaluation practice through leadership, culture, systems, support and resources. It builds on existing frameworks from other fields to incorporate political, funding and administrative factors. This study provides an evidence-based model of evaluation capacity that organisations, funders and policy makers can use to plan and implement more effective evaluation capacity building strategies within organisations and the wider prevention field.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.evalprogplan.2021.102019" - }, { "id": "31816119", "doi": "https://doi.org/10.1002/sim.8443", @@ -28696,21 +28679,21 @@ "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/sim.8443; doi:https://doi.org/10.1002/sim.8443; html:https://europepmc.org/articles/PMC7028099; pdf:https://europepmc.org/articles/PMC7028099?pdf=render" }, { - "id": "38609437", - "doi": "https://doi.org/10.1038/s41746-024-01062-3", - "title": "Self-supervised learning for human activity recognition using 700,000 person-days of wearable data.", - "authorString": "Yuan H, Chan S, Creagh AP, Tong C, Acquah A, Clifton DA, Doherty A.", + "id": "34756707", + "doi": "https://doi.org/10.1016/j.evalprogplan.2021.102019", + "title": "How practitioner, organisational and system-level factors act to influence health promotion evaluation capacity: Validation of a conceptual framework.", + "authorString": "Schwarzman J, Bauman A, Gabbe BJ, Rissel C, Shilton T, Smith BJ.", "authorAffiliations": "", - "journalTitle": "NPJ digital medicine", - "pubYear": "2024", - "date": "2024-04-12", - "isOpenAccess": "Y", - "keywords": "", + "journalTitle": "Evaluation and program planning", + "pubYear": "2022", + "date": "2021-10-20", + "isOpenAccess": "N", + "keywords": "Path analysis; Primary Prevention; Health Promotion; Confirmatory Factor Analysis; Evaluation Capacity", "nationalPriorities": "", "healthCategories": "", - "abstract": "Accurate physical activity monitoring is essential to understand the impact of physical activity on one's physical health and overall well-being. However, advances in human activity recognition algorithms have been constrained by the limited availability of large labelled datasets. This study aims to leverage recent advances in self-supervised learning to exploit the large-scale UK Biobank accelerometer dataset-a 700,000 person-days unlabelled dataset-in order to build models with vastly improved generalisability and accuracy. Our resulting models consistently outperform strong baselines across eight benchmark datasets, with an F1 relative improvement of 2.5-130.9% (median 24.4%). More importantly, in contrast to previous reports, our results generalise across external datasets, cohorts, living environments, and sensor devices. Our open-sourced pre-trained models will be valuable in domains with limited labelled data or where good sampling coverage (across devices, populations, and activities) is hard to achieve.", + "abstract": "The need to improve the practice and quality of evaluation in the health promotion and disease prevention field is widely recognised. In order to plan, implement and evaluate health promotion evaluation capacity building efforts, there is a need to better understand the practitioner, organisational and system-level determinants of evaluation capacity and practice. This study aimed to assess the validity Evaluation Practice Analysis Survey (EPAS) constructs using confirmatory factor analysis and validate a conceptual framework of health promotion evaluation capacity using path analysis. Experienced Australian health promotion practitioners completed the survey (n\u00a0=\u00a0219). Twenty-one of the original 23 EPAS scales were assessed as reliable and valid. The final model was found to have good fit (\u03c7214 =\u00a018.72, p\u00a0=\u00a00.18, root mean square error of approximation\u00a0=\u00a00.04, 90% CI 0.00-0.82, Comparative Fit Index\u00a0=\u00a01.00, standardised root mean square residual\u00a0=\u00a00.04). This model supports the role of the organisation in facilitating evaluation practice through leadership, culture, systems, support and resources. It builds on existing frameworks from other fields to incorporate political, funding and administrative factors. This study provides an evidence-based model of evaluation capacity that organisations, funders and policy makers can use to plan and implement more effective evaluation capacity building strategies within organisations and the wider prevention field.", "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41746-024-01062-3.pdf; doi:https://doi.org/10.1038/s41746-024-01062-3; html:https://europepmc.org/articles/PMC11015005; pdf:https://europepmc.org/articles/PMC11015005?pdf=render" + "urls": "doi:https://doi.org/10.1016/j.evalprogplan.2021.102019" }, { "id": "37907686", @@ -28729,6 +28712,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41397-023-00317-8; html:https://europepmc.org/articles/PMC10661738; pdf:https://europepmc.org/articles/PMC10661738?pdf=render" }, + { + "id": "38609437", + "doi": "https://doi.org/10.1038/s41746-024-01062-3", + "title": "Self-supervised learning for human activity recognition using 700,000 person-days of wearable data.", + "authorString": "Yuan H, Chan S, Creagh AP, Tong C, Acquah A, Clifton DA, Doherty A.", + "authorAffiliations": "", + "journalTitle": "NPJ digital medicine", + "pubYear": "2024", + "date": "2024-04-12", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Accurate physical activity monitoring is essential to understand the impact of physical activity on one's physical health and overall well-being. However, advances in human activity recognition algorithms have been constrained by the limited availability of large labelled datasets. This study aims to leverage recent advances in self-supervised learning to exploit the large-scale UK Biobank accelerometer dataset-a 700,000 person-days unlabelled dataset-in order to build models with vastly improved generalisability and accuracy. Our resulting models consistently outperform strong baselines across eight benchmark datasets, with an F1 relative improvement of 2.5-130.9% (median 24.4%). More importantly, in contrast to previous reports, our results generalise across external datasets, cohorts, living environments, and sensor devices. Our open-sourced pre-trained models will be valuable in domains with limited labelled data or where good sampling coverage (across devices, populations, and activities) is hard to achieve.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41746-024-01062-3.pdf; doi:https://doi.org/10.1038/s41746-024-01062-3; html:https://europepmc.org/articles/PMC11015005; pdf:https://europepmc.org/articles/PMC11015005?pdf=render" + }, { "id": "32247548", "doi": "https://doi.org/10.1016/j.tips.2020.03.003", @@ -28933,23 +28933,6 @@ "laySummary": "", "urls": "pdf:https://discovery.ucl.ac.uk/10135735/1/Asselbergs_10.1515_dmdi-2021-0104.pdf; doi:https://doi.org/10.1515/dmpt-2021-0104" }, - { - "id": "38115587", - "doi": "https://doi.org/10.1089/neu.2023.0464", - "title": "The Australian Traumatic Brain Injury Initiative: Systematic Review of Predictive Value of Biological Markers for People With Moderate-Severe Traumatic Brain Injury.", - "authorString": "Bagg MK, Hellewell SC, Keeves J, Antonic-Baker A, McKimmie A, Hicks AJ, Gadowski A, Newcombe VFJ, Barlow KM, Balogh ZJ, Ross JP, Law M, Caeyenberghs K, Parizel PM, Thorne J, Papini M, Gill G, Jefferson A, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Gabbe BJ, Fitzgerald M.", - "authorAffiliations": "", - "journalTitle": "Journal of neurotrauma", - "pubYear": "2024", - "date": "2024-03-08", - "isOpenAccess": "N", - "keywords": "Tomography, X-ray computed; Tissues; Biomarkers; Magnetic Resonance Imaging; Body Fluids; Common Data Elements; Brain Injuries, Traumatic; Systematic Review [Publication Type]", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to co-design a data resource to predict outcomes for people with moderate-severe traumatic brain injury (TBI) across Australia. Fundamental to this resource is the data dictionary, which is an ontology of data items. Here, we report the systematic review and consensus process for inclusion of biological markers in the data dictionary. Standardized database searches were implemented from inception through April 2022. English-language studies evaluating association between a fluid, tissue, or imaging marker and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Records were screened using a prioritization algorithm and saturation threshold in Research Screener. Full-length records were then screened in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association, and high-value predictors were discussed in a consensus process. Searches retrieved 106,593 records; 1,417 full-length records were screened, resulting in 546 included records. Two hundred thirty-nine individual markers were extracted, evaluated against 101 outcomes. Forty-one markers were judged to be high-value predictors of 15 outcomes. Fluid markers retained following the consensus process included ubiquitin C-terminal hydrolase L1 (UCH-L1), S100, and glial fibrillary acidic protein (GFAP). Imaging markers included computed tomography (CT) scores (e.g., Marshall scores), pathological observations (e.g., hemorrhage, midline shift), and magnetic resonance imaging (MRI) classification (e.g., diffuse axonal injury). Clinical context and time of sampling of potential predictive indicators are important considerations for utility. This systematic review and consensus process has identified fluid and imaging biomarkers with high predictive value of clinical and long-term outcomes following moderate-severe TBI.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1089/neu.2023.0464" - }, { "id": "34237806", "doi": "https://doi.org/10.1515/dmdi-2021-0104", @@ -28967,6 +28950,23 @@ "laySummary": "", "urls": "pdf:https://discovery.ucl.ac.uk/10135735/1/Asselbergs_10.1515_dmdi-2021-0104.pdf; doi:https://doi.org/10.1515/dmdi-2021-0104" }, + { + "id": "38115587", + "doi": "https://doi.org/10.1089/neu.2023.0464", + "title": "The Australian Traumatic Brain Injury Initiative: Systematic Review of Predictive Value of Biological Markers for People With Moderate-Severe Traumatic Brain Injury.", + "authorString": "Bagg MK, Hellewell SC, Keeves J, Antonic-Baker A, McKimmie A, Hicks AJ, Gadowski A, Newcombe VFJ, Barlow KM, Balogh ZJ, Ross JP, Law M, Caeyenberghs K, Parizel PM, Thorne J, Papini M, Gill G, Jefferson A, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Gabbe BJ, Fitzgerald M.", + "authorAffiliations": "", + "journalTitle": "Journal of neurotrauma", + "pubYear": "2024", + "date": "2024-03-08", + "isOpenAccess": "N", + "keywords": "Tomography, X-ray computed; Tissues; Biomarkers; Magnetic Resonance Imaging; Body Fluids; Common Data Elements; Brain Injuries, Traumatic; Systematic Review [Publication Type]", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to co-design a data resource to predict outcomes for people with moderate-severe traumatic brain injury (TBI) across Australia. Fundamental to this resource is the data dictionary, which is an ontology of data items. Here, we report the systematic review and consensus process for inclusion of biological markers in the data dictionary. Standardized database searches were implemented from inception through April 2022. English-language studies evaluating association between a fluid, tissue, or imaging marker and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Records were screened using a prioritization algorithm and saturation threshold in Research Screener. Full-length records were then screened in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association, and high-value predictors were discussed in a consensus process. Searches retrieved 106,593 records; 1,417 full-length records were screened, resulting in 546 included records. Two hundred thirty-nine individual markers were extracted, evaluated against 101 outcomes. Forty-one markers were judged to be high-value predictors of 15 outcomes. Fluid markers retained following the consensus process included ubiquitin C-terminal hydrolase L1 (UCH-L1), S100, and glial fibrillary acidic protein (GFAP). Imaging markers included computed tomography (CT) scores (e.g., Marshall scores), pathological observations (e.g., hemorrhage, midline shift), and magnetic resonance imaging (MRI) classification (e.g., diffuse axonal injury). Clinical context and time of sampling of potential predictive indicators are important considerations for utility. This systematic review and consensus process has identified fluid and imaging biomarkers with high predictive value of clinical and long-term outcomes following moderate-severe TBI.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1089/neu.2023.0464" + }, { "id": "32907797", "doi": "https://doi.org/10.1136/bmj.m3210", @@ -29375,23 +29375,6 @@ "laySummary": "", "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081749; doi:https://doi.org/10.1016/j.jinf.2021.04.027; html:https://europepmc.org/articles/PMC8081749; pdf:https://europepmc.org/articles/PMC8081749?pdf=render" }, - { - "id": "38082486", - "doi": "https://doi.org/10.1681/asn.0000000000000271", - "title": "Effects of Empagliflozin on Fluid Overload, Weight, and Blood Pressure in CKD.", - "authorString": "Mayne KJ, Staplin N, Keane DF, Wanner C, Brenner S, Cejka V, Stegbauer J, Judge PK, Preiss D, Emberson J, Trinca D, Dayanandan R, Lee R, Nolan J, Omata A, Green JB, Cherney DZI, Hooi LS, Pontremoli R, Tuttle KR, Lees JS, Mark PB, Davies SJ, Hauske SJ, Steubl D, Br\u00fcckmann M, Landray MJ, Baigent C, Haynes R, Herrington WG, EMPA-KIDNEY Collaborative Group.", - "authorAffiliations": "", - "journalTitle": "Journal of the American Society of Nephrology : JASN", - "pubYear": "2024", - "date": "2023-12-12", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Significance statement

SGLT2 inhibitors reduce risk of kidney progression, AKI, and cardiovascular disease, but the mechanisms of benefit are incompletely understood. Bioimpedance spectroscopy can estimate body water and fat mass. One quarter of the EMPA-KIDNEY bioimpedance substudy CKD population had clinically significant levels of bioimpedance-derived \"Fluid Overload\" at recruitment. Empagliflozin induced a prompt and sustained reduction in \"Fluid Overload,\" irrespective of sex, diabetes, and baseline N-terminal pro B-type natriuretic peptide or eGFR. No significant effect on bioimpedance-derived fat mass was observed. The effects of SGLT2 inhibitors on body water may be one of the contributing mechanisms by which they mediate effects on cardiovascular risk.

Background

CKD is associated with fluid excess that can be estimated by bioimpedance spectroscopy. We aimed to assess effects of sodium glucose co-transporter 2 inhibition on bioimpedance-derived \"Fluid Overload\" and adiposity in a CKD population.

Methods

EMPA-KIDNEY was a double-blind placebo-controlled trial of empagliflozin 10 mg once daily in patients with CKD at risk of progression. In a substudy, bioimpedance measurements were added to the main trial procedures at randomization and at 2- and 18-month follow-up visits. The substudy's primary outcome was the study-average difference in absolute \"Fluid Overload\" (an estimate of excess extracellular water) analyzed using a mixed model repeated measures approach.

Results

The 660 substudy participants were broadly representative of the 6609-participant trial population. Substudy mean baseline absolute \"Fluid Overload\" was 0.4\u00b11.7 L. Compared with placebo, the overall mean absolute \"Fluid Overload\" difference among those allocated empagliflozin was -0.24 L (95% confidence interval [CI], -0.38 to -0.11), with similar sized differences at 2 and 18 months, and in prespecified subgroups. Total body water differences comprised between-group differences in extracellular water of -0.49 L (95% CI, -0.69 to -0.30, including the -0.24 L \"Fluid Overload\" difference) and a -0.30 L (95% CI, -0.57 to -0.03) difference in intracellular water. There was no significant effect of empagliflozin on bioimpedance-derived adipose tissue mass (-0.28 kg [95% CI, -1.41 to 0.85]). The between-group difference in weight was -0.7 kg (95% CI, -1.3 to -0.1).

Conclusions

In a broad range of patients with CKD, empagliflozin resulted in a sustained reduction in a bioimpedance-derived estimate of fluid overload, with no statistically significant effect on fat mass.

Trial registration

Clinicaltrials.gov: NCT03594110 ; EuDRACT: 2017-002971-24 ( https://eudract.ema.europa.eu/ ).", - "laySummary": "", - "urls": "doi:https://doi.org/10.1681/ASN.0000000000000271; html:https://europepmc.org/articles/PMC7615589; pdf:https://europepmc.org/articles/PMC7615589?pdf=render" - }, { "id": "34040552", "doi": "https://doi.org/10.3389/fpsyt.2021.627996", @@ -29443,6 +29426,23 @@ "laySummary": "", "urls": "pdf:https://europepmc.org/articles/pmc6330072?pdf=render; doi:https://doi.org/10.1097/CCM.0000000000003424; html:https://europepmc.org/articles/PMC6330072; pdf:https://europepmc.org/articles/PMC6330072?pdf=render; doi:https://doi.org/10.1097/ccm.0000000000003424" }, + { + "id": "38082486", + "doi": "https://doi.org/10.1681/asn.0000000000000271", + "title": "Effects of Empagliflozin on Fluid Overload, Weight, and Blood Pressure in CKD.", + "authorString": "Mayne KJ, Staplin N, Keane DF, Wanner C, Brenner S, Cejka V, Stegbauer J, Judge PK, Preiss D, Emberson J, Trinca D, Dayanandan R, Lee R, Nolan J, Omata A, Green JB, Cherney DZI, Hooi LS, Pontremoli R, Tuttle KR, Lees JS, Mark PB, Davies SJ, Hauske SJ, Steubl D, Br\u00fcckmann M, Landray MJ, Baigent C, Haynes R, Herrington WG, EMPA-KIDNEY Collaborative Group.", + "authorAffiliations": "", + "journalTitle": "Journal of the American Society of Nephrology : JASN", + "pubYear": "2024", + "date": "2023-12-12", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Significance statement

SGLT2 inhibitors reduce risk of kidney progression, AKI, and cardiovascular disease, but the mechanisms of benefit are incompletely understood. Bioimpedance spectroscopy can estimate body water and fat mass. One quarter of the EMPA-KIDNEY bioimpedance substudy CKD population had clinically significant levels of bioimpedance-derived \"Fluid Overload\" at recruitment. Empagliflozin induced a prompt and sustained reduction in \"Fluid Overload,\" irrespective of sex, diabetes, and baseline N-terminal pro B-type natriuretic peptide or eGFR. No significant effect on bioimpedance-derived fat mass was observed. The effects of SGLT2 inhibitors on body water may be one of the contributing mechanisms by which they mediate effects on cardiovascular risk.

Background

CKD is associated with fluid excess that can be estimated by bioimpedance spectroscopy. We aimed to assess effects of sodium glucose co-transporter 2 inhibition on bioimpedance-derived \"Fluid Overload\" and adiposity in a CKD population.

Methods

EMPA-KIDNEY was a double-blind placebo-controlled trial of empagliflozin 10 mg once daily in patients with CKD at risk of progression. In a substudy, bioimpedance measurements were added to the main trial procedures at randomization and at 2- and 18-month follow-up visits. The substudy's primary outcome was the study-average difference in absolute \"Fluid Overload\" (an estimate of excess extracellular water) analyzed using a mixed model repeated measures approach.

Results

The 660 substudy participants were broadly representative of the 6609-participant trial population. Substudy mean baseline absolute \"Fluid Overload\" was 0.4\u00b11.7 L. Compared with placebo, the overall mean absolute \"Fluid Overload\" difference among those allocated empagliflozin was -0.24 L (95% confidence interval [CI], -0.38 to -0.11), with similar sized differences at 2 and 18 months, and in prespecified subgroups. Total body water differences comprised between-group differences in extracellular water of -0.49 L (95% CI, -0.69 to -0.30, including the -0.24 L \"Fluid Overload\" difference) and a -0.30 L (95% CI, -0.57 to -0.03) difference in intracellular water. There was no significant effect of empagliflozin on bioimpedance-derived adipose tissue mass (-0.28 kg [95% CI, -1.41 to 0.85]). The between-group difference in weight was -0.7 kg (95% CI, -1.3 to -0.1).

Conclusions

In a broad range of patients with CKD, empagliflozin resulted in a sustained reduction in a bioimpedance-derived estimate of fluid overload, with no statistically significant effect on fat mass.

Trial registration

Clinicaltrials.gov: NCT03594110 ; EuDRACT: 2017-002971-24 ( https://eudract.ema.europa.eu/ ).", + "laySummary": "", + "urls": "doi:https://doi.org/10.1681/ASN.0000000000000271; html:https://europepmc.org/articles/PMC7615589; pdf:https://europepmc.org/articles/PMC7615589?pdf=render" + }, { "id": "33036417", "doi": "https://doi.org/10.3390/ijerph17197320", @@ -29545,23 +29545,6 @@ "laySummary": "", "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fimmu.2022.1032331/pdf; doi:https://doi.org/10.3389/fimmu.2022.1032331; html:https://europepmc.org/articles/PMC9624227; pdf:https://europepmc.org/articles/PMC9624227?pdf=render" }, - { - "id": "37339333", - "doi": "https://doi.org/10.1002/jia2.26104", - "title": "COVID-19 among adults living with HIV: correlates of mortality among public sector healthcare users in Western Cape, South Africa.", - "authorString": "Kassanjee R, Davies MA, Ngwenya O, Osei-Yeboah R, Jacobs T, Morden E, Timmerman V, Britz S, Mendelson M, Taljaard J, Riou J, Boulle A, Tiffin N, Zinyakatira N.", - "authorAffiliations": "", - "journalTitle": "Journal of the International AIDS Society", - "pubYear": "2023", - "date": "2023-06-01", - "isOpenAccess": "Y", - "keywords": "Mortality; HIV; South Africa; Cd4 Count; Covid-19; Sars-cov-2", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty about the role of HIV disease severity on COVID-19 outcomes, especially in lower-income settings. We studied the association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH.

Methods

We analysed observational cohort data on all PWH aged \u226515 years experiencing a diagnosed SARS-CoV-2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID-19 vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period.

Results

Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17,831 first-diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults.

Conclusions

Mortality was strongly associated with suboptimal HIV control, and the prevalence of these risk factors increased in later COVID-19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimized.", - "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jia2.26104; doi:https://doi.org/10.1002/jia2.26104; html:https://europepmc.org/articles/PMC10281639; pdf:https://europepmc.org/articles/PMC10281639?pdf=render" - }, { "id": "31964672", "doi": "https://doi.org/10.1136/bmjopen-2019-033318", @@ -29579,6 +29562,23 @@ "laySummary": "This study which includes over 40 thousant adults in the UK, aims to assess whether there are links between different levels of physical activity and educational achievements. It found that lower educational achievement was associated with higher travel and work related physical activity, but not leisure time activity. They found this difference to be larger in men than in women, and also in white compared to black individuals.", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/10/1/e033318.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-033318; html:https://europepmc.org/articles/PMC7045199; pdf:https://europepmc.org/articles/PMC7045199?pdf=render" }, + { + "id": "37339333", + "doi": "https://doi.org/10.1002/jia2.26104", + "title": "COVID-19 among adults living with HIV: correlates of mortality among public sector healthcare users in Western Cape, South Africa.", + "authorString": "Kassanjee R, Davies MA, Ngwenya O, Osei-Yeboah R, Jacobs T, Morden E, Timmerman V, Britz S, Mendelson M, Taljaard J, Riou J, Boulle A, Tiffin N, Zinyakatira N.", + "authorAffiliations": "", + "journalTitle": "Journal of the International AIDS Society", + "pubYear": "2023", + "date": "2023-06-01", + "isOpenAccess": "Y", + "keywords": "Mortality; HIV; South Africa; Cd4 Count; Covid-19; Sars-cov-2", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty about the role of HIV disease severity on COVID-19 outcomes, especially in lower-income settings. We studied the association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH.

Methods

We analysed observational cohort data on all PWH aged \u226515 years experiencing a diagnosed SARS-CoV-2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID-19 vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period.

Results

Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17,831 first-diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults.

Conclusions

Mortality was strongly associated with suboptimal HIV control, and the prevalence of these risk factors increased in later COVID-19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimized.", + "laySummary": "", + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jia2.26104; doi:https://doi.org/10.1002/jia2.26104; html:https://europepmc.org/articles/PMC10281639; pdf:https://europepmc.org/articles/PMC10281639?pdf=render" + }, { "id": "36482104", "doi": "https://doi.org/10.1038/s41591-022-02100-x", @@ -29596,23 +29596,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41591-022-02100-x.pdf; doi:https://doi.org/10.1038/s41591-022-02100-x; html:https://europepmc.org/articles/PMC9800274; pdf:https://europepmc.org/articles/PMC9800274?pdf=render" }, - { - "id": "37348789", - "doi": "https://doi.org/10.1016/j.jhep.2023.05.046", - "title": "Liver disease is a significant risk factor for cardiovascular outcomes - A UK Biobank study.", - "authorString": "Roca-Fernandez A, Banerjee R, Thomaides-Brears H, Telford A, Sanyal A, Neubauer S, Nichols TE, Raman B, McCracken C, Petersen SE, Ntusi NA, Cuthbertson DJ, Lai M, Dennis A, Banerjee A.", - "authorAffiliations": "", - "journalTitle": "Journal of hepatology", - "pubYear": "2023", - "date": "2023-06-20", - "isOpenAccess": "N", - "keywords": "Cardiac; MRI; Imaging; Hepatic; Heart Failure; liver disease; Cvd; Nafld; Atrial Fibrilliation", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background & aims

Chronic liver disease (CLD) is associated with increased cardiovascular disease (CVD) risk. We investigated whether early signs of liver disease (measured by iron-corrected T1-mapping [cT1]) were associated with an increased risk of major CVD events.

Methods

Liver disease activity (cT1) and fat (proton density fat fraction [PDFF]) were measured using LiverMultiScan\u00ae between January 2016 and February 2020 in the UK Biobank imaging sub-study. Using multivariable Cox regression, we explored associations between liver cT1 (MRI) and primary CVD (coronary artery disease, atrial fibrillation [AF], embolism/vascular events, heart failure [HF] and stroke), and CVD hospitalisation and all-cause mortality. Liver blood biomarkers, general metabolism biomarkers, and demographics were also included. Subgroup analysis was conducted in those without metabolic syndrome (defined as at least three of: a large waist, high triglycerides, low high-density lipoprotein cholesterol, increased systolic blood pressure, or elevated haemoglobin A1c).

Results

A total of 33,616 participants (mean age 65 years, mean BMI 26\u00a0kg/m2, mean haemoglobin A1c 35\u00a0mmol/mol) had complete MRI liver data with linked clinical outcomes (median time to major CVD event onset: 1.4 years [range: 0.002-5.1]; follow-up: 2.5 years [range: 1.1-5.2]). Liver disease activity (cT1), but not liver fat (PDFF), was associated with higher risk of any major CVD event (hazard ratio 1.14; 95% CI 1.03-1.26; p\u00a0= 0.008), AF (1.30; 1.12-1.51; p <0.001); HF (1.30; 1.09-1.56; p= 0.004); CVD hospitalisation (1.27; 1.18-1.37; p <0.001) and all-cause mortality (1.19; 1.02-1.38; p\u00a0= 0.026). FIB-4 index was associated with HF (1.06; 1.01-1.10; p\u00a0= 0.007). Risk of CVD hospitalisation was independently associated with cT1 in individuals without metabolic syndrome (1.26; 1.13-1.4; p <0.001).

Conclusion

Liver disease activity, by cT1, was independently associated with a higher risk of incident CVD and all-cause mortality, independent of pre-existing metabolic syndrome, liver fibrosis or fat.

Impact and implications

Chronic liver disease (CLD) is associated with a twofold greater incidence of cardiovascular disease. Our work shows that early liver disease on iron-corrected T1 mapping was associated with a higher risk of major cardiovascular disease (14%), cardiovascular disease hospitalisation (27%) and all-cause mortality (19%). These findings highlight the prognostic relevance of a comprehensive evaluation of liver health in populations at risk of CVD and/or CLD, even in the absence of clinical manifestations or metabolic syndrome, when there is an opportunity to modify/address risk factors and prevent disease progression. As such, they are relevant to patients, carers, clinicians, and policymakers.", - "laySummary": "", - "urls": "pdf:http://www.journal-of-hepatology.eu/article/S0168827823004208/pdf; doi:https://doi.org/10.1016/j.jhep.2023.05.046" - }, { "id": "32401709", "doi": "https://doi.org/10.1016/s2468-2667(20)30112-2", @@ -29630,6 +29613,23 @@ "laySummary": "Chandan et al. comment on the effect the covid pandemic may have on domestic violence and propose surveillance for domestic violence is needed. ", "urls": "pdf:http://www.thelancet.com/article/S2468266720301122/pdf; doi:https://doi.org/10.1016/S2468-2667(20)30112-2; html:https://europepmc.org/articles/PMC7252171; pdf:https://europepmc.org/articles/PMC7252171?pdf=render" }, + { + "id": "37348789", + "doi": "https://doi.org/10.1016/j.jhep.2023.05.046", + "title": "Liver disease is a significant risk factor for cardiovascular outcomes - A UK Biobank study.", + "authorString": "Roca-Fernandez A, Banerjee R, Thomaides-Brears H, Telford A, Sanyal A, Neubauer S, Nichols TE, Raman B, McCracken C, Petersen SE, Ntusi NA, Cuthbertson DJ, Lai M, Dennis A, Banerjee A.", + "authorAffiliations": "", + "journalTitle": "Journal of hepatology", + "pubYear": "2023", + "date": "2023-06-20", + "isOpenAccess": "N", + "keywords": "Cardiac; MRI; Imaging; Hepatic; Heart Failure; liver disease; Cvd; Nafld; Atrial Fibrilliation", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background & aims

Chronic liver disease (CLD) is associated with increased cardiovascular disease (CVD) risk. We investigated whether early signs of liver disease (measured by iron-corrected T1-mapping [cT1]) were associated with an increased risk of major CVD events.

Methods

Liver disease activity (cT1) and fat (proton density fat fraction [PDFF]) were measured using LiverMultiScan\u00ae between January 2016 and February 2020 in the UK Biobank imaging sub-study. Using multivariable Cox regression, we explored associations between liver cT1 (MRI) and primary CVD (coronary artery disease, atrial fibrillation [AF], embolism/vascular events, heart failure [HF] and stroke), and CVD hospitalisation and all-cause mortality. Liver blood biomarkers, general metabolism biomarkers, and demographics were also included. Subgroup analysis was conducted in those without metabolic syndrome (defined as at least three of: a large waist, high triglycerides, low high-density lipoprotein cholesterol, increased systolic blood pressure, or elevated haemoglobin A1c).

Results

A total of 33,616 participants (mean age 65 years, mean BMI 26\u00a0kg/m2, mean haemoglobin A1c 35\u00a0mmol/mol) had complete MRI liver data with linked clinical outcomes (median time to major CVD event onset: 1.4 years [range: 0.002-5.1]; follow-up: 2.5 years [range: 1.1-5.2]). Liver disease activity (cT1), but not liver fat (PDFF), was associated with higher risk of any major CVD event (hazard ratio 1.14; 95% CI 1.03-1.26; p\u00a0= 0.008), AF (1.30; 1.12-1.51; p <0.001); HF (1.30; 1.09-1.56; p= 0.004); CVD hospitalisation (1.27; 1.18-1.37; p <0.001) and all-cause mortality (1.19; 1.02-1.38; p\u00a0= 0.026). FIB-4 index was associated with HF (1.06; 1.01-1.10; p\u00a0= 0.007). Risk of CVD hospitalisation was independently associated with cT1 in individuals without metabolic syndrome (1.26; 1.13-1.4; p <0.001).

Conclusion

Liver disease activity, by cT1, was independently associated with a higher risk of incident CVD and all-cause mortality, independent of pre-existing metabolic syndrome, liver fibrosis or fat.

Impact and implications

Chronic liver disease (CLD) is associated with a twofold greater incidence of cardiovascular disease. Our work shows that early liver disease on iron-corrected T1 mapping was associated with a higher risk of major cardiovascular disease (14%), cardiovascular disease hospitalisation (27%) and all-cause mortality (19%). These findings highlight the prognostic relevance of a comprehensive evaluation of liver health in populations at risk of CVD and/or CLD, even in the absence of clinical manifestations or metabolic syndrome, when there is an opportunity to modify/address risk factors and prevent disease progression. As such, they are relevant to patients, carers, clinicians, and policymakers.", + "laySummary": "", + "urls": "pdf:http://www.journal-of-hepatology.eu/article/S0168827823004208/pdf; doi:https://doi.org/10.1016/j.jhep.2023.05.046" + }, { "id": "35244709", "doi": "https://doi.org/10.1093/europace/euac022", @@ -29647,23 +29647,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/europace/euac022; doi:https://doi.org/10.1093/europace/euac022; html:https://europepmc.org/articles/PMC9326851; pdf:https://europepmc.org/articles/PMC9326851?pdf=render" }, - { - "id": "36869930", - "doi": "https://doi.org/10.1007/s00520-023-07633-6", - "title": "Cost consequences of unscheduled emergency admissions in cancer patients in the last year of life.", - "authorString": "McFerran E, Cairnduff V, Elder R, Gavin A, Lawler M.", - "authorAffiliations": "", - "journalTitle": "Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer", - "pubYear": "2023", - "date": "2023-03-04", - "isOpenAccess": "Y", - "keywords": "Neoplasms; Death; Palliative care; Emergency Care; Cost Consequences", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

Cancer is a leading cause of death. This paper examines the utilisation of unscheduled emergency end-of-life healthcare and estimates expenditure in this domain. We explore care patterns and quantify the likely benefits from service reconfigurations which may influence rates of hospital admission and deaths.

Methods

Using prevalence-based retrospective data from the Northern Ireland General Registrar's Office linked by cancer diagnosis to Patient Administration episode data for unscheduled emergency care (1st January 2014 to 31st December 2015), we estimate unscheduled-emergency-care costs in the last year of life. We model potential resources released by reductions in length-of-stay for cancer patients. Linear regression examined patient characteristics affecting length of stay.

Results

A total of 3134 cancer patients used 60,746 days of unscheduled emergency care (average 19.5 days). Of these, 48.9% had \u22651 admission during their last 28 days of life. Total estimated cost was \u00a328,684,261, averaging \u00a39200 per person. Lung cancer patients had the highest proportion of admissions (23.2%, mean length of stay = 17.9 days, mean cost=\u00a37224). The highest service use and total cost was in those diagnosed at stage IV (38.4%), who\u00a0required 22,099 days of care, costing \u00a39,629,014. Palliative care support, identified in 25.5% of patients, contributed \u00a31,322,328. A 3-day reduction in\u00a0the mean length of stay with a 10% reduction in admissions, could reduce costs by \u00a37.37 million. Regression analyses explained 41% of length-of-stay variability.

Conclusions

The cost burden from unscheduled care use in the last year of life of cancer patients is significant. Opportunities to prioritise service reconfiguration for high-costing users emphasized lung and colorectal cancers as offering the greatest potential to influence outcomes.", - "laySummary": "", - "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07633-6.pdf; doi:https://doi.org/10.1007/s00520-023-07633-6; html:https://europepmc.org/articles/PMC9985568; pdf:https://europepmc.org/articles/PMC9985568?pdf=render" - }, { "id": "34173614", "doi": "https://doi.org/10.1016/s2666-7568(20)30012-x", @@ -29681,6 +29664,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/s2666-7568(20)30012-x; doi:https://doi.org/10.1016/S2666-7568(20)30012-X; html:https://europepmc.org/articles/PMC7574931; pdf:https://europepmc.org/articles/PMC7574931?pdf=render" }, + { + "id": "36869930", + "doi": "https://doi.org/10.1007/s00520-023-07633-6", + "title": "Cost consequences of unscheduled emergency admissions in cancer patients in the last year of life.", + "authorString": "McFerran E, Cairnduff V, Elder R, Gavin A, Lawler M.", + "authorAffiliations": "", + "journalTitle": "Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer", + "pubYear": "2023", + "date": "2023-03-04", + "isOpenAccess": "Y", + "keywords": "Neoplasms; Death; Palliative care; Emergency Care; Cost Consequences", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

Cancer is a leading cause of death. This paper examines the utilisation of unscheduled emergency end-of-life healthcare and estimates expenditure in this domain. We explore care patterns and quantify the likely benefits from service reconfigurations which may influence rates of hospital admission and deaths.

Methods

Using prevalence-based retrospective data from the Northern Ireland General Registrar's Office linked by cancer diagnosis to Patient Administration episode data for unscheduled emergency care (1st January 2014 to 31st December 2015), we estimate unscheduled-emergency-care costs in the last year of life. We model potential resources released by reductions in length-of-stay for cancer patients. Linear regression examined patient characteristics affecting length of stay.

Results

A total of 3134 cancer patients used 60,746 days of unscheduled emergency care (average 19.5 days). Of these, 48.9% had \u22651 admission during their last 28 days of life. Total estimated cost was \u00a328,684,261, averaging \u00a39200 per person. Lung cancer patients had the highest proportion of admissions (23.2%, mean length of stay = 17.9 days, mean cost=\u00a37224). The highest service use and total cost was in those diagnosed at stage IV (38.4%), who\u00a0required 22,099 days of care, costing \u00a39,629,014. Palliative care support, identified in 25.5% of patients, contributed \u00a31,322,328. A 3-day reduction in\u00a0the mean length of stay with a 10% reduction in admissions, could reduce costs by \u00a37.37 million. Regression analyses explained 41% of length-of-stay variability.

Conclusions

The cost burden from unscheduled care use in the last year of life of cancer patients is significant. Opportunities to prioritise service reconfiguration for high-costing users emphasized lung and colorectal cancers as offering the greatest potential to influence outcomes.", + "laySummary": "", + "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07633-6.pdf; doi:https://doi.org/10.1007/s00520-023-07633-6; html:https://europepmc.org/articles/PMC9985568; pdf:https://europepmc.org/articles/PMC9985568?pdf=render" + }, { "id": "34930919", "doi": "https://doi.org/10.1038/s41467-021-26280-1", @@ -30021,23 +30021,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.7189/jogh.11.01010; doi:https://doi.org/10.7189/jogh.11.01010; html:https://europepmc.org/articles/PMC8763336; pdf:https://europepmc.org/articles/PMC8763336?pdf=render" }, - { - "id": "38280393", - "doi": "https://doi.org/10.1016/s2352-3018(23)00272-2", - "title": "Longitudinal trends in causes of death among adults with HIV on antiretroviral therapy in Europe and North America from 1996 to 2020: a collaboration of cohort studies.", - "authorString": "Trickey A, McGinnis K, Gill MJ, Abgrall S, Berenguer J, Wyen C, Hessamfar M, Reiss P, Kusejko K, Silverberg MJ, Imaz A, Teira R, d'Arminio Monforte A, Zangerle R, Guest JL, Papastamopoulos V, Crane H, Sterling TR, Grabar S, Ingle SM, Sterne JAC.", - "authorAffiliations": "", - "journalTitle": "The lancet. HIV", - "pubYear": "2024", - "date": "2024-01-24", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Mortality rates among people with HIV have fallen since 1996 following the widespread availability of effective antiretroviral therapy (ART). Patterns of cause-specific mortality are evolving as the population with HIV ages. We aimed to investigate longitudinal trends in cause-specific mortality among people with HIV starting ART in Europe and North America.

Methods

In this collaborative observational cohort study, we used data from 17 European and North American HIV cohorts contributing data to the Antiretroviral Therapy Cohort Collaboration. We included data for people with HIV who started ART between 1996 and 2020 at the age of 16 years or older. Causes of death were classified into a single cause by both a clinician and an algorithm if International Classification of Diseases, Ninth Revision or Tenth Revision data were available, or independently by two clinicians. Disagreements were resolved through panel discussion. We used Poisson models to compare cause-specific mortality rates during the calendar periods 1996-99, 2000-03, 2004-07, 2008-11, 2012-15, and 2016-20, adjusted for time-updated age, CD4 count, and whether the individual was ART-naive at the start of each period.

Findings

Among 189\u2009301 people with HIV included in this study, 16\u2009832 (8\u00b79%) deaths were recorded during 1 519\u2009200 person-years of follow-up. 13\u2009180 (78\u00b73%) deaths were classified by cause: the most common causes were AIDS (4203 deaths; 25\u00b70%), non-AIDS non-hepatitis malignancy (2311; 13\u00b77%), and cardiovascular or heart-related (1403; 8\u00b73%) mortality. The proportion of deaths due to AIDS declined from 49% during 1996-99 to 16% during 2016-20. Rates of all-cause mortality per 1000 person-years decreased from 16\u00b78 deaths (95% CI 15\u00b74-18\u00b74) during 1996-99 to 7\u00b79 deaths (7\u00b76-8\u00b72) during 2016-20. Rates of all-cause mortality declined with time: the average adjusted mortality rate ratio per calendar period was 0\u00b785 (95% CI 0\u00b784-0\u00b786). Rates of cause-specific mortality also declined: the most pronounced reduction was for AIDS-related mortality (0\u00b781; 0\u00b779-0\u00b783). There were also reductions in rates of cardiovascular-related (0\u00b783, 0\u00b779-0\u00b787), liver-related (0\u00b788, 0\u00b784-0\u00b793), non-AIDS infection-related (0\u00b791, 0\u00b786-0\u00b796), non-AIDS-non-hepatocellular carcinoma malignancy-related (0\u00b794, 0\u00b790-0\u00b797), and suicide or accident-related mortality (0\u00b789, 0\u00b782-0\u00b795). Mortality rates among people who acquired HIV through injecting drug use increased in women (1\u00b707, 1\u00b700-1\u00b714) and decreased slightly in men (0\u00b796, 0\u00b793-0\u00b799).

Interpretation

Reductions of most major causes of death, particularly AIDS-related deaths among people with HIV on ART, were not seen for all subgroups. Interventions targeted at high-risk groups, substance use, and comorbidities might further increase life expectancy in people with HIV towards that in the general population.

Funding

US National Institute on Alcohol Abuse and Alcoholism.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S2352-3018(23)00272-2" - }, { "id": "32935062", "doi": "https://doi.org/10.23889/ijpds.v5i2.1383", @@ -30055,6 +30038,23 @@ "laySummary": "", "urls": "pdf:https://ijpds.org/article/download/1383/2566; doi:https://doi.org/10.23889/ijpds.v5i2.1383; html:https://europepmc.org/articles/PMC7473253; pdf:https://europepmc.org/articles/PMC7473253?pdf=render" }, + { + "id": "38280393", + "doi": "https://doi.org/10.1016/s2352-3018(23)00272-2", + "title": "Longitudinal trends in causes of death among adults with HIV on antiretroviral therapy in Europe and North America from 1996 to 2020: a collaboration of cohort studies.", + "authorString": "Trickey A, McGinnis K, Gill MJ, Abgrall S, Berenguer J, Wyen C, Hessamfar M, Reiss P, Kusejko K, Silverberg MJ, Imaz A, Teira R, d'Arminio Monforte A, Zangerle R, Guest JL, Papastamopoulos V, Crane H, Sterling TR, Grabar S, Ingle SM, Sterne JAC.", + "authorAffiliations": "", + "journalTitle": "The lancet. HIV", + "pubYear": "2024", + "date": "2024-01-24", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Mortality rates among people with HIV have fallen since 1996 following the widespread availability of effective antiretroviral therapy (ART). Patterns of cause-specific mortality are evolving as the population with HIV ages. We aimed to investigate longitudinal trends in cause-specific mortality among people with HIV starting ART in Europe and North America.

Methods

In this collaborative observational cohort study, we used data from 17 European and North American HIV cohorts contributing data to the Antiretroviral Therapy Cohort Collaboration. We included data for people with HIV who started ART between 1996 and 2020 at the age of 16 years or older. Causes of death were classified into a single cause by both a clinician and an algorithm if International Classification of Diseases, Ninth Revision or Tenth Revision data were available, or independently by two clinicians. Disagreements were resolved through panel discussion. We used Poisson models to compare cause-specific mortality rates during the calendar periods 1996-99, 2000-03, 2004-07, 2008-11, 2012-15, and 2016-20, adjusted for time-updated age, CD4 count, and whether the individual was ART-naive at the start of each period.

Findings

Among 189\u2009301 people with HIV included in this study, 16\u2009832 (8\u00b79%) deaths were recorded during 1 519\u2009200 person-years of follow-up. 13\u2009180 (78\u00b73%) deaths were classified by cause: the most common causes were AIDS (4203 deaths; 25\u00b70%), non-AIDS non-hepatitis malignancy (2311; 13\u00b77%), and cardiovascular or heart-related (1403; 8\u00b73%) mortality. The proportion of deaths due to AIDS declined from 49% during 1996-99 to 16% during 2016-20. Rates of all-cause mortality per 1000 person-years decreased from 16\u00b78 deaths (95% CI 15\u00b74-18\u00b74) during 1996-99 to 7\u00b79 deaths (7\u00b76-8\u00b72) during 2016-20. Rates of all-cause mortality declined with time: the average adjusted mortality rate ratio per calendar period was 0\u00b785 (95% CI 0\u00b784-0\u00b786). Rates of cause-specific mortality also declined: the most pronounced reduction was for AIDS-related mortality (0\u00b781; 0\u00b779-0\u00b783). There were also reductions in rates of cardiovascular-related (0\u00b783, 0\u00b779-0\u00b787), liver-related (0\u00b788, 0\u00b784-0\u00b793), non-AIDS infection-related (0\u00b791, 0\u00b786-0\u00b796), non-AIDS-non-hepatocellular carcinoma malignancy-related (0\u00b794, 0\u00b790-0\u00b797), and suicide or accident-related mortality (0\u00b789, 0\u00b782-0\u00b795). Mortality rates among people who acquired HIV through injecting drug use increased in women (1\u00b707, 1\u00b700-1\u00b714) and decreased slightly in men (0\u00b796, 0\u00b793-0\u00b799).

Interpretation

Reductions of most major causes of death, particularly AIDS-related deaths among people with HIV on ART, were not seen for all subgroups. Interventions targeted at high-risk groups, substance use, and comorbidities might further increase life expectancy in people with HIV towards that in the general population.

Funding

US National Institute on Alcohol Abuse and Alcoholism.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/S2352-3018(23)00272-2" + }, { "id": "36343994", "doi": "https://doi.org/10.1136/bmjopen-2022-063159", @@ -30191,23 +30191,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/cen.13990" }, - { - "id": "36093379", - "doi": "https://doi.org/10.1016/j.isci.2022.105079", - "title": "Epidemiologic information discovery from open-access COVID-19 case reports via pretrained language model.", - "authorString": "Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wong ZSY, Xu XK, Sun Y.", - "authorAffiliations": "", - "journalTitle": "iScience", - "pubYear": "2022", - "date": "2022-09-05", - "isOpenAccess": "Y", - "keywords": "Artificial intelligence; Virology; Machine Learning; Health Sciences", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Although open-access data are increasingly common and useful to epidemiological research, the curation of such datasets is resource-intensive and time-consuming. Despite the existence of a major source of COVID-19 data, the regularly disclosed case reports were often written in natural language with an unstructured format. Here, we propose a computational framework that can automatically extract epidemiological information from open-access COVID-19 case reports. We develop this framework by coupling a language model developed using deep neural networks with training samples compiled using an optimized data annotation strategy. When applied to the COVID-19 case reports collected from mainland China, our framework outperforms all other state-of-the-art deep learning models. The information extracted from our approach is highly consistent with that obtained from the gold-standard manual coding, with a matching rate of 80%. To disseminate our algorithm, we provide an open-access online platform that is able to estimate key epidemiological statistics in real time, with much less effort for data curation.", - "laySummary": "", - "urls": "pdf:http://www.cell.com/article/S2589004222013517/pdf; doi:https://doi.org/10.1016/j.isci.2022.105079; html:https://europepmc.org/articles/PMC9441477; pdf:https://europepmc.org/articles/PMC9441477?pdf=render" - }, { "id": "33306713", "doi": "https://doi.org/10.1371/journal.pone.0243383", @@ -30225,6 +30208,23 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0243383&type=printable; doi:https://doi.org/10.1371/journal.pone.0243383; html:https://europepmc.org/articles/PMC7732076; pdf:https://europepmc.org/articles/PMC7732076?pdf=render" }, + { + "id": "36093379", + "doi": "https://doi.org/10.1016/j.isci.2022.105079", + "title": "Epidemiologic information discovery from open-access COVID-19 case reports via pretrained language model.", + "authorString": "Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wong ZSY, Xu XK, Sun Y.", + "authorAffiliations": "", + "journalTitle": "iScience", + "pubYear": "2022", + "date": "2022-09-05", + "isOpenAccess": "Y", + "keywords": "Artificial intelligence; Virology; Machine Learning; Health Sciences", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Although open-access data are increasingly common and useful to epidemiological research, the curation of such datasets is resource-intensive and time-consuming. Despite the existence of a major source of COVID-19 data, the regularly disclosed case reports were often written in natural language with an unstructured format. Here, we propose a computational framework that can automatically extract epidemiological information from open-access COVID-19 case reports. We develop this framework by coupling a language model developed using deep neural networks with training samples compiled using an optimized data annotation strategy. When applied to the COVID-19 case reports collected from mainland China, our framework outperforms all other state-of-the-art deep learning models. The information extracted from our approach is highly consistent with that obtained from the gold-standard manual coding, with a matching rate of 80%. To disseminate our algorithm, we provide an open-access online platform that is able to estimate key epidemiological statistics in real time, with much less effort for data curation.", + "laySummary": "", + "urls": "pdf:http://www.cell.com/article/S2589004222013517/pdf; doi:https://doi.org/10.1016/j.isci.2022.105079; html:https://europepmc.org/articles/PMC9441477; pdf:https://europepmc.org/articles/PMC9441477?pdf=render" + }, { "id": "37719788", "doi": "https://doi.org/10.1093/noajnl/vdad096", @@ -30361,23 +30361,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.12688/wellcomeopenres.16431.2; html:https://europepmc.org/articles/PMC7901498; pdf:https://europepmc.org/articles/PMC7901498?pdf=render" }, - { - "id": "38438269", - "doi": "https://doi.org/10.3399/bjgp.2023.0214", - "title": "Post-hospitalisation asthma management in primary care: a retrospective cohort study.", - "authorString": "Punyadasa D, Simms-Williams N, Adderley NJ, Thayakaran R, Mansur AH, Nirantharakumar K, Nagakumar P, Haroon S.", - "authorAffiliations": "", - "journalTitle": "The British journal of general practice : the journal of the Royal College of General Practitioners", - "pubYear": "2024", - "date": "2024-05-30", - "isOpenAccess": "Y", - "keywords": "Management; Asthma; Cohort studies; Primary Health Care; Ethnic And Racial Minorities; Post-hospitalisation", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Clinical guidelines recommend that patients admitted to hospital for asthma attacks are reviewed in primary care following hospital discharge.

Aim

To evaluate asthma management in primary care following a hospital admission for asthma and its associations with patient characteristics.

Design and setting

A retrospective cohort study using English primary care data from the Clinical Practice Research Datalink Aurum database and linked Hospital Episode Statistics Admitted Patient Care data.

Method

Patients with asthma aged \u22655 years who had at least one asthma-related hospital admission from 1 January 2017 to 31 December 2019 were included. The primary outcome was a composite of any of the following delivered in primary care within 28 days from hospital discharge: asthma review, asthma management plan, asthma medication prescriptions, demonstration of inhaler technique, or smoking cessation counselling. The association between patient characteristics and delivery of clinical care was assessed using logistic regression.

Results

The study included 17 457 patients. A total of 10 515 (60.2%) patients received the primary outcome within 28 days of hospital discharge. There were 2311 (13.2%) who received an asthma review, 1459 (8.4%) an asthma management plan, 9996 (57.3%) an asthma medication, 1500 (8.6%) a demonstration of inhaler technique, and 52 (1.2% of smokers) had smoking cessation counselling. Patients from Black ethnic minority groups received less of this care (27%-54% lower odds, depending on age). However, short-acting bronchodilator prescriptions in the previous year were associated with an increased likelihood of the primary outcome.

Conclusion

A significant proportion of patients do not receive timely follow-up in primary care following asthma-related admissions to hospital, particularly among Black ethnic minority groups.", - "laySummary": "", - "urls": "doi:https://doi.org/10.3399/BJGP.2023.0214; html:https://europepmc.org/articles/PMC10947362; pdf:https://europepmc.org/articles/PMC10947362?pdf=render" - }, { "id": "32807724", "doi": "https://doi.org/10.1016/j.auec.2020.07.007", @@ -30412,6 +30395,23 @@ "laySummary": "", "urls": "pdf:https://cronfa.swan.ac.uk/Record/cronfa50368/Download/0050368-25062019091637.pdf; doi:https://doi.org/10.1016/j.burns.2019.04.006" }, + { + "id": "38438269", + "doi": "https://doi.org/10.3399/bjgp.2023.0214", + "title": "Post-hospitalisation asthma management in primary care: a retrospective cohort study.", + "authorString": "Punyadasa D, Simms-Williams N, Adderley NJ, Thayakaran R, Mansur AH, Nirantharakumar K, Nagakumar P, Haroon S.", + "authorAffiliations": "", + "journalTitle": "The British journal of general practice : the journal of the Royal College of General Practitioners", + "pubYear": "2024", + "date": "2024-05-30", + "isOpenAccess": "Y", + "keywords": "Management; Asthma; Cohort studies; Primary Health Care; Ethnic And Racial Minorities; Post-hospitalisation", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Clinical guidelines recommend that patients admitted to hospital for asthma attacks are reviewed in primary care following hospital discharge.

Aim

To evaluate asthma management in primary care following a hospital admission for asthma and its associations with patient characteristics.

Design and setting

A retrospective cohort study using English primary care data from the Clinical Practice Research Datalink Aurum database and linked Hospital Episode Statistics Admitted Patient Care data.

Method

Patients with asthma aged \u22655 years who had at least one asthma-related hospital admission from 1 January 2017 to 31 December 2019 were included. The primary outcome was a composite of any of the following delivered in primary care within 28 days from hospital discharge: asthma review, asthma management plan, asthma medication prescriptions, demonstration of inhaler technique, or smoking cessation counselling. The association between patient characteristics and delivery of clinical care was assessed using logistic regression.

Results

The study included 17 457 patients. A total of 10 515 (60.2%) patients received the primary outcome within 28 days of hospital discharge. There were 2311 (13.2%) who received an asthma review, 1459 (8.4%) an asthma management plan, 9996 (57.3%) an asthma medication, 1500 (8.6%) a demonstration of inhaler technique, and 52 (1.2% of smokers) had smoking cessation counselling. Patients from Black ethnic minority groups received less of this care (27%-54% lower odds, depending on age). However, short-acting bronchodilator prescriptions in the previous year were associated with an increased likelihood of the primary outcome.

Conclusion

A significant proportion of patients do not receive timely follow-up in primary care following asthma-related admissions to hospital, particularly among Black ethnic minority groups.", + "laySummary": "", + "urls": "doi:https://doi.org/10.3399/BJGP.2023.0214; html:https://europepmc.org/articles/PMC10947362; pdf:https://europepmc.org/articles/PMC10947362?pdf=render" + }, { "id": "35513530", "doi": "https://doi.org/10.1038/s41591-022-01781-8", @@ -30463,23 +30463,6 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S221326002300262X/pdf; doi:https://doi.org/10.1016/S2213-2600(23)00262-X; html:https://europepmc.org/articles/PMC7615263; pdf:https://europepmc.org/articles/PMC7615263?pdf=render" }, - { - "id": "34611362", - "doi": "https://doi.org/10.1038/s41588-021-00944-6", - "title": "Polygenic basis and biomedical consequences of telomere length variation.", - "authorString": "Codd V, Wang Q, Allara E, Musicha C, Kaptoge S, Stoma S, Jiang T, Hamby SE, Braund PS, Bountziouka V, Budgeon CA, Denniff M, Swinfield C, Papakonstantinou M, Sheth S, Nanus DE, Warner SC, Wang M, Khera AV, Eales J, Ouwehand WH, Thompson JR, Di Angelantonio E, Wood AM, Butterworth AS, Danesh JN, Nelson CP, Samani NJ.", - "authorAffiliations": "", - "journalTitle": "Nature genetics", - "pubYear": "2021", - "date": "2021-10-05", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Telomeres, the end fragments of chromosomes, play key roles in cellular proliferation and senescence. Here we characterize the genetic architecture of naturally occurring variation in leukocyte telomere length (LTL) and identify causal links between LTL and biomedical phenotypes in 472,174 well-characterized UK Biobank participants. We identified 197 independent sentinel variants associated with LTL at 138 genomic loci (108 new). Genetically determined differences in LTL were associated with multiple biological traits, ranging from height to bone marrow function, as well as several diseases spanning neoplastic, vascular and inflammatory pathologies. Finally, we estimated that, at the age of 40\u2009years, people with an LTL >1\u2009s.d. shorter than the population mean had a 2.5-year-lower life expectancy compared with the group with \u22651\u2009s.d. longer LDL. Overall, we furnish new insights into the genetic regulation of LTL, reveal wide-ranging influences of LTL on physiological traits, diseases and longevity, and provide a powerful resource available to the global research community.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41588-021-00944-6.pdf; doi:https://doi.org/10.1038/s41588-021-00944-6; html:https://europepmc.org/articles/PMC8492471; pdf:https://europepmc.org/articles/PMC8492471?pdf=render" - }, { "id": "33472714", "doi": "https://doi.org/10.1017/s1368980021000197", @@ -30497,6 +30480,23 @@ "laySummary": "", "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/274F1A424FA99A10625C3447D256A318/S1368980021000197a.pdf/div-class-title-diet-and-risk-of-gastro-oesophageal-reflux-disease-in-the-melbourne-collaborative-cohort-study-div.pdf; doi:https://doi.org/10.1017/S1368980021000197; html:https://europepmc.org/articles/PMC11082811; pdf:https://europepmc.org/articles/PMC11082811?pdf=render; doi:https://doi.org/10.1017/s1368980021000197" }, + { + "id": "34611362", + "doi": "https://doi.org/10.1038/s41588-021-00944-6", + "title": "Polygenic basis and biomedical consequences of telomere length variation.", + "authorString": "Codd V, Wang Q, Allara E, Musicha C, Kaptoge S, Stoma S, Jiang T, Hamby SE, Braund PS, Bountziouka V, Budgeon CA, Denniff M, Swinfield C, Papakonstantinou M, Sheth S, Nanus DE, Warner SC, Wang M, Khera AV, Eales J, Ouwehand WH, Thompson JR, Di Angelantonio E, Wood AM, Butterworth AS, Danesh JN, Nelson CP, Samani NJ.", + "authorAffiliations": "", + "journalTitle": "Nature genetics", + "pubYear": "2021", + "date": "2021-10-05", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Telomeres, the end fragments of chromosomes, play key roles in cellular proliferation and senescence. Here we characterize the genetic architecture of naturally occurring variation in leukocyte telomere length (LTL) and identify causal links between LTL and biomedical phenotypes in 472,174 well-characterized UK Biobank participants. We identified 197 independent sentinel variants associated with LTL at 138 genomic loci (108 new). Genetically determined differences in LTL were associated with multiple biological traits, ranging from height to bone marrow function, as well as several diseases spanning neoplastic, vascular and inflammatory pathologies. Finally, we estimated that, at the age of 40\u2009years, people with an LTL >1\u2009s.d. shorter than the population mean had a 2.5-year-lower life expectancy compared with the group with \u22651\u2009s.d. longer LDL. Overall, we furnish new insights into the genetic regulation of LTL, reveal wide-ranging influences of LTL on physiological traits, diseases and longevity, and provide a powerful resource available to the global research community.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41588-021-00944-6.pdf; doi:https://doi.org/10.1038/s41588-021-00944-6; html:https://europepmc.org/articles/PMC8492471; pdf:https://europepmc.org/articles/PMC8492471?pdf=render" + }, { "id": "33986429", "doi": "https://doi.org/10.1038/s41598-021-89743-x", @@ -30565,23 +30565,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41366-021-00896-1.pdf; doi:https://doi.org/10.1038/s41366-021-00896-1; html:https://europepmc.org/articles/PMC8455324; pdf:https://europepmc.org/articles/PMC8455324?pdf=render" }, - { - "id": "36215124", - "doi": "https://doi.org/10.1161/circgen.121.003598", - "title": "Gene Sequencing Identifies Perturbation in Nitric Oxide Signaling as a Nonlipid Molecular Subtype of Coronary Artery Disease.", - "authorString": "Khera AV, Wang M, Chaffin M, Emdin CA, Samani NJ, Schunkert H, Watkins H, McPherson R, Erdmann J, Elosua R, Boerwinkle E, Ardissino D, Butterworth AS, Di Angelantonio E, Naheed A, Danesh J, Chowdhury R, Krumholz HM, Sheu WH, Rich SS, Rotter JI, Chen YI, Gabriel S, Lander ES, Saleheen D, Kathiresan S.", - "authorAffiliations": "", - "journalTitle": "Circulation. Genomic and precision medicine", - "pubYear": "2022", - "date": "2022-10-10", - "isOpenAccess": "N", - "keywords": "Atherosclerosis; coronary artery disease; Genetic Association Studies; Nitric Oxide Synthase Type Iii; Precision Medicine", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

A key goal of precision medicine is to disaggregate common, complex diseases into discrete molecular subtypes. Rare coding variants in the low-density lipoprotein receptor gene (LDLR) are identified in 1% to 2% of coronary artery disease (CAD) patients, defining a molecular subtype with risk driven by hypercholesterolemia.

Methods

To search for additional subtypes, we compared the frequency of rare, predicted loss-of-function and damaging missense variants aggregated within a given gene in 41 081 CAD cases versus 217 115 controls.

Results

Rare variants in LDLR were most strongly associated with CAD, present in 1% of cases and associated with 4.4-fold increased CAD risk. A second subtype was characterized by variants in endothelial nitric oxide synthase gene (NOS3), a key enzyme regulating vascular tone, endothelial function, and platelet aggregation. A rare predicted loss-of-function or damaging missense variants in NOS3 was present in 0.6% of cases and associated with 2.42-fold increased risk of CAD (95% CI, 1.80-3.26; P=5.50\u00d710-9). These variants were associated with higher systolic blood pressure (+3.25 mm Hg; [95% CI, 1.86-4.65]; P=5.00\u00d710-6) and increased risk of hypertension (adjusted odds ratio 1.31; [95% CI, 1.14-1.51]; P=2.00\u00d710-4) but not circulating cholesterol concentrations, suggesting that, beyond lipid pathways, nitric oxide synthesis is a key nonlipid driver of CAD risk.

Conclusions

Beyond LDLR, we identified an additional nonlipid molecular subtype of CAD characterized by rare variants in the NOS3 gene.", - "laySummary": "", - "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.121.003598; doi:https://doi.org/10.1161/CIRCGEN.121.003598; html:https://europepmc.org/articles/PMC9771961; pdf:https://europepmc.org/articles/PMC9771961?pdf=render; doi:https://doi.org/10.1161/circgen.121.003598" - }, { "id": "32704413", "doi": "https://doi.org/10.1167/tvst.9.2.7", @@ -30600,21 +30583,21 @@ "urls": "pdf:https://tvst.arvojournals.org/arvo/content_public/journal/tvst/938366/i2164-2591-9-2-7_1597165820.03912.pdf; doi:https://doi.org/10.1167/tvst.9.2.7; html:https://europepmc.org/articles/PMC7346877; pdf:https://europepmc.org/articles/PMC7346877?pdf=render" }, { - "id": "37865101", - "doi": "https://doi.org/10.1016/s2213-8587(23)00253-x", - "title": "Empagliflozin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.", - "authorString": "RECOVERY Collaborative Group.", + "id": "36215124", + "doi": "https://doi.org/10.1161/circgen.121.003598", + "title": "Gene Sequencing Identifies Perturbation in Nitric Oxide Signaling as a Nonlipid Molecular Subtype of Coronary Artery Disease.", + "authorString": "Khera AV, Wang M, Chaffin M, Emdin CA, Samani NJ, Schunkert H, Watkins H, McPherson R, Erdmann J, Elosua R, Boerwinkle E, Ardissino D, Butterworth AS, Di Angelantonio E, Naheed A, Danesh J, Chowdhury R, Krumholz HM, Sheu WH, Rich SS, Rotter JI, Chen YI, Gabriel S, Lander ES, Saleheen D, Kathiresan S.", "authorAffiliations": "", - "journalTitle": "The lancet. Diabetes & endocrinology", - "pubYear": "2023", - "date": "2023-10-18", - "isOpenAccess": "Y", - "keywords": "", + "journalTitle": "Circulation. Genomic and precision medicine", + "pubYear": "2022", + "date": "2022-10-10", + "isOpenAccess": "N", + "keywords": "Atherosclerosis; coronary artery disease; Genetic Association Studies; Nitric Oxide Synthase Type Iii; Precision Medicine", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Empagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic, and haemodynamic effects. The RECOVERY trial aimed to assess its safety and efficacy in patients admitted to hospital with COVID-19.

Methods

In the randomised, controlled, open-label RECOVERY trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. In this analysis, we assess eligible and consenting adults who were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus oral empagliflozin 10 mg once daily for 28 days or until discharge (whichever came first) using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. On March 3, 2023 the independent data monitoring committee recommended that the investigators review the data and recruitment was consequently stopped on March 7, 2023. The ongoing RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between July 28, 2021 and March 6, 2023, 4271 patients were randomly allocated to receive either empagliflozin (2113 patients) or usual care alone (2158 patients). Primary and secondary outcome data were known for greater than 99% of randomly assigned patients. Overall, 289 (14%) of 2113 patients allocated to empagliflozin and 307 (14%) of 2158 patients allocated to usual care died within 28 days (rate ratio 0\u00b796 [95% CI 0\u00b782-1\u00b713]; p=0\u00b764). There was no evidence of significant differences in duration of hospitalisation (median 8 days for both groups) or the proportion of patients discharged from hospital alive within 28 days (1678 [79%] in the empagliflozin group vs 1677 [78%] in the usual care group; rate ratio 1\u00b703 [95% CI 0\u00b796-1\u00b710]; p=0\u00b744). Among those not on invasive mechanical ventilation at baseline, there was no evidence of a significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (338 [16%] of 2084 vs 371 [17%] of 2143; risk ratio 0\u00b795 [95% CI 0\u00b784-1\u00b708]; p=0\u00b744). Two serious adverse events believed to be related to empagliflozin were reported: both were ketosis without acidosis.

Interpretation

In adults hospitalised with COVID-19, empagliflozin was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death so is not indicated for the treatment of such patients unless there is an established indication due to a different condition such as diabetes.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (MC_PC_19056), and Wellcome Trust (222406/Z/20/Z).

Translations

For the Nepali, Hindi, Indonesian (Bahasa) and Vietnamese translations of the abstract see Supplementary Materials section.", + "abstract": "

Background

A key goal of precision medicine is to disaggregate common, complex diseases into discrete molecular subtypes. Rare coding variants in the low-density lipoprotein receptor gene (LDLR) are identified in 1% to 2% of coronary artery disease (CAD) patients, defining a molecular subtype with risk driven by hypercholesterolemia.

Methods

To search for additional subtypes, we compared the frequency of rare, predicted loss-of-function and damaging missense variants aggregated within a given gene in 41 081 CAD cases versus 217 115 controls.

Results

Rare variants in LDLR were most strongly associated with CAD, present in 1% of cases and associated with 4.4-fold increased CAD risk. A second subtype was characterized by variants in endothelial nitric oxide synthase gene (NOS3), a key enzyme regulating vascular tone, endothelial function, and platelet aggregation. A rare predicted loss-of-function or damaging missense variants in NOS3 was present in 0.6% of cases and associated with 2.42-fold increased risk of CAD (95% CI, 1.80-3.26; P=5.50\u00d710-9). These variants were associated with higher systolic blood pressure (+3.25 mm Hg; [95% CI, 1.86-4.65]; P=5.00\u00d710-6) and increased risk of hypertension (adjusted odds ratio 1.31; [95% CI, 1.14-1.51]; P=2.00\u00d710-4) but not circulating cholesterol concentrations, suggesting that, beyond lipid pathways, nitric oxide synthesis is a key nonlipid driver of CAD risk.

Conclusions

Beyond LDLR, we identified an additional nonlipid molecular subtype of CAD characterized by rare variants in the NOS3 gene.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S2213-8587(23)00253-X; html:https://europepmc.org/articles/PMC10957483; pdf:https://europepmc.org/articles/PMC10957483?pdf=render" + "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.121.003598; doi:https://doi.org/10.1161/CIRCGEN.121.003598; html:https://europepmc.org/articles/PMC9771961; pdf:https://europepmc.org/articles/PMC9771961?pdf=render; doi:https://doi.org/10.1161/circgen.121.003598" }, { "id": "32781946", @@ -30650,6 +30633,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/jacamr/article-pdf/5/2/dlad039/49747584/dlad039.pdf; doi:https://doi.org/10.1093/jacamr/dlad039; html:https://europepmc.org/articles/PMC10072237; pdf:https://europepmc.org/articles/PMC10072237?pdf=render" }, + { + "id": "37865101", + "doi": "https://doi.org/10.1016/s2213-8587(23)00253-x", + "title": "Empagliflozin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.", + "authorString": "RECOVERY Collaborative Group.", + "authorAffiliations": "", + "journalTitle": "The lancet. Diabetes & endocrinology", + "pubYear": "2023", + "date": "2023-10-18", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Empagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic, and haemodynamic effects. The RECOVERY trial aimed to assess its safety and efficacy in patients admitted to hospital with COVID-19.

Methods

In the randomised, controlled, open-label RECOVERY trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. In this analysis, we assess eligible and consenting adults who were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus oral empagliflozin 10 mg once daily for 28 days or until discharge (whichever came first) using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. On March 3, 2023 the independent data monitoring committee recommended that the investigators review the data and recruitment was consequently stopped on March 7, 2023. The ongoing RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between July 28, 2021 and March 6, 2023, 4271 patients were randomly allocated to receive either empagliflozin (2113 patients) or usual care alone (2158 patients). Primary and secondary outcome data were known for greater than 99% of randomly assigned patients. Overall, 289 (14%) of 2113 patients allocated to empagliflozin and 307 (14%) of 2158 patients allocated to usual care died within 28 days (rate ratio 0\u00b796 [95% CI 0\u00b782-1\u00b713]; p=0\u00b764). There was no evidence of significant differences in duration of hospitalisation (median 8 days for both groups) or the proportion of patients discharged from hospital alive within 28 days (1678 [79%] in the empagliflozin group vs 1677 [78%] in the usual care group; rate ratio 1\u00b703 [95% CI 0\u00b796-1\u00b710]; p=0\u00b744). Among those not on invasive mechanical ventilation at baseline, there was no evidence of a significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (338 [16%] of 2084 vs 371 [17%] of 2143; risk ratio 0\u00b795 [95% CI 0\u00b784-1\u00b708]; p=0\u00b744). Two serious adverse events believed to be related to empagliflozin were reported: both were ketosis without acidosis.

Interpretation

In adults hospitalised with COVID-19, empagliflozin was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death so is not indicated for the treatment of such patients unless there is an established indication due to a different condition such as diabetes.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (MC_PC_19056), and Wellcome Trust (222406/Z/20/Z).

Translations

For the Nepali, Hindi, Indonesian (Bahasa) and Vietnamese translations of the abstract see Supplementary Materials section.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/S2213-8587(23)00253-X; html:https://europepmc.org/articles/PMC10957483; pdf:https://europepmc.org/articles/PMC10957483?pdf=render" + }, { "id": "36423925", "doi": "https://doi.org/10.1136/thorax-2022-219591", @@ -30990,23 +30990,6 @@ "laySummary": "", "urls": "pdf:http://www.ajconline.org/article/S0002914921012418/pdf; doi:https://doi.org/10.1016/j.amjcard.2021.12.022" }, - { - "id": "33017023", - "doi": "https://doi.org/10.1001/jamaneurol.2020.3502", - "title": "Trends in Optic Neuritis Incidence and Prevalence in the UK and Association With Systemic and Neurologic Disease.", - "authorString": "Braithwaite T, Subramanian A, Petzold A, Galloway J, Adderley NJ, Mollan SP, Plant GT, Nirantharakumar K, Denniston AK.", - "authorAffiliations": "", - "journalTitle": "JAMA neurology", - "pubYear": "2020", - "date": "2020-12-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Importance

Epidemiologic data on optic neuritis (ON) incidence and associations with immune-mediated inflammatory diseases (IMIDs) are sparse.

Objective

To estimate 22-year trends in ON prevalence and incidence and association with IMIDs in the United Kingdom.

Design, setting, and participants

This cohort study analyzed data from The Health Improvement Network from January 1, 1995, to September 1, 2019. The study included 10\u202f937\u202f511 patients 1 year or older with 75.2 million person-years' follow-up. Annual ON incidence rates were estimated yearly (January 1, 1997, to December 31, 2018), and annual ON prevalence was estimated by performing sequential cross-sectional studies on data collected on January 1 each year for the same period. Data for 1995, 1996, and 2019 were excluded as incomplete. Risk factors for ON were explored in a cohort analysis from January 1, 1997, to December 31, 2018. Matched case-control and retrospective cohort studies were performed using data from January 1, 1995, to September 1, 2019, to explore the odds of antecedent diagnosis and hazard of incident diagnosis of 66 IMIDs in patients compared with controls.

Exposures

Optic neuritis.

Main outcomes and measures

Annual point prevalence and incidence rates of ON, adjusted incident rate ratios (IRRs) for risk factors, and adjusted odds ratios (ORs) and adjusted hazard ratios (HRs) for 66 IMIDs.

Results

A total of 10\u202f937\u202f511 patients (median [IQR] age at cohort entry, 32.6 [18.0-50.4] years; 5 571 282 [50.9%] female) were studied. A total of 1962 of 2826 patients (69.4%) with incident ON were female and 1192 of 1290 92.4%) were White, with a mean (SD) age of 35.6 (15.6) years. Overall incidence across 22 years was stable at 3.7 (95% CI, 3.6-3.9) per 100\u202f000 person-years. Annual point prevalence (per 100\u202f000 population) increased with database maturity, from 69.3 (95% CI, 57.2-81.3) in 1997 to 114.8 (95% CI, 111.0-118.6) in 2018. The highest risk of incident ON was associated with female sex, obesity, reproductive age, smoking, and residence at higher latitude, with significantly lower risk in South Asian or mixed race/ethnicity compared with White people. Patients with ON had significantly higher odds of prior multiple sclerosis (MS) (OR,\u200998.22; 95% CI, 65.40-147.52), syphilis (OR,\u20095.76; 95% CI, 1.39-23.96), Mycoplasma (OR,\u20093.90; 95% CI, 1.09-13.93), vasculitis (OR,\u20093.70; 95% CI, 1.68-8.15), sarcoidosis (OR,\u20092.50; 95% CI, 1.21-5.18), Epstein-Barr virus (OR,\u20092.29; 95% CI, 1.80-2.92), Crohn disease (OR,\u20091.97; 95% CI, 1.13-3.43), and psoriasis (OR,\u20091.28; 95% CI, 1.03-1.58). Patients with ON had a significantly higher hazard of incident MS (HR,\u2009284.97; 95% CI, 167.85-483.81), Beh\u00e7et disease (HR,\u200917.39; 95% CI, 1.55-195.53), sarcoidosis (HR,\u200914.80; 95% CI, 4.86-45.08), vasculitis (HR,\u20094.89; 95% CI, 1.82-13.10), Sj\u00f6gren syndrome (HR,\u20093.48; 95% CI, 1.38-8.76), and herpetic infection (HR,\u20091.68; 95% CI, 1.24-2.28).

Conclusions and relevance

The UK incidence of ON is stable. Even though predominantly associated with MS, ON has numerous other associations with IMIDs. Although individually rare, together these associations outnumber MS-associated ON and typically require urgent management to preserve sight.", - "laySummary": "", - "urls": "pdf:http://pure-oai.bham.ac.uk/ws/files/100688542/NEU20_1602R_Merged_PDF.pdf; doi:https://doi.org/10.1001/jamaneurol.2020.3502; html:https://europepmc.org/articles/PMC7536630; doi:https://doi.org/10.1001/jamaneurol.2020.3502" - }, { "id": "32702311", "doi": "https://doi.org/10.1016/s1470-2045(20)30392-2", @@ -31024,6 +31007,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S1470204520303922/pdf; doi:https://doi.org/10.1016/S1470-2045(20)30392-2; html:https://europepmc.org/articles/PMC7116538; pdf:https://europepmc.org/articles/PMC7116538?pdf=render" }, + { + "id": "33017023", + "doi": "https://doi.org/10.1001/jamaneurol.2020.3502", + "title": "Trends in Optic Neuritis Incidence and Prevalence in the UK and Association With Systemic and Neurologic Disease.", + "authorString": "Braithwaite T, Subramanian A, Petzold A, Galloway J, Adderley NJ, Mollan SP, Plant GT, Nirantharakumar K, Denniston AK.", + "authorAffiliations": "", + "journalTitle": "JAMA neurology", + "pubYear": "2020", + "date": "2020-12-01", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Importance

Epidemiologic data on optic neuritis (ON) incidence and associations with immune-mediated inflammatory diseases (IMIDs) are sparse.

Objective

To estimate 22-year trends in ON prevalence and incidence and association with IMIDs in the United Kingdom.

Design, setting, and participants

This cohort study analyzed data from The Health Improvement Network from January 1, 1995, to September 1, 2019. The study included 10\u202f937\u202f511 patients 1 year or older with 75.2 million person-years' follow-up. Annual ON incidence rates were estimated yearly (January 1, 1997, to December 31, 2018), and annual ON prevalence was estimated by performing sequential cross-sectional studies on data collected on January 1 each year for the same period. Data for 1995, 1996, and 2019 were excluded as incomplete. Risk factors for ON were explored in a cohort analysis from January 1, 1997, to December 31, 2018. Matched case-control and retrospective cohort studies were performed using data from January 1, 1995, to September 1, 2019, to explore the odds of antecedent diagnosis and hazard of incident diagnosis of 66 IMIDs in patients compared with controls.

Exposures

Optic neuritis.

Main outcomes and measures

Annual point prevalence and incidence rates of ON, adjusted incident rate ratios (IRRs) for risk factors, and adjusted odds ratios (ORs) and adjusted hazard ratios (HRs) for 66 IMIDs.

Results

A total of 10\u202f937\u202f511 patients (median [IQR] age at cohort entry, 32.6 [18.0-50.4] years; 5 571 282 [50.9%] female) were studied. A total of 1962 of 2826 patients (69.4%) with incident ON were female and 1192 of 1290 92.4%) were White, with a mean (SD) age of 35.6 (15.6) years. Overall incidence across 22 years was stable at 3.7 (95% CI, 3.6-3.9) per 100\u202f000 person-years. Annual point prevalence (per 100\u202f000 population) increased with database maturity, from 69.3 (95% CI, 57.2-81.3) in 1997 to 114.8 (95% CI, 111.0-118.6) in 2018. The highest risk of incident ON was associated with female sex, obesity, reproductive age, smoking, and residence at higher latitude, with significantly lower risk in South Asian or mixed race/ethnicity compared with White people. Patients with ON had significantly higher odds of prior multiple sclerosis (MS) (OR,\u200998.22; 95% CI, 65.40-147.52), syphilis (OR,\u20095.76; 95% CI, 1.39-23.96), Mycoplasma (OR,\u20093.90; 95% CI, 1.09-13.93), vasculitis (OR,\u20093.70; 95% CI, 1.68-8.15), sarcoidosis (OR,\u20092.50; 95% CI, 1.21-5.18), Epstein-Barr virus (OR,\u20092.29; 95% CI, 1.80-2.92), Crohn disease (OR,\u20091.97; 95% CI, 1.13-3.43), and psoriasis (OR,\u20091.28; 95% CI, 1.03-1.58). Patients with ON had a significantly higher hazard of incident MS (HR,\u2009284.97; 95% CI, 167.85-483.81), Beh\u00e7et disease (HR,\u200917.39; 95% CI, 1.55-195.53), sarcoidosis (HR,\u200914.80; 95% CI, 4.86-45.08), vasculitis (HR,\u20094.89; 95% CI, 1.82-13.10), Sj\u00f6gren syndrome (HR,\u20093.48; 95% CI, 1.38-8.76), and herpetic infection (HR,\u20091.68; 95% CI, 1.24-2.28).

Conclusions and relevance

The UK incidence of ON is stable. Even though predominantly associated with MS, ON has numerous other associations with IMIDs. Although individually rare, together these associations outnumber MS-associated ON and typically require urgent management to preserve sight.", + "laySummary": "", + "urls": "pdf:http://pure-oai.bham.ac.uk/ws/files/100688542/NEU20_1602R_Merged_PDF.pdf; doi:https://doi.org/10.1001/jamaneurol.2020.3502; html:https://europepmc.org/articles/PMC7536630; doi:https://doi.org/10.1001/jamaneurol.2020.3502" + }, { "id": "34347787", "doi": "https://doi.org/10.1371/journal.pone.0253809", @@ -31143,6 +31143,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.neuroimage.2022.119452; doi:https://doi.org/10.1016/j.neuroimage.2022.119452; html:https://europepmc.org/articles/PMC10933779; pdf:https://europepmc.org/articles/PMC10933779?pdf=render" }, + { + "id": "34345870", + "doi": "https://doi.org/10.1016/j.bbih.2021.100286", + "title": "The effects of genotype on inflammatory response in hippocampal progenitor cells: A computational approach.", + "authorString": "Lee H, Metz A, McDiarmid A, Palmos A, Lee SH, Curtis CJ, Patel H, Newhouse SJ, Thuret S.", + "authorAffiliations": "", + "journalTitle": "Brain, behavior, & immunity - health", + "pubYear": "2021", + "date": "2021-08-01", + "isOpenAccess": "Y", + "keywords": "Hippocampus; Neurogenesis; Inflammation; Neural stem cells; in vitro model; single nucleotide polymorphisms SNP; Eqtl; Gene Variants", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Cell culture models are valuable tools to study biological mechanisms underlying health and disease in a controlled environment. Although their genotype influences their phenotype, subtle genetic variations in cell lines are rarely characterised and taken into account for in vitro studies. To investigate how the genetic makeup of a cell line might affect the cellular response to inflammation, we characterised the single nucleotide variants (SNPs) relevant to inflammation-related genes in an established hippocampal progenitor cell line (HPC0A07/03C) that is frequently used as an in vitro model for hippocampal neurogenesis (HN). SNPs were identified using a genotyping array, and genes associated with chronic inflammatory and neuroinflammatory response gene ontology terms were retrieved using the AmiGO application. SNPs associated with these genes were then extracted from the genotyping dataset, for which a literature search was conducted, yielding relevant research articles for a total of 17 SNPs. Of these variants, 10 were found to potentially affect hippocampal neurogenesis whereby a majority (n=7) is likely to reduce neurogenesis under inflammatory conditions. Taken together, the existing literature seems to suggest that all stages of hippocampal neurogenesis could be negatively affected due to the genetic makeup in HPC0A07/03C cells under inflammation. Additional experiments will be needed to validate these specific findings in a laboratory setting. However, this computational approach already confirms that in vitro studies in general should control for cell lines subtle genetic variations which could mask or exacerbate findings.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.bbih.2021.100286; doi:https://doi.org/10.1016/j.bbih.2021.100286; html:https://europepmc.org/articles/PMC8261829; pdf:https://europepmc.org/articles/PMC8261829?pdf=render" + }, { "id": "37981722", "doi": "https://doi.org/10.1093/aje/kwad232", @@ -31177,23 +31194,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41598-022-22218-9.pdf; doi:https://doi.org/10.1038/s41598-022-22218-9; html:https://europepmc.org/articles/PMC9637114; pdf:https://europepmc.org/articles/PMC9637114?pdf=render" }, - { - "id": "34345870", - "doi": "https://doi.org/10.1016/j.bbih.2021.100286", - "title": "The effects of genotype on inflammatory response in hippocampal progenitor cells: A computational approach.", - "authorString": "Lee H, Metz A, McDiarmid A, Palmos A, Lee SH, Curtis CJ, Patel H, Newhouse SJ, Thuret S.", - "authorAffiliations": "", - "journalTitle": "Brain, behavior, & immunity - health", - "pubYear": "2021", - "date": "2021-08-01", - "isOpenAccess": "Y", - "keywords": "Hippocampus; Neurogenesis; Inflammation; Neural stem cells; in vitro model; single nucleotide polymorphisms SNP; Eqtl; Gene Variants", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Cell culture models are valuable tools to study biological mechanisms underlying health and disease in a controlled environment. Although their genotype influences their phenotype, subtle genetic variations in cell lines are rarely characterised and taken into account for in vitro studies. To investigate how the genetic makeup of a cell line might affect the cellular response to inflammation, we characterised the single nucleotide variants (SNPs) relevant to inflammation-related genes in an established hippocampal progenitor cell line (HPC0A07/03C) that is frequently used as an in vitro model for hippocampal neurogenesis (HN). SNPs were identified using a genotyping array, and genes associated with chronic inflammatory and neuroinflammatory response gene ontology terms were retrieved using the AmiGO application. SNPs associated with these genes were then extracted from the genotyping dataset, for which a literature search was conducted, yielding relevant research articles for a total of 17 SNPs. Of these variants, 10 were found to potentially affect hippocampal neurogenesis whereby a majority (n=7) is likely to reduce neurogenesis under inflammatory conditions. Taken together, the existing literature seems to suggest that all stages of hippocampal neurogenesis could be negatively affected due to the genetic makeup in HPC0A07/03C cells under inflammation. Additional experiments will be needed to validate these specific findings in a laboratory setting. However, this computational approach already confirms that in vitro studies in general should control for cell lines subtle genetic variations which could mask or exacerbate findings.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.bbih.2021.100286; doi:https://doi.org/10.1016/j.bbih.2021.100286; html:https://europepmc.org/articles/PMC8261829; pdf:https://europepmc.org/articles/PMC8261829?pdf=render" - }, { "id": "35212847", "doi": "https://doi.org/10.1007/s00455-022-10425-5", @@ -31262,23 +31262,6 @@ "laySummary": "", "urls": "pdf:https://www.karger.com/Article/Pdf/517521; doi:https://doi.org/10.1159/000517521" }, - { - "id": "37730620", - "doi": "https://doi.org/10.1186/s13643-023-02333-y", - "title": "What is known about what works in community-involved decision-making relating to urban green and blue spaces? A realist review protocol.", - "authorString": "Rahtz E, Bell SL, Nurse A, Wheeler BW, Guell C, Elliott LR, Thompson CW, McDougall CW, Lovell R.", - "authorAffiliations": "", - "journalTitle": "Systematic reviews", - "pubYear": "2023", - "date": "2023-09-20", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

There is now a relatively well-established evidence base suggesting that greener living environments and time spent in urban green and blue spaces (UGBS) can be beneficial for human health and wellbeing. However, benefits are not universal and there remain widespread social inequalities in access to such resources and experiences, particularly along axes of class, race, ethnicity, age and disability, and in relation to efforts to increase the availability and accessibility of such spaces. These injustices often relate to distributive, procedural and recognition-based processes. There is growing interest in how to ensure that efforts to increase access to or use of UGBS (whether through infrastructural or social programmes) result in equitable outcomes whilst minimising potential for exacerbating existing inequalities and injustices. Community engagement is considered an important step towards more inclusive UGBS decision-making, from planning and design to management and maintenance processes. It is thought to contribute to better and more widely trusted decisions, enhanced democracy, community satisfaction, civic interest and feelings of green space ownership, and greater longevity of UGBS projects. However, uneven representation and barriers to participation can create imbalances and undermine these benefits.

Methods

An iterative, multi-stage realist-inspired review will be conducted to ask what works, in what context and in what ways relating to the meaningful involvement of communities in UGBS decision-making, focusing on the skills, capacities and capabilities of different stakeholders and the role of contexts and processes. 'Effectiveness' (or what works) will be understood as a multifaceted outcome, encompassing both the processes and results of community engagement efforts. Following a scoping stage to identify initial programme theory, inclusion/exclusion criteria and derive search terms, relevant databases and grey literature will be searched to identify interdisciplinary literature in two phases. The first phase will be used to further develop programme theories, which will be articulated as 'if then' statements. The second phase searches will be used to identify sources to further explore and evidence the programme and formal theory. We will assess all includable evidence for conceptual richness, prioritising more conceptually rich sources if needed.

Discussion

The realist synthesis will explore the key context, mechanism and outcome configurations that appear to explain if and how different approaches to community-involved UGBS decision-making are or are not effective. We will consider factors such as different conceptualisations of community, and if and how they have been involved in UGBS decision-making; the types of tools and approaches used; and the socio-cultural and political or governance structures within which decision-making takes place.", - "laySummary": "", - "urls": "pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02333-y; doi:https://doi.org/10.1186/s13643-023-02333-y; html:https://europepmc.org/articles/PMC10512649; pdf:https://europepmc.org/articles/PMC10512649?pdf=render" - }, { "id": "35434685", "doi": "https://doi.org/10.1016/j.lanepe.2022.100381", @@ -31296,6 +31279,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.lanepe.2022.100381; doi:https://doi.org/10.1016/j.lanepe.2022.100381; html:https://europepmc.org/articles/PMC8996067; pdf:https://europepmc.org/articles/PMC8996067?pdf=render" }, + { + "id": "37730620", + "doi": "https://doi.org/10.1186/s13643-023-02333-y", + "title": "What is known about what works in community-involved decision-making relating to urban green and blue spaces? A realist review protocol.", + "authorString": "Rahtz E, Bell SL, Nurse A, Wheeler BW, Guell C, Elliott LR, Thompson CW, McDougall CW, Lovell R.", + "authorAffiliations": "", + "journalTitle": "Systematic reviews", + "pubYear": "2023", + "date": "2023-09-20", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

There is now a relatively well-established evidence base suggesting that greener living environments and time spent in urban green and blue spaces (UGBS) can be beneficial for human health and wellbeing. However, benefits are not universal and there remain widespread social inequalities in access to such resources and experiences, particularly along axes of class, race, ethnicity, age and disability, and in relation to efforts to increase the availability and accessibility of such spaces. These injustices often relate to distributive, procedural and recognition-based processes. There is growing interest in how to ensure that efforts to increase access to or use of UGBS (whether through infrastructural or social programmes) result in equitable outcomes whilst minimising potential for exacerbating existing inequalities and injustices. Community engagement is considered an important step towards more inclusive UGBS decision-making, from planning and design to management and maintenance processes. It is thought to contribute to better and more widely trusted decisions, enhanced democracy, community satisfaction, civic interest and feelings of green space ownership, and greater longevity of UGBS projects. However, uneven representation and barriers to participation can create imbalances and undermine these benefits.

Methods

An iterative, multi-stage realist-inspired review will be conducted to ask what works, in what context and in what ways relating to the meaningful involvement of communities in UGBS decision-making, focusing on the skills, capacities and capabilities of different stakeholders and the role of contexts and processes. 'Effectiveness' (or what works) will be understood as a multifaceted outcome, encompassing both the processes and results of community engagement efforts. Following a scoping stage to identify initial programme theory, inclusion/exclusion criteria and derive search terms, relevant databases and grey literature will be searched to identify interdisciplinary literature in two phases. The first phase will be used to further develop programme theories, which will be articulated as 'if then' statements. The second phase searches will be used to identify sources to further explore and evidence the programme and formal theory. We will assess all includable evidence for conceptual richness, prioritising more conceptually rich sources if needed.

Discussion

The realist synthesis will explore the key context, mechanism and outcome configurations that appear to explain if and how different approaches to community-involved UGBS decision-making are or are not effective. We will consider factors such as different conceptualisations of community, and if and how they have been involved in UGBS decision-making; the types of tools and approaches used; and the socio-cultural and political or governance structures within which decision-making takes place.", + "laySummary": "", + "urls": "pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02333-y; doi:https://doi.org/10.1186/s13643-023-02333-y; html:https://europepmc.org/articles/PMC10512649; pdf:https://europepmc.org/articles/PMC10512649?pdf=render" + }, { "id": "33453763", "doi": "https://doi.org/10.1016/s2468-1253(21)00005-4", @@ -31313,23 +31313,6 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S2468125321000054/pdf; doi:https://doi.org/10.1016/S2468-1253(21)00005-4; html:https://europepmc.org/articles/PMC7808901; pdf:https://europepmc.org/articles/PMC7808901?pdf=render" }, - { - "id": "37872160", - "doi": "https://doi.org/10.1038/s41467-023-42284-5", - "title": "Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease.", - "authorString": "Williams AT, Chen J, Coley K, Batini C, Izquierdo A, Packer R, Abner E, Kanoni S, Shepherd DJ, Free RC, Hollox EJ, Brunskill NJ, Ntalla I, Reeve N, Brightling CE, Venn L, Adams E, Bee C, Wallace SE, Pareek M, Hansell AL, Esko T, Estonian Biobank Research Team, Stow D, Jacobs BM, van Heel DA, Genes & Health Research Team, Hennah W, Rao BS, Dudbridge F, Wain LV, Shrine N, Tobin MD, John C.", - "authorAffiliations": "", - "journalTitle": "Nature communications", - "pubYear": "2023", - "date": "2023-10-23", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Thyroid hormones play a critical role in regulation of multiple physiological functions and thyroid dysfunction is associated with substantial morbidity. Here, we use electronic health records to undertake a genome-wide association study of thyroid-stimulating hormone (TSH) levels, with a total sample size of 247,107. We identify 158 novel genetic associations, more than doubling the number of known associations with TSH, and implicate 112 putative causal genes, of which 76 are not previously implicated. A polygenic score for TSH is associated with TSH levels in African, South Asian, East Asian, Middle Eastern and admixed American ancestries, and associated with hypothyroidism and other thyroid disease in South Asians. In Europeans, the TSH polygenic score is associated with thyroid disease, including thyroid cancer and age-of-onset of hypothyroidism and hyperthyroidism. We develop pathway-specific genetic risk scores for TSH levels and use these in phenome-wide association studies to identify potential consequences of pathway perturbation. Together, these findings demonstrate the potential utility of genetic associations to inform future therapeutics and risk prediction for thyroid diseases.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41467-023-42284-5.pdf; doi:https://doi.org/10.1038/s41467-023-42284-5; html:https://europepmc.org/articles/PMC10593800; pdf:https://europepmc.org/articles/PMC10593800?pdf=render" - }, { "id": "30102210", "doi": "https://doi.org/10.1016/s1470-2045(18)30425-x", @@ -31348,21 +31331,21 @@ "urls": "doi:https://doi.org/10.1016/S1470-2045(18)30425-X" }, { - "id": "33928785", - "doi": "https://doi.org/10.1161/circulationaha.120.049844", - "title": "Unfolded Protein Response as a Compensatory Mechanism and Potential Therapeutic Target in PLN R14del Cardiomyopathy.", - "authorString": "Feyen DAM, Perea-Gil I, Maas RGC, Harakalova M, Gavidia AA, Arthur Ataam J, Wu TH, Vink A, Pei J, Vadgama N, Suurmeijer AJ, Te Rijdt WP, Vu M, Amatya PL, Prado M, Zhang Y, Dunkenberger L, Sluijter JPG, Sallam K, Asselbergs FW, Mercola M, Karakikes I.", + "id": "37872160", + "doi": "https://doi.org/10.1038/s41467-023-42284-5", + "title": "Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease.", + "authorString": "Williams AT, Chen J, Coley K, Batini C, Izquierdo A, Packer R, Abner E, Kanoni S, Shepherd DJ, Free RC, Hollox EJ, Brunskill NJ, Ntalla I, Reeve N, Brightling CE, Venn L, Adams E, Bee C, Wallace SE, Pareek M, Hansell AL, Esko T, Estonian Biobank Research Team, Stow D, Jacobs BM, van Heel DA, Genes & Health Research Team, Hennah W, Rao BS, Dudbridge F, Wain LV, Shrine N, Tobin MD, John C.", "authorAffiliations": "", - "journalTitle": "Circulation", - "pubYear": "2021", - "date": "2021-04-30", - "isOpenAccess": "N", - "keywords": "Unfolded protein response; Models, Biological; Induced Pluripotent Stem Cells; Phospholamban; Cardiomyopathy, Dilated; Sequence Analysis, Rna", + "journalTitle": "Nature communications", + "pubYear": "2023", + "date": "2023-10-23", + "isOpenAccess": "Y", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Phospholamban (PLN) is a critical regulator of calcium cycling and contractility in the heart. The loss of arginine at position 14 in PLN (R14del) is associated with dilated cardiomyopathy with a high prevalence of ventricular arrhythmias. How the R14 deletion causes dilated cardiomyopathy is poorly understood, and there are no disease-specific therapies.

Methods

We used single-cell RNA sequencing to uncover PLN R14del disease mechanisms in human induced pluripotent stem cells (hiPSC-CMs). We used both 2-dimensional and 3-dimensional functional contractility assays to evaluate the impact of modulating disease-relevant pathways in PLN R14del hiPSC-CMs.

Results

Modeling of the PLN R14del cardiomyopathy with isogenic pairs of hiPSC-CMs recapitulated the contractile deficit associated with the disease in vitro. Single-cell RNA sequencing revealed the induction of the unfolded protein response (UPR) pathway in PLN R14del compared with isogenic control hiPSC-CMs. The activation of UPR was also evident in the hearts from PLN R14del patients. Silencing of each of the 3 main UPR signaling branches (IRE1, ATF6, or PERK) by siRNA exacerbated the contractile dysfunction of PLN R14del hiPSC-CMs. We explored the therapeutic potential of activating the UPR with a small molecule activator, BiP (binding immunoglobulin protein) inducer X. PLN R14del hiPSC-CMs treated with BiP protein inducer X showed a dose-dependent amelioration of the contractility deficit in both 2-dimensional cultures and 3-dimensional engineered heart tissues without affecting calcium homeostasis.

Conclusions

Together, these findings suggest that the UPR exerts a protective effect in the setting of PLN R14del cardiomyopathy and that modulation of the UPR might be exploited therapeutically.", + "abstract": "Thyroid hormones play a critical role in regulation of multiple physiological functions and thyroid dysfunction is associated with substantial morbidity. Here, we use electronic health records to undertake a genome-wide association study of thyroid-stimulating hormone (TSH) levels, with a total sample size of 247,107. We identify 158 novel genetic associations, more than doubling the number of known associations with TSH, and implicate 112 putative causal genes, of which 76 are not previously implicated. A polygenic score for TSH is associated with TSH levels in African, South Asian, East Asian, Middle Eastern and admixed American ancestries, and associated with hypothyroidism and other thyroid disease in South Asians. In Europeans, the TSH polygenic score is associated with thyroid disease, including thyroid cancer and age-of-onset of hypothyroidism and hyperthyroidism. We develop pathway-specific genetic risk scores for TSH levels and use these in phenome-wide association studies to identify potential consequences of pathway perturbation. Together, these findings demonstrate the potential utility of genetic associations to inform future therapeutics and risk prediction for thyroid diseases.", "laySummary": "", - "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.049844; doi:https://doi.org/10.1161/CIRCULATIONAHA.120.049844; html:https://europepmc.org/articles/PMC8667423; pdf:https://europepmc.org/articles/PMC8667423?pdf=render; doi:https://doi.org/10.1161/circulationaha.120.049844" + "urls": "pdf:https://www.nature.com/articles/s41467-023-42284-5.pdf; doi:https://doi.org/10.1038/s41467-023-42284-5; html:https://europepmc.org/articles/PMC10593800; pdf:https://europepmc.org/articles/PMC10593800?pdf=render" }, { "id": "32619549", @@ -31399,21 +31382,21 @@ "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.119.013684; doi:https://doi.org/10.1161/JAHA.119.013684; html:https://europepmc.org/articles/PMC7428631; pdf:https://europepmc.org/articles/PMC7428631?pdf=render" }, { - "id": "35568032", - "doi": "https://doi.org/10.1016/j.ajhg.2022.04.009", - "title": "Whole-exome sequencing identifies rare genetic variants associated with human plasma metabolites.", - "authorString": "Bomba L, Walter K, Guo Q, Surendran P, Kundu K, Nongmaithem S, Karim MA, Stewart ID, Langenberg C, Danesh J, Di Angelantonio E, Roberts DJ, Ouwehand WH, INTERVAL study, Dunham I, Butterworth AS, Soranzo N.", + "id": "33928785", + "doi": "https://doi.org/10.1161/circulationaha.120.049844", + "title": "Unfolded Protein Response as a Compensatory Mechanism and Potential Therapeutic Target in PLN R14del Cardiomyopathy.", + "authorString": "Feyen DAM, Perea-Gil I, Maas RGC, Harakalova M, Gavidia AA, Arthur Ataam J, Wu TH, Vink A, Pei J, Vadgama N, Suurmeijer AJ, Te Rijdt WP, Vu M, Amatya PL, Prado M, Zhang Y, Dunkenberger L, Sluijter JPG, Sallam K, Asselbergs FW, Mercola M, Karakikes I.", "authorAffiliations": "", - "journalTitle": "American journal of human genetics", - "pubYear": "2022", - "date": "2022-05-13", - "isOpenAccess": "Y", - "keywords": "Sequencing; Proteomics; drug targets; Metabolomics; Endophenotypes; Loss-of-function; Metabolon; Wgs; Wes; Rare Genetic Variant", + "journalTitle": "Circulation", + "pubYear": "2021", + "date": "2021-04-30", + "isOpenAccess": "N", + "keywords": "Unfolded protein response; Models, Biological; Induced Pluripotent Stem Cells; Phospholamban; Cardiomyopathy, Dilated; Sequence Analysis, Rna", "nationalPriorities": "", "healthCategories": "", - "abstract": "Metabolite levels measured in the human population are endophenotypes for biological processes. We combined sequencing data for 3,924 (whole-exome sequencing, WES, discovery) and 2,805 (whole-genome sequencing, WGS, replication) donors from a prospective cohort of blood donors in England. We used multiple approaches to select and aggregate rare genetic variants (minor allele frequency [MAF]\u00a0<\u00a00.1%) in protein-coding regions and tested their associations with 995 metabolites measured in plasma by using ultra-high-performance liquid chromatography-tandem mass spectrometry. We identified 40 novel associations implicating rare coding variants (27 genes and 38 metabolites), of which 28 (15 genes and 28 metabolites) were replicated. We developed algorithms to prioritize putative driver variants at each locus and used mediation and Mendelian randomization analyses to test directionality at associations of metabolite and protein levels at the ACY1 locus. Overall, 66% of reported associations implicate gene targets of approved drugs or bioactive drug-like compounds, contributing to drug targets' validating efforts.", + "abstract": "

Background

Phospholamban (PLN) is a critical regulator of calcium cycling and contractility in the heart. The loss of arginine at position 14 in PLN (R14del) is associated with dilated cardiomyopathy with a high prevalence of ventricular arrhythmias. How the R14 deletion causes dilated cardiomyopathy is poorly understood, and there are no disease-specific therapies.

Methods

We used single-cell RNA sequencing to uncover PLN R14del disease mechanisms in human induced pluripotent stem cells (hiPSC-CMs). We used both 2-dimensional and 3-dimensional functional contractility assays to evaluate the impact of modulating disease-relevant pathways in PLN R14del hiPSC-CMs.

Results

Modeling of the PLN R14del cardiomyopathy with isogenic pairs of hiPSC-CMs recapitulated the contractile deficit associated with the disease in vitro. Single-cell RNA sequencing revealed the induction of the unfolded protein response (UPR) pathway in PLN R14del compared with isogenic control hiPSC-CMs. The activation of UPR was also evident in the hearts from PLN R14del patients. Silencing of each of the 3 main UPR signaling branches (IRE1, ATF6, or PERK) by siRNA exacerbated the contractile dysfunction of PLN R14del hiPSC-CMs. We explored the therapeutic potential of activating the UPR with a small molecule activator, BiP (binding immunoglobulin protein) inducer X. PLN R14del hiPSC-CMs treated with BiP protein inducer X showed a dose-dependent amelioration of the contractility deficit in both 2-dimensional cultures and 3-dimensional engineered heart tissues without affecting calcium homeostasis.

Conclusions

Together, these findings suggest that the UPR exerts a protective effect in the setting of PLN R14del cardiomyopathy and that modulation of the UPR might be exploited therapeutically.", "laySummary": "", - "urls": "pdf:https://www.repository.cam.ac.uk/bitstream/1810/337646/3/1-s2.0-S0002929722001574-main.pdf; doi:https://doi.org/10.1016/j.ajhg.2022.04.009; html:https://europepmc.org/articles/PMC9247822; pdf:https://europepmc.org/articles/PMC9247822?pdf=render" + "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.049844; doi:https://doi.org/10.1161/CIRCULATIONAHA.120.049844; html:https://europepmc.org/articles/PMC8667423; pdf:https://europepmc.org/articles/PMC8667423?pdf=render; doi:https://doi.org/10.1161/circulationaha.120.049844" }, { "id": "31657946", @@ -31432,6 +31415,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1164/rccm.201903-0673OC" }, + { + "id": "35568032", + "doi": "https://doi.org/10.1016/j.ajhg.2022.04.009", + "title": "Whole-exome sequencing identifies rare genetic variants associated with human plasma metabolites.", + "authorString": "Bomba L, Walter K, Guo Q, Surendran P, Kundu K, Nongmaithem S, Karim MA, Stewart ID, Langenberg C, Danesh J, Di Angelantonio E, Roberts DJ, Ouwehand WH, INTERVAL study, Dunham I, Butterworth AS, Soranzo N.", + "authorAffiliations": "", + "journalTitle": "American journal of human genetics", + "pubYear": "2022", + "date": "2022-05-13", + "isOpenAccess": "Y", + "keywords": "Sequencing; Proteomics; drug targets; Metabolomics; Endophenotypes; Loss-of-function; Metabolon; Wgs; Wes; Rare Genetic Variant", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Metabolite levels measured in the human population are endophenotypes for biological processes. We combined sequencing data for 3,924 (whole-exome sequencing, WES, discovery) and 2,805 (whole-genome sequencing, WGS, replication) donors from a prospective cohort of blood donors in England. We used multiple approaches to select and aggregate rare genetic variants (minor allele frequency [MAF]\u00a0<\u00a00.1%) in protein-coding regions and tested their associations with 995 metabolites measured in plasma by using ultra-high-performance liquid chromatography-tandem mass spectrometry. We identified 40 novel associations implicating rare coding variants (27 genes and 38 metabolites), of which 28 (15 genes and 28 metabolites) were replicated. We developed algorithms to prioritize putative driver variants at each locus and used mediation and Mendelian randomization analyses to test directionality at associations of metabolite and protein levels at the ACY1 locus. Overall, 66% of reported associations implicate gene targets of approved drugs or bioactive drug-like compounds, contributing to drug targets' validating efforts.", + "laySummary": "", + "urls": "pdf:https://www.repository.cam.ac.uk/bitstream/1810/337646/3/1-s2.0-S0002929722001574-main.pdf; doi:https://doi.org/10.1016/j.ajhg.2022.04.009; html:https://europepmc.org/articles/PMC9247822; pdf:https://europepmc.org/articles/PMC9247822?pdf=render" + }, { "id": "36962407", "doi": "https://doi.org/10.1371/journal.pgph.0000292", @@ -31449,23 +31449,6 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0000292&type=printable; doi:https://doi.org/10.1371/journal.pgph.0000292; html:https://europepmc.org/articles/PMC10021216; pdf:https://europepmc.org/articles/PMC10021216?pdf=render" }, - { - "id": "37210036", - "doi": "https://doi.org/10.1016/j.jacc.2023.05.005", - "title": "Individualized Family Screening for Arrhythmogenic Right Ventricular\u00a0Cardiomyopathy.", - "authorString": "Muller SA, Gasperetti A, Bosman LP, Schmidt AF, Baas AF, Amin AS, Houweling AC, Wilde AAM, Compagnucci P, Targetti M, Casella M, Cal\u00f2 L, Tondo C, van der Harst P, Asselbergs FW, van Tintelen JP, Oerlemans MIFJ, Te Riele ASJM.", - "authorAffiliations": "", - "journalTitle": "Journal of the American College of Cardiology", - "pubYear": "2023", - "date": "2023-05-18", - "isOpenAccess": "N", - "keywords": "ventricular arrhythmia; Predictors; Screening Interval; Arvc; Family Screening", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Clinical guidelines recommend regular screening for arrhythmogenic right ventricular cardiomyopathy (ARVC) to monitor at-risk relatives, resulting in a significant burden on clinical resources. Prioritizing relatives on their probability of developing definite ARVC may provide more efficient patient care.

Objectives

The aim of this study was to determine the predictors and probability of ARVC development over time among at-risk relatives.

Methods

A total of 136 relatives (46% men, median age 25.5 years [IQR: 15.8-44.4 years]) from the Netherlands Arrhythmogenic Cardiomyopathy Registry without definite ARVC by 2010 task force criteria were included. Phenotype was ascertained using electrocardiography, Holter monitoring, and cardiac imaging. Subjects were divided into groups with \"possible ARVC\" (only genetic or familial predisposition) and \"borderline ARVC\" (1\u00a0minor task force criterion plus genetic or familial predisposition). Cox regression was performed to determine predictors and multistate modeling to assess the probability of ARVC development. Results were replicated in an unrelated Italian cohort (57% men, median age 37.0 years [IQR: 25.4-50.4 years]).

Results

At baseline, 93 subjects (68%) had possible ARVC, and 43 (32%) had borderline ARVC. Follow-up was available for 123 relatives (90%). After 8.1 years (IQR: 4.2-11.4 years), 41 (33%) had developed definite ARVC. Independent of baseline phenotype, symptomatic subjects (P\u00a0=\u00a00.014) and those 20 to 30 years of age (P\u00a0=\u00a00.002) had a higher hazard of developing definite ARVC. Furthermore, patients with borderline ARVC had a higher probability of developing definite ARVC compared with those with possible ARVC (1-year probability 13% vs 0.6%, 3-year probability 35% vs 5%; P\u00a0< 0.01). External replication showed comparable results (P > 0.05).

Conclusions

Symptomatic relatives, those 20 to 30 years of age, and those with borderline ARVC have a higher probability of developing definite ARVC. These patients may benefit from more frequent follow-up, while others may be monitored less often.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jacc.2023.05.005" - }, { "id": "31650125", "doi": "https://doi.org/10.1016/s2589-7500(19)30012-3", @@ -31483,6 +31466,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/s2589-7500(19)30012-3; doi:https://doi.org/10.1016/S2589-7500(19)30012-3; html:https://europepmc.org/articles/PMC6798263; pdf:https://europepmc.org/articles/PMC6798263?pdf=render" }, + { + "id": "37210036", + "doi": "https://doi.org/10.1016/j.jacc.2023.05.005", + "title": "Individualized Family Screening for Arrhythmogenic Right Ventricular\u00a0Cardiomyopathy.", + "authorString": "Muller SA, Gasperetti A, Bosman LP, Schmidt AF, Baas AF, Amin AS, Houweling AC, Wilde AAM, Compagnucci P, Targetti M, Casella M, Cal\u00f2 L, Tondo C, van der Harst P, Asselbergs FW, van Tintelen JP, Oerlemans MIFJ, Te Riele ASJM.", + "authorAffiliations": "", + "journalTitle": "Journal of the American College of Cardiology", + "pubYear": "2023", + "date": "2023-05-18", + "isOpenAccess": "N", + "keywords": "ventricular arrhythmia; Predictors; Screening Interval; Arvc; Family Screening", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Clinical guidelines recommend regular screening for arrhythmogenic right ventricular cardiomyopathy (ARVC) to monitor at-risk relatives, resulting in a significant burden on clinical resources. Prioritizing relatives on their probability of developing definite ARVC may provide more efficient patient care.

Objectives

The aim of this study was to determine the predictors and probability of ARVC development over time among at-risk relatives.

Methods

A total of 136 relatives (46% men, median age 25.5 years [IQR: 15.8-44.4 years]) from the Netherlands Arrhythmogenic Cardiomyopathy Registry without definite ARVC by 2010 task force criteria were included. Phenotype was ascertained using electrocardiography, Holter monitoring, and cardiac imaging. Subjects were divided into groups with \"possible ARVC\" (only genetic or familial predisposition) and \"borderline ARVC\" (1\u00a0minor task force criterion plus genetic or familial predisposition). Cox regression was performed to determine predictors and multistate modeling to assess the probability of ARVC development. Results were replicated in an unrelated Italian cohort (57% men, median age 37.0 years [IQR: 25.4-50.4 years]).

Results

At baseline, 93 subjects (68%) had possible ARVC, and 43 (32%) had borderline ARVC. Follow-up was available for 123 relatives (90%). After 8.1 years (IQR: 4.2-11.4 years), 41 (33%) had developed definite ARVC. Independent of baseline phenotype, symptomatic subjects (P\u00a0=\u00a00.014) and those 20 to 30 years of age (P\u00a0=\u00a00.002) had a higher hazard of developing definite ARVC. Furthermore, patients with borderline ARVC had a higher probability of developing definite ARVC compared with those with possible ARVC (1-year probability 13% vs 0.6%, 3-year probability 35% vs 5%; P\u00a0< 0.01). External replication showed comparable results (P > 0.05).

Conclusions

Symptomatic relatives, those 20 to 30 years of age, and those with borderline ARVC have a higher probability of developing definite ARVC. These patients may benefit from more frequent follow-up, while others may be monitored less often.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.jacc.2023.05.005" + }, { "id": "30862657", "doi": "https://doi.org/10.2337/dc18-2004", @@ -31534,23 +31534,6 @@ "laySummary": "", "urls": "pdf:https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-021-02561-2; doi:https://doi.org/10.1186/s13059-021-02561-2; html:https://europepmc.org/articles/PMC8667531; pdf:https://europepmc.org/articles/PMC8667531?pdf=render" }, - { - "id": "35193912", - "doi": "https://doi.org/10.1136/bmjopen-2021-053884", - "title": "Variation in health visiting contacts for children in England: cross-sectional analysis of the 2-2\u00bd year review using administrative data (Community Services Dataset, CSDS).", - "authorString": "Fraser C, Harron K, Barlow J, Bennett S, Woods G, Shand J, Kendall S, Woodman J.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2022", - "date": "2022-02-22", - "isOpenAccess": "Y", - "keywords": "Public Health; Community Child Health; Child Protection; Organisation Of Health Services", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

The 2-2\u00bd year universal health visiting review in England is a key time point for assessing child development and promoting school readiness. We aimed to ascertain which children were least likely to receive their 2-2\u00bd year review and whether there were additional non-mandated contacts for children who missed this review.

Design, setting, participants

Cross-sectional analysis of the 2-2\u00bd year review and additional health visiting contacts for 181 130 children aged 2 in England 2018/2019, stratified by ethnicity, deprivation, safeguarding vulnerability indicator and Looked After Child status.

Analysis

We used data from 33 local authorities submitting highly complete data on health visiting contacts to the Community Services Dataset. We calculated the percentage of children with a recorded 2-2\u00bd year review and/or any additional health visiting contacts and average number of contacts, by child characteristic.

Results

The most deprived children were slightly less likely to receive a 2-2\u00bd year review than the least deprived children (72% vs 78%) and Looked After Children much less likely, compared with other children (44% vs 69%). When all additional contacts were included, the pattern was reversed (deprivation) or disappeared (Looked After children). A substantial proportion of all children (24%), children with a 'safeguarding vulnerability' (22%) and Looked After children (29%) did not have a record of either a 2-2\u00bd year review or any other face-to-face contact in the year.

Conclusions

A substantial minority of children aged 2 with known vulnerabilities did not see the health visiting team at all in the year. Some higher need children (eg, deprived and Looked After) appeared to be seeing the health visiting team but not receiving their mandated health review. Further work is needed to establish the reasons for this, and potential solutions. There is an urgent need to improve the quality of national health visiting data.", - "laySummary": "", - "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e053884.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-053884; html:https://europepmc.org/articles/PMC8867374; pdf:https://europepmc.org/articles/PMC8867374?pdf=render" - }, { "id": "31863937", "doi": "https://doi.org/10.1016/j.aap.2019.105333", @@ -31568,6 +31551,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.aap.2019.105333" }, + { + "id": "35193912", + "doi": "https://doi.org/10.1136/bmjopen-2021-053884", + "title": "Variation in health visiting contacts for children in England: cross-sectional analysis of the 2-2\u00bd year review using administrative data (Community Services Dataset, CSDS).", + "authorString": "Fraser C, Harron K, Barlow J, Bennett S, Woods G, Shand J, Kendall S, Woodman J.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2022", + "date": "2022-02-22", + "isOpenAccess": "Y", + "keywords": "Public Health; Community Child Health; Child Protection; Organisation Of Health Services", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

The 2-2\u00bd year universal health visiting review in England is a key time point for assessing child development and promoting school readiness. We aimed to ascertain which children were least likely to receive their 2-2\u00bd year review and whether there were additional non-mandated contacts for children who missed this review.

Design, setting, participants

Cross-sectional analysis of the 2-2\u00bd year review and additional health visiting contacts for 181 130 children aged 2 in England 2018/2019, stratified by ethnicity, deprivation, safeguarding vulnerability indicator and Looked After Child status.

Analysis

We used data from 33 local authorities submitting highly complete data on health visiting contacts to the Community Services Dataset. We calculated the percentage of children with a recorded 2-2\u00bd year review and/or any additional health visiting contacts and average number of contacts, by child characteristic.

Results

The most deprived children were slightly less likely to receive a 2-2\u00bd year review than the least deprived children (72% vs 78%) and Looked After Children much less likely, compared with other children (44% vs 69%). When all additional contacts were included, the pattern was reversed (deprivation) or disappeared (Looked After children). A substantial proportion of all children (24%), children with a 'safeguarding vulnerability' (22%) and Looked After children (29%) did not have a record of either a 2-2\u00bd year review or any other face-to-face contact in the year.

Conclusions

A substantial minority of children aged 2 with known vulnerabilities did not see the health visiting team at all in the year. Some higher need children (eg, deprived and Looked After) appeared to be seeing the health visiting team but not receiving their mandated health review. Further work is needed to establish the reasons for this, and potential solutions. There is an urgent need to improve the quality of national health visiting data.", + "laySummary": "", + "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e053884.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-053884; html:https://europepmc.org/articles/PMC8867374; pdf:https://europepmc.org/articles/PMC8867374?pdf=render" + }, { "id": "35386996", "doi": "https://doi.org/10.3389/falgy.2021.677677", @@ -31636,23 +31636,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/kead038/49101708/kead038.pdf; doi:https://doi.org/10.1093/rheumatology/kead038; html:https://europepmc.org/articles/PMC10629784; pdf:https://europepmc.org/articles/PMC10629784?pdf=render" }, - { - "id": "38296965", - "doi": "https://doi.org/10.1038/s41467-023-43644-x", - "title": "Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.", - "authorString": "RECOVERY Collaborative Group, Horby PW, Peto L, Staplin N, Campbell M, Pessoa-Amorim G, Mafham M, Emberson JR, Stewart R, Prudon B, Uriel A, Green CA, Dhasmana DJ, Malein F, Majumdar J, Collini P, Shurmer J, Yates B, Baillie JK, Buch MH, Day J, Faust SN, Jaki T, Jeffery K, Juszczak E, Knight M, Lim WS, Montgomery A, Mumford A, Rowan K, Thwaites G, Haynes R, Landray MJ.", - "authorAffiliations": "", - "journalTitle": "Nature communications", - "pubYear": "2024", - "date": "2024-01-31", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p\u2009=\u20090.40). There was no significant effect of DMF on any secondary outcome.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41467-023-43644-x.pdf; doi:https://doi.org/10.1038/s41467-023-43644-x; html:https://europepmc.org/articles/PMC10831058; pdf:https://europepmc.org/articles/PMC10831058?pdf=render" - }, { "id": "35861818", "doi": "https://doi.org/10.1161/jaha.121.025473", @@ -31670,6 +31653,23 @@ "laySummary": "", "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.025473; doi:https://doi.org/10.1161/JAHA.121.025473; html:https://europepmc.org/articles/PMC9707810; pdf:https://europepmc.org/articles/PMC9707810?pdf=render" }, + { + "id": "38296965", + "doi": "https://doi.org/10.1038/s41467-023-43644-x", + "title": "Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.", + "authorString": "RECOVERY Collaborative Group, Horby PW, Peto L, Staplin N, Campbell M, Pessoa-Amorim G, Mafham M, Emberson JR, Stewart R, Prudon B, Uriel A, Green CA, Dhasmana DJ, Malein F, Majumdar J, Collini P, Shurmer J, Yates B, Baillie JK, Buch MH, Day J, Faust SN, Jaki T, Jeffery K, Juszczak E, Knight M, Lim WS, Montgomery A, Mumford A, Rowan K, Thwaites G, Haynes R, Landray MJ.", + "authorAffiliations": "", + "journalTitle": "Nature communications", + "pubYear": "2024", + "date": "2024-01-31", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p\u2009=\u20090.40). There was no significant effect of DMF on any secondary outcome.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41467-023-43644-x.pdf; doi:https://doi.org/10.1038/s41467-023-43644-x; html:https://europepmc.org/articles/PMC10831058; pdf:https://europepmc.org/articles/PMC10831058?pdf=render" + }, { "id": "33184391", "doi": "https://doi.org/10.1038/s41598-020-76816-6", @@ -31806,23 +31806,6 @@ "laySummary": "", "urls": "pdf:https://thorax.bmj.com/content/thoraxjnl/76/9/860.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2020-216512; html:https://europepmc.org/articles/PMC8011425; pdf:https://europepmc.org/articles/PMC8011425?pdf=render" }, - { - "id": "36357634", - "doi": "https://doi.org/10.1007/s00467-022-05789-7", - "title": "Shared genetic risk across different presentations of gene test-negative idiopathic nephrotic syndrome.", - "authorString": "Downie ML, Gupta S, Chan MMY, Sadeghi-Alavijeh O, Cao J, Parekh RS, Diz CB, Bierzynska A, Levine AP, Pepper RJ, Stanescu H, Saleem MA, Kleta R, Bockenhauer D, Koziell AB, Gale DP.", - "authorAffiliations": "", - "journalTitle": "Pediatric nephrology (Berlin, Germany)", - "pubYear": "2023", - "date": "2022-11-10", - "isOpenAccess": "Y", - "keywords": "Paediatrics; Minimal Change Disease; Focal Segmental Glomerulosclerosis; Monogenic; Genetic Risk Score; Steroid-resistant Nephrotic Syndrome; Steroid-sensitive Nephrotic Syndrome", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Idiop athic nephrotic syndrome (INS) is classified in children according to response to initial corticosteroid therapy into steroid-sensitive (SSNS) and steroid-resistant nephrotic syndrome (SRNS), and in adults according to histology into minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). However, there is well-recognised phenotypic overlap between these entities. Genome-wide association studies (GWAS) have shown a strong association between SSNS and variation at HLA, suggesting an underlying immunological basis. We sought to determine whether a risk score generated from genetic variants associated with SSNS could be used to gain insight into the pathophysiology of INS presenting in other ways.

Methods

We developed an SSNS genetic risk score (SSNS-GRS) from the five variants independently associated with childhood SSNS in a previous European GWAS. We quantified SSNS-GRS in independent cohorts of European individuals with childhood SSNS, non-monogenic SRNS, MCD, and FSGS, and contrasted them with SSNS-GRS quantified in individuals with monogenic SRNS, membranous nephropathy (a different immune-mediated disease-causing nephrotic syndrome), and healthy controls.

Results

The SSNS-GRS was significantly elevated in cohorts with SSNS, non-monogenic SRNS, MCD, and FSGS compared to healthy participants and those with membranous nephropathy. The SSNS-GRS in all cohorts with non-monogenic INS were also significantly elevated compared to those with monogenic SRNS.

Conclusions

The shared genetic risk factors among patients with different presentations of INS strongly suggests a shared autoimmune pathogenesis when monogenic causes are excluded. Use of the SSNS-GRS, in addition to testing for monogenic causes, may help to classify patients presenting with INS. A higher resolution version of the Graphical abstract is available as Supplementary information.", - "laySummary": "", - "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00467-022-05789-7.pdf; doi:https://doi.org/10.1007/s00467-022-05789-7; html:https://europepmc.org/articles/PMC10154254; pdf:https://europepmc.org/articles/PMC10154254?pdf=render" - }, { "id": "31145509", "doi": "https://doi.org/10.1002/gepi.22215", @@ -31840,6 +31823,23 @@ "laySummary": "", "urls": "pdf:https://pure.rug.nl/ws/files/89611268/Manduchi_et_al_2019_Genetic_Epidemiology.pdf; doi:https://doi.org/10.1002/gepi.22215; html:https://europepmc.org/articles/PMC6687530; pdf:https://europepmc.org/articles/PMC6687530?pdf=render; doi:https://doi.org/10.1002/gepi.22215" }, + { + "id": "36357634", + "doi": "https://doi.org/10.1007/s00467-022-05789-7", + "title": "Shared genetic risk across different presentations of gene test-negative idiopathic nephrotic syndrome.", + "authorString": "Downie ML, Gupta S, Chan MMY, Sadeghi-Alavijeh O, Cao J, Parekh RS, Diz CB, Bierzynska A, Levine AP, Pepper RJ, Stanescu H, Saleem MA, Kleta R, Bockenhauer D, Koziell AB, Gale DP.", + "authorAffiliations": "", + "journalTitle": "Pediatric nephrology (Berlin, Germany)", + "pubYear": "2023", + "date": "2022-11-10", + "isOpenAccess": "Y", + "keywords": "Paediatrics; Minimal Change Disease; Focal Segmental Glomerulosclerosis; Monogenic; Genetic Risk Score; Steroid-resistant Nephrotic Syndrome; Steroid-sensitive Nephrotic Syndrome", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Idiop athic nephrotic syndrome (INS) is classified in children according to response to initial corticosteroid therapy into steroid-sensitive (SSNS) and steroid-resistant nephrotic syndrome (SRNS), and in adults according to histology into minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). However, there is well-recognised phenotypic overlap between these entities. Genome-wide association studies (GWAS) have shown a strong association between SSNS and variation at HLA, suggesting an underlying immunological basis. We sought to determine whether a risk score generated from genetic variants associated with SSNS could be used to gain insight into the pathophysiology of INS presenting in other ways.

Methods

We developed an SSNS genetic risk score (SSNS-GRS) from the five variants independently associated with childhood SSNS in a previous European GWAS. We quantified SSNS-GRS in independent cohorts of European individuals with childhood SSNS, non-monogenic SRNS, MCD, and FSGS, and contrasted them with SSNS-GRS quantified in individuals with monogenic SRNS, membranous nephropathy (a different immune-mediated disease-causing nephrotic syndrome), and healthy controls.

Results

The SSNS-GRS was significantly elevated in cohorts with SSNS, non-monogenic SRNS, MCD, and FSGS compared to healthy participants and those with membranous nephropathy. The SSNS-GRS in all cohorts with non-monogenic INS were also significantly elevated compared to those with monogenic SRNS.

Conclusions

The shared genetic risk factors among patients with different presentations of INS strongly suggests a shared autoimmune pathogenesis when monogenic causes are excluded. Use of the SSNS-GRS, in addition to testing for monogenic causes, may help to classify patients presenting with INS. A higher resolution version of the Graphical abstract is available as Supplementary information.", + "laySummary": "", + "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00467-022-05789-7.pdf; doi:https://doi.org/10.1007/s00467-022-05789-7; html:https://europepmc.org/articles/PMC10154254; pdf:https://europepmc.org/articles/PMC10154254?pdf=render" + }, { "id": "36210800", "doi": "https://doi.org/10.1038/s43856-022-00189-2", @@ -31874,6 +31874,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/jcem/article-pdf/106/5/1255/41848481/dgab067.pdf; doi:https://doi.org/10.1210/clinem/dgab067; html:https://europepmc.org/articles/PMC7928949" }, + { + "id": "31055854", + "doi": "https://doi.org/10.5694/mja2.50143", + "title": "Traumatic spinal cord injury in Victoria, 2007-2016.", + "authorString": "Beck B, Cameron PA, Braaf S, Nunn A, Fitzgerald MC, Judson RT, Teague WJ, Lennox A, Middleton JW, Harrison JE, Gabbe BJ.", + "authorAffiliations": "", + "journalTitle": "The Medical journal of Australia", + "pubYear": "2019", + "date": "2019-05-01", + "isOpenAccess": "N", + "keywords": "Spinal cord injuries; epidemiology; Traumatology; Trauma, Nervous System", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

To investigate trends in the incidence and causes of traumatic spinal cord injury (TSCI) in Victoria over a 10-year period.

Design, setting, participants

Retrospective cohort study: analysis of Victorian State Trauma Registry (VSTR) data for people who sustained TSCIs during 2007-2016.

Main outcomes and measures

Temporal trends in population-based incidence rates of TSCI (injury to the spinal cord with an Abbreviated Injury Scale [AIS] score of 4 or more).

Results

There were 706 cases of TSCI, most the result of transport events (269 cases, 38%) or low falls (197 cases, 28%). The overall crude incidence of TSCI was 1.26 cases per 100\u00a0000 population (95% CI, 1.17-1.36 per 100\u00a0000 population), and did not change over the study period (incidence rate ratio [IRR], 1.01; 95% CI, 0.99-1.04). However, the incidence of TSCI resulting from low falls increased by 9% per year (95% CI, 4-15%). The proportion of TSCI cases classified as incomplete tetraplegia increased from 41% in 2007 to 55% in 2016 (P\u00a0<\u00a00.001). Overall in-hospital mortality was 15% (104 deaths), and was highest among people aged 65 years or more (31%, 70 deaths).

Conclusions

Given the devastating consequences of TSCI, improved primary prevention strategies are needed, particularly as the incidence of TSCI did not decline over the study period. The epidemiologic profile of TSCI has shifted, with an increasing number of TSCI events in older adults. This change has implications for prevention, acute and post-discharge care, and support.", + "laySummary": "", + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.5694/mja2.50143; doi:https://doi.org/10.5694/mja2.50143" + }, { "id": "35238940", "doi": "https://doi.org/10.1093/ndt/gfac040", @@ -31908,23 +31925,6 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jvh.13863; doi:https://doi.org/10.1111/jvh.13863; html:https://europepmc.org/articles/PMC10526649; pdf:https://europepmc.org/articles/PMC10526649?pdf=render" }, - { - "id": "31055854", - "doi": "https://doi.org/10.5694/mja2.50143", - "title": "Traumatic spinal cord injury in Victoria, 2007-2016.", - "authorString": "Beck B, Cameron PA, Braaf S, Nunn A, Fitzgerald MC, Judson RT, Teague WJ, Lennox A, Middleton JW, Harrison JE, Gabbe BJ.", - "authorAffiliations": "", - "journalTitle": "The Medical journal of Australia", - "pubYear": "2019", - "date": "2019-05-01", - "isOpenAccess": "N", - "keywords": "Spinal cord injuries; epidemiology; Traumatology; Trauma, Nervous System", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

To investigate trends in the incidence and causes of traumatic spinal cord injury (TSCI) in Victoria over a 10-year period.

Design, setting, participants

Retrospective cohort study: analysis of Victorian State Trauma Registry (VSTR) data for people who sustained TSCIs during 2007-2016.

Main outcomes and measures

Temporal trends in population-based incidence rates of TSCI (injury to the spinal cord with an Abbreviated Injury Scale [AIS] score of 4 or more).

Results

There were 706 cases of TSCI, most the result of transport events (269 cases, 38%) or low falls (197 cases, 28%). The overall crude incidence of TSCI was 1.26 cases per 100\u00a0000 population (95% CI, 1.17-1.36 per 100\u00a0000 population), and did not change over the study period (incidence rate ratio [IRR], 1.01; 95% CI, 0.99-1.04). However, the incidence of TSCI resulting from low falls increased by 9% per year (95% CI, 4-15%). The proportion of TSCI cases classified as incomplete tetraplegia increased from 41% in 2007 to 55% in 2016 (P\u00a0<\u00a00.001). Overall in-hospital mortality was 15% (104 deaths), and was highest among people aged 65 years or more (31%, 70 deaths).

Conclusions

Given the devastating consequences of TSCI, improved primary prevention strategies are needed, particularly as the incidence of TSCI did not decline over the study period. The epidemiologic profile of TSCI has shifted, with an increasing number of TSCI events in older adults. This change has implications for prevention, acute and post-discharge care, and support.", - "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.5694/mja2.50143; doi:https://doi.org/10.5694/mja2.50143" - }, { "id": "36256701", "doi": "https://doi.org/10.1093/eurjcn/zvac098", @@ -32027,6 +32027,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41467-022-31626-4.pdf; doi:https://doi.org/10.1038/s41467-022-31626-4; html:https://europepmc.org/articles/PMC9283523; pdf:https://europepmc.org/articles/PMC9283523?pdf=render" }, + { + "id": "33021418", + "doi": "https://doi.org/10.1080/09273948.2020.1799038", + "title": "Noninvasive Instrument-based Tests for Detecting and Measuring Vitreous Inflammation in Uveitis: A Systematic Review.", + "authorString": "Liu X, Hui BT, Way C, Beese S, Adriano A, Keane PA, Moore DJ, Denniston AK.", + "authorAffiliations": "", + "journalTitle": "Ocular immunology and inflammation", + "pubYear": "2022", + "date": "2020-10-06", + "isOpenAccess": "Y", + "keywords": "Imaging; Diagnostic test; Systematic review; Vitreous; ultrasound; Uveitis; optical coherence tomography; Vitritis; Retinal Photography; Vitreous Inflammation", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Purpose

This systematic review aims to identify instrument-based tests for quantifying vitreous inflammation in uveitis, report the test reliability and the level of correlation with clinician grading.

Methods

Studies describing instrument-based tests for detecting vitreous inflammation were identified by searching bibliographic databases and trials registers. Test reliability measures and level of correlation with clinician vitreous haze grading are extracted.

Results

Twelve studies describing ultrasound, optical coherence tomography (OCT), and retinal photography for detecting vitreous inflammation were included: Ultrasound was used for detection of disease features, whereas OCT and retinal photography provided quantifiable measurements. Correlation with clinician grading for OCT was 0.53-0.60 (three studies) and for retinal photography was 0.51 (1 study). Both instruments showed high inter- and intra-observer reliability (>0.70 intraclass correlation and Cohen's kappa), where reported in four studies.

Conclusion

Retinal photography and OCT are able to detect and measure vitreous inflammation. Both techniques are reliable, automatable, and warrant further evaluation.", + "laySummary": "", + "urls": "pdf:https://www.tandfonline.com/doi/pdf/10.1080/09273948.2020.1799038?needAccess=true; doi:https://doi.org/10.1080/09273948.2020.1799038; html:https://europepmc.org/articles/PMC8935946; pdf:https://europepmc.org/articles/PMC8935946?pdf=render" + }, { "id": "35279265", "doi": "https://doi.org/10.1016/s2213-2600(21)00511-7", @@ -32062,21 +32079,21 @@ "urls": "pdf:https://adc.bmj.com/content/archdischild/107/10/e31.full.pdf; doi:https://doi.org/10.1136/archdischild-2021-323681; html:https://europepmc.org/articles/PMC9271837; pdf:https://europepmc.org/articles/PMC9271837?pdf=render" }, { - "id": "33021418", - "doi": "https://doi.org/10.1080/09273948.2020.1799038", - "title": "Noninvasive Instrument-based Tests for Detecting and Measuring Vitreous Inflammation in Uveitis: A Systematic Review.", - "authorString": "Liu X, Hui BT, Way C, Beese S, Adriano A, Keane PA, Moore DJ, Denniston AK.", + "id": "31702773", + "doi": "https://doi.org/10.1093/bioinformatics/btz796", + "title": "Model selection for metabolomics: predicting diagnosis of coronary artery disease using automated machine learning.", + "authorString": "Orlenko A, Kofink D, Lyytik\u00e4inen LP, Nikus K, Mishra P, Kuukasj\u00e4rvi P, Karhunen PJ, K\u00e4h\u00f6nen M, Laurikka JO, Lehtim\u00e4ki T, Asselbergs FW, Moore JH.", "authorAffiliations": "", - "journalTitle": "Ocular immunology and inflammation", - "pubYear": "2022", - "date": "2020-10-06", + "journalTitle": "Bioinformatics (Oxford, England)", + "pubYear": "2020", + "date": "2020-03-01", "isOpenAccess": "Y", - "keywords": "Imaging; Diagnostic test; Systematic review; Vitreous; ultrasound; Uveitis; optical coherence tomography; Vitritis; Retinal Photography; Vitreous Inflammation", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Purpose

This systematic review aims to identify instrument-based tests for quantifying vitreous inflammation in uveitis, report the test reliability and the level of correlation with clinician grading.

Methods

Studies describing instrument-based tests for detecting vitreous inflammation were identified by searching bibliographic databases and trials registers. Test reliability measures and level of correlation with clinician vitreous haze grading are extracted.

Results

Twelve studies describing ultrasound, optical coherence tomography (OCT), and retinal photography for detecting vitreous inflammation were included: Ultrasound was used for detection of disease features, whereas OCT and retinal photography provided quantifiable measurements. Correlation with clinician grading for OCT was 0.53-0.60 (three studies) and for retinal photography was 0.51 (1 study). Both instruments showed high inter- and intra-observer reliability (>0.70 intraclass correlation and Cohen's kappa), where reported in four studies.

Conclusion

Retinal photography and OCT are able to detect and measure vitreous inflammation. Both techniques are reliable, automatable, and warrant further evaluation.", + "abstract": "

Motivation

Selecting the optimal machine learning (ML) model for a given dataset is often challenging. Automated ML (AutoML) has emerged as a powerful tool for enabling the automatic selection of ML methods and parameter settings for the prediction of biomedical endpoints. Here, we apply the tree-based pipeline optimization tool (TPOT) to predict angiographic diagnoses of coronary artery disease (CAD). With TPOT, ML models are represented as expression trees and optimal pipelines discovered using a stochastic search method called genetic programing. We provide some guidelines for TPOT-based ML pipeline selection and optimization-based on various clinical phenotypes and high-throughput metabolic profiles in the Angiography and Genes Study (ANGES).

Results

We analyzed nuclear magnetic resonance-derived lipoprotein and metabolite profiles in the ANGES cohort with a goal to identify the role of non-obstructive CAD patients in CAD diagnostics. We performed a comparative analysis of TPOT-generated ML pipelines with selected ML classifiers, optimized with a grid search approach, applied to two phenotypic CAD profiles. As a result, TPOT-generated ML pipelines that outperformed grid search optimized models across multiple performance metrics including balanced accuracy and area under the precision-recall curve. With the selected models, we demonstrated that the phenotypic profile that distinguishes non-obstructive CAD patients from no CAD patients is associated with higher precision, suggesting a discrepancy in the underlying processes between these phenotypes.

Availability and implementation

TPOT is freely available via http://epistasislab.github.io/tpot/.

Supplementary information

Supplementary data are available at Bioinformatics online.", "laySummary": "", - "urls": "pdf:https://www.tandfonline.com/doi/pdf/10.1080/09273948.2020.1799038?needAccess=true; doi:https://doi.org/10.1080/09273948.2020.1799038; html:https://europepmc.org/articles/PMC8935946; pdf:https://europepmc.org/articles/PMC8935946?pdf=render" + "urls": "pdf:https://academic.oup.com/bioinformatics/article-pdf/36/6/1772/36089203/btz796.pdf; doi:https://doi.org/10.1093/bioinformatics/btz796; html:https://europepmc.org/articles/PMC7703753; pdf:https://europepmc.org/articles/PMC7703753?pdf=render" }, { "id": "38040695", @@ -32095,23 +32112,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41467-023-43522-6.pdf; doi:https://doi.org/10.1038/s41467-023-43522-6; html:https://europepmc.org/articles/PMC10692198; pdf:https://europepmc.org/articles/PMC10692198?pdf=render" }, - { - "id": "31702773", - "doi": "https://doi.org/10.1093/bioinformatics/btz796", - "title": "Model selection for metabolomics: predicting diagnosis of coronary artery disease using automated machine learning.", - "authorString": "Orlenko A, Kofink D, Lyytik\u00e4inen LP, Nikus K, Mishra P, Kuukasj\u00e4rvi P, Karhunen PJ, K\u00e4h\u00f6nen M, Laurikka JO, Lehtim\u00e4ki T, Asselbergs FW, Moore JH.", - "authorAffiliations": "", - "journalTitle": "Bioinformatics (Oxford, England)", - "pubYear": "2020", - "date": "2020-03-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Motivation

Selecting the optimal machine learning (ML) model for a given dataset is often challenging. Automated ML (AutoML) has emerged as a powerful tool for enabling the automatic selection of ML methods and parameter settings for the prediction of biomedical endpoints. Here, we apply the tree-based pipeline optimization tool (TPOT) to predict angiographic diagnoses of coronary artery disease (CAD). With TPOT, ML models are represented as expression trees and optimal pipelines discovered using a stochastic search method called genetic programing. We provide some guidelines for TPOT-based ML pipeline selection and optimization-based on various clinical phenotypes and high-throughput metabolic profiles in the Angiography and Genes Study (ANGES).

Results

We analyzed nuclear magnetic resonance-derived lipoprotein and metabolite profiles in the ANGES cohort with a goal to identify the role of non-obstructive CAD patients in CAD diagnostics. We performed a comparative analysis of TPOT-generated ML pipelines with selected ML classifiers, optimized with a grid search approach, applied to two phenotypic CAD profiles. As a result, TPOT-generated ML pipelines that outperformed grid search optimized models across multiple performance metrics including balanced accuracy and area under the precision-recall curve. With the selected models, we demonstrated that the phenotypic profile that distinguishes non-obstructive CAD patients from no CAD patients is associated with higher precision, suggesting a discrepancy in the underlying processes between these phenotypes.

Availability and implementation

TPOT is freely available via http://epistasislab.github.io/tpot/.

Supplementary information

Supplementary data are available at Bioinformatics online.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/bioinformatics/article-pdf/36/6/1772/36089203/btz796.pdf; doi:https://doi.org/10.1093/bioinformatics/btz796; html:https://europepmc.org/articles/PMC7703753; pdf:https://europepmc.org/articles/PMC7703753?pdf=render" - }, { "id": "35762393", "doi": "https://doi.org/10.1093/oncolo/oyac117", @@ -32299,23 +32299,6 @@ "laySummary": "", "urls": "pdf:https://bmchealthservres.biomedcentral.com/track/pdf/10.1186/s12913-022-07607-0; doi:https://doi.org/10.1186/s12913-022-07607-0; html:https://europepmc.org/articles/PMC8859903; pdf:https://europepmc.org/articles/PMC8859903?pdf=render" }, - { - "id": "36408685", - "doi": "https://doi.org/10.1161/circheartfailure.122.009526", - "title": "Multimarker Analysis of Serially Measured GDF-15, NT-proBNP, ST2, GAL-3, cTnI, Creatinine, and Prognosis in Acute Heart Failure.", - "authorString": "G\u00fcrg\u00f6ze MT, van Vark LC, Baart SJ, Kardys I, Akkerhuis KM, Manintveld OC, Postmus D, Hillege HL, Lesman-Leegte I, Asselbergs FW, Brunner-la-Rocca HP, van den Bos EJ, Orsel JG, de Ridder SPJ, Pinto YM, Boersma E.", - "authorAffiliations": "", - "journalTitle": "Circulation. Heart failure", - "pubYear": "2023", - "date": "2022-11-21", - "isOpenAccess": "Y", - "keywords": "Prognosis; Biomarkers; Heart Failure; Growth Differentiation Factor 15", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk.

Methods

TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling.

Results

Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78-2.57) unadjusted, 1.96 (1.49-2.53) after adjustment for clinical confounders and 1.44 (1.05-1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78-3.33) and 1.52 (1.15-2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785).

Conclusions

Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates. Multiple biomarkers should be considered for stratification in clinical practice.

Registration

URL: https://www.trialregister.nl/trial/1783; Unique Identifier: NTR1893. (The trial can be found temporarily at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR1893.).", - "laySummary": "", - "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCHEARTFAILURE.122.009526; doi:https://doi.org/10.1161/CIRCHEARTFAILURE.122.009526; html:https://europepmc.org/articles/PMC9833118; pdf:https://europepmc.org/articles/PMC9833118?pdf=render" - }, { "id": "35193920", "doi": "https://doi.org/10.1136/bmjopen-2021-055773", @@ -32333,6 +32316,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e055773.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055773; html:https://europepmc.org/articles/PMC8867343; pdf:https://europepmc.org/articles/PMC8867343?pdf=render" }, + { + "id": "36408685", + "doi": "https://doi.org/10.1161/circheartfailure.122.009526", + "title": "Multimarker Analysis of Serially Measured GDF-15, NT-proBNP, ST2, GAL-3, cTnI, Creatinine, and Prognosis in Acute Heart Failure.", + "authorString": "G\u00fcrg\u00f6ze MT, van Vark LC, Baart SJ, Kardys I, Akkerhuis KM, Manintveld OC, Postmus D, Hillege HL, Lesman-Leegte I, Asselbergs FW, Brunner-la-Rocca HP, van den Bos EJ, Orsel JG, de Ridder SPJ, Pinto YM, Boersma E.", + "authorAffiliations": "", + "journalTitle": "Circulation. Heart failure", + "pubYear": "2023", + "date": "2022-11-21", + "isOpenAccess": "Y", + "keywords": "Prognosis; Biomarkers; Heart Failure; Growth Differentiation Factor 15", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk.

Methods

TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling.

Results

Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78-2.57) unadjusted, 1.96 (1.49-2.53) after adjustment for clinical confounders and 1.44 (1.05-1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78-3.33) and 1.52 (1.15-2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785).

Conclusions

Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates. Multiple biomarkers should be considered for stratification in clinical practice.

Registration

URL: https://www.trialregister.nl/trial/1783; Unique Identifier: NTR1893. (The trial can be found temporarily at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR1893.).", + "laySummary": "", + "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCHEARTFAILURE.122.009526; doi:https://doi.org/10.1161/CIRCHEARTFAILURE.122.009526; html:https://europepmc.org/articles/PMC9833118; pdf:https://europepmc.org/articles/PMC9833118?pdf=render" + }, { "id": "35251129", "doi": "https://doi.org/10.3389/fgene.2022.818574", @@ -32402,38 +32402,38 @@ "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.120.002963; doi:https://doi.org/10.1161/CIRCGEN.120.002963; html:https://europepmc.org/articles/PMC8284356; pdf:https://europepmc.org/articles/PMC8284356?pdf=render; doi:https://doi.org/10.1161/circgen.120.002963" }, { - "id": "33090454", - "doi": "https://doi.org/10.1111/bjd.19597", - "title": "Atopic eczema and obesity: a population-based study.", - "authorString": "Ascott A, Mansfield KE, Schonmann Y, Mulick A, Abuabara K, Roberts A, Smeeth L, Langan SM.", + "id": "32222069", + "doi": "https://doi.org/10.1111/bjd.19052", + "title": "Risk of hospitalization and death due to infection in people with psoriasis: a population-based cohort study using the Clinical Practice Research Datalink.", + "authorString": "Yiu ZZN, Parisi R, Lunt M, Warren RB, Griffiths CEM, Langan SM, Ashcroft DM.", "authorAffiliations": "", "journalTitle": "The British journal of dermatology", "pubYear": "2021", - "date": "2020-12-01", + "date": "2020-05-12", "isOpenAccess": "N", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Atopic eczema is a common chronic inflammatory skin disease. Research suggests an association between atopic eczema and obesity, with inconsistent evidence from European populations.

Objectives

To explore the association between diagnosed atopic eczema and being overweight or obese, and whether increased atopic eczema severity was associated with higher body mass index.

Methods

We undertook a cross-sectional analysis within a cohort of adults (matched by age, sex and general practice) with and without a diagnosis of atopic eczema. We used primary care (Clinical Practice Research Datalink Gold) and linked hospital admissions data (1998-2016). We used conditional logistic regression to compare the odds of being overweight or obese (adjusting for confounders and potential mediators) in those with atopic eczema (mild, moderate and severe, and all eczema) vs. those without.

Results

We identified 441\u00a0746 people with atopic eczema, matched to 1\u00a0849\u00a0722 without. People with atopic eczema had slightly higher odds of being overweight or obese vs. those without [odds ratio (OR) 1\u00b708, 95% confidence interval (CI) 1\u00b707-1\u00b709] after adjusting for age, asthma and socioeconomic deprivation. Adjusting for potential mediators (high-dose glucocorticoids, harmful alcohol use, anxiety, depression, smoking) had a minimal impact on effect estimates (OR 1\u00b707, 95% CI 1\u00b706-1\u00b708). We saw no evidence that odds of being overweight or obese increased with increasing atopic eczema severity, and there was no association in people with severe eczema.

Conclusions

We found evidence of a small overall association between atopic eczema and being overweight or obese. However, there was no association with obesity among those with the most severe eczema. Our findings are largely reassuring for this prevalent patient group who may already have an increased risk of cardiovascular disease.", + "abstract": "

Background

Psoriasis is associated with risk factors for serious infections, but the independent relationship between psoriasis and serious infection is as yet unclear.

Objectives

To determine whether people with psoriasis have a higher risk of hospitalization due to any infection, respiratory infections, soft-tissue and skin infections, or a higher risk of death due to infection.

Methods

We conducted a cohort study of people (\u2265 18 years) with psoriasis using the UK Clinical Practice Research Datalink (CPRD GOLD) linked to Hospital Episode Statistics (HES) and Office for National Statistics (ONS) mortality records between 1 April 2003 and 31 December 2016, and matched with up to six comparators on age, sex and general practice. Hospitalization was ascertained from HES records; death was ascertained from ONS mortality records. Stratified Cox proportional hazard models were estimated, with stepwise adjustment in different models for potential confounders or mediators between psoriasis and serious infection.

Results

There were 69\u00a0315 people with psoriasis and 338\u00a0620 comparators who were followed up for a median (interquartile range) of 4\u00b79 (5\u00b79) and 5\u00b71 (6\u00b73) years, respectively. People with psoriasis had a higher incidence rate of serious infection [20\u00b75 per 1000 person-years, 95% confidence interval (CI) 20\u00b70-21\u00b70, n = 7631] compared with those without psoriasis (16\u00b71 per 1000 person-years, 95% CI 15\u00b79-16\u00b73, n = 30\u00a0761). The fully adjusted hazard ratio for the association between psoriasis and serious infection was 1\u00b736 (95% CI 1\u00b731-1\u00b740), with similar results across the other outcomes.

Conclusions

Psoriasis is associated with a small increase in the risk of serious infection. Further research is needed to understand how psoriasis predisposes to a higher risk of infection.", "laySummary": "", - "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4658151/1/Ascott-etal-2020_Atopic_eczema_and-obesity.pdf; doi:https://doi.org/10.1111/bjd.19597" + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.19052; doi:https://doi.org/10.1111/bjd.19052" }, { - "id": "32222069", - "doi": "https://doi.org/10.1111/bjd.19052", - "title": "Risk of hospitalization and death due to infection in people with psoriasis: a population-based cohort study using the Clinical Practice Research Datalink.", - "authorString": "Yiu ZZN, Parisi R, Lunt M, Warren RB, Griffiths CEM, Langan SM, Ashcroft DM.", + "id": "33090454", + "doi": "https://doi.org/10.1111/bjd.19597", + "title": "Atopic eczema and obesity: a population-based study.", + "authorString": "Ascott A, Mansfield KE, Schonmann Y, Mulick A, Abuabara K, Roberts A, Smeeth L, Langan SM.", "authorAffiliations": "", "journalTitle": "The British journal of dermatology", "pubYear": "2021", - "date": "2020-05-12", + "date": "2020-12-01", "isOpenAccess": "N", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Psoriasis is associated with risk factors for serious infections, but the independent relationship between psoriasis and serious infection is as yet unclear.

Objectives

To determine whether people with psoriasis have a higher risk of hospitalization due to any infection, respiratory infections, soft-tissue and skin infections, or a higher risk of death due to infection.

Methods

We conducted a cohort study of people (\u2265 18 years) with psoriasis using the UK Clinical Practice Research Datalink (CPRD GOLD) linked to Hospital Episode Statistics (HES) and Office for National Statistics (ONS) mortality records between 1 April 2003 and 31 December 2016, and matched with up to six comparators on age, sex and general practice. Hospitalization was ascertained from HES records; death was ascertained from ONS mortality records. Stratified Cox proportional hazard models were estimated, with stepwise adjustment in different models for potential confounders or mediators between psoriasis and serious infection.

Results

There were 69\u00a0315 people with psoriasis and 338\u00a0620 comparators who were followed up for a median (interquartile range) of 4\u00b79 (5\u00b79) and 5\u00b71 (6\u00b73) years, respectively. People with psoriasis had a higher incidence rate of serious infection [20\u00b75 per 1000 person-years, 95% confidence interval (CI) 20\u00b70-21\u00b70, n = 7631] compared with those without psoriasis (16\u00b71 per 1000 person-years, 95% CI 15\u00b79-16\u00b73, n = 30\u00a0761). The fully adjusted hazard ratio for the association between psoriasis and serious infection was 1\u00b736 (95% CI 1\u00b731-1\u00b740), with similar results across the other outcomes.

Conclusions

Psoriasis is associated with a small increase in the risk of serious infection. Further research is needed to understand how psoriasis predisposes to a higher risk of infection.", + "abstract": "

Background

Atopic eczema is a common chronic inflammatory skin disease. Research suggests an association between atopic eczema and obesity, with inconsistent evidence from European populations.

Objectives

To explore the association between diagnosed atopic eczema and being overweight or obese, and whether increased atopic eczema severity was associated with higher body mass index.

Methods

We undertook a cross-sectional analysis within a cohort of adults (matched by age, sex and general practice) with and without a diagnosis of atopic eczema. We used primary care (Clinical Practice Research Datalink Gold) and linked hospital admissions data (1998-2016). We used conditional logistic regression to compare the odds of being overweight or obese (adjusting for confounders and potential mediators) in those with atopic eczema (mild, moderate and severe, and all eczema) vs. those without.

Results

We identified 441\u00a0746 people with atopic eczema, matched to 1\u00a0849\u00a0722 without. People with atopic eczema had slightly higher odds of being overweight or obese vs. those without [odds ratio (OR) 1\u00b708, 95% confidence interval (CI) 1\u00b707-1\u00b709] after adjusting for age, asthma and socioeconomic deprivation. Adjusting for potential mediators (high-dose glucocorticoids, harmful alcohol use, anxiety, depression, smoking) had a minimal impact on effect estimates (OR 1\u00b707, 95% CI 1\u00b706-1\u00b708). We saw no evidence that odds of being overweight or obese increased with increasing atopic eczema severity, and there was no association in people with severe eczema.

Conclusions

We found evidence of a small overall association between atopic eczema and being overweight or obese. However, there was no association with obesity among those with the most severe eczema. Our findings are largely reassuring for this prevalent patient group who may already have an increased risk of cardiovascular disease.", "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.19052; doi:https://doi.org/10.1111/bjd.19052" + "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4658151/1/Ascott-etal-2020_Atopic_eczema_and-obesity.pdf; doi:https://doi.org/10.1111/bjd.19597" }, { "id": "33637859", @@ -32469,23 +32469,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.rse.2021.112339; doi:https://doi.org/10.1016/j.rse.2021.112339; html:https://europepmc.org/articles/PMC7985619; pdf:https://europepmc.org/articles/PMC7985619?pdf=render" }, - { - "id": "35144751", - "doi": "https://doi.org/10.1016/j.jacc.2021.11.045", - "title": "Echocardiographic Deformation Imaging\u00a0for Early Detection of Genetic\u00a0Cardiomyopathies: JACC Review Topic of the Week.", - "authorString": "Taha K, Kirkels FP, Teske AJ, Asselbergs FW, van Tintelen JP, Doevendans PA, Kutty S, Haugaa KH, Cramer MJ.", - "authorAffiliations": "", - "journalTitle": "Journal of the American College of Cardiology", - "pubYear": "2022", - "date": "2022-02-01", - "isOpenAccess": "N", - "keywords": "Early Detection; Speckle Tracking; Family Screening; Deformation Imaging; Genetic Cardiomyopathy", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Clinical screening of the relatives of patients with genetic cardiomyopathies is challenging, as they often lack detectable cardiac abnormalities at presentation. Life-threatening adverse events can already occur in these early stages of disease, so sensitive tools to reveal the earliest signs of disease are needed. The utility of echocardiographic deformation imaging for early detection has been explored for this population in multiple studies but has not been broadly implemented in clinical practice. The authors discuss contemporary evidence on the utility of deformation imaging in relatives of patients with genetic cardiomyopathies. The available body of data shows that deformation imaging reveals early disease-specific abnormalities in dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic cardiomyopathy. Deformation imaging seems promising to enhance the screening and follow-up protocols in relatives, and the authors propose measures to accelerate its implementation in clinical care.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jacc.2021.11.045; doi:https://doi.org/10.1016/j.jacc.2021.11.045" - }, { "id": "33493433", "doi": "https://doi.org/10.1016/s1470-2045(20)30743-9", @@ -32503,6 +32486,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S1470204520307439/pdf; doi:https://doi.org/10.1016/S1470-2045(20)30743-9; html:https://europepmc.org/articles/PMC7825861; pdf:https://europepmc.org/articles/PMC7825861?pdf=render" }, + { + "id": "35144751", + "doi": "https://doi.org/10.1016/j.jacc.2021.11.045", + "title": "Echocardiographic Deformation Imaging\u00a0for Early Detection of Genetic\u00a0Cardiomyopathies: JACC Review Topic of the Week.", + "authorString": "Taha K, Kirkels FP, Teske AJ, Asselbergs FW, van Tintelen JP, Doevendans PA, Kutty S, Haugaa KH, Cramer MJ.", + "authorAffiliations": "", + "journalTitle": "Journal of the American College of Cardiology", + "pubYear": "2022", + "date": "2022-02-01", + "isOpenAccess": "N", + "keywords": "Early Detection; Speckle Tracking; Family Screening; Deformation Imaging; Genetic Cardiomyopathy", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Clinical screening of the relatives of patients with genetic cardiomyopathies is challenging, as they often lack detectable cardiac abnormalities at presentation. Life-threatening adverse events can already occur in these early stages of disease, so sensitive tools to reveal the earliest signs of disease are needed. The utility of echocardiographic deformation imaging for early detection has been explored for this population in multiple studies but has not been broadly implemented in clinical practice. The authors discuss contemporary evidence on the utility of deformation imaging in relatives of patients with genetic cardiomyopathies. The available body of data shows that deformation imaging reveals early disease-specific abnormalities in dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic cardiomyopathy. Deformation imaging seems promising to enhance the screening and follow-up protocols in relatives, and the authors propose measures to accelerate its implementation in clinical care.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.jacc.2021.11.045; doi:https://doi.org/10.1016/j.jacc.2021.11.045" + }, { "id": "34468736", "doi": "https://doi.org/10.1093/europace/euab162", @@ -32673,23 +32673,6 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1008605&type=printable; doi:https://doi.org/10.1371/journal.pgen.1008605; html:https://europepmc.org/articles/PMC7108731; pdf:https://europepmc.org/articles/PMC7108731?pdf=render" }, - { - "id": "37075078", - "doi": "https://doi.org/10.1371/journal.pmed.1004223", - "title": "The association between antihypertensive treatment and serious adverse events by age and frailty: A cohort study.", - "authorString": "Sheppard JP, Koshiaris C, Stevens R, Lay-Flurrie S, Banerjee A, Bellows BK, Clegg A, Hobbs FDR, Payne RA, Swain S, Usher-Smith JA, McManus RJ.", - "authorAffiliations": "", - "journalTitle": "PLoS medicine", - "pubYear": "2023", - "date": "2023-04-19", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Antihypertensives are effective at reducing the risk of cardiovascular disease, but limited data exist quantifying their association with serious adverse events, particularly in older people with frailty. This study aimed to examine this association using nationally representative electronic health record data.

Methods and findings

This was a retrospective cohort study utilising linked data from 1,256 general practices across England held within the Clinical Practice Research Datalink between 1998 and 2018. Included patients were aged 40+ years, with a systolic blood pressure reading between 130 and 179 mm Hg, and not previously prescribed antihypertensive treatment. The main exposure was defined as a first prescription of antihypertensive treatment. The primary outcome was hospitalisation or death within 10 years from falls. Secondary outcomes were hypotension, syncope, fractures, acute kidney injury, electrolyte abnormalities, and primary care attendance with gout. The association between treatment and these serious adverse events was examined by Cox regression adjusted for propensity score. This propensity score was generated from a multivariable logistic regression model with patient characteristics, medical history and medication prescriptions as covariates, and new antihypertensive treatment as the outcome. Subgroup analyses were undertaken by age and frailty. Of 3,834,056 patients followed for a median of 7.1 years, 484,187 (12.6%) were prescribed new antihypertensive treatment in the 12 months before the index date (baseline). Antihypertensives were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.23, 95% confidence interval (CI) 1.21 to 1.26), hypotension (aHR 1.32, 95% CI 1.29 to 1.35), syncope (aHR 1.20, 95% CI 1.17 to 1.22), acute kidney injury (aHR 1.44, 95% CI 1.41 to 1.47), electrolyte abnormalities (aHR 1.45, 95% CI 1.43 to 1.48), and primary care attendance with gout (aHR 1.35, 95% CI 1.32 to 1.37). The absolute risk of serious adverse events with treatment was very low, with 6 fall events per 10,000 patients treated per year. In older patients (80 to 89 years) and those with severe frailty, this absolute risk was increased, with 61 and 84 fall events per 10,000 patients treated per year (respectively). Findings were consistent in sensitivity analyses using different approaches to address confounding and taking into account the competing risk of death. A strength of this analysis is that it provides evidence regarding the association between antihypertensive treatment and serious adverse events, in a population of patients more representative than those enrolled in previous randomised controlled trials. Although treatment effect estimates fell within the 95% CIs of those from such trials, these analyses were observational in nature and so bias from unmeasured confounding cannot be ruled out.

Conclusions

Antihypertensive treatment was associated with serious adverse events. Overall, the absolute risk of this harm was low, with the exception of older patients and those with moderate to severe frailty, where the risks were similar to the likelihood of benefit from treatment. In these populations, physicians may want to consider alternative approaches to management of blood pressure and refrain from prescribing new treatment.", - "laySummary": "", - "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004223&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004223; html:https://europepmc.org/articles/PMC10155987; pdf:https://europepmc.org/articles/PMC10155987?pdf=render" - }, { "id": "31699727", "doi": "https://doi.org/10.1136/bmjopen-2019-030882", @@ -32707,6 +32690,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/9/11/e030882.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-030882; html:https://europepmc.org/articles/PMC6858135; pdf:https://europepmc.org/articles/PMC6858135?pdf=render" }, + { + "id": "37075078", + "doi": "https://doi.org/10.1371/journal.pmed.1004223", + "title": "The association between antihypertensive treatment and serious adverse events by age and frailty: A cohort study.", + "authorString": "Sheppard JP, Koshiaris C, Stevens R, Lay-Flurrie S, Banerjee A, Bellows BK, Clegg A, Hobbs FDR, Payne RA, Swain S, Usher-Smith JA, McManus RJ.", + "authorAffiliations": "", + "journalTitle": "PLoS medicine", + "pubYear": "2023", + "date": "2023-04-19", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Antihypertensives are effective at reducing the risk of cardiovascular disease, but limited data exist quantifying their association with serious adverse events, particularly in older people with frailty. This study aimed to examine this association using nationally representative electronic health record data.

Methods and findings

This was a retrospective cohort study utilising linked data from 1,256 general practices across England held within the Clinical Practice Research Datalink between 1998 and 2018. Included patients were aged 40+ years, with a systolic blood pressure reading between 130 and 179 mm Hg, and not previously prescribed antihypertensive treatment. The main exposure was defined as a first prescription of antihypertensive treatment. The primary outcome was hospitalisation or death within 10 years from falls. Secondary outcomes were hypotension, syncope, fractures, acute kidney injury, electrolyte abnormalities, and primary care attendance with gout. The association between treatment and these serious adverse events was examined by Cox regression adjusted for propensity score. This propensity score was generated from a multivariable logistic regression model with patient characteristics, medical history and medication prescriptions as covariates, and new antihypertensive treatment as the outcome. Subgroup analyses were undertaken by age and frailty. Of 3,834,056 patients followed for a median of 7.1 years, 484,187 (12.6%) were prescribed new antihypertensive treatment in the 12 months before the index date (baseline). Antihypertensives were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.23, 95% confidence interval (CI) 1.21 to 1.26), hypotension (aHR 1.32, 95% CI 1.29 to 1.35), syncope (aHR 1.20, 95% CI 1.17 to 1.22), acute kidney injury (aHR 1.44, 95% CI 1.41 to 1.47), electrolyte abnormalities (aHR 1.45, 95% CI 1.43 to 1.48), and primary care attendance with gout (aHR 1.35, 95% CI 1.32 to 1.37). The absolute risk of serious adverse events with treatment was very low, with 6 fall events per 10,000 patients treated per year. In older patients (80 to 89 years) and those with severe frailty, this absolute risk was increased, with 61 and 84 fall events per 10,000 patients treated per year (respectively). Findings were consistent in sensitivity analyses using different approaches to address confounding and taking into account the competing risk of death. A strength of this analysis is that it provides evidence regarding the association between antihypertensive treatment and serious adverse events, in a population of patients more representative than those enrolled in previous randomised controlled trials. Although treatment effect estimates fell within the 95% CIs of those from such trials, these analyses were observational in nature and so bias from unmeasured confounding cannot be ruled out.

Conclusions

Antihypertensive treatment was associated with serious adverse events. Overall, the absolute risk of this harm was low, with the exception of older patients and those with moderate to severe frailty, where the risks were similar to the likelihood of benefit from treatment. In these populations, physicians may want to consider alternative approaches to management of blood pressure and refrain from prescribing new treatment.", + "laySummary": "", + "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004223&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004223; html:https://europepmc.org/articles/PMC10155987; pdf:https://europepmc.org/articles/PMC10155987?pdf=render" + }, { "id": "29966429", "doi": "https://doi.org/10.1177/2047487318785228", @@ -32758,23 +32758,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1177/0300060520931298; doi:https://doi.org/10.1177/0300060520931298; html:https://europepmc.org/articles/PMC7307394; pdf:https://europepmc.org/articles/PMC7307394?pdf=render" }, - { - "id": "38388497", - "doi": "https://doi.org/10.1038/s41467-024-45355-3", - "title": "Concordance of randomised controlled trials for artificial intelligence interventions with the CONSORT-AI reporting guidelines.", - "authorString": "Martindale APL, Ng B, Ngai V, Kale AU, Ferrante di Ruffano L, Golub RM, Collins GS, Moher D, McCradden MD, Oakden-Rayner L, Rivera SC, Calvert M, Kelly CJ, Lee CS, Yau C, Chan AW, Keane PA, Beam AL, Denniston AK, Liu X.", - "authorAffiliations": "", - "journalTitle": "Nature communications", - "pubYear": "2024", - "date": "2024-02-22", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The Consolidated Standards of Reporting Trials extension for Artificial Intelligence interventions (CONSORT-AI) was published in September 2020. Since its publication, several randomised controlled trials (RCTs) of AI interventions have been published but their completeness and transparency of reporting is unknown. This systematic review assesses the completeness of reporting of AI RCTs following publication of CONSORT-AI and provides a comprehensive summary of RCTs published in recent years. 65 RCTs were identified, mostly conducted in China (37%) and USA (18%). Median concordance with CONSORT-AI reporting was 90% (IQR 77-94%), although only 10 RCTs explicitly reported its use. Several items were consistently under-reported, including algorithm version, accessibility of the AI intervention or code, and references to a study protocol. Only 3 of 52 included journals explicitly endorsed or mandated CONSORT-AI. Despite a generally high concordance amongst recent AI RCTs, some AI-specific considerations remain systematically poorly reported. Further encouragement of CONSORT-AI adoption by journals and funders may enable more complete adoption of the full CONSORT-AI guidelines.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41467-024-45355-3.pdf; doi:https://doi.org/10.1038/s41467-024-45355-3; html:https://europepmc.org/articles/PMC10883966; pdf:https://europepmc.org/articles/PMC10883966?pdf=render" - }, { "id": "33414548", "doi": "https://doi.org/10.1038/s41588-020-00751-5", @@ -32792,6 +32775,23 @@ "laySummary": "", "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612925; doi:https://doi.org/10.1038/s41588-020-00751-5; html:https://europepmc.org/articles/PMC7612925; pdf:https://europepmc.org/articles/PMC7612925?pdf=render; doi:https://doi.org/10.1038/s41588-020-00751-5" }, + { + "id": "38388497", + "doi": "https://doi.org/10.1038/s41467-024-45355-3", + "title": "Concordance of randomised controlled trials for artificial intelligence interventions with the CONSORT-AI reporting guidelines.", + "authorString": "Martindale APL, Ng B, Ngai V, Kale AU, Ferrante di Ruffano L, Golub RM, Collins GS, Moher D, McCradden MD, Oakden-Rayner L, Rivera SC, Calvert M, Kelly CJ, Lee CS, Yau C, Chan AW, Keane PA, Beam AL, Denniston AK, Liu X.", + "authorAffiliations": "", + "journalTitle": "Nature communications", + "pubYear": "2024", + "date": "2024-02-22", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The Consolidated Standards of Reporting Trials extension for Artificial Intelligence interventions (CONSORT-AI) was published in September 2020. Since its publication, several randomised controlled trials (RCTs) of AI interventions have been published but their completeness and transparency of reporting is unknown. This systematic review assesses the completeness of reporting of AI RCTs following publication of CONSORT-AI and provides a comprehensive summary of RCTs published in recent years. 65 RCTs were identified, mostly conducted in China (37%) and USA (18%). Median concordance with CONSORT-AI reporting was 90% (IQR 77-94%), although only 10 RCTs explicitly reported its use. Several items were consistently under-reported, including algorithm version, accessibility of the AI intervention or code, and references to a study protocol. Only 3 of 52 included journals explicitly endorsed or mandated CONSORT-AI. Despite a generally high concordance amongst recent AI RCTs, some AI-specific considerations remain systematically poorly reported. Further encouragement of CONSORT-AI adoption by journals and funders may enable more complete adoption of the full CONSORT-AI guidelines.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41467-024-45355-3.pdf; doi:https://doi.org/10.1038/s41467-024-45355-3; html:https://europepmc.org/articles/PMC10883966; pdf:https://europepmc.org/articles/PMC10883966?pdf=render" + }, { "id": "33391794", "doi": "https://doi.org/10.1098/rsos.200958", @@ -33047,23 +33047,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.bja.2021.10.038; doi:https://doi.org/10.1016/j.bja.2021.10.038" }, - { - "id": "34648354", - "doi": "https://doi.org/10.1126/science.abj1541", - "title": "Mapping the proteo-genomic convergence of human diseases.", - "authorString": "Pietzner M, Wheeler E, Carrasco-Zanini J, Cortes A, Koprulu M, W\u00f6rheide MA, Oerton E, Cook J, Stewart ID, Kerrison ND, Luan J, Raffler J, Arnold M, Arlt W, O'Rahilly S, Kastenm\u00fcller G, Gamazon ER, Hingorani AD, Scott RA, Wareham NJ, Langenberg C.", - "authorAffiliations": "", - "journalTitle": "Science (New York, N.Y.)", - "pubYear": "2021", - "date": "2021-11-12", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Characterization of the genetic regulation of proteins is essential for understanding disease etiology and developing therapies. We identified 10,674 genetic associations for 3892 plasma proteins to create a cis-anchored gene-protein-disease map of 1859 connections that highlights strong cross-disease biological convergence. This proteo-genomic map provides a framework to connect etiologically related diseases, to provide biological context for new or emerging disorders, and to integrate different biological domains to establish mechanisms for known gene-disease links. Our results identify proteo-genomic connections within and between diseases and establish the value of cis-protein variants for annotation of likely causal disease genes at loci identified in genome-wide association studies, thereby addressing a major barrier to experimental validation and clinical translation of genetic discoveries.", - "laySummary": "", - "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9904207; doi:https://doi.org/10.1126/science.abj1541; html:https://europepmc.org/articles/PMC9904207; pdf:https://europepmc.org/articles/PMC9904207?pdf=render; doi:https://doi.org/10.1126/science.abj1541" - }, { "id": "31820220", "doi": "https://doi.org/10.1007/s10926-019-09867-w", @@ -33099,21 +33082,21 @@ "urls": "pdf:https://cardiab.biomedcentral.com/track/pdf/10.1186/s12933-019-0972-4; doi:https://doi.org/10.1186/s12933-019-0972-4; html:https://europepmc.org/articles/PMC6900858; pdf:https://europepmc.org/articles/PMC6900858?pdf=render" }, { - "id": "37060915", - "doi": "https://doi.org/10.1016/s0140-6736(23)00510-x", - "title": "Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial.", - "authorString": "RECOVERY Collaborative Group. Electronic address: recoverytrial@ndph.ox.ac.uk, RECOVERY Collaborative Group.", + "id": "34648354", + "doi": "https://doi.org/10.1126/science.abj1541", + "title": "Mapping the proteo-genomic convergence of human diseases.", + "authorString": "Pietzner M, Wheeler E, Carrasco-Zanini J, Cortes A, Koprulu M, W\u00f6rheide MA, Oerton E, Cook J, Stewart ID, Kerrison ND, Luan J, Raffler J, Arnold M, Arlt W, O'Rahilly S, Kastenm\u00fcller G, Gamazon ER, Hingorani AD, Scott RA, Wareham NJ, Langenberg C.", "authorAffiliations": "", - "journalTitle": "Lancet (London, England)", - "pubYear": "2023", - "date": "2023-04-13", - "isOpenAccess": "Y", + "journalTitle": "Science (New York, N.Y.)", + "pubYear": "2021", + "date": "2021-11-12", + "isOpenAccess": "N", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group.

Methods

This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation <92% on room air) were randomly allocated (1:1) to either usual care with higher dose corticosteroids (dexamethasone 20 mg once daily for 5 days followed by 10 mg dexamethasone once daily for 5 days or until discharge if sooner) or usual standard of care alone (which included dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality among all randomised participants. On May 11, 2022, the independent data monitoring committee recommended stopping recruitment of patients receiving no oxygen or simple oxygen only due to safety concerns. We report the results for these participants only. Recruitment of patients receiving ventilatory support is ongoing. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1\u00b759 [95% CI 1\u00b720-2\u00b710]; p=0\u00b70012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3\u00b77% [95% CI 0\u00b77-6\u00b76]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7\u00b74% [95% CI 3\u00b72-11\u00b75]).

Interpretation

In patients hospitalised for COVID-19 with clinical hypoxia who required either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared with usual care, which included low-dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation.

Funding

UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust.", + "abstract": "Characterization of the genetic regulation of proteins is essential for understanding disease etiology and developing therapies. We identified 10,674 genetic associations for 3892 plasma proteins to create a cis-anchored gene-protein-disease map of 1859 connections that highlights strong cross-disease biological convergence. This proteo-genomic map provides a framework to connect etiologically related diseases, to provide biological context for new or emerging disorders, and to integrate different biological domains to establish mechanisms for known gene-disease links. Our results identify proteo-genomic connections within and between diseases and establish the value of cis-protein variants for annotation of likely causal disease genes at loci identified in genome-wide association studies, thereby addressing a major barrier to experimental validation and clinical translation of genetic discoveries.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/s0140-6736(23)00510-x; doi:https://doi.org/10.1016/S0140-6736(23)00510-X; html:https://europepmc.org/articles/PMC10156147; pdf:https://europepmc.org/articles/PMC10156147?pdf=render" + "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9904207; doi:https://doi.org/10.1126/science.abj1541; html:https://europepmc.org/articles/PMC9904207; pdf:https://europepmc.org/articles/PMC9904207?pdf=render; doi:https://doi.org/10.1126/science.abj1541" }, { "id": "37117689", @@ -33132,6 +33115,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s43016-021-00309-6.pdf; doi:https://doi.org/10.1038/s43016-021-00309-6" }, + { + "id": "37060915", + "doi": "https://doi.org/10.1016/s0140-6736(23)00510-x", + "title": "Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial.", + "authorString": "RECOVERY Collaborative Group. Electronic address: recoverytrial@ndph.ox.ac.uk, RECOVERY Collaborative Group.", + "authorAffiliations": "", + "journalTitle": "Lancet (London, England)", + "pubYear": "2023", + "date": "2023-04-13", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group.

Methods

This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation <92% on room air) were randomly allocated (1:1) to either usual care with higher dose corticosteroids (dexamethasone 20 mg once daily for 5 days followed by 10 mg dexamethasone once daily for 5 days or until discharge if sooner) or usual standard of care alone (which included dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality among all randomised participants. On May 11, 2022, the independent data monitoring committee recommended stopping recruitment of patients receiving no oxygen or simple oxygen only due to safety concerns. We report the results for these participants only. Recruitment of patients receiving ventilatory support is ongoing. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1\u00b759 [95% CI 1\u00b720-2\u00b710]; p=0\u00b70012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3\u00b77% [95% CI 0\u00b77-6\u00b76]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7\u00b74% [95% CI 3\u00b72-11\u00b75]).

Interpretation

In patients hospitalised for COVID-19 with clinical hypoxia who required either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared with usual care, which included low-dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation.

Funding

UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/s0140-6736(23)00510-x; doi:https://doi.org/10.1016/S0140-6736(23)00510-X; html:https://europepmc.org/articles/PMC10156147; pdf:https://europepmc.org/articles/PMC10156147?pdf=render" + }, { "id": "35907789", "doi": "https://doi.org/10.1186/s12859-022-04838-0", @@ -33183,23 +33183,6 @@ "laySummary": "", "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.768245/pdf; doi:https://doi.org/10.3389/fcvm.2021.768245; html:https://europepmc.org/articles/PMC8649951; pdf:https://europepmc.org/articles/PMC8649951?pdf=render" }, - { - "id": "38613554", - "doi": "https://doi.org/10.1016/j.jcmg.2024.01.009", - "title": "Cardiovascular Magnetic Resonance Reference Ranges From the Healthy\u00a0Hearts Consortium.", - "authorString": "Raisi-Estabragh Z, Szabo L, McCracken C, B\u00fclow R, Aquaro GD, Andre F, Le TT, Such\u00e1 D, Condurache DG, Salih AM, Chadalavada S, Aung N, Lee AM, Harvey NC, Leiner T, Chin CWL, Friedrich MG, Barison A, D\u00f6rr M, Petersen SE.", - "authorAffiliations": "", - "journalTitle": "JACC. Cardiovascular imaging", - "pubYear": "2024", - "date": "2024-03-26", - "isOpenAccess": "N", - "keywords": "Artificial intelligence; Automated analysis; Sex differences; Ethnicity; Cardiovascular Magnetic Resonance; Healthy Reference Ranges", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

The absence of population-stratified cardiovascular magnetic resonance (CMR) reference ranges from large cohorts is a major shortcoming for clinical care.

Objectives

This paper provides age-, sex-, and ethnicity-specific CMR reference ranges for atrial and ventricular metrics from the Healthy Hearts Consortium, an international collaborative comprising 9,088 CMR studies from verified healthy individuals, covering the complete adult age spectrum across both sexes, and with the highest ethnic diversity reported to date.

Methods

CMR studies were analyzed using certified software with batch processing capability (cvi42, version 5.14 prototype, Circle Cardiovascular Imaging) by 2 expert readers. Three segmentation methods (smooth, papillary, anatomic) were used to contour the endocardial and epicardial borders of the ventricles and atria from long- and short-axis cine series. Clinically established ventricular and atrial metrics were extracted and stratified by age, sex, and ethnicity. Variations by segmentation method, scanner vendor, and magnet strength were examined. Reference ranges are reported as 95% prediction intervals.

Results

The sample included 4,452 (49.0%) men and 4,636 (51.0%) women with average age of 61.1 \u00b1 12.9 years (range: 18-83 years). Among these, 7,424 (81.7%) were from White, 510 (5.6%) South Asian, 478 (5.3%) mixed/other, 341 (3.7%) Black, and 335 (3.7%) Chinese ethnicities. Images were acquired using 1.5-T (n\u00a0=\u00a08,779; 96.6%) and 3.0-T (n\u00a0=\u00a0309; 3.4%) scanners from Siemens (n\u00a0=\u00a08,299; 91.3%), Philips (n\u00a0=\u00a0498; 5.5%), and GE (n\u00a0=\u00a0291, 3.2%).

Conclusions

This work represents a resource with healthy CMR-derived volumetric reference ranges ready for clinical implementation.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jcmg.2024.01.009" - }, { "id": "31564467", "doi": "https://doi.org/10.1016/s2215-0366(19)30369-4", @@ -33217,6 +33200,23 @@ "laySummary": "", "urls": "pdf:http://pure-oai.bham.ac.uk/ws/files/77236664/Chandan_et_al_The_burden_of_mental_ill_health_associated_with_childhood_maltreatment_in_the_UK_using_The_Health_Improvement_Network_database_The_Lancet_Psychiatry_2019.pdf; doi:https://doi.org/10.1016/S2215-0366(19)30369-4" }, + { + "id": "38613554", + "doi": "https://doi.org/10.1016/j.jcmg.2024.01.009", + "title": "Cardiovascular Magnetic Resonance Reference Ranges From the Healthy\u00a0Hearts Consortium.", + "authorString": "Raisi-Estabragh Z, Szabo L, McCracken C, B\u00fclow R, Aquaro GD, Andre F, Le TT, Such\u00e1 D, Condurache DG, Salih AM, Chadalavada S, Aung N, Lee AM, Harvey NC, Leiner T, Chin CWL, Friedrich MG, Barison A, D\u00f6rr M, Petersen SE.", + "authorAffiliations": "", + "journalTitle": "JACC. Cardiovascular imaging", + "pubYear": "2024", + "date": "2024-03-26", + "isOpenAccess": "N", + "keywords": "Artificial intelligence; Automated analysis; Sex differences; Ethnicity; Cardiovascular Magnetic Resonance; Healthy Reference Ranges", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

The absence of population-stratified cardiovascular magnetic resonance (CMR) reference ranges from large cohorts is a major shortcoming for clinical care.

Objectives

This paper provides age-, sex-, and ethnicity-specific CMR reference ranges for atrial and ventricular metrics from the Healthy Hearts Consortium, an international collaborative comprising 9,088 CMR studies from verified healthy individuals, covering the complete adult age spectrum across both sexes, and with the highest ethnic diversity reported to date.

Methods

CMR studies were analyzed using certified software with batch processing capability (cvi42, version 5.14 prototype, Circle Cardiovascular Imaging) by 2 expert readers. Three segmentation methods (smooth, papillary, anatomic) were used to contour the endocardial and epicardial borders of the ventricles and atria from long- and short-axis cine series. Clinically established ventricular and atrial metrics were extracted and stratified by age, sex, and ethnicity. Variations by segmentation method, scanner vendor, and magnet strength were examined. Reference ranges are reported as 95% prediction intervals.

Results

The sample included 4,452 (49.0%) men and 4,636 (51.0%) women with average age of 61.1 \u00b1 12.9 years (range: 18-83 years). Among these, 7,424 (81.7%) were from White, 510 (5.6%) South Asian, 478 (5.3%) mixed/other, 341 (3.7%) Black, and 335 (3.7%) Chinese ethnicities. Images were acquired using 1.5-T (n\u00a0=\u00a08,779; 96.6%) and 3.0-T (n\u00a0=\u00a0309; 3.4%) scanners from Siemens (n\u00a0=\u00a08,299; 91.3%), Philips (n\u00a0=\u00a0498; 5.5%), and GE (n\u00a0=\u00a0291, 3.2%).

Conclusions

This work represents a resource with healthy CMR-derived volumetric reference ranges ready for clinical implementation.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.jcmg.2024.01.009" + }, { "id": "35247983", "doi": "https://doi.org/10.1186/s12877-021-02673-1", @@ -33268,6 +33268,23 @@ "laySummary": "", "urls": "pdf:https://gh.bmj.com/content/bmjgh/6/9/e006204.full.pdf; doi:https://doi.org/10.1136/bmjgh-2021-006204; html:https://europepmc.org/articles/PMC8413469; pdf:https://europepmc.org/articles/PMC8413469?pdf=render" }, + { + "id": "31233103", + "doi": "https://doi.org/10.1093/bioinformatics/btz469", + "title": "PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations.", + "authorString": "Kamat MA, Blackshaw JA, Young R, Surendran P, Burgess S, Danesh J, Butterworth AS, Staley JR.", + "authorAffiliations": "", + "journalTitle": "Bioinformatics (Oxford, England)", + "pubYear": "2019", + "date": "2019-11-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "Applied Analytics", + "healthCategories": "", + "abstract": "

Summary

PhenoScanner is a curated database of publicly available results from large-scale genetic association studies in humans. This online tool facilitates 'phenome scans', where genetic variants are cross-referenced for association with many phenotypes of different types. Here we present a major update of PhenoScanner ('PhenoScanner V2'), including over 150 million genetic variants and more than 65 billion associations (compared to 350 million associations in PhenoScanner V1) with diseases and traits, gene expression, metabolite and protein levels, and epigenetic markers. The query options have been extended to include searches by genes, genomic regions and phenotypes, as well as for genetic variants. All variants are positionally annotated using the Variant Effect Predictor and the phenotypes are mapped to Experimental Factor Ontology terms. Linkage disequilibrium statistics from the 1000 Genomes project can be used to search for phenotype associations with proxy variants.

Availability and implementation

PhenoScanner V2 is available at www.phenoscanner.medschl.cam.ac.uk.", + "laySummary": "Kamat et al. developed an improved version of phenoscanner which is a publicly available large-scale genetic dataset for evaluation of genetic associations.", + "urls": "pdf:https://academic.oup.com/bioinformatics/article-pdf/35/22/4851/30706861/btz469.pdf; doi:https://doi.org/10.1093/bioinformatics/btz469; html:https://europepmc.org/articles/PMC6853652; pdf:https://europepmc.org/articles/PMC6853652?pdf=render" + }, { "id": "35365070", "doi": "https://doi.org/10.1186/s12879-022-07268-8", @@ -33302,23 +33319,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41598-021-86331-x.pdf; doi:https://doi.org/10.1038/s41598-021-86331-x; html:https://europepmc.org/articles/PMC8062687; pdf:https://europepmc.org/articles/PMC8062687?pdf=render" }, - { - "id": "31233103", - "doi": "https://doi.org/10.1093/bioinformatics/btz469", - "title": "PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations.", - "authorString": "Kamat MA, Blackshaw JA, Young R, Surendran P, Burgess S, Danesh J, Butterworth AS, Staley JR.", - "authorAffiliations": "", - "journalTitle": "Bioinformatics (Oxford, England)", - "pubYear": "2019", - "date": "2019-11-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "Applied Analytics", - "healthCategories": "", - "abstract": "

Summary

PhenoScanner is a curated database of publicly available results from large-scale genetic association studies in humans. This online tool facilitates 'phenome scans', where genetic variants are cross-referenced for association with many phenotypes of different types. Here we present a major update of PhenoScanner ('PhenoScanner V2'), including over 150 million genetic variants and more than 65 billion associations (compared to 350 million associations in PhenoScanner V1) with diseases and traits, gene expression, metabolite and protein levels, and epigenetic markers. The query options have been extended to include searches by genes, genomic regions and phenotypes, as well as for genetic variants. All variants are positionally annotated using the Variant Effect Predictor and the phenotypes are mapped to Experimental Factor Ontology terms. Linkage disequilibrium statistics from the 1000 Genomes project can be used to search for phenotype associations with proxy variants.

Availability and implementation

PhenoScanner V2 is available at www.phenoscanner.medschl.cam.ac.uk.", - "laySummary": "Kamat et al. developed an improved version of phenoscanner which is a publicly available large-scale genetic dataset for evaluation of genetic associations.", - "urls": "pdf:https://academic.oup.com/bioinformatics/article-pdf/35/22/4851/30706861/btz469.pdf; doi:https://doi.org/10.1093/bioinformatics/btz469; html:https://europepmc.org/articles/PMC6853652; pdf:https://europepmc.org/articles/PMC6853652?pdf=render" - }, { "id": "34503513", "doi": "https://doi.org/10.1186/s12916-021-02087-1", @@ -33336,23 +33336,6 @@ "laySummary": "", "urls": "pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-021-02087-1; doi:https://doi.org/10.1186/s12916-021-02087-1; html:https://europepmc.org/articles/PMC8431908; pdf:https://europepmc.org/articles/PMC8431908?pdf=render" }, - { - "id": "37605204", - "doi": "https://doi.org/10.1186/s12916-023-03013-3", - "title": "The development of a core outcome set for studies of pregnant women with multimorbidity.", - "authorString": "Lee SI, Hanley S, Vowles Z, Plachcinski R, Moss N, Singh M, Gale C, Fagbamigbe AF, Azcoaga-Lorenzo A, Subramanian A, Taylor B, Nelson-Piercy C, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Dolk H, Hope H, Phillips K, Abel KM, Eastwood KA, Kent L, Locock L, Loane M, Mhereeg M, Brocklehurst P, McCann S, Brophy S, Wambua S, Hemali Sudasinghe SPB, Thangaratinam S, Nirantharakumar K, Black M, MuM-PreDiCT Group.", - "authorAffiliations": "", - "journalTitle": "BMC medicine", - "pubYear": "2023", - "date": "2023-08-21", - "isOpenAccess": "Y", - "keywords": "Pregnancy; Maternity; Outcome; Multimorbidity; Multiple Chronic Conditions; Core Outcome Set; Multiple Long-term Conditions", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Heterogeneity in reported outcomes can limit the synthesis of research evidence. A core outcome set informs what outcomes are important and should be measured as a minimum in all future studies. We report the development of a core outcome set applicable to observational and interventional studies of pregnant women with multimorbidity.

Methods

We developed the core outcome set in four stages: (i) a systematic literature search, (ii) three focus groups with UK stakeholders, (iii) two rounds of Delphi surveys with international stakeholders and (iv) two international virtual consensus meetings. Stakeholders included women with multimorbidity and experience of pregnancy in the last 5 years, or are planning a pregnancy, their partners, health or social care professionals and researchers. Study adverts were shared through stakeholder charities and organisations.

Results

Twenty-six studies were included in the systematic literature search (2017 to 2021) reporting 185 outcomes. Thematic analysis of the focus groups added a further 28 outcomes. Two hundred and nine stakeholders completed the first Delphi survey. One hundred and sixteen stakeholders completed the second Delphi survey where 45 outcomes reached Consensus In (\u226570% of all participants rating an outcome as Critically Important). Thirteen stakeholders reviewed 15 Borderline outcomes in the first consensus meeting and included seven additional outcomes. Seventeen stakeholders reviewed these 52 outcomes in a second consensus meeting, the threshold was \u226580% of all participants voting for inclusion. The final core outcome set included 11 outcomes. The five maternal outcomes were as follows: maternal death, severe maternal morbidity, change in existing long-term conditions (physical and mental), quality and experience of care and development of new mental health conditions. The six child outcomes were as follows: survival of baby, gestational age at birth, neurodevelopmental conditions/impairment, quality of life, birth weight and separation of baby from mother for health care needs.

Conclusions

Multimorbidity in pregnancy is a new and complex clinical research area. Following a rigorous process, this complexity was meaningfully reduced to a core outcome set that balances the views of a diverse stakeholder group.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s12916-023-03013-3; html:https://europepmc.org/articles/PMC10441728; pdf:https://europepmc.org/articles/PMC10441728?pdf=render" - }, { "id": "31912232", "doi": "https://doi.org/10.1007/s00394-019-02170-7", @@ -33387,6 +33370,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/bioinformatics/article-pdf/36/24/5632/36899551/btaa1079.pdf; doi:https://doi.org/10.1093/bioinformatics/btaa1079; html:https://europepmc.org/articles/PMC8023682; pdf:https://europepmc.org/articles/PMC8023682?pdf=render" }, + { + "id": "37605204", + "doi": "https://doi.org/10.1186/s12916-023-03013-3", + "title": "The development of a core outcome set for studies of pregnant women with multimorbidity.", + "authorString": "Lee SI, Hanley S, Vowles Z, Plachcinski R, Moss N, Singh M, Gale C, Fagbamigbe AF, Azcoaga-Lorenzo A, Subramanian A, Taylor B, Nelson-Piercy C, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Dolk H, Hope H, Phillips K, Abel KM, Eastwood KA, Kent L, Locock L, Loane M, Mhereeg M, Brocklehurst P, McCann S, Brophy S, Wambua S, Hemali Sudasinghe SPB, Thangaratinam S, Nirantharakumar K, Black M, MuM-PreDiCT Group.", + "authorAffiliations": "", + "journalTitle": "BMC medicine", + "pubYear": "2023", + "date": "2023-08-21", + "isOpenAccess": "Y", + "keywords": "Pregnancy; Maternity; Outcome; Multimorbidity; Multiple Chronic Conditions; Core Outcome Set; Multiple Long-term Conditions", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Heterogeneity in reported outcomes can limit the synthesis of research evidence. A core outcome set informs what outcomes are important and should be measured as a minimum in all future studies. We report the development of a core outcome set applicable to observational and interventional studies of pregnant women with multimorbidity.

Methods

We developed the core outcome set in four stages: (i) a systematic literature search, (ii) three focus groups with UK stakeholders, (iii) two rounds of Delphi surveys with international stakeholders and (iv) two international virtual consensus meetings. Stakeholders included women with multimorbidity and experience of pregnancy in the last 5 years, or are planning a pregnancy, their partners, health or social care professionals and researchers. Study adverts were shared through stakeholder charities and organisations.

Results

Twenty-six studies were included in the systematic literature search (2017 to 2021) reporting 185 outcomes. Thematic analysis of the focus groups added a further 28 outcomes. Two hundred and nine stakeholders completed the first Delphi survey. One hundred and sixteen stakeholders completed the second Delphi survey where 45 outcomes reached Consensus In (\u226570% of all participants rating an outcome as Critically Important). Thirteen stakeholders reviewed 15 Borderline outcomes in the first consensus meeting and included seven additional outcomes. Seventeen stakeholders reviewed these 52 outcomes in a second consensus meeting, the threshold was \u226580% of all participants voting for inclusion. The final core outcome set included 11 outcomes. The five maternal outcomes were as follows: maternal death, severe maternal morbidity, change in existing long-term conditions (physical and mental), quality and experience of care and development of new mental health conditions. The six child outcomes were as follows: survival of baby, gestational age at birth, neurodevelopmental conditions/impairment, quality of life, birth weight and separation of baby from mother for health care needs.

Conclusions

Multimorbidity in pregnancy is a new and complex clinical research area. Following a rigorous process, this complexity was meaningfully reduced to a core outcome set that balances the views of a diverse stakeholder group.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s12916-023-03013-3; html:https://europepmc.org/articles/PMC10441728; pdf:https://europepmc.org/articles/PMC10441728?pdf=render" + }, { "id": "33821553", "doi": "https://doi.org/10.1002/jia2.25697", @@ -33557,6 +33557,23 @@ "laySummary": "", "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fmicb.2023.1070340/pdf; doi:https://doi.org/10.3389/fmicb.2023.1070340; html:https://europepmc.org/articles/PMC10043416; pdf:https://europepmc.org/articles/PMC10043416?pdf=render" }, + { + "id": "33325834", + "doi": "https://doi.org/10.2196/23530", + "title": "Cystic Fibrosis Point of Personalized Detection (CFPOPD): An Interactive Web Application.", + "authorString": "Wolfe C, Pestian T, Gecili E, Su W, Keogh RH, Pestian JP, Seid M, Diggle PJ, Ziady A, Clancy JP, Grossoehme DH, Szczesniak RD, Brokamp C.", + "authorAffiliations": "", + "journalTitle": "JMIR medical informatics", + "pubYear": "2020", + "date": "2020-12-16", + "isOpenAccess": "Y", + "keywords": "Chronic disease; Clinical Decision Support; Medical Monitoring; Clinical Decision Rules; Application Programming Interface", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Despite steady gains in life expectancy, individuals with cystic fibrosis (CF) lung disease still experience rapid pulmonary decline throughout their clinical course, which can ultimately end in respiratory failure. Point-of-care tools for accurate and timely information regarding the risk of rapid decline is essential for clinical decision support.

Objective

This study aims to translate a novel algorithm for earlier, more accurate prediction of rapid lung function decline in patients with CF into an interactive web-based application that can be integrated within electronic health record systems, via collaborative development with clinicians.

Methods

Longitudinal clinical history, lung function measurements, and time-invariant characteristics were obtained for 30,879 patients with CF who were followed in the US Cystic Fibrosis Foundation Patient Registry (2003-2015). We iteratively developed the application using the R Shiny framework and by conducting a qualitative study with care provider focus groups (N=17).

Results

A clinical conceptual model and 4 themes were identified through coded feedback from application users: (1) ambiguity in rapid decline, (2) clinical utility, (3) clinical significance, and (4) specific suggested revisions. These themes were used to revise our application to the currently released version, available online for exploration. This study has advanced the application's potential prognostic utility for monitoring individuals with CF lung disease. Further application development will incorporate additional clinical characteristics requested by the users and also a more modular layout that can be useful for care provider and family interactions.

Conclusions

Our framework for creating an interactive and visual analytics platform enables generalized development of applications to synthesize, model, and translate electronic health data, thereby enhancing clinical decision support and improving care and health outcomes for chronic diseases and disorders. A prospective implementation study is necessary to evaluate this tool's effectiveness regarding increased communication, enhanced shared decision-making, and improved clinical outcomes for patients with CF.", + "laySummary": "", + "urls": "pdf:https://medinform.jmir.org/2020/12/e23530/PDF; doi:https://doi.org/10.2196/23530; html:https://europepmc.org/articles/PMC7773511" + }, { "id": "32951912", "doi": "https://doi.org/10.1016/j.jhep.2020.08.030", @@ -33592,21 +33609,21 @@ "urls": "doi:https://doi.org/10.1038/s41598-023-33391-w; doi:https://doi.org/10.1038/s41598-023-33391-w; html:https://europepmc.org/articles/PMC10199085; pdf:https://europepmc.org/articles/PMC10199085?pdf=render" }, { - "id": "33325834", - "doi": "https://doi.org/10.2196/23530", - "title": "Cystic Fibrosis Point of Personalized Detection (CFPOPD): An Interactive Web Application.", - "authorString": "Wolfe C, Pestian T, Gecili E, Su W, Keogh RH, Pestian JP, Seid M, Diggle PJ, Ziady A, Clancy JP, Grossoehme DH, Szczesniak RD, Brokamp C.", + "id": "34965929", + "doi": "https://doi.org/10.1136/bmj-2021-065834", + "title": "GP consultation rates for sequelae after acute covid-19 in patients managed in the community or hospital in the UK: population based study.", + "authorString": "Whittaker HR, Gulea C, Koteci A, Kallis C, Morgan AD, Iwundu C, Weeks M, Gupta R, Quint JK.", "authorAffiliations": "", - "journalTitle": "JMIR medical informatics", - "pubYear": "2020", - "date": "2020-12-16", + "journalTitle": "BMJ (Clinical research ed.)", + "pubYear": "2021", + "date": "2021-12-29", "isOpenAccess": "Y", - "keywords": "Chronic disease; Clinical Decision Support; Medical Monitoring; Clinical Decision Rules; Application Programming Interface", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Despite steady gains in life expectancy, individuals with cystic fibrosis (CF) lung disease still experience rapid pulmonary decline throughout their clinical course, which can ultimately end in respiratory failure. Point-of-care tools for accurate and timely information regarding the risk of rapid decline is essential for clinical decision support.

Objective

This study aims to translate a novel algorithm for earlier, more accurate prediction of rapid lung function decline in patients with CF into an interactive web-based application that can be integrated within electronic health record systems, via collaborative development with clinicians.

Methods

Longitudinal clinical history, lung function measurements, and time-invariant characteristics were obtained for 30,879 patients with CF who were followed in the US Cystic Fibrosis Foundation Patient Registry (2003-2015). We iteratively developed the application using the R Shiny framework and by conducting a qualitative study with care provider focus groups (N=17).

Results

A clinical conceptual model and 4 themes were identified through coded feedback from application users: (1) ambiguity in rapid decline, (2) clinical utility, (3) clinical significance, and (4) specific suggested revisions. These themes were used to revise our application to the currently released version, available online for exploration. This study has advanced the application's potential prognostic utility for monitoring individuals with CF lung disease. Further application development will incorporate additional clinical characteristics requested by the users and also a more modular layout that can be useful for care provider and family interactions.

Conclusions

Our framework for creating an interactive and visual analytics platform enables generalized development of applications to synthesize, model, and translate electronic health data, thereby enhancing clinical decision support and improving care and health outcomes for chronic diseases and disorders. A prospective implementation study is necessary to evaluate this tool's effectiveness regarding increased communication, enhanced shared decision-making, and improved clinical outcomes for patients with CF.", + "abstract": "

Objectives

To describe the rates for consulting a general practitioner (GP) for sequelae after acute covid-19 in patients admitted to hospital with covid-19 and those managed in the community, and to determine how the rates change over time for patients in the community and after vaccination for covid-19.

Design

Population based study.

Setting

1392 general practices in England contributing to the Clinical Practice Research Datalink Aurum database.

Participants

456\u2009002 patients with a diagnosis of covid-19 between 1 August 2020 and 14 February 2021 (44.7% men; median age 61 years), admitted to hospital within two weeks of diagnosis or managed in the community, and followed-up for a maximum of 9.2 months. A negative control group included individuals without covid-19 (n=38\u2009511) and patients with influenza before the pandemic (n=21\u2009803).

Main outcome measures

Comparison of rates for consulting a GP for new symptoms, diseases, prescriptions, and healthcare use in individuals admitted to hospital and those managed in the community, separately, before and after covid-19 infection, using Cox regression and negative binomial regression for healthcare use. The analysis was repeated for the negative control and influenza cohorts. In individuals in the community, outcomes were also described over time after a diagnosis of covid-19, and compared before and after vaccination for individuals who were symptomatic after covid-19 infection, using negative binomial regression.

Results

Relative to the negative control and influenza cohorts, patients in the community (n=437\u2009943) had significantly higher GP consultation rates for multiple sequelae, and the most common were loss of smell or taste, or both (adjusted hazard ratio 5.28, 95% confidence interval 3.89 to 7.17, P<0.001); venous thromboembolism (3.35, 2.87 to 3.91, P<0.001); lung fibrosis (2.41, 1.37 to 4.25, P=0.002), and muscle pain (1.89, 1.63 to 2.20, P<0.001); and also for healthcare use after a diagnosis of covid-19 compared with 12 months before infection. For absolute proportions, the most common outcomes \u22654 weeks after a covid-19 diagnosis in patients in the community were joint pain (2.5%), anxiety (1.2%), and prescriptions for non-steroidal anti-inflammatory drugs (1.2%). Patients admitted to hospital (n=18\u2009059) also had significantly higher GP consultation rates for multiple sequelae, most commonly for venous thromboembolism (16.21, 11.28 to 23.31, P<0.001), nausea (4.64, 2.24 to 9.21, P<0.001), prescriptions for paracetamol (3.68, 2.86 to 4.74, P<0.001), renal failure (3.42, 2.67 to 4.38, P<0.001), and healthcare use after a covid-19 diagnosis compared with 12 months before infection. For absolute proportions, the most common outcomes \u22654 weeks after a covid-19 diagnosis in patients admitted to hospital were venous thromboembolism (3.5%), joint pain (2.7%), and breathlessness (2.8%). In patients in the community, anxiety and depression, abdominal pain, diarrhoea, general pain, nausea, chest tightness, and tinnitus persisted throughout follow-up. GP consultation rates were reduced for all symptoms, prescriptions, and healthcare use, except for neuropathic pain, cognitive impairment, strong opiates, and paracetamol use in patients in the community after the first vaccination dose for covid-19 relative to before vaccination. GP consultation rates were also reduced for ischaemic heart disease, asthma, and gastro-oesophageal disease.

Conclusions

GP consultation rates for sequelae after acute covid-19 infection differed between patients with covid-19 who were admitted to hospital and those managed in the community. For individuals in the community, rates of some sequelae decreased over time but those for others, such as anxiety and depression, persisted. Rates of some outcomes decreased after vaccination in this group.", "laySummary": "", - "urls": "pdf:https://medinform.jmir.org/2020/12/e23530/PDF; doi:https://doi.org/10.2196/23530; html:https://europepmc.org/articles/PMC7773511" + "urls": "pdf:https://www.bmj.com/content/bmj/375/bmj-2021-065834.full.pdf; doi:https://doi.org/10.1136/bmj-2021-065834; html:https://europepmc.org/articles/PMC8715128; pdf:https://europepmc.org/articles/PMC8715128?pdf=render" }, { "id": "37647632", @@ -33626,21 +33643,21 @@ "urls": "doi:https://doi.org/10.1182/blood.2023020118; html:https://europepmc.org/articles/PMC10733830" }, { - "id": "34965929", - "doi": "https://doi.org/10.1136/bmj-2021-065834", - "title": "GP consultation rates for sequelae after acute covid-19 in patients managed in the community or hospital in the UK: population based study.", - "authorString": "Whittaker HR, Gulea C, Koteci A, Kallis C, Morgan AD, Iwundu C, Weeks M, Gupta R, Quint JK.", + "id": "30649175", + "doi": "https://doi.org/10.1001/jamacardio.2018.4537", + "title": "Cardiovascular Risk Factors Associated With Venous Thromboembolism.", + "authorString": "Gregson J, Kaptoge S, Bolton T, Pennells L, Willeit P, Burgess S, Bell S, Sweeting M, Rimm EB, Kabrhel C, Z\u00f6ller B, Assmann G, Gudnason V, Folsom AR, Arndt V, Fletcher A, Norman PE, Nordestgaard BG, Kitamura A, Mahmoodi BK, Whincup PH, Knuiman M, Salomaa V, Meisinger C, Koenig W, Kavousi M, V\u00f6lzke H, Cooper JA, Ninomiya T, Casiglia E, Rodriguez B, Ben-Shlomo Y, Despr\u00e9s JP, Simons L, Barrett-Connor E, Bj\u00f6rkelund C, Notdurfter M, Kromhout D, Price J, Sutherland SE, Sundstr\u00f6m J, Kauhanen J, Gallacher J, Beulens JWJ, Dankner R, Cooper C, Giampaoli S, Deen JF, G\u00f3mez de la C\u00e1mara A, Kuller LH, Rosengren A, Svensson PJ, Nagel D, Crespo CJ, Brenner H, Albertorio-Diaz JR, Atkins R, Brunner EJ, Shipley M, Nj\u00f8lstad I, Lawlor DA, van der Schouw YT, Selmer RM, Trevisan M, Verschuren WMM, Greenland P, Wassertheil-Smoller S, Lowe GDO, Wood AM, Butterworth AS, Thompson SG, Danesh J, Di Angelantonio E, Meade T, Emerging Risk Factors Collaboration.", "authorAffiliations": "", - "journalTitle": "BMJ (Clinical research ed.)", - "pubYear": "2021", - "date": "2021-12-29", + "journalTitle": "JAMA cardiology", + "pubYear": "2019", + "date": "2019-02-01", "isOpenAccess": "Y", "keywords": "", - "nationalPriorities": "", + "nationalPriorities": "Understanding the Causes of Disease", "healthCategories": "", - "abstract": "

Objectives

To describe the rates for consulting a general practitioner (GP) for sequelae after acute covid-19 in patients admitted to hospital with covid-19 and those managed in the community, and to determine how the rates change over time for patients in the community and after vaccination for covid-19.

Design

Population based study.

Setting

1392 general practices in England contributing to the Clinical Practice Research Datalink Aurum database.

Participants

456\u2009002 patients with a diagnosis of covid-19 between 1 August 2020 and 14 February 2021 (44.7% men; median age 61 years), admitted to hospital within two weeks of diagnosis or managed in the community, and followed-up for a maximum of 9.2 months. A negative control group included individuals without covid-19 (n=38\u2009511) and patients with influenza before the pandemic (n=21\u2009803).

Main outcome measures

Comparison of rates for consulting a GP for new symptoms, diseases, prescriptions, and healthcare use in individuals admitted to hospital and those managed in the community, separately, before and after covid-19 infection, using Cox regression and negative binomial regression for healthcare use. The analysis was repeated for the negative control and influenza cohorts. In individuals in the community, outcomes were also described over time after a diagnosis of covid-19, and compared before and after vaccination for individuals who were symptomatic after covid-19 infection, using negative binomial regression.

Results

Relative to the negative control and influenza cohorts, patients in the community (n=437\u2009943) had significantly higher GP consultation rates for multiple sequelae, and the most common were loss of smell or taste, or both (adjusted hazard ratio 5.28, 95% confidence interval 3.89 to 7.17, P<0.001); venous thromboembolism (3.35, 2.87 to 3.91, P<0.001); lung fibrosis (2.41, 1.37 to 4.25, P=0.002), and muscle pain (1.89, 1.63 to 2.20, P<0.001); and also for healthcare use after a diagnosis of covid-19 compared with 12 months before infection. For absolute proportions, the most common outcomes \u22654 weeks after a covid-19 diagnosis in patients in the community were joint pain (2.5%), anxiety (1.2%), and prescriptions for non-steroidal anti-inflammatory drugs (1.2%). Patients admitted to hospital (n=18\u2009059) also had significantly higher GP consultation rates for multiple sequelae, most commonly for venous thromboembolism (16.21, 11.28 to 23.31, P<0.001), nausea (4.64, 2.24 to 9.21, P<0.001), prescriptions for paracetamol (3.68, 2.86 to 4.74, P<0.001), renal failure (3.42, 2.67 to 4.38, P<0.001), and healthcare use after a covid-19 diagnosis compared with 12 months before infection. For absolute proportions, the most common outcomes \u22654 weeks after a covid-19 diagnosis in patients admitted to hospital were venous thromboembolism (3.5%), joint pain (2.7%), and breathlessness (2.8%). In patients in the community, anxiety and depression, abdominal pain, diarrhoea, general pain, nausea, chest tightness, and tinnitus persisted throughout follow-up. GP consultation rates were reduced for all symptoms, prescriptions, and healthcare use, except for neuropathic pain, cognitive impairment, strong opiates, and paracetamol use in patients in the community after the first vaccination dose for covid-19 relative to before vaccination. GP consultation rates were also reduced for ischaemic heart disease, asthma, and gastro-oesophageal disease.

Conclusions

GP consultation rates for sequelae after acute covid-19 infection differed between patients with covid-19 who were admitted to hospital and those managed in the community. For individuals in the community, rates of some sequelae decreased over time but those for others, such as anxiety and depression, persisted. Rates of some outcomes decreased after vaccination in this group.", + "abstract": "

Importance

It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE).

Objective

To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism.

Design, setting, and participants

This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731\u202f728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421\u202f537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018.

Exposures

A panel of several established cardiovascular risk factors.

Main outcomes and measures

Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE,\u20091041; coronary heart disease [CHD], 25\u202f131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI).

Results

Of the 731\u202f728 participants from the ERFC, 403\u202f396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421\u202f537 participants from the UK Biobank, 233\u202f699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers.

Conclusions and relevance

Older age, smoking, and adiposity were consistently associated with higher VTE risk.", "laySummary": "", - "urls": "pdf:https://www.bmj.com/content/bmj/375/bmj-2021-065834.full.pdf; doi:https://doi.org/10.1136/bmj-2021-065834; html:https://europepmc.org/articles/PMC8715128; pdf:https://europepmc.org/articles/PMC8715128?pdf=render" + "urls": "pdf:https://pdxscholar.library.pdx.edu/cgi/viewcontent.cgi?article=1451&context=sph_facpub; doi:https://doi.org/10.1001/jamacardio.2018.4537; html:https://europepmc.org/articles/PMC6386140" }, { "id": "32680743", @@ -33659,23 +33676,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jphys.2020.06.008; doi:https://doi.org/10.1016/j.jphys.2020.06.008" }, - { - "id": "30649175", - "doi": "https://doi.org/10.1001/jamacardio.2018.4537", - "title": "Cardiovascular Risk Factors Associated With Venous Thromboembolism.", - "authorString": "Gregson J, Kaptoge S, Bolton T, Pennells L, Willeit P, Burgess S, Bell S, Sweeting M, Rimm EB, Kabrhel C, Z\u00f6ller B, Assmann G, Gudnason V, Folsom AR, Arndt V, Fletcher A, Norman PE, Nordestgaard BG, Kitamura A, Mahmoodi BK, Whincup PH, Knuiman M, Salomaa V, Meisinger C, Koenig W, Kavousi M, V\u00f6lzke H, Cooper JA, Ninomiya T, Casiglia E, Rodriguez B, Ben-Shlomo Y, Despr\u00e9s JP, Simons L, Barrett-Connor E, Bj\u00f6rkelund C, Notdurfter M, Kromhout D, Price J, Sutherland SE, Sundstr\u00f6m J, Kauhanen J, Gallacher J, Beulens JWJ, Dankner R, Cooper C, Giampaoli S, Deen JF, G\u00f3mez de la C\u00e1mara A, Kuller LH, Rosengren A, Svensson PJ, Nagel D, Crespo CJ, Brenner H, Albertorio-Diaz JR, Atkins R, Brunner EJ, Shipley M, Nj\u00f8lstad I, Lawlor DA, van der Schouw YT, Selmer RM, Trevisan M, Verschuren WMM, Greenland P, Wassertheil-Smoller S, Lowe GDO, Wood AM, Butterworth AS, Thompson SG, Danesh J, Di Angelantonio E, Meade T, Emerging Risk Factors Collaboration.", - "authorAffiliations": "", - "journalTitle": "JAMA cardiology", - "pubYear": "2019", - "date": "2019-02-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "Understanding the Causes of Disease", - "healthCategories": "", - "abstract": "

Importance

It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE).

Objective

To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism.

Design, setting, and participants

This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731\u202f728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421\u202f537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018.

Exposures

A panel of several established cardiovascular risk factors.

Main outcomes and measures

Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE,\u20091041; coronary heart disease [CHD], 25\u202f131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI).

Results

Of the 731\u202f728 participants from the ERFC, 403\u202f396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421\u202f537 participants from the UK Biobank, 233\u202f699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers.

Conclusions and relevance

Older age, smoking, and adiposity were consistently associated with higher VTE risk.", - "laySummary": "", - "urls": "pdf:https://pdxscholar.library.pdx.edu/cgi/viewcontent.cgi?article=1451&context=sph_facpub; doi:https://doi.org/10.1001/jamacardio.2018.4537; html:https://europepmc.org/articles/PMC6386140" - }, { "id": "35849350", "doi": "https://doi.org/10.1093/nar/gkac612", @@ -33744,23 +33744,6 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ppul.24314; doi:https://doi.org/10.1002/ppul.24314; html:https://europepmc.org/articles/PMC6617805; pdf:https://europepmc.org/articles/PMC6617805?pdf=render" }, - { - "id": "38548763", - "doi": "https://doi.org/10.1038/s41467-024-46982-6", - "title": "The SARS-CoV-2 neutralizing antibody response to SD1 and its evasion by BA.2.86.", - "authorString": "Zhou D, Supasa P, Liu C, Dijokaite-Guraliuc A, Duyvesteyn HME, Selvaraj M, Mentzer AJ, Das R, Dejnirattisai W, Temperton N, Klenerman P, Dunachie SJ, Fry EE, Mongkolsapaya J, Ren J, Stuart DI, Screaton GR.", - "authorAffiliations": "", - "journalTitle": "Nature communications", - "pubYear": "2024", - "date": "2024-03-28", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Under pressure from neutralising antibodies induced by vaccination or infection the SARS-CoV-2 spike gene has become a hotspot for evolutionary change, leading to the failure of all mAbs developed for clinical use. Most potent antibodies bind to the receptor binding domain which has become heavily mutated. Here we study responses to a conserved epitope in sub-domain-1 (SD1) of spike which have become more prominent because of mutational escape from antibodies directed to the receptor binding domain. Some SD1 reactive mAbs show potent and broad neutralization of SARS-CoV-2 variants. We structurally map the dominant SD1 epitope and provide a mechanism of action by blocking interaction with ACE2. Mutations in SD1 have not been sustained to date, but one, E554K, leads to escape from mAbs. This mutation has now emerged in several sublineages including BA.2.86, reflecting selection pressure on the virus exerted by the increasing prominence of the anti-SD1 response.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41467-024-46982-6.pdf; doi:https://doi.org/10.1038/s41467-024-46982-6; html:https://europepmc.org/articles/PMC10978878; pdf:https://europepmc.org/articles/PMC10978878?pdf=render" - }, { "id": "35103484", "doi": "https://doi.org/10.1161/circgen.121.003553", @@ -33778,6 +33761,23 @@ "laySummary": "", "urls": "pdf:https://discovery.ucl.ac.uk/10145750/1/CIRCGEN.121.003553.pdf; doi:https://doi.org/10.1161/CIRCGEN.121.003553; html:https://europepmc.org/articles/PMC7612391; pdf:https://europepmc.org/articles/PMC7612391?pdf=render" }, + { + "id": "38548763", + "doi": "https://doi.org/10.1038/s41467-024-46982-6", + "title": "The SARS-CoV-2 neutralizing antibody response to SD1 and its evasion by BA.2.86.", + "authorString": "Zhou D, Supasa P, Liu C, Dijokaite-Guraliuc A, Duyvesteyn HME, Selvaraj M, Mentzer AJ, Das R, Dejnirattisai W, Temperton N, Klenerman P, Dunachie SJ, Fry EE, Mongkolsapaya J, Ren J, Stuart DI, Screaton GR.", + "authorAffiliations": "", + "journalTitle": "Nature communications", + "pubYear": "2024", + "date": "2024-03-28", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Under pressure from neutralising antibodies induced by vaccination or infection the SARS-CoV-2 spike gene has become a hotspot for evolutionary change, leading to the failure of all mAbs developed for clinical use. Most potent antibodies bind to the receptor binding domain which has become heavily mutated. Here we study responses to a conserved epitope in sub-domain-1 (SD1) of spike which have become more prominent because of mutational escape from antibodies directed to the receptor binding domain. Some SD1 reactive mAbs show potent and broad neutralization of SARS-CoV-2 variants. We structurally map the dominant SD1 epitope and provide a mechanism of action by blocking interaction with ACE2. Mutations in SD1 have not been sustained to date, but one, E554K, leads to escape from mAbs. This mutation has now emerged in several sublineages including BA.2.86, reflecting selection pressure on the virus exerted by the increasing prominence of the anti-SD1 response.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41467-024-46982-6.pdf; doi:https://doi.org/10.1038/s41467-024-46982-6; html:https://europepmc.org/articles/PMC10978878; pdf:https://europepmc.org/articles/PMC10978878?pdf=render" + }, { "id": "32413819", "doi": "https://doi.org/10.1016/j.dsx.2020.04.050", @@ -33829,23 +33829,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/schizophreniabulletin/article-pdf/47/2/405/36620462/sbaa126.pdf; doi:https://doi.org/10.1093/schbul/sbaa126; html:https://europepmc.org/articles/PMC7965059; pdf:https://europepmc.org/articles/PMC7965059?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa126" }, - { - "id": "31780306", - "doi": "https://doi.org/10.1016/s2215-0366(19)30298-6", - "title": "Pharmacoepidemiology research: delivering evidence about drug safety and effectiveness in mental health.", - "authorString": "Davis KAS, Farooq S, Hayes JF, John A, Lee W, MacCabe JH, McIntosh A, Osborn DPJ, Stewart RJ, Woelbert E.", - "authorAffiliations": "", - "journalTitle": "The lancet. Psychiatry", - "pubYear": "2020", - "date": "2019-11-25", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Research that provides an evidence base for the pharmacotherapy of people with mental disorders is needed. The abundance of digital data has facilitated pharmacoepidemiology and, in particular, observational research on the effectiveness of real-world medication. Advantages of pharmacoepidemiological research are the availability of large patient samples, and coverage of under-researched subpopulations in their naturalistic conditions. Such research is also cheaper and quicker to do than randomised controlled trials, meaning that issues regarding generic medication, stopping medication (deprescribing), and long-term outcomes are more likely to be addressed. Pharmacoepidemiological methods can also be extended to pharmacovigilance and to aid the development of new purposes for existing drugs. Drawbacks of observational pharmacoepidemiological studies come from the non-randomised nature of treatment selection, leading to confounding by indication. Potential methods for managing this drawback include active comparison groups, within-individual designs, and propensity scoring. Many of the more rigorous pharmacoepidemiology studies have been strengthened through multiple analytical approaches triangulated to improve confidence in inferred causal relationships. With developments in data resources and analytical techniques, it is encouraging that guidelines are beginning to include evidence from robust observational pharmacoepidemiological studies alongside randomised controlled trials. Collaboration between guideline writers and researchers involved in pharmacoepidemiology could help researchers to answer the questions that are important to policy makers and ensure that results are integrated into the evidence base. Further development of statistical and data science techniques, alongside public engagement and capacity building (data resources and researcher base), will be necessary to take full advantage of future opportunities.", - "laySummary": "", - "urls": "html:https://eprints.keele.ac.uk/6650/1/Pharamcoepidemiology%20Lancet%20Psych%202019%20submitted%20version.docx; doi:https://doi.org/10.1016/S2215-0366(19)30298-6" - }, { "id": "33185016", "doi": "https://doi.org/10.1002/art.41593", @@ -33863,6 +33846,23 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/art.41593; doi:https://doi.org/10.1002/art.41593; html:https://europepmc.org/articles/PMC8252419; pdf:https://europepmc.org/articles/PMC8252419?pdf=render" }, + { + "id": "31780306", + "doi": "https://doi.org/10.1016/s2215-0366(19)30298-6", + "title": "Pharmacoepidemiology research: delivering evidence about drug safety and effectiveness in mental health.", + "authorString": "Davis KAS, Farooq S, Hayes JF, John A, Lee W, MacCabe JH, McIntosh A, Osborn DPJ, Stewart RJ, Woelbert E.", + "authorAffiliations": "", + "journalTitle": "The lancet. Psychiatry", + "pubYear": "2020", + "date": "2019-11-25", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Research that provides an evidence base for the pharmacotherapy of people with mental disorders is needed. The abundance of digital data has facilitated pharmacoepidemiology and, in particular, observational research on the effectiveness of real-world medication. Advantages of pharmacoepidemiological research are the availability of large patient samples, and coverage of under-researched subpopulations in their naturalistic conditions. Such research is also cheaper and quicker to do than randomised controlled trials, meaning that issues regarding generic medication, stopping medication (deprescribing), and long-term outcomes are more likely to be addressed. Pharmacoepidemiological methods can also be extended to pharmacovigilance and to aid the development of new purposes for existing drugs. Drawbacks of observational pharmacoepidemiological studies come from the non-randomised nature of treatment selection, leading to confounding by indication. Potential methods for managing this drawback include active comparison groups, within-individual designs, and propensity scoring. Many of the more rigorous pharmacoepidemiology studies have been strengthened through multiple analytical approaches triangulated to improve confidence in inferred causal relationships. With developments in data resources and analytical techniques, it is encouraging that guidelines are beginning to include evidence from robust observational pharmacoepidemiological studies alongside randomised controlled trials. Collaboration between guideline writers and researchers involved in pharmacoepidemiology could help researchers to answer the questions that are important to policy makers and ensure that results are integrated into the evidence base. Further development of statistical and data science techniques, alongside public engagement and capacity building (data resources and researcher base), will be necessary to take full advantage of future opportunities.", + "laySummary": "", + "urls": "html:https://eprints.keele.ac.uk/6650/1/Pharamcoepidemiology%20Lancet%20Psych%202019%20submitted%20version.docx; doi:https://doi.org/10.1016/S2215-0366(19)30298-6" + }, { "id": "35068290", "doi": "https://doi.org/10.1080/09537104.2021.2003317", @@ -34118,23 +34118,6 @@ "laySummary": "", "urls": "pdf:https://portlandpress.com/biochemj/article-pdf/479/8/901/932114/bcj-2022-0105.pdf; doi:https://doi.org/10.1042/BCJ20220105; html:https://europepmc.org/articles/PMC9162461; pdf:https://europepmc.org/articles/PMC9162461?pdf=render" }, - { - "id": "35717168", - "doi": "https://doi.org/10.1186/s12879-022-07490-4", - "title": "The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020.", - "authorString": "Knight GM, Pham TM, Stimson J, Funk S, Jafari Y, Pople D, Evans S, Yin M, Brown CS, Bhattacharya A, Hope R, Semple MG, ISARIC4C Investigators, CMMID COVID-19 Working Group, Read JM, Cooper BS, Robotham JV.", - "authorAffiliations": "", - "journalTitle": "BMC infectious diseases", - "pubYear": "2022", - "date": "2022-06-18", - "isOpenAccess": "Y", - "keywords": "Mathematical Modelling; Nosocomial Transmission; Covid-19; Sars-cov-2", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

SARS-CoV-2 is known to transmit in hospital settings, but the contribution of infections acquired in hospitals to the epidemic at a national scale is unknown.

Methods

We used comprehensive national English datasets to determine the number of COVID-19 patients with identified hospital-acquired infections (with symptom onset >\u20097\u00a0days after admission and before discharge) in acute English hospitals up to August 2020. As patients may leave the hospital prior to detection of infection or have rapid symptom onset, we combined measures of the length of stay and the incubation period distribution to estimate how many hospital-acquired infections may have been missed. We used simulations to estimate the total number (identified and unidentified) of symptomatic hospital-acquired infections, as well as infections due to onward community transmission from missed hospital-acquired infections, to 31st July 2020.

Results

In our dataset of hospitalised COVID-19 patients in acute English hospitals with a recorded symptom onset date (n\u2009=\u200965,028), 7% were classified as hospital-acquired. We estimated that only 30% (range across weeks and 200 simulations: 20-41%) of symptomatic hospital-acquired infections would be identified, with up to 15% (mean, 95% range over 200 simulations: 14.1-15.8%) of cases currently classified as community-acquired COVID-19 potentially linked to hospital transmission. We estimated that 26,600 (25,900 to 27,700) individuals acquired a symptomatic SARS-CoV-2 infection in an acute Trust in England before 31st July 2020, resulting in 15,900 (15,200-16,400) or 20.1% (19.2-20.7%) of all identified hospitalised COVID-19 cases.

Conclusions

Transmission of SARS-CoV-2 to hospitalised patients likely caused approximately a fifth of identified cases of hospitalised COVID-19 in the \"first wave\" in England, but less than 1% of all infections in England. Using time to symptom onset from admission for inpatients as a detection method likely misses a substantial proportion (>\u200960%) of hospital-acquired infections.", - "laySummary": "", - "urls": "pdf:https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-022-07490-4; doi:https://doi.org/10.1186/s12879-022-07490-4; html:https://europepmc.org/articles/PMC9206097; pdf:https://europepmc.org/articles/PMC9206097?pdf=render" - }, { "id": "35000827", "doi": "https://doi.org/10.1016/j.clon.2021.12.017", @@ -34152,6 +34135,23 @@ "laySummary": "", "urls": "pdf:http://www.clinicaloncologyonline.net/article/S0936655521005161/pdf; doi:https://doi.org/10.1016/j.clon.2021.12.017" }, + { + "id": "35717168", + "doi": "https://doi.org/10.1186/s12879-022-07490-4", + "title": "The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020.", + "authorString": "Knight GM, Pham TM, Stimson J, Funk S, Jafari Y, Pople D, Evans S, Yin M, Brown CS, Bhattacharya A, Hope R, Semple MG, ISARIC4C Investigators, CMMID COVID-19 Working Group, Read JM, Cooper BS, Robotham JV.", + "authorAffiliations": "", + "journalTitle": "BMC infectious diseases", + "pubYear": "2022", + "date": "2022-06-18", + "isOpenAccess": "Y", + "keywords": "Mathematical Modelling; Nosocomial Transmission; Covid-19; Sars-cov-2", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

SARS-CoV-2 is known to transmit in hospital settings, but the contribution of infections acquired in hospitals to the epidemic at a national scale is unknown.

Methods

We used comprehensive national English datasets to determine the number of COVID-19 patients with identified hospital-acquired infections (with symptom onset >\u20097\u00a0days after admission and before discharge) in acute English hospitals up to August 2020. As patients may leave the hospital prior to detection of infection or have rapid symptom onset, we combined measures of the length of stay and the incubation period distribution to estimate how many hospital-acquired infections may have been missed. We used simulations to estimate the total number (identified and unidentified) of symptomatic hospital-acquired infections, as well as infections due to onward community transmission from missed hospital-acquired infections, to 31st July 2020.

Results

In our dataset of hospitalised COVID-19 patients in acute English hospitals with a recorded symptom onset date (n\u2009=\u200965,028), 7% were classified as hospital-acquired. We estimated that only 30% (range across weeks and 200 simulations: 20-41%) of symptomatic hospital-acquired infections would be identified, with up to 15% (mean, 95% range over 200 simulations: 14.1-15.8%) of cases currently classified as community-acquired COVID-19 potentially linked to hospital transmission. We estimated that 26,600 (25,900 to 27,700) individuals acquired a symptomatic SARS-CoV-2 infection in an acute Trust in England before 31st July 2020, resulting in 15,900 (15,200-16,400) or 20.1% (19.2-20.7%) of all identified hospitalised COVID-19 cases.

Conclusions

Transmission of SARS-CoV-2 to hospitalised patients likely caused approximately a fifth of identified cases of hospitalised COVID-19 in the \"first wave\" in England, but less than 1% of all infections in England. Using time to symptom onset from admission for inpatients as a detection method likely misses a substantial proportion (>\u200960%) of hospital-acquired infections.", + "laySummary": "", + "urls": "pdf:https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-022-07490-4; doi:https://doi.org/10.1186/s12879-022-07490-4; html:https://europepmc.org/articles/PMC9206097; pdf:https://europepmc.org/articles/PMC9206097?pdf=render" + }, { "id": "34910136", "doi": "https://doi.org/10.1093/eurheartj/ehab863", @@ -34220,23 +34220,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41746-020-00357-5.pdf; doi:https://doi.org/10.1038/s41746-020-00357-5; html:https://europepmc.org/articles/PMC7648058; pdf:https://europepmc.org/articles/PMC7648058?pdf=render" }, - { - "id": "37789377", - "doi": "https://doi.org/10.1186/s12943-023-01863-2", - "title": "Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures.", - "authorString": "Figiel S, Yin W, Doultsinos D, Erickson A, Poulose N, Singh R, Magnussen A, Anbarasan T, Teague R, He M, Lundeberg J, Loda M, Verrill C, Colling R, Gill PS, Bryant RJ, Hamdy FC, Woodcock DJ, Mills IG, Cussenot O, Lamb AD.", - "authorAffiliations": "", - "journalTitle": "Molecular cancer", - "pubYear": "2023", - "date": "2023-10-03", - "isOpenAccess": "Y", - "keywords": "prostate cancer; Virtual Biopsy; Spatial Transcriptomics; Prognostic Genetic Signatures", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Genetic signatures have added a molecular dimension to prognostics and therapeutic decision-making. However, tumour heterogeneity in prostate cancer and current sampling methods could confound accurate assessment. Based on previously published spatial transcriptomic data from multifocal prostate cancer, we created virtual biopsy models that mimic conventional biopsy placement and core size. We then analysed the gene expression of different prognostic signatures (OncotypeDx\u00ae, Decipher\u00ae, Prostadiag\u00ae) using a step-wise approach with increasing resolution from pseudo-bulk analysis of the whole biopsy, to differentiation by tissue subtype (benign, stroma, tumour), followed by distinct tumour grade and finally clonal resolution. The gene expression profile of virtual tumour biopsies revealed clear differences between grade groups and tumour clones, compared to a benign control, which were not reflected in bulk analyses. This suggests that bulk analyses of whole biopsies or tumour-only areas, as used in clinical practice, may provide an inaccurate assessment of gene profiles. The type of tissue, the grade of the tumour and the clonal composition all influence the gene expression in a biopsy. Clinical decision making based on biopsy genomics should be made with caution while we await more precise targeting and cost-effective spatial analyses.", - "laySummary": "", - "urls": "pdf:https://molecular-cancer.biomedcentral.com/counter/pdf/10.1186/s12943-023-01863-2; doi:https://doi.org/10.1186/s12943-023-01863-2; html:https://europepmc.org/articles/PMC10546768; pdf:https://europepmc.org/articles/PMC10546768?pdf=render" - }, { "id": "35482474", "doi": "https://doi.org/10.1111/bjd.21627", @@ -34254,6 +34237,23 @@ "laySummary": "", "urls": "pdf:https://kclpure.kcl.ac.uk/ws/files/177671246/Br_J_Dermatol_2022_Ramessur_Biomarkers_of_disease_progression_in_people_with_psoriasis_a_scoping_review.pdf; doi:https://doi.org/10.1111/bjd.21627; html:https://europepmc.org/articles/PMC9796834; pdf:https://europepmc.org/articles/PMC9796834?pdf=render" }, + { + "id": "37789377", + "doi": "https://doi.org/10.1186/s12943-023-01863-2", + "title": "Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures.", + "authorString": "Figiel S, Yin W, Doultsinos D, Erickson A, Poulose N, Singh R, Magnussen A, Anbarasan T, Teague R, He M, Lundeberg J, Loda M, Verrill C, Colling R, Gill PS, Bryant RJ, Hamdy FC, Woodcock DJ, Mills IG, Cussenot O, Lamb AD.", + "authorAffiliations": "", + "journalTitle": "Molecular cancer", + "pubYear": "2023", + "date": "2023-10-03", + "isOpenAccess": "Y", + "keywords": "prostate cancer; Virtual Biopsy; Spatial Transcriptomics; Prognostic Genetic Signatures", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Genetic signatures have added a molecular dimension to prognostics and therapeutic decision-making. However, tumour heterogeneity in prostate cancer and current sampling methods could confound accurate assessment. Based on previously published spatial transcriptomic data from multifocal prostate cancer, we created virtual biopsy models that mimic conventional biopsy placement and core size. We then analysed the gene expression of different prognostic signatures (OncotypeDx\u00ae, Decipher\u00ae, Prostadiag\u00ae) using a step-wise approach with increasing resolution from pseudo-bulk analysis of the whole biopsy, to differentiation by tissue subtype (benign, stroma, tumour), followed by distinct tumour grade and finally clonal resolution. The gene expression profile of virtual tumour biopsies revealed clear differences between grade groups and tumour clones, compared to a benign control, which were not reflected in bulk analyses. This suggests that bulk analyses of whole biopsies or tumour-only areas, as used in clinical practice, may provide an inaccurate assessment of gene profiles. The type of tissue, the grade of the tumour and the clonal composition all influence the gene expression in a biopsy. Clinical decision making based on biopsy genomics should be made with caution while we await more precise targeting and cost-effective spatial analyses.", + "laySummary": "", + "urls": "pdf:https://molecular-cancer.biomedcentral.com/counter/pdf/10.1186/s12943-023-01863-2; doi:https://doi.org/10.1186/s12943-023-01863-2; html:https://europepmc.org/articles/PMC10546768; pdf:https://europepmc.org/articles/PMC10546768?pdf=render" + }, { "id": "31588514", "doi": "https://doi.org/10.1093/ptj/pzz151", @@ -34441,23 +34441,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.neuroimage.2021.118235; doi:https://doi.org/10.1016/j.neuroimage.2021.118235; html:https://europepmc.org/articles/PMC7611820; pdf:https://europepmc.org/articles/PMC7611820?pdf=render" }, - { - "id": "36717723", - "doi": "https://doi.org/10.1038/s41590-022-01380-2", - "title": "A patient-centric modeling framework captures recovery from SARS-CoV-2 infection.", - "authorString": "Ruffieux H, Hanson AL, Lodge S, Lawler NG, Whiley L, Gray N, Nolan TH, Bergamaschi L, Mescia F, Turner L, de Sa A, Pelly VS, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) BioResource COVID-19 Collaboration, Kotagiri P, Kingston N, Bradley JR, Holmes E, Wist J, Nicholson JK, Lyons PA, Smith KGC, Richardson S, Bantug GR, Hess C.", - "authorAffiliations": "", - "journalTitle": "Nature immunology", - "pubYear": "2023", - "date": "2023-01-30", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The biology driving individual patient responses to severe acute respiratory syndrome coronavirus 2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data and covering a year after disease onset, from 215 infected individuals with differing disease severities. Our analyses revealed distinct 'systemic recovery' profiles, with specific progression and resolution of the inflammatory, immune cell, metabolic and clinical responses. In particular, we found a strong inter-patient and intra-patient temporal covariation of innate immune cell numbers, kynurenine metabolites and lipid metabolites, which highlighted candidate immunologic and metabolic pathways influencing the restoration of homeostasis, the risk of death and that of long COVID. Based on these data, we identified a composite signature predictive of systemic recovery, using a joint model on cellular and molecular parameters measured soon after disease onset. New predictions can be generated using the online tool http://shiny.mrc-bsu.cam.ac.uk/apps/covid-19-systemic-recovery-prediction-app , designed to test our findings prospectively.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41590-022-01380-2.pdf; doi:https://doi.org/10.1038/s41590-022-01380-2; html:https://europepmc.org/articles/PMC9892000; pdf:https://europepmc.org/articles/PMC9892000?pdf=render" - }, { "id": "30382236", "doi": "https://doi.org/10.1038/s41433-018-0229-6", @@ -34475,6 +34458,23 @@ "laySummary": "Perrott et al. reviewed strengths and limitations of an eye (retinal) imagining method for diagnosis of a condition affecting the central part of the retina (the macula). This degenerative condition may result in loss of central vision in older adults. Perrott et al. concluded that diagnostic accuracy depends on both method and equipment. ", "urls": "pdf:https://www.nature.com/articles/s41433-018-0229-6.pdf; doi:https://doi.org/10.1038/s41433-018-0229-6; html:https://europepmc.org/articles/PMC6367454; pdf:https://europepmc.org/articles/PMC6367454?pdf=render; doi:https://doi.org/10.1038/s41433-018-0229-6" }, + { + "id": "36717723", + "doi": "https://doi.org/10.1038/s41590-022-01380-2", + "title": "A patient-centric modeling framework captures recovery from SARS-CoV-2 infection.", + "authorString": "Ruffieux H, Hanson AL, Lodge S, Lawler NG, Whiley L, Gray N, Nolan TH, Bergamaschi L, Mescia F, Turner L, de Sa A, Pelly VS, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) BioResource COVID-19 Collaboration, Kotagiri P, Kingston N, Bradley JR, Holmes E, Wist J, Nicholson JK, Lyons PA, Smith KGC, Richardson S, Bantug GR, Hess C.", + "authorAffiliations": "", + "journalTitle": "Nature immunology", + "pubYear": "2023", + "date": "2023-01-30", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The biology driving individual patient responses to severe acute respiratory syndrome coronavirus 2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data and covering a year after disease onset, from 215 infected individuals with differing disease severities. Our analyses revealed distinct 'systemic recovery' profiles, with specific progression and resolution of the inflammatory, immune cell, metabolic and clinical responses. In particular, we found a strong inter-patient and intra-patient temporal covariation of innate immune cell numbers, kynurenine metabolites and lipid metabolites, which highlighted candidate immunologic and metabolic pathways influencing the restoration of homeostasis, the risk of death and that of long COVID. Based on these data, we identified a composite signature predictive of systemic recovery, using a joint model on cellular and molecular parameters measured soon after disease onset. New predictions can be generated using the online tool http://shiny.mrc-bsu.cam.ac.uk/apps/covid-19-systemic-recovery-prediction-app , designed to test our findings prospectively.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41590-022-01380-2.pdf; doi:https://doi.org/10.1038/s41590-022-01380-2; html:https://europepmc.org/articles/PMC9892000; pdf:https://europepmc.org/articles/PMC9892000?pdf=render" + }, { "id": "37542272", "doi": "https://doi.org/10.1186/s12916-023-02948-x", @@ -34883,23 +34883,6 @@ "laySummary": "", "urls": "pdf:https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-020-04951-6; doi:https://doi.org/10.1186/s13063-020-04951-6; html:https://europepmc.org/articles/PMC7788716; pdf:https://europepmc.org/articles/PMC7788716?pdf=render" }, - { - "id": "35288697", - "doi": "https://doi.org/10.1038/s41591-022-01750-1", - "title": "COVID-19 and resilience of healthcare systems in ten countries.", - "authorString": "Arsenault C, Gage A, Kim MK, Kapoor NR, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bedregal P, Doubova SV, Dulal M, Gadeka DD, Gordon-Strachan G, Mariam DH, Hensman D, Joseph JP, Kaewkamjornchai P, Eshetu MK, Gelaw SK, Kubota S, Leerapan B, Margozzini P, Mebratie AD, Mehata S, Moshabela M, Mthethwa L, Nega A, Oh J, Park S, Passi-Solar \u00c1, P\u00e9rez-Cuevas R, Phengsavanh A, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Valenzuela Gui\u00f1ez F, Bauhoff S, Kruk ME.", - "authorAffiliations": "", - "journalTitle": "Nature medicine", - "pubYear": "2022", - "date": "2022-03-14", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Declines in health service use during the Coronavirus Disease 2019 (COVID-19) pandemic could have important effects on population health. In this study, we used an interrupted time series design to assess the immediate effect of the pandemic on 31 health services in two low-income (Ethiopia and Haiti), six middle-income\ufeff (Ghana, Lao People's Democratic Republic, Mexico, Nepal, South Africa and Thailand) and high-income (Chile and South Korea) countries. Despite efforts to maintain health services, disruptions of varying magnitude and duration were found in every country, with no clear patterns by country income group or pandemic intensity. Disruptions in health services often preceded COVID-19 waves. Cancer screenings, TB screening and detection and HIV testing were most affected (26-96% declines). Total outpatient visits declined by 9-40% at national levels and remained lower than predicted by the end of 2020. Maternal health services were disrupted in approximately half of the countries, with declines ranging from 5% to 33%. Child vaccinations were disrupted for shorter periods, but we estimate that catch-up campaigns might not have reached all children missed. By contrast, provision of antiretrovirals for HIV was not affected. By the end of 2020, substantial disruptions remained in half of the countries. Preliminary data for 2021 indicate that disruptions likely persisted. Although a portion of the declines observed might result from decreased needs during lockdowns (from fewer infectious illnesses or injuries), a larger share likely reflects a shortfall of health system resilience. Countries must plan to compensate for missed healthcare during the current pandemic and invest in strategies for better health system resilience for future emergencies.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41591-022-01750-1.pdf; doi:https://doi.org/10.1038/s41591-022-01750-1; html:https://europepmc.org/articles/PMC9205770; pdf:https://europepmc.org/articles/PMC9205770?pdf=render" - }, { "id": "32835195", "doi": "https://doi.org/10.1016/s2589-7500(20)30134-5", @@ -34917,6 +34900,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/s2589-7500(20)30134-5; doi:https://doi.org/10.1016/S2589-7500(20)30134-5; html:https://europepmc.org/articles/PMC7292602; pdf:https://europepmc.org/articles/PMC7292602?pdf=render" }, + { + "id": "35288697", + "doi": "https://doi.org/10.1038/s41591-022-01750-1", + "title": "COVID-19 and resilience of healthcare systems in ten countries.", + "authorString": "Arsenault C, Gage A, Kim MK, Kapoor NR, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bedregal P, Doubova SV, Dulal M, Gadeka DD, Gordon-Strachan G, Mariam DH, Hensman D, Joseph JP, Kaewkamjornchai P, Eshetu MK, Gelaw SK, Kubota S, Leerapan B, Margozzini P, Mebratie AD, Mehata S, Moshabela M, Mthethwa L, Nega A, Oh J, Park S, Passi-Solar \u00c1, P\u00e9rez-Cuevas R, Phengsavanh A, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Valenzuela Gui\u00f1ez F, Bauhoff S, Kruk ME.", + "authorAffiliations": "", + "journalTitle": "Nature medicine", + "pubYear": "2022", + "date": "2022-03-14", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Declines in health service use during the Coronavirus Disease 2019 (COVID-19) pandemic could have important effects on population health. In this study, we used an interrupted time series design to assess the immediate effect of the pandemic on 31 health services in two low-income (Ethiopia and Haiti), six middle-income\ufeff (Ghana, Lao People's Democratic Republic, Mexico, Nepal, South Africa and Thailand) and high-income (Chile and South Korea) countries. Despite efforts to maintain health services, disruptions of varying magnitude and duration were found in every country, with no clear patterns by country income group or pandemic intensity. Disruptions in health services often preceded COVID-19 waves. Cancer screenings, TB screening and detection and HIV testing were most affected (26-96% declines). Total outpatient visits declined by 9-40% at national levels and remained lower than predicted by the end of 2020. Maternal health services were disrupted in approximately half of the countries, with declines ranging from 5% to 33%. Child vaccinations were disrupted for shorter periods, but we estimate that catch-up campaigns might not have reached all children missed. By contrast, provision of antiretrovirals for HIV was not affected. By the end of 2020, substantial disruptions remained in half of the countries. Preliminary data for 2021 indicate that disruptions likely persisted. Although a portion of the declines observed might result from decreased needs during lockdowns (from fewer infectious illnesses or injuries), a larger share likely reflects a shortfall of health system resilience. Countries must plan to compensate for missed healthcare during the current pandemic and invest in strategies for better health system resilience for future emergencies.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41591-022-01750-1.pdf; doi:https://doi.org/10.1038/s41591-022-01750-1; html:https://europepmc.org/articles/PMC9205770; pdf:https://europepmc.org/articles/PMC9205770?pdf=render" + }, { "id": "34555069", "doi": "https://doi.org/10.1371/journal.pone.0257361", @@ -34968,6 +34968,23 @@ "laySummary": "", "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02218-8; doi:https://doi.org/10.1186/s12916-021-02218-8; html:https://europepmc.org/articles/PMC8787919; pdf:https://europepmc.org/articles/PMC8787919?pdf=render" }, + { + "id": "33064085", + "doi": "https://doi.org/10.2196/17003", + "title": "Impact of Electronic Health Record Interface Design on Unsafe Prescribing of Ciclosporin, Tacrolimus, and Diltiazem: Cohort Study in English National Health Service Primary Care.", + "authorString": "MacKenna B, Bacon S, Walker AJ, Curtis HJ, Croker R, Goldacre B.", + "authorAffiliations": "", + "journalTitle": "Journal of medical Internet research", + "pubYear": "2020", + "date": "2020-10-16", + "isOpenAccess": "Y", + "keywords": "Diltiazem; Prescribing; Ciclosporin; Primary Care; Tacrolimus; Electronic Health Records; Clinical Software; Branded Prescribing", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

In England, national safety guidance recommends that ciclosporin, tacrolimus, and diltiazem are prescribed by brand name due to their narrow therapeutic windows and, in the case of tacrolimus, to reduce the chance of organ transplantation rejection. Various small studies have shown that changes to electronic health record (EHR) system interfaces can affect prescribing choices.

Objective

Our objectives were to assess variation by EHR systems in breach of safety guidance around prescribing of ciclosporin, tacrolimus, and diltiazem, and to conduct user-interface research into the causes of such breaches.

Methods

We carried out a retrospective cohort study using prescribing data in English primary care. Participants were English general practices and their respective EHR systems. The main outcome measures were (1) the variation in ratio of safety breaches to adherent prescribing in all practices and (2) the description of observations of EHR system usage.

Results

A total of 2,575,411 prescriptions were issued in 2018 for ciclosporin, tacrolimus, and diltiazem (over 60 mg); of these, 316,119 prescriptions breached NHS guidance (12.27%). Breaches were most common among users of the EMIS EHR system (breaches in 18.81% of ciclosporin and tacrolimus prescriptions and in 17.99% of diltiazem prescriptions), but breaches were observed in all EHR systems.

Conclusions

Design choices in EHR systems strongly influence safe prescribing of ciclosporin, tacrolimus, and diltiazem, and breaches are prevalent in general practices in England. We recommend that all EHR vendors review their systems to increase safe prescribing of these medicines in line with national guidance. Almost all clinical practice is now mediated through an EHR system; further quantitative research into the effect of EHR system design on clinical practice is long overdue.", + "laySummary": "", + "urls": "pdf:https://www.jmir.org/2020/10/e17003/PDF; doi:https://doi.org/10.2196/17003; html:https://europepmc.org/articles/PMC7600019" + }, { "id": "34725404", "doi": "https://doi.org/10.1038/s41598-021-00748-y", @@ -35003,21 +35020,21 @@ "urls": "pdf:http://www.thelancet.com/article/S258953702200147X/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101417; html:https://europepmc.org/articles/PMC9048584; pdf:https://europepmc.org/articles/PMC9048584?pdf=render" }, { - "id": "33064085", - "doi": "https://doi.org/10.2196/17003", - "title": "Impact of Electronic Health Record Interface Design on Unsafe Prescribing of Ciclosporin, Tacrolimus, and Diltiazem: Cohort Study in English National Health Service Primary Care.", - "authorString": "MacKenna B, Bacon S, Walker AJ, Curtis HJ, Croker R, Goldacre B.", + "id": "33829489", + "doi": "https://doi.org/10.1111/bjd.20140", + "title": "Defining trajectories of response in patients with psoriasis treated with biologic therapies.", + "authorString": "Geifman N, Azadbakht N, Zeng J, Wilkinson T, Dand N, Buchan I, Stocken D, Di Meglio P, Warren RB, Barker JN, Reynolds NJ, Barnes MR, Smith CH, Griffiths CEM, Peek N, BADBIR Study Group, on behalf of the PSORT Consortium.", "authorAffiliations": "", - "journalTitle": "Journal of medical Internet research", - "pubYear": "2020", - "date": "2020-10-16", - "isOpenAccess": "Y", - "keywords": "Diltiazem; Prescribing; Ciclosporin; Primary Care; Tacrolimus; Electronic Health Records; Clinical Software; Branded Prescribing", + "journalTitle": "The British journal of dermatology", + "pubYear": "2021", + "date": "2021-06-04", + "isOpenAccess": "N", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

In England, national safety guidance recommends that ciclosporin, tacrolimus, and diltiazem are prescribed by brand name due to their narrow therapeutic windows and, in the case of tacrolimus, to reduce the chance of organ transplantation rejection. Various small studies have shown that changes to electronic health record (EHR) system interfaces can affect prescribing choices.

Objective

Our objectives were to assess variation by EHR systems in breach of safety guidance around prescribing of ciclosporin, tacrolimus, and diltiazem, and to conduct user-interface research into the causes of such breaches.

Methods

We carried out a retrospective cohort study using prescribing data in English primary care. Participants were English general practices and their respective EHR systems. The main outcome measures were (1) the variation in ratio of safety breaches to adherent prescribing in all practices and (2) the description of observations of EHR system usage.

Results

A total of 2,575,411 prescriptions were issued in 2018 for ciclosporin, tacrolimus, and diltiazem (over 60 mg); of these, 316,119 prescriptions breached NHS guidance (12.27%). Breaches were most common among users of the EMIS EHR system (breaches in 18.81% of ciclosporin and tacrolimus prescriptions and in 17.99% of diltiazem prescriptions), but breaches were observed in all EHR systems.

Conclusions

Design choices in EHR systems strongly influence safe prescribing of ciclosporin, tacrolimus, and diltiazem, and breaches are prevalent in general practices in England. We recommend that all EHR vendors review their systems to increase safe prescribing of these medicines in line with national guidance. Almost all clinical practice is now mediated through an EHR system; further quantitative research into the effect of EHR system design on clinical practice is long overdue.", + "abstract": "

Background

The effectiveness and cost-effectiveness of biologic therapies for psoriasis are significantly compromised by variable treatment responses. Thus, more precise management of psoriasis is needed.

Objectives

To identify subgroups of patients with psoriasis treated with biologic therapies, based on changes in their disease activity over time, that may better inform patient management.

Methods

We applied latent class mixed modelling to identify trajectory-based patient subgroups from longitudinal, routine clinical data on disease severity, as measured by the Psoriasis Area and Severity Index (PASI), from 3546 patients in the British Association of Dermatologists Biologics and Immunomodulators Register, as well as in an independent cohort of 2889 patients pooled across four clinical trials.

Results

We discovered four discrete classes of global response trajectories, each characterized in terms of time to response, size of effect and relapse. Each class was associated with differing clinical characteristics, e.g. body mass index, baseline PASI and prevalence of different manifestations. The results were verified in a second cohort of clinical trial participants, where similar trajectories following the initiation of biologic therapy were identified. Further, we found differential associations of the genetic marker HLA-C*06:02 between our registry-identified trajectories.

Conclusions

These subgroups, defined by change in disease over time, may be indicative of distinct endotypes driven by different biological mechanisms and may help inform the management of patients with psoriasis. Future work will aim to further delineate these mechanisms by extensively characterizing the subgroups with additional molecular and pharmacological data.", "laySummary": "", - "urls": "pdf:https://www.jmir.org/2020/10/e17003/PDF; doi:https://doi.org/10.2196/17003; html:https://europepmc.org/articles/PMC7600019" + "urls": "doi:https://doi.org/10.1111/bjd.20140" }, { "id": "35710247", @@ -35037,21 +35054,21 @@ "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/6/e060280.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-060280; html:https://europepmc.org/articles/PMC9207897; pdf:https://europepmc.org/articles/PMC9207897?pdf=render" }, { - "id": "33829489", - "doi": "https://doi.org/10.1111/bjd.20140", - "title": "Defining trajectories of response in patients with psoriasis treated with biologic therapies.", - "authorString": "Geifman N, Azadbakht N, Zeng J, Wilkinson T, Dand N, Buchan I, Stocken D, Di Meglio P, Warren RB, Barker JN, Reynolds NJ, Barnes MR, Smith CH, Griffiths CEM, Peek N, BADBIR Study Group, on behalf of the PSORT Consortium.", + "id": "33742045", + "doi": "https://doi.org/10.1038/s41598-021-85354-8", + "title": "Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma.", + "authorString": "Roberts HE, Lopopolo M, Pagnamenta AT, Sharma E, Parkes D, Lonie L, Freeman C, Knight SJL, Lunter G, Dreau H, Lockstone H, Taylor JC, Schuh A, Bowden R, Buck D.", "authorAffiliations": "", - "journalTitle": "The British journal of dermatology", + "journalTitle": "Scientific reports", "pubYear": "2021", - "date": "2021-06-04", - "isOpenAccess": "N", + "date": "2021-03-19", + "isOpenAccess": "Y", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

The effectiveness and cost-effectiveness of biologic therapies for psoriasis are significantly compromised by variable treatment responses. Thus, more precise management of psoriasis is needed.

Objectives

To identify subgroups of patients with psoriasis treated with biologic therapies, based on changes in their disease activity over time, that may better inform patient management.

Methods

We applied latent class mixed modelling to identify trajectory-based patient subgroups from longitudinal, routine clinical data on disease severity, as measured by the Psoriasis Area and Severity Index (PASI), from 3546 patients in the British Association of Dermatologists Biologics and Immunomodulators Register, as well as in an independent cohort of 2889 patients pooled across four clinical trials.

Results

We discovered four discrete classes of global response trajectories, each characterized in terms of time to response, size of effect and relapse. Each class was associated with differing clinical characteristics, e.g. body mass index, baseline PASI and prevalence of different manifestations. The results were verified in a second cohort of clinical trial participants, where similar trajectories following the initiation of biologic therapy were identified. Further, we found differential associations of the genetic marker HLA-C*06:02 between our registry-identified trajectories.

Conclusions

These subgroups, defined by change in disease over time, may be indicative of distinct endotypes driven by different biological mechanisms and may help inform the management of patients with psoriasis. Future work will aim to further delineate these mechanisms by extensively characterizing the subgroups with additional molecular and pharmacological data.", + "abstract": "Recent advances in throughput and accuracy mean that the Oxford Nanopore Technologies PromethION platform is a now a viable solution for genome sequencing. Much of the validation of bioinformatic tools for this long-read data has focussed on calling germline variants (including structural variants). Somatic variants are outnumbered many-fold by germline variants and their detection is further complicated by the effects of tumour purity/subclonality. Here, we evaluate the extent to which Nanopore sequencing enables detection and analysis of somatic variation. We do this through sequencing tumour and germline genomes for a patient with diffuse B-cell lymphoma and comparing results with 150\u00a0bp short-read sequencing of the same samples. Calling germline single nucleotide variants (SNVs) from specific chromosomes of the long-read data achieved good specificity and sensitivity. However, results of somatic SNV calling highlight the need for the development of specialised joint calling algorithms. We find the comparative genome-wide performance of different tools varies significantly between structural variant types, and suggest long reads are especially advantageous for calling large somatic deletions and duplications. Finally, we highlight the utility of long reads for phasing clinically relevant variants, confirming that a somatic 1.6\u00a0Mb deletion and a p.(Arg249Met) mutation involving TP53 are oriented in trans.", "laySummary": "", - "urls": "doi:https://doi.org/10.1111/bjd.20140" + "urls": "pdf:https://www.nature.com/articles/s41598-021-85354-8.pdf; doi:https://doi.org/10.1038/s41598-021-85354-8; html:https://europepmc.org/articles/PMC7979876; pdf:https://europepmc.org/articles/PMC7979876?pdf=render" }, { "id": "32247823", @@ -35070,23 +35087,6 @@ "laySummary": "", "urls": "pdf:http://www.journal-of-hepatology.eu/article/S016882782030194X/pdf; doi:https://doi.org/10.1016/j.jhep.2020.03.032; html:https://europepmc.org/articles/PMC7372222; pdf:https://europepmc.org/articles/PMC7372222?pdf=render" }, - { - "id": "33742045", - "doi": "https://doi.org/10.1038/s41598-021-85354-8", - "title": "Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma.", - "authorString": "Roberts HE, Lopopolo M, Pagnamenta AT, Sharma E, Parkes D, Lonie L, Freeman C, Knight SJL, Lunter G, Dreau H, Lockstone H, Taylor JC, Schuh A, Bowden R, Buck D.", - "authorAffiliations": "", - "journalTitle": "Scientific reports", - "pubYear": "2021", - "date": "2021-03-19", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Recent advances in throughput and accuracy mean that the Oxford Nanopore Technologies PromethION platform is a now a viable solution for genome sequencing. Much of the validation of bioinformatic tools for this long-read data has focussed on calling germline variants (including structural variants). Somatic variants are outnumbered many-fold by germline variants and their detection is further complicated by the effects of tumour purity/subclonality. Here, we evaluate the extent to which Nanopore sequencing enables detection and analysis of somatic variation. We do this through sequencing tumour and germline genomes for a patient with diffuse B-cell lymphoma and comparing results with 150\u00a0bp short-read sequencing of the same samples. Calling germline single nucleotide variants (SNVs) from specific chromosomes of the long-read data achieved good specificity and sensitivity. However, results of somatic SNV calling highlight the need for the development of specialised joint calling algorithms. We find the comparative genome-wide performance of different tools varies significantly between structural variant types, and suggest long reads are especially advantageous for calling large somatic deletions and duplications. Finally, we highlight the utility of long reads for phasing clinically relevant variants, confirming that a somatic 1.6\u00a0Mb deletion and a p.(Arg249Met) mutation involving TP53 are oriented in trans.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41598-021-85354-8.pdf; doi:https://doi.org/10.1038/s41598-021-85354-8; html:https://europepmc.org/articles/PMC7979876; pdf:https://europepmc.org/articles/PMC7979876?pdf=render" - }, { "id": "33480434", "doi": "https://doi.org/10.1093/pubmed/fdaa267", @@ -35359,23 +35359,6 @@ "laySummary": "", "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00109/pdf; doi:https://doi.org/10.3389/fpsyt.2019.00109; html:https://europepmc.org/articles/PMC6436079; pdf:https://europepmc.org/articles/PMC6436079?pdf=render" }, - { - "id": "37269091", - "doi": "https://doi.org/10.1177/10870547231172763", - "title": "Remote Administration of ADHD-Sensitive Cognitive Tasks: A Pilot Study.", - "authorString": "Sun S, Denyer H, Sankesara H, Deng Q, Ranjan Y, Conde P, Rashid Z, Bendayan R, Asherson P, Bilbow A, Groom M, Hollis C, Folarin AA, Dobson RJB, Kuntsi J.", - "authorAffiliations": "", - "journalTitle": "Journal of attention disorders", - "pubYear": "2023", - "date": "2023-06-02", - "isOpenAccess": "Y", - "keywords": "ADHD; Remote Monitoring; Response Inhibition; Attention Regulation; Radar-base", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

We assessed the feasibility and validity of remote researcher-led administration and self-administration of modified versions of two cognitive tasks sensitive to ADHD, a four-choice reaction time task (Fast task) and a combined Continuous Performance Test/Go No-Go task (CPT/GNG), through a new remote measurement technology system.

Method

We compared the cognitive performance measures (mean and variability of reaction times (MRT, RTV), omission errors (OE) and commission errors (CE)) at a remote baseline researcher-led administration and three remote self-administration sessions between participants with and without ADHD (n\u2009=\u200940).

Results

The most consistent group differences were found for RTV, MRT and CE at the baseline researcher-led administration and the first self-administration, with 8 of the 10 comparisons statistically significant and all comparisons indicating medium to large effect sizes.

Conclusion

Remote administration of cognitive tasks successfully captured the difficulties with response inhibition and regulation of attention, supporting the feasibility and validity of remote assessments.", - "laySummary": "", - "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/10870547231172763; doi:https://doi.org/10.1177/10870547231172763; html:https://europepmc.org/articles/PMC10291103; pdf:https://europepmc.org/articles/PMC10291103?pdf=render" - }, { "id": "31040096", "doi": "https://doi.org/10.1016/s2352-4642(19)30114-2", @@ -35393,6 +35376,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S2352464219301142/pdf; doi:https://doi.org/10.1016/S2352-4642(19)30114-2" }, + { + "id": "37269091", + "doi": "https://doi.org/10.1177/10870547231172763", + "title": "Remote Administration of ADHD-Sensitive Cognitive Tasks: A Pilot Study.", + "authorString": "Sun S, Denyer H, Sankesara H, Deng Q, Ranjan Y, Conde P, Rashid Z, Bendayan R, Asherson P, Bilbow A, Groom M, Hollis C, Folarin AA, Dobson RJB, Kuntsi J.", + "authorAffiliations": "", + "journalTitle": "Journal of attention disorders", + "pubYear": "2023", + "date": "2023-06-02", + "isOpenAccess": "Y", + "keywords": "ADHD; Remote Monitoring; Response Inhibition; Attention Regulation; Radar-base", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

We assessed the feasibility and validity of remote researcher-led administration and self-administration of modified versions of two cognitive tasks sensitive to ADHD, a four-choice reaction time task (Fast task) and a combined Continuous Performance Test/Go No-Go task (CPT/GNG), through a new remote measurement technology system.

Method

We compared the cognitive performance measures (mean and variability of reaction times (MRT, RTV), omission errors (OE) and commission errors (CE)) at a remote baseline researcher-led administration and three remote self-administration sessions between participants with and without ADHD (n\u2009=\u200940).

Results

The most consistent group differences were found for RTV, MRT and CE at the baseline researcher-led administration and the first self-administration, with 8 of the 10 comparisons statistically significant and all comparisons indicating medium to large effect sizes.

Conclusion

Remote administration of cognitive tasks successfully captured the difficulties with response inhibition and regulation of attention, supporting the feasibility and validity of remote assessments.", + "laySummary": "", + "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/10870547231172763; doi:https://doi.org/10.1177/10870547231172763; html:https://europepmc.org/articles/PMC10291103; pdf:https://europepmc.org/articles/PMC10291103?pdf=render" + }, { "id": "30014898", "doi": "https://doi.org/10.1016/j.envres.2018.07.015", @@ -35750,23 +35750,6 @@ "laySummary": "", "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fmed.2019.00048/pdf; doi:https://doi.org/10.3389/fmed.2019.00048; html:https://europepmc.org/articles/PMC6449432; pdf:https://europepmc.org/articles/PMC6449432?pdf=render" }, - { - "id": "31358974", - "doi": "https://doi.org/10.1038/s41562-019-0653-z", - "title": "New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders.", - "authorString": "Evangelou E, Gao H, Chu C, Ntritsos G, Blakeley P, Butts AR, Pazoki R, Suzuki H, Koskeridis F, Yiorkas AM, Karaman I, Elliott J, Luo Q, Aeschbacher S, Bartz TM, Baumeister SE, Braund PS, Brown MR, Brody JA, Clarke TK, Dimou N, Faul JD, Homuth G, Jackson AU, Kentistou KA, Joshi PK, Lemaitre RN, Lind PA, Lyytik\u00e4inen LP, Mangino M, Milaneschi Y, Nelson CP, Nolte IM, Per\u00e4l\u00e4 MM, Polasek O, Porteous D, Ratliff SM, Smith JA, Stan\u010d\u00e1kov\u00e1 A, Teumer A, Tuominen S, Th\u00e9riault S, Vangipurapu J, Whitfield JB, Wood A, Yao J, Yu B, Zhao W, Arking DE, Auvinen J, Liu C, M\u00e4nnikk\u00f6 M, Risch L, Rotter JI, Snieder H, Veijola J, Blakemore AI, Boehnke M, Campbell H, Conen D, Eriksson JG, Grabe HJ, Guo X, van der Harst P, Hartman CA, Hayward C, Heath AC, Jarvelin MR, K\u00e4h\u00f6nen M, Kardia SLR, K\u00fchne M, Kuusisto J, Laakso M, Lahti J, Lehtim\u00e4ki T, McIntosh AM, Mohlke KL, Morrison AC, Martin NG, Oldehinkel AJ, Penninx BWJH, Psaty BM, Raitakari OT, Rudan I, Samani NJ, Scott LJ, Spector TD, Verweij N, Weir DR, Wilson JF, Levy D, Tzoulaki I, Bell JD, Matthews PM, Rothenfluh A, Desrivi\u00e8res S, Schumann G, Elliott P.", - "authorAffiliations": "", - "journalTitle": "Nature human behaviour", - "pubYear": "2019", - "date": "2019-07-29", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g\u2009d-1) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 new common loci and investigated their potential functional importance using magnetic resonance imaging data and gene expression studies. We identify genetic pathways associated with alcohol consumption and suggest genetic mechanisms that are shared with neuropsychiatric disorders such as schizophrenia.", - "laySummary": "", - "urls": "pdf:https://boris.unibe.ch/174991/1/nihms-1649425.pdf; doi:https://doi.org/10.1038/s41562-019-0653-z; html:https://europepmc.org/articles/PMC7711277; pdf:https://europepmc.org/articles/PMC7711277?pdf=render; doi:https://doi.org/10.1038/s41562-019-0653-z" - }, { "id": "36204496", "doi": "https://doi.org/10.1177/23992026211048421", @@ -35784,6 +35767,23 @@ "laySummary": "", "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/23992026211048421; doi:https://doi.org/10.1177/23992026211048421; html:https://europepmc.org/articles/PMC9413596; pdf:https://europepmc.org/articles/PMC9413596?pdf=render" }, + { + "id": "31358974", + "doi": "https://doi.org/10.1038/s41562-019-0653-z", + "title": "New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders.", + "authorString": "Evangelou E, Gao H, Chu C, Ntritsos G, Blakeley P, Butts AR, Pazoki R, Suzuki H, Koskeridis F, Yiorkas AM, Karaman I, Elliott J, Luo Q, Aeschbacher S, Bartz TM, Baumeister SE, Braund PS, Brown MR, Brody JA, Clarke TK, Dimou N, Faul JD, Homuth G, Jackson AU, Kentistou KA, Joshi PK, Lemaitre RN, Lind PA, Lyytik\u00e4inen LP, Mangino M, Milaneschi Y, Nelson CP, Nolte IM, Per\u00e4l\u00e4 MM, Polasek O, Porteous D, Ratliff SM, Smith JA, Stan\u010d\u00e1kov\u00e1 A, Teumer A, Tuominen S, Th\u00e9riault S, Vangipurapu J, Whitfield JB, Wood A, Yao J, Yu B, Zhao W, Arking DE, Auvinen J, Liu C, M\u00e4nnikk\u00f6 M, Risch L, Rotter JI, Snieder H, Veijola J, Blakemore AI, Boehnke M, Campbell H, Conen D, Eriksson JG, Grabe HJ, Guo X, van der Harst P, Hartman CA, Hayward C, Heath AC, Jarvelin MR, K\u00e4h\u00f6nen M, Kardia SLR, K\u00fchne M, Kuusisto J, Laakso M, Lahti J, Lehtim\u00e4ki T, McIntosh AM, Mohlke KL, Morrison AC, Martin NG, Oldehinkel AJ, Penninx BWJH, Psaty BM, Raitakari OT, Rudan I, Samani NJ, Scott LJ, Spector TD, Verweij N, Weir DR, Wilson JF, Levy D, Tzoulaki I, Bell JD, Matthews PM, Rothenfluh A, Desrivi\u00e8res S, Schumann G, Elliott P.", + "authorAffiliations": "", + "journalTitle": "Nature human behaviour", + "pubYear": "2019", + "date": "2019-07-29", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g\u2009d-1) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 new common loci and investigated their potential functional importance using magnetic resonance imaging data and gene expression studies. We identify genetic pathways associated with alcohol consumption and suggest genetic mechanisms that are shared with neuropsychiatric disorders such as schizophrenia.", + "laySummary": "", + "urls": "pdf:https://boris.unibe.ch/174991/1/nihms-1649425.pdf; doi:https://doi.org/10.1038/s41562-019-0653-z; html:https://europepmc.org/articles/PMC7711277; pdf:https://europepmc.org/articles/PMC7711277?pdf=render; doi:https://doi.org/10.1038/s41562-019-0653-z" + }, { "id": "36208161", "doi": "https://doi.org/10.1093/eurheartj/ehac426", @@ -35853,21 +35853,21 @@ "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.054302; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.054302; html:https://europepmc.org/articles/PMC8360674; pdf:https://europepmc.org/articles/PMC8360674?pdf=render" }, { - "id": "32327693", - "doi": "https://doi.org/10.1038/s42003-020-0921-5", - "title": "Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis.", - "authorString": "Oskarsson GR, Oddsson A, Magnusson MK, Kristjansson RP, Halldorsson GH, Ferkingstad E, Zink F, Helgadottir A, Ivarsdottir EV, Arnadottir GA, Jensson BO, Katrinardottir H, Sveinbjornsson G, Kristinsdottir AM, Lee AL, Saemundsdottir J, Stefansdottir L, Sigurdsson JK, Davidsson OB, Benonisdottir S, Jonasdottir A, Jonasdottir A, Jonsson S, Gudmundsson RL, Asselbergs FW, Tragante V, Gunnarsson B, Masson G, Thorleifsson G, Rafnar T, Holm H, Olafsson I, Onundarson PT, Gudbjartsson DF, Norddahl GL, Thorsteinsdottir U, Sulem P, Stefansson K.", + "id": "31204027", + "doi": "https://doi.org/10.1016/j.injury.2019.06.012", + "title": "Comparing the outcomes of isolated, serious traumatic brain injury in older adults managed at major trauma centres and neurosurgical services: A registry-based cohort study.", + "authorString": "Dunn MS, Beck B, Simpson PM, Cameron PA, Kennedy M, Maiden M, Judson R, Gabbe BJ.", "authorAffiliations": "", - "journalTitle": "Communications biology", - "pubYear": "2020", - "date": "2020-04-23", - "isOpenAccess": "Y", - "keywords": "", + "journalTitle": "Injury", + "pubYear": "2019", + "date": "2019-06-10", + "isOpenAccess": "N", + "keywords": "Traumatic brain injury; Functional Outcome; Older Adult; Tbi; Trauma Systems", "nationalPriorities": "", "healthCategories": "", - "abstract": "Hemoglobin is the essential oxygen-carrying molecule in humans and is regulated by cellular iron and oxygen sensing mechanisms. To search for novel variants associated with hemoglobin concentration, we performed genome-wide association studies of hemoglobin concentration using a combined set of 684,122 individuals from Iceland and the UK. Notably, we found seven novel variants, six rare coding and one common, at the ACO1 locus associating with either decreased or increased hemoglobin concentration. Of these variants, the missense Cys506Ser and the stop-gained Lys334Ter mutations are specific to eight and ten generation pedigrees, respectively, and have the two largest effects in the study (EffectCys506Ser\u2009=\u2009-1.61\u2009SD, CI95\u2009=\u2009[-1.98, -1.35]; EffectLys334Ter\u2009=\u20090.63\u2009SD, CI95\u2009=\u2009[0.36, 0.91]). We also find Cys506Ser to associate with increased risk of persistent anemia (OR\u2009=\u200917.1, P\u2009=\u20092\u2009\u00d7\u200910-14). The strong bidirectional effects seen in this study implicate ACO1, a known iron sensing molecule, as a major homeostatic regulator of hemoglobin concentration.", + "abstract": "

Background

The incidence of older adult traumatic brain injury (TBI) is increasing in both high and middle to low-income countries. It is unknown whether older adults with isolated, serious TBI can be safely managed outside of major trauma centres. This registry based cohort study aimed to compare mortality and functional outcomes of older adults with isolated, serious TBI who were managed at specialised Major Trauma Services (MTS) and Metropolitan Neurosurgical Services (MNS).

Method

Older adults (65 years and over) who sustained an isolated, serious TBI following a low fall (from standing or \u2264 1\u2009m) were extracted from the Victorian State Trauma Registry from 2007 to 2016. Multivariable models were fitted to assess the association between hospital designation (MTS vs. MNS) and the two outcomes of interest: in-hospital mortality and functional outcome, adjusting for potential confounders. Functional outcomes were measured using the Glasgow Outcome Scale Extended at six months post-injury.

Results

From 2007-2016, there were 1904 older adults who sustained an isolated, serious TBI from a low fall who received definitive care at an MTS (n\u2009=\u20091124) or an MNS (n\u2009=\u2009780). After adjusting for confounders, there was no mortality benefit for patients managed at an MTS over an MNS (OR\u2009=\u20090.84; 95% CI: 0.65, 1.08; P\u2009=\u20090.17) or improvement in functional outcome six months post-injury (OR\u2009=\u20091.13; 95% CI: 0.94, 1.36; P\u2009=\u20090.21).

Conclusion

For older adults with isolated, serious TBI following a low fall, there was no difference in mortality or functional outcome based on definitive management at an MTS or an MNS. This confirms that MNS without the added designation of a major trauma centre are a suitable destination for the management of isolated, serious TBI in older adults.", "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s42003-020-0921-5.pdf; doi:https://doi.org/10.1038/s42003-020-0921-5; html:https://europepmc.org/articles/PMC7181819; pdf:https://europepmc.org/articles/PMC7181819?pdf=render" + "urls": "doi:https://doi.org/10.1016/j.injury.2019.06.012" }, { "id": "36696816", @@ -35887,21 +35887,21 @@ "urls": "doi:https://doi.org/10.1016/j.ebiom.2023.104441; doi:https://doi.org/10.1016/j.ebiom.2023.104441; html:https://europepmc.org/articles/PMC9879767; pdf:https://europepmc.org/articles/PMC9879767?pdf=render" }, { - "id": "31204027", - "doi": "https://doi.org/10.1016/j.injury.2019.06.012", - "title": "Comparing the outcomes of isolated, serious traumatic brain injury in older adults managed at major trauma centres and neurosurgical services: A registry-based cohort study.", - "authorString": "Dunn MS, Beck B, Simpson PM, Cameron PA, Kennedy M, Maiden M, Judson R, Gabbe BJ.", + "id": "32327693", + "doi": "https://doi.org/10.1038/s42003-020-0921-5", + "title": "Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis.", + "authorString": "Oskarsson GR, Oddsson A, Magnusson MK, Kristjansson RP, Halldorsson GH, Ferkingstad E, Zink F, Helgadottir A, Ivarsdottir EV, Arnadottir GA, Jensson BO, Katrinardottir H, Sveinbjornsson G, Kristinsdottir AM, Lee AL, Saemundsdottir J, Stefansdottir L, Sigurdsson JK, Davidsson OB, Benonisdottir S, Jonasdottir A, Jonasdottir A, Jonsson S, Gudmundsson RL, Asselbergs FW, Tragante V, Gunnarsson B, Masson G, Thorleifsson G, Rafnar T, Holm H, Olafsson I, Onundarson PT, Gudbjartsson DF, Norddahl GL, Thorsteinsdottir U, Sulem P, Stefansson K.", "authorAffiliations": "", - "journalTitle": "Injury", - "pubYear": "2019", - "date": "2019-06-10", - "isOpenAccess": "N", - "keywords": "Traumatic brain injury; Functional Outcome; Older Adult; Tbi; Trauma Systems", + "journalTitle": "Communications biology", + "pubYear": "2020", + "date": "2020-04-23", + "isOpenAccess": "Y", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

The incidence of older adult traumatic brain injury (TBI) is increasing in both high and middle to low-income countries. It is unknown whether older adults with isolated, serious TBI can be safely managed outside of major trauma centres. This registry based cohort study aimed to compare mortality and functional outcomes of older adults with isolated, serious TBI who were managed at specialised Major Trauma Services (MTS) and Metropolitan Neurosurgical Services (MNS).

Method

Older adults (65 years and over) who sustained an isolated, serious TBI following a low fall (from standing or \u2264 1\u2009m) were extracted from the Victorian State Trauma Registry from 2007 to 2016. Multivariable models were fitted to assess the association between hospital designation (MTS vs. MNS) and the two outcomes of interest: in-hospital mortality and functional outcome, adjusting for potential confounders. Functional outcomes were measured using the Glasgow Outcome Scale Extended at six months post-injury.

Results

From 2007-2016, there were 1904 older adults who sustained an isolated, serious TBI from a low fall who received definitive care at an MTS (n\u2009=\u20091124) or an MNS (n\u2009=\u2009780). After adjusting for confounders, there was no mortality benefit for patients managed at an MTS over an MNS (OR\u2009=\u20090.84; 95% CI: 0.65, 1.08; P\u2009=\u20090.17) or improvement in functional outcome six months post-injury (OR\u2009=\u20091.13; 95% CI: 0.94, 1.36; P\u2009=\u20090.21).

Conclusion

For older adults with isolated, serious TBI following a low fall, there was no difference in mortality or functional outcome based on definitive management at an MTS or an MNS. This confirms that MNS without the added designation of a major trauma centre are a suitable destination for the management of isolated, serious TBI in older adults.", + "abstract": "Hemoglobin is the essential oxygen-carrying molecule in humans and is regulated by cellular iron and oxygen sensing mechanisms. To search for novel variants associated with hemoglobin concentration, we performed genome-wide association studies of hemoglobin concentration using a combined set of 684,122 individuals from Iceland and the UK. Notably, we found seven novel variants, six rare coding and one common, at the ACO1 locus associating with either decreased or increased hemoglobin concentration. Of these variants, the missense Cys506Ser and the stop-gained Lys334Ter mutations are specific to eight and ten generation pedigrees, respectively, and have the two largest effects in the study (EffectCys506Ser\u2009=\u2009-1.61\u2009SD, CI95\u2009=\u2009[-1.98, -1.35]; EffectLys334Ter\u2009=\u20090.63\u2009SD, CI95\u2009=\u2009[0.36, 0.91]). We also find Cys506Ser to associate with increased risk of persistent anemia (OR\u2009=\u200917.1, P\u2009=\u20092\u2009\u00d7\u200910-14). The strong bidirectional effects seen in this study implicate ACO1, a known iron sensing molecule, as a major homeostatic regulator of hemoglobin concentration.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.injury.2019.06.012" + "urls": "pdf:https://www.nature.com/articles/s42003-020-0921-5.pdf; doi:https://doi.org/10.1038/s42003-020-0921-5; html:https://europepmc.org/articles/PMC7181819; pdf:https://europepmc.org/articles/PMC7181819?pdf=render" }, { "id": "36541441", @@ -36243,23 +36243,6 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/11/e056601.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-056601; html:https://europepmc.org/articles/PMC8573296; pdf:https://europepmc.org/articles/PMC8573296?pdf=render" }, - { - "id": "38296292", - "doi": "https://doi.org/10.1136/bmjopen-2023-078135", - "title": "Risk factor associations for severe COVID-19, influenza and pneumonia in people with diabetes to inform future pandemic preparations: UK population-based cohort study.", - "authorString": "Hopkins R, Young KG, Thomas NJ, Godwin J, Raja D, Mateen BA, Challen RJ, Vollmer SJ, Shields BM, McGovern AP, Dennis JM.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2024", - "date": "2024-01-31", - "isOpenAccess": "Y", - "keywords": "risk factors; Electronic Health Records; Diabetes & Endocrinology; Covid-19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

This study aimed to compare clinical and sociodemographic risk factors for severe COVID-19, influenza and pneumonia, in people with diabetes.

Design

Population-based cohort study.

Setting

UK primary care records (Clinical Practice Research Datalink) linked to mortality and hospital records.

Participants

Individuals with type 1 and type 2 diabetes (COVID-19 cohort: n=43\u2009033\u2009type 1 diabetes and n=584\u2009854\u2009type 2 diabetes, influenza and pneumonia cohort: n=42\u2009488\u2009type 1 diabetes and n=585\u2009289\u2009type 2 diabetes).

Primary and secondary outcome measures

COVID-19 hospitalisation from 1 February 2020 to 31 October 2020 (pre-COVID-19 vaccination roll-out), and influenza and pneumonia hospitalisation from 1 September 2016 to 31 May 2019 (pre-COVID-19 pandemic). Secondary outcomes were COVID-19 and pneumonia mortality. Associations between clinical and sociodemographic risk factors and each outcome were assessed using multivariable Cox proportional hazards models. In people with type 2 diabetes, we explored modifying effects of glycated haemoglobin (HbA1c) and body mass index (BMI) by age, sex and ethnicity.

Results

In type 2 diabetes, poor glycaemic control and severe obesity were consistently associated with increased risk of hospitalisation for COVID-19, influenza and pneumonia. The highest HbA1c and BMI-associated relative risks were observed in people aged under 70 years. Sociodemographic-associated risk differed markedly by respiratory infection, particularly for ethnicity. Compared with people of white ethnicity, black and south Asian groups had a greater risk of COVID-19 hospitalisation, but a lesser risk of pneumonia hospitalisation. Risk factor associations for type 1 diabetes and for type 2 diabetes mortality were broadly consistent with the primary analysis.

Conclusions

Clinical risk factors of high HbA1c and severe obesity are consistently associated with severe outcomes from COVID-19, influenza and pneumonia, especially in younger people. In contrast, associations with sociodemographic risk factors differed by type of respiratory infection. This emphasises that risk stratification should be specific to individual respiratory infections.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bmjopen-2023-078135; html:https://europepmc.org/articles/PMC10831438; pdf:https://europepmc.org/articles/PMC10831438?pdf=render" - }, { "id": "34732839", "doi": "https://doi.org/10.1038/s41379-021-00953-0", @@ -36277,6 +36260,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41379-021-00953-0.pdf; doi:https://doi.org/10.1038/s41379-021-00953-0; html:https://europepmc.org/articles/PMC8964416; pdf:https://europepmc.org/articles/PMC8964416?pdf=render" }, + { + "id": "38296292", + "doi": "https://doi.org/10.1136/bmjopen-2023-078135", + "title": "Risk factor associations for severe COVID-19, influenza and pneumonia in people with diabetes to inform future pandemic preparations: UK population-based cohort study.", + "authorString": "Hopkins R, Young KG, Thomas NJ, Godwin J, Raja D, Mateen BA, Challen RJ, Vollmer SJ, Shields BM, McGovern AP, Dennis JM.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2024", + "date": "2024-01-31", + "isOpenAccess": "Y", + "keywords": "risk factors; Electronic Health Records; Diabetes & Endocrinology; Covid-19", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

This study aimed to compare clinical and sociodemographic risk factors for severe COVID-19, influenza and pneumonia, in people with diabetes.

Design

Population-based cohort study.

Setting

UK primary care records (Clinical Practice Research Datalink) linked to mortality and hospital records.

Participants

Individuals with type 1 and type 2 diabetes (COVID-19 cohort: n=43\u2009033\u2009type 1 diabetes and n=584\u2009854\u2009type 2 diabetes, influenza and pneumonia cohort: n=42\u2009488\u2009type 1 diabetes and n=585\u2009289\u2009type 2 diabetes).

Primary and secondary outcome measures

COVID-19 hospitalisation from 1 February 2020 to 31 October 2020 (pre-COVID-19 vaccination roll-out), and influenza and pneumonia hospitalisation from 1 September 2016 to 31 May 2019 (pre-COVID-19 pandemic). Secondary outcomes were COVID-19 and pneumonia mortality. Associations between clinical and sociodemographic risk factors and each outcome were assessed using multivariable Cox proportional hazards models. In people with type 2 diabetes, we explored modifying effects of glycated haemoglobin (HbA1c) and body mass index (BMI) by age, sex and ethnicity.

Results

In type 2 diabetes, poor glycaemic control and severe obesity were consistently associated with increased risk of hospitalisation for COVID-19, influenza and pneumonia. The highest HbA1c and BMI-associated relative risks were observed in people aged under 70 years. Sociodemographic-associated risk differed markedly by respiratory infection, particularly for ethnicity. Compared with people of white ethnicity, black and south Asian groups had a greater risk of COVID-19 hospitalisation, but a lesser risk of pneumonia hospitalisation. Risk factor associations for type 1 diabetes and for type 2 diabetes mortality were broadly consistent with the primary analysis.

Conclusions

Clinical risk factors of high HbA1c and severe obesity are consistently associated with severe outcomes from COVID-19, influenza and pneumonia, especially in younger people. In contrast, associations with sociodemographic risk factors differed by type of respiratory infection. This emphasises that risk stratification should be specific to individual respiratory infections.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/bmjopen-2023-078135; html:https://europepmc.org/articles/PMC10831438; pdf:https://europepmc.org/articles/PMC10831438?pdf=render" + }, { "id": "35211795", "doi": "https://doi.org/10.1007/s00467-022-05440-5", @@ -36328,23 +36328,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41397-023-00307-w.pdf; doi:https://doi.org/10.1038/s41397-023-00307-w; html:https://europepmc.org/articles/PMC10506906; pdf:https://europepmc.org/articles/PMC10506906?pdf=render" }, - { - "id": "34937765", - "doi": "https://doi.org/10.1136/injuryprev-2021-044309", - "title": "Predictors of health-related quality of life following injury in childhood and adolescence: a pooled analysis.", - "authorString": "Dipnall JF, Rivara FP, Lyons RA, Ameratunga S, Brussoni M, Lecky FE, Bradley C, Beck B, Lyons J, Schneeberg A, Harrison JE, Gabbe BJ.", - "authorAffiliations": "", - "journalTitle": "Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention", - "pubYear": "2022", - "date": "2021-12-22", - "isOpenAccess": "N", - "keywords": "Public Health; Disability; Longitudinal", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Injury is a leading contributor to the global disease burden in children and places children at risk for adverse and lasting impacts on their health-related quality of life (HRQoL) and development. This study aimed to identify key predictors of HRQoL following injury in childhood and adolescence.

Methods

Data from 2259 injury survivors (<18 years when injured) were pooled from four longitudinal cohort studies (Australia, Canada, UK, USA) from the paediatric Validating Injury Burden Estimates Study (VIBES-Junior). Outcomes were the Paediatric Quality of Life Inventory (PedsQL) total, physical, psychosocial functioning scores at 1, 3-4, 6, 12, 24 months postinjury.

Results

Mean PedsQL total score increased with higher socioeconomic status and decreased with increasing age. It was lower for transport-related incidents, \u22651 comorbidities, intentional injuries, spinal cord injury, vertebral column fracture, moderate/severe traumatic brain injury and fracture of patella/tibia/fibula/ankle. Mean PedsQL physical score was lower for females, fracture of femur, fracture of pelvis and burns. Mean PedsQL psychosocial score was lower for asphyxiation/non-fatal submersion and muscle/tendon/dislocation injuries.

Conclusions

Postinjury HRQoL was associated with survivors' socioeconomic status, intent, mechanism of injury and comorbidity status. Patterns of physical and psychosocial functioning postinjury differed according to sex and nature of injury sustained. The findings improve understanding of the long-term individual and societal impacts of injury in the early part of life and guide the prioritisation of prevention efforts, inform health and social service planning to help reduce injury burden, and help guide future Global Burden of Disease estimates.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/injuryprev-2021-044309" - }, { "id": "31950891", "doi": "https://doi.org/10.1192/bjo.2019.96", @@ -36363,21 +36346,21 @@ "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/6EF9FC74DC5A744C9D841DD649992ABE/S2056472419000966a.pdf/div-class-title-predicting-high-cost-care-in-a-mental-health-setting-div.pdf; doi:https://doi.org/10.1192/bjo.2019.96; html:https://europepmc.org/articles/PMC7001466; pdf:https://europepmc.org/articles/PMC7001466?pdf=render" }, { - "id": "34441449", - "doi": "https://doi.org/10.3390/diagnostics11081516", - "title": "Stability of OCT and OCTA in the Intensive Therapy Unit Setting.", - "authorString": "Courtie EF, Kale AU, Hui BTK, Liu X, Capewell NI, Bishop JRB, Whitehouse T, Veenith T, Logan A, Denniston AK, Blanch RJ.", + "id": "34937765", + "doi": "https://doi.org/10.1136/injuryprev-2021-044309", + "title": "Predictors of health-related quality of life following injury in childhood and adolescence: a pooled analysis.", + "authorString": "Dipnall JF, Rivara FP, Lyons RA, Ameratunga S, Brussoni M, Lecky FE, Bradley C, Beck B, Lyons J, Schneeberg A, Harrison JE, Gabbe BJ.", "authorAffiliations": "", - "journalTitle": "Diagnostics (Basel, Switzerland)", - "pubYear": "2021", - "date": "2021-08-23", - "isOpenAccess": "Y", - "keywords": "Stability; Critical Care; Optical Coherence Tomography Angiography", + "journalTitle": "Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention", + "pubYear": "2022", + "date": "2021-12-22", + "isOpenAccess": "N", + "keywords": "Public Health; Disability; Longitudinal", "nationalPriorities": "", "healthCategories": "", - "abstract": "To assess the stability of retinal structure and blood flow measures over time and in different clinical settings using portable optical coherence tomography angiography (OCTA) as a potential biomarker of central perfusion in critical illness, 18 oesophagectomy patients completed retinal structure and blood flow measurements by portable OCT and OCTA in the eye clinic and intensive therapy unit (ITU) across three timepoints: (1) pre-operation in a clinic setting; (2) 24-48 h post-operation during ITU admission; and (3) seven days post-operation, if the patient was still admitted. Blood flow and macular structural measures were stable between the examination settings, with no consistent variation between pre- and post-operation scans, while retinal nerve fibre layer thickness increased in the post-operative scans (+2.31 \u00b5m, p = 0.001). Foveal avascular zone (FAZ) measurements were the most stable, with an intraclass correlation coefficient of up to 0.92 for right eye FAZ area. Blood flow and structural measures were lower in left eyes than right eyes. Retinal blood flow assessed in patients before and during an ITU stay using portable OCTA showed no systematic differences between the clinical settings. The stability of retinal blood flow measures suggests the potential for portable OCTA to provide clinically useful measures in ITU patients.", + "abstract": "

Background

Injury is a leading contributor to the global disease burden in children and places children at risk for adverse and lasting impacts on their health-related quality of life (HRQoL) and development. This study aimed to identify key predictors of HRQoL following injury in childhood and adolescence.

Methods

Data from 2259 injury survivors (<18 years when injured) were pooled from four longitudinal cohort studies (Australia, Canada, UK, USA) from the paediatric Validating Injury Burden Estimates Study (VIBES-Junior). Outcomes were the Paediatric Quality of Life Inventory (PedsQL) total, physical, psychosocial functioning scores at 1, 3-4, 6, 12, 24 months postinjury.

Results

Mean PedsQL total score increased with higher socioeconomic status and decreased with increasing age. It was lower for transport-related incidents, \u22651 comorbidities, intentional injuries, spinal cord injury, vertebral column fracture, moderate/severe traumatic brain injury and fracture of patella/tibia/fibula/ankle. Mean PedsQL physical score was lower for females, fracture of femur, fracture of pelvis and burns. Mean PedsQL psychosocial score was lower for asphyxiation/non-fatal submersion and muscle/tendon/dislocation injuries.

Conclusions

Postinjury HRQoL was associated with survivors' socioeconomic status, intent, mechanism of injury and comorbidity status. Patterns of physical and psychosocial functioning postinjury differed according to sex and nature of injury sustained. The findings improve understanding of the long-term individual and societal impacts of injury in the early part of life and guide the prioritisation of prevention efforts, inform health and social service planning to help reduce injury burden, and help guide future Global Burden of Disease estimates.", "laySummary": "", - "urls": "pdf:https://www.mdpi.com/2075-4418/11/8/1516/pdf?version=1629792973; doi:https://doi.org/10.3390/diagnostics11081516; html:https://europepmc.org/articles/PMC8394026; pdf:https://europepmc.org/articles/PMC8394026?pdf=render" + "urls": "doi:https://doi.org/10.1136/injuryprev-2021-044309" }, { "id": "34151246", @@ -36396,6 +36379,23 @@ "laySummary": "", "urls": "pdf:http://www.cjcopen.ca/article/S2589790X21001554/pdf; doi:https://doi.org/10.1016/j.cjco.2021.05.020; html:https://europepmc.org/articles/PMC8205551; pdf:https://europepmc.org/articles/PMC8205551?pdf=render" }, + { + "id": "34441449", + "doi": "https://doi.org/10.3390/diagnostics11081516", + "title": "Stability of OCT and OCTA in the Intensive Therapy Unit Setting.", + "authorString": "Courtie EF, Kale AU, Hui BTK, Liu X, Capewell NI, Bishop JRB, Whitehouse T, Veenith T, Logan A, Denniston AK, Blanch RJ.", + "authorAffiliations": "", + "journalTitle": "Diagnostics (Basel, Switzerland)", + "pubYear": "2021", + "date": "2021-08-23", + "isOpenAccess": "Y", + "keywords": "Stability; Critical Care; Optical Coherence Tomography Angiography", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "To assess the stability of retinal structure and blood flow measures over time and in different clinical settings using portable optical coherence tomography angiography (OCTA) as a potential biomarker of central perfusion in critical illness, 18 oesophagectomy patients completed retinal structure and blood flow measurements by portable OCT and OCTA in the eye clinic and intensive therapy unit (ITU) across three timepoints: (1) pre-operation in a clinic setting; (2) 24-48 h post-operation during ITU admission; and (3) seven days post-operation, if the patient was still admitted. Blood flow and macular structural measures were stable between the examination settings, with no consistent variation between pre- and post-operation scans, while retinal nerve fibre layer thickness increased in the post-operative scans (+2.31 \u00b5m, p = 0.001). Foveal avascular zone (FAZ) measurements were the most stable, with an intraclass correlation coefficient of up to 0.92 for right eye FAZ area. Blood flow and structural measures were lower in left eyes than right eyes. Retinal blood flow assessed in patients before and during an ITU stay using portable OCTA showed no systematic differences between the clinical settings. The stability of retinal blood flow measures suggests the potential for portable OCTA to provide clinically useful measures in ITU patients.", + "laySummary": "", + "urls": "pdf:https://www.mdpi.com/2075-4418/11/8/1516/pdf?version=1629792973; doi:https://doi.org/10.3390/diagnostics11081516; html:https://europepmc.org/articles/PMC8394026; pdf:https://europepmc.org/articles/PMC8394026?pdf=render" + }, { "id": "30928767", "doi": "https://doi.org/10.1016/j.evalprogplan.2019.03.002", @@ -36430,23 +36430,6 @@ "laySummary": "", "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621615; doi:https://doi.org/10.1038/s44161-022-00171-0; html:https://europepmc.org/articles/PMC10621615; pdf:https://europepmc.org/articles/PMC10621615?pdf=render; doi:https://doi.org/10.1038/s44161-022-00171-0" }, - { - "id": "35606419", - "doi": "https://doi.org/10.1038/s41593-022-01074-w", - "title": "Phenotypic and genetic associations of quantitative magnetic susceptibility in UK Biobank brain imaging.", - "authorString": "Wang C, Martins-Bach AB, Alfaro-Almagro F, Douaud G, Klein JC, Llera A, Fiscone C, Bowtell R, Elliott LT, Smith SM, Tendler BC, Miller KL.", - "authorAffiliations": "", - "journalTitle": "Nature neuroscience", - "pubYear": "2022", - "date": "2022-05-23", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "A key aim in epidemiological neuroscience is identification of markers to assess brain health and monitor therapeutic interventions. Quantitative susceptibility mapping (QSM) is an emerging magnetic resonance imaging technique that measures tissue magnetic susceptibility and has been shown to detect pathological changes in tissue iron, myelin and calcification. We present an open resource of QSM-based imaging measures of multiple brain structures in 35,273 individuals from the UK Biobank prospective epidemiological study. We identify statistically significant associations of 251 phenotypes with magnetic susceptibility that include body iron, disease, diet and alcohol consumption. Genome-wide associations relate magnetic susceptibility to 76 replicating clusters of genetic variants with biological functions involving iron, calcium, myelin and extracellular matrix. These patterns of associations include relationships that are unique to QSM, in particular being complementary to T2* signal decay time measures. These new imaging phenotypes are being integrated into the core UK Biobank measures provided to researchers worldwide, creating the potential to discover new, non-invasive markers of brain health.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41593-022-01074-w.pdf; doi:https://doi.org/10.1038/s41593-022-01074-w; html:https://europepmc.org/articles/PMC9174052; pdf:https://europepmc.org/articles/PMC9174052?pdf=render" - }, { "id": "35509371", "doi": "https://doi.org/10.12688/wellcomeopenres.16883.2", @@ -36464,6 +36447,23 @@ "laySummary": "", "urls": "pdf:https://wellcomeopenresearch.org/articles/6-149/v2/pdf; doi:https://doi.org/10.12688/wellcomeopenres.16883.2; html:https://europepmc.org/articles/PMC9046903; pdf:https://europepmc.org/articles/PMC9046903?pdf=render" }, + { + "id": "35606419", + "doi": "https://doi.org/10.1038/s41593-022-01074-w", + "title": "Phenotypic and genetic associations of quantitative magnetic susceptibility in UK Biobank brain imaging.", + "authorString": "Wang C, Martins-Bach AB, Alfaro-Almagro F, Douaud G, Klein JC, Llera A, Fiscone C, Bowtell R, Elliott LT, Smith SM, Tendler BC, Miller KL.", + "authorAffiliations": "", + "journalTitle": "Nature neuroscience", + "pubYear": "2022", + "date": "2022-05-23", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "A key aim in epidemiological neuroscience is identification of markers to assess brain health and monitor therapeutic interventions. Quantitative susceptibility mapping (QSM) is an emerging magnetic resonance imaging technique that measures tissue magnetic susceptibility and has been shown to detect pathological changes in tissue iron, myelin and calcification. We present an open resource of QSM-based imaging measures of multiple brain structures in 35,273 individuals from the UK Biobank prospective epidemiological study. We identify statistically significant associations of 251 phenotypes with magnetic susceptibility that include body iron, disease, diet and alcohol consumption. Genome-wide associations relate magnetic susceptibility to 76 replicating clusters of genetic variants with biological functions involving iron, calcium, myelin and extracellular matrix. These patterns of associations include relationships that are unique to QSM, in particular being complementary to T2* signal decay time measures. These new imaging phenotypes are being integrated into the core UK Biobank measures provided to researchers worldwide, creating the potential to discover new, non-invasive markers of brain health.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41593-022-01074-w.pdf; doi:https://doi.org/10.1038/s41593-022-01074-w; html:https://europepmc.org/articles/PMC9174052; pdf:https://europepmc.org/articles/PMC9174052?pdf=render" + }, { "id": "35258317", "doi": "https://doi.org/10.1161/jaha.121.024260", @@ -36668,23 +36668,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jaad.2021.07.066; doi:https://doi.org/10.1016/j.jaad.2021.07.066; html:https://europepmc.org/articles/PMC7612892; pdf:https://europepmc.org/articles/PMC7612892?pdf=render" }, - { - "id": "36245269", - "doi": "https://doi.org/10.15252/embj.2022111857", - "title": "Cryo-EM structures of perforin-2 in isolation and assembled on a membrane suggest a mechanism for pore formation.", - "authorString": "Yu X, Ni T, Munson G, Zhang P, Gilbert RJC.", - "authorAffiliations": "", - "journalTitle": "The EMBO journal", - "pubYear": "2022", - "date": "2022-10-17", - "isOpenAccess": "Y", - "keywords": "Cryo-electron Tomography; Cryo-em; Subtomogram Averaging; Pore-forming Protein; Perforin-2", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Perforin-2 (PFN2, MPEG1) is a key pore-forming protein in mammalian innate immunity restricting intracellular bacteria proliferation. It forms a membrane-bound pre-pore complex that converts to a pore-forming structure upon acidification; but its mechanism of conformational transition has been debated. Here we used cryo-electron microscopy, tomography and subtomogram averaging to determine structures of PFN2 in pre-pore and pore conformations in isolation and bound to liposomes. In isolation and upon acidification, the pre-assembled complete pre-pore rings convert to pores in both flat ring and twisted conformations. On membranes, in\u00a0situ assembled PFN2 pre-pores display various degrees of completeness; whereas PFN2 pores are mainly incomplete arc structures that follow the same subunit packing arrangements as found in isolation. Both assemblies on membranes use their P2 \u03b2-hairpin for binding to the lipid membrane surface. Overall, these structural snapshots suggest a molecular mechanism for PFN2 pre-pore to pore transition on a targeted membrane, potentially using the twisted pore as an intermediate or alternative state to the flat conformation, with the capacity to cause bilayer distortion during membrane insertion.", - "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.15252/embj.2022111857; doi:https://doi.org/10.15252/embj.2022111857; html:https://europepmc.org/articles/PMC9713709; pdf:https://europepmc.org/articles/PMC9713709?pdf=render" - }, { "id": "34110679", "doi": "https://doi.org/10.1002/1878-0261.13038", @@ -36702,6 +36685,23 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/1878-0261.13038; doi:https://doi.org/10.1002/1878-0261.13038; html:https://europepmc.org/articles/PMC8486593; pdf:https://europepmc.org/articles/PMC8486593?pdf=render" }, + { + "id": "36245269", + "doi": "https://doi.org/10.15252/embj.2022111857", + "title": "Cryo-EM structures of perforin-2 in isolation and assembled on a membrane suggest a mechanism for pore formation.", + "authorString": "Yu X, Ni T, Munson G, Zhang P, Gilbert RJC.", + "authorAffiliations": "", + "journalTitle": "The EMBO journal", + "pubYear": "2022", + "date": "2022-10-17", + "isOpenAccess": "Y", + "keywords": "Cryo-electron Tomography; Cryo-em; Subtomogram Averaging; Pore-forming Protein; Perforin-2", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Perforin-2 (PFN2, MPEG1) is a key pore-forming protein in mammalian innate immunity restricting intracellular bacteria proliferation. It forms a membrane-bound pre-pore complex that converts to a pore-forming structure upon acidification; but its mechanism of conformational transition has been debated. Here we used cryo-electron microscopy, tomography and subtomogram averaging to determine structures of PFN2 in pre-pore and pore conformations in isolation and bound to liposomes. In isolation and upon acidification, the pre-assembled complete pre-pore rings convert to pores in both flat ring and twisted conformations. On membranes, in\u00a0situ assembled PFN2 pre-pores display various degrees of completeness; whereas PFN2 pores are mainly incomplete arc structures that follow the same subunit packing arrangements as found in isolation. Both assemblies on membranes use their P2 \u03b2-hairpin for binding to the lipid membrane surface. Overall, these structural snapshots suggest a molecular mechanism for PFN2 pre-pore to pore transition on a targeted membrane, potentially using the twisted pore as an intermediate or alternative state to the flat conformation, with the capacity to cause bilayer distortion during membrane insertion.", + "laySummary": "", + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.15252/embj.2022111857; doi:https://doi.org/10.15252/embj.2022111857; html:https://europepmc.org/articles/PMC9713709; pdf:https://europepmc.org/articles/PMC9713709?pdf=render" + }, { "id": "35051442", "doi": "https://doi.org/10.1016/j.jviromet.2022.114471", @@ -36821,23 +36821,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41591-021-01275-z.pdf; doi:https://doi.org/10.1038/s41591-021-01275-z" }, - { - "id": "36647047", - "doi": "https://doi.org/10.1186/s12916-022-02722-5", - "title": "Polypharmacy during pregnancy and\u00a0associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019.", - "authorString": "Subramanian A, Azcoaga-Lorenzo A, Anand A, Phillips K, Lee SI, Cockburn N, Fagbamigbe AF, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Hope H, Kennedy JI, Abel KM, Eastwood KA, Locock L, Black M, Loane M, Moss N, Plachcinski R, Thangaratinam S, Brophy S, Agrawal U, Vowles Z, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.", - "authorAffiliations": "", - "journalTitle": "BMC medicine", - "pubYear": "2023", - "date": "2023-01-16", - "isOpenAccess": "Y", - "keywords": "Pregnancy; Prescriptions; Polypharmacy; Medications; Multimorbidity; Multiple Medications; Multiple Long-term Conditions", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy.

Methods

A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register. Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period. Logistic regression models were performed to identify risk factors for polypharmacy.

Results

During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%. Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs). Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese [aOR: 1.16 (1.14-1.18) and 1.55 (1.53-1.57)], belonging to an ethnic minority group [aOR: 2.40 (2.33-2.47), 1.71 (1.65-1.76), 1.41 (1.35-1.47) and 1.39 (1.30-1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women] and smoking or previously smoking [aOR: 1.19 (1.18-1.20) and 1.05 (1.03-1.06)]. Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy.

Conclusions

The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus.", - "laySummary": "", - "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02722-5; doi:https://doi.org/10.1186/s12916-022-02722-5; html:https://europepmc.org/articles/PMC9843951; pdf:https://europepmc.org/articles/PMC9843951?pdf=render" - }, { "id": "31675503", "doi": "https://doi.org/10.1016/j.cell.2019.10.004", @@ -36855,6 +36838,23 @@ "laySummary": "", "urls": "pdf:http://www.cell.com/article/S0092867419311201/pdf; doi:https://doi.org/10.1016/j.cell.2019.10.004; html:https://europepmc.org/articles/PMC7202134; pdf:https://europepmc.org/articles/PMC7202134?pdf=render; doi:https://doi.org/10.1016/j.cell.2019.10.004" }, + { + "id": "36647047", + "doi": "https://doi.org/10.1186/s12916-022-02722-5", + "title": "Polypharmacy during pregnancy and\u00a0associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019.", + "authorString": "Subramanian A, Azcoaga-Lorenzo A, Anand A, Phillips K, Lee SI, Cockburn N, Fagbamigbe AF, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Hope H, Kennedy JI, Abel KM, Eastwood KA, Locock L, Black M, Loane M, Moss N, Plachcinski R, Thangaratinam S, Brophy S, Agrawal U, Vowles Z, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.", + "authorAffiliations": "", + "journalTitle": "BMC medicine", + "pubYear": "2023", + "date": "2023-01-16", + "isOpenAccess": "Y", + "keywords": "Pregnancy; Prescriptions; Polypharmacy; Medications; Multimorbidity; Multiple Medications; Multiple Long-term Conditions", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy.

Methods

A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register. Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period. Logistic regression models were performed to identify risk factors for polypharmacy.

Results

During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%. Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs). Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese [aOR: 1.16 (1.14-1.18) and 1.55 (1.53-1.57)], belonging to an ethnic minority group [aOR: 2.40 (2.33-2.47), 1.71 (1.65-1.76), 1.41 (1.35-1.47) and 1.39 (1.30-1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women] and smoking or previously smoking [aOR: 1.19 (1.18-1.20) and 1.05 (1.03-1.06)]. Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy.

Conclusions

The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus.", + "laySummary": "", + "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02722-5; doi:https://doi.org/10.1186/s12916-022-02722-5; html:https://europepmc.org/articles/PMC9843951; pdf:https://europepmc.org/articles/PMC9843951?pdf=render" + }, { "id": "34732073", "doi": "https://doi.org/10.1161/strokeaha.121.034787", @@ -36872,23 +36872,6 @@ "laySummary": "", "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.121.034787; doi:https://doi.org/10.1161/STROKEAHA.121.034787; html:https://europepmc.org/articles/PMC8607920; pdf:https://europepmc.org/articles/PMC8607920?pdf=render; doi:https://doi.org/10.1161/strokeaha.121.034787" }, - { - "id": "34216337", - "doi": "https://doi.org/10.1007/s10552-021-01466-6", - "title": "Physical activity in relation to circulating hormone concentrations in 117,100 men in UK Biobank.", - "authorString": "Watts EL, Perez-Cornago A, Doherty A, Allen NE, Fensom GK, Tin Tin S, Key TJ, Travis RC.", - "authorAffiliations": "", - "journalTitle": "Cancer causes & control : CCC", - "pubYear": "2021", - "date": "2021-07-03", - "isOpenAccess": "Y", - "keywords": "Testosterone; IGF-I; Physical Activity; Accelerometer; Shbg; Uk Biobank", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Purpose

Physical activity may reduce the risk of some types of cancer in men. Biological mechanisms may involve changes in hormone concentrations; however, this relationship is not well established. Therefore, we aimed to investigate the associations of physical activity with circulating insulin-like growth factor-I (IGF-I), sex hormone-binding globulin (SHBG, which modifies sex hormone activity), and total and free testosterone concentrations, and the extent these associations might be mediated by body mass index (BMI).

Methods

Circulating concentrations of these hormones and anthropometric measurements and self-reported physical activity data were available for 117,100 healthy male UK Biobank participants at recruitment. Objectively measured accelerometer physical activity levels were also collected on average 5.7\u00a0years after recruitment in 28,000 men. Geometric means of hormone concentrations were estimated using multivariable-adjusted analysis of variance, with and without adjustment for BMI.

Results

The associations between physical activity and hormones were modest and similar for objectively measured (accelerometer) and self-reported physical activity. Compared to men with the lowest objectively measured physical activity, men with high physical activity levels had 14% and 8% higher concentrations of SHBG and total testosterone, respectively, and these differences were attenuated to 6% and 3% following adjustment for BMI.

Conclusion

Our results suggest that the associations of physical activity with the hormones investigated are, at most, modest; and following adjustment for BMI, the small associations with SHBG and total testosterone were largely attenuated. Therefore, it is unlikely that changes in these circulating hormones explain the associations of physical activity with risk of cancer either independently or via BMI.", - "laySummary": "", - "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s10552-021-01466-6.pdf; doi:https://doi.org/10.1007/s10552-021-01466-6; html:https://europepmc.org/articles/PMC8492588; pdf:https://europepmc.org/articles/PMC8492588?pdf=render" - }, { "id": "31073125", "doi": "https://doi.org/10.1038/s41533-019-0132-z", @@ -36906,6 +36889,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41533-019-0132-z.pdf; doi:https://doi.org/10.1038/s41533-019-0132-z; html:https://europepmc.org/articles/PMC6509212; pdf:https://europepmc.org/articles/PMC6509212?pdf=render" }, + { + "id": "34216337", + "doi": "https://doi.org/10.1007/s10552-021-01466-6", + "title": "Physical activity in relation to circulating hormone concentrations in 117,100 men in UK Biobank.", + "authorString": "Watts EL, Perez-Cornago A, Doherty A, Allen NE, Fensom GK, Tin Tin S, Key TJ, Travis RC.", + "authorAffiliations": "", + "journalTitle": "Cancer causes & control : CCC", + "pubYear": "2021", + "date": "2021-07-03", + "isOpenAccess": "Y", + "keywords": "Testosterone; IGF-I; Physical Activity; Accelerometer; Shbg; Uk Biobank", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Purpose

Physical activity may reduce the risk of some types of cancer in men. Biological mechanisms may involve changes in hormone concentrations; however, this relationship is not well established. Therefore, we aimed to investigate the associations of physical activity with circulating insulin-like growth factor-I (IGF-I), sex hormone-binding globulin (SHBG, which modifies sex hormone activity), and total and free testosterone concentrations, and the extent these associations might be mediated by body mass index (BMI).

Methods

Circulating concentrations of these hormones and anthropometric measurements and self-reported physical activity data were available for 117,100 healthy male UK Biobank participants at recruitment. Objectively measured accelerometer physical activity levels were also collected on average 5.7\u00a0years after recruitment in 28,000 men. Geometric means of hormone concentrations were estimated using multivariable-adjusted analysis of variance, with and without adjustment for BMI.

Results

The associations between physical activity and hormones were modest and similar for objectively measured (accelerometer) and self-reported physical activity. Compared to men with the lowest objectively measured physical activity, men with high physical activity levels had 14% and 8% higher concentrations of SHBG and total testosterone, respectively, and these differences were attenuated to 6% and 3% following adjustment for BMI.

Conclusion

Our results suggest that the associations of physical activity with the hormones investigated are, at most, modest; and following adjustment for BMI, the small associations with SHBG and total testosterone were largely attenuated. Therefore, it is unlikely that changes in these circulating hormones explain the associations of physical activity with risk of cancer either independently or via BMI.", + "laySummary": "", + "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s10552-021-01466-6.pdf; doi:https://doi.org/10.1007/s10552-021-01466-6; html:https://europepmc.org/articles/PMC8492588; pdf:https://europepmc.org/articles/PMC8492588?pdf=render" + }, { "id": "32514173", "doi": "https://doi.org/10.1038/s41591-020-0941-1", @@ -37127,23 +37127,6 @@ "laySummary": "Grist et al. team trained computers to analyse brain images from children for identification of tumours. They\u2019ve shown that applying analytical methods to enable machine distinguishes between the entire brain area and the tumour area in the images more than 80% improves how machine analyses the image to identify exact tumour area. ", "urls": "doi:https://doi.org/10.1016/j.nicl.2020.102172; doi:https://doi.org/10.1016/j.nicl.2020.102172; html:https://europepmc.org/articles/PMC7005468; pdf:https://europepmc.org/articles/PMC7005468?pdf=render" }, - { - "id": "35322056", - "doi": "https://doi.org/10.1038/s41598-022-08351-5", - "title": "Automated quality assessment of large digitised histology cohorts by artificial intelligence.", - "authorString": "Haghighat M, Browning L, Sirinukunwattana K, Malacrino S, Khalid Alham N, Colling R, Cui Y, Rakha E, Hamdy FC, Verrill C, Rittscher J.", - "authorAffiliations": "", - "journalTitle": "Scientific reports", - "pubYear": "2022", - "date": "2022-03-23", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Research using whole slide images (WSIs) of histopathology slides has increased exponentially over recent years. Glass slides from retrospective cohorts, some with patient follow-up data are digitised for the development and validation of artificial intelligence (AI) tools. Such resources, therefore, become very important, with the need to ensure that their quality is of the standard necessary for downstream AI development. However, manual quality control of large cohorts of WSIs by visual assessment is unfeasible, and whilst quality control AI algorithms exist, these focus on bespoke aspects of image quality, e.g. focus, or use traditional machine-learning methods, which are unable to classify the range of potential image artefacts that should be considered. In this study, we have trained and validated a multi-task deep neural network to automate the process of quality control of a large retrospective cohort of prostate cases from which glass slides have been scanned several years after production, to determine both the usability of the images at the diagnostic level (considered in this study to be the minimal standard for research) and the common image artefacts present. Using a two-layer approach, quality overlays of WSIs were generated from a quality assessment (QA) undertaken at patch-level at [Formula: see text] magnification. From these quality overlays the slide-level quality scores were predicted and then compared to those generated by three specialist urological pathologists, with a Pearson correlation of 0.89 for overall 'usability' (at a diagnostic level), and 0.87 and 0.82 for focus and H&E staining quality scores respectively. To demonstrate its wider potential utility, we subsequently applied our QA pipeline to the TCGA prostate cancer cohort and to a colorectal cancer cohort, for comparison. Our model, designated as PathProfiler, indicates comparable predicted usability of images from the cohorts assessed (86-90% of WSIs predicted to be usable), and perhaps more significantly is able to predict WSIs that could benefit from an intervention such as re-scanning or re-staining for quality improvement. We have shown in this study that AI can be used to automate the process of quality control of large retrospective WSI cohorts to maximise their utility for research.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41598-022-08351-5.pdf; doi:https://doi.org/10.1038/s41598-022-08351-5; html:https://europepmc.org/articles/PMC8943120; pdf:https://europepmc.org/articles/PMC8943120?pdf=render" - }, { "id": "33012285", "doi": "https://doi.org/10.1186/s12916-020-01779-4", @@ -37161,6 +37144,23 @@ "laySummary": "", "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01779-4; doi:https://doi.org/10.1186/s12916-020-01779-4; html:https://europepmc.org/articles/PMC7533154; pdf:https://europepmc.org/articles/PMC7533154?pdf=render" }, + { + "id": "35322056", + "doi": "https://doi.org/10.1038/s41598-022-08351-5", + "title": "Automated quality assessment of large digitised histology cohorts by artificial intelligence.", + "authorString": "Haghighat M, Browning L, Sirinukunwattana K, Malacrino S, Khalid Alham N, Colling R, Cui Y, Rakha E, Hamdy FC, Verrill C, Rittscher J.", + "authorAffiliations": "", + "journalTitle": "Scientific reports", + "pubYear": "2022", + "date": "2022-03-23", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Research using whole slide images (WSIs) of histopathology slides has increased exponentially over recent years. Glass slides from retrospective cohorts, some with patient follow-up data are digitised for the development and validation of artificial intelligence (AI) tools. Such resources, therefore, become very important, with the need to ensure that their quality is of the standard necessary for downstream AI development. However, manual quality control of large cohorts of WSIs by visual assessment is unfeasible, and whilst quality control AI algorithms exist, these focus on bespoke aspects of image quality, e.g. focus, or use traditional machine-learning methods, which are unable to classify the range of potential image artefacts that should be considered. In this study, we have trained and validated a multi-task deep neural network to automate the process of quality control of a large retrospective cohort of prostate cases from which glass slides have been scanned several years after production, to determine both the usability of the images at the diagnostic level (considered in this study to be the minimal standard for research) and the common image artefacts present. Using a two-layer approach, quality overlays of WSIs were generated from a quality assessment (QA) undertaken at patch-level at [Formula: see text] magnification. From these quality overlays the slide-level quality scores were predicted and then compared to those generated by three specialist urological pathologists, with a Pearson correlation of 0.89 for overall 'usability' (at a diagnostic level), and 0.87 and 0.82 for focus and H&E staining quality scores respectively. To demonstrate its wider potential utility, we subsequently applied our QA pipeline to the TCGA prostate cancer cohort and to a colorectal cancer cohort, for comparison. Our model, designated as PathProfiler, indicates comparable predicted usability of images from the cohorts assessed (86-90% of WSIs predicted to be usable), and perhaps more significantly is able to predict WSIs that could benefit from an intervention such as re-scanning or re-staining for quality improvement. We have shown in this study that AI can be used to automate the process of quality control of large retrospective WSI cohorts to maximise their utility for research.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41598-022-08351-5.pdf; doi:https://doi.org/10.1038/s41598-022-08351-5; html:https://europepmc.org/articles/PMC8943120; pdf:https://europepmc.org/articles/PMC8943120?pdf=render" + }, { "id": "32360702", "doi": "https://doi.org/10.1016/j.ijcard.2020.04.068", @@ -37349,38 +37349,38 @@ "urls": "pdf:https://www.nature.com/articles/s41467-020-14717-y.pdf; doi:https://doi.org/10.1038/s41467-020-14717-y; html:https://europepmc.org/articles/PMC7033171; pdf:https://europepmc.org/articles/PMC7033171?pdf=render" }, { - "id": "33617936", - "doi": "https://doi.org/10.1016/j.jhin.2021.02.012", - "title": "Global and national estimates of the number of healthcare workers at high risk of SARS-CoV-2 infection.", - "authorString": "McCarthy CV, Sandmann FG, CMMID COVID-19 Working Group, Jit M.", + "id": "33714592", + "doi": "https://doi.org/10.1016/j.mayocp.2021.02.007", + "title": "Place and Underlying Cause of Death During the COVID-19 Pandemic: Retrospective Cohort Study of 3.5 Million Deaths in England and Wales, 2014 to 2020.", + "authorString": "Wu J, Mafham M, Mamas MA, Rashid M, Kontopantelis E, Deanfield JE, de Belder MA, Gale CP.", "authorAffiliations": "", - "journalTitle": "The Journal of hospital infection", + "journalTitle": "Mayo Clinic proceedings", "pubYear": "2021", - "date": "2021-02-20", + "date": "2021-02-16", "isOpenAccess": "Y", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "", + "abstract": "

Objective

To describe the place and cause of death during the coronavirus disease 2019 (COVID-19) pandemic to assess its impact on excess mortality.

Methods

This national death registry included all adult (aged \u226518 years) deaths in England and Wales between January 1, 2014, and June 30, 2020. Daily deaths during the COVID-19 pandemic were compared against the expected daily deaths, estimated with use of the Farrington surveillance algorithm for daily historical data between 2014 and 2020 by place and cause of death.

Results

Between March 2 and June 30, 2020, there was an excess mortality of 57,860 (a proportional increase of 35%) compared with the expected deaths, of which 50,603 (87%) were COVID-19 related. At home, only 14% (2267) of the 16,190 excess deaths were related to COVID-19, with 5963 deaths due to cancer and 2485 deaths due to cardiac disease, few of which involved COVID-19. In care homes or hospices, 61% (15,623) of the 25,611 excess deaths were related to COVID-19, 5539 of which were due to respiratory disease, and most of these (4315 deaths) involved COVID-19. In the hospital, there were 16,174 fewer deaths than expected that did not involve COVID-19, with 4088 fewer deaths due to cancer and 1398 fewer deaths due to cardiac disease than expected.

Conclusion

The COVID-19 pandemic has resulted in a large excess of deaths in care homes that were poorly characterized and likely to be the result of undiagnosed COVID-19. There was a smaller but important and ongoing excess in deaths at home, particularly from cancer and cardiac disease, suggesting public avoidance of hospital care for non-COVID-19 conditions.", "laySummary": "", - "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4660358/1/Global%20and%20national%20estimates%20of%20the%20number%20of%20healthcare%20workers%20at%20high%20risk%20of%20SARS-CoV-2%20infection.pdf; doi:https://doi.org/10.1016/j.jhin.2021.02.012; html:https://europepmc.org/articles/PMC7896121; pdf:https://europepmc.org/articles/PMC7896121?pdf=render" + "urls": "pdf:http://www.mayoclinicproceedings.org/article/S0025619621001397/pdf; doi:https://doi.org/10.1016/j.mayocp.2021.02.007; html:https://europepmc.org/articles/PMC7885692; pdf:https://europepmc.org/articles/PMC7885692?pdf=render" }, { - "id": "33714592", - "doi": "https://doi.org/10.1016/j.mayocp.2021.02.007", - "title": "Place and Underlying Cause of Death During the COVID-19 Pandemic: Retrospective Cohort Study of 3.5 Million Deaths in England and Wales, 2014 to 2020.", - "authorString": "Wu J, Mafham M, Mamas MA, Rashid M, Kontopantelis E, Deanfield JE, de Belder MA, Gale CP.", + "id": "33617936", + "doi": "https://doi.org/10.1016/j.jhin.2021.02.012", + "title": "Global and national estimates of the number of healthcare workers at high risk of SARS-CoV-2 infection.", + "authorString": "McCarthy CV, Sandmann FG, CMMID COVID-19 Working Group, Jit M.", "authorAffiliations": "", - "journalTitle": "Mayo Clinic proceedings", + "journalTitle": "The Journal of hospital infection", "pubYear": "2021", - "date": "2021-02-16", + "date": "2021-02-20", "isOpenAccess": "Y", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Objective

To describe the place and cause of death during the coronavirus disease 2019 (COVID-19) pandemic to assess its impact on excess mortality.

Methods

This national death registry included all adult (aged \u226518 years) deaths in England and Wales between January 1, 2014, and June 30, 2020. Daily deaths during the COVID-19 pandemic were compared against the expected daily deaths, estimated with use of the Farrington surveillance algorithm for daily historical data between 2014 and 2020 by place and cause of death.

Results

Between March 2 and June 30, 2020, there was an excess mortality of 57,860 (a proportional increase of 35%) compared with the expected deaths, of which 50,603 (87%) were COVID-19 related. At home, only 14% (2267) of the 16,190 excess deaths were related to COVID-19, with 5963 deaths due to cancer and 2485 deaths due to cardiac disease, few of which involved COVID-19. In care homes or hospices, 61% (15,623) of the 25,611 excess deaths were related to COVID-19, 5539 of which were due to respiratory disease, and most of these (4315 deaths) involved COVID-19. In the hospital, there were 16,174 fewer deaths than expected that did not involve COVID-19, with 4088 fewer deaths due to cancer and 1398 fewer deaths due to cardiac disease than expected.

Conclusion

The COVID-19 pandemic has resulted in a large excess of deaths in care homes that were poorly characterized and likely to be the result of undiagnosed COVID-19. There was a smaller but important and ongoing excess in deaths at home, particularly from cancer and cardiac disease, suggesting public avoidance of hospital care for non-COVID-19 conditions.", + "abstract": "", "laySummary": "", - "urls": "pdf:http://www.mayoclinicproceedings.org/article/S0025619621001397/pdf; doi:https://doi.org/10.1016/j.mayocp.2021.02.007; html:https://europepmc.org/articles/PMC7885692; pdf:https://europepmc.org/articles/PMC7885692?pdf=render" + "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4660358/1/Global%20and%20national%20estimates%20of%20the%20number%20of%20healthcare%20workers%20at%20high%20risk%20of%20SARS-CoV-2%20infection.pdf; doi:https://doi.org/10.1016/j.jhin.2021.02.012; html:https://europepmc.org/articles/PMC7896121; pdf:https://europepmc.org/articles/PMC7896121?pdf=render" }, { "id": "38448586", @@ -37569,23 +37569,6 @@ "laySummary": "", "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-01906-9; doi:https://doi.org/10.1186/s12916-021-01906-9; html:https://europepmc.org/articles/PMC7854026; pdf:https://europepmc.org/articles/PMC7854026?pdf=render" }, - { - "id": "35861824", - "doi": "https://doi.org/10.1161/jaha.121.025935", - "title": "Candidate Plasma Biomarkers to Detect Anthracycline-Related Cardiomyopathy in Childhood Cancer Survivors: A Case Control Study in the Dutch Childhood Cancer Survivor Study.", - "authorString": "Leerink JM, Feijen EAM, Moerland PD, de Baat EC, Merkx R, van der Pal HJH, Tissing WJE, Louwerens M, van den Heuvel-Eibrink MM, Versluys AB, Asselbergs FW, Sammani A, Teske AJ, van Dalen EC, van der Heiden-van der Loo M, van Dulmen-den Broeder E, de Vries ACH, Kapusta L, Loonen J, Pinto YM, Kremer LCM, Mavinkurve-Groothuis AMC, Kok WEM.", - "authorAffiliations": "", - "journalTitle": "Journal of the American Heart Association", - "pubYear": "2022", - "date": "2022-07-13", - "isOpenAccess": "Y", - "keywords": "Biomarkers; Childhood Cancer Survivors; Cardio\u2010oncology; Chemokine Ligands; Cancer Therapy\u2013related Cardiac Dysfunction; Anthracycline\u2010related Cardiomyopathy", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Background Plasma biomarkers may aid in the detection of anthracycline-related cardiomyopathy (ACMP). However, the currently available biomarkers have limited diagnostic value in long-term childhood cancer survivors. This study sought to identify diagnostic plasma biomarkers for ACMP in childhood cancer survivors. Methods and Results We measured 275 plasma proteins in 28 ACMP cases with left ventricular ejection fraction <45%, 29 anthracycline-treated controls with left ventricular ejection fraction \u226553% matched on sex, time after cancer, and anthracycline dose, and 29 patients with genetically determined dilated cardiomyopathy with left ventricular ejection fraction <45%. Multivariable linear regression was used to identify differentially expressed proteins. Elastic net model, including clinical characteristics, was used to assess discrimination of proteins diagnostic for ACMP. NT-proBNP (N-terminal pro-B-type natriuretic peptide) and the inflammatory markers CCL19 (C-C motif chemokine ligands 19) and CCL20, PSPD (pulmonary surfactant protein-D), and PTN (pleiotrophin) were significantly upregulated in ACMP compared with controls. An elastic net model selected 45 proteins, including NT-proBNP, CCL19, CCL20 and PSPD, but not PTN, that discriminated ACMP cases from controls with an area under the receiver operating characteristic curve (AUC) of 0.78. This model was not superior to a model including NT-proBNP and clinical characteristics (AUC=0.75; P=0.766). However, when excluding 8 ACMP cases with heart failure, the full model was superior to that including only NT-proBNP and clinical characteristics (AUC=0.75 versus AUC=0.50; P=0.022). The same 45 proteins also showed good discrimination between dilated cardiomyopathy and controls (AUC=0.89), underscoring their association with cardiomyopathy. Conclusions We identified 3 specific inflammatory proteins as candidate plasma biomarkers for ACMP in long-term childhood cancer survivors and demonstrated protein overlap with dilated cardiomyopathy.", - "laySummary": "", - "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.025935; doi:https://doi.org/10.1161/JAHA.121.025935; html:https://europepmc.org/articles/PMC9707839; pdf:https://europepmc.org/articles/PMC9707839?pdf=render" - }, { "id": "30609404", "doi": "https://doi.org/10.1016/j.ajhg.2018.11.014", @@ -37603,6 +37586,23 @@ "laySummary": "", "urls": "pdf:http://www.cell.com/article/S0002929718304221/pdf; doi:https://doi.org/10.1016/j.ajhg.2018.11.014; html:https://europepmc.org/articles/PMC6323624; pdf:https://europepmc.org/articles/PMC6323624?pdf=render; doi:https://doi.org/10.1016/j.ajhg.2018.11.014" }, + { + "id": "35861824", + "doi": "https://doi.org/10.1161/jaha.121.025935", + "title": "Candidate Plasma Biomarkers to Detect Anthracycline-Related Cardiomyopathy in Childhood Cancer Survivors: A Case Control Study in the Dutch Childhood Cancer Survivor Study.", + "authorString": "Leerink JM, Feijen EAM, Moerland PD, de Baat EC, Merkx R, van der Pal HJH, Tissing WJE, Louwerens M, van den Heuvel-Eibrink MM, Versluys AB, Asselbergs FW, Sammani A, Teske AJ, van Dalen EC, van der Heiden-van der Loo M, van Dulmen-den Broeder E, de Vries ACH, Kapusta L, Loonen J, Pinto YM, Kremer LCM, Mavinkurve-Groothuis AMC, Kok WEM.", + "authorAffiliations": "", + "journalTitle": "Journal of the American Heart Association", + "pubYear": "2022", + "date": "2022-07-13", + "isOpenAccess": "Y", + "keywords": "Biomarkers; Childhood Cancer Survivors; Cardio\u2010oncology; Chemokine Ligands; Cancer Therapy\u2013related Cardiac Dysfunction; Anthracycline\u2010related Cardiomyopathy", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Background Plasma biomarkers may aid in the detection of anthracycline-related cardiomyopathy (ACMP). However, the currently available biomarkers have limited diagnostic value in long-term childhood cancer survivors. This study sought to identify diagnostic plasma biomarkers for ACMP in childhood cancer survivors. Methods and Results We measured 275 plasma proteins in 28 ACMP cases with left ventricular ejection fraction <45%, 29 anthracycline-treated controls with left ventricular ejection fraction \u226553% matched on sex, time after cancer, and anthracycline dose, and 29 patients with genetically determined dilated cardiomyopathy with left ventricular ejection fraction <45%. Multivariable linear regression was used to identify differentially expressed proteins. Elastic net model, including clinical characteristics, was used to assess discrimination of proteins diagnostic for ACMP. NT-proBNP (N-terminal pro-B-type natriuretic peptide) and the inflammatory markers CCL19 (C-C motif chemokine ligands 19) and CCL20, PSPD (pulmonary surfactant protein-D), and PTN (pleiotrophin) were significantly upregulated in ACMP compared with controls. An elastic net model selected 45 proteins, including NT-proBNP, CCL19, CCL20 and PSPD, but not PTN, that discriminated ACMP cases from controls with an area under the receiver operating characteristic curve (AUC) of 0.78. This model was not superior to a model including NT-proBNP and clinical characteristics (AUC=0.75; P=0.766). However, when excluding 8 ACMP cases with heart failure, the full model was superior to that including only NT-proBNP and clinical characteristics (AUC=0.75 versus AUC=0.50; P=0.022). The same 45 proteins also showed good discrimination between dilated cardiomyopathy and controls (AUC=0.89), underscoring their association with cardiomyopathy. Conclusions We identified 3 specific inflammatory proteins as candidate plasma biomarkers for ACMP in long-term childhood cancer survivors and demonstrated protein overlap with dilated cardiomyopathy.", + "laySummary": "", + "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.025935; doi:https://doi.org/10.1161/JAHA.121.025935; html:https://europepmc.org/articles/PMC9707839; pdf:https://europepmc.org/articles/PMC9707839?pdf=render" + }, { "id": "34645462", "doi": "https://doi.org/10.1186/s12974-021-02287-9", @@ -37875,23 +37875,6 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.15252/embj.2021108610; doi:https://doi.org/10.15252/embj.2021108610; html:https://europepmc.org/articles/PMC8561637; pdf:https://europepmc.org/articles/PMC8561637?pdf=render" }, - { - "id": "33722066", - "doi": "https://doi.org/10.1161/circinterventions.120.009434", - "title": "Clopidogrel Versus Ticagrelor or Prasugrel After Primary Percutaneous Coronary Intervention According to CYP2C19 Genotype: A POPular Genetics Subanalysis.", - "authorString": "Claassens DMF, Bergmeijer TO, Vos GJA, Hermanides RS, van 't Hof AWJ, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, Asselbergs FW, Mosterd A, Herrman JR, Dewilde WJM, Janssen PWA, Kelder JC, Mahmoodi BK, Deneer VHM, Ten Berg JM.", - "authorAffiliations": "", - "journalTitle": "Circulation. Cardiovascular interventions", - "pubYear": "2021", - "date": "2021-03-16", - "isOpenAccess": "N", - "keywords": "Myocardial infarction; Percutaneous coronary intervention; acute coronary syndrome; Clopidogrel; Genetic Testing; Pharmacogenetics; Ticagrelor", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "[Figure: see text].", - "laySummary": "", - "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCINTERVENTIONS.120.009434; doi:https://doi.org/10.1161/CIRCINTERVENTIONS.120.009434" - }, { "id": "33332257", "doi": "https://doi.org/10.1099/mgen.0.000434", @@ -37909,6 +37892,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1099/mgen.0.000434; doi:https://doi.org/10.1099/mgen.0.000434; html:https://europepmc.org/articles/PMC8116680; pdf:https://europepmc.org/articles/PMC8116680?pdf=render" }, + { + "id": "33722066", + "doi": "https://doi.org/10.1161/circinterventions.120.009434", + "title": "Clopidogrel Versus Ticagrelor or Prasugrel After Primary Percutaneous Coronary Intervention According to CYP2C19 Genotype: A POPular Genetics Subanalysis.", + "authorString": "Claassens DMF, Bergmeijer TO, Vos GJA, Hermanides RS, van 't Hof AWJ, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, Asselbergs FW, Mosterd A, Herrman JR, Dewilde WJM, Janssen PWA, Kelder JC, Mahmoodi BK, Deneer VHM, Ten Berg JM.", + "authorAffiliations": "", + "journalTitle": "Circulation. Cardiovascular interventions", + "pubYear": "2021", + "date": "2021-03-16", + "isOpenAccess": "N", + "keywords": "Myocardial infarction; Percutaneous coronary intervention; acute coronary syndrome; Clopidogrel; Genetic Testing; Pharmacogenetics; Ticagrelor", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "[Figure: see text].", + "laySummary": "", + "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCINTERVENTIONS.120.009434; doi:https://doi.org/10.1161/CIRCINTERVENTIONS.120.009434" + }, { "id": "32895551", "doi": "https://doi.org/10.1038/s41588-020-0682-6", @@ -37926,23 +37926,6 @@ "laySummary": "", "urls": "pdf:https://ueaeprints.uea.ac.uk/id/eprint/76368/1/Zheng_et_al_final_manuscript.pdf; doi:https://doi.org/10.1038/s41588-020-0682-6; html:https://europepmc.org/articles/PMC7610464; pdf:https://europepmc.org/articles/PMC7610464?pdf=render" }, - { - "id": "37188768", - "doi": "https://doi.org/10.1038/s42003-023-04836-9", - "title": "Fine-mapping of retinal vascular complexity loci identifies Notch regulation as a shared mechanism with myocardial infarction outcomes.", - "authorString": "Villaplana-Velasco A, Pigeyre M, Engelmann J, Rawlik K, Canela-Xandri O, Tochel C, Lona-Durazo F, Mookiah MRK, Doney A, Parra EJ, Trucco E, MacGillivray T, Rannikmae K, Tenesa A, Pairo-Castineira E, Bernabeu MO.", - "authorAffiliations": "", - "journalTitle": "Communications biology", - "pubYear": "2023", - "date": "2023-05-15", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "There is increasing evidence that the complexity of the retinal vasculature measured as fractal dimension, Df, might offer earlier insights into the progression of coronary artery disease (CAD) before traditional biomarkers can be detected. This association could be partly explained by a common genetic basis; however, the genetic component of Df is poorly understood. We present a genome-wide association study (GWAS) of 38,000 individuals with white British ancestry from the UK Biobank aimed to comprehensively study the genetic component of Df and analyse its relationship with CAD. We replicated 5 Df loci and found 4 additional loci with suggestive significance (P\u2009<\u20091e-05) to contribute to Df variation, which previously were reported in retinal tortuosity and complexity, hypertension, and CAD studies. Significant negative genetic correlation estimates support the inverse relationship between Df and CAD, and between Df and myocardial infarction (MI), one of CAD's fatal outcomes. Fine-mapping of Df loci revealed Notch signalling regulatory variants supporting a shared mechanism with MI outcomes. We developed a predictive model for MI incident cases, recorded over a 10-year period following clinical and ophthalmic evaluation, combining clinical information, Df, and a CAD polygenic risk score. Internal cross-validation demonstrated a considerable improvement in the area under the curve (AUC) of our predictive model (AUC\u2009=\u20090.770\u2009\u00b1\u20090.001) when comparing with an established risk model, SCORE, (AUC\u2009=\u20090.741\u2009\u00b1\u20090.002) and extensions thereof leveraging the PRS (AUC\u2009=\u20090.728\u2009\u00b1\u20090.001). This evidences that Df provides risk information beyond demographic, lifestyle, and genetic risk factors. Our findings shed new light on the genetic basis of Df, unveiling a common control with MI, and highlighting the benefits of its application in individualised MI risk prediction.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s42003-023-04836-9; html:https://europepmc.org/articles/PMC10185685; pdf:https://europepmc.org/articles/PMC10185685?pdf=render" - }, { "id": "35908569", "doi": "https://doi.org/10.1016/s0140-6736(22)01109-6", @@ -37960,6 +37943,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S0140673622011096/pdf; doi:https://doi.org/10.1016/S0140-6736(22)01109-6; html:https://europepmc.org/articles/PMC9333998; pdf:https://europepmc.org/articles/PMC9333998?pdf=render" }, + { + "id": "37188768", + "doi": "https://doi.org/10.1038/s42003-023-04836-9", + "title": "Fine-mapping of retinal vascular complexity loci identifies Notch regulation as a shared mechanism with myocardial infarction outcomes.", + "authorString": "Villaplana-Velasco A, Pigeyre M, Engelmann J, Rawlik K, Canela-Xandri O, Tochel C, Lona-Durazo F, Mookiah MRK, Doney A, Parra EJ, Trucco E, MacGillivray T, Rannikmae K, Tenesa A, Pairo-Castineira E, Bernabeu MO.", + "authorAffiliations": "", + "journalTitle": "Communications biology", + "pubYear": "2023", + "date": "2023-05-15", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "There is increasing evidence that the complexity of the retinal vasculature measured as fractal dimension, Df, might offer earlier insights into the progression of coronary artery disease (CAD) before traditional biomarkers can be detected. This association could be partly explained by a common genetic basis; however, the genetic component of Df is poorly understood. We present a genome-wide association study (GWAS) of 38,000 individuals with white British ancestry from the UK Biobank aimed to comprehensively study the genetic component of Df and analyse its relationship with CAD. We replicated 5 Df loci and found 4 additional loci with suggestive significance (P\u2009<\u20091e-05) to contribute to Df variation, which previously were reported in retinal tortuosity and complexity, hypertension, and CAD studies. Significant negative genetic correlation estimates support the inverse relationship between Df and CAD, and between Df and myocardial infarction (MI), one of CAD's fatal outcomes. Fine-mapping of Df loci revealed Notch signalling regulatory variants supporting a shared mechanism with MI outcomes. We developed a predictive model for MI incident cases, recorded over a 10-year period following clinical and ophthalmic evaluation, combining clinical information, Df, and a CAD polygenic risk score. Internal cross-validation demonstrated a considerable improvement in the area under the curve (AUC) of our predictive model (AUC\u2009=\u20090.770\u2009\u00b1\u20090.001) when comparing with an established risk model, SCORE, (AUC\u2009=\u20090.741\u2009\u00b1\u20090.002) and extensions thereof leveraging the PRS (AUC\u2009=\u20090.728\u2009\u00b1\u20090.001). This evidences that Df provides risk information beyond demographic, lifestyle, and genetic risk factors. Our findings shed new light on the genetic basis of Df, unveiling a common control with MI, and highlighting the benefits of its application in individualised MI risk prediction.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1038/s42003-023-04836-9; html:https://europepmc.org/articles/PMC10185685; pdf:https://europepmc.org/articles/PMC10185685?pdf=render" + }, { "id": "37538507", "doi": "https://doi.org/10.1016/j.rpth.2023.100175", @@ -38080,38 +38080,38 @@ "urls": "pdf:http://www.thelancet.com/article/S014067362032465X/pdf; doi:https://doi.org/10.1016/S0140-6736(20)32465-X; html:https://europepmc.org/articles/PMC7831890; pdf:https://europepmc.org/articles/PMC7831890?pdf=render" }, { - "id": "35962208", - "doi": "https://doi.org/10.1038/s41591-022-01951-8", - "title": "Publisher Correction: Reporting guideline for the early-stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI.", - "authorString": "Vasey B, Nagendran M, Campbell B, Clifton DA, Collins GS, Denaxas S, Denniston AK, Faes L, Geerts B, Ibrahim M, Liu X, Mateen BA, Mathur P, McCradden MD, Morgan L, Ordish J, Rogers C, Saria S, Ting DSW, Watkinson P, Weber W, Wheatstone P, McCulloch P, DECIDE-AI expert group.", + "id": "31792462", + "doi": "https://doi.org/10.1038/s41591-019-0665-2", + "title": "Plasma protein patterns as comprehensive indicators of health.", + "authorString": "Williams SA, Kivimaki M, Langenberg C, Hingorani AD, Casas JP, Bouchard C, Jonasson C, Sarzynski MA, Shipley MJ, Alexander L, Ash J, Bauer T, Chadwick J, Datta G, DeLisle RK, Hagar Y, Hinterberg M, Ostroff R, Weiss S, Ganz P, Wareham NJ.", "authorAffiliations": "", "journalTitle": "Nature medicine", - "pubYear": "2022", - "date": "2022-10-01", + "pubYear": "2019", + "date": "2019-12-02", "isOpenAccess": "N", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "", + "abstract": "Proteins are effector molecules that mediate the functions of genes1,2 and modulate comorbidities3-10, behaviors and drug treatments11. They represent an enormous potential resource for personalized, systemic and data-driven diagnosis, prevention, monitoring and treatment. However, the concept of using plasma proteins for individualized health assessment across many health conditions simultaneously has not been tested. Here, we show that plasma protein expression patterns strongly encode for multiple different health states, future disease risks and lifestyle behaviors. We developed and validated protein-phenotype models for 11\u2009different health indicators: liver fat, kidney filtration, percentage body fat, visceral fat mass, lean body mass, cardiopulmonary fitness, physical activity, alcohol consumption, cigarette smoking, diabetes risk and primary cardiovascular event risk. The analyses were prospectively planned, documented and executed at scale on archived samples and clinical data, with a total of ~85\u2009million protein measurements in 16,894\u2009participants. Our proof-of-concept study demonstrates that protein expression patterns reliably encode for many different health issues, and that large-scale protein scanning12-16 coupled with machine learning is viable for the development and future simultaneous delivery of multiple measures of health. We anticipate that, with further validation and the addition of more protein-phenotype models, this approach could enable a single-source, individualized so-called liquid health check.", "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41591-022-01951-8.pdf; doi:https://doi.org/10.1038/s41591-022-01951-8" + "urls": "pdf:https://europepmc.org/articles/pmc6922049?pdf=render; doi:https://doi.org/10.1038/s41591-019-0665-2; html:https://europepmc.org/articles/PMC6922049; pdf:https://europepmc.org/articles/PMC6922049?pdf=render; doi:https://doi.org/10.1038/s41591-019-0665-2" }, { - "id": "31792462", - "doi": "https://doi.org/10.1038/s41591-019-0665-2", - "title": "Plasma protein patterns as comprehensive indicators of health.", - "authorString": "Williams SA, Kivimaki M, Langenberg C, Hingorani AD, Casas JP, Bouchard C, Jonasson C, Sarzynski MA, Shipley MJ, Alexander L, Ash J, Bauer T, Chadwick J, Datta G, DeLisle RK, Hagar Y, Hinterberg M, Ostroff R, Weiss S, Ganz P, Wareham NJ.", + "id": "35962208", + "doi": "https://doi.org/10.1038/s41591-022-01951-8", + "title": "Publisher Correction: Reporting guideline for the early-stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI.", + "authorString": "Vasey B, Nagendran M, Campbell B, Clifton DA, Collins GS, Denaxas S, Denniston AK, Faes L, Geerts B, Ibrahim M, Liu X, Mateen BA, Mathur P, McCradden MD, Morgan L, Ordish J, Rogers C, Saria S, Ting DSW, Watkinson P, Weber W, Wheatstone P, McCulloch P, DECIDE-AI expert group.", "authorAffiliations": "", "journalTitle": "Nature medicine", - "pubYear": "2019", - "date": "2019-12-02", + "pubYear": "2022", + "date": "2022-10-01", "isOpenAccess": "N", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "Proteins are effector molecules that mediate the functions of genes1,2 and modulate comorbidities3-10, behaviors and drug treatments11. They represent an enormous potential resource for personalized, systemic and data-driven diagnosis, prevention, monitoring and treatment. However, the concept of using plasma proteins for individualized health assessment across many health conditions simultaneously has not been tested. Here, we show that plasma protein expression patterns strongly encode for multiple different health states, future disease risks and lifestyle behaviors. We developed and validated protein-phenotype models for 11\u2009different health indicators: liver fat, kidney filtration, percentage body fat, visceral fat mass, lean body mass, cardiopulmonary fitness, physical activity, alcohol consumption, cigarette smoking, diabetes risk and primary cardiovascular event risk. The analyses were prospectively planned, documented and executed at scale on archived samples and clinical data, with a total of ~85\u2009million protein measurements in 16,894\u2009participants. Our proof-of-concept study demonstrates that protein expression patterns reliably encode for many different health issues, and that large-scale protein scanning12-16 coupled with machine learning is viable for the development and future simultaneous delivery of multiple measures of health. We anticipate that, with further validation and the addition of more protein-phenotype models, this approach could enable a single-source, individualized so-called liquid health check.", + "abstract": "", "laySummary": "", - "urls": "pdf:https://europepmc.org/articles/pmc6922049?pdf=render; doi:https://doi.org/10.1038/s41591-019-0665-2; html:https://europepmc.org/articles/PMC6922049; pdf:https://europepmc.org/articles/PMC6922049?pdf=render; doi:https://doi.org/10.1038/s41591-019-0665-2" + "urls": "pdf:https://www.nature.com/articles/s41591-022-01951-8.pdf; doi:https://doi.org/10.1038/s41591-022-01951-8" }, { "id": "34458849", @@ -38317,23 +38317,6 @@ "laySummary": "", "urls": "pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/95846/7/1-s2.0-S1201971222001291-main.pdf; doi:https://doi.org/10.1016/j.ijid.2022.02.051; html:https://europepmc.org/articles/PMC8882068; pdf:https://europepmc.org/articles/PMC8882068?pdf=render" }, - { - "id": "34796246", - "doi": "https://doi.org/10.1093/ofid/ofab496", - "title": "Acceptability, Usability, and Performance of Lateral Flow Immunoassay Tests for Severe Acute Respiratory Syndrome Coronavirus 2 Antibodies: REACT-2 Study of Self-Testing in Nonhealthcare Key Workers.", - "authorString": "Davies B, Araghi M, Moshe M, Gao H, Bennet K, Jenkins J, Atchison C, Darzi A, Ashby D, Riley S, Barclay W, Elliott P, Ward H, Cooke G.", - "authorAffiliations": "", - "journalTitle": "Open forum infectious diseases", - "pubYear": "2021", - "date": "2021-10-04", - "isOpenAccess": "Y", - "keywords": "Sensitivity and specificity; Antibody testing; Sars-cov-2; Covid-19 Diagnostic Testing", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Seroprevalence studies are essential to understand the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Various technologies, including laboratory assays and point-of-care self-tests, are available for antibody testing. The interpretation of seroprevalence studies requires comparative data on the performance of antibody tests.

Methods

In June 2020, current and former members of the United Kingdom police forces and fire service performed a self-test lateral flow immunoassay (LFIA), had a nurse-performed LFIA, and provided a venous blood sample for enzyme-linked immunosorbent assay (ELISA). We present the prevalence of antibodies to SARS-CoV-2 and the acceptability and usability of self-test LFIAs, and we determine the sensitivity and specificity of LFIAs compared with laboratory ELISA.

Results

In this cohort of 5189 current and former members of the police service and 263 members of the fire service, 7.4% (396 of 5348; 95% confidence interval [CI], 6.7-8.1) were antibody positive. Seroprevalence was 8.9% (95% CI, 6.9-11.4) in those under 40 years, 11.5% (95% CI, 8.8-15.0) in those of nonwhite ethnicity, and 7.8% (95% CI, 7.1-8.7) in those currently working. Self-test LFIA had an acceptability of 97.7% and a usability of 90.0%. There was substantial agreement between within-participant LFIA results (kappa 0.80; 95% CI, 0.77-0.83). The LFIAs had a similar performance: compared with ELISA, sensitivity was 82.1% (95% CI, 77.7-86.0) self-test and 76.4% (95% CI, 71.9-80.5) nurse-performed with specificity of 97.8% (95% CI, 97.3-98.2) and 98.5% (95% CI, 98.1-98.8), respectively.

Conclusions

A greater proportion of this nonhealthcare key worker cohort showed evidence of previous infection with SARS-CoV-2 than the general population at 6.0% (95% CI, 5.8-6.1) after the first wave in England. The high acceptability and usability reported by participants and similar performance of self-test and nurse-performed LFIAs indicate that the self-test LFIA is fit for purpose for home testing in occupational and community prevalence studies.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/ofid/article-pdf/8/11/ofab496/41174715/ofab496.pdf; doi:https://doi.org/10.1093/ofid/ofab496; html:https://europepmc.org/articles/PMC8522420; pdf:https://europepmc.org/articles/PMC8522420?pdf=render" - }, { "id": "31478583", "doi": "https://doi.org/10.1002/ejhf.1615", @@ -38351,6 +38334,23 @@ "laySummary": "This study looked at 6562 people with severe heart failure and whether there was an association between taking beta-blockers (a drug to control heart rate) and heart disease. They used a national Swedish registry of patients with heart failure and compared those who were taking beta blockers (866 patients) to those not taking beta blockers (866 patients). The study found that patients who were taking beta blockers tended also to have lower risk of heart complications and were more likely to survive.", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejhf.1615; doi:https://doi.org/10.1002/ejhf.1615" }, + { + "id": "34796246", + "doi": "https://doi.org/10.1093/ofid/ofab496", + "title": "Acceptability, Usability, and Performance of Lateral Flow Immunoassay Tests for Severe Acute Respiratory Syndrome Coronavirus 2 Antibodies: REACT-2 Study of Self-Testing in Nonhealthcare Key Workers.", + "authorString": "Davies B, Araghi M, Moshe M, Gao H, Bennet K, Jenkins J, Atchison C, Darzi A, Ashby D, Riley S, Barclay W, Elliott P, Ward H, Cooke G.", + "authorAffiliations": "", + "journalTitle": "Open forum infectious diseases", + "pubYear": "2021", + "date": "2021-10-04", + "isOpenAccess": "Y", + "keywords": "Sensitivity and specificity; Antibody testing; Sars-cov-2; Covid-19 Diagnostic Testing", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Seroprevalence studies are essential to understand the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Various technologies, including laboratory assays and point-of-care self-tests, are available for antibody testing. The interpretation of seroprevalence studies requires comparative data on the performance of antibody tests.

Methods

In June 2020, current and former members of the United Kingdom police forces and fire service performed a self-test lateral flow immunoassay (LFIA), had a nurse-performed LFIA, and provided a venous blood sample for enzyme-linked immunosorbent assay (ELISA). We present the prevalence of antibodies to SARS-CoV-2 and the acceptability and usability of self-test LFIAs, and we determine the sensitivity and specificity of LFIAs compared with laboratory ELISA.

Results

In this cohort of 5189 current and former members of the police service and 263 members of the fire service, 7.4% (396 of 5348; 95% confidence interval [CI], 6.7-8.1) were antibody positive. Seroprevalence was 8.9% (95% CI, 6.9-11.4) in those under 40 years, 11.5% (95% CI, 8.8-15.0) in those of nonwhite ethnicity, and 7.8% (95% CI, 7.1-8.7) in those currently working. Self-test LFIA had an acceptability of 97.7% and a usability of 90.0%. There was substantial agreement between within-participant LFIA results (kappa 0.80; 95% CI, 0.77-0.83). The LFIAs had a similar performance: compared with ELISA, sensitivity was 82.1% (95% CI, 77.7-86.0) self-test and 76.4% (95% CI, 71.9-80.5) nurse-performed with specificity of 97.8% (95% CI, 97.3-98.2) and 98.5% (95% CI, 98.1-98.8), respectively.

Conclusions

A greater proportion of this nonhealthcare key worker cohort showed evidence of previous infection with SARS-CoV-2 than the general population at 6.0% (95% CI, 5.8-6.1) after the first wave in England. The high acceptability and usability reported by participants and similar performance of self-test and nurse-performed LFIAs indicate that the self-test LFIA is fit for purpose for home testing in occupational and community prevalence studies.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/ofid/article-pdf/8/11/ofab496/41174715/ofab496.pdf; doi:https://doi.org/10.1093/ofid/ofab496; html:https://europepmc.org/articles/PMC8522420; pdf:https://europepmc.org/articles/PMC8522420?pdf=render" + }, { "id": "33087179", "doi": "https://doi.org/10.1186/s12916-020-01790-9", @@ -38402,23 +38402,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.19191/EP20.5-6.S1.P179.088" }, - { - "id": "37286573", - "doi": "https://doi.org/10.1038/s41467-023-38383-y", - "title": "Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism.", - "authorString": "Iglesias MJ, Sanchez-Rivera L, Ibrahim-Kosta M, Naudin C, Munsch G, Goumidi L, Farm M, Smith PM, Thibord F, Kral-Pointner JB, Hong MG, Suchon P, Germain M, Schrottmaier W, Dusart P, Boland A, Kotol D, Edfors F, Koprulu M, Pietzner M, Langenberg C, Damrauer SM, Johnson AD, Klarin DM, Smith NL, Smadja DM, Holmstr\u00f6m M, Magnusson M, Silveira A, Uhl\u00e9n M, Renn\u00e9 T, Martinez-Perez A, Emmerich J, Deleuze JF, Antovic J, Soria Fernandez JM, Assinger A, Schwenk JM, Souto Andres JC, Morange PE, Butler LM, Tr\u00e9gou\u00ebt DA, Odeberg J.", - "authorAffiliations": "", - "journalTitle": "Nature communications", - "pubYear": "2023", - "date": "2023-06-07", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement Factor H Related 5 protein (CFHR5), a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41467-023-38383-y.pdf; doi:https://doi.org/10.1038/s41467-023-38383-y; html:https://europepmc.org/articles/PMC10247781; pdf:https://europepmc.org/articles/PMC10247781?pdf=render" - }, { "id": "32097451", "doi": "https://doi.org/10.1093/ije/dyaa015", @@ -38436,6 +38419,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ije/article-pdf/49/4/1140/34275903/dyaa015.pdf; doi:https://doi.org/10.1093/ije/dyaa015; html:https://europepmc.org/articles/PMC7660148; pdf:https://europepmc.org/articles/PMC7660148?pdf=render; doi:https://doi.org/10.1093/ije/dyaa015" }, + { + "id": "37286573", + "doi": "https://doi.org/10.1038/s41467-023-38383-y", + "title": "Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism.", + "authorString": "Iglesias MJ, Sanchez-Rivera L, Ibrahim-Kosta M, Naudin C, Munsch G, Goumidi L, Farm M, Smith PM, Thibord F, Kral-Pointner JB, Hong MG, Suchon P, Germain M, Schrottmaier W, Dusart P, Boland A, Kotol D, Edfors F, Koprulu M, Pietzner M, Langenberg C, Damrauer SM, Johnson AD, Klarin DM, Smith NL, Smadja DM, Holmstr\u00f6m M, Magnusson M, Silveira A, Uhl\u00e9n M, Renn\u00e9 T, Martinez-Perez A, Emmerich J, Deleuze JF, Antovic J, Soria Fernandez JM, Assinger A, Schwenk JM, Souto Andres JC, Morange PE, Butler LM, Tr\u00e9gou\u00ebt DA, Odeberg J.", + "authorAffiliations": "", + "journalTitle": "Nature communications", + "pubYear": "2023", + "date": "2023-06-07", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement Factor H Related 5 protein (CFHR5), a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41467-023-38383-y.pdf; doi:https://doi.org/10.1038/s41467-023-38383-y; html:https://europepmc.org/articles/PMC10247781; pdf:https://europepmc.org/articles/PMC10247781?pdf=render" + }, { "id": "32706893", "doi": "https://doi.org/10.1182/bloodadvances.2020002230", @@ -38487,23 +38487,6 @@ "laySummary": "", "urls": "pdf:https://ora.ox.ac.uk/objects/uuid:3e48f9e0-d3c3-41ec-99ff-cc64d141d6cf/files/rcz30pt21m; doi:https://doi.org/10.1093/nar/gkab291; html:https://europepmc.org/articles/PMC8287915; pdf:https://europepmc.org/articles/PMC8287915?pdf=render" }, - { - "id": "35103486", - "doi": "https://doi.org/10.1128/msystems.01132-21", - "title": "Using Community Ecology Theory and Computational Microbiome Methods To Study Human Milk as a Biological System.", - "authorString": "Shenhav L, Azad MB.", - "authorAffiliations": "", - "journalTitle": "mSystems", - "pubYear": "2022", - "date": "2022-02-01", - "isOpenAccess": "Y", - "keywords": "Lactation; Human Milk; Breastfeeding; Chronobiology; Computational Methods; System Biology; Human Microbiome; Community Ecology Theory", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Human milk is a complex and dynamic biological system that has evolved to optimally nourish and protect human infants. Yet, according to a recent priority-setting review, \"our current understanding of human milk composition and its individual components and their functions fails to fully recognize the importance of the chronobiology and systems biology of human milk in the context of milk synthesis, optimal timing and duration of feeding, and period of lactation\" (P. Christian et al., Am J Clin Nutr 113:1063-1072, 2021, https://doi.org/10.1093/ajcn/nqab075). We attribute this critical knowledge gap to three major reasons as follows. (i) Studies have typically examined each subsystem of the mother-milk-infant \"triad\" in isolation and often focus on a single element or component (e.g., maternal lactation physiology or milk microbiome or milk oligosaccharides or infant microbiome or infant gut physiology). This undermines our ability to develop comprehensive representations of the interactions between these elements and study their response to external perturbations. (ii) Multiomics studies are often cross-sectional, presenting a snapshot of milk composition, largely ignoring the temporal variability during lactation. The lack of temporal resolution precludes the characterization and inference of robust interactions between the dynamic subsystems of the triad. (iii) We lack computational methods to represent and decipher the complex ecosystem of the mother-milk-infant triad and its environment. In this review, we advocate for longitudinal multiomics data collection and demonstrate how incorporating knowledge gleaned from microbial community ecology and computational methods developed for microbiome research can serve as an anchor to advance the study of human milk and its many components as a \"system within a system.\"", - "laySummary": "", - "urls": "doi:https://doi.org/10.1128/msystems.01132-21; doi:https://doi.org/10.1128/msystems.01132-21; html:https://europepmc.org/articles/PMC8805635; pdf:https://europepmc.org/articles/PMC8805635?pdf=render" - }, { "id": "30681347", "doi": "https://doi.org/10.1161/circgen.118.002328", @@ -38521,6 +38504,23 @@ "laySummary": "", "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.118.002328; doi:https://doi.org/10.1161/CIRCGEN.118.002328; html:https://europepmc.org/articles/PMC6380958; pdf:https://europepmc.org/articles/PMC6380958?pdf=render; doi:https://doi.org/10.1161/circgen.118.002328" }, + { + "id": "35103486", + "doi": "https://doi.org/10.1128/msystems.01132-21", + "title": "Using Community Ecology Theory and Computational Microbiome Methods To Study Human Milk as a Biological System.", + "authorString": "Shenhav L, Azad MB.", + "authorAffiliations": "", + "journalTitle": "mSystems", + "pubYear": "2022", + "date": "2022-02-01", + "isOpenAccess": "Y", + "keywords": "Lactation; Human Milk; Breastfeeding; Chronobiology; Computational Methods; System Biology; Human Microbiome; Community Ecology Theory", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Human milk is a complex and dynamic biological system that has evolved to optimally nourish and protect human infants. Yet, according to a recent priority-setting review, \"our current understanding of human milk composition and its individual components and their functions fails to fully recognize the importance of the chronobiology and systems biology of human milk in the context of milk synthesis, optimal timing and duration of feeding, and period of lactation\" (P. Christian et al., Am J Clin Nutr 113:1063-1072, 2021, https://doi.org/10.1093/ajcn/nqab075). We attribute this critical knowledge gap to three major reasons as follows. (i) Studies have typically examined each subsystem of the mother-milk-infant \"triad\" in isolation and often focus on a single element or component (e.g., maternal lactation physiology or milk microbiome or milk oligosaccharides or infant microbiome or infant gut physiology). This undermines our ability to develop comprehensive representations of the interactions between these elements and study their response to external perturbations. (ii) Multiomics studies are often cross-sectional, presenting a snapshot of milk composition, largely ignoring the temporal variability during lactation. The lack of temporal resolution precludes the characterization and inference of robust interactions between the dynamic subsystems of the triad. (iii) We lack computational methods to represent and decipher the complex ecosystem of the mother-milk-infant triad and its environment. In this review, we advocate for longitudinal multiomics data collection and demonstrate how incorporating knowledge gleaned from microbial community ecology and computational methods developed for microbiome research can serve as an anchor to advance the study of human milk and its many components as a \"system within a system.\"", + "laySummary": "", + "urls": "doi:https://doi.org/10.1128/msystems.01132-21; doi:https://doi.org/10.1128/msystems.01132-21; html:https://europepmc.org/articles/PMC8805635; pdf:https://europepmc.org/articles/PMC8805635?pdf=render" + }, { "id": "30772400", "doi": "https://doi.org/10.1016/j.neuroimage.2019.02.028", @@ -38606,23 +38606,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.aucc.2021.05.013" }, - { - "id": "37565978", - "doi": "https://doi.org/10.1016/j.jchf.2023.07.007", - "title": "Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies: Results From a Dutch Multicenter Cohort Study.", - "authorString": "Jansen M, de Brouwer R, Hassanzada F, Schoemaker AE, Schmidt AF, Kooijman-Reumerman MD, Bracun V, Slieker MG, Dooijes D, Vermeer AMC, Wilde AAM, Amin AS, Lekanne Deprez RH, Herkert JC, Christiaans I, de Boer RA, Jongbloed JDH, van Tintelen JP, Asselbergs FW, Baas AF.", - "authorAffiliations": "", - "journalTitle": "JACC. Heart failure", - "pubYear": "2024", - "date": "2023-08-09", - "isOpenAccess": "N", - "keywords": "Myosin; Screening; Prognosis; Cardiomyopathy; Penetrance; Myh7", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

MYH7 variants cause hypertrophic cardiomyopathy (HCM), noncompaction cardiomyopathy (NCCM), and dilated cardiomyopathy (DCM). Screening of relatives of patients with genetic cardiomyopathy is recommended from 10 to 12 years of age onward, irrespective of the affected gene.

Objectives

This study sought to study the penetrance and prognosis of MYH7 variant-associated cardiomyopathies.

Methods

In this multicenter cohort study, penetrance and major cardiomyopathy-related events (MCEs) were assessed in carriers of (likely) pathogenic MYH7 variants by using Kaplan-Meier curves and log-rank tests. Prognostic factors were evaluated using Cox regression with time-dependent coefficients.

Results

In total, 581 subjects (30.1% index patients, 48.4% male, median age 37.0 years [IQR: 19.5-50.2 years]) were included. HCM was diagnosed in 226 subjects, NCCM in 70, and DCM in 55. Early penetrance and MCEs (age\u00a0<12 years) were common among NCCM-associated variant carriers (21.2% and 12.0%, respectively) and DCM-associated variant carriers (15.3% and 10.0%, respectively), compared with HCM-associated variant carriers (2.9% and 2.1%, respectively). Penetrance was significantly increased in carriers of converter region variants (adjusted HR: 1.87; 95%\u00a0CI: 1.15-3.04; P\u00a0=\u00a00.012) and at age\u00a0\u22641 year in NCCM-associated or DCM-associated variant carriers (adjusted HR: 21.17; 95%\u00a0CI: 4.81-93.20; P\u00a0< 0.001) and subjects with a family history of early MCEs (adjusted HR: 2.45; 95%\u00a0CI: 1.09-5.50; P\u00a0=\u00a00.030). The risk of MCE was increased in subjects with a family history of early MCEs (adjusted HR: 1.82; 95%\u00a0CI: 1.15-2.87; P\u00a0=\u00a00.010) and at age\u00a0\u22645 years in NCCM-associated or DCM-associated variant carriers (adjusted HR: 38.82; 95%\u00a0CI:\u00a05.16-291.88; P\u00a0< 0.001).

Conclusions

MYH7 variants can cause cardiomyopathies and MCEs at a young age. Screening at younger ages may\u00a0be warranted, particularly in carriers of NCCM- or DCM-associated variants and/or with a family history of MCEs at\u00a0<12 years.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jchf.2023.07.007" - }, { "id": "32862087", "doi": "https://doi.org/10.1016/j.atherosclerosis.2020.07.014", @@ -38640,6 +38623,23 @@ "laySummary": "", "urls": "pdf:http://www.atherosclerosis-journal.com/article/S0021915020303816/pdf; doi:https://doi.org/10.1016/j.atherosclerosis.2020.07.014" }, + { + "id": "37565978", + "doi": "https://doi.org/10.1016/j.jchf.2023.07.007", + "title": "Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies: Results From a Dutch Multicenter Cohort Study.", + "authorString": "Jansen M, de Brouwer R, Hassanzada F, Schoemaker AE, Schmidt AF, Kooijman-Reumerman MD, Bracun V, Slieker MG, Dooijes D, Vermeer AMC, Wilde AAM, Amin AS, Lekanne Deprez RH, Herkert JC, Christiaans I, de Boer RA, Jongbloed JDH, van Tintelen JP, Asselbergs FW, Baas AF.", + "authorAffiliations": "", + "journalTitle": "JACC. Heart failure", + "pubYear": "2024", + "date": "2023-08-09", + "isOpenAccess": "N", + "keywords": "Myosin; Screening; Prognosis; Cardiomyopathy; Penetrance; Myh7", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

MYH7 variants cause hypertrophic cardiomyopathy (HCM), noncompaction cardiomyopathy (NCCM), and dilated cardiomyopathy (DCM). Screening of relatives of patients with genetic cardiomyopathy is recommended from 10 to 12 years of age onward, irrespective of the affected gene.

Objectives

This study sought to study the penetrance and prognosis of MYH7 variant-associated cardiomyopathies.

Methods

In this multicenter cohort study, penetrance and major cardiomyopathy-related events (MCEs) were assessed in carriers of (likely) pathogenic MYH7 variants by using Kaplan-Meier curves and log-rank tests. Prognostic factors were evaluated using Cox regression with time-dependent coefficients.

Results

In total, 581 subjects (30.1% index patients, 48.4% male, median age 37.0 years [IQR: 19.5-50.2 years]) were included. HCM was diagnosed in 226 subjects, NCCM in 70, and DCM in 55. Early penetrance and MCEs (age\u00a0<12 years) were common among NCCM-associated variant carriers (21.2% and 12.0%, respectively) and DCM-associated variant carriers (15.3% and 10.0%, respectively), compared with HCM-associated variant carriers (2.9% and 2.1%, respectively). Penetrance was significantly increased in carriers of converter region variants (adjusted HR: 1.87; 95%\u00a0CI: 1.15-3.04; P\u00a0=\u00a00.012) and at age\u00a0\u22641 year in NCCM-associated or DCM-associated variant carriers (adjusted HR: 21.17; 95%\u00a0CI: 4.81-93.20; P\u00a0< 0.001) and subjects with a family history of early MCEs (adjusted HR: 2.45; 95%\u00a0CI: 1.09-5.50; P\u00a0=\u00a00.030). The risk of MCE was increased in subjects with a family history of early MCEs (adjusted HR: 1.82; 95%\u00a0CI: 1.15-2.87; P\u00a0=\u00a00.010) and at age\u00a0\u22645 years in NCCM-associated or DCM-associated variant carriers (adjusted HR: 38.82; 95%\u00a0CI:\u00a05.16-291.88; P\u00a0< 0.001).

Conclusions

MYH7 variants can cause cardiomyopathies and MCEs at a young age. Screening at younger ages may\u00a0be warranted, particularly in carriers of NCCM- or DCM-associated variants and/or with a family history of MCEs at\u00a0<12 years.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.jchf.2023.07.007" + }, { "id": "31382511", "doi": "https://doi.org/10.3390/toxins11080454", @@ -39048,23 +39048,6 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/1660-4601/16/8/1325/pdf?version=1555077276; doi:https://doi.org/10.3390/ijerph16081325; html:https://europepmc.org/articles/PMC6517898; pdf:https://europepmc.org/articles/PMC6517898?pdf=render" }, - { - "id": "35523486", - "doi": "https://doi.org/10.1136/bmjopen-2021-059258", - "title": "Using digital health tools for the Remote Assessment of Treatment Prognosis in Depression (RAPID): a study protocol for a feasibility study.", - "authorString": "de Angel V, Lewis S, Munir S, Matcham F, Dobson R, Hotopf M.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2022", - "date": "2022-05-06", - "isOpenAccess": "Y", - "keywords": "Mental health; Anxiety Disorders; Health Informatics; Depression & Mood Disorders", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

Digital health tools such as smartphones and wearable devices could improve psychological treatment outcomes in depression through more accurate and comprehensive measures of patient behaviour. However, in this emerging field, most studies are small and based on student populations outside of a clinical setting. The current study aims to determine the feasibility and acceptability of using smartphones and wearable devices to collect behavioural and clinical data in people undergoing therapy for depressive disorders and establish the extent to which they can be potentially useful biomarkers of depression and recovery after treatment.

Methods and analysis

This is an observational, prospective cohort study of 65 people attending psychological therapy for depression in multiple London-based sites. It will collect continuous passive data from smartphone sensors and a Fitbit fitness tracker, and deliver questionnaires, speech tasks and cognitive assessments through smartphone-based apps. Objective data on sleep, physical activity, location, Bluetooth contact, smartphone use and heart rate will be gathered for 7 months, and compared with clinical and contextual data. A mixed methods design, including a qualitative interview of patient experiences, will be used to evaluate key feasibility indicators, digital phenotypes of depression and therapy prognosis. Patient and public involvement was sought for participant-facing documents and the study design of the current research proposal.

Ethics and dissemination

Ethical approval has been obtained from the London Westminster Research Ethics Committee, and the Health Research Authority, Integrated Research Application System (project ID: 270918). Privacy and confidentiality will be guaranteed and the procedures for handling, processing, storage and destruction of the data will comply with the General Data Protection Regulation. Findings from this study will form part of a doctoral thesis, will be presented at national and international meetings or academic conferences and will generate manuscripts to be submitted to peer-reviewed journals.

Trial registration number

https://doi.org/10.17605/OSF.IO/PMYTA.", - "laySummary": "", - "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/5/e059258.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-059258; html:https://europepmc.org/articles/PMC9083394; pdf:https://europepmc.org/articles/PMC9083394?pdf=render" - }, { "id": "31806382", "doi": "https://doi.org/10.1016/j.injury.2019.11.023", @@ -39082,6 +39065,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.injury.2019.11.023" }, + { + "id": "35523486", + "doi": "https://doi.org/10.1136/bmjopen-2021-059258", + "title": "Using digital health tools for the Remote Assessment of Treatment Prognosis in Depression (RAPID): a study protocol for a feasibility study.", + "authorString": "de Angel V, Lewis S, Munir S, Matcham F, Dobson R, Hotopf M.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2022", + "date": "2022-05-06", + "isOpenAccess": "Y", + "keywords": "Mental health; Anxiety Disorders; Health Informatics; Depression & Mood Disorders", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

Digital health tools such as smartphones and wearable devices could improve psychological treatment outcomes in depression through more accurate and comprehensive measures of patient behaviour. However, in this emerging field, most studies are small and based on student populations outside of a clinical setting. The current study aims to determine the feasibility and acceptability of using smartphones and wearable devices to collect behavioural and clinical data in people undergoing therapy for depressive disorders and establish the extent to which they can be potentially useful biomarkers of depression and recovery after treatment.

Methods and analysis

This is an observational, prospective cohort study of 65 people attending psychological therapy for depression in multiple London-based sites. It will collect continuous passive data from smartphone sensors and a Fitbit fitness tracker, and deliver questionnaires, speech tasks and cognitive assessments through smartphone-based apps. Objective data on sleep, physical activity, location, Bluetooth contact, smartphone use and heart rate will be gathered for 7 months, and compared with clinical and contextual data. A mixed methods design, including a qualitative interview of patient experiences, will be used to evaluate key feasibility indicators, digital phenotypes of depression and therapy prognosis. Patient and public involvement was sought for participant-facing documents and the study design of the current research proposal.

Ethics and dissemination

Ethical approval has been obtained from the London Westminster Research Ethics Committee, and the Health Research Authority, Integrated Research Application System (project ID: 270918). Privacy and confidentiality will be guaranteed and the procedures for handling, processing, storage and destruction of the data will comply with the General Data Protection Regulation. Findings from this study will form part of a doctoral thesis, will be presented at national and international meetings or academic conferences and will generate manuscripts to be submitted to peer-reviewed journals.

Trial registration number

https://doi.org/10.17605/OSF.IO/PMYTA.", + "laySummary": "", + "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/5/e059258.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-059258; html:https://europepmc.org/articles/PMC9083394; pdf:https://europepmc.org/articles/PMC9083394?pdf=render" + }, { "id": "36568709", "doi": "https://doi.org/10.1136/bmjmed-2022-000215", @@ -39303,23 +39303,6 @@ "laySummary": "", "urls": "pdf:https://bmjophth.bmj.com/content/bmjophth/5/1/e000481.full.pdf; doi:https://doi.org/10.1136/bmjophth-2020-000481; html:https://europepmc.org/articles/PMC7375431; pdf:https://europepmc.org/articles/PMC7375431?pdf=render" }, - { - "id": "35585198", - "doi": "https://doi.org/10.1038/s41591-022-01772-9", - "title": "Reporting guideline for the early-stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI.", - "authorString": "Vasey B, Nagendran M, Campbell B, Clifton DA, Collins GS, Denaxas S, Denniston AK, Faes L, Geerts B, Ibrahim M, Liu X, Mateen BA, Mathur P, McCradden MD, Morgan L, Ordish J, Rogers C, Saria S, Ting DSW, Watkinson P, Weber W, Wheatstone P, McCulloch P, DECIDE-AI expert group.", - "authorAffiliations": "", - "journalTitle": "Nature medicine", - "pubYear": "2022", - "date": "2022-05-18", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "A growing number of artificial intelligence (AI)-based clinical decision support systems are showing promising performance in preclinical, in silico evaluation, but few have yet demonstrated real benefit to patient care. Early-stage clinical evaluation is important to assess an AI system's actual clinical performance at small scale, ensure its safety, evaluate the human factors surrounding its use and pave the way to further large-scale trials. However, the reporting of these early studies remains inadequate. The present statement provides a multi-stakeholder, consensus-based reporting guideline for the Developmental and Exploratory Clinical Investigations of DEcision support systems driven by Artificial Intelligence (DECIDE-AI). We conducted a two-round, modified Delphi process to collect and analyze expert opinion on the reporting of early clinical evaluation of AI systems. Experts were recruited from 20 pre-defined stakeholder categories. The final composition and wording of the guideline was determined at a virtual consensus meeting. The checklist and the Explanation & Elaboration (E&E) sections were refined based on feedback from a qualitative evaluation process. In total, 123 experts participated in the first round of Delphi, 138 in the second round, 16 in the consensus meeting and 16 in the qualitative evaluation. The DECIDE-AI reporting guideline comprises 17 AI-specific reporting items (made of 28 subitems) and ten generic reporting items, with an E&E paragraph provided for each. Through consultation and consensus with a range of stakeholders, we developed a guideline comprising key items that should be reported in early-stage clinical studies of AI-based decision support systems in healthcare. By providing an actionable checklist of minimal reporting items, the DECIDE-AI guideline will facilitate the appraisal of these studies and replicability of their findings.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41591-022-01772-9.pdf; doi:https://doi.org/10.1038/s41591-022-01772-9" - }, { "id": "35042708", "doi": "https://doi.org/10.1136/bmjopen-2021-055572", @@ -39337,6 +39320,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/1/e055572.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055572; html:https://europepmc.org/articles/PMC8768913; pdf:https://europepmc.org/articles/PMC8768913?pdf=render" }, + { + "id": "35585198", + "doi": "https://doi.org/10.1038/s41591-022-01772-9", + "title": "Reporting guideline for the early-stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI.", + "authorString": "Vasey B, Nagendran M, Campbell B, Clifton DA, Collins GS, Denaxas S, Denniston AK, Faes L, Geerts B, Ibrahim M, Liu X, Mateen BA, Mathur P, McCradden MD, Morgan L, Ordish J, Rogers C, Saria S, Ting DSW, Watkinson P, Weber W, Wheatstone P, McCulloch P, DECIDE-AI expert group.", + "authorAffiliations": "", + "journalTitle": "Nature medicine", + "pubYear": "2022", + "date": "2022-05-18", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "A growing number of artificial intelligence (AI)-based clinical decision support systems are showing promising performance in preclinical, in silico evaluation, but few have yet demonstrated real benefit to patient care. Early-stage clinical evaluation is important to assess an AI system's actual clinical performance at small scale, ensure its safety, evaluate the human factors surrounding its use and pave the way to further large-scale trials. However, the reporting of these early studies remains inadequate. The present statement provides a multi-stakeholder, consensus-based reporting guideline for the Developmental and Exploratory Clinical Investigations of DEcision support systems driven by Artificial Intelligence (DECIDE-AI). We conducted a two-round, modified Delphi process to collect and analyze expert opinion on the reporting of early clinical evaluation of AI systems. Experts were recruited from 20 pre-defined stakeholder categories. The final composition and wording of the guideline was determined at a virtual consensus meeting. The checklist and the Explanation & Elaboration (E&E) sections were refined based on feedback from a qualitative evaluation process. In total, 123 experts participated in the first round of Delphi, 138 in the second round, 16 in the consensus meeting and 16 in the qualitative evaluation. The DECIDE-AI reporting guideline comprises 17 AI-specific reporting items (made of 28 subitems) and ten generic reporting items, with an E&E paragraph provided for each. Through consultation and consensus with a range of stakeholders, we developed a guideline comprising key items that should be reported in early-stage clinical studies of AI-based decision support systems in healthcare. By providing an actionable checklist of minimal reporting items, the DECIDE-AI guideline will facilitate the appraisal of these studies and replicability of their findings.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41591-022-01772-9.pdf; doi:https://doi.org/10.1038/s41591-022-01772-9" + }, { "id": "37067557", "doi": "https://doi.org/10.1007/s00134-023-07039-2", @@ -39405,23 +39405,6 @@ "laySummary": "", "urls": "pdf:https://breast-cancer-research.biomedcentral.com/track/pdf/10.1186/s13058-021-01465-0; doi:https://doi.org/10.1186/s13058-021-01465-0; html:https://europepmc.org/articles/PMC8482562; pdf:https://europepmc.org/articles/PMC8482562?pdf=render" }, - { - "id": "36029521", - "doi": "https://doi.org/10.1093/ije/dyac171", - "title": "Cohort Profile: The United Kingdom Research study into Ethnicity and COVID-19 outcomes in Healthcare workers (UK-REACH).", - "authorString": "Bryant L, Free RC, Woolf K, Melbourne C, Guyatt AL, John C, Gupta A, Gray LJ, Nellums L, Martin CA, McManus IC, Garwood C, Modhawdia V, Carr S, Wain LV, Tobin MD, Khunti K, Akubakar I, Pareek M, UK-REACH Collaborative Group+.", - "authorAffiliations": "", - "journalTitle": "International journal of epidemiology", - "pubYear": "2023", - "date": "2023-02-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/ije/article-pdf/52/1/e38/49127215/dyac171.pdf; doi:https://doi.org/10.1093/ije/dyac171; html:https://europepmc.org/articles/PMC9452183; pdf:https://europepmc.org/articles/PMC9452183?pdf=render" - }, { "id": "32558637", "doi": "https://doi.org/10.1099/mgen.0.000393", @@ -39439,6 +39422,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1099/mgen.0.000393; doi:https://doi.org/10.1099/mgen.0.000393; html:https://europepmc.org/articles/PMC7478626; pdf:https://europepmc.org/articles/PMC7478626?pdf=render" }, + { + "id": "36029521", + "doi": "https://doi.org/10.1093/ije/dyac171", + "title": "Cohort Profile: The United Kingdom Research study into Ethnicity and COVID-19 outcomes in Healthcare workers (UK-REACH).", + "authorString": "Bryant L, Free RC, Woolf K, Melbourne C, Guyatt AL, John C, Gupta A, Gray LJ, Nellums L, Martin CA, McManus IC, Garwood C, Modhawdia V, Carr S, Wain LV, Tobin MD, Khunti K, Akubakar I, Pareek M, UK-REACH Collaborative Group+.", + "authorAffiliations": "", + "journalTitle": "International journal of epidemiology", + "pubYear": "2023", + "date": "2023-02-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/ije/article-pdf/52/1/e38/49127215/dyac171.pdf; doi:https://doi.org/10.1093/ije/dyac171; html:https://europepmc.org/articles/PMC9452183; pdf:https://europepmc.org/articles/PMC9452183?pdf=render" + }, { "id": "31171806", "doi": "https://doi.org/10.1038/s41598-019-44907-8", @@ -39541,23 +39541,6 @@ "laySummary": "", "urls": "pdf:https://bmcmedethics.biomedcentral.com/counter/pdf/10.1186/s12910-022-00875-9; doi:https://doi.org/10.1186/s12910-022-00875-9; html:https://europepmc.org/articles/PMC9756740; pdf:https://europepmc.org/articles/PMC9756740?pdf=render" }, - { - "id": "34490590", - "doi": "https://doi.org/10.1007/s40256-021-00496-4", - "title": "Cost Effectiveness of a CYP2C19 Genotype-Guided Strategy in Patients with Acute Myocardial Infarction: Results from the POPular Genetics Trial.", - "authorString": "Claassens DMF, van Dorst PWM, Vos GJA, Bergmeijer TO, Hermanides RS, van 't Hof AWJ, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, Asselbergs FW, Mosterd A, Herrman JR, Dewilde WJM, Postma MJ, Deneer VHM, Ten Berg JM, Boersma C.", - "authorAffiliations": "", - "journalTitle": "American journal of cardiovascular drugs : drugs, devices, and other interventions", - "pubYear": "2022", - "date": "2021-09-07", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

The POPular Genetics trial demonstrated that a CYP2C19 genotype-guided P2Y12 inhibitor strategy reduced bleeding rates compared with standard treatment with ticagrelor or prasugrel without increasing thrombotic event rates after primary percutaneous coronary intervention (PCI).

Objective

In this analysis, we aimed to evaluate the cost effectiveness of a genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel.

Methods

A 1-year decision tree based on the POPular Genetics trial in combination with a lifelong Markov model was developed to compare costs and quality-adjusted life-years (QALYs) between a genotype-guided and a standard P2Y12 inhibitor strategy in patients with myocardial infarction undergoing primary PCI. The cost-effectiveness analysis was conducted from a Dutch healthcare system perspective. Within-trial survival and utility data were combined with lifetime projections to evaluate lifetime cost effectiveness for a cohort of 1000 patients. Costs and utilities were discounted at 4 and 1.5%, respectively, according to Dutch guidelines for health economic studies. Besides deterministic and probabilistic sensitivity analyses, several scenario analyses were also conducted (different time horizons, different discount rates, equal prices for P2Y12 inhibitors, and equal distribution of thrombotic events between the two strategies).

Results

Base-case analysis with a hypothetical cohort of 1000 subjects demonstrated 8.98 QALYs gained and \u20ac725,550.69 in cost savings for the genotype-guided strategy (dominant). The deterministic and probabilistic sensitivity analysis confirmed the robustness of the model and the cost-effectiveness results. In scenario analyses, the genotype-guided strategy remained dominant.

Conclusion

In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel resulted in QALYs gained and cost savings.

Trial registration

Clinicaltrials.gov number: NCT01761786, Netherlands trial register number: NL2872.", - "laySummary": "", - "urls": "pdf:https://pure.rug.nl/ws/files/223545267/Cost_Effectiveness_of_a_CYP2C19_Genotype_Guided_Strategy_in_Patients_with_Acute_Myocardial_Infarction_Results_from_the_POPular_Genetics_Trial.pdf; doi:https://doi.org/10.1007/s40256-021-00496-4" - }, { "id": "36522333", "doi": "https://doi.org/10.1038/s41467-022-35454-4", @@ -39575,6 +39558,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41467-022-35454-4.pdf; doi:https://doi.org/10.1038/s41467-022-35454-4; html:https://europepmc.org/articles/PMC9753891; pdf:https://europepmc.org/articles/PMC9753891?pdf=render" }, + { + "id": "34490590", + "doi": "https://doi.org/10.1007/s40256-021-00496-4", + "title": "Cost Effectiveness of a CYP2C19 Genotype-Guided Strategy in Patients with Acute Myocardial Infarction: Results from the POPular Genetics Trial.", + "authorString": "Claassens DMF, van Dorst PWM, Vos GJA, Bergmeijer TO, Hermanides RS, van 't Hof AWJ, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, Asselbergs FW, Mosterd A, Herrman JR, Dewilde WJM, Postma MJ, Deneer VHM, Ten Berg JM, Boersma C.", + "authorAffiliations": "", + "journalTitle": "American journal of cardiovascular drugs : drugs, devices, and other interventions", + "pubYear": "2022", + "date": "2021-09-07", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

The POPular Genetics trial demonstrated that a CYP2C19 genotype-guided P2Y12 inhibitor strategy reduced bleeding rates compared with standard treatment with ticagrelor or prasugrel without increasing thrombotic event rates after primary percutaneous coronary intervention (PCI).

Objective

In this analysis, we aimed to evaluate the cost effectiveness of a genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel.

Methods

A 1-year decision tree based on the POPular Genetics trial in combination with a lifelong Markov model was developed to compare costs and quality-adjusted life-years (QALYs) between a genotype-guided and a standard P2Y12 inhibitor strategy in patients with myocardial infarction undergoing primary PCI. The cost-effectiveness analysis was conducted from a Dutch healthcare system perspective. Within-trial survival and utility data were combined with lifetime projections to evaluate lifetime cost effectiveness for a cohort of 1000 patients. Costs and utilities were discounted at 4 and 1.5%, respectively, according to Dutch guidelines for health economic studies. Besides deterministic and probabilistic sensitivity analyses, several scenario analyses were also conducted (different time horizons, different discount rates, equal prices for P2Y12 inhibitors, and equal distribution of thrombotic events between the two strategies).

Results

Base-case analysis with a hypothetical cohort of 1000 subjects demonstrated 8.98 QALYs gained and \u20ac725,550.69 in cost savings for the genotype-guided strategy (dominant). The deterministic and probabilistic sensitivity analysis confirmed the robustness of the model and the cost-effectiveness results. In scenario analyses, the genotype-guided strategy remained dominant.

Conclusion

In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel resulted in QALYs gained and cost savings.

Trial registration

Clinicaltrials.gov number: NCT01761786, Netherlands trial register number: NL2872.", + "laySummary": "", + "urls": "pdf:https://pure.rug.nl/ws/files/223545267/Cost_Effectiveness_of_a_CYP2C19_Genotype_Guided_Strategy_in_Patients_with_Acute_Myocardial_Infarction_Results_from_the_POPular_Genetics_Trial.pdf; doi:https://doi.org/10.1007/s40256-021-00496-4" + }, { "id": "37132645", "doi": "https://doi.org/10.1017/s0033291721002257", @@ -39592,23 +39592,6 @@ "laySummary": "", "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/F28CB69D452C5EFDAFF77D0FE59FC094/S0033291721002257a.pdf/div-class-title-life-expectancy-mortality-risks-and-cause-of-death-in-patients-with-serious-mental-illness-in-south-east-london-a-comparison-between-2008-2012-and-2013-2017-div.pdf; doi:https://doi.org/10.1017/S0033291721002257; html:https://europepmc.org/articles/PMC9975985; pdf:https://europepmc.org/articles/PMC9975985?pdf=render" }, - { - "id": "38783292", - "doi": "https://doi.org/10.1186/s12939-024-02198-0", - "title": "Discrimination, disadvantage and disempowerment during COVID-19: a qualitative intrasectional analysis of the lived experiences of an ethnically diverse healthcare workforce in the United Kingdom.", - "authorString": "Gogoi M, Qureshi I, Chaloner J, Al-Oraibi A, Reilly H, Wobi F, Agbonmwandolor JO, Ekezie W, Hassan O, Lal Z, Kapilashrami A, Nellums L, Pareek M, UK-REACH Study Collaborative Group Members.", - "authorAffiliations": "", - "journalTitle": "International journal for equity in health", - "pubYear": "2024", - "date": "2024-05-23", - "isOpenAccess": "Y", - "keywords": "Discrimination; Healthcare Workers; Disadvantage; Disempowerment; Covid-19 Pandemic; Intersectionality; Intrasectionalism", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Healthcare workers (HCWs) in the United Kingdom (UK) have faced many challenges during the COVID-19 pandemic, some of these arising out of their social positions. Existing literature explicating these challenges (e.g., lack of appropriate PPE, redeployment, understaffing) have highlighted inequities in how these have been experienced by HCWs based on ethnicity, gender or, job role. In this paper, we move a step ahead and examine how the intersection of these social positions have impacted HCWs' experiences of challenges during the pandemic.

Methods

We collected qualitative data, using interviews and focus groups, from 164 HCWs from different ethnicities, gender, job roles, migration statuses, and regions in the United Kingdom (UK) between December 2020 and July 2021. Interviews and focus groups were conducted online or by telephone, and recorded with participants' permission. Recordings were transcribed and a hybrid thematic analytical approach integrating inductive data-driven codes with deductive ones informed by an intersectional framework was adopted to analyse the transcripts.

Results

Thematic analysis of transcripts identified disempowerment, disadvantage and, discrimination as the three main themes around which HCWs' experiences of challenges were centred, based on their intersecting identities (e.g., ethnicity gender, and/or migration status). Our analysis also acknowledges that disadvantages faced by HCWs were linked to systemic and structural factors at the micro, meso and macro ecosystemic levels. This merging of analysis which is grounded in intersectionality and considers the ecosystemic levels has been termed as 'intrasectionalism'.

Discussion

Our research demonstrates how an intrasectional lens can help better understand how different forms of mutually reinforcing inequities exist at all levels within the healthcare workforce and how these impact HCWs from certain backgrounds who face greater disadvantage, discrimination and disempowerment, particularly during times of crisis like the COVID-19 pandemic.", - "laySummary": "", - "urls": "pdf:https://equityhealthj.biomedcentral.com/counter/pdf/10.1186/s12939-024-02198-0; doi:https://doi.org/10.1186/s12939-024-02198-0; html:https://europepmc.org/articles/PMC11118759; pdf:https://europepmc.org/articles/PMC11118759?pdf=render" - }, { "id": "33199917", "doi": "https://doi.org/10.1038/s41588-020-00725-7", @@ -39626,6 +39609,23 @@ "laySummary": "", "urls": "pdf:https://europepmc.org/articles/pmc7116530?pdf=render; doi:https://doi.org/10.1038/s41588-020-00725-7; html:https://europepmc.org/articles/PMC7116530; pdf:https://europepmc.org/articles/PMC7116530?pdf=render; doi:https://doi.org/10.1038/s41588-020-00725-7" }, + { + "id": "38783292", + "doi": "https://doi.org/10.1186/s12939-024-02198-0", + "title": "Discrimination, disadvantage and disempowerment during COVID-19: a qualitative intrasectional analysis of the lived experiences of an ethnically diverse healthcare workforce in the United Kingdom.", + "authorString": "Gogoi M, Qureshi I, Chaloner J, Al-Oraibi A, Reilly H, Wobi F, Agbonmwandolor JO, Ekezie W, Hassan O, Lal Z, Kapilashrami A, Nellums L, Pareek M, UK-REACH Study Collaborative Group Members.", + "authorAffiliations": "", + "journalTitle": "International journal for equity in health", + "pubYear": "2024", + "date": "2024-05-23", + "isOpenAccess": "Y", + "keywords": "Discrimination; Healthcare Workers; Disadvantage; Disempowerment; Covid-19 Pandemic; Intersectionality; Intrasectionalism", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Healthcare workers (HCWs) in the United Kingdom (UK) have faced many challenges during the COVID-19 pandemic, some of these arising out of their social positions. Existing literature explicating these challenges (e.g., lack of appropriate PPE, redeployment, understaffing) have highlighted inequities in how these have been experienced by HCWs based on ethnicity, gender or, job role. In this paper, we move a step ahead and examine how the intersection of these social positions have impacted HCWs' experiences of challenges during the pandemic.

Methods

We collected qualitative data, using interviews and focus groups, from 164 HCWs from different ethnicities, gender, job roles, migration statuses, and regions in the United Kingdom (UK) between December 2020 and July 2021. Interviews and focus groups were conducted online or by telephone, and recorded with participants' permission. Recordings were transcribed and a hybrid thematic analytical approach integrating inductive data-driven codes with deductive ones informed by an intersectional framework was adopted to analyse the transcripts.

Results

Thematic analysis of transcripts identified disempowerment, disadvantage and, discrimination as the three main themes around which HCWs' experiences of challenges were centred, based on their intersecting identities (e.g., ethnicity gender, and/or migration status). Our analysis also acknowledges that disadvantages faced by HCWs were linked to systemic and structural factors at the micro, meso and macro ecosystemic levels. This merging of analysis which is grounded in intersectionality and considers the ecosystemic levels has been termed as 'intrasectionalism'.

Discussion

Our research demonstrates how an intrasectional lens can help better understand how different forms of mutually reinforcing inequities exist at all levels within the healthcare workforce and how these impact HCWs from certain backgrounds who face greater disadvantage, discrimination and disempowerment, particularly during times of crisis like the COVID-19 pandemic.", + "laySummary": "", + "urls": "pdf:https://equityhealthj.biomedcentral.com/counter/pdf/10.1186/s12939-024-02198-0; doi:https://doi.org/10.1186/s12939-024-02198-0; html:https://europepmc.org/articles/PMC11118759; pdf:https://europepmc.org/articles/PMC11118759?pdf=render" + }, { "id": "32127008", "doi": "https://doi.org/10.1186/s13059-020-01969-6", @@ -39643,23 +39643,6 @@ "laySummary": "", "urls": "pdf:https://genomebiology.biomedcentral.com/track/pdf/10.1186/s13059-020-01969-6; doi:https://doi.org/10.1186/s13059-020-01969-6; html:https://europepmc.org/articles/PMC7053107; pdf:https://europepmc.org/articles/PMC7053107?pdf=render" }, - { - "id": "35617980", - "doi": "https://doi.org/10.1016/s0140-6736(22)00532-3", - "title": "Measuring the availability of human resources for health and its relationship to universal health coverage for 204 countries and territories from 1990 to 2019: a systematic analysis for the Global Burden of Disease Study 2019.", - "authorString": "GBD 2019 Human Resources for Health Collaborators.", - "authorAffiliations": "", - "journalTitle": "Lancet (London, England)", - "pubYear": "2022", - "date": "2022-05-23", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Human resources for health (HRH) include a range of occupations that aim to promote or improve human health. The UN Sustainable Development Goals (SDGs) and the WHO Health Workforce 2030 strategy have drawn attention to the importance of HRH for achieving policy priorities such as universal health coverage (UHC). Although previous research has found substantial global disparities in HRH, the absence of comparable cross-national estimates of existing workforces has hindered efforts to quantify workforce requirements to meet health system goals. We aimed to use comparable and standardised data sources to estimate HRH densities globally, and to examine the relationship between a subset of HRH cadres and UHC effective coverage performance.

Methods

Through the International Labour Organization and Global Health Data Exchange databases, we identified 1404 country-years of data from labour force surveys and 69 country-years of census data, with detailed microdata on health-related employment. From the WHO National Health Workforce Accounts, we identified 2950 country-years of data. We mapped data from all occupational coding systems to the International Standard Classification of Occupations 1988 (ISCO-88), allowing for standardised estimation of densities for 16 categories of health workers across the full time series. Using data from 1990 to 2019 for 196 of 204 countries and territories, covering seven Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) super-regions and 21 regions, we applied spatiotemporal Gaussian process regression (ST-GPR) to model HRH densities from 1990 to 2019 for all countries and territories. We used stochastic frontier meta-regression to model the relationship between the UHC effective coverage index and densities for the four categories of health workers enumerated in SDG indicator 3.c.1 pertaining to HRH: physicians, nurses and midwives, dentistry personnel, and pharmaceutical personnel. We identified minimum workforce density thresholds required to meet a specified target of 80 out of 100 on the UHC effective coverage index, and quantified national shortages with respect to those minimum thresholds.

Findings

We estimated that, in 2019, the world had 104\u00b70 million (95% uncertainty interval 83\u00b75-128\u00b70) health workers, including 12\u00b78 million (9\u00b77-16\u00b76) physicians, 29\u00b78 million (23\u00b73-37\u00b77) nurses and midwives, 4\u00b76 million (3\u00b76-6\u00b70) dentistry personnel, and 5\u00b72 million (4\u00b70-6\u00b77) pharmaceutical personnel. We calculated a global physician density of 16\u00b77 (12\u00b76-21\u00b76) per 10\u2009000 population, and a nurse and midwife density of 38\u00b76 (30\u00b71-48\u00b78) per 10\u2009000 population. We found the GBD super-regions of sub-Saharan Africa, south Asia, and north Africa and the Middle East had the lowest HRH densities. To reach 80 out of 100 on the UHC effective coverage index, we estimated that, per 10\u2009000 population, at least 20\u00b77 physicians, 70\u00b76 nurses and midwives, 8\u00b72 dentistry personnel, and 9\u00b74 pharmaceutical personnel would be needed. In total, the 2019 national health workforces fell short of these minimum thresholds by 6\u00b74 million physicians, 30\u00b76 million nurses and midwives, 3\u00b73 million dentistry personnel, and 2\u00b79 million pharmaceutical personnel.

Interpretation

Considerable expansion of the world's health workforce is needed to achieve high levels of UHC effective coverage. The largest shortages are in low-income settings, highlighting the need for increased financing and coordination to train, employ, and retain human resources in the health sector. Actual HRH shortages might be larger than estimated because minimum thresholds for each cadre of health workers are benchmarked on health systems that most efficiently translate human resources into UHC attainment.

Funding

Bill & Melinda Gates Foundation.", - "laySummary": "", - "urls": "pdf:http://www.thelancet.com/article/S0140673622005323/pdf; doi:https://doi.org/10.1016/S0140-6736(22)00532-3; html:https://europepmc.org/articles/PMC9168805" - }, { "id": "33075408", "doi": "https://doi.org/10.1016/j.jaci.2020.10.007", @@ -39677,6 +39660,23 @@ "laySummary": "", "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4659367/1/Factors%20associated%20with%20adverse%20COVID-19%20outcomes%20in%20patients%20with%20psoriasis-insights%20from%20a%20global%20registry-based%20study.pdf; doi:https://doi.org/10.1016/j.jaci.2020.10.007; html:https://europepmc.org/articles/PMC7566694; pdf:https://europepmc.org/articles/PMC7566694?pdf=render" }, + { + "id": "35617980", + "doi": "https://doi.org/10.1016/s0140-6736(22)00532-3", + "title": "Measuring the availability of human resources for health and its relationship to universal health coverage for 204 countries and territories from 1990 to 2019: a systematic analysis for the Global Burden of Disease Study 2019.", + "authorString": "GBD 2019 Human Resources for Health Collaborators.", + "authorAffiliations": "", + "journalTitle": "Lancet (London, England)", + "pubYear": "2022", + "date": "2022-05-23", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Human resources for health (HRH) include a range of occupations that aim to promote or improve human health. The UN Sustainable Development Goals (SDGs) and the WHO Health Workforce 2030 strategy have drawn attention to the importance of HRH for achieving policy priorities such as universal health coverage (UHC). Although previous research has found substantial global disparities in HRH, the absence of comparable cross-national estimates of existing workforces has hindered efforts to quantify workforce requirements to meet health system goals. We aimed to use comparable and standardised data sources to estimate HRH densities globally, and to examine the relationship between a subset of HRH cadres and UHC effective coverage performance.

Methods

Through the International Labour Organization and Global Health Data Exchange databases, we identified 1404 country-years of data from labour force surveys and 69 country-years of census data, with detailed microdata on health-related employment. From the WHO National Health Workforce Accounts, we identified 2950 country-years of data. We mapped data from all occupational coding systems to the International Standard Classification of Occupations 1988 (ISCO-88), allowing for standardised estimation of densities for 16 categories of health workers across the full time series. Using data from 1990 to 2019 for 196 of 204 countries and territories, covering seven Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) super-regions and 21 regions, we applied spatiotemporal Gaussian process regression (ST-GPR) to model HRH densities from 1990 to 2019 for all countries and territories. We used stochastic frontier meta-regression to model the relationship between the UHC effective coverage index and densities for the four categories of health workers enumerated in SDG indicator 3.c.1 pertaining to HRH: physicians, nurses and midwives, dentistry personnel, and pharmaceutical personnel. We identified minimum workforce density thresholds required to meet a specified target of 80 out of 100 on the UHC effective coverage index, and quantified national shortages with respect to those minimum thresholds.

Findings

We estimated that, in 2019, the world had 104\u00b70 million (95% uncertainty interval 83\u00b75-128\u00b70) health workers, including 12\u00b78 million (9\u00b77-16\u00b76) physicians, 29\u00b78 million (23\u00b73-37\u00b77) nurses and midwives, 4\u00b76 million (3\u00b76-6\u00b70) dentistry personnel, and 5\u00b72 million (4\u00b70-6\u00b77) pharmaceutical personnel. We calculated a global physician density of 16\u00b77 (12\u00b76-21\u00b76) per 10\u2009000 population, and a nurse and midwife density of 38\u00b76 (30\u00b71-48\u00b78) per 10\u2009000 population. We found the GBD super-regions of sub-Saharan Africa, south Asia, and north Africa and the Middle East had the lowest HRH densities. To reach 80 out of 100 on the UHC effective coverage index, we estimated that, per 10\u2009000 population, at least 20\u00b77 physicians, 70\u00b76 nurses and midwives, 8\u00b72 dentistry personnel, and 9\u00b74 pharmaceutical personnel would be needed. In total, the 2019 national health workforces fell short of these minimum thresholds by 6\u00b74 million physicians, 30\u00b76 million nurses and midwives, 3\u00b73 million dentistry personnel, and 2\u00b79 million pharmaceutical personnel.

Interpretation

Considerable expansion of the world's health workforce is needed to achieve high levels of UHC effective coverage. The largest shortages are in low-income settings, highlighting the need for increased financing and coordination to train, employ, and retain human resources in the health sector. Actual HRH shortages might be larger than estimated because minimum thresholds for each cadre of health workers are benchmarked on health systems that most efficiently translate human resources into UHC attainment.

Funding

Bill & Melinda Gates Foundation.", + "laySummary": "", + "urls": "pdf:http://www.thelancet.com/article/S0140673622005323/pdf; doi:https://doi.org/10.1016/S0140-6736(22)00532-3; html:https://europepmc.org/articles/PMC9168805" + }, { "id": "37263751", "doi": "https://doi.org/10.1183/13993003.01667-2022", @@ -39729,21 +39729,21 @@ "urls": "pdf:https://www.nature.com/articles/s41467-019-13585-5.pdf; doi:https://doi.org/10.1038/s41467-019-13585-5; html:https://europepmc.org/articles/PMC6915786; pdf:https://europepmc.org/articles/PMC6915786?pdf=render" }, { - "id": "37923486", - "doi": "https://doi.org/10.1016/s2352-3018(23)00233-3", - "title": "Integrase strand-transfer inhibitor use and cardiovascular events in adults with HIV: an emulation of target trials in the HIV-CAUSAL Collaboration and the Antiretroviral Therapy Cohort Collaboration.", - "authorString": "Rein SM, Lodi S, Logan RW, Touloumi G, Antoniadou A, Wittkop L, Bonnet F, van Sighem A, van der Valk M, Reiss P, Klein MB, Young J, Jarrin I, d'Arminio Monforte A, Tavelli A, Meyer L, Tran L, Gill MJ, Lang R, Surial B, Haas AD, Justice AC, Rentsch CT, Phillips A, Sabin CA, Miro JM, Trickey A, Ingle SM, Sterne JAC, Hern\u00e1n MA, Antiretroviral Therapy Cohort Collaboration and the HIV-CAUSAL Collaboration.", + "id": "31711539", + "doi": "https://doi.org/10.1186/s13326-019-0211-7", + "title": "Text mining brain imaging reports.", + "authorString": "Alex B, Grover C, Tobin R, Sudlow C, Mair G, Whiteley W.", "authorAffiliations": "", - "journalTitle": "The lancet. HIV", - "pubYear": "2023", - "date": "2023-11-01", - "isOpenAccess": "N", - "keywords": "", + "journalTitle": "Journal of biomedical semantics", + "pubYear": "2019", + "date": "2019-11-12", + "isOpenAccess": "Y", + "keywords": "Stroke Classification; Text Mining; Electronic Healthcare Records; Neuroimaging Reports", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

A recent observational study suggested that the risk of cardiovascular events could be higher among antiretroviral therapy (ART)-naive individuals with HIV who receive integrase strand-transfer inhibitor (INSTI)-based ART than among those who receive other ART regimens. We aimed to emulate target trials separately in ART-naive and ART-experienced individuals with HIV to examine the effect of using INSTI-based regimens versus other ART regimens on the 4-year risk of cardiovascular events.

Methods

We used routinely recorded clinical data from 12 cohorts that collected information on cardiovascular events, BMI, and blood pressure from two international consortia of cohorts of people with HIV from Europe and North America. For the target trial in individuals who had previously never used ART (ie, ART-naive), eligibility criteria were aged 18 years or older, a detectable HIV-RNA measurement while ART-naive (>50 copies per mL), and no history of a cardiovascular event or cancer. Eligibility criteria for the target trial in those with previous use of non-INSTI-based ART (ie, ART-experienced) were the same except that individuals had to have been on at least one non-INSTI-based ART regimen and be virally suppressed (\u226450 copies per mL). We assessed eligibility for both trials for each person-month between January, 2013, and January, 2023, and assigned individuals to the treatment strategy that was compatible with their data. We estimated the standardised 4-year risks of cardiovascular events (myocardial infarction, stroke, or invasive cardiovascular procedure) via pooled logistic regression models adjusting for time and baseline covariates. In per-protocol analyses, we censored individuals if they deviated from their assigned treatment strategy for more than 2 months and weighted uncensored individuals by the inverse of their time-varying probability of remaining uncensored. The denominator of the weight was estimated via a pooled logistic model that included baseline and time-varying covariates.

Findings

The analysis in ART-naive individuals included 10\u2008767 INSTI initiators and 8292 non-initiators of INSTI. There were 43 cardiovascular events in INSTI initiators (median follow-up of 29 months; IQR 15-45) and 52 in non-initiators (39 months; 18-47): standardised 4-year risks were 0\u00b776% (95% CI 0\u00b751 to 1\u00b704) in INSTI initiators and 0\u00b775% (0\u00b754 to 0\u00b798) in non-INSTI initiators; risk ratio 1\u00b701 (0\u00b757 to 1\u00b757); risk difference 0\u00b70089% (-0\u00b743 to 0\u00b736). The analysis in ART-experienced individuals included 7875 INSTI initiators and 373\u2008965 non-initiators. There were 56 events in INSTI initiators (median follow-up 18 months; IQR 9-29) and 3103 events (808 unique) in non-INSTI initiators (26 months; 15-37) in non-initiators: standardised 4-year risks 1\u00b741% (95% CI 0\u00b788 to 2\u00b703) in INSTI initiators and 1\u00b748% (1\u00b728 to 1\u00b771) in non-initiators; risk ratio 0\u00b795 (0\u00b760 to 1\u00b736); risk difference -0\u00b7068% (-0\u00b760 to 0\u00b752).

Interpretation

We estimated that INSTI use did not result in a clinically meaningful increase of cardiovascular events in ART-naive and ART-experienced individuals with HIV.

Funding

National Institute of Allergy and Infectious Diseases and National Institute on Alcohol Abuse and Alcoholism.", + "abstract": "

Background

With the improvements to text mining technology and the availability of large unstructured Electronic Healthcare Records (EHR) datasets, it is now possible to extract structured information from raw text contained within EHR at reasonably high accuracy. We describe a text mining system for classifying radiologists' reports of CT and MRI brain scans, assigning labels indicating occurrence and type of stroke, as well as other observations. Our system, the Edinburgh Information Extraction for Radiology reports (EdIE-R) system, which we describe here, was developed and tested on a collection of radiology reports.The work reported in this paper is based on 1168 radiology reports from the Edinburgh Stroke Study (ESS), a hospital-based register of stroke and transient ischaemic attack patients. We manually created annotations for this data in parallel with developing the rule-based EdIE-R system to identify phenotype information related to stroke in radiology reports. This process was iterative and domain expert feedback was considered at each iteration to adapt and tune the EdIE-R text mining system which identifies entities, negation and relations between entities in each report and determines report-level labels (phenotypes).

Results

The inter-annotator agreement (IAA) for all types of annotations is high at 96.96 for entities, 96.46 for negation, 95.84 for relations and 94.02 for labels. The equivalent system scores on the blind test set are equally high at 95.49 for entities, 94.41 for negation, 98.27 for relations and 96.39 for labels for the first annotator and 96.86, 96.01, 96.53 and 92.61, respectively for the second annotator.

Conclusion

Automated reading of such EHR data at such high levels of accuracies opens up avenues for population health monitoring and audit, and can provide a resource for epidemiological studies. We are in the process of validating EdIE-R in separate larger cohorts in NHS England and Scotland. The manually annotated ESS corpus will be available for research purposes on application.", "laySummary": "", - "urls": "pdf:https://research-information.bris.ac.uk/files/382068016/Rev2_clean_InstiCVD.pdf; doi:https://doi.org/10.1016/S2352-3018(23)00233-3" + "urls": "pdf:https://jbiomedsem.biomedcentral.com/track/pdf/10.1186/s13326-019-0211-7; doi:https://doi.org/10.1186/s13326-019-0211-7; html:https://europepmc.org/articles/PMC6849161; pdf:https://europepmc.org/articles/PMC6849161?pdf=render" }, { "id": "36914875", @@ -39763,21 +39763,21 @@ "urls": "pdf:https://www.nature.com/articles/s41588-023-01314-0.pdf; doi:https://doi.org/10.1038/s41588-023-01314-0; html:https://europepmc.org/articles/PMC10011137; pdf:https://europepmc.org/articles/PMC10011137?pdf=render" }, { - "id": "31711539", - "doi": "https://doi.org/10.1186/s13326-019-0211-7", - "title": "Text mining brain imaging reports.", - "authorString": "Alex B, Grover C, Tobin R, Sudlow C, Mair G, Whiteley W.", + "id": "37923486", + "doi": "https://doi.org/10.1016/s2352-3018(23)00233-3", + "title": "Integrase strand-transfer inhibitor use and cardiovascular events in adults with HIV: an emulation of target trials in the HIV-CAUSAL Collaboration and the Antiretroviral Therapy Cohort Collaboration.", + "authorString": "Rein SM, Lodi S, Logan RW, Touloumi G, Antoniadou A, Wittkop L, Bonnet F, van Sighem A, van der Valk M, Reiss P, Klein MB, Young J, Jarrin I, d'Arminio Monforte A, Tavelli A, Meyer L, Tran L, Gill MJ, Lang R, Surial B, Haas AD, Justice AC, Rentsch CT, Phillips A, Sabin CA, Miro JM, Trickey A, Ingle SM, Sterne JAC, Hern\u00e1n MA, Antiretroviral Therapy Cohort Collaboration and the HIV-CAUSAL Collaboration.", "authorAffiliations": "", - "journalTitle": "Journal of biomedical semantics", - "pubYear": "2019", - "date": "2019-11-12", - "isOpenAccess": "Y", - "keywords": "Stroke Classification; Text Mining; Electronic Healthcare Records; Neuroimaging Reports", + "journalTitle": "The lancet. HIV", + "pubYear": "2023", + "date": "2023-11-01", + "isOpenAccess": "N", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

With the improvements to text mining technology and the availability of large unstructured Electronic Healthcare Records (EHR) datasets, it is now possible to extract structured information from raw text contained within EHR at reasonably high accuracy. We describe a text mining system for classifying radiologists' reports of CT and MRI brain scans, assigning labels indicating occurrence and type of stroke, as well as other observations. Our system, the Edinburgh Information Extraction for Radiology reports (EdIE-R) system, which we describe here, was developed and tested on a collection of radiology reports.The work reported in this paper is based on 1168 radiology reports from the Edinburgh Stroke Study (ESS), a hospital-based register of stroke and transient ischaemic attack patients. We manually created annotations for this data in parallel with developing the rule-based EdIE-R system to identify phenotype information related to stroke in radiology reports. This process was iterative and domain expert feedback was considered at each iteration to adapt and tune the EdIE-R text mining system which identifies entities, negation and relations between entities in each report and determines report-level labels (phenotypes).

Results

The inter-annotator agreement (IAA) for all types of annotations is high at 96.96 for entities, 96.46 for negation, 95.84 for relations and 94.02 for labels. The equivalent system scores on the blind test set are equally high at 95.49 for entities, 94.41 for negation, 98.27 for relations and 96.39 for labels for the first annotator and 96.86, 96.01, 96.53 and 92.61, respectively for the second annotator.

Conclusion

Automated reading of such EHR data at such high levels of accuracies opens up avenues for population health monitoring and audit, and can provide a resource for epidemiological studies. We are in the process of validating EdIE-R in separate larger cohorts in NHS England and Scotland. The manually annotated ESS corpus will be available for research purposes on application.", + "abstract": "

Background

A recent observational study suggested that the risk of cardiovascular events could be higher among antiretroviral therapy (ART)-naive individuals with HIV who receive integrase strand-transfer inhibitor (INSTI)-based ART than among those who receive other ART regimens. We aimed to emulate target trials separately in ART-naive and ART-experienced individuals with HIV to examine the effect of using INSTI-based regimens versus other ART regimens on the 4-year risk of cardiovascular events.

Methods

We used routinely recorded clinical data from 12 cohorts that collected information on cardiovascular events, BMI, and blood pressure from two international consortia of cohorts of people with HIV from Europe and North America. For the target trial in individuals who had previously never used ART (ie, ART-naive), eligibility criteria were aged 18 years or older, a detectable HIV-RNA measurement while ART-naive (>50 copies per mL), and no history of a cardiovascular event or cancer. Eligibility criteria for the target trial in those with previous use of non-INSTI-based ART (ie, ART-experienced) were the same except that individuals had to have been on at least one non-INSTI-based ART regimen and be virally suppressed (\u226450 copies per mL). We assessed eligibility for both trials for each person-month between January, 2013, and January, 2023, and assigned individuals to the treatment strategy that was compatible with their data. We estimated the standardised 4-year risks of cardiovascular events (myocardial infarction, stroke, or invasive cardiovascular procedure) via pooled logistic regression models adjusting for time and baseline covariates. In per-protocol analyses, we censored individuals if they deviated from their assigned treatment strategy for more than 2 months and weighted uncensored individuals by the inverse of their time-varying probability of remaining uncensored. The denominator of the weight was estimated via a pooled logistic model that included baseline and time-varying covariates.

Findings

The analysis in ART-naive individuals included 10\u2008767 INSTI initiators and 8292 non-initiators of INSTI. There were 43 cardiovascular events in INSTI initiators (median follow-up of 29 months; IQR 15-45) and 52 in non-initiators (39 months; 18-47): standardised 4-year risks were 0\u00b776% (95% CI 0\u00b751 to 1\u00b704) in INSTI initiators and 0\u00b775% (0\u00b754 to 0\u00b798) in non-INSTI initiators; risk ratio 1\u00b701 (0\u00b757 to 1\u00b757); risk difference 0\u00b70089% (-0\u00b743 to 0\u00b736). The analysis in ART-experienced individuals included 7875 INSTI initiators and 373\u2008965 non-initiators. There were 56 events in INSTI initiators (median follow-up 18 months; IQR 9-29) and 3103 events (808 unique) in non-INSTI initiators (26 months; 15-37) in non-initiators: standardised 4-year risks 1\u00b741% (95% CI 0\u00b788 to 2\u00b703) in INSTI initiators and 1\u00b748% (1\u00b728 to 1\u00b771) in non-initiators; risk ratio 0\u00b795 (0\u00b760 to 1\u00b736); risk difference -0\u00b7068% (-0\u00b760 to 0\u00b752).

Interpretation

We estimated that INSTI use did not result in a clinically meaningful increase of cardiovascular events in ART-naive and ART-experienced individuals with HIV.

Funding

National Institute of Allergy and Infectious Diseases and National Institute on Alcohol Abuse and Alcoholism.", "laySummary": "", - "urls": "pdf:https://jbiomedsem.biomedcentral.com/track/pdf/10.1186/s13326-019-0211-7; doi:https://doi.org/10.1186/s13326-019-0211-7; html:https://europepmc.org/articles/PMC6849161; pdf:https://europepmc.org/articles/PMC6849161?pdf=render" + "urls": "pdf:https://research-information.bris.ac.uk/files/382068016/Rev2_clean_InstiCVD.pdf; doi:https://doi.org/10.1016/S2352-3018(23)00233-3" }, { "id": "37418234", @@ -40119,6 +40119,23 @@ "laySummary": "", "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.118.002436; doi:https://doi.org/10.1161/CIRCGEN.118.002436" }, + { + "id": "34972825", + "doi": "https://doi.org/10.1038/s41564-021-01029-0", + "title": "Improving local prevalence estimates of SARS-CoV-2 infections using a causal debiasing framework.", + "authorString": "Nicholson G, Lehmann B, Padellini T, Pouwels KB, Jersakova R, Lomax J, King RE, Mallon AM, Diggle PJ, Richardson S, Blangiardo M, Holmes C.", + "authorAffiliations": "", + "journalTitle": "Nature microbiology", + "pubYear": "2022", + "date": "2021-12-31", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Global and national surveillance of SARS-CoV-2 epidemiology is mostly based on targeted schemes focused on testing individuals with symptoms. These tested groups are often unrepresentative of the wider population and exhibit test positivity rates that are biased upwards compared with the true population prevalence. Such data are routinely used to infer infection prevalence and the effective reproduction number, Rt, which affects public health policy. Here, we describe a causal framework that provides debiased fine-scale spatiotemporal estimates by combining targeted test counts with data from a randomized surveillance study in the United Kingdom called REACT. Our probabilistic model includes a bias parameter that captures the increased probability of an infected individual being tested, relative to a non-infected individual, and transforms observed test counts to debiased estimates of the true underlying local prevalence and Rt. We validated our approach on held-out REACT data over a 7-month period. Furthermore, our local estimates of Rt are indicative of 1-week- and 2-week-ahead changes in SARS-CoV-2-positive case numbers. We also observed increases in estimated local prevalence and Rt that reflect the spread of the Alpha and Delta variants. Our results illustrate how randomized surveys can augment targeted testing to improve statistical accuracy in monitoring the spread of emerging and ongoing infectious disease.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41564-021-01029-0.pdf; doi:https://doi.org/10.1038/s41564-021-01029-0; html:https://europepmc.org/articles/PMC8727294; pdf:https://europepmc.org/articles/PMC8727294?pdf=render" + }, { "id": "33248277", "doi": "https://doi.org/10.1016/j.jclinepi.2020.11.014", @@ -40137,21 +40154,21 @@ "urls": "pdf:http://www.jclinepi.com/article/S0895435620311859/pdf; doi:https://doi.org/10.1016/j.jclinepi.2020.11.014" }, { - "id": "34972825", - "doi": "https://doi.org/10.1038/s41564-021-01029-0", - "title": "Improving local prevalence estimates of SARS-CoV-2 infections using a causal debiasing framework.", - "authorString": "Nicholson G, Lehmann B, Padellini T, Pouwels KB, Jersakova R, Lomax J, King RE, Mallon AM, Diggle PJ, Richardson S, Blangiardo M, Holmes C.", + "id": "36717224", + "doi": "https://doi.org/10.1136/archdischild-2022-324548", + "title": "Parents' Experiences of Communication in Neonatal Care (PEC): a neonatal survey refined for real-time parent feedback.", + "authorString": "Sakonidou S, Kotzamanis S, Tallett A, Poots AJ, Modi N, Bell D, Gale C.", "authorAffiliations": "", - "journalTitle": "Nature microbiology", - "pubYear": "2022", - "date": "2021-12-31", + "journalTitle": "Archives of disease in childhood. Fetal and neonatal edition", + "pubYear": "2023", + "date": "2023-01-30", "isOpenAccess": "Y", - "keywords": "", + "keywords": "Intensive care units; Child Health Services; Paediatrics; Neonatology; Intensive Care Units, Neonatal", "nationalPriorities": "", "healthCategories": "", - "abstract": "Global and national surveillance of SARS-CoV-2 epidemiology is mostly based on targeted schemes focused on testing individuals with symptoms. These tested groups are often unrepresentative of the wider population and exhibit test positivity rates that are biased upwards compared with the true population prevalence. Such data are routinely used to infer infection prevalence and the effective reproduction number, Rt, which affects public health policy. Here, we describe a causal framework that provides debiased fine-scale spatiotemporal estimates by combining targeted test counts with data from a randomized surveillance study in the United Kingdom called REACT. Our probabilistic model includes a bias parameter that captures the increased probability of an infected individual being tested, relative to a non-infected individual, and transforms observed test counts to debiased estimates of the true underlying local prevalence and Rt. We validated our approach on held-out REACT data over a 7-month period. Furthermore, our local estimates of Rt are indicative of 1-week- and 2-week-ahead changes in SARS-CoV-2-positive case numbers. We also observed increases in estimated local prevalence and Rt that reflect the spread of the Alpha and Delta variants. Our results illustrate how randomized surveys can augment targeted testing to improve statistical accuracy in monitoring the spread of emerging and ongoing infectious disease.", + "abstract": "

Objective

Assessing parent experiences of neonatal services can help improve quality of care; however, there is no formally evaluated UK instrument available to assess this prospectively. Our objective was to refine an existing retrospective survey for 'real-time' feedback.

Methods

Co-led by a parent representative, we recruited a convenience sample of parents of infants in a London tertiary neonatal unit. Our steering group selected questions from the existing retrospective 61-question Picker survey (2014), added and revised questions assessing communication and parent involvement. We established face validity, ensuring questions adequately captured the topic, conducted parent cognitive interviews to evaluate parental understanding of questions,and adapted the survey in three revision cycles. We evaluated survey performance.

Results

The revised Parents' Experiences of Communication in Neonatal Care (PEC) survey contains 28 questions (10 new) focusing on communication and parent involvement. We cognitively interviewed six parents, and 67 parents completed 197 PEC surveys in the survey performance evaluation. Missing entries exceeded 5% for nine questions; we removed one and format-adjusted the rest as they had performed well during cognitive testing. There was strong inter-item correlation between two question pairs; however, all were retained as they individually assessed important concepts.

Conclusion

Revised from the original 61-question Picker survey, the 28-question PEC survey is the first UK instrument formally evaluated to assess parent experience while infants are still receiving neonatal care. Developed with parents, it focuses on communication and parent involvement, enabling continuous assessment and iterative improvement of family-centred interventions in neonatal care.", "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41564-021-01029-0.pdf; doi:https://doi.org/10.1038/s41564-021-01029-0; html:https://europepmc.org/articles/PMC8727294; pdf:https://europepmc.org/articles/PMC8727294?pdf=render" + "urls": "pdf:https://fn.bmj.com/content/fetalneonatal/early/2023/01/30/archdischild-2022-324548.full.pdf; doi:https://doi.org/10.1136/archdischild-2022-324548; html:https://europepmc.org/articles/PMC10314049; pdf:https://europepmc.org/articles/PMC10314049?pdf=render" }, { "id": "37601966", @@ -40170,23 +40187,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.xgen.2023.100361; doi:https://doi.org/10.1016/j.xgen.2023.100361; html:https://europepmc.org/articles/PMC10435379; pdf:https://europepmc.org/articles/PMC10435379?pdf=render" }, - { - "id": "36717224", - "doi": "https://doi.org/10.1136/archdischild-2022-324548", - "title": "Parents' Experiences of Communication in Neonatal Care (PEC): a neonatal survey refined for real-time parent feedback.", - "authorString": "Sakonidou S, Kotzamanis S, Tallett A, Poots AJ, Modi N, Bell D, Gale C.", - "authorAffiliations": "", - "journalTitle": "Archives of disease in childhood. Fetal and neonatal edition", - "pubYear": "2023", - "date": "2023-01-30", - "isOpenAccess": "Y", - "keywords": "Intensive care units; Child Health Services; Paediatrics; Neonatology; Intensive Care Units, Neonatal", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

Assessing parent experiences of neonatal services can help improve quality of care; however, there is no formally evaluated UK instrument available to assess this prospectively. Our objective was to refine an existing retrospective survey for 'real-time' feedback.

Methods

Co-led by a parent representative, we recruited a convenience sample of parents of infants in a London tertiary neonatal unit. Our steering group selected questions from the existing retrospective 61-question Picker survey (2014), added and revised questions assessing communication and parent involvement. We established face validity, ensuring questions adequately captured the topic, conducted parent cognitive interviews to evaluate parental understanding of questions,and adapted the survey in three revision cycles. We evaluated survey performance.

Results

The revised Parents' Experiences of Communication in Neonatal Care (PEC) survey contains 28 questions (10 new) focusing on communication and parent involvement. We cognitively interviewed six parents, and 67 parents completed 197 PEC surveys in the survey performance evaluation. Missing entries exceeded 5% for nine questions; we removed one and format-adjusted the rest as they had performed well during cognitive testing. There was strong inter-item correlation between two question pairs; however, all were retained as they individually assessed important concepts.

Conclusion

Revised from the original 61-question Picker survey, the 28-question PEC survey is the first UK instrument formally evaluated to assess parent experience while infants are still receiving neonatal care. Developed with parents, it focuses on communication and parent involvement, enabling continuous assessment and iterative improvement of family-centred interventions in neonatal care.", - "laySummary": "", - "urls": "pdf:https://fn.bmj.com/content/fetalneonatal/early/2023/01/30/archdischild-2022-324548.full.pdf; doi:https://doi.org/10.1136/archdischild-2022-324548; html:https://europepmc.org/articles/PMC10314049; pdf:https://europepmc.org/articles/PMC10314049?pdf=render" - }, { "id": "32435697", "doi": "https://doi.org/10.1038/s41746-020-0267-x", @@ -40255,23 +40255,6 @@ "laySummary": "", "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00127-022-02221-1.pdf; doi:https://doi.org/10.1007/s00127-022-02221-1; html:https://europepmc.org/articles/PMC9477900; pdf:https://europepmc.org/articles/PMC9477900?pdf=render" }, - { - "id": "35876478", - "doi": "https://doi.org/10.3201/eid2808.211787", - "title": "Lack of Evidence for Ribavirin Treatment of Lassa Fever in Systematic Review of Published and Unpublished Studies1.", - "authorString": "Cheng HY, French CE, Salam AP, Dawson S, McAleenan A, McGuinness LA, Savovi\u0107 J, Horby PW, Sterne JAC.", - "authorAffiliations": "", - "journalTitle": "Emerging infectious diseases", - "pubYear": "2022", - "date": "2022-08-01", - "isOpenAccess": "Y", - "keywords": "Viruses; Bias; Ribavirin; Systematic review; Observational Study; Lassa Fever", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Ribavirin has been used widely to treat Lassa fever in West Africa since the 1980s. However, few studies have systematically appraised the evidence for its use. We conducted a systematic review of published and unpublished literature retrieved from electronic databases and gray literature from inception to March 8, 2022. We identified 13 studies of the comparative effectiveness of ribavirin versus no ribavirin treatment on mortality outcomes, including unpublished data from a study in Sierra Leone provided through a US Freedom of Information Act request. Although ribavirin was associated with decreased mortality rates, results of these studies were at critical or serious risk for bias when appraised using the ROBINS-I tool. Important risks for bias related to lack of control for confounders, immortal time bias, and missing outcome data. Robust evidence supporting the use of ribavirin in Lassa fever is lacking. Well-conducted clinical trials to elucidate the effectiveness of ribavirin for Lassa fever are needed.", - "laySummary": "", - "urls": "pdf:https://wwwnc.cdc.gov/eid/article/28/8/pdfs/21-1787.pdf; doi:https://doi.org/10.3201/eid2808.211787; html:https://europepmc.org/articles/PMC9328902; pdf:https://europepmc.org/articles/PMC9328902?pdf=render" - }, { "id": "34151270", "doi": "https://doi.org/10.1136/bmjno-2021-000133", @@ -40290,21 +40273,21 @@ "urls": "pdf:https://neurologyopen.bmj.com/content/bmjno/3/1/e000133.full.pdf; doi:https://doi.org/10.1136/bmjno-2021-000133; html:https://europepmc.org/articles/PMC8183200; pdf:https://europepmc.org/articles/PMC8183200?pdf=render" }, { - "id": "38432242", - "doi": "https://doi.org/10.1016/s2352-3026(24)00030-9", - "title": "Haemoglobin thresholds to define anaemia from age 6 months to 65 years: estimates from international data sources.", - "authorString": "Braat S, Fielding KL, Han J, Jackson VE, Zaloumis S, Xu JXH, Moir-Meyer G, Blaauwendraad SM, Jaddoe VWV, Gaillard R, Parkin PC, Borkhoff CM, Keown-Stoneman CDG, Birken CS, Maguire JL, Genes & Health Research Team, Bahlo M, Davidson EM, Pasricha SR.", + "id": "35876478", + "doi": "https://doi.org/10.3201/eid2808.211787", + "title": "Lack of Evidence for Ribavirin Treatment of Lassa Fever in Systematic Review of Published and Unpublished Studies1.", + "authorString": "Cheng HY, French CE, Salam AP, Dawson S, McAleenan A, McGuinness LA, Savovi\u0107 J, Horby PW, Sterne JAC.", "authorAffiliations": "", - "journalTitle": "The Lancet. Haematology", - "pubYear": "2024", - "date": "2024-02-29", + "journalTitle": "Emerging infectious diseases", + "pubYear": "2022", + "date": "2022-08-01", "isOpenAccess": "Y", - "keywords": "", + "keywords": "Viruses; Bias; Ribavirin; Systematic review; Observational Study; Lassa Fever", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Detection of anaemia is crucial for clinical medicine and public health. Current WHO anaemia definitions are based on statistical thresholds (fifth centiles) set more than 50 years ago. We sought to establish evidence for the statistical haemoglobin thresholds for anaemia that can be applied globally and inform WHO and clinical guidelines.

Methods

In this analysis we identified international data sources from populations in the USA, England, Australia, China, the Netherlands, Canada, Ecuador, and Bangladesh with sufficient clinical and laboratory information collected between 1998 and 2020 to obtain a healthy reference sample. Individuals with clinical or biochemical evidence of a condition that could reduce haemoglobin concentrations were excluded. We estimated haemoglobin thresholds (ie, 5th centiles) for children aged 6-23 months, 24-59 months, 5-11 years, and 12-17 years, and adults aged 18-65 years (including during pregnancy) for individual datasets and pooled across data sources. We also collated findings from three large-scale genetic studies to summarise genetic variants affecting haemoglobin concentrations in different ancestral populations.

Findings

We identified eight data sources comprising 18 individual datasets that were eligible for inclusion in the analysis. In pooled analyses, the haemoglobin fifth centile was 104\u00b74 g/L (90% CI 103\u00b75-105\u00b73) in 924 children aged 6-23 months, 110\u00b72 g/L (109\u00b75-110\u00b79) in 1874 children aged 24-59 months, and 114\u00b74 g/L (113\u00b76-115\u00b72) in 1839 children aged 5-11 years. Values diverged by sex in adolescents and adults. In pooled analyses, the fifth centile was 122\u00b72 g/L (90% CI 121\u00b73-123\u00b71) in 1741 female adolescents aged 12-17 years and 128\u00b72 g/L (126\u00b74-130\u00b70) in 1103 male adolescents aged 12-17 years. In pooled analyses of adults aged 18-65 years, the fifth centile was 119\u00b77 g/L (90% CI 119\u00b71-120\u00b73) in 3640 non-pregnant females and 134\u00b79 g/L (134\u00b72-135\u00b76) in 2377 males. Fifth centiles in pregnancy were 110\u00b73 g/L (90% CI 109\u00b75-111\u00b70) in the first trimester (n=772) and 105\u00b79 g/L (104\u00b70-107\u00b77) in the second trimester (n=111), with insufficient data for analysis in the third trimester. There were insufficient data for adults older than 65 years. We did not identify ancestry-specific high prevalence of non-clinically relevant genetic variants that influence haemoglobin concentrations.

Interpretation

Our results enable global harmonisation of clinical and public health haemoglobin thresholds for diagnosis of anaemia. Haemoglobin thresholds are similar between sexes until adolescence, after which males have higher thresholds than females. We did not find any evidence that thresholds should differ between people of differering ancestries.

Funding

World Health Organization and the Bill & Melinda Gates Foundation.", + "abstract": "Ribavirin has been used widely to treat Lassa fever in West Africa since the 1980s. However, few studies have systematically appraised the evidence for its use. We conducted a systematic review of published and unpublished literature retrieved from electronic databases and gray literature from inception to March 8, 2022. We identified 13 studies of the comparative effectiveness of ribavirin versus no ribavirin treatment on mortality outcomes, including unpublished data from a study in Sierra Leone provided through a US Freedom of Information Act request. Although ribavirin was associated with decreased mortality rates, results of these studies were at critical or serious risk for bias when appraised using the ROBINS-I tool. Important risks for bias related to lack of control for confounders, immortal time bias, and missing outcome data. Robust evidence supporting the use of ribavirin in Lassa fever is lacking. Well-conducted clinical trials to elucidate the effectiveness of ribavirin for Lassa fever are needed.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S2352-3026(24)00030-9; html:https://europepmc.org/articles/PMC10983828; pdf:https://europepmc.org/articles/PMC10983828?pdf=render" + "urls": "pdf:https://wwwnc.cdc.gov/eid/article/28/8/pdfs/21-1787.pdf; doi:https://doi.org/10.3201/eid2808.211787; html:https://europepmc.org/articles/PMC9328902; pdf:https://europepmc.org/articles/PMC9328902?pdf=render" }, { "id": "31160290", @@ -40323,6 +40306,23 @@ "laySummary": "", "urls": "pdf:https://aac.asm.org/content/aac/63/8/e00400-19.full.pdf; doi:https://doi.org/10.1128/AAC.00400-19; html:https://europepmc.org/articles/PMC6658746; pdf:https://europepmc.org/articles/PMC6658746?pdf=render; doi:https://doi.org/10.1128/aac.00400-19" }, + { + "id": "38432242", + "doi": "https://doi.org/10.1016/s2352-3026(24)00030-9", + "title": "Haemoglobin thresholds to define anaemia from age 6 months to 65 years: estimates from international data sources.", + "authorString": "Braat S, Fielding KL, Han J, Jackson VE, Zaloumis S, Xu JXH, Moir-Meyer G, Blaauwendraad SM, Jaddoe VWV, Gaillard R, Parkin PC, Borkhoff CM, Keown-Stoneman CDG, Birken CS, Maguire JL, Genes & Health Research Team, Bahlo M, Davidson EM, Pasricha SR.", + "authorAffiliations": "", + "journalTitle": "The Lancet. Haematology", + "pubYear": "2024", + "date": "2024-02-29", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Detection of anaemia is crucial for clinical medicine and public health. Current WHO anaemia definitions are based on statistical thresholds (fifth centiles) set more than 50 years ago. We sought to establish evidence for the statistical haemoglobin thresholds for anaemia that can be applied globally and inform WHO and clinical guidelines.

Methods

In this analysis we identified international data sources from populations in the USA, England, Australia, China, the Netherlands, Canada, Ecuador, and Bangladesh with sufficient clinical and laboratory information collected between 1998 and 2020 to obtain a healthy reference sample. Individuals with clinical or biochemical evidence of a condition that could reduce haemoglobin concentrations were excluded. We estimated haemoglobin thresholds (ie, 5th centiles) for children aged 6-23 months, 24-59 months, 5-11 years, and 12-17 years, and adults aged 18-65 years (including during pregnancy) for individual datasets and pooled across data sources. We also collated findings from three large-scale genetic studies to summarise genetic variants affecting haemoglobin concentrations in different ancestral populations.

Findings

We identified eight data sources comprising 18 individual datasets that were eligible for inclusion in the analysis. In pooled analyses, the haemoglobin fifth centile was 104\u00b74 g/L (90% CI 103\u00b75-105\u00b73) in 924 children aged 6-23 months, 110\u00b72 g/L (109\u00b75-110\u00b79) in 1874 children aged 24-59 months, and 114\u00b74 g/L (113\u00b76-115\u00b72) in 1839 children aged 5-11 years. Values diverged by sex in adolescents and adults. In pooled analyses, the fifth centile was 122\u00b72 g/L (90% CI 121\u00b73-123\u00b71) in 1741 female adolescents aged 12-17 years and 128\u00b72 g/L (126\u00b74-130\u00b70) in 1103 male adolescents aged 12-17 years. In pooled analyses of adults aged 18-65 years, the fifth centile was 119\u00b77 g/L (90% CI 119\u00b71-120\u00b73) in 3640 non-pregnant females and 134\u00b79 g/L (134\u00b72-135\u00b76) in 2377 males. Fifth centiles in pregnancy were 110\u00b73 g/L (90% CI 109\u00b75-111\u00b70) in the first trimester (n=772) and 105\u00b79 g/L (104\u00b70-107\u00b77) in the second trimester (n=111), with insufficient data for analysis in the third trimester. There were insufficient data for adults older than 65 years. We did not identify ancestry-specific high prevalence of non-clinically relevant genetic variants that influence haemoglobin concentrations.

Interpretation

Our results enable global harmonisation of clinical and public health haemoglobin thresholds for diagnosis of anaemia. Haemoglobin thresholds are similar between sexes until adolescence, after which males have higher thresholds than females. We did not find any evidence that thresholds should differ between people of differering ancestries.

Funding

World Health Organization and the Bill & Melinda Gates Foundation.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/S2352-3026(24)00030-9; html:https://europepmc.org/articles/PMC10983828; pdf:https://europepmc.org/articles/PMC10983828?pdf=render" + }, { "id": "36180121", "doi": "https://doi.org/10.1136/bmjopen-2021-057712", @@ -40561,23 +40561,6 @@ "laySummary": "", "urls": "pdf:https://ora.ox.ac.uk/objects/uuid:3a84eaef-5966-4690-b5d3-658070577382/files/s3197xm84x; doi:https://doi.org/10.1038/s41593-021-00826-4; html:https://europepmc.org/articles/PMC7610742; pdf:https://europepmc.org/articles/PMC7610742?pdf=render" }, - { - "id": "31350032", - "doi": "https://doi.org/10.1016/j.burns.2019.07.003", - "title": "Epidemiology of burn-related fatalities in Australia and New Zealand, 2009-2015.", - "authorString": "McInnes JA, Cleland HJ, Cameron PA, Darton A, Tracy LM, Wood FM, Singer Y, Gabbe BJ.", - "authorAffiliations": "", - "journalTitle": "Burns : journal of the International Society for Burn Injuries", - "pubYear": "2019", - "date": "2019-07-24", - "isOpenAccess": "N", - "keywords": "Burns; Mortality; Australia; New Zealand; epidemiology; Fatality", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Knowledge of the epidemiology of burn-related fatalities is limited, with most previous studies based on hospital and burn centre data only.

Aims

To describe the epidemiological characteristics of all burn-related fatalities in Australia and New Zealand, and to identify any trends in burn-related fatality incidence over the study period.

Methods

Data from the National Coronial Information System, including data for pre-hospital and in-hospital burn-related fatality cases, was used to examine the characteristics of burn-related fatalities occurring in Australia and New Zealand from 2009 to 2015. Burn-related fatality rates per 100,000 population were estimated, and incidence trends assessed using Poisson regression analysis.

Results

Of the 310 burn-related fatalities that occurred in Australia and New Zealand, 2009-2015, 41% occurred in a pre-hospital setting. Overall, most burn-related fatality cases were fire related, occurred at home, and were of people aged 41-80\u2009years. One quarter of all burn-related fatalities were a result of intentional self-harm. The population incidence of all burn-related fatalities combined, and for NSW, decreased over the study period.

Conclusions

This study has identified the importance of examining all burn-related fatalities. If this is not done, vulnerable population subgroups will be missed and prevention efforts poorly targeted.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.burns.2019.07.003" - }, { "id": "32095773", "doi": "https://doi.org/10.1159/000503957", @@ -40595,6 +40578,23 @@ "laySummary": "The authors of this publication have developed a set of guidelines for planning, running and writing up research that uses mobile technologies in clinical trials. The guidelines they have put together should make it easer for patient experience to be recorded in clinical trials.", "urls": "pdf:https://www.karger.com/Article/Pdf/503957; doi:https://doi.org/10.1159/000503957; html:https://europepmc.org/articles/PMC7011727; pdf:https://europepmc.org/articles/PMC7011727?pdf=render; doi:https://doi.org/10.1159/000503957" }, + { + "id": "31350032", + "doi": "https://doi.org/10.1016/j.burns.2019.07.003", + "title": "Epidemiology of burn-related fatalities in Australia and New Zealand, 2009-2015.", + "authorString": "McInnes JA, Cleland HJ, Cameron PA, Darton A, Tracy LM, Wood FM, Singer Y, Gabbe BJ.", + "authorAffiliations": "", + "journalTitle": "Burns : journal of the International Society for Burn Injuries", + "pubYear": "2019", + "date": "2019-07-24", + "isOpenAccess": "N", + "keywords": "Burns; Mortality; Australia; New Zealand; epidemiology; Fatality", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Knowledge of the epidemiology of burn-related fatalities is limited, with most previous studies based on hospital and burn centre data only.

Aims

To describe the epidemiological characteristics of all burn-related fatalities in Australia and New Zealand, and to identify any trends in burn-related fatality incidence over the study period.

Methods

Data from the National Coronial Information System, including data for pre-hospital and in-hospital burn-related fatality cases, was used to examine the characteristics of burn-related fatalities occurring in Australia and New Zealand from 2009 to 2015. Burn-related fatality rates per 100,000 population were estimated, and incidence trends assessed using Poisson regression analysis.

Results

Of the 310 burn-related fatalities that occurred in Australia and New Zealand, 2009-2015, 41% occurred in a pre-hospital setting. Overall, most burn-related fatality cases were fire related, occurred at home, and were of people aged 41-80\u2009years. One quarter of all burn-related fatalities were a result of intentional self-harm. The population incidence of all burn-related fatalities combined, and for NSW, decreased over the study period.

Conclusions

This study has identified the importance of examining all burn-related fatalities. If this is not done, vulnerable population subgroups will be missed and prevention efforts poorly targeted.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.burns.2019.07.003" + }, { "id": "32709645", "doi": "https://doi.org/10.1136/bmjopen-2019-035968", @@ -40935,23 +40935,6 @@ "laySummary": "", "urls": "pdf:https://research-information.bris.ac.uk/ws/files/338319463/Movement_Disorders_2022_Reid_MED27_SLC6A7_and_MPPE1_Variants_in_a_Complex_Neurodevelopmental_Disorder_with_Severe.pdf; doi:https://doi.org/10.1002/mds.29147; html:https://europepmc.org/articles/PMC9796674; pdf:https://europepmc.org/articles/PMC9796674?pdf=render" }, - { - "id": "33185739", - "doi": "https://doi.org/10.1007/s00395-020-00828-6", - "title": "Functional investigation of the coronary artery disease gene SVEP1.", - "authorString": "Winkler MJ, M\u00fcller P, Sharifi AM, Wobst J, Winter H, Mokry M, Ma L, van der Laan SW, Pang S, Miritsch B, Hinterdobler J, Werner J, Stiller B, G\u00fcldener U, Webb TR, Asselbergs FW, Bj\u00f6rkegren JLM, Maegdefessel L, Schunkert H, Sager HB, Kessler T.", - "authorAffiliations": "", - "journalTitle": "Basic research in cardiology", - "pubYear": "2020", - "date": "2020-11-13", - "isOpenAccess": "Y", - "keywords": "Genetics; Atherosclerosis; coronary artery disease; Svep1", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "A missense variant of the sushi, von Willebrand factor type A, EGF and pentraxin domain containing protein 1 (SVEP1) is genome-wide significantly associated with coronary artery disease. The mechanisms how SVEP1 impacts atherosclerosis are not known. We found endothelial cells (EC) and vascular smooth muscle cells to represent the major cellular source of SVEP1 in plaques. Plaques were larger in atherosclerosis-prone Svep1 haploinsufficient (ApoE-/-Svep1+/-) compared to Svep1 wild-type mice (ApoE-/-Svep1+/+) and ApoE-/-Svep1+/- mice displayed elevated plaque neutrophil, Ly6Chigh monocyte, and macrophage numbers. We assessed how leukocytes accumulated more inside plaques in ApoE-/-Svep1+/- mice and found enhanced leukocyte recruitment from blood into plaques. In vitro, we examined how SVEP1 deficiency promotes leukocyte recruitment and found elevated expression of the leukocyte attractant chemokine (C-X-C motif) ligand 1 (CXCL1) in EC after incubation with missense compared to wild-type SVEP1. Increasing wild-type SVEP1 levels silenced endothelial CXCL1 release. In line, plasma Cxcl1 levels were elevated in ApoE-/-Svep1+/- mice. Our studies reveal an atheroprotective role of SVEP1. Deficiency of wild-type Svep1 increased endothelial CXCL1 expression leading to enhanced recruitment of proinflammatory leukocytes from blood to plaque. Consequently, elevated vascular inflammation resulted in enhanced plaque progression in Svep1 deficiency.", - "laySummary": "", - "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00395-020-00828-6.pdf; doi:https://doi.org/10.1007/s00395-020-00828-6; html:https://europepmc.org/articles/PMC7666586; pdf:https://europepmc.org/articles/PMC7666586?pdf=render" - }, { "id": "34563995", "doi": "https://doi.org/10.1016/j.schres.2021.09.006", @@ -40969,6 +40952,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.schres.2021.09.006; doi:https://doi.org/10.1016/j.schres.2021.09.006; html:https://europepmc.org/articles/PMC8653908" }, + { + "id": "33185739", + "doi": "https://doi.org/10.1007/s00395-020-00828-6", + "title": "Functional investigation of the coronary artery disease gene SVEP1.", + "authorString": "Winkler MJ, M\u00fcller P, Sharifi AM, Wobst J, Winter H, Mokry M, Ma L, van der Laan SW, Pang S, Miritsch B, Hinterdobler J, Werner J, Stiller B, G\u00fcldener U, Webb TR, Asselbergs FW, Bj\u00f6rkegren JLM, Maegdefessel L, Schunkert H, Sager HB, Kessler T.", + "authorAffiliations": "", + "journalTitle": "Basic research in cardiology", + "pubYear": "2020", + "date": "2020-11-13", + "isOpenAccess": "Y", + "keywords": "Genetics; Atherosclerosis; coronary artery disease; Svep1", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "A missense variant of the sushi, von Willebrand factor type A, EGF and pentraxin domain containing protein 1 (SVEP1) is genome-wide significantly associated with coronary artery disease. The mechanisms how SVEP1 impacts atherosclerosis are not known. We found endothelial cells (EC) and vascular smooth muscle cells to represent the major cellular source of SVEP1 in plaques. Plaques were larger in atherosclerosis-prone Svep1 haploinsufficient (ApoE-/-Svep1+/-) compared to Svep1 wild-type mice (ApoE-/-Svep1+/+) and ApoE-/-Svep1+/- mice displayed elevated plaque neutrophil, Ly6Chigh monocyte, and macrophage numbers. We assessed how leukocytes accumulated more inside plaques in ApoE-/-Svep1+/- mice and found enhanced leukocyte recruitment from blood into plaques. In vitro, we examined how SVEP1 deficiency promotes leukocyte recruitment and found elevated expression of the leukocyte attractant chemokine (C-X-C motif) ligand 1 (CXCL1) in EC after incubation with missense compared to wild-type SVEP1. Increasing wild-type SVEP1 levels silenced endothelial CXCL1 release. In line, plasma Cxcl1 levels were elevated in ApoE-/-Svep1+/- mice. Our studies reveal an atheroprotective role of SVEP1. Deficiency of wild-type Svep1 increased endothelial CXCL1 expression leading to enhanced recruitment of proinflammatory leukocytes from blood to plaque. Consequently, elevated vascular inflammation resulted in enhanced plaque progression in Svep1 deficiency.", + "laySummary": "", + "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00395-020-00828-6.pdf; doi:https://doi.org/10.1007/s00395-020-00828-6; html:https://europepmc.org/articles/PMC7666586; pdf:https://europepmc.org/articles/PMC7666586?pdf=render" + }, { "id": "36810190", "doi": "https://doi.org/10.1136/bmjebm-2023-112253", @@ -41003,23 +41003,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41467-019-12682-9.pdf; doi:https://doi.org/10.1038/s41467-019-12682-9; html:https://europepmc.org/articles/PMC6805929; pdf:https://europepmc.org/articles/PMC6805929?pdf=render" }, - { - "id": "36347531", - "doi": "https://doi.org/10.1136/bmj-2022-070918", - "title": "Development and external validation of a risk prediction model for falls in patients with an indication for antihypertensive treatment: retrospective cohort study.", - "authorString": "Archer L, Koshiaris C, Lay-Flurrie S, Snell KIE, Riley RD, Stevens R, Banerjee A, Usher-Smith JA, Clegg A, Payne RA, Hobbs FDR, McManus RJ, Sheppard JP, STRAtifying Treatments In the multi-morbid Frail elderlY (STRATIFY) investigators.", - "authorAffiliations": "", - "journalTitle": "BMJ (Clinical research ed.)", - "pubYear": "2022", - "date": "2022-11-08", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

To develop and externally validate the STRAtifying Treatments In the multi-morbid Frail elderlY (STRATIFY)-Falls clinical prediction model to identify the risk of hospital admission or death from a fall in patients with an indication for antihypertensive treatment.

Design

Retrospective cohort study.

Setting

Primary care data from electronic health records contained within the UK Clinical Practice Research Datalink (CPRD).

Participants

Patients aged 40 years or older with at least one blood pressure measurement between 130 mm Hg and 179 mm Hg.

Main outcome measure

First serious fall, defined as hospital admission or death with a primary diagnosis of a fall within 10 years of the index date (12 months after cohort entry). Model development was conducted using a Fine-Gray approach in data from CPRD GOLD, accounting for the competing risk of death from other causes, with subsequent recalibration at one, five, and 10 years using pseudo values. External validation was conducted using data from CPRD Aurum, with performance assessed through calibration curves and the observed to expected ratio, C statistic, and D statistic, pooled across general practices, and clinical utility using decision curve analysis at thresholds around 10%.

Results

Analysis included 1\u2009772\u2009600 patients (experiencing 62\u2009691 serious falls) from CPRD GOLD used in model development, and 3\u2009805\u2009366 (experiencing 206\u2009956 serious falls) from CPRD Aurum in the external validation. The final model consisted of 24 predictors, including age, sex, ethnicity, alcohol consumption, living in an area of high social deprivation, a history of falls, multiple sclerosis, and prescriptions of antihypertensives, antidepressants, hypnotics, and anxiolytics. Upon external validation, the recalibrated model showed good discrimination, with pooled C statistics of 0.833 (95% confidence interval 0.831 to 0.835) and 0.843 (0.841 to 0.844) at five and 10 years, respectively. Original model calibration was poor on visual inspection and although this was improved with recalibration, under-prediction of risk remained (observed to expected ratio at 10 years 1.839, 95% confidence interval 1.811 to 1.865). Nevertheless, decision curve analysis suggests potential clinical utility, with net benefit larger than other strategies.

Conclusions

This prediction model uses commonly recorded clinical characteristics and distinguishes well between patients at high and low risk of falls in the next 1-10 years. Although miscalibration was evident on external validation, the model still had potential clinical utility around risk thresholds of 10% and so could be useful in routine clinical practice to help identify those at high risk of falls who might benefit from closer monitoring or early intervention to prevent future falls. Further studies are needed to explore the appropriate thresholds that maximise the model's clinical utility and cost effectiveness.", - "laySummary": "", - "urls": "pdf:https://www.bmj.com/content/bmj/379/bmj-2022-070918.full.pdf; doi:https://doi.org/10.1136/bmj-2022-070918; html:https://europepmc.org/articles/PMC9641577" - }, { "id": "35411997", "doi": "https://doi.org/10.1111/tmi.13752", @@ -41037,6 +41020,23 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/tmi.13752; doi:https://doi.org/10.1111/tmi.13752; html:https://europepmc.org/articles/PMC9115442; pdf:https://europepmc.org/articles/PMC9115442?pdf=render" }, + { + "id": "36347531", + "doi": "https://doi.org/10.1136/bmj-2022-070918", + "title": "Development and external validation of a risk prediction model for falls in patients with an indication for antihypertensive treatment: retrospective cohort study.", + "authorString": "Archer L, Koshiaris C, Lay-Flurrie S, Snell KIE, Riley RD, Stevens R, Banerjee A, Usher-Smith JA, Clegg A, Payne RA, Hobbs FDR, McManus RJ, Sheppard JP, STRAtifying Treatments In the multi-morbid Frail elderlY (STRATIFY) investigators.", + "authorAffiliations": "", + "journalTitle": "BMJ (Clinical research ed.)", + "pubYear": "2022", + "date": "2022-11-08", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

To develop and externally validate the STRAtifying Treatments In the multi-morbid Frail elderlY (STRATIFY)-Falls clinical prediction model to identify the risk of hospital admission or death from a fall in patients with an indication for antihypertensive treatment.

Design

Retrospective cohort study.

Setting

Primary care data from electronic health records contained within the UK Clinical Practice Research Datalink (CPRD).

Participants

Patients aged 40 years or older with at least one blood pressure measurement between 130 mm Hg and 179 mm Hg.

Main outcome measure

First serious fall, defined as hospital admission or death with a primary diagnosis of a fall within 10 years of the index date (12 months after cohort entry). Model development was conducted using a Fine-Gray approach in data from CPRD GOLD, accounting for the competing risk of death from other causes, with subsequent recalibration at one, five, and 10 years using pseudo values. External validation was conducted using data from CPRD Aurum, with performance assessed through calibration curves and the observed to expected ratio, C statistic, and D statistic, pooled across general practices, and clinical utility using decision curve analysis at thresholds around 10%.

Results

Analysis included 1\u2009772\u2009600 patients (experiencing 62\u2009691 serious falls) from CPRD GOLD used in model development, and 3\u2009805\u2009366 (experiencing 206\u2009956 serious falls) from CPRD Aurum in the external validation. The final model consisted of 24 predictors, including age, sex, ethnicity, alcohol consumption, living in an area of high social deprivation, a history of falls, multiple sclerosis, and prescriptions of antihypertensives, antidepressants, hypnotics, and anxiolytics. Upon external validation, the recalibrated model showed good discrimination, with pooled C statistics of 0.833 (95% confidence interval 0.831 to 0.835) and 0.843 (0.841 to 0.844) at five and 10 years, respectively. Original model calibration was poor on visual inspection and although this was improved with recalibration, under-prediction of risk remained (observed to expected ratio at 10 years 1.839, 95% confidence interval 1.811 to 1.865). Nevertheless, decision curve analysis suggests potential clinical utility, with net benefit larger than other strategies.

Conclusions

This prediction model uses commonly recorded clinical characteristics and distinguishes well between patients at high and low risk of falls in the next 1-10 years. Although miscalibration was evident on external validation, the model still had potential clinical utility around risk thresholds of 10% and so could be useful in routine clinical practice to help identify those at high risk of falls who might benefit from closer monitoring or early intervention to prevent future falls. Further studies are needed to explore the appropriate thresholds that maximise the model's clinical utility and cost effectiveness.", + "laySummary": "", + "urls": "pdf:https://www.bmj.com/content/bmj/379/bmj-2022-070918.full.pdf; doi:https://doi.org/10.1136/bmj-2022-070918; html:https://europepmc.org/articles/PMC9641577" + }, { "id": "31822727", "doi": "https://doi.org/10.1038/s41598-019-55098-7", @@ -41139,23 +41139,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41467-021-25703-3.pdf; doi:https://doi.org/10.1038/s41467-021-25703-3; html:https://europepmc.org/articles/PMC8463530; pdf:https://europepmc.org/articles/PMC8463530?pdf=render" }, - { - "id": "37414900", - "doi": "https://doi.org/10.1038/s41591-023-02429-x", - "title": "A multi-ancestry polygenic risk score improves risk prediction for coronary artery disease.", - "authorString": "Patel AP, Wang M, Ruan Y, Koyama S, Clarke SL, Yang X, Tcheandjieu C, Agrawal S, Fahed AC, Ellinor PT, Genes & Health Research Team; the Million Veteran Program, Tsao PS, Sun YV, Cho K, Wilson PWF, Assimes TL, van Heel DA, Butterworth AS, Aragam KG, Natarajan P, Khera AV.", - "authorAffiliations": "", - "journalTitle": "Nature medicine", - "pubYear": "2023", - "date": "2023-07-06", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Identification of individuals at highest risk of coronary artery disease (CAD)-ideally before onset-remains an important public health need. Prior studies have developed genome-wide polygenic scores to enable risk stratification, reflecting the substantial inherited component to CAD risk. Here we develop a new and significantly improved polygenic score for CAD, termed GPSMult, that incorporates genome-wide association data across five ancestries for CAD (>269,000 cases and >1,178,000 controls) and ten CAD risk factors. GPSMult strongly associated with prevalent CAD (odds ratio per standard deviation 2.14, 95% confidence interval 2.10-2.19, P\u2009<\u20090.001) in UK Biobank participants of European ancestry, identifying 20.0% of the population with 3-fold increased risk and conversely 13.9% with 3-fold decreased risk as compared with those in the middle quintile. GPSMult was also associated with incident CAD events (hazard ratio per standard deviation 1.73, 95% confidence interval 1.70-1.76, P\u2009<\u20090.001), identifying 3% of healthy individuals with risk of future CAD events equivalent to those with existing disease and significantly improving risk discrimination and reclassification. Across multiethnic, external validation datasets inclusive of 33,096, 124,467, 16,433 and 16,874 participants of African, European, Hispanic and South Asian ancestry, respectively, GPSMult demonstrated increased strength of associations across all ancestries and outperformed all available previously published CAD polygenic scores. These data contribute a new GPSMult for CAD to the field and provide a generalizable framework for how large-scale integration of genetic association data for CAD and related traits from diverse populations can meaningfully improve polygenic risk prediction.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41591-023-02429-x.pdf; doi:https://doi.org/10.1038/s41591-023-02429-x; html:https://europepmc.org/articles/PMC10353935; pdf:https://europepmc.org/articles/PMC10353935?pdf=render" - }, { "id": "37645200", "doi": "https://doi.org/10.12688/openreseurope.13860.2", @@ -41173,6 +41156,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.12688/openreseurope.13860.2; html:https://europepmc.org/articles/PMC10445835; pdf:https://europepmc.org/articles/PMC10445835?pdf=render" }, + { + "id": "37414900", + "doi": "https://doi.org/10.1038/s41591-023-02429-x", + "title": "A multi-ancestry polygenic risk score improves risk prediction for coronary artery disease.", + "authorString": "Patel AP, Wang M, Ruan Y, Koyama S, Clarke SL, Yang X, Tcheandjieu C, Agrawal S, Fahed AC, Ellinor PT, Genes & Health Research Team; the Million Veteran Program, Tsao PS, Sun YV, Cho K, Wilson PWF, Assimes TL, van Heel DA, Butterworth AS, Aragam KG, Natarajan P, Khera AV.", + "authorAffiliations": "", + "journalTitle": "Nature medicine", + "pubYear": "2023", + "date": "2023-07-06", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Identification of individuals at highest risk of coronary artery disease (CAD)-ideally before onset-remains an important public health need. Prior studies have developed genome-wide polygenic scores to enable risk stratification, reflecting the substantial inherited component to CAD risk. Here we develop a new and significantly improved polygenic score for CAD, termed GPSMult, that incorporates genome-wide association data across five ancestries for CAD (>269,000 cases and >1,178,000 controls) and ten CAD risk factors. GPSMult strongly associated with prevalent CAD (odds ratio per standard deviation 2.14, 95% confidence interval 2.10-2.19, P\u2009<\u20090.001) in UK Biobank participants of European ancestry, identifying 20.0% of the population with 3-fold increased risk and conversely 13.9% with 3-fold decreased risk as compared with those in the middle quintile. GPSMult was also associated with incident CAD events (hazard ratio per standard deviation 1.73, 95% confidence interval 1.70-1.76, P\u2009<\u20090.001), identifying 3% of healthy individuals with risk of future CAD events equivalent to those with existing disease and significantly improving risk discrimination and reclassification. Across multiethnic, external validation datasets inclusive of 33,096, 124,467, 16,433 and 16,874 participants of African, European, Hispanic and South Asian ancestry, respectively, GPSMult demonstrated increased strength of associations across all ancestries and outperformed all available previously published CAD polygenic scores. These data contribute a new GPSMult for CAD to the field and provide a generalizable framework for how large-scale integration of genetic association data for CAD and related traits from diverse populations can meaningfully improve polygenic risk prediction.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41591-023-02429-x.pdf; doi:https://doi.org/10.1038/s41591-023-02429-x; html:https://europepmc.org/articles/PMC10353935; pdf:https://europepmc.org/articles/PMC10353935?pdf=render" + }, { "id": "31317072", "doi": "https://doi.org/10.1002/lrh2.10191", @@ -41683,23 +41683,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ageing/article-pdf/51/4/afac090/43408856/afac090.pdf; doi:https://doi.org/10.1093/ageing/afac090; html:https://europepmc.org/articles/PMC9034697; pdf:https://europepmc.org/articles/PMC9034697?pdf=render" }, - { - "id": "38839884", - "doi": "https://doi.org/10.1038/s41588-024-01763-1", - "title": "Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction.", - "authorString": "Schormair B, Zhao C, Bell S, Didriksen M, Nawaz MS, Schandra N, Stefani A, H\u00f6gl B, Dauvilliers Y, Bachmann CG, Kemlink D, Sonka K, Paulus W, Trenkwalder C, Oertel WH, Hornyak M, Teder-Laving M, Metspalu A, Hadjigeorgiou GM, Polo O, Fietze I, Ross OA, Wszolek ZK, Ibrahim A, Bergmann M, Kittke V, Harrer P, Dowsett J, Chenini S, Ostrowski SR, S\u00f8rensen E, Erikstrup C, Pedersen OB, Topholm Bruun M, Nielsen KR, Butterworth AS, Soranzo N, Ouwehand WH, Roberts DJ, Danesh J, Burchell B, Furlotte NA, Nandakumar P, 23andMe Research Team, D.E.S.I.R. study group, Earley CJ, Ondo WG, Xiong L, Desautels A, Perola M, Vodicka P, Dina C, Stoll M, Franke A, Lieb W, Stewart AFR, Shah SH, Gieger C, Peters A, Rye DB, Rouleau GA, Berger K, Stefansson H, Ullum H, Stefansson K, Hinds DA, Di Angelantonio E, Oexle K, Winkelmann J.", - "authorAffiliations": "", - "journalTitle": "Nature genetics", - "pubYear": "2024", - "date": "2024-06-05", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes (rg\u2009=\u20090.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC)\u2009=\u20090.82-0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41588-024-01763-1.pdf; doi:https://doi.org/10.1038/s41588-024-01763-1" - }, { "id": "34767815", "doi": "https://doi.org/10.1016/j.jid.2021.08.446", @@ -41717,6 +41700,23 @@ "laySummary": "", "urls": "pdf:http://www.jidonline.org/article/S0022202X21024738/pdf; doi:https://doi.org/10.1016/j.jid.2021.08.446" }, + { + "id": "38839884", + "doi": "https://doi.org/10.1038/s41588-024-01763-1", + "title": "Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction.", + "authorString": "Schormair B, Zhao C, Bell S, Didriksen M, Nawaz MS, Schandra N, Stefani A, H\u00f6gl B, Dauvilliers Y, Bachmann CG, Kemlink D, Sonka K, Paulus W, Trenkwalder C, Oertel WH, Hornyak M, Teder-Laving M, Metspalu A, Hadjigeorgiou GM, Polo O, Fietze I, Ross OA, Wszolek ZK, Ibrahim A, Bergmann M, Kittke V, Harrer P, Dowsett J, Chenini S, Ostrowski SR, S\u00f8rensen E, Erikstrup C, Pedersen OB, Topholm Bruun M, Nielsen KR, Butterworth AS, Soranzo N, Ouwehand WH, Roberts DJ, Danesh J, Burchell B, Furlotte NA, Nandakumar P, 23andMe Research Team, D.E.S.I.R. study group, Earley CJ, Ondo WG, Xiong L, Desautels A, Perola M, Vodicka P, Dina C, Stoll M, Franke A, Lieb W, Stewart AFR, Shah SH, Gieger C, Peters A, Rye DB, Rouleau GA, Berger K, Stefansson H, Ullum H, Stefansson K, Hinds DA, Di Angelantonio E, Oexle K, Winkelmann J.", + "authorAffiliations": "", + "journalTitle": "Nature genetics", + "pubYear": "2024", + "date": "2024-06-05", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes (rg\u2009=\u20090.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC)\u2009=\u20090.82-0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41588-024-01763-1.pdf; doi:https://doi.org/10.1038/s41588-024-01763-1" + }, { "id": "31479209", "doi": "https://doi.org/10.1056/nejmoa1907096", @@ -41785,23 +41785,6 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/eat.23834; doi:https://doi.org/10.1002/eat.23834; html:https://europepmc.org/articles/PMC9874817; pdf:https://europepmc.org/articles/PMC9874817?pdf=render" }, - { - "id": "32762905", - "doi": "https://doi.org/10.1016/j.jacc.2020.06.024", - "title": "Validation of a Genome-Wide Polygenic\u00a0Score for Coronary Artery\u00a0Disease in\u00a0South Asians.", - "authorString": "Wang M, Menon R, Mishra S, Patel AP, Chaffin M, Tanneeru D, Deshmukh M, Mathew O, Apte S, Devanboo CS, Sundaram S, Lakshmipathy P, Murugan S, Sharma KK, Rajendran K, Santhosh S, Thachathodiyl R, Ahamed H, Balegadde AV, Alexander T, Swaminathan K, Gupta R, Mullasari AS, Sigamani A, Kanchi M, Peterson AS, Butterworth AS, Danesh J, Di Angelantonio E, Naheed A, Inouye M, Chowdhury R, Vedam RL, Kathiresan S, Gupta R, Khera AV.", - "authorAffiliations": "", - "journalTitle": "Journal of the American College of Cardiology", - "pubYear": "2020", - "date": "2020-08-01", - "isOpenAccess": "N", - "keywords": "coronary artery disease; Genomic Medicine; South Asian; Polygenic Score", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Genome-wide polygenic scores (GPS) integrate information from many common DNA variants into a single number. Because rates of coronary artery disease (CAD) are substantially higher among South Asians, a GPS to identify high-risk individuals may be particularly useful in this population.

Objectives

This analysis used summary statistics from a prior genome-wide association study to derive a new GPSCAD for South Asians.

Methods

This GPSCAD was validated in 7,244 South Asian UK Biobank participants and tested in 491 individuals from a case-control study in Bangladesh. Next, a static ancestry and GPSCAD reference distribution was built using whole-genome sequencing from 1,522 Indian individuals, and a framework was tested for projecting individuals onto this static ancestry and GPSCAD reference distribution using 1,800 CAD cases and 1,163 control subjects newly recruited in India.

Results

The GPSCAD, containing 6,630,150 common DNA variants, had an odds ratio (OR) per SD of 1.58 in South Asian UK Biobank participants and 1.60 in the Bangladeshi study (p\u00a0<\u00a00.001 for each). Next, individuals of the Indian case-control study were projected onto static reference distributions, observing an OR/SD of 1.66 (p\u00a0<\u00a00.001). Compared with the middle quintile, risk for CAD was most pronounced for those in the top 5% of the GPSCAD distribution-ORs of 4.16, 2.46, and 3.22 in the South Asian UK Biobank, Bangladeshi, and Indian studies, respectively (p\u00a0<\u00a00.05 for each).

Conclusions

The new GPSCAD has been developed and tested using 3 distinct South Asian studies, and provides a generalizable framework for ancestry-specific GPS assessment.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jacc.2020.06.024; doi:https://doi.org/10.1016/j.jacc.2020.06.024; html:https://europepmc.org/articles/PMC7592606; pdf:https://europepmc.org/articles/PMC7592606?pdf=render; doi:https://doi.org/10.1016/j.jacc.2020.06.024" - }, { "id": "31115347", "doi": "https://doi.org/10.2196/12412", @@ -41819,6 +41802,23 @@ "laySummary": "", "urls": "pdf:https://www.jmir.org/2019/5/e12412/PDF; doi:https://doi.org/10.2196/12412; html:https://europepmc.org/articles/PMC6547770" }, + { + "id": "32762905", + "doi": "https://doi.org/10.1016/j.jacc.2020.06.024", + "title": "Validation of a Genome-Wide Polygenic\u00a0Score for Coronary Artery\u00a0Disease in\u00a0South Asians.", + "authorString": "Wang M, Menon R, Mishra S, Patel AP, Chaffin M, Tanneeru D, Deshmukh M, Mathew O, Apte S, Devanboo CS, Sundaram S, Lakshmipathy P, Murugan S, Sharma KK, Rajendran K, Santhosh S, Thachathodiyl R, Ahamed H, Balegadde AV, Alexander T, Swaminathan K, Gupta R, Mullasari AS, Sigamani A, Kanchi M, Peterson AS, Butterworth AS, Danesh J, Di Angelantonio E, Naheed A, Inouye M, Chowdhury R, Vedam RL, Kathiresan S, Gupta R, Khera AV.", + "authorAffiliations": "", + "journalTitle": "Journal of the American College of Cardiology", + "pubYear": "2020", + "date": "2020-08-01", + "isOpenAccess": "N", + "keywords": "coronary artery disease; Genomic Medicine; South Asian; Polygenic Score", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Genome-wide polygenic scores (GPS) integrate information from many common DNA variants into a single number. Because rates of coronary artery disease (CAD) are substantially higher among South Asians, a GPS to identify high-risk individuals may be particularly useful in this population.

Objectives

This analysis used summary statistics from a prior genome-wide association study to derive a new GPSCAD for South Asians.

Methods

This GPSCAD was validated in 7,244 South Asian UK Biobank participants and tested in 491 individuals from a case-control study in Bangladesh. Next, a static ancestry and GPSCAD reference distribution was built using whole-genome sequencing from 1,522 Indian individuals, and a framework was tested for projecting individuals onto this static ancestry and GPSCAD reference distribution using 1,800 CAD cases and 1,163 control subjects newly recruited in India.

Results

The GPSCAD, containing 6,630,150 common DNA variants, had an odds ratio (OR) per SD of 1.58 in South Asian UK Biobank participants and 1.60 in the Bangladeshi study (p\u00a0<\u00a00.001 for each). Next, individuals of the Indian case-control study were projected onto static reference distributions, observing an OR/SD of 1.66 (p\u00a0<\u00a00.001). Compared with the middle quintile, risk for CAD was most pronounced for those in the top 5% of the GPSCAD distribution-ORs of 4.16, 2.46, and 3.22 in the South Asian UK Biobank, Bangladeshi, and Indian studies, respectively (p\u00a0<\u00a00.05 for each).

Conclusions

The new GPSCAD has been developed and tested using 3 distinct South Asian studies, and provides a generalizable framework for ancestry-specific GPS assessment.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.jacc.2020.06.024; doi:https://doi.org/10.1016/j.jacc.2020.06.024; html:https://europepmc.org/articles/PMC7592606; pdf:https://europepmc.org/articles/PMC7592606?pdf=render; doi:https://doi.org/10.1016/j.jacc.2020.06.024" + }, { "id": "30842207", "doi": "https://doi.org/10.1136/heartjnl-2019-314763", @@ -42040,23 +42040,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jadr.2021.100201; doi:https://doi.org/10.1016/j.jadr.2021.100201; html:https://europepmc.org/articles/PMC8689407" }, - { - "id": "33887342", - "doi": "https://doi.org/10.1016/j.ijcard.2021.04.029", - "title": "Clopidogrel in noncarriers of CYP2C19 loss-of-function alleles versus ticagrelor in elderly patients with acute coronary syndrome: A pre-specified sub analysis from the POPular Genetics and POPular Age trials CYP2C19 alleles in elderly patients.", - "authorString": "Claassens DMF, Gimbel ME, Bergmeijer TO, Vos GJA, Hermanides RS, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, de Vrey EA, Heestermans TACM, Jukema JW, von Birgelen C, Waalewijn RA, Hofma SH, den Hartog FR, Voskuil M, Van't Hof AWJ, Asselbergs FW, Mosterd A, Herrman JR, Dewilde W, Mahmoodi BK, Deneer VHM, Ten Berg JM.", - "authorAffiliations": "", - "journalTitle": "International journal of cardiology", - "pubYear": "2021", - "date": "2021-04-20", - "isOpenAccess": "N", - "keywords": "Genotyping; Myocardial infarction; CYP2C19; Pharmacogenetics; Older; P2y12", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Patients with acute coronary syndrome (ACS) who are carrying CYP2C19 loss-of-function alleles derive less benefit from clopidogrel treatment. Despite this, in elderly patients, clopidogrel might be preferred over more potent P2Y12 inhibitors due to a lower bleeding risk. Whether CYP2C19 genotype-guided antiplatelet treatment in the elderly could be of benefit has not been studied specifically.

Methods

Patients aged 70 years and older with known CYP2C19*2 and *3 genotype were identified from the POPular Genetics and POPular Age trials. Noncarriers of loss-of-function alleles treated with clopidogrel were compared to patients, irrespective of CYP2C19 genotype, treated with ticagrelor and to clopidogrel treated carriers of loss-of-function alleles. We assessed net clinical benefit (all-cause death, myocardial infarction, stroke and Platelet Inhibition and Patient Outcomes (PLATO) major bleeding), atherothrombotic outcomes (cardiovascular death, myocardial infarction, stroke) and bleeding outcomes (PLATO major and minor bleeding).

Results

A total of 991 patients were assessed. There was no significant difference in net clinical benefit (17.2% vs. 15.1%, adjusted hazard ratio (adjHR) 1.05, 95% confidence interval (CI) 0.77-1.44), atherothrombotic outcomes (9.7% vs. 9.2%, adjHR 1.00, 95%CI 0.66-1.50), and bleeding outcomes (17.7% vs. 19.8%, adjHR 0.80, 95%CI 0.62-1.12) between clopidogrel in noncarriers of loss-of-function alleles and ticagrelor respectively.

Conclusion

In ACS patients aged 70 years and older, there was no significant difference in net clinical benefit and atherothrombotic outcomes between noncarriers of a loss-of-function allele treated with clopidogrel and patients treated with ticagrelor. The bleeding rate was numerically; though not statistically significant, lower in patients using clopidogrel.", - "laySummary": "", - "urls": "pdf:https://pure.rug.nl/ws/files/200111410/1_s2.0_S0167527321006653_main.pdf; doi:https://doi.org/10.1016/j.ijcard.2021.04.029" - }, { "id": "34820659", "doi": "https://doi.org/10.1016/j.xgen.2021.100028", @@ -42074,6 +42057,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.xgen.2021.100028; doi:https://doi.org/10.1016/j.xgen.2021.100028; html:https://europepmc.org/articles/PMC8591903; pdf:https://europepmc.org/articles/PMC8591903?pdf=render" }, + { + "id": "33887342", + "doi": "https://doi.org/10.1016/j.ijcard.2021.04.029", + "title": "Clopidogrel in noncarriers of CYP2C19 loss-of-function alleles versus ticagrelor in elderly patients with acute coronary syndrome: A pre-specified sub analysis from the POPular Genetics and POPular Age trials CYP2C19 alleles in elderly patients.", + "authorString": "Claassens DMF, Gimbel ME, Bergmeijer TO, Vos GJA, Hermanides RS, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, de Vrey EA, Heestermans TACM, Jukema JW, von Birgelen C, Waalewijn RA, Hofma SH, den Hartog FR, Voskuil M, Van't Hof AWJ, Asselbergs FW, Mosterd A, Herrman JR, Dewilde W, Mahmoodi BK, Deneer VHM, Ten Berg JM.", + "authorAffiliations": "", + "journalTitle": "International journal of cardiology", + "pubYear": "2021", + "date": "2021-04-20", + "isOpenAccess": "N", + "keywords": "Genotyping; Myocardial infarction; CYP2C19; Pharmacogenetics; Older; P2y12", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Patients with acute coronary syndrome (ACS) who are carrying CYP2C19 loss-of-function alleles derive less benefit from clopidogrel treatment. Despite this, in elderly patients, clopidogrel might be preferred over more potent P2Y12 inhibitors due to a lower bleeding risk. Whether CYP2C19 genotype-guided antiplatelet treatment in the elderly could be of benefit has not been studied specifically.

Methods

Patients aged 70 years and older with known CYP2C19*2 and *3 genotype were identified from the POPular Genetics and POPular Age trials. Noncarriers of loss-of-function alleles treated with clopidogrel were compared to patients, irrespective of CYP2C19 genotype, treated with ticagrelor and to clopidogrel treated carriers of loss-of-function alleles. We assessed net clinical benefit (all-cause death, myocardial infarction, stroke and Platelet Inhibition and Patient Outcomes (PLATO) major bleeding), atherothrombotic outcomes (cardiovascular death, myocardial infarction, stroke) and bleeding outcomes (PLATO major and minor bleeding).

Results

A total of 991 patients were assessed. There was no significant difference in net clinical benefit (17.2% vs. 15.1%, adjusted hazard ratio (adjHR) 1.05, 95% confidence interval (CI) 0.77-1.44), atherothrombotic outcomes (9.7% vs. 9.2%, adjHR 1.00, 95%CI 0.66-1.50), and bleeding outcomes (17.7% vs. 19.8%, adjHR 0.80, 95%CI 0.62-1.12) between clopidogrel in noncarriers of loss-of-function alleles and ticagrelor respectively.

Conclusion

In ACS patients aged 70 years and older, there was no significant difference in net clinical benefit and atherothrombotic outcomes between noncarriers of a loss-of-function allele treated with clopidogrel and patients treated with ticagrelor. The bleeding rate was numerically; though not statistically significant, lower in patients using clopidogrel.", + "laySummary": "", + "urls": "pdf:https://pure.rug.nl/ws/files/200111410/1_s2.0_S0167527321006653_main.pdf; doi:https://doi.org/10.1016/j.ijcard.2021.04.029" + }, { "id": "31730918", "doi": "https://doi.org/10.1016/j.jclinepi.2019.11.006", @@ -42584,23 +42584,6 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003498&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003498; html:https://europepmc.org/articles/PMC7808664; pdf:https://europepmc.org/articles/PMC7808664?pdf=render" }, - { - "id": "38428419", - "doi": "https://doi.org/10.1016/j.xgen.2024.100511", - "title": "Genomic evolution shapes prostate cancer disease type.", - "authorString": "Woodcock DJ, Sahli A, Teslo R, Bhandari V, Gruber AJ, Ziubroniewicz A, Gundem G, Xu Y, Butler A, Anokian E, Pope BJ, Jung CH, Tarabichi M, Dentro SC, Farmery JHR, CRUK ICGC Prostate Group, Van Loo P, Warren AY, Gnanapragasam V, Hamdy FC, Bova GS, Foster CS, Neal DE, Lu YJ, Kote-Jarai Z, Fraser M, Bristow RG, Boutros PC, Costello AJ, Corcoran NM, Hovens CM, Massie CE, Lynch AG, Brewer DS, Eeles RA, Cooper CS, Wedge DC.", - "authorAffiliations": "", - "journalTitle": "Cell genomics", - "pubYear": "2024", - "date": "2024-02-29", - "isOpenAccess": "Y", - "keywords": "prostate cancer; Ordering; Cancer Evolution; Ar Binding; Evotype Model; Evotypes", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype tumors diverge from those of the Canonical-evotype through the stochastic accumulation of genetic alterations associated with disruptions to androgen receptor DNA binding. Our model unifies many previous molecular observations, providing a powerful new framework to investigate prostate cancer disease progression.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.xgen.2024.100511; html:https://europepmc.org/articles/PMC10943594; pdf:https://europepmc.org/articles/PMC10943594?pdf=render" - }, { "id": "32979922", "doi": "https://doi.org/10.1186/s12933-020-01130-4", @@ -42618,6 +42601,23 @@ "laySummary": "", "urls": "pdf:https://cardiab.biomedcentral.com/track/pdf/10.1186/s12933-020-01130-4; doi:https://doi.org/10.1186/s12933-020-01130-4; html:https://europepmc.org/articles/PMC7520021; pdf:https://europepmc.org/articles/PMC7520021?pdf=render" }, + { + "id": "38428419", + "doi": "https://doi.org/10.1016/j.xgen.2024.100511", + "title": "Genomic evolution shapes prostate cancer disease type.", + "authorString": "Woodcock DJ, Sahli A, Teslo R, Bhandari V, Gruber AJ, Ziubroniewicz A, Gundem G, Xu Y, Butler A, Anokian E, Pope BJ, Jung CH, Tarabichi M, Dentro SC, Farmery JHR, CRUK ICGC Prostate Group, Van Loo P, Warren AY, Gnanapragasam V, Hamdy FC, Bova GS, Foster CS, Neal DE, Lu YJ, Kote-Jarai Z, Fraser M, Bristow RG, Boutros PC, Costello AJ, Corcoran NM, Hovens CM, Massie CE, Lynch AG, Brewer DS, Eeles RA, Cooper CS, Wedge DC.", + "authorAffiliations": "", + "journalTitle": "Cell genomics", + "pubYear": "2024", + "date": "2024-02-29", + "isOpenAccess": "Y", + "keywords": "prostate cancer; Ordering; Cancer Evolution; Ar Binding; Evotype Model; Evotypes", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype tumors diverge from those of the Canonical-evotype through the stochastic accumulation of genetic alterations associated with disruptions to androgen receptor DNA binding. Our model unifies many previous molecular observations, providing a powerful new framework to investigate prostate cancer disease progression.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.xgen.2024.100511; html:https://europepmc.org/articles/PMC10943594; pdf:https://europepmc.org/articles/PMC10943594?pdf=render" + }, { "id": "33442528", "doi": "https://doi.org/10.1140/epjds/s13688-020-00257-4", @@ -42805,23 +42805,6 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S0140673620320134/pdf; doi:https://doi.org/10.1016/S0140-6736(20)32013-4; html:https://europepmc.org/articles/PMC7535623" }, - { - "id": "37681566", - "doi": "https://doi.org/10.1161/jaha.123.030280", - "title": "Age at Menopause and the Risk of Stroke: Observational and Mendelian Randomization Analysis in 204\u2009244 Postmenopausal Women.", - "authorString": "Tschiderer L, Peters SAE, van der Schouw YT, van Westing AC, Tong TYN, Willeit P, Seekircher L, Moreno-Iribas C, Huerta JM, Crous-Bou M, S\u00f6derholm M, Schulze MB, Johansson C, Sj\u00e4lander S, Heath AK, Macciotta A, Dahm CC, Ibsen DB, Pala V, Mellemkj\u00e6r L, Burgess S, Wood A, Kaaks R, Katzke V, Amiano P, Rodriguez-Barranco M, Engstr\u00f6m G, Weiderpass E, Tj\u00f8nneland A, Halkj\u00e6r J, Panico S, Danesh J, Butterworth A, Onland-Moret NC.", - "authorAffiliations": "", - "journalTitle": "Journal of the American Heart Association", - "pubYear": "2023", - "date": "2023-09-08", - "isOpenAccess": "Y", - "keywords": "Stroke; Age At Menopause; Mendelian Randomization Analysis; Observational Analysis", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Background Observational studies have shown that women with an early menopause are at higher risk of stroke compared with women with a later menopause. However, associations with stroke subtypes are inconsistent, and the causality is unclear. Methods and Results We analyzed data of the UK Biobank and EPIC-CVD (European Prospective Investigation Into Cancer and Nutrition-Cardiovascular Diseases) study. A total of 204\u2009244 postmenopausal women without a history of stroke at baseline were included (7883 from EPIC-CVD [5292 from the subcohort], 196\u2009361 from the UK Biobank). Pooled mean baseline age was 58.9\u2009years (SD, 5.8), and pooled mean age at menopause was 47.8\u2009years (SD, 6.2). Over a median follow-up of 12.6\u2009years (interquartile range, 11.8-13.3), 6770 women experienced a stroke (5155 ischemic strokes, 1615 hemorrhagic strokes, 976 intracerebral hemorrhages, and 639 subarachnoid hemorrhages). In multivariable adjusted observational Cox regression analyses, the pooled hazard ratios per 5\u2009years younger age at menopause were 1.09 (95% CI, 1.07-1.12) for stroke, 1.09 (95% CI, 1.06-1.13) for ischemic stroke, 1.10 (95% CI, 1.04-1.16) for hemorrhagic stroke, 1.14 (95% CI, 1.08-1.20) for intracerebral hemorrhage, and 1.00 (95% CI, 0.84-1.20) for subarachnoid hemorrhage. When using 2-sample Mendelian randomization analysis, we found no statistically significant association between genetically proxied age at menopause and risk of any type of stroke. Conclusions In our study, earlier age at menopause was related to a higher risk of stroke. We found no statistically significant association between genetically proxied age at menopause and risk of stroke, suggesting no causal relationship.", - "laySummary": "", - "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.030280; doi:https://doi.org/10.1161/JAHA.123.030280; html:https://europepmc.org/articles/PMC10547274; pdf:https://europepmc.org/articles/PMC10547274?pdf=render" - }, { "id": "33421867", "doi": "https://doi.org/10.1016/j.jad.2020.12.053", @@ -42856,6 +42839,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41541-020-00267-3.pdf; doi:https://doi.org/10.1038/s41541-020-00267-3; html:https://europepmc.org/articles/PMC7794334; pdf:https://europepmc.org/articles/PMC7794334?pdf=render" }, + { + "id": "37681566", + "doi": "https://doi.org/10.1161/jaha.123.030280", + "title": "Age at Menopause and the Risk of Stroke: Observational and Mendelian Randomization Analysis in 204\u2009244 Postmenopausal Women.", + "authorString": "Tschiderer L, Peters SAE, van der Schouw YT, van Westing AC, Tong TYN, Willeit P, Seekircher L, Moreno-Iribas C, Huerta JM, Crous-Bou M, S\u00f6derholm M, Schulze MB, Johansson C, Sj\u00e4lander S, Heath AK, Macciotta A, Dahm CC, Ibsen DB, Pala V, Mellemkj\u00e6r L, Burgess S, Wood A, Kaaks R, Katzke V, Amiano P, Rodriguez-Barranco M, Engstr\u00f6m G, Weiderpass E, Tj\u00f8nneland A, Halkj\u00e6r J, Panico S, Danesh J, Butterworth A, Onland-Moret NC.", + "authorAffiliations": "", + "journalTitle": "Journal of the American Heart Association", + "pubYear": "2023", + "date": "2023-09-08", + "isOpenAccess": "Y", + "keywords": "Stroke; Age At Menopause; Mendelian Randomization Analysis; Observational Analysis", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Background Observational studies have shown that women with an early menopause are at higher risk of stroke compared with women with a later menopause. However, associations with stroke subtypes are inconsistent, and the causality is unclear. Methods and Results We analyzed data of the UK Biobank and EPIC-CVD (European Prospective Investigation Into Cancer and Nutrition-Cardiovascular Diseases) study. A total of 204\u2009244 postmenopausal women without a history of stroke at baseline were included (7883 from EPIC-CVD [5292 from the subcohort], 196\u2009361 from the UK Biobank). Pooled mean baseline age was 58.9\u2009years (SD, 5.8), and pooled mean age at menopause was 47.8\u2009years (SD, 6.2). Over a median follow-up of 12.6\u2009years (interquartile range, 11.8-13.3), 6770 women experienced a stroke (5155 ischemic strokes, 1615 hemorrhagic strokes, 976 intracerebral hemorrhages, and 639 subarachnoid hemorrhages). In multivariable adjusted observational Cox regression analyses, the pooled hazard ratios per 5\u2009years younger age at menopause were 1.09 (95% CI, 1.07-1.12) for stroke, 1.09 (95% CI, 1.06-1.13) for ischemic stroke, 1.10 (95% CI, 1.04-1.16) for hemorrhagic stroke, 1.14 (95% CI, 1.08-1.20) for intracerebral hemorrhage, and 1.00 (95% CI, 0.84-1.20) for subarachnoid hemorrhage. When using 2-sample Mendelian randomization analysis, we found no statistically significant association between genetically proxied age at menopause and risk of any type of stroke. Conclusions In our study, earlier age at menopause was related to a higher risk of stroke. We found no statistically significant association between genetically proxied age at menopause and risk of stroke, suggesting no causal relationship.", + "laySummary": "", + "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.030280; doi:https://doi.org/10.1161/JAHA.123.030280; html:https://europepmc.org/articles/PMC10547274; pdf:https://europepmc.org/articles/PMC10547274?pdf=render" + }, { "id": "32877352", "doi": "https://doi.org/10.2196/19992", @@ -43009,23 +43009,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/jtm/article-pdf/27/5/taaa068/33666000/taaa068.pdf; doi:https://doi.org/10.1093/jtm/taaa068; html:https://europepmc.org/articles/PMC7239177; pdf:https://europepmc.org/articles/PMC7239177?pdf=render" }, - { - "id": "34090494", - "doi": "https://doi.org/10.1186/s13063-021-05284-8", - "title": "A framework for handling missing accelerometer outcome data in trials.", - "authorString": "Tackney MS, Cook DG, Stahl D, Ismail K, Williamson E, Carpenter J.", - "authorAffiliations": "", - "journalTitle": "Trials", - "pubYear": "2021", - "date": "2021-06-05", - "isOpenAccess": "Y", - "keywords": "Clinical Trial; Missing Data; Accelerometer; Multiple Imputation; Wearables", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Accelerometers and other wearable devices are increasingly being used in clinical trials to provide an objective measure of the impact of an intervention on physical activity. Missing data are ubiquitous in this setting, typically for one of two reasons: patients may not wear the device as per protocol, and/or the device may fail to collect data (e.g. flat battery, water damage). However, it is not always possible to distinguish whether the participant stopped wearing the device, or if the participant is wearing the device but staying still. Further, a lack of consensus in the literature on how to aggregate the data before analysis (hourly, daily, weekly) leads to a lack of consensus in how to define a \"missing\" outcome. Different trials have adopted different definitions (ranging from having insufficient step counts in a day, through to missing a certain number of days in a week). We propose an analysis framework that uses wear time to define missingness on the epoch and day level, and propose a multiple imputation approach, at the day level, which treats partially observed daily step counts as right censored. This flexible approach allows the inclusion of auxiliary variables, and is consistent with almost all the primary analysis models described in the literature, and readily allows sensitivity analysis (to the missing at random assumption) to be performed. Having presented our framework, we illustrate its application to the analysis of the 2019 MOVE-IT trial of motivational interviewing to increase exercise.", - "laySummary": "", - "urls": "pdf:https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-021-05284-8; doi:https://doi.org/10.1186/s13063-021-05284-8; html:https://europepmc.org/articles/PMC8178870; pdf:https://europepmc.org/articles/PMC8178870?pdf=render" - }, { "id": "32543438", "doi": "https://doi.org/10.1016/j.healthplace.2020.102355", @@ -43043,6 +43026,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.healthplace.2020.102355; doi:https://doi.org/10.1016/j.healthplace.2020.102355; html:https://europepmc.org/articles/PMC7214342" }, + { + "id": "34090494", + "doi": "https://doi.org/10.1186/s13063-021-05284-8", + "title": "A framework for handling missing accelerometer outcome data in trials.", + "authorString": "Tackney MS, Cook DG, Stahl D, Ismail K, Williamson E, Carpenter J.", + "authorAffiliations": "", + "journalTitle": "Trials", + "pubYear": "2021", + "date": "2021-06-05", + "isOpenAccess": "Y", + "keywords": "Clinical Trial; Missing Data; Accelerometer; Multiple Imputation; Wearables", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Accelerometers and other wearable devices are increasingly being used in clinical trials to provide an objective measure of the impact of an intervention on physical activity. Missing data are ubiquitous in this setting, typically for one of two reasons: patients may not wear the device as per protocol, and/or the device may fail to collect data (e.g. flat battery, water damage). However, it is not always possible to distinguish whether the participant stopped wearing the device, or if the participant is wearing the device but staying still. Further, a lack of consensus in the literature on how to aggregate the data before analysis (hourly, daily, weekly) leads to a lack of consensus in how to define a \"missing\" outcome. Different trials have adopted different definitions (ranging from having insufficient step counts in a day, through to missing a certain number of days in a week). We propose an analysis framework that uses wear time to define missingness on the epoch and day level, and propose a multiple imputation approach, at the day level, which treats partially observed daily step counts as right censored. This flexible approach allows the inclusion of auxiliary variables, and is consistent with almost all the primary analysis models described in the literature, and readily allows sensitivity analysis (to the missing at random assumption) to be performed. Having presented our framework, we illustrate its application to the analysis of the 2019 MOVE-IT trial of motivational interviewing to increase exercise.", + "laySummary": "", + "urls": "pdf:https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-021-05284-8; doi:https://doi.org/10.1186/s13063-021-05284-8; html:https://europepmc.org/articles/PMC8178870; pdf:https://europepmc.org/articles/PMC8178870?pdf=render" + }, { "id": "32855398", "doi": "https://doi.org/10.1038/s41467-020-18060-0", @@ -43230,23 +43230,6 @@ "laySummary": "", "urls": "pdf:https://oem.bmj.com/content/oemed/80/7/399.full.pdf; doi:https://doi.org/10.1136/oemed-2022-108700; html:https://europepmc.org/articles/PMC10314065; pdf:https://europepmc.org/articles/PMC10314065?pdf=render" }, - { - "id": "33203707", - "doi": "https://doi.org/10.2337/dc20-1328", - "title": "Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations.", - "authorString": "Zheng JS, Luan J, Sofianopoulou E, Imamura F, Stewart ID, Day FR, Pietzner M, Wheeler E, Lotta LA, Gundersen TE, Amiano P, Ardanaz E, Chirlaque MD, Fagherazzi G, Franks PW, Kaaks R, Laouali N, Mancini FR, Nilsson PM, Onland-Moret NC, Olsen A, Overvad K, Panico S, Palli D, Ricceri F, Rolandsson O, Spijkerman AMW, S\u00e1nchez MJ, Schulze MB, Sala N, Sieri S, Tj\u00f8nneland A, Tumino R, van der Schouw YT, Weiderpass E, Riboli E, Danesh J, Butterworth AS, Sharp SJ, Langenberg C, Forouhi NG, Wareham NJ.", - "authorAffiliations": "", - "journalTitle": "Diabetes care", - "pubYear": "2021", - "date": "2020-11-17", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes.

Research design and methods

We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants.

Results

We identified 11 genomic regions associated with plasma vitamin C (P < 5 \u00d7 10-8), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10).

Conclusions

These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.", - "laySummary": "", - "urls": "pdf:https://diabetesjournals.org/care/article-pdf/44/1/98/532486/dc201328.pdf; doi:https://doi.org/10.2337/dc20-1328; html:https://europepmc.org/articles/PMC7783939; pdf:https://europepmc.org/articles/PMC7783939?pdf=render" - }, { "id": "32062083", "doi": "https://doi.org/10.1016/j.neuroimage.2020.116604", @@ -43264,6 +43247,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.neuroimage.2020.116604; doi:https://doi.org/10.1016/j.neuroimage.2020.116604; html:https://europepmc.org/articles/PMC7086233" }, + { + "id": "33203707", + "doi": "https://doi.org/10.2337/dc20-1328", + "title": "Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations.", + "authorString": "Zheng JS, Luan J, Sofianopoulou E, Imamura F, Stewart ID, Day FR, Pietzner M, Wheeler E, Lotta LA, Gundersen TE, Amiano P, Ardanaz E, Chirlaque MD, Fagherazzi G, Franks PW, Kaaks R, Laouali N, Mancini FR, Nilsson PM, Onland-Moret NC, Olsen A, Overvad K, Panico S, Palli D, Ricceri F, Rolandsson O, Spijkerman AMW, S\u00e1nchez MJ, Schulze MB, Sala N, Sieri S, Tj\u00f8nneland A, Tumino R, van der Schouw YT, Weiderpass E, Riboli E, Danesh J, Butterworth AS, Sharp SJ, Langenberg C, Forouhi NG, Wareham NJ.", + "authorAffiliations": "", + "journalTitle": "Diabetes care", + "pubYear": "2021", + "date": "2020-11-17", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes.

Research design and methods

We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants.

Results

We identified 11 genomic regions associated with plasma vitamin C (P < 5 \u00d7 10-8), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10).

Conclusions

These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.", + "laySummary": "", + "urls": "pdf:https://diabetesjournals.org/care/article-pdf/44/1/98/532486/dc201328.pdf; doi:https://doi.org/10.2337/dc20-1328; html:https://europepmc.org/articles/PMC7783939; pdf:https://europepmc.org/articles/PMC7783939?pdf=render" + }, { "id": "31005938", "doi": "https://doi.org/10.1136/bmjopen-2018-027289", @@ -43519,23 +43519,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.neuroimage.2020.117002; doi:https://doi.org/10.1016/j.neuroimage.2020.117002; html:https://europepmc.org/articles/PMC7610719; pdf:https://europepmc.org/articles/PMC7610719?pdf=render" }, - { - "id": "33595074", - "doi": "https://doi.org/10.1093/aje/kwab031", - "title": "Prediction of Cardiovascular Disease Risk Accounting for Future Initiation of Statin Treatment.", - "authorString": "Xu Z, Arnold M, Stevens D, Kaptoge S, Pennells L, Sweeting MJ, Barrett J, Di Angelantonio E, Wood AM.", - "authorAffiliations": "", - "journalTitle": "American journal of epidemiology", - "pubYear": "2021", - "date": "2021-10-01", - "isOpenAccess": "Y", - "keywords": "Longitudinal data; Cardiovascular disease; Risk Prediction; Electronic Health Records; Treatment Drop-in; Future Statin Initiation", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Cardiovascular disease (CVD) risk-prediction models are used to identify high-risk individuals and guide statin initiation. However, these models are usually derived from individuals who might initiate statins during follow-up. We present a simple approach to address statin initiation to predict \"statin-naive\" CVD risk. We analyzed primary care data (2004-2017) from the UK Clinical Practice Research Datalink for 1,678,727 individuals (aged 40-85 years) without CVD or statin treatment history at study entry. We derived age- and sex-specific prediction models including conventional risk factors and a time-dependent effect of statin initiation constrained to 25% risk reduction (from trial results). We compared predictive performance and measures of public-health impact (e.g., number needed to screen to prevent 1 event) against models ignoring statin initiation. During a median follow-up of 8.9 years, 103,163 individuals developed CVD. In models accounting for (versus ignoring) statin initiation, 10-year CVD risk predictions were slightly higher; predictive performance was moderately improved. However, few individuals were reclassified to a high-risk threshold, resulting in negligible improvements in number needed to screen to prevent 1 event. In conclusion, incorporating statin effects from trial results into risk-prediction models enables statin-naive CVD risk estimation and provides moderate gains in predictive ability but had a limited impact on treatment decision-making under current guidelines in this population.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/aje/article-pdf/190/10/2000/40491073/kwab031.pdf; doi:https://doi.org/10.1093/aje/kwab031; html:https://europepmc.org/articles/PMC8485151; pdf:https://europepmc.org/articles/PMC8485151?pdf=render" - }, { "id": "32025702", "doi": "https://doi.org/10.1093/gigascience/giaa007", @@ -43553,6 +43536,23 @@ "laySummary": "The authors compared the accuracy of data processing steps (called bioinformatics pipelines) for identifying different types of bacteria, and which antibiotics they are resistant to. They identified which processes were most likely to introduce errors for different bacteria, and make recommendations about which pipelines should be used.", "urls": "pdf:https://watermark.silverchair.com/giaa007.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAArgwggK0BgkqhkiG9w0BBwagggKlMIICoQIBADCCApoGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM317Vywl4J0MoRskUAgEQgIICa7pwfJ56Mly4Anv1BPEAmwtKXOLcmFeMLRa66xhgPdK6Ci4Aw3rp4lJMizin326QALNQsODRERKONUxtXgEWVQAk130Fd7XbP6mDWd-0WqGT3cSidkfYveDUH3QNU5fMzLfCj598hrJEAk1z7LTkxKHEy9DQWfFNTCjY53IC7QawbMnwVvVq_lpTKlRP8_qZiTe8qiEKqWNVZ6woCjOc2Rro01EG5_atdzA8zpmJq2R4tx28FbVmIM7dsgYcT7L9DYQIcPQwJxaZSleSNtEyNXeo-WcHn_ezUiaRb0lthzfWPPdge5nY3tlFAelL_HeYo6jn4CkFdniFC28Gr7TuFnrJyj28_OsKYJICwvgwmNPj-T5rf9MGAMgBV3SLK6l87grZuO1r4Q8AfpvbJY9vHrDDayBzhuXMW_g2CFpQDYzMp4tGX8Yu3uS5qDWR81xG0Xqf5p0i0wsw1ZD1ZDA8tla87WrJCjbGwWjoXx2ihhyp6aXc4DC_8FCavms7sXqxQEsoVtDp6hvmpDsPPSvdGRAOjKeaQD2mWFi_3U7ndjd2_0dGVvsD5zDl0_GrRV8QEGNDocCzvibp-DyCby-tfRS4UsoqVA96Gs3ZgVtZzcQbcDt3C069xpbFOJD2rqJ4oyiGdUUh9uWDxgQFKiRvQZbblRH-htJ8tPKjv371GO1Wm6E-asCRSjCkT4vRP3lzDlab36iWZVp5vS5XoumjEnV9wxKBEqkYGywEdZUlG57ygWi11YTdMK3EYXbFqU0xFXvw34Sdl47d5bUDjYEEcxBciYLJqWhQKY9opr4bt5T3SCS107QDE4VOmd4; doi:https://doi.org/10.1093/gigascience/giaa007; html:https://europepmc.org/articles/PMC7002876; pdf:https://europepmc.org/articles/PMC7002876?pdf=render" }, + { + "id": "33595074", + "doi": "https://doi.org/10.1093/aje/kwab031", + "title": "Prediction of Cardiovascular Disease Risk Accounting for Future Initiation of Statin Treatment.", + "authorString": "Xu Z, Arnold M, Stevens D, Kaptoge S, Pennells L, Sweeting MJ, Barrett J, Di Angelantonio E, Wood AM.", + "authorAffiliations": "", + "journalTitle": "American journal of epidemiology", + "pubYear": "2021", + "date": "2021-10-01", + "isOpenAccess": "Y", + "keywords": "Longitudinal data; Cardiovascular disease; Risk Prediction; Electronic Health Records; Treatment Drop-in; Future Statin Initiation", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Cardiovascular disease (CVD) risk-prediction models are used to identify high-risk individuals and guide statin initiation. However, these models are usually derived from individuals who might initiate statins during follow-up. We present a simple approach to address statin initiation to predict \"statin-naive\" CVD risk. We analyzed primary care data (2004-2017) from the UK Clinical Practice Research Datalink for 1,678,727 individuals (aged 40-85 years) without CVD or statin treatment history at study entry. We derived age- and sex-specific prediction models including conventional risk factors and a time-dependent effect of statin initiation constrained to 25% risk reduction (from trial results). We compared predictive performance and measures of public-health impact (e.g., number needed to screen to prevent 1 event) against models ignoring statin initiation. During a median follow-up of 8.9 years, 103,163 individuals developed CVD. In models accounting for (versus ignoring) statin initiation, 10-year CVD risk predictions were slightly higher; predictive performance was moderately improved. However, few individuals were reclassified to a high-risk threshold, resulting in negligible improvements in number needed to screen to prevent 1 event. In conclusion, incorporating statin effects from trial results into risk-prediction models enables statin-naive CVD risk estimation and provides moderate gains in predictive ability but had a limited impact on treatment decision-making under current guidelines in this population.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/aje/article-pdf/190/10/2000/40491073/kwab031.pdf; doi:https://doi.org/10.1093/aje/kwab031; html:https://europepmc.org/articles/PMC8485151; pdf:https://europepmc.org/articles/PMC8485151?pdf=render" + }, { "id": "36982069", "doi": "https://doi.org/10.3390/ijerph20065161", @@ -43587,23 +43587,6 @@ "laySummary": "", "urls": "pdf:https://clinicalepigeneticsjournal.biomedcentral.com/counter/pdf/10.1186/s13148-021-01043-3; doi:https://doi.org/10.1186/s13148-021-01043-3; html:https://europepmc.org/articles/PMC7989210; pdf:https://europepmc.org/articles/PMC7989210?pdf=render" }, - { - "id": "35908040", - "doi": "https://doi.org/10.1038/s41597-022-01534-9", - "title": "ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19.", - "authorString": "ISARIC Clinical Characterization Group, Garcia-Gallo E, Merson L, Kennon K, Kelly S, Citarella BW, Fryer DV, Shrapnel S, Lee J, Duque S, Fuentes YV, Balan V, Smith S, Wei J, Gon\u00e7alves BP, Russell CD, Sigfrid L, Dagens A, Olliaro PL, Baruch J, Kartsonaki C, Dunning J, Rojek A, Rashan A, Beane A, Murthy S, Reyes LF.", - "authorAffiliations": "", - "journalTitle": "Scientific data", - "pubYear": "2022", - "date": "2022-07-30", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41597-022-01534-9.pdf; doi:https://doi.org/10.1038/s41597-022-01534-9; html:https://europepmc.org/articles/PMC9339000; pdf:https://europepmc.org/articles/PMC9339000?pdf=render" - }, { "id": "31485076", "doi": "https://doi.org/10.1038/s41586-019-1530-7", @@ -43621,6 +43604,23 @@ "laySummary": "", "urls": "pdf:https://europepmc.org/articles/pmc6795553?pdf=render; doi:https://doi.org/10.1038/s41586-019-1530-7; html:https://europepmc.org/articles/PMC6795553; pdf:https://europepmc.org/articles/PMC6795553?pdf=render" }, + { + "id": "35908040", + "doi": "https://doi.org/10.1038/s41597-022-01534-9", + "title": "ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19.", + "authorString": "ISARIC Clinical Characterization Group, Garcia-Gallo E, Merson L, Kennon K, Kelly S, Citarella BW, Fryer DV, Shrapnel S, Lee J, Duque S, Fuentes YV, Balan V, Smith S, Wei J, Gon\u00e7alves BP, Russell CD, Sigfrid L, Dagens A, Olliaro PL, Baruch J, Kartsonaki C, Dunning J, Rojek A, Rashan A, Beane A, Murthy S, Reyes LF.", + "authorAffiliations": "", + "journalTitle": "Scientific data", + "pubYear": "2022", + "date": "2022-07-30", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41597-022-01534-9.pdf; doi:https://doi.org/10.1038/s41597-022-01534-9; html:https://europepmc.org/articles/PMC9339000; pdf:https://europepmc.org/articles/PMC9339000?pdf=render" + }, { "id": "36210437", "doi": "https://doi.org/10.1186/s12916-022-02588-7", @@ -44369,23 +44369,6 @@ "laySummary": "", "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.057888; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.057888; html:https://europepmc.org/articles/PMC9047645; pdf:https://europepmc.org/articles/PMC9047645?pdf=render" }, - { - "id": "34516908", - "doi": "https://doi.org/10.1126/sciadv.abh0534", - "title": "Cell-free DNA TAPS provides multimodal information for early cancer detection.", - "authorString": "Siejka-Zieli\u0144ska P, Cheng J, Jackson F, Liu Y, Soonawalla Z, Reddy S, Silva M, Puta L, McCain MV, Culver EL, Bekkali N, Schuster-B\u00f6ckler B, Palamara PF, Mann D, Reeves H, Barnes E, Sivakumar S, Song CX.", - "authorAffiliations": "", - "journalTitle": "Science advances", - "pubYear": "2021", - "date": "2021-09-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Multimodal, genome-wide characterization of epigenetic and genetic information in circulating cell-free DNA (cfDNA) could enable more sensitive early cancer detection, but it is technologically challenging. Recently, we developed TET-assisted pyridine borane sequencing (TAPS), which is a mild, bisulfite-free method for base-resolution direct DNA methylation sequencing. Here, we optimized TAPS for cfDNA (cfTAPS) to provide high-quality and high-depth whole-genome cell-free methylomes. We applied cfTAPS to 85 cfDNA samples from patients with hepatocellular carcinoma (HCC) or pancreatic ductal adenocarcinoma (PDAC) and noncancer controls. From only 10 ng of cfDNA (1 to 3 ml of plasma), we generated the most comprehensive cfDNA methylome to date. We demonstrated that cfTAPS provides multimodal information about cfDNA characteristics, including DNA methylation, tissue of origin, and DNA fragmentation. Integrated analysis of these epigenetic and genetic features enables accurate identification of early HCC and PDAC.", - "laySummary": "", - "urls": "pdf:https://www.science.org/doi/pdf/10.1126/sciadv.abh0534?download=true; doi:https://doi.org/10.1126/sciadv.abh0534; html:https://europepmc.org/articles/PMC8442905; pdf:https://europepmc.org/articles/PMC8442905?pdf=render" - }, { "id": "30498058", "doi": "https://doi.org/10.1136/archdischild-2018-315866", @@ -44403,6 +44386,23 @@ "laySummary": "This study looked at whether there is a link between gestational length of a child (the length of time of pregnancy) and the likelihood of permanent hearing impairment. The authors looked at data from over 19000 children from a study called the Millenium Cohort Study. They found that shorter gestational length did not increase the likelihood of childhood permanent hearting impairment. However, they found that children who had neonatal illness (illness in the immediate days after birth), if they were Bangladeshi or Pakistani in ethnicity, or if they were born to younger mothers.", "urls": "pdf:https://adc.bmj.com/content/archdischild/105/2/187.full.pdf; doi:https://doi.org/10.1136/archdischild-2018-315866; html:https://europepmc.org/articles/PMC7025723; pdf:https://europepmc.org/articles/PMC7025723?pdf=render" }, + { + "id": "34516908", + "doi": "https://doi.org/10.1126/sciadv.abh0534", + "title": "Cell-free DNA TAPS provides multimodal information for early cancer detection.", + "authorString": "Siejka-Zieli\u0144ska P, Cheng J, Jackson F, Liu Y, Soonawalla Z, Reddy S, Silva M, Puta L, McCain MV, Culver EL, Bekkali N, Schuster-B\u00f6ckler B, Palamara PF, Mann D, Reeves H, Barnes E, Sivakumar S, Song CX.", + "authorAffiliations": "", + "journalTitle": "Science advances", + "pubYear": "2021", + "date": "2021-09-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Multimodal, genome-wide characterization of epigenetic and genetic information in circulating cell-free DNA (cfDNA) could enable more sensitive early cancer detection, but it is technologically challenging. Recently, we developed TET-assisted pyridine borane sequencing (TAPS), which is a mild, bisulfite-free method for base-resolution direct DNA methylation sequencing. Here, we optimized TAPS for cfDNA (cfTAPS) to provide high-quality and high-depth whole-genome cell-free methylomes. We applied cfTAPS to 85 cfDNA samples from patients with hepatocellular carcinoma (HCC) or pancreatic ductal adenocarcinoma (PDAC) and noncancer controls. From only 10 ng of cfDNA (1 to 3 ml of plasma), we generated the most comprehensive cfDNA methylome to date. We demonstrated that cfTAPS provides multimodal information about cfDNA characteristics, including DNA methylation, tissue of origin, and DNA fragmentation. Integrated analysis of these epigenetic and genetic features enables accurate identification of early HCC and PDAC.", + "laySummary": "", + "urls": "pdf:https://www.science.org/doi/pdf/10.1126/sciadv.abh0534?download=true; doi:https://doi.org/10.1126/sciadv.abh0534; html:https://europepmc.org/articles/PMC8442905; pdf:https://europepmc.org/articles/PMC8442905?pdf=render" + }, { "id": "34857774", "doi": "https://doi.org/10.1038/s41598-021-00854-x", @@ -45457,23 +45457,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.omtm.2021.06.012; doi:https://doi.org/10.1016/j.omtm.2021.06.012; html:https://europepmc.org/articles/PMC8322039; pdf:https://europepmc.org/articles/PMC8322039?pdf=render" }, - { - "id": "38177345", - "doi": "https://doi.org/10.1038/s41588-023-01596-4", - "title": "Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference.", - "authorString": "Meng X, Navoly G, Giannakopoulou O, Levey DF, Koller D, Pathak GA, Koen N, Lin K, Adams MJ, Renter\u00eda ME, Feng Y, Gaziano JM, Stein DJ, Zar HJ, Campbell ML, van Heel DA, Trivedi B, Finer S, McQuillin A, Bass N, Chundru VK, Martin HC, Huang QQ, Valkovskaya M, Chu CY, Kanjira S, Kuo PH, Chen HC, Tsai SJ, Liu YL, Kendler KS, Peterson RE, Cai N, Fang Y, Sen S, Scott LJ, Burmeister M, Loos RJF, Preuss MH, Actkins KV, Davis LK, Uddin M, Wani AH, Wildman DE, Aiello AE, Ursano RJ, Kessler RC, Kanai M, Okada Y, Sakaue S, Rabinowitz JA, Maher BS, Uhl G, Eaton W, Cruz-Fuentes CS, Martinez-Levy GA, Campos AI, Millwood IY, Chen Z, Li L, Wassertheil-Smoller S, Jiang Y, Tian C, Martin NG, Mitchell BL, Byrne EM, Awasthi S, Coleman JRI, Ripke S, PGC-MDD Working Group, China Kadoorie Biobank Collaborative Group, 23andMe Research Team, Genes and Health Research Team, BioBank Japan Project, Sofer T, Walters RG, McIntosh AM, Polimanti R, Dunn EC, Stein MB, Gelernter J, Lewis CM, Kuchenbaecker K.", - "authorAffiliations": "", - "journalTitle": "Nature genetics", - "pubYear": "2024", - "date": "2024-01-04", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41588-023-01596-4.pdf; doi:https://doi.org/10.1038/s41588-023-01596-4; html:https://europepmc.org/articles/PMC10864182; pdf:https://europepmc.org/articles/PMC10864182?pdf=render" - }, { "id": "34193486", "doi": "https://doi.org/10.1136/bmjopen-2020-045105", @@ -45491,6 +45474,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e045105.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-045105; html:https://europepmc.org/articles/PMC8246371; pdf:https://europepmc.org/articles/PMC8246371?pdf=render" }, + { + "id": "38177345", + "doi": "https://doi.org/10.1038/s41588-023-01596-4", + "title": "Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference.", + "authorString": "Meng X, Navoly G, Giannakopoulou O, Levey DF, Koller D, Pathak GA, Koen N, Lin K, Adams MJ, Renter\u00eda ME, Feng Y, Gaziano JM, Stein DJ, Zar HJ, Campbell ML, van Heel DA, Trivedi B, Finer S, McQuillin A, Bass N, Chundru VK, Martin HC, Huang QQ, Valkovskaya M, Chu CY, Kanjira S, Kuo PH, Chen HC, Tsai SJ, Liu YL, Kendler KS, Peterson RE, Cai N, Fang Y, Sen S, Scott LJ, Burmeister M, Loos RJF, Preuss MH, Actkins KV, Davis LK, Uddin M, Wani AH, Wildman DE, Aiello AE, Ursano RJ, Kessler RC, Kanai M, Okada Y, Sakaue S, Rabinowitz JA, Maher BS, Uhl G, Eaton W, Cruz-Fuentes CS, Martinez-Levy GA, Campos AI, Millwood IY, Chen Z, Li L, Wassertheil-Smoller S, Jiang Y, Tian C, Martin NG, Mitchell BL, Byrne EM, Awasthi S, Coleman JRI, Ripke S, PGC-MDD Working Group, China Kadoorie Biobank Collaborative Group, 23andMe Research Team, Genes and Health Research Team, BioBank Japan Project, Sofer T, Walters RG, McIntosh AM, Polimanti R, Dunn EC, Stein MB, Gelernter J, Lewis CM, Kuchenbaecker K.", + "authorAffiliations": "", + "journalTitle": "Nature genetics", + "pubYear": "2024", + "date": "2024-01-04", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41588-023-01596-4.pdf; doi:https://doi.org/10.1038/s41588-023-01596-4; html:https://europepmc.org/articles/PMC10864182; pdf:https://europepmc.org/articles/PMC10864182?pdf=render" + }, { "id": "32492392", "doi": "https://doi.org/10.1016/j.cmet.2020.05.007",